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Mouse models for understanding human developmental anomalies
The mouse experimental system presents an opportunity for studying the nature of the underlying mutagenic damage and the molecular pathogenesis of this class of anomalies by virtue of the accessibility of the zygote and its descendant blastomeres. Such studies could contribute to the understanding of the etiology of certain sporadic but common human malformations. The vulnerability of the zygotes to mutagens as demonstrated in the studies described in this report should be a major consideration in chemical safety evaluation. It raises questions regarding the danger to human zygotes when the mother is exposed to drugs and environmental chemicals.
Generoso, W.M.
The new dysmorphology: application of insights from basic developmental biology to the understanding of human birth defects.
Information obtained from studies of developmental and cellular processes in lower organisms is beginning to make significant contributions to the understanding of the pathogenesis of human birth defects, and it is now becoming possible to treat birth defects as inborn errors of development. Mutations in genes for transcription factors, receptors, cell adhesion molecules, intercellular junctions, molecules involved in signal transduction, growth factors, structural proteins, enzymes, and transporters have been identified in genetically caused human malformations and dysplasias. The identification of these mutations and the analysis of their developmental effects have been greatly facilitated by the existence of natural or engineered models in the mouse and even of related mutations in Drosophila, and in some instances a remarkable conservation of function in development has been observed, even between widely separated species.
Epstein, C J
Developmental Approaches to Understanding and Treating Autism
Over the past decade our understanding of early social communication development in young children with autism has undergone a remarkable change. We now know something about how young children with autism process the social world in a very different way from typical children. This has led to truly developmental models of autism. In turn, these have had profound impacts on
Tony Charman
Many human accelerated regions are developmental enhancers
The genetic changes underlying the dramatic differences in form and function between humans and other primates are largely unknown, although it is clear that gene regulatory changes play an important role. To identify regulatory sequences with potentially human-specific functions, we and others used comparative genomics to find non-coding regions conserved across mammals that have acquired many sequence changes in humans since divergence from chimpanzees. These regions are good candidates for performing human-specific regulatory functions. Here, we analysed the DNA sequence, evolutionary history, histone modifications, chromatin state and transcription factor (TF) binding sites of a combined set of 2649 non-coding human accelerated regions (ncHARs) and predicted that at least 30% of them function as developmental enhancers. We prioritized the predicted ncHAR enhancers using analysis of TF binding site gain and loss, along with the functional annotations and expression patterns of nearby genes. We then tested both the human and chimpanzee sequence for 29 ncHARs in transgenic mice, and found 24 novel developmental enhancers active in both species, 17 of which had very consistent patterns of activity in specific embryonic tissues. Of these ncHAR enhancers, five drove expression patterns suggestive of different activity for the human and chimpanzee sequence at embryonic day 11.5. The changes to human non-coding DNA in these ncHAR enhancers may modify the complex patterns of gene expression necessary for proper development in a human-specific manner and are thus promising candidates for understanding the genetic basis of human-specific biology.
Capra, John A.; Erwin, Genevieve D.; McKinsey, Gabriel; Rubenstein, John L. R.; Pollard, Katherine S.
Developmental Patterns in the Understanding of Social and Physical Transitivity.
ERIC Educational Resources Information Center
Two studies examined developmental patterns in understanding physical and social transitivity in 6- to 11-year olds. Findings revealed no significant correlations between social judgments and judgments concerning length. Results suggested that children possess two distinct strategies for making transitive judgments that correspond to the logical�
Markovits, Henry; Dumas, Claude
How Neuropsychology Informs Our Understanding of Developmental Disorders
ERIC Educational Resources Information Center
This review includes 1) an explanation of what neuropsychology is, 2) a brief history of how developmental cognitive neuroscience emerged from earlier neuropsychological approaches to understanding atypical development, 3) three recent examples that illustrate the benefits of this approach, 4) issues and challenges this approach must face, and 5)�
Pennington, Bruce F.
Children's understanding of scientific concepts: A developmental study
NASA Astrophysics Data System (ADS)
Combining theory-oriented inquiry and research that aims to improve instruction is a major goal of neo-Piagetian theory. Within this tradition, Case's (1992) developmental model enables educational researchers to conduct a detailed analysis of the structural and conceptual changes that occur in children's representation of knowledge in different domains at various points in their development. In so doing, it is now possible for educators to first assess children's "entering competence" in a specific subject and then set developmentally realistic instructional goals. Using Case's (1992) model as a theoretical framework, a developmental study was conducted investigating children's understanding of scientific phenomena, specifically buoyancy, at the ages of 6, 8, and 10 years. The main goal was to determine whether or not children's conceptual levels of understanding change systematically with age in a progressive manner consistent with neo-Piagetian stages of development hypothesized by Case. Participants attended one elementary school in a suburban school district near Vancouver, B.C. Sixty children were individually administered a set of five buoyancy tasks that varied in level of difficulty and involved objects of different weights, shapes and sizes. Each student was asked to predict whether an object would float or sink in different liquids and to support their prediction with an explanation. Analyses using the neo-Piagetian approach of articulating the semantic and syntactic nature of children's mental structures were conducted on the students' responses. Shape, size, weight and substance were identified as the semantic components of buoyancy which are syntactically related Using Case's dimensional metric for classifying different levels of conceptual understanding of buoyancy, the results of the study confirmed that children's understanding of buoyancy did progress through the developmental sequence as hypothesized. The structural progression from predimensional through to integrated bidimensional reasoning captured the general developmental pattern of children's understanding of buoyancy from the ages of 6 to 10 years. A statistical analysis of the responses showed significant differences between each age group. In summary, the results of the study suggested an age-related and hierarchical progression in conceptual understanding that was consistent with the age-level postulates of Case's (1992) developmental model.
Bickerton, Gillian Valerie
Contemporary Issues in Toxicology: A New Frontier in Understanding the Mechanisms of Developmental Abnormalities.
National Technical Information Service (NTIS)
The paper reviews some of the important issues that may lead to understanding basic developmental processes and mechanisms by which toxic agents may interfere with normal and abnormal development. Approximately 70% of developmental defects are of unknown ...
C. A. Kimmel W. M. Generoso R. D. Thomas K. S. Bakshi
Cognitive and developmental components of understanding the nature of science
NASA Astrophysics Data System (ADS)
The purpose of this study is to determine the degree to which years of education, college major, or reflective judgment stage influences individual's understandings of the nature of science. Using a cross-sectional design influenced by the literature describing the development of reflective judgment and nature of science understandings, this study encompasses the viewpoints of 323 individuals from ninth grade through graduate study. This research involves the careful selection of instruments for assessing these two complex constructs, and the processes used to select and rate participants responses is described in detail. Multinomial ordinal regression was used to determine the significance of educational level, major, and reflective judgment on nature of science views. Results indicate that high school students as a whole are least likely to respond appropriately to questions about the nature of science. However, the performance of college students is inconsistent with predictions, college freshmen more often select the desired response than college seniors or graduate students. Additionally, college major has no significant impact on nature of science understandings. Reflective judgment, a term that describes cognitive developmental model of advanced thinking skills, is found to have the most significant correlations with nature of science views. Reflective thinkers are more likely to select the desired nature of science response than quasi-reflective and pre-reflective thinkers for six of the ten questions. Discussion of results is followed by implications for science teaching and learning in K-12 classrooms.
Dotger, Sharon
Understanding enjoyment in youth sport: A developmental perspective
ObjectivesHistorically, the youth sport emotional response literature focused mainly on stress and enjoyment. Although research on these emotional responses has been significant, no systematic examination of these responses from a developmental perspective has been undertaken and therefore, developmental influence and implications for competitive youth sport are largely unknown. To begin to address this issue, the present study examined the developmental
Paul J. McCarthy; Marc V. Jones; David Clark-Carter
Toward a Systems-Level Understanding of Developmental Regulatory Networks
Developmental regulatory networks constitute all the interconnections among molecular components that guide embryonic development. Developmental transcriptional regulatory networks are circuits of transcription factors and cis-acting DNA elements that control expression of downstream regulatory and effector genes. Developmental networks comprise functional subnetworks that are deployed sequentially in requisite spatiotemporal patterns. Here we discuss integrative genomics approaches for elucidating transcriptional regulatory networks, with an emphasis on those involved in Drosophila mesoderm development and mammalian embryonic stem cell maintenance and differentiation. As examples of regulatory subnetworks, we consider the transcriptional and signaling regulation of genes that interact to control cell morphology and migration. Finally, we describe integrative experimental and computational strategies for defining the entirety of molecular interactions underlying developmental regulatory networks.
Busser, Brian W.; Bulyk, Martha L.; Michelson, Alan M.
Developmental Issues in Understanding, Assessing, and Managing Pediatric Pain
\\u000a Infants, children, and adolescents presenting with pain differ dramatically in physical, cognitive, emotional, behavioral,\\u000a and social characteristics. This chapter presents an overview of basic concepts that should be understood in the delivery\\u000a of developmentally appropriate care and addresses their relevance to pain assessment and management. The developmental issues\\u000a concern variations in maturation and growth in perception and central processing of
Kenneth D. Craig; Christine T. Korol
Stacking of blocks by chimpanzees: developmental processes and physical understanding.
The stacking-block task has been used to assess cognitive development in both humans and chimpanzees. The present study reports three aspects of stacking behavior in chimpanzees: spontaneous development, acquisition process following training, and physical understanding assessed through a cylindrical-block task. Over 3 years of longitudinal observation of block manipulation, one of three infant chimpanzees spontaneously started to stack up cubic blocks at the age of 2 years and 7 months. The other two infants began stacking up blocks at 3 years and 1 month, although only after the introduction of training by a human tester who rewarded stacking behavior. Cylindrical blocks were then introduced to assess physical understanding in object-object combinations in three infant (aged 3-4) and three adult chimpanzees. The flat surfaces of cylinders are suitable for stacking, while the rounded surface is not. Block manipulation was described using sequential codes and analyzed focusing on failure, cause, and solution in the task. Three of the six subjects (one infant and two adults) stacked up cylindrical blocks efficiently: frequently changing the cylinders' orientation without contacting the round side to other blocks. Rich experience in stacking cubes may facilitate subjects' stacking of novel, cylindrical shapes from the beginning. The other three subjects were less efficient in stacking cylinders and used variable strategies to achieve the goal. Nevertheless, they began to learn the effective way of stacking over the course of testing, after about 15 sessions (75 trials). PMID:16909233
Hayashi, Misato
Understanding individual human mobility patterns
Despite their importance for urban planning, traffic forecasting, and the\\u000aspread of biological and mobile viruses, our understanding of the basic laws\\u000agoverning human motion remains limited thanks to the lack of tools to monitor\\u000athe time resolved location of individuals. Here we study the trajectory of\\u000a100,000 anonymized mobile phone users whose position is tracked for a six month
Marta C. Gonz�lez; C�sar A. Hidalgo; Albert-L�szl� Barab�si
Understanding individual human mobility patterns.
Despite their importance for urban planning, traffic forecasting and the spread of biological and mobile viruses, our understanding of the basic laws governing human motion remains limited owing to the lack of tools to monitor the time-resolved location of individuals. Here we study the trajectory of 100,000 anonymized mobile phone users whose position is tracked for a six-month period. We find that, in contrast with the random trajectories predicted by the prevailing L�vy flight and random walk models, human trajectories show a high degree of temporal and spatial regularity, each individual being characterized by a time-independent characteristic travel distance and a significant probability to return to a few highly frequented locations. After correcting for differences in travel distances and the inherent anisotropy of each trajectory, the individual travel patterns collapse into a single spatial probability distribution, indicating that, despite the diversity of their travel history, humans follow simple reproducible patterns. This inherent similarity in travel patterns could impact all phenomena driven by human mobility, from epidemic prevention to emergency response, urban planning and agent-based modelling. PMID:18528393
Gonz�lez, Marta C; Hidalgo, C�sar A; Barab�si, Albert-L�szl�
Modeling anesthetic developmental neurotoxicity using human stem cells
Mounting pre-clinical evidence in rodents and non-human primates has demonstrated that prolonged exposure of developing animals to general anesthetics can induce widespread neuronal cell death followed by long-term memory and learning disabilities. In vitro experimental evidence from cultured neonatal animal neurons confirmed the in vivo findings. However, there is no direct clinical evidence of the detrimental effects of anesthetics in human fetuses, infants, or children. Development of an in vitro neurogenesis system using human stem cells has opened up avenues of research for advancing our understanding of human brain development and the issues relevant to anesthetic-induced developmental toxicity in human neuronal lineages. Recent studies from our group, as well as other groups, showed that isoflurane influences human neural stem cell proliferation and neurogenesis, while ketamine induces neuroapoptosis. Application of this high throughput in vitro stem cell neurogenesis approach is a major stride toward assuring the safety of anesthetic agents in young children. This in vitro human model allows us to (1) screen the toxic effects of various anesthetics under controlled conditions during intense neuronal growth, (2) find the trigger for the anesthetic-induced catastrophic chain of toxic events, and (3) develop prevention strategies to avoid this toxic effect. In this paper, we reviewed the current findings in anesthetic-induced neurotoxicity studies, specifically focusing on the in vitro human stem cell model.
Bai, Xiaowen; Twaroski, Danielle; Bosnjak, Zeljko J.
Developmental Science: Integrating Knowledge About Dynamic Processes in Human Development
There is an increasing need to develop an interdisciplinary model that describes the dynamic processes in human development.\\u000a During the last decades several different theories depicting dynamic developmental processes have been formulated. In this\\u000a chapter we briefly introduce these approaches and argue that developmental systems perspective (DSP) is one of the more promising\\u000a approaches to depict how developmental patterns arise.
Herbert Scheithauer; Kay Niebank; Angela Ittel
A Developmental-Biological Perspective of Human Communication Competency.
ERIC Educational Resources Information Center
Teachers and researchers of public speaking, rhetoric, small group, or interpersonal communication are all affected by research in communication competence. This essay discusses the consequences of applying a developmental-biological perspective to understanding the nature of communication competence. (PD)
Johnson, John R.
Understanding loneliness during adolescence: developmental changes that increase the risk of perceived social isolation.
Loneliness is typically defined in terms of feeling states. In this review, we take a somewhat different approach, describing loneliness in terms of perceived social isolation. Vulnerabilities to perceived social isolation differ across the lifespan. Unique properties of adolescence are identified that carry special risk for perceived social isolation. These include (but are not limited to) developmental changes in companions, developmental changes in autonomy and individuation, identity exploration, cognitive maturation, developmental changes in social perspective taking, and physical maturation. Scholars are encouraged to consider loneliness through the lens of perceived social isolation so as to better understand how the experience of physical isolation varies across adolescence. PMID:23866959
Laursen, Brett; Hartl, Amy C
Defining Early Human NK Cell Developmental Stages in Primary and Secondary Lymphoid Tissues
A better understanding of human NK cell development in vivo is crucial to exploit NK cells for immunotherapy. Here, we identified seven distinctive NK cell developmental stages in bone marrow of single donors using 10-color flow cytometry and found that NK cell development is accompanied by early expression of stimulatory co-receptor CD244 in vivo. Further analysis of cord blood (CB),
Diana N. Eissens; Jan Spanholtz; Arnold van der Meer; Bram van Cranenbroek; Harry Dolstra; Jaap Kwekkeboom; Frank W. M. B. Preijers; Irma Joosten
Developmental Atlas of the Early First Trimester Human Embryo
Rapid advances in medical imaging are facilitating the clinical assessment of first trimester human embryos at increasingly earlier stages. To obtain data on early human development, we used magnetic resonance (MR) imaging and episcopic fluorescence capture (EFIC) to acquire digital images of human embryos spanning the time of dynamic tissue remodeling and organogenesis (Carnegie stages 13 to 23). These imaging data sets are readily resectioned digitally in arbitrary planes, suitable for rapid high-resolution three-dimensional (3D) observation. Using these imaging datasets, a web accessible digital Human Embryo Atlas (http://apps.nhlbi.nih.gov/humanaltas) was created containing serial 2D images of human embryos in three standard histological planes � sagittal, frontal, and transverse. In addition, annotations and 3D reconstructions were generated for visualizing different anatomical structures. Overall, this Human Embryo Atlas is a unique resource that provides morphologic data of human developmental anatomy that can accelerate basic research investigations into developmental mechanisms that underlie human congenital anomalies.
Yamada, Shigehito; Samtani, Rajeev R; Lee, Elaine S; Lockett, Elizabeth; Uwabe, Chigako; Shiota, Kohei; Anderson, Stasia A; Lo, Cecilia W
Theory of Mind "Emotion", Developmental Characteristics and Social Understanding in Children and Adolescents with Intellectual Disabilities
ERIC Educational Resources Information Center
Patterns of development of ToM-emotion abilities in intellectually disabled (ID) children and typically developing (TD) children matched on their developmental age were investigated. The links between cognition, language, social understanding and ToM-emotion abilities were examined. EDEI-R (Perron-Borelli, M. (1996). "Echelles Differentielles�
Thirion-Marissiaux, Anne-Francoise; Nader-Grosbois, Nathalie
Theory of Mind "Beliefs", Developmental Characteristics and Social Understanding in Children and Adolescents with Intellectual Disabilities
ERIC Educational Resources Information Center
Patterns of development of ToM belief abilities in intellectually disabled (ID) children and typically developing (TD) children matched on their developmental age were investigated. The links between cognition, language, social understanding and ToM belief abilities were examined. EDEI-R [Perron-Borelli M. (1996). "Echelles Differentielles�
Thirion-Marissiaux, Anne-Francoise; Nader-Grosbois, Nathalie
What Community College Developmental Mathematics Students Understand about Mathematics, Part 2: The Interviews
ERIC Educational Resources Information Center
In a prior issue of "MathAMATYC Educator," we reported on our efforts to find out what community college developmental mathematics students understand about mathematics (Stigler, Givvin, & Thompson, 2010). Our work painted a distressing picture of students' mathematical knowledge. No matter what kind of mathematical question we asked, students�
Givvin, Karen B.; Stigler, James W.; Thompson, Belinda J.
Characterizing Key Developmental Understandings and Pedagogically Powerful Ideas within a Statistical Knowledge for Teaching Framework
ERIC Educational Resources Information Center
A hypothetical framework to characterize statistical knowledge for teaching (SKT) is described. Empirical grounding for the framework is provided by artifacts from an undergraduate course for prospective teachers that concentrated on the development of SKT. The theoretical notion of "key developmental understanding" (KDU) is used to identify�
Groth, Randall E.
The EvoDevoCI: A Concept Inventory for Gauging Students' Understanding of Evolutionary Developmental Biology
The American Association for the Advancement of Science 2011 report Vision and Change in Undergraduate Biology Education encourages the teaching of developmental biology as an important part of teaching evolution. Recently, however, we found that biology majors often lack the developmental knowledge needed to understand evolutionary developmental biology, or �evo-devo.� To assist in efforts to improve evo-devo instruction among undergraduate biology majors, we designed a concept inventory (CI) for evolutionary developmental biology, the EvoDevoCI. The CI measures student understanding of six core evo-devo concepts using four scenarios and 11 multiple-choice items, all inspired by authentic scientific examples. Distracters were designed to represent the common conceptual difficulties students have with each evo-devo concept. The tool was validated by experts and administered at four institutions to 1191 students during preliminary (n = 652) and final (n = 539) field trials. We used student responses to evaluate the readability, difficulty, discriminability, validity, and reliability of the EvoDevoCI, which included items ranging in difficulty from 0.22�0.55 and in discriminability from 0.19�0.38. Such measures suggest the EvoDevoCI is an effective tool for assessing student understanding of evo-devo concepts and the prevalence of associated common conceptual difficulties among both novice and advanced undergraduate biology majors.
Perez, Kathryn E.; Hiatt, Anna; Davis, Gregory K.; Trujillo, Caleb; French, Donald P.; Terry, Mark; Price, Rebecca M.
Understanding adverse events: human factors.
(1) Human rather than technical failures now represent the greatest threat to complex and potentially hazardous systems. This includes healthcare systems. (2) Managing the human risks will never be 100% effective. Human fallibility can be moderated, but it cannot be eliminated. (3) Different error types have different underlying mechanisms, occur in different parts of the organisation, and require different methods of risk management. The basic distinctions are between: Slips, lapses, trips, and fumbles (execution failures) and mistakes (planning or problem solving failures). Mistakes are divided into rule based mistakes and knowledge based mistakes. Errors (information-handling problems) and violations (motivational problems) Active versus latent failures. Active failures are committed by those in direct contact with the patient, latent failures arise in organisational and managerial spheres and their adverse effects may take a long time to become evident. (4) Safety significant errors occur at all levels of the system, not just at the sharp end. Decisions made in the upper echelons of the organisation create the conditions in the workplace that subsequently promote individual errors and violations. Latent failures are present long before an accident and are hence prime candidates for principled risk management. (5) Measures that involve sanctions and exhortations (that is, moralistic measures directed to those at the sharp end) have only very limited effectiveness, especially so in the case of highly trained professionals. (6) Human factors problems are a product of a chain of causes in which the individual psychological factors (that is, momentary inattention, forgetting, etc) are the last and least manageable links. Attentional "capture" (preoccupation or distraction) is a necessary condition for the commission of slips and lapses. Yet, its occurrence is almost impossible to predict or control effectively. The same is true of the factors associated with forgetting. States of mind contributing to error are thus extremely difficult to manage; they can happen to the best of people at any time. (7) People do not act in isolation. Their behaviour is shaped by circumstances. The same is true for errors and violations. The likelihood of an unsafe act being committed is heavily influenced by the nature of the task and by the local workplace conditions. These, in turn, are the product of "upstream" organisational factors. Great gains in safety can ve achieved through relatively small modifications of equipment and workplaces. (8) Automation and increasing advanced equipment do not cure human factors problems, they merely relocate them. In contrast, training people to work effectively in teams costs little, but has achieved significant enhancements of human performance in aviation. (9) Effective risk management depends critically on a confidential and preferable anonymous incident monitoring system that records the individual, task, situational, and organisational factors associated with incidents and near misses. (10) Effective risk management means the simultaneous and targeted deployment of limited remedial resources at different levels of the system: the individual or team, the task, the situation, and the organisation as a whole.
Reason, J
Human Developmental Enhancers Conserved between Deuterostomes and Protostomes
The identification of homologies, whether morphological, molecular, or genetic, is fundamental to our understanding of common biological principles. Homologies bridging the great divide between deuterostomes and protostomes have served as the basis for current models of animal evolution and development. It is now appreciated that these two clades share a common developmental toolkit consisting of conserved transcription factors and signaling
Shoa L. Clarke; Julia E. VanderMeer; Aaron M. Wenger; Bruce T. Schaar; Nadav Ahituv; Gill Bejerano
Evolutionary and developmental foundations of human knowledge
What are the brain and cognitive systems that allow humans to play baseball, compute square roots, cook souffl?s, or navigate the Tokyo subways? It may seem that studies of human infants and of non-human animals will tell us little about these abilities, because only educated, enculturated human adults engage in organized games, formal mathematics, gourmet cooking, or map-reading. In this
Marc D. Hauser; Elizabeth Spelke
Developmental neuroimaging of the human ventral visual cortex
Here, we review recent results that investigate the development of the human ventral stream from child- hood, through adolescence and into adulthood. Conver- ging evidence suggests a differential developmental trajectory across ventral stream regions, in which face- selective regions show a particularly long developmen- tal time course, taking more than a decade to become adult-like. We discuss the implications of
Kalanit Grill-Spector; Golijeh Golarai; John Gabrieli
Developmental neuroimaging of the human ventral visual cortex
Here, we review recent results that investigate the development of the human ventral stream from childhood, through adolescence and into adulthood. Converging evidence suggests a differential developmental trajectory across ventral stream regions, in which face-selective regions show a particularly long developmental time course, taking more than a decade to become adult-like. We discuss the implications of these recent findings, how they relate to age-dependent improvements in recognition memory performance and propose possible neural mechanisms that might underlie this development. These results have important implications regarding the role of experience in shaping the ventral stream and the nature of the underlying representations.
Grill-Spector, Kalanit; Golarai, Golijeh; Gabrieli, John
The EvoDevoCI: A Concept Inventory for Gauging Students' Understanding of Evolutionary Developmental Biology
ERIC Educational Resources Information Center
The American Association for the Advancement of Science 2011 report "Vision and Change in Undergraduate Biology Education" encourages the teaching of developmental biology as an important part of teaching evolution. Recently, however, we found that biology majors often lack the developmental knowledge needed to understand evolutionary�
Perez, Kathryn E.; Hiatt, Anna; Davis, Gregory K.; Trujillo, Caleb; French, Donald P.; Terry, Mark; Price, Rebecca M.
Understanding the Social Relationship Between Humans and Virtual Humans
Our review surveys a range of human-human relationship models and research that might provide insights to understanding the social relationship between humans and virtual humans. This involves investigating several social constructs (expectations, communication, trust, etc.) that are identified as key variables that influence the relationship between people and how these variables should be implemented in the design for an effective
Sung Park; Richard Catrambone
Developmental atlas of the early first trimester human embryo.
Rapid advances in medical imaging are facilitating the clinical assessment of first-trimester human embryos at increasingly earlier stages. To obtain data on early human development, we used magnetic resonance (MR) imaging and episcopic fluorescence capture (EFIC) to acquire digital images of human embryos spanning the time of dynamic tissue remodeling and organogenesis (Carnegie stages 13 to 23). These imaging data sets are readily resectioned digitally in arbitrary planes, suitable for rapid high-resolution three-dimensional (3D) observation. Using these imaging datasets, a web-accessible digital Human Embryo Atlas (http://apps.devbio.pitt.edu/humanatlas/) was created containing serial 2D images of human embryos in three standard histological planes: sagittal, frontal, and transverse. In addition, annotations and 3D reconstructions were generated for visualizing different anatomical structures. Overall, this Human Embryo Atlas is a unique resource that provides morphologic data of human developmental anatomy that can accelerate basic research investigations into developmental mechanisms that underlie human congenital anomalies. PMID:20503356
Yamada, Shigehito; Samtani, Rajeev R; Lee, Elaine S; Lockett, Elizabeth; Uwabe, Chigako; Shiota, Kohei; Anderson, Stasia A; Lo, Cecilia W
If you could turn back time: understanding transgenerational latent effects of developmental exposure to contaminants.
Latent effects result from embryonic experiences but manifest in later stages of ontogeny. Our objective was to better understand how developmental exposure to contaminants influence life history traits and tolerance to novel stress in the freshwater gastropod, Physa pomilia. Ten egg masses were exposed to each of three initial treatments including control, 2.5�?g/L cadmium (Cd), and 10�?g/L Cd; there was no effect of this initial treatment on hatching success. At hatching, snails were transferred to cadmium-free water. Three weeks later, snails were divided among four secondary treatments including control, 50�?g/L Cd, 150�?g/L Cd, and 35��C. Developmental Cd exposure plus secondary temperature stress caused the most adverse effects. Surprisingly, developmental Cd exposure alone was enough to cause significant decreases in reproductive success a generation later. That effects can manifest as transgenerational decrements in reproductive success suggests that latent effects are important and have longer lasting consequences than previously considered. PMID:24121266
Kimberly, David A; Salice, Christopher J
Children's understanding of the immune system: Integrating the cognitive-developmental and intuitive theories' perspectives
NASA Astrophysics Data System (ADS)
Traditional cognitive-developmental researchers have provided a large body of evidence supporting the stage-like progression of children's cognitive development. Further, from this body of research comes evidence that children's understanding of HIV/AIDS develops in much the same way as their understanding of other illness-related concepts. Researchers from a newer perspective assert that biological concepts develop from intuitive theories. In general, as children are exposed to relevant content and have opportunities to organize this information, their theories become more accurate and differentiated. According to this perspective, there are no broad structural constraints on developing concepts, as asserted by cognitive developmental theorists. The purpose of the current study was two-fold: to provide support for both theoretical perspectives, while at the same time to explore children's conceptualizations of the immune system, which has not been done previously in the cognitive-developmental literature. One hundred ninety children ranging in age from 4 years old through 11 years old, and a group of adults, participated. Each participant was interviewed regarding health concepts and the body's function in maintaining health. Participants were also asked to report if they had certain experiences that would have led to relevant content exposure. Qualitative analyses were utilized to code the interviews with rubrics based on both theoretical perspectives. Quantitative analyses consisted of a series of univariate ANOVAs (and post hoc tests when appropriate) examining all three coding variables (accuracy, differentiation, and developmental level) across various age-group combinations and exposure groups. Results of these analyses provided support for both theoretical perspectives. When the data were analyzed for developmental level by all ages, a stage-like progression consistent with Piagetian stages emerged. When accuracy and differentiation were examined (intuitive theories perspective), discrete groups could not be formed. Instead, a gradual increase in accuracy and differentiation was observed. Additional support for this perspective was found when the responses of participants who had additional exposure provided responses that were more accurate, differentiated, and sophisticated than those of participants with no additional exposure. Theoretical and educational implications of these findings are discussed.
Landry-Boozer, Kristine L.
Theories of Human Development that Enhance an Understanding of the College Transition Process
ERIC Educational Resources Information Center
Background/Context: Although theories of human development often play a central role in K-12 pedagogical practices, evidence suggests that developmental theories have not been used extensively to understand the college transition process or to develop programs to support students during these transitions. Purpose/Objective/Research Question/Focus�
Guiffrida, Douglas A.
Ecological Human Brain and Young Children's "Naturalist Intelligence" from the Perspective of Developmentally and Culturally Appropriate Practice (DCAP).
ERIC Educational Resources Information Center
Based on the view that young children have a different intellectual culture from adults' in the way they know and understand nature, this paper explores ecological human brain development, children's intellectual culture of naturalist intelligence, and developmentally and culturally congruent curricula for young children. The paper discusses the�
Hyun, Eunsook
Short faces, big tongues: developmental origin of the human chin.
During the course of human evolution, the retraction of the face underneath the braincase, and closer to the cervical column, has reduced the horizontal dimension of the vocal tract. By contrast, the relative size of the tongue has not been reduced, implying a rearrangement of the space at the back of the vocal tract to allow breathing and swallowing. This may have left a morphological signature such as a chin (mental prominence) that can potentially be interpreted in Homo. Long considered an autopomorphic trait of Homo sapiens, various extinct hominins show different forms of mental prominence. These features may be the evolutionary by-product of equivalent developmental constraints correlated with an enlarged tongue. In order to investigate developmental mechanisms related to this hypothesis, we compare modern 34 human infants against 8 chimpanzee fetuses, whom development of the mandibular symphysis passes through similar stages. The study sets out to test that the shared ontogenetic shape changes of the symphysis observed in both species are driven by the same factor--space restriction at the back of the vocal tract and the associated arrangement of the tongue and hyoid bone. We apply geometric morphometric methods to extensive three-dimensional anatomical landmarks and semilandmarks configuration, capturing the geometry of the cervico-craniofacial complex including the hyoid bone, tongue muscle and the mandible. We demonstrate that in both species, the forward displacement of the mental region derives from the arrangement of the tongue and hyoid bone, in order to cope with the relative horizontal narrowing of the oral cavity. Because humans and chimpanzees share this pattern of developmental integration, the different forms of mental prominence seen in some extinct hominids likely originate from equivalent ontogenetic constraints. Variations in this process could account for similar morphologies. PMID:24260566
Coquerelle, Michael; Prados-Frutos, Juan Carlos; Rojo, Rosa; Mitteroecker, Philipp; Bastir, Markus
Understanding the relationship between actual:ideal discrepancies and depressive symptoms: A developmental examination.
Self-discrepancy theory (SDT) is one framework for understanding how goal failure is associated with depressive symptoms. The present studies sought to examine the variance in depressive symptoms explained by actual:ideal discrepancies, beyond what is accounted for by actual-self ratings. Additionally, gender and grade were examined as potential moderators in the relationship. In Study 1 (N�=�228), discrepancies accounted for additional variance in the level of depressive symptoms beyond what was explained by actual-self ratings in a college sample. In Study 2 (N�=�192), while similar global patterns were found, gender and grade differences emerged. For boys, the relationship between actual:ideal discrepancies and depressive symptoms was due to actual-self ratings. For girls, a developmental pattern suggested that actual:ideal discrepancies become more important to the prediction of depressive symptoms among older girls. Implications for the emergence of the discrepancy-depression association are discussed. PMID:24931564
Stevens, Erin N; Lovejoy, M Christine; Pittman, Laura D
Human Developmental Enhancers Conserved between Deuterostomes and Protostomes
The identification of homologies, whether morphological, molecular, or genetic, is fundamental to our understanding of common biological principles. Homologies bridging the great divide between deuterostomes and protostomes have served as the basis for current models of animal evolution and development. It is now appreciated that these two clades share a common developmental toolkit consisting of conserved transcription factors and signaling pathways. These patterning genes sometimes show common expression patterns and genetic interactions, suggesting the existence of similar or even conserved regulatory apparatus. However, previous studies have found no regulatory sequence conserved between deuterostomes and protostomes. Here we describe the first such enhancers, which we call bilaterian conserved regulatory elements (Bicores). Bicores show conservation of sequence and gene synteny. Sequence conservation of Bicores reflects conserved patterns of transcription factor binding sites. We predict that Bicores act as response elements to signaling pathways, and we show that Bicores are developmental enhancers that drive expression of transcriptional repressors in the vertebrate central nervous system. Although the small number of identified Bicores suggests extensive rewiring of cis-regulation between the protostome and deuterostome clades, additional Bicores may be revealed as our understanding of cis-regulatory logic and sample of bilaterian genomes continue to grow.
Clarke, Shoa L.; VanderMeer, Julia E.; Wenger, Aaron M.; Schaar, Bruce T.; Ahituv, Nadav; Bejerano, Gill
Chol understandings of suicide and human agency.
According to ethnographic material collected since 2003, the Chol Mayan indigenous people in southern Mexico have different causal explanations for suicide. It can be attributed to witchcraft that forces victims to take their lives against their own will, to excessive drinking, or to fate determined by God. However, it can also be conceived of as a conscious decision made by a person overwhelmed by daily problems. Drawing from the theoretical framework developed by Laura M. Ahearn, inspired by practice theory, the paper contends that these different explanations operate within two different logics or understandings of human agency. The first logic attributes responsibility to supernatural causes such as witchcraft or divine destiny, and reflects Chol notions of personhood. The second logic accepts personal responsibility for suicide, and is related to processes of social change such as the introduction of wage labor, education and a market economy. The contemporary Chol resort to both logics to make sense of the human drama of suicide. PMID:22382678
Imberton, Gracia
Understanding Immigrant College Students: Applying a Developmental Ecology Framework to the Practice of Academic Advising
ERIC Educational Resources Information Center
Immigrant college student populations continue to grow, but the complexity of their unique needs and issues remain relatively unknown. To gain a better understanding of the multiple contextual factors impacting immigrant students from a systems-based approach, I applied Bronfenbrenner's (1977) human ecology framework to the study. Students�
Stebleton, Michael J.
Understanding human dynamics in microblog posting activities
NASA Astrophysics Data System (ADS)
Human activity patterns are an important issue in behavior dynamics research. Empirical evidence indicates that human activity patterns can be characterized by a heavy-tailed inter-event time distribution. However, most researchers give an understanding by only modeling the power-law feature of the inter-event time distribution, and those overlooked non-power-law features are likely to be nontrivial. In this work, we propose a behavior dynamics model, called the finite memory model, in which humans adaptively change their activity rates based on a finite memory of recent activities, which is driven by inherent individual interest. Theoretical analysis shows a finite memory model can properly explain various heavy-tailed inter-event time distributions, including a regular power law and some non-power-law deviations. To validate the model, we carry out an empirical study based on microblogging activity from thousands of microbloggers in the Celebrity Hall of the Sina microblog. The results show further that the model is reasonably effective. We conclude that finite memory is an effective dynamics element to describe the heavy-tailed human activity pattern.
Jiang, Zhihong; Zhang, Yubao; Wang, Hui; Li, Pei
Global expression profiling reveals genetic programs underlying the developmental divergence between mouse and human embryogenesis
Background Mouse has served as an excellent model for studying human development and diseases due to its similarity to human. Advances in transgenic and knockout studies in mouse have dramatically strengthened the use of this model and significantly improved our understanding of gene function during development in the past few decades. More recently, global gene expression analyses have revealed novel features in early embryogenesis up to gastrulation stages and have indeed provided molecular evidence supporting the conservation in early development in human and mouse. On the other hand, little information is known about the gene regulatory networks governing the subsequent organogenesis. Importantly, mouse and human development diverges during organogenesis. For instance, the mouse embryo is born around the end of organogenesis while in human the subsequent fetal period of ongoing growth and maturation of most organs spans more than 2/3 of human embryogenesis. While two recent studies reported the gene expression profiles during human organogenesis, no global gene expression analysis had been done for mouse organogenesis. Results Here we report a detailed analysis of the global gene expression profiles from egg to the end of organogenesis in mouse. Our studies have revealed distinct temporal regulation patterns for genes belonging to different functional (Gene Ontology or GO) categories that support their roles during organogenesis. More importantly, comparative analyses identify both conserved and divergent gene regulation programs in mouse and human organogenesis, with the latter likely responsible for the developmental divergence between the two species, and further suggest a novel developmental strategy during vertebrate evolution. Conclusions We have reported here the first genome-wide gene expression analysis of the entire mouse embryogenesis and compared the transcriptome atlas during mouse and human embryogenesis. Given our earlier observation that genes function in a given process tends to be developmentally co-regulated during organogenesis, our microarray data here should help to identify genes associated with mouse development and/or infer the developmental functions of unknown genes. In addition, our study might be useful for invesgtigating the molecular basis of vertebrate evolution.
Developmental gene expression profiles of the human pathogen Schistosoma japonicum
Background The schistosome blood flukes are complex trematodes and cause a chronic parasitic disease of significant public health importance worldwide, schistosomiasis. Their life cycle is characterised by distinct parasitic and free-living phases involving mammalian and snail hosts and freshwater. Microarray analysis was used to profile developmental gene expression in the Asian species, Schistosoma japonicum. Total RNAs were isolated from the three distinct environmental phases of the lifecycle � aquatic/snail (eggs, miracidia, sporocysts, cercariae), juvenile (lung schistosomula and paired but pre-egg laying adults) and adult (paired, mature males and egg-producing females, both examined separately). Advanced analyses including ANOVA, principal component analysis, and hierarchal clustering provided a global synopsis of gene expression relationships among the different developmental stages of the schistosome parasite. Results Gene expression profiles were linked to the major environmental settings through which the developmental stages of the fluke have to adapt during the course of its life cycle. Gene ontologies of the differentially expressed genes revealed a wide range of functions and processes. In addition, stage-specific, differentially expressed genes were identified that were involved in numerous biological pathways and functions including calcium signalling, sphingolipid metabolism and parasite defence. Conclusion The findings provide a comprehensive database of gene expression in an important human pathogen, including transcriptional changes in genes involved in evasion of the host immune response, nutrient acquisition, energy production, calcium signalling, sphingolipid metabolism, egg production and tegumental function during development. This resource should help facilitate the identification and prioritization of new anti-schistosome drug and vaccine targets for the control of schistosomiasis.
Gobert, Geoffrey N; Moertel, Luke; Brindley, Paul J; McManus, Donald P
Assessment measures used in developmental neurotoxicology are reviewed for their comparability in humans and laboratory animals, and their ability to detect comparable, adverse effects across species. ompounds used for these comparisons include: abuse substances, anticonvulsant d...
Evolutionary and developmental contributions for understanding the organization of the basal ganglia.
Herein we take advantage of the evolutionary developmental biology approach in order to improve our understanding of both the functional organization and the evolution of the basal ganglia, with a particular focus on the globus pallidus. Therefore, we review data on the expression of developmental regulatory genes (that play key roles in patterning, regional specification and/or morphogenesis), gene function and fate mapping available in different vertebrate species, which are useful to (a) understand the embryonic origin and basic features of each neuron subtype of the basal ganglia (including neurotransmitter/neuropeptide expression and connectivity patterns); (b) identify the same (homologous) subpopulations in different species and the degree of variation or conservation throughout phylogeny, and (c) identify possible mechanisms that may explain the evolution of the basal ganglia. These data show that the globus pallidus of rodents contains two major subpopulations of GABAergic projection neurons: (1) neurons containing parvalbumin and neurotensin-related hexapetide (LANT6), with descending projections to the subthalamus and substantia nigra, which originate from progenitors expressing Nkx2.1, primarily located in the pallidal embryonic domain (medial ganglionic eminence), and (2) neurons containing preproenkephalin (and possibly calbindin), with ascending projections to the striatum, which appear to originate from progenitors expressing Islet1 in the striatal embryonic domain (lateral ganglionic eminence). Based on data on Nkx2.1, Islet1, LANT6 and proenkephalin, it appears that both cell types are also present in the globus pallidus/dorsal pallidum of chicken, frog and lungfish. In chicken, the globus pallidus also contains neurons expressing substance P (SP), perhaps originating in the striatal embryonic domain. In ray-finned and cartilaginous fishes, the pallidum contains at least the Nkx2.1 lineage cell population (likely representing the neurons containing LANT6). Based on the presence of neurons containing enkephalin or SP, it is possible that the pallidum of these animals also includes the Islet1 lineage cell subpopulation, and both neuron subtypes were likely present in the pallidum of the first jawed vertebrates. In contrast, lampreys (jawless fishes) appear to lack the pallidal embryonic domain and the Nkx2.1 lineage cell population that mainly characterize the pallidum in jawed vertebrates. In the absence of data in other jawless fishes, the ancestral condition in vertebrates remains to be elucidated. Perhaps, a major event in telencephalic evolution was the novel expression of Nkx2.1 in the subpallium, which has been related to Hedgehog expression and changes in the regulatory region of Nkx2.1. PMID:24776992
Medina, Loreta; Abell�n, Antonio; Vicario, Alba; Desfilis, Ester
Social Understanding and Social Lives: From Toddlerhood through to the Transition to School. Essays in Developmental Psychology
ERIC Educational Resources Information Center
Over the past thirty years, researchers have documented a remarkable growth in children's social understanding between toddlerhood and the early school years. However, it is still unclear why some children's awareness of others' thoughts and feelings lags so far behind that of their peers. Based on research that spans an extended developmental�
Hughes, Claire
Many pesticides cxause reproductive or developmental toxicity at high doses in animal models, but effects in humans at environmental exposure levels are difficult to assess. Human data on reproductive and developmental outcomes for currently used pesticides may help to define ris...
Understanding human functioning using graphical models
Background Functioning and disability are universal human experiences. However, our current understanding of functioning from a comprehensive perspective is limited. The development of the International Classification of Functioning, Disability and Health (ICF) on the one hand and recent developments in graphical modeling on the other hand might be combined and open the door to a more comprehensive understanding of human functioning. The objective of our paper therefore is to explore how graphical models can be used in the study of ICF data for a range of applications. Methods We show the applicability of graphical models on ICF data for different tasks: Visualization of the dependence structure of the data set, dimension reduction and comparison of subpopulations. Moreover, we further developed and applied recent findings in causal inference using graphical models to estimate bounds on intervention effects in an observational study with many variables and without knowing the underlying causal structure. Results In each field, graphical models could be applied giving results of high face-validity. In particular, graphical models could be used for visualization of functioning in patients with spinal cord injury. The resulting graph consisted of several connected components which can be used for dimension reduction. Moreover, we found that the differences in the dependence structures between subpopulations were relevant and could be systematically analyzed using graphical models. Finally, when estimating bounds on causal effects of ICF categories on general health perceptions among patients with chronic health conditions, we found that the five ICF categories that showed the strongest effect were plausible. Conclusions Graphical Models are a flexible tool and lend themselves for a wide range of applications. In particular, studies involving ICF data seem to be suited for analysis using graphical models.
Predicting human developmental toxicity of pharmaceuticals using human embryonic stem cells and metabolomics
Teratogens, substances that may cause fetal abnormalities during development, are responsible for a significant number of birth defects. Animal models used to predict teratogenicity often do not faithfully correlate to human response. Here, we seek to develop a more predictive developmental toxicity model based on an in vitro method that utilizes both human embryonic stem (hES) cells and metabolomics to discover biomarkers of developmental toxicity. We developed a method where hES cells were dosed with several drugs of known teratogenicity then LC-MS analysis was performed to measure changes in abundance levels of small molecules in response to drug dosing. Statistical analysis was employed to select for specific mass features that can provide a prediction of the developmental toxicity of a substance. These molecules can serve as biomarkers of developmental toxicity, leading to better prediction of teratogenicity. In particular, our work shows a correlation between teratogenicity and changes of greater than 10% in the ratio of arginine to asymmetric dimethylarginine levels. In addition, this study resulted in the establishment of a predictive model based on the most informative mass features. This model was subsequently tested for its predictive accuracy in two blinded studies using eight drugs of known teratogenicity, where it correctly predicted the teratogenicity for seven of the eight drugs. Thus, our initial data shows that this platform is a robust alternative to animal and other in vitro models for the prediction of the developmental toxicity of chemicals that may also provide invaluable information about the underlying biochemical pathways.
West, Paul R., E-mail: firstname.lastname@example.com [Stemina Biomarker Discovery, Inc., 504 S. Rosa Rd., Suite 150, Madison, WI 53719 (United States); Weir, April M.; Smith, Alan M.; Donley, Elizabeth L.R. [Stemina Biomarker Discovery, Inc., 504 S. Rosa Rd., Suite 150, Madison, WI 53719 (United States); Cezar, Gabriela G. [Stemina Biomarker Discovery, Inc., 504 S. Rosa Rd., Suite 150, Madison, WI 53719 (United States); University of Wisconsin-Madison, Department of Animal Sciences, 1675 Observatory Drive, Madison, WI 53706 (United States)
Being Human: A Resource Guide in Human Growth and Development for the Developmentally Disabled.
ERIC Educational Resources Information Center
The resource guide is intended to help practitioners develop curricula in human growth and development for developmentally disabled students. A matrix guide is presented for evaluating clients in three domains (social identity, health and hygiene, and physiological identity). Behavioral indicators are then noted which relate to adaptive behaviors�
Ogle, Peggy
Moving Targets: A Developmental Framework for Understanding Children's Changes following Disasters
ERIC Educational Resources Information Center
This paper proposes a developmental framework for disaster studies with children that allows researchers to explore the interaction between developmental change (defined as change that is extended, self-regulated, qualitative, and progressive) and cataclysmic change. It outlines three levels of analysis related to disasters: 1) observing the harm�
Franks, Bridget A.
Understanding MSW Student Anxiety and Resistance to Multicultural Learning: A Developmental Perspective
ERIC Educational Resources Information Center
This article situates expected anxiety and resistance to multicultural learning within the broader context of cognitive, behavioral and affective stages through which MSW students typically progress. The authors discuss the challenges to multicultural learning and the developmental phases of students. The ways in which these developmental stages�
Deal, Kathleen Holtz; Hyde, Cheryl A.
Functional aspects of developmental toxicity of polyhalogenated aromatic hydrocarbons in experimental animals and human infants
A scientific evaluation was made of functionalspects of developmental toxicity of polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) in experimental animals and in human infants. Persistent neurobehavioral, reproductive and endocrine alterations were observed in experimental animals, following in utero and lactational exposure to PCBs, PCDDs and PCDFs. The lowest observable adverse effect levels (LOAELs) for developmental neurobehavioral
Abraham Brouwer; Ulf G. Ahlborg; Martin Van den Berg; Linda S. Birnbaum; E. Ruud Boersma; Bart Bosveld; Michael S. Denison; L. Earl Gray; Lars Hagmar; Edel Holene; Marcel Huisman; Sandra W. Jacobson; Joseph L. Jacobson; Corine Koopman-Esseboom; Janna G. Koppe; Beverly M. Kulig; Dennis C. Morse; Gina Muckle; Richard E. Peterson; Pieter J. J. Sauer; Richard F. Seegal; Annette E. Smits-Van Prooije; Bert C. L. Touwen; Nynke Weisglas-Kuperus; Gerhard Winneke
Dental Approach to Craniofacial Syndromes: How Can Developmental Fields Show Us a New Way to Understand Pathogenesis?
The paper consists of three parts. Part 1: Definition of Syndromes. Focus is given to craniofacial syndromes in which abnormal traits in the dentition are associated symptoms. In the last decade, research has concentrated on phenotype, genotype, growth, development, function, and treatment. Part 2: Syndromes before Birth. How can the initial malformation sites in these syndromes be studied and what can we learn from it? In this section, deviations observed in syndromes prenatally will be highlighted and compared to the normal human embryological craniofacial development. Specific focus will be given to developmental fields studied on animal tissue and transferred to human cranial development. Part 3: Developmental Fields Affected in Two Craniofacial Syndromes. Analysis of primary and permanent dentitions can determine whether a syndrome affects a single craniofacial field or several fields. This distinction is essential for insight into craniofacial syndromes. The dentition, thus, becomes central in diagnostics and evaluation of the pathogenesis. Developmental fields can explore and advance the concept of dental approaches to craniofacial syndromes. Discussion. As deviations in teeth persist and do not reorganize during growth and development, the dentition is considered useful for distinguishing between syndrome pathogenesis manifested in a single developmental field and in several fields.
Kjaer, Inger
A scientific evaluation was made of functional aspects of developmental toxicity of polychlorinated biphenyls (PCBs)-dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) in experimental animals and in human infants. ersistent neurobehavioral, reproductive, and endocrine alteration...
Understanding African American Adolescents' Identity Development: A Relational Developmental Systems Perspective
ERIC Educational Resources Information Center
This article examines the development of African American adolescents' identity using a relational developmental systems theory framework, which led to the expectation that identity development is linked to both the reduction of risk behaviors and the promotion of African American adolescents' healthy development. Different personological theories�
Brittian, Aerika S.
Towards a Conceptual Basis for Understanding Developmental Guidance and Counselling Model
ERIC Educational Resources Information Center
Comprehensive developmental guidance and counselling model is a 21st century school counselling intervention emphasizing school guidance curriculum, individual student planning, responsive counselling services and system support. The aims of this paper therefore, were to articulately define comprehensive guidance and counselling within the�
Aluede, Oyaziwo; Imonikhe, Justina; Afen-Akpaida, Justina
QSAR models of developmental toxicity (devtox) have met with limited regulatory acceptance due to the use of ill-defined endpoints, lack of biological interpretability, and poor model performance. More generally, the lack of biological inference of many QSAR models is often due t...
Friendship estimation model for social robots to understand human relationships
This work reports the friendship estimation model we designed for social robots that understand human social relationships. Our interactive robot autonomously interacts with humans with its human-like body properties, and as a result, induces the humans' friendly group behavior upon direct interaction. Based on these features, as well as inspired by a survey in psychology research on friendship, we propose
Takayuki Kanda; Hiroshi Ishiguro
Ecological Approaches to Understanding Human Crowding.
ERIC Educational Resources Information Center
Characteristics of the ecological approach to perception are presented. The affordance concept and its relevance is emphasized. Human crowding is discussed in affordance terms. There is a comparison given between present affordance analysis and ecological analysis. (Author/SA)
Baron, Reuben M.
Visual Analytic for Improving Human Terrain Understanding.
National Technical Information Service (NTIS)
Visual analytics are a growing area of research within the Department of Defense that targets the effective interleaving of analytical reasoning with interactive interfaces. Capitalizing on the human capacity for spatial reasoning, visual analytics enhanc...
E. Heilman J. Richardson M. Mittrick T. Hanratty
Understanding African American Adolescents' Identity Development: A Relational Developmental Systems Perspective
This article examines the development of African American adolescents� identity using a relational developmental systems theory framework, which led to the expectation that identity development is linked to both the reduction of risk behaviors and the promotion of African American adolescents� healthy development. Different personological theories of identity development were discussed, including Erikson�s theory of psychosocial development and Marcia�s theory of identity statuses. Developmental systems theory was used to further the literature on African American adolescents� identity development, by integrating various views of identity development as they pertain to these youth. Furthermore, the formation of many aspects of identity may be an important coping and resilience process for such youth. In addition, directions for future research are discussed, including a consideration of the complexity of diversity that exists within the African American adolescent population, and a call for more longitudinal assessments of identity development is presented.
Brittian, Aerika S.
Understanding human-induced climate change
NASA Astrophysics Data System (ADS)
There are many difficulties in communicating the urgency of human-induced climate change. In this paper we focus on two. The assumption of no climate change is pervasive in scientific circles and elsewhere, unless proven otherwise, in spite of global studies to the contrary. This exceedingly conservative approach produces Type II errors: a false negative. It wrongly concludes there is no human influence, when there is. This kind of error is very common! And it is perpetrated by climate scientists. It is exacerbated by shortcomings in datasets (length, inhomogeneities) and models (inability to replicate the phenomenon of interest (hurricanes, tornadoes, thunderstorms, monsoons, blocking) owing to grid sizes and numerical constraints, and model errors.) The result is a gross understatement of the human influence on climate. The second issue is distinguishing weather versus climate. We ask "even if there is a well determined climate change, say 2�C increase in global mean temperature 50 years from now, how would the weather be different?" In fact much of the time the weather would be familiar - except perhaps occurring at different times of the year. The 2012 "June temperatures in March" in the United States is a case in point. Hence the main impacts occur when records are broken in summer, when conditions go well outside of any previously experienced, as has happened in the United States in 2011 and 2012, and Russia in 2010. The resulting widespread droughts, heat waves and wildfires have been devastating. Breaking records at other times of the year can leave a mark (warmer winters, more bugs etc) but seem more benign although not to ecosystems.
Trenberth, K. E.
Understanding complexity in the human brain
Although the ultimate aim of neuroscientific enquiry is to gain an understanding of the brain and how its workings relate to the mind, the majority of current efforts are largely focused on small questions using increasingly detailed data. However, it might be possible to successfully address the larger question of mind�brain mechanisms if the cumulative findings from these neuroscientific studies are coupled with complementary approaches from physics and philosophy. The brain, we argue, can be understood as a complex system or network, in which mental states emerge from the interaction between multiple physical and functional levels. Achieving further conceptual progress will crucially depend on broad-scale discussions regarding the properties of cognition and the tools that are currently available or must be developed in order to study mind�brain mechanisms.
Bassett, Danielle S.; Gazzaniga, Michael S.
Identifying developmental toxicity pathways for a subset of ToxCast chemicals using human embryonic stem cells and metabolomics
Metabolomics analysis was performed on the supernatant of human embryonic stem (hES) cell cultures exposed to a blinded subset of 11 chemicals selected from the chemical library of EPA's ToxCast Trade-Mark-Sign chemical screening and prioritization research project. Metabolites from hES cultures were evaluated for known and novel signatures that may be indicative of developmental toxicity. Significant fold changes in endogenous metabolites were detected for 83 putatively annotated mass features in response to the subset of ToxCast chemicals. The annotations were mapped to specific human metabolic pathways. This revealed strong effects on pathways for nicotinate and nicotinamide metabolism, pantothenate and CoA biosynthesis, glutathione metabolism, and arginine and proline metabolism pathways. Predictivity for adverse outcomes in mammalian prenatal developmental toxicity studies used ToxRefDB and other sources of information, including Stemina Biomarker Discovery's predictive DevTox Registered-Sign model trained on 23 pharmaceutical agents of known developmental toxicity and differing potency. The model initially predicted developmental toxicity from the blinded ToxCast compounds in concordance with animal data with 73% accuracy. Retraining the model with data from the unblinded test compounds at one concentration level increased the predictive accuracy for the remaining concentrations to 83%. These preliminary results on a 11-chemical subset of the ToxCast chemical library indicate that metabolomics analysis of the hES secretome provides information valuable for predictive modeling and mechanistic understanding of mammalian developmental toxicity. -- Highlights: Black-Right-Pointing-Pointer We tested 11 environmental compounds in a hESC metabolomics platform. Black-Right-Pointing-Pointer Significant changes in secreted small molecule metabolites were observed. Black-Right-Pointing-Pointer Perturbed mass features map to pathways critical for normal development and pregnancy. Black-Right-Pointing-Pointer Arginine, proline, nicotinate, nicotinamide and glutathione pathways were affected.
Kleinstreuer, N.C., E-mail: email@example.com [NCCT, US EPA, RTP, NC 27711 (United States); Smith, A.M.; West, P.R.; Conard, K.R.; Fontaine, B.R. [Stemina Biomarker Discovery, Inc., Madison, WI 53719 (United States)] [Stemina Biomarker Discovery, Inc., Madison, WI 53719 (United States); Weir-Hauptman, A.M. [Covance, Inc., Madison, WI 53704 (United States)] [Covance, Inc., Madison, WI 53704 (United States); Palmer, J.A. [Stemina Biomarker Discovery, Inc., Madison, WI 53719 (United States)] [Stemina Biomarker Discovery, Inc., Madison, WI 53719 (United States); Knudsen, T.B.; Dix, D.J. [NCCT, US EPA, RTP, NC 27711 (United States)] [NCCT, US EPA, RTP, NC 27711 (United States); Donley, E.L.R. [Stemina Biomarker Discovery, Inc., Madison, WI 53719 (United States)] [Stemina Biomarker Discovery, Inc., Madison, WI 53719 (United States); Cezar, G.G. [Stemina Biomarker Discovery, Inc., Madison, WI 53719 (United States) [Stemina Biomarker Discovery, Inc., Madison, WI 53719 (United States); University of Wisconsin-Madison, Madison, WI 53706 (United States)
Developmental changes in the transcriptome of human cerebral cortex tissue: long noncoding RNA transcripts.
The human neocortex is characterized by protracted developmental intervals of synaptogenesis and myelination, which allow for an extended period of learning. The molecular basis of these and other postnatal developmental changes in the human cerebral cortex remain incompletely understood. Recently, a new large class of mammalian genes, encoding nonmessenger, long nonprotein-coding ribonucleic acid (lncRNA) molecules has been discovered. Although their function remains uncertain, numerous lncRNAs have primate-specific sequences and/or show evidence of rapid, lineage-specific evolution, making them potentially relevant to the evolution of unique human neural properties. To examine the hypothesis that lncRNA expression varies with age, potentially paralleling known developmental trends in synaptogenesis, myelination, and energetics, we quantified levels of nearly 6000 lncRNAs in 36 surgically resected human neocortical samples (primarily derived from temporal cortex) spanning infancy to adulthood. Our analysis identified 8 lncRNA genes with distinct developmental expression patterns. These lncRNA genes contained anthropoid-specific exons, as well as splice sites and polyadenylation signals that resided in primate-specific sequences. To our knowledge, our study is the first to describe developmental expression profiles of lncRNA in surgically resected in vivo human brain tissue. Future analysis of the functional relevance of these transcripts to neural development and energy metabolism is warranted. PMID:23377288
Lipovich, Leonard; Tarca, Adi L; Cai, Juan; Jia, Hui; Chugani, Harry T; Sterner, Kirstin N; Grossman, Lawrence I; Uddin, Monica; Hof, Patrick R; Sherwood, Chet C; Kuzawa, Christopher W; Goodman, Morris; Wildman, Derek E
Constructive Criticism and Social Lies: A Developmental Sequence for Understanding Honesty and Kindness in Social Interactions
To provide an assessment of the dynamics of development of complex sociomoral concepts, a 10-step scale for assessing development of understanding relations between honesty and kindness was administered under multiple assessment conditions to 113 youths who were 9�20 years old. The sequence proved to be both scalable and reliable, even while level of understanding varied greatly as a function of
Susie D. Lamborn; Kurt W. Fischer; Sandra Pipp
Temperament and parenting: implications for understanding developmental pathways to conduct disorder.
This article reviews research linking a number of temperamental vulnerabilities that can place a child at risk for developing severe conduct problems. One primary focus of this article is on how certain temperamental vulnerabilities can disrupt normal developmental processes during early childhood, such as the development of emotional regulatory abilities and the development of the affective components of conscience, to place a child at risk for acting in an antisocial and aggressive manner. A second focus of the paper is on how the quality of parenting that a child experiences interacts with the child's temperament to either increase or decrease the child's risk for problem behavior. Identifying those parent factors that can enhance the development of children at risk for conduct problems due to temperamental vulnerabilities could be very important for enhancing interventions for children with severe behavior problems. PMID:16402009
Robison, S D; Frick, P J; Sheffield Morris, A
Complex developmental patterns of histone modifications associated with the human ?-globin switch in primary cells
1) Objective: The regulation of the ?-globin switch remains undetermined and understanding this mechanism has important benefits for clinical and basic science. Histone modifications regulate gene expression and this study determines the presence of three important histone modifications across the ?-globin locus in erythroblasts with different ?-like globin expression profiles. Understanding the chromatin associated with weak ? gene expression in bone marrow cells is an important objective with the goal of ultimately inducing postnatal expression of ?-globin to cure ?-hemoglobinopathies. 2) Methods: These studies use uncultured primary fetal and bone marrow erythroblasts and human ES cell derived primitive-like erythroblasts. Chromatin immunoprecipitation (ChIP) with antibodies against modified histones reveals DNA associated with such histones. Precipitated DNA is quantitated by real time PCR for 40 sites across the locus. 3) Results: The distribution of histone modifications differs at each developmental stage. The most highly expressed genes at each stage are embedded within large domains of modifications associated with expression (H3ac and H3K4me2). Moderately expressed genes have H3ac and H3K4me2 in the immediate area around the gene. H3K9me2, a mark associated with gene suppression, is present at the ? and ? genes in bone marrow cells, suggesting active suppression of these genes. 4) Conclusion: This study reveals complex patterns of histone modifications associated with highly expressed, moderately expressed and unexpressed genes. Activation of ? postnatally will likely require extensive modification of the histones in a large domain around the ? genes.
Hsu, Mei; Richardson, Christine A.; Olivier, Emmanuel; Bouhassira, Eric E.; Lowrey, Christopher H.; Fiering, Steven
Cell-Cycle Control of Developmentally Regulated Transcription Factors Accounts for Heterogeneity in Human Pluripotent Cells
Summary Heterogeneity within pluripotent stem cell (PSC) populations is indicative of dynamic changes that occur when cells drift between different states. Although the role of metastability in PSCs is unclear, it appears to reflect heterogeneity in cell signaling. Using the Fucci cell-cycle indicator system, we show that elevated expression of developmental regulators in G1 is a major determinant of heterogeneity in human embryonic stem cells. Although signaling pathways remain active throughout the cell cycle, their contribution to heterogeneous gene expression is restricted to G1. Surprisingly, we identify dramatic changes in the levels of global 5-hydroxymethylcytosine, an unanticipated source of epigenetic heterogeneity that is tightly linked to cell-cycle progression and the expression of developmental regulators. When we evaluated gene expression in differentiating cells, we found that cell-cycle regulation of developmental regulators was maintained during lineage specification. Cell-cycle regulation of developmentally regulated transcription factors is therefore an inherent feature of the mechanisms underpinning differentiation.
Singh, Amar M.; Chappell, James; Trost, Robert; Lin, Li; Wang, Tao; Tang, Jie; Wu, Hao; Zhao, Shaying; Jin, Peng; Dalton, Stephen
"Unwilling" versus "Unable": Chimpanzees' Understanding of Human Intentional Action
ERIC Educational Resources Information Center
Understanding the intentional actions of others is a fundamental part of human social cognition and behavior. An important question is therefore whether other animal species, especially our nearest relatives the chimpanzees, also understand the intentional actions of others. Here we show that chimpanzees spontaneously (without training) behave�
Call, Josep; Hare, Brian; Carpenter, Malinda; Tomasello, Michael
The Developmental Progression of Understanding of Mind during a Hiding Game
ERIC Educational Resources Information Center
In this longitudinal study, 52 typically developing preschoolers engaged in a hiding game with their mothers when children were 42-, 54-, and 66-months old. Children's understanding of mind, positive affect, and engagement with the task were rated, and mothers' utterances were coded for role and content. Analyses confirmed that some facets of�
Nelson, P. Brooke; Adamson, Lauren B.; Bakeman, Roger
Developmental Sequences in Children's Understanding of Death with Implications for Counselors.
ERIC Educational Resources Information Center
Proposes children develop an understanding about death in an orderly sequence progressing from total unawareness in early childhood to the point of logical consideration in terms of cause and effect. Discusses implications for parents, teachers, and counselors for helping children deal with death. (RC)
Matter, Darryl E.; Matter, Roxana Marie
Teaching Algorithmic Problem Solving or Conceptual Understanding: Role of Developmental Level, Mental Capacity, and Cognitive Style.
ERIC Educational Resources Information Center
It has been shown previously that many students solve chemistry problems using only algorithmic strategies and do not understand the chemical concepts on which the problems are based. It is plausible to suggest that if the information is presented in differing formats the cognitive demand of a problem changes. The main objective of this study�
Niaz, Mansoor; Robinson, William R.
Fibrillin1 in Human Cartilage: Developmental Expression and Formation of Special Banded Fibers
SUMMARY The molecular basis for Marfan's syndrome (MS), a heritable disorder of con- nective tissue, is now known to reside in mutations in FBN1, the gene for fibrillin-1. Classic phenotypic manifestations of MS include several skeletal abnormalities associated primarily with overgrowth of long bones. As a first step towards understanding how mutations in FBN1 result in skeletal abnormalities, the developmental
Douglas R. Keene; C. Diana Jordan; Dieter P. Reinhardt; Catherine C. Ridgway; Robert N. Ono; Glen M. Corson; Margaret Fairhurst; Michael D. Sussman; Vincent A. Memoli; Lynn Y. Sakai
Different forms of human odor memory: a developmental study
Recognizing odors is an important biological function, both in the animal kingdom as well as for humans. It has been debated whether there exist different forms of human odor memory. For verbal memory, the concept of recollection and familiarity for conscious and unconscious recognition is widely accepted. Here we introduce a similar model for human odor memory. We use a
Johann P. Lehrner; Peter Walla; Matthias Laska; L�der Deecke
Mental retardation genes in drosophila: New approaches to understanding and treating developmental brain disorders
Drosophila melanogaster is emerging as a valuable genetic model system for the study of mental retardation (MR). MR genes are remarkably similar between humans and fruit flies. Cognitive behavioral assays can detect reductions in learning and memory in flies with mutations in MR genes. Neuroanatomical methods, including some at single-neuron resolu- tion, are helping to reveal the cellular bases of
Linda L. Restifo
The Juvenile Transition: A Developmental Switch Point in Human Life History
ERIC Educational Resources Information Center
This paper presents a new perspective on the transition from early to middle childhood (i.e., human juvenility), investigated in an integrative evolutionary framework. Juvenility is a crucial life history stage, when social learning and interaction with peers become central developmental functions; here it is argued that the "juvenile transition"�
Del Giudice, Marco; Angeleri, Romina; Manera, Valeria
Autonomous developmental control of human embryonic globin gene switching in transgenic mice
The mechanisms by which expression of the {beta}-like globin genes are developmentally regulated are under intense investigation. The temporal control of human embryonic ({epsilon}) globin expression was analyzed. A 3.7-kilobase (kb) fragment that contained the entire human {epsilon}-globin gene was linked to a 2.5-kb cassette of the locus control region (LCR), and the developmental time of expression of this construct was studied in transgenic mice. The human {epsilon}-globin transgene was expressed in yolk sac-derived primitive erythroid cells, but not in fetal liver or bone marrow-derived definitive erythroid cells. The absence of {epsilon} gene expression in definitive erythroid cells suggests that the developmental regulation of the {epsilon}-globin gene depends only on the presence of the LCR and the {epsilon}-globin gene itself (that is, an autonomous negative control mechanism). The autonomy of {epsilon}-globin gene developmental control distinguishes it from the competitive mechanism of regulation of {gamma} and {beta}-globin genes, and therefore, suggests that at least two distinct mechanisms function in human hemoglobin switching.
Raich, N.; Enver, T.; Nakamoto, B.; Josephson, B.; Papayannopoulou, T.; Stamatoyannopoulos, G. (Univ. of Washington, Seattle (USA))
The Workshop on the Qualitative and Quantitative Comparability of Human and Animal Developmental Neurotoxicity was convened by the U.S. Environmental Protection Agency (EPA) and the National Institute on Drug Abuse to address issues related to when testing should be required, wha...
Curriculum Guide for a Course on Human Sexuality and the Developmentally Disabled. Working Paper No. 80.
ERIC Educational Resources Information Center
Presented is a model of a graduate course for students from a variety of disciplines on human sexuality and the developmentally disabled. Course objectives are said to include competencies in designing and administering programs to foster appropriate sexual behavior and in assisting parents to deal with their children's sexuality. Seven resources�
Steinbock, Elizabeth A.; Brummer, Esther R.
Methods to identify and characterize developmental neurotoxicity for human health risk assessment. II: neuropathology.
Neuropathologic assessment of chemically induced developmental alterations in the nervous system for regulatory purposes is a multifactorial, complex process. This calls for careful qualitative and quantitative morphologic study of numerous brains at several developmental stages in rats. Quantitative evaluation may include such basic methods as determination of brain weight and dimensions as well as the progressively more complex approaches of linear, areal, or stereologic measurement of brain sections. Histologic evaluation employs routine stains (such as hematoxylin and eosin), which can be complemented by a variety of special and immunohistochemical procedures. These brain studies are augmented by morphologic assessment of selected peripheral nervous system structures. Studies of this nature require a high level of technical skill as well as special training on the part of the pathologist. The pathologist should have knowledge of normal microscopic neuroanatomy/neuronal circuitry and an understanding of basic principles of developmental neurobiology, such as familiarity with the patterns of physiologic or programmed cell de
Garman, R H; Fix, A S; Jortner, B S; Jensen, K F; Hardisty, J F; Claudio, L; Ferenc, S
Evidence for Developmental Programming of Cerebral Laterality in Humans
Adverse fetal environments are associated with depression, reduced cognitive ability and increased stress responsiveness in later life, but underlying mechanisms are unknown. Environmental pressures on the fetus, resulting from variations in placental function and maternal nutrition, health and stress might alter neurodevelopment, promoting the development of some brain regions over others. As asymmetry of cerebral activity, with greater right hemisphere activity, has been associated with psychopathology, we hypothesized that regional specialization during fetal life might be reflected persistently in the relative activity of the cerebral hemispheres. We tested this hypothesis in 140 healthy 8�9 year-old children, using tympanic membrane temperature to assess relative blood flow to the cerebral hemispheres at rest and following psychosocial stress (Trier Social Stress Test for Children). Their birth weight and placental weight had already been measured when their mothers took part in a previous study of pregnancy outcomes. We found that children who had a smaller weight at birth had evidence of greater blood flow to the right hemisphere than to the left hemisphere (r?=??.09, P?=?.29 at rest; r?=??.18, P?=?.04 following stress). This finding was strengthened if the children had a relatively low birth weight for their placental weight (r?=??.17, P?=?.05 at rest; r?=??.31, P?=?.0005 following stress). Our findings suggest that lateralization of cerebral activity is influenced persistently by early developmental experiences, with possible consequences for long-term neurocognitive function.
Jones, Alexander; Osmond, Clive; Godfrey, Keith M.; Phillips, David I. W.
Understanding the relationships between air quality and human health
Although there has been substantial progress in improving ambient air quality in the United States, atmospheric concentrations of ozone and fine particulate matter (PM2.5) continue to exceed the National Ambient Air Quality Standards in many locations. Consequently, a large portion of the U.S. population continues to be exposed to unhealthful levels of ozone and fine particles. This issue of EM, entitled 'Understanding the relationships between air quality and human health' presents a series of articles that focus on the relationships between air quality and human health - what we know so far and the challenges that remain. Their titles are: Understanding the effects of air pollution on human health; Assessing population exposures in studies of human health effects of PM2.5; Establishing a national environmental public health tracking network; Linking air quality and exposure models; and On alert: air quality forecasting and health advisory warnings.
S.T. Rao
A human pluripotent stem cell platform for assessing developmental neural toxicity screening
A lack of affordable and effective testing and screening procedures mean surprisingly little is known about the health hazards of many of the tens of thousands of chemicals in use in the world today. The recent rise in the number of children affected by neurological disorders such as autism has stirred valuable debate about the role chemicals play in our daily life, highlighting the need for improved methods of assessing chemicals for developmental neural toxicity. Current methods of testing chemicals for developmental neural toxicity include animal testing with rats or mice and in vitro testing using cultured primary cells or cell lines. Here, we review the current state of neural toxicity screening, analyze the limitations of these methods and, under the National Institutes of Health's new Microphysiological Systems initiative, describe a human pluripotent stem cell-based platform for developmental neural toxicity screens.
The Various Roles of Animal Models in Understanding Human Development
ERIC Educational Resources Information Center
In this article, the authors take a very conservative view of the contribution of animal models to an understanding of human development. We do not think that homologies can be readily documented with even our most closely related relatives' behavior and psychological functioning. The major contribution of animal models is their provision of food�
Gottlieb, Gilbert; Lickliter, Robert
The contribution of novel brain imaging techniques to understanding the neurobiology of mental retardation and developmental disabilities.
Studying the biological mechanisms underlying mental retardation and developmental disabilities (MR/DD) is a very complex task. This is due to the wide heterogeneity of etiologies and pathways that lead to MR/DD. Breakthroughs in genetics and molecular biology and the development of sophisticated brain imaging techniques during the last decades have facilitated the emergence of a field called Behavioral Neurogenetics. Behavioral Neurogenetics focuses on studying genetic diseases with known etiologies that are manifested by unique cognitive and behavioral phenotypes. In this review, we describe the principles of magnetic resonance imaging (MRI) techniques, including structural MRI, functional MRI, and diffusion tensor imaging (DTI), and how they are implemented in the study of Williams (WS), velocardiofacial (VCFS), and fragile X (FXS) syndromes. From WS we learn that dorsal stream abnormalities can be associated with visuospatial deficits; VCFS is a model for exploring the molecular and brain pathways that lead to psychiatric disorders for which subjects with MR/DD are at increased risk; and finally, findings from multimodal imaging techniques show that aberrant frontal-striatal connections are implicated in the executive function and attentional deficits of subjects with FXS. By deciphering the molecular pathways and brain structure and function associated with cognitive deficits, we will gain a better understanding of the pathophysiology of MR/DD, which will eventually make possible more specific treatments for this population. PMID:16240408
Gothelf, Doron; Furfaro, Joyce A; Penniman, Lauren C; Glover, Gary H; Reiss, Allan L
Developmental potential of human oocytes reconstructed by transferring somatic cell nuclei into polyspermic zygote cytoplasm
The generation of patient-specific nuclear transfer embryonic stem cells holds huge promise in modern regenerative medicine and cell-based drug discovery. Since human in vivo matured oocytes are not readily available, human therapeutic cloning is developing slowly. Here, we investigated for the first time whether human polyspermic zygotes could support preimplantation development of cloned embryos. Our results showed that polyspermic zygotes could be used as recipients for human somatic cell nuclear transfer (SCNT). The preimplantation developmental potential of SCNT embryos from polyspermic zygotes was limited to the 8-cell stage. Since ES cell lines can be derived from single blastomeres, these results may have important significance for human ES cells derived by SCNT. In addition, confocal images demonstrated that all of the SCNT embryos that failed to cleave showed abnormal microtubule organization. The results of the present study suggest that polyspermic human zygotes could be used as a potential source of recipient cytoplasm for SCNT.
Fan, Yong; Chen, Xinjie; Luo, Yumei; Chen, Xiaolin; Li, Shaoying; Huang, Yulin [Institute of Gynecology and Obstetrics, The Third Affiliated Hospital of Guangzhou Medical College, Duobao Road 63, Guangzhou, Guangdong (China)] [Institute of Gynecology and Obstetrics, The Third Affiliated Hospital of Guangzhou Medical College, Duobao Road 63, Guangzhou, Guangdong (China); Sun, Xiaofang, E-mail: firstname.lastname@example.com [Institute of Gynecology and Obstetrics, The Third Affiliated Hospital of Guangzhou Medical College, Duobao Road 63, Guangzhou, Guangdong (China)] [Institute of Gynecology and Obstetrics, The Third Affiliated Hospital of Guangzhou Medical College, Duobao Road 63, Guangzhou, Guangdong (China)
The significance of the subplate for evolution and developmental plasticity of the human brain
The human life-history is characterized by long development and introduction of new developmental stages, such as childhood and adolescence. The developing brain had important role in these life-history changes because it is expensive tissue which uses up to 80% of resting metabolic rate (RMR) in the newborn and continues to use almost 50% of it during the first 5 postnatal years. Our hominid ancestors managed to lift-up metabolic constraints to increase in brain size by several interrelated ecological, behavioral and social adaptations, such as dietary change, invention of cooking, creation of family-bonded reproductive units, and life-history changes. This opened new vistas for the developing brain, because it became possible to metabolically support transient patterns of brain organization as well as developmental brain plasticity for much longer period and with much greater number of neurons and connectivity combinations in comparison to apes. This included the shaping of cortical connections through the interaction with infant's social environment, which probably enhanced typically human evolution of language, cognition and self-awareness. In this review, we propose that the transient subplate zone and its postnatal remnant (interstitial neurons of the gyral white matter) probably served as the main playground for evolution of these developmental shifts, and describe various features that makes human subplate uniquely positioned to have such a role in comparison with other primates.
Judas, Milos; Sedmak, Goran; Kostovic, Ivica
Cell-cycle control of developmentally regulated transcription factors accounts for heterogeneity in human pluripotent cells.
Heterogeneity within pluripotent stem cell (PSC) populations is indicative of dynamic changes that occur when cells drift between different states. Although the role of metastability in PSCs is unclear, it appears to reflect heterogeneity in cell signaling. Using the Fucci cell-cycle indicator system, we show that elevated expression of developmental regulators in G1 is a major determinant of heterogeneity in human embryonic stem cells. Although signaling pathways remain active throughout the cell cycle, their contribution to heterogeneous gene expression is restricted to G1. Surprisingly, we identify dramatic changes in the levels of global 5-hydroxymethylcytosine, an unanticipated source of epigenetic heterogeneity that is tightly linked to cell-cycle progression and the expression of developmental regulators. When we evaluated gene expression in differentiating cells, we found that cell-cycle regulation of developmental regulators was maintained during lineage specification. Cell-cycle regulation of developmentally regulated transcription factors is therefore an inherent feature of the mechanisms underpinning differentiation. PMID:24371808
Singh, Amar M; Chappell, James; Trost, Robert; Lin, Li; Wang, Tao; Tang, Jie; Wu, Hao; Zhao, Shaying; Jin, Peng; Dalton, Stephen
Developmental stages in human embryos: revised and new measurements.
The staging of human embryos, as distinct from seriation, depends on a morphological scheme devised by Streeter and completed by O'Rahilly, who proposed the term Carnegie stages. To avoid misconceptions and errors, and to place new findings in perspective, it is necessary to summarize the essentials of the Carnegie system: (1) Twenty-three stages cover the embryonic period, i. e. the first 8 postfertilizational weeks of development. (2) The system is based on internal as well as external features, and the use of only external criteria is subject to serious limitations. For example, precise delineation of stages 19-23 and of the embryonic-fetal transition depends on histological examination. (3) Prenatal measurements are not an integral component of the staging system, and hence a stage should never be assigned merely on the basis of embryonic length. A 20-mm embryo, for example, could belong to any of three stages. Measurements, however, are important for the assessment of age, and very few measurements are available for staged embryos. Presented here and based on accurate staging are the maximum diameter of the chorionic sac, the crown-heel length, the greatest length exclusive of the lower limbs, the biparietal diameter, the head circumference, the length of the hindbrain, the total length of the brain, and the lengths of the limbs as well as of their segments, including the foot length. (4) Prenatal ages are also not an integral part of the staging system and hence a stage should never be assigned merely on the basis of prenatal age. Ages, however, are of clinical importance and their estimate has been rendered more precise by accurate timing of fertilization followed by ultrasonography. Prenatal age is postfertilizational and hence some 2 weeks less than the postmenstrual interval. The term gestational age is ambiguous and should be discarded. Presented here is a new graph showing proposed estimates of age in relation to stages and based on current information. PMID:20185898
O'Rahilly, Ronan; M�ller, Fabiola
Understanding Dyslexia in Children through Human Development Theories
Dyslexia is a specific learning disability that is neurological in origin, with an estimated overall worldwide prevalence of 5�10% of the population. It is characterised by difficulties in reading, accuracy, fluency, spelling and decoding abilities. The majority of publications reviewed indicated that screening is performed at the preschool level. Screening can also be conducted at birth or the first year of life. Understanding human development theory, for example, Piaget�s human development theory, may help determine at which stage of childhood development dyslexia is more detectable, and therefore guide the management of this disability. The objective of this review is to provide a brief and updated overview of dyslexia and its management in children through human development issues.
Al-Shidhani, Thuraya Ahmed; Arora, Vinita
MBD2 contributes to developmental silencing of the human ?-globin gene
During erythroid development the embryonic ?-globin gene becomes silenced as erythropoiesis shifts from the yolk sac to the fetal liver where ?-globin gene expression predominates. Previous studies have shown that the ?-globin gene is autonomously silenced through promoter proximal cis-acting sequences in adult erythroid cells. We have shown a role for the methylcytosine binding domain protein 2 (MBD2) in the developmental silencing of the avian embryonic ?-globin and human fetal ?-globin genes. To determine the roles of MBD2 and DNA methylation in human ?-globin gene silencing, transgenic mice containing all sequences extending from the 5? hypersensitive site 5 (HS5) of the ?-globin locus LCR to the human ?-globin gene promoter were generated. These mice show correct developmental expression and autonomous silencing of the transgene. Either the absence of MBD2 or treatment with the DNA methyltransferase inhibitor 5-azacytidine increases ?-globin transgene expression by 15�20 fold in adult mice. Adult mice containing the entire human ?-globin locus also show an increase in expression of both the ?-globin gene transgene and endogenous ?Y and ?H1 genes in the absence of MBD2. These results indicate the human ?-globin gene is subject to multilayered silencing mediated in part by MBD2.
Rupon, Jeremy W.; Wang, Shou Zhen; Gnanapragasam, Merlin; Labropoulos, Stefanos; Ginder, Gordon D.
A Developmental Shift from Positive to Negative Connectivity in Human Amygdala-Prefrontal Circuitry
Recent human imaging and animal studies highlight the importance of frontoamygdala circuitry in the regulation of emotional behavior and its disruption in anxiety-related disorders. While tracing studies have suggested changes in amygdala-cortical connectivity through the adolescent period in rodents, less is known about the reciprocal connections within this circuitry across human development, when these circuits are being fine-tuned and substantial changes in emotional control are observed. The present study examined developmental changes in amygdala-prefrontal circuitry across the ages of 4 to 22 years using task-based functional magnetic resonance imaging (fMRI). Results suggest positive amygdala-prefrontal connectivity in early childhood that switches to negative functional connectivity during the transition to adolescence. Amygdala-mPFC functional connectivity was significantly positive (greater than zero) among participants younger than ten, whereas functional connectivity was significantly negative (less than zero) among participants ten years and older, over and above the effect of amygdala reactivity. The developmental switch in functional connectivity was paralleled by a steady decline in amygdala reactivity. Moreover, the valence switch might explain age-related improvement in task performance and a developmentally normative decline in anxiety. Initial positive connectivity followed by a valence shift to negative connectivity provides a neurobiological basis for regulatory development and may present novel insight into a more general process of developing regulatory connections.
Gee, Dylan G.; Humphreys, Kathryn L.; Flannery, Jessica; Goff, Bonnie; Telzer, Eva H.; Shapiro, Mor; Hare, Todd A.; Bookheimer, Susan Y.; Tottenham, Nim
Engraftable human neural stem cells respond to developmental cues, replace neurons, and express foreign genes.
Stable clones of neural stem cells (NSCs) have been isolated from the human fetal telencephalon. These self-renewing clones give rise to all fundamental neural lineages in vitro. Following transplantation into germinal zones of the newborn mouse brain they participate in aspects of normal development, including migration along established migratory pathways to disseminated central nervous system regions, differentiation into multiple developmentally and regionally appropriate cell types, and nondisruptive interspersion with host progenitors and their progeny. These human NSCs can be genetically engineered and are capable of expressing foreign transgenes in vivo. Supporting their gene therapy potential, secretory products from NSCs can correct a prototypical genetic metabolic defect in neurons and glia in vitro. The human NSCs can also replace specific deficient neuronal populations. Cryopreservable human NSCs may be propagated by both epigenetic and genetic means that are comparably safe and effective. By analogy to rodent NSCs, these observations may allow the development of NSC transplantation for a range of disorders. PMID:9831031
Flax, J D; Aurora, S; Yang, C; Simonin, C; Wills, A M; Billinghurst, L L; Jendoubi, M; Sidman, R L; Wolfe, J H; Kim, S U; Snyder, E Y
Variation at Genes Influencing Facial Morphology Are Not Associated with Developmental Imprecision in Human Faces
Facial asymmetries are commonly used as a proxy for human developmental imprecision resulting from inbreeding, and thus reduced genetic heterozygosity. Several environmental factors influence human facial asymmetry (e.g., health care, parasites), but the generalizability of findings on genetic stressors has been limited in humans by sample characteristics (island populations, endogamy) and indirect genetic assessment (inference from pedigrees). In a sample of 3215 adult humans from the Rotterdam Study, we therefore studied the relationship of facial asymmetry, estimated from nine mid-facial landmarks, with genetic variation at 102 single nucleotide polymorphism (SNP) loci recently associated with facial shape variation. We further tested whether the degree of individual heterozygosity is negatively correlated with facial asymmetry. An ANOVA tree regression did not identify any SNP relating to either fluctuating asymmetry or total asymmetry. In a general linear model, only age and sex�but neither heterozygosity nor any SNP previously reported to covary with facial shape�was significantly related to total or fluctuating asymmetry of the midface. Our study does not corroborate the common assumption in evolutionary and behavioral biology that morphological asymmetries reflect heterozygosity. Our results, however, may be affected by a relatively small degree of inbreeding, a relatively stable environment, and an advanced age in the Rotterdam sample. Further large-scale genetic studies, including gene expression studies, are necessary to validate the genetic and developmental origin of morphological asymmetries.
Windhager, Sonja; Schaschl, Helmut; Schaefer, Katrin; Mitteroecker, Philipp; Huber, Susanne; Wallner, Bernard; Fieder, Martin
Simplified ontologies allowing comparison of developmental mammalian gene expression
Model organisms represent an important resource for understanding the fundamental aspects of mammalian biology. Mapping of biological phenomena between model organisms is complex and if it is to be meaningful, a simplified representation can be a powerful means for comparison. The Developmental eVOC ontologies presented here are simplified orthogonal ontologies describing the temporal and spatial distribution of developmental human and mouse anatomy. We demonstrate the ontologies by identifying genes showing a bias for developmental brain expression in human and mouse.
Kruger, Adele; Hofmann, Oliver; Carninci, Piero; Hayashizaki, Yoshihide; Hide, Winston
Methods to identify and characterize developmental neurotoxicity for human health risk assessment. I: behavioral effects.
Alterations in nervous system function after exposure to a developmental neurotoxicant may be identified and characterized using neurobehavioral methods. A number of methods can evaluate alterations in sensory, motor, and cognitive functions in laboratory animals exposed to toxicants during nervous system development. Fundamental issues underlying proper use and interpretation of these methods include a) consideration of the scientific goal in experimental design, b) selection of an appropriate animal model, c) expertise of the investigator, d) adequate statistical analysis, and e) proper data interpretation. Strengths and weaknesses of the assessment methods include sensitivity, selectivity, practicality, and variability. Research could improve current behavioral methods by providing a better understanding of the relationship between alterations in motor function and changes in the underlying structure of these systems. Research is also needed to develop simple and sensitive assays for use in screening assessments of sensory and cognitive function. Assessment methods are being developed to examine other nervous system functions, including social behavior, autonomic processes, and biologic rhythms. Social behaviors are modified by many classes of developmental neurotoxicants and hormonally active compounds that may act either through neuroendocrine mechanisms or by directly influencing brain morphology or neurochemistry. Autonomic and thermoregulatory functions have been the province of physiologists and neurobiologists rather than toxicologists, but this may change as developmental neurotoxicology progresses and toxicologists apply techniques developed by other disciplines to examine changes in function after toxicant exposure.
Cory-Slechta, D A; Crofton, K M; Foran, J A; Ross, J F; Sheets, L P; Weiss, B; Mileson, B
Invited commentary: Improving the human condition through rigorous, applied developmental research.
This invited commentary describes the shifts toward a more positive characterization of young people over the past 30�years. After describing the new focus on the strengths of young people and the need to ground our understanding in developmental science, it provides an overview of the major contributions of this special issue to the field of positive youth development. Taken together, the groundbreaking work on the 4-H study demonstrates the increasing methodological and statistical sophistication of this strength-based approach. PMID:24723049
Rhodes, Jean E
A Developmental Stage-Specific Switch from DAZL to BOLL Occurs during Fetal Oogenesis in Humans, but Not Mice
The Deleted in Azoospermia gene family encodes three germ cell-specific RNA-binding proteins (DAZ, DAZL and BOLL) that are essential for gametogenesis in diverse species. Targeted disruption of Boll in mice causes male-specific spermiogenic defects, but females are apparently fertile. Overexpression of human BOLL promotes the derivation of germ cell-like cells from genetically female (XX), but not male (XY) human ES cells however, suggesting a functional role for BOLL in regulating female gametogenesis in humans. Whether BOLL is expressed during oogenesis in mammals also remains unclear. We have therefore investigated the expression of BOLL during fetal oogenesis in humans and mice. We demonstrate that BOLL protein is expressed in the germ cells of the human fetal ovary, at a later developmental stage than, and almost mutually-exclusive to, the expression of DAZL. Strikingly, BOLL is downregulated, and DAZL re-expressed, as primordial follicles form, revealing BOLL expression to be restricted to a narrow window during fetal oogenesis. By quantifying the extent of co-expression of DAZL and BOLL with markers of meiosis, we show that this window likely corresponds to the later stages of meiotic prophase I. Finally, we demonstrate that Boll is also transiently expressed during oogenesis in the fetal mouse ovary, but is simultaneously co-expressed within the same germ cells as Dazl. These data reveal significant similarities and differences between the expression of BOLL homologues during oogenesis in humans and mice, and raise questions as to the validity of the Boll-/- mouse as a model for understanding BOLL function during human oogenesis.
He, Jing; Stewart, Kayleigh; Kinnell, Hazel L.; Anderson, Richard A.; Childs, Andrew J.
NTP-CERHR Monograph on the Potential Human Reproductive and Developmental Effects of Propylene Glycol (PG).
The National Toxicology Program (NTP) Center for the Evaluation of Risks to Human Reproduction (CERHR) conducted an evaluation of the potential for propylene glycol (PG) to cause adverse effects on reproduction and development in humans. PG was selected for evaluation because of the potential for widespread human exposure through its use in food, tobacco, pharmaceutical products, cosmetics, various paints and coatings and as an antifreeze and de-icing solution. PG is a small, hydroxy-substituted hydrocarbon used as a chemical intermediate in the production of unsaturated polyester resins and in the production of plasticizers. The results of this evaluation on PG are published in an NTP-CERHR monograph which includes: 1) the NTP Brief, 2) the Expert Panel Report on the Reproductive and Developmental Toxicity of Propylene Glycol, and 3) public comments received on the Expert Panel Report. As stated in the NTP Brief, the NTP reached the following conclusions regarding the possible effects of exposure to PG on human development and reproduction. There is negligible concern for adverse developmental and reproductive effects in humans at current, proposed, or estimated exposure levels. There is no direct evidence that exposure of people to PG adversely affects reproduction or development. Studies in pregnant laboratory animals at oral doses of PG greater than 1,200 mg/kg body weight/ day and up to 10,400 mg/kg body weight/day in mice, did not produce developmental toxicity in offspring. In a continuous breeding study, no effects on fertility were observed in male or female mice at doses up to 10,100 mg/kg body weight/day in drinking water. The pharmacokinetics of PG indicates that the lack of adverse effects observed in laboratory animals is relevant to humans. The rate-limiting step in PG metabolism is conversion to the more toxic lactaldehyde product by alcohol dehydrogenase. Studies indicate that this enzyme saturates in humans at doses 8-10- fold lower than in rats and rabbits, thus affording less toxicity in humans. It is estimated that the average daily intake of PG from food products in the US is 34 mg/kg body weight/day for a 70 kg person, which is over 300 -fold lower than the highest dose tested in laboratory animals. NTP-CERHR monographs are transmitted to federal and state agencies, interested parties, and the public and are available in electronic PDF format on the CERHR web site (http://cerhr.niehs.nih.gov) and in printed text or CD-ROM from the CERHR (National Institute of Environmental Health Sciences, P.O. Box 12233, MD EC-32, Research Triangle Park, NC; fax: 919-316-4511). PMID:15995735
The Decline of Cross-Species Intersensory Perception in Human Infants: Underlying Mechanisms & Its Developmental Persistence
The current study investigated the mechanisms underlying the developmental decline in cross-species intersensory matching first reported by Lewkowicz and Ghazanfar (2006) and whether the decline persists into later development. Experiment 1 investigated whether infants can match monkey vocalizations to asynchronously presented faces and found that neither 4�6 nor 8�10 month-old infants did. Experiment 1 also assessed whether a visual processing deficit may account for the developmental decline in cross-species matching and indicated that it does not because both age groups discriminated silent monkey calls. Experiment 2 investigated whether an auditory processing deficit may account for the decline and indicated that it does not because 8�10 month-old infants discriminated the acoustic versions of the calls. Finally, Experiment 3 asked whether the developmental decline persists into later development by testing cross-species intersensory matching in 12- and 18-month-old infants and showed that it does because neither age group made intersensory matches. Together, these results bolster prior evidence of a decline in cross-species intersensory integration in early human development and shed new light on the mechanisms underlying it.
Lewkowicz, David J.; Sowinski, Ryan; Place, Silvia
Mitochondrial function in the human oocyte and embryo and their role in developmental competence.
The role of mitochondria as a nexus of developmental regulation in mammalian oogenesis and early embryogenesis is emerging from basic research in model species and from clinical studies in infertility treatments that require in vitro fertilization and embryo culture. Here, mitochondrial bioenergetic activities and roles in calcium homeostasis, regulation of cytoplasmic redox state, and signal transduction are discussed with respect to outcome in general, and as possible etiologies of chromosomal defects, maturation and fertilization failure in human oocytes, and as causative factors in early human embryo demise. At present, the ability of mitochondria to balance ATP supply and demand is considered the most critical factor with respect to fertilization competence for the oocyte and developmental competence for the embryo. mtDNA copy number, the timing of mtDNA replication during oocyte maturation, and the numerical size of the mitochondrial complement in the oocyte are evaluated with respect to their relative contribution to the establishment of developmental competence. Rather than net cytoplasmic bioenergetic capacity, the notion of functional compartmentalization of mitochondria is presented as a means by which ATP may be differentially supplied and localized within the cytoplasm by virtue of stage-specific changes in mitochondrial density and potential (??m). Abnormal patterns of calcium release and sequestration detected at fertilization in the human appear to have coincident effects on levels of mitochondrial ATP generation. These aberrations are not uncommon in oocytes obtained after ovarian hyperstimulation for in vitro fertilization. The possibility that defects in mitochondrial calcium regulation or bioenergetic homeostasis could have negative downstream development consequences, including imprinting disorders, is discussed in the context of signaling pathways and cytoplasmic redox state. PMID:20933103
Van Blerkom, Jonathan
A comparative developmental study of impulsivity in rats and humans: the role of reward sensitivity.
The present study was conducted to test the hypothesis that differences in reward sensitivity between adolescents and adults account for differences in impulsivity. In a comparative study, we examined preferences for various concentrations of sucrose solutions as an operational measure of reward sensitivity in adolescent and adult rats and humans. Humans also completed self-report measures of impulsivity and reward sensitivity. There was some indication that adolescents preferred sweeter solutions compared to adults. Also, adolescents scored substantially higher on impulsivity. However, adolescents and adults did not differ in self-ratings of reward sensitivity and personality scores were not consistently related to sucrose preferences. The data highlight some of the benefits and issues that arise with developing comparative measures in humans and animals. Future comparative research using alternative behavioral paradigms is necessary to determine if and how changes in reward sensitivity influence developmental shifts in impulsivity. PMID:15251916
Vaidya, Jatin G; Grippo, Angela J; Johnson, Alan Kim; Watson, David
Developmental trajectories during adolescence in males and females: a cross-species understanding of underlying brain changes
Adolescence is a transitional period between childhood and adulthood that encompasses vast changes within brain systems that parallel some, but not all, behavioral changes. Elevations in emotional reactivity and reward processing follow an inverted U shape in terms of onset and remission, with the peak occurring during adolescence. However, cognitive processing follows a more linear course of development. This review will focus on changes within key structures and will highlight the relationships between brain changes and behavior, with evidence spanning from functional magnetic resonance imaging (fMRI) in humans to molecular studies of receptor and signaling factors in animals. Adolescent changes in neuronal substrates will be used to understand how typical and atypical behaviors arise during adolescence. We draw upon clinical and preclinical studies to provide a neural framework for defining adolescence and its role in the transition to adulthood.
Brenhouse, Heather C.; Andersen, Susan L.
Human Ntera2 cells as a predictive in vitro test system for developmental neurotoxicity.
Developmental neurotoxicity (DNT) of environmental chemicals is a serious threat to human health. Current DNT testing guidelines propose investigations in rodents, which require large numbers of animals. With regard to the "3Rs" (reduction, replacement, and refinement) of animal testing, alternative testing strategies are needed in order to refine and reduce animal experiments and allow faster and less expensive screening. The goal of this study was to establish components for a human cell-based test system to assess DNT potential of chemicals at an early stage of brain development. A human neural precursor cell line should be tested for suitability for semi-automated high-throughput DNT screening. We established assays suitable for detecting disturbances in two basic processes of brain development in 96-well scale: neuronal differentiation and migration using the human Ntera2 (NT2) cell line. We assessed the effects of four test compounds with well-established DNT potential in comparison with three compounds without specific DNT potential. We found that human NT2 cell cultures treated with the morphogen, retinoic acid, imitate neuronal differentiation, and migration in vitro. The developmental neurotoxicants methylmercury chloride, sodium arsenite, sodium valproate, and methylazoxymethanol significantly reduced the expression of the neuronal marker ?-tubulin type III and decreased the migration distance in developing NT2 cells. Both endpoints, differentiation and migration, can be read out directly in a standard fluorescence plate reader, enabling high-throughput screening. We conclude that NT2 cell tests are likely to become valuable components of a human cell-based modular in vitro DNT test systems. PMID:23917397
Stern, Michael; Gierse, Andrea; Tan, Saime; Bicker, Gerd
Understanding the Diversity: A Taxonomy for Postsecondary Education Programs and Services for Students with Intellectual and Developmental Disabilities
ERIC Educational Resources Information Center
The number of postsecondary education (PSE) programs for individuals with intellectual and developmental disabilities (IDD) has been steadily growing over the last few decades. There has been little public information regarding these programs and schools. Consequently, students, families, and researchers alike lack details about the various�
McEathron, Mary A.; Beuhring, Trisha; Maynard, Amelia; Mavis, Ann
The Contribution of Novel Brain Imaging Techniques to Understanding the Neurobiology of Mental Retardation and Developmental Disabilities
ERIC Educational Resources Information Center
Studying the biological mechanisms underlying mental retardation and developmental disabilities (MR/DD) is a very complex task. This is due to the wide heterogeneity of etiologies and pathways that lead to MR/DD. Breakthroughs in genetics and molecular biology and the development of sophisticated brain imaging techniques during the last decades�
Gothelf, Doron; Furfaro, Joyce A.; Penniman, Lauren C.; Glover, Gary H.; Reiss, Allan L.
Model organisms inform the search for the genes and developmental pathology underlying malformations of the human hindbrain
Congenital malformations the human hindbrain, including the cerebellum, are poorly understood largely because their recognition is a relatively recent advance for imaging diagnostics. Cerebellar malformations are the most obvious and best characterized hindbrain malformations due to their relative ease to view by MRI and the recent identification of several causative genes1. Malformations of the pons and medulla have also been described both in isolation and in association with cerebellar malformations2. Although little is understood regarding the specific developmental pathologies underlying hindbrain malformations in humans, much is known regarding the mechanisms and genes driving hindbrain development in vertebrate model organisms. Thus, studies in vertebrate models provide a developmental framework in which to categorize human hindbrain malformations and serve to inform our thinking regarding disrupted developmental processes and candidate genes. Here we survey the basic principles of vertebrate hindbrain development and integrate our current knowledge of human hindbrain malformations into this framework.
Aldinger, Kimberly A.; Elsen, Gina E.; Prince, Victoria E.; Millen, Kathleen J.
Polybrominated Diphenyl Ethers Induce Developmental Neurotoxicity in a Human in Vitro Model: Evidence for Endocrine Disruption
Background Polybrominated diphenyl ethers (PBDEs) are persistent and bioaccumulative flame retardants, which are found in rising concentrations in human tissues. They are of concern for human health because animal studies have shown that they possess the potential to be developmentally neurotoxic. Objective Because there is little knowledge of the effects of PBDEs on human brain cells, we investigated their toxic potential for human neural development in vitro. Moreover, we studied the involvement of thyroid hormone (TH) disruption in the effects caused by PBDEs. Methods We used the two PBDE congeners BDE-47 and BDE-99 (0.1�10 ?M), which are most prominent in human tissues. As a model of neural development, we employed primary fetal human neural progenitor cells (hNPCs), which are cultured as neurospheres and mimic basic processes of brain development in vitro: proliferation, migration, and differentiation. Results PBDEs do not disturb hNPC proliferation but decrease migration distance of hNPCs. Moreover, they cause a reduction of differentiation into neurons and oligodendrocytes. Simultaneous exposure with the TH receptor (THR) agonist triiodothyronine rescues these effects on migration and differentiation, whereas the THR antagonist NH-3 does not exert an additive effect. Conclusion PBDEs disturb development of hNPCs in vitro via endocrine disruption of cellular TH signaling at concentrations that might be of relevance for human exposure.
Schreiber, Timm; Gassmann, Kathrin; Gotz, Christine; Hubenthal, Ulrike; Moors, Michaela; Krause, Guido; Merk, Hans F.; Nguyen, Ngoc-Ha; Scanlan, Thomas S.; Abel, Josef; Rose, Christine R.; Fritsche, Ellen
How evolutionary principles improve the understanding of human health and disease
An appreciation of the fundamental principles of evolutionary biology provides new insights into major diseases and enables an integrated understanding of human biology and medicine. However, there is a lack of awareness of their importance amongst physicians, medical researchers, and educators, all of whom tend to focus on the mechanistic (proximate) basis for disease, excluding consideration of evolutionary (ultimate) reasons. The key principles of evolutionary medicine are that selection acts on fitness, not health or longevity; that our evolutionary history does not cause disease, but rather impacts on our risk of disease in particular environments; and that we are now living in novel environments compared to those in which we evolved. We consider these evolutionary principles in conjunction with population genetics and describe several pathways by which evolutionary processes can affect disease risk. These perspectives provide a more cohesive framework for gaining insights into the determinants of health and disease. Coupled with complementary insights offered by advances in genomic, epigenetic, and developmental biology research, evolutionary perspectives offer an important addition to understanding disease. Further, there are a number of aspects of evolutionary medicine that can add considerably to studies in other domains of contemporary evolutionary studies.
Gluckman, Peter D; Low, Felicia M; Buklijas, Tatjana; Hanson, Mark A; Beedle, Alan S
The progeny of Legionella pneumophila in human macrophages shows unique developmental traits.
The Gram-negative bacterium Legionella pneumophila is an intracellular parasite of amoebae and an accidental human pathogen that causes a noncommunicable atypical pneumonia known as Legionnaires' disease (LD). In some mammalian cells (e.g. HeLa), L.�pneumophila follows a biphasic developmental cycle, differentiating between a replicative form that actively multiplies intracellularly, and a mature infectious form (MIF) that emerges as progeny. To date, it is not known whether the L.�pneumophila progenies that emerge from amoebae and human macrophages reach similar developmental stages. Here, we demonstrate that in relation to the fully differentiated and highly infectious MIFs that emerge from amoebae, the L.�pneumophila progeny that emerges from macrophages is morphologically undifferentiated, less resistant to antibiotics and less able to initiate infections. However, the L.�pneumophila progeny from macrophages did not show any defects in intracellular growth. We thus concluded that macrophage infection with L.�pneumophila yields a low number of bona fide MIFs. Because MIFs are the transmissive forms of L.�pneumophila produced in vivo, our results showing that they are not efficiently produced in cultured macrophages provide an initial insight into why LD is not communicable. PMID:24206397
Abdelhady, Hany; Gardu�o, Rafael A
Flavonoids as Antioxidants and Developmental Regulators: Relative Significance in Plants and Humans
Phenylpropanoids, particularly flavonoids have been recently suggested as playing primary antioxidant functions in the responses of plants to a wide range of abiotic stresses. Furthermore, flavonoids are effective endogenous regulators of auxin movement, thus behaving as developmental regulators. Flavonoids are capable of controlling the development of individual organs and the whole-plant; and, hence, to contribute to stress-induced morphogenic responses of plants. The significance of flavonoids as scavengers of reactive oxygen species (ROS) in humans has been recently questioned, based on the observation that the flavonoid concentration in plasma and most tissues is too low to effectively reduce ROS. Instead, flavonoids may play key roles as signaling molecules in mammals, through their ability to interact with a wide range of protein kinases, including mitogen-activated protein kinases (MAPK), that supersede key steps of cell growth and differentiation. Here we discuss about the relative significance of flavonoids as reducing agents and signaling molecules in plants and humans. We show that structural features conferring ROS-scavenger ability to flavonoids are also required to effectively control developmental processes in eukaryotic cells.
Brunetti, Cecilia; Di Ferdinando, Martina; Fini, Alessio; Pollastri, Susanna; Tattini, Massimiliano
Developmental changes in the spatial organization of neurons in the neocortex of humans and common chimpanzees.
In adult humans the prefrontal cortex possesses wider minicolumns and more neuropil space than other cortical regions. These aspects of prefrontal cortex architecture, furthermore, are increased in comparison to chimpanzees and other great apes. In order to determine the developmental appearance of this human cortical specialization, we examined the spatial organization of neurons in four cortical regions (frontal pole [Brodmann's area 10], primary motor [area 4], primary somatosensory [area 3b], and prestriate visual cortex [area 18]) in chimpanzees and humans from birth to approximately the time of adolescence (11 years of age). Horizontal spacing distance (HSD) and gray level ratio (GLR) of layer III neurons were measured in Nissl-stained sections. In both human and chimpanzee area 10, HSD was significantly higher in the postweaning specimens compared to the preweaning ones. No significant age-related differences were seen in the other regions in either species. In concert with other recent studies, the current findings suggest that there is a relatively slower maturation of area 10 in both humans and chimpanzees as compared to other cortical regions, and that further refinement of the spatial organization of neurons within this prefrontal area in humans takes place after the postweaning periods included here. PMID:23839595
Teffer, Kate; Buxhoeveden, Daniel P; Stimpson, Cheryl D; Fobbs, Archibald J; Schapiro, Steven J; Baze, Wallace B; McArthur, Mark J; Hopkins, William D; Hof, Patrick R; Sherwood, Chet C; Semendeferi, Katerina
Safety and side effects of ayahuasca in humans--an overview focusing on developmental toxicology.
Despite being relatively well studied from a botanical, chemical, and (acute) pharmacological perspective, little is known about the possible toxic effects of ayahuasca (an hallucinogenic brew used for magico-ritual purposes) in pregnant women and in their children, and the potential toxicity of long-term ayahuasca consumption. It is the main objective of the present text to do an overview of the risks and possible toxic effects of ayahuasca in humans, reviewing studies on the acute ayahuasca administration to humans, on the possible risks associated with long-term consumption by adults and adolescents, and on the possible toxic effects on pregnant animals and in their offspring. Acute ayahuasca administration, as well as long-term consumption of this beverage, does not seem to be seriously toxic to humans. Although some nonhuman developmental studies suggested possible toxic effects of ayahuasca or of some of its alkaloids, the limited human literature on adolescents exposed to ayahuasca as early as in the uterus reports no serious toxic effects of the ritual consumption of the brew. Researchers must take caution when extrapolating nonhuman data to humans and more data are needed in basic and human research before a definite opinion can be made regarding the possible toxic effects of ayahuasca in pregnant women and in their children. PMID:23662333
dos Santos, Rafael Guimar�es
Understanding and Predicting Human Behavior for Social Communities
NASA Astrophysics Data System (ADS)
Over the last years, with the rapid advance in technology, it is becoming increasingly feasible for people to take advantage of the devices and services in the surrounding environment to remain "connected" and continuously enjoy the activity they are engaged in, be it sports, entertainment, or work. Such a ubiquitous computing environment will allow everyone permanent access to the Internet anytime, anywhere and anyhow [1]. Nevertheless, despite the evolution of services, social aspects remain in the roots of every human behavior and activities. Great examples of such phenomena are online social networks, which engage users in a way never seen before in the online world. At the same time, being aware and communicating context is a key part of human interaction and is a particularly powerful concept when applied to a community of users where services can be made more personalized and useful. Altogether, harvesting context to reason and learn about user behavior will further enhance the future multimedia vision where services can be composed and customized according to user context. Moreover, it will help us to understand users in a better way.
Simoes, Jose; Magedanz, Thomas
Priming 3D cultures of human mesenchymal stromal cells toward cartilage formation via developmental pathways.
The field of regenerative medicine has increasingly recognized the importance to be inspired by developmental processes to identify signaling pathways crucial for 3D organogenesis and tissue regeneration. Here, we aimed at recapitulating the first events occurring during limb development (ie, cell condensation and expansion of an undifferentiated mesenchymal cell population) to prime 3D cultures of human bone marrow-derived mesenchymal stromal/stem cells (hBM-MSC) toward the chondrogenic route. Based on embryonic development studies, we hypothesized that Wnt3a and fibroblast growth factor 2 (FGF2) induce hBM-MSC to proliferate in 3D culture as an undifferentiated pool of progenitors (defined by clonogenic capacity and expression of typical markers), retaining chondrogenic potential upon induction by suitable morphogens. hBM-MSC were responsive to Wnt signaling in 3D pellet culture, as assessed by significant upregulation of main target genes and increase of unphosphorylated ?-catenin levels. Wnt3a was able to induce a five-fold increase in the number of proliferating hBM-MSC (6.4% vs. 1.3% in the vehicle condition), although total DNA content of the 3D construct was decreasing over time. Preconditioning with Wnt3a improved transforming growth factor-?1 mediated chondrogenesis (30% more glycosaminoglycans/cell in average). In contrast to developmental and 2D MSC culture models, FGF2 antagonized the Wnt-mediated effects. Interestingly, the CD146? subpopulation was found to be more responsive to Wnt3a. The presented data indicate a possible strategy to prime 3D cultures of hBM-MSC by invoking a "developmental engineering" approach. The study also identifies some opportunities and challenges to cross-fertilize skeletal development models and 3D hBM-MSC culture systems. PMID:23777290
Centola, Matteo; Tonnarelli, Beatrice; Sch�ren, Stefan; Glaser, Nicolas; Barbero, Andrea; Martin, Ivan
Developmental trajectory of the endocannabinoid system in human dorsolateral prefrontal cortex
Background Endocannabinoids provide control over cortical neurotransmission. We investigated the developmental expression of key genes in the endocannabinoid system across human postnatal life and determined whether they correspond to the development of markers for inhibitory interneurons, which shape cortical development. We used microarray with qPCR validation and in situ hybridisation to quantify mRNA for the central endocannabinoid receptor CB1R, endocannabinoid synthetic enzymes (DAGL? for 2-arachidonylglycerol [2-AG] and NAPE-PLD for anandamide), and inactivating enzymes (MGL and ABHD6 for 2-AG and FAAH for anandamide) in human dorsolateral prefrontal cortex (39?days - 49?years). Results CB1R mRNA decreases until adulthood, particularly in layer II, after peaking between neonates and toddlers. DAGL? mRNA expression is lowest in early life and adulthood, peaking between school age and young adulthood. MGL expression declines after peaking in infancy, while ABHD6 increases from neonatal age. NAPE-PLD and FAAH expression increase steadily after infancy, peaking in adulthood. Conclusions Stronger endocannabinoid regulation of presynaptic neurotransmission in both supragranular and infragranular cortical layers as indexed through higher CB1R mRNA may occur within the first few years of human life. After adolescence, higher mRNA levels of the anandamide synthetic and inactivating enzymes NAPE-PLD and FAAH suggest that a late developmental switch may occur where anandamide is more strongly regulated after adolescence than earlier in life. Thus, expression of key genes in the endocannabinoid system changes with maturation of cortical function.
Annual Research Review: A developmental psychopathology approach to understanding callous-unemotional traits in children and adolescents with serious conduct problems.
Recent research has suggested that the presence of significant levels of callous-unemotional (CU) traits designates a clinically important and etiologically distinct subgroup of children and adolescents with serious conduct problems. Based on this research, CU traits have been included in the most recent revision of the Diagnostic and Statistical Manual of Mental Disorders - 5th Edition (DSM-5; American Psychiatric Association, 2013) - as a specifier for the diagnosis of conduct disorder. In this review, we attempt to understand CU traits within a developmental psychopathological framework. Specifically, we summarize research on the normal development of the prosocial emotions of empathy and guilt (i.e., conscience) and we illustrate how the development of CU traits can be viewed as the normal development of conscience gone awry. Furthermore, we review research on the stability of CU traits across different developmental periods and highlight factors that can influence this stability. Finally, we highlight the implications of this developmental psychopathological framework for future etiological research, for assessment and diagnostic classification, and for treatment of children with serious conduct problems. PMID:24117854
Frick, Paul J; Ray, James V; Thornton, Laura C; Kahn, Rachel E
Allelic diversity in human developmental neurogenetics: insights into biology and disease
One of the biggest challenges in neuroscience is illuminating the architecture of developmental brain disorders, which include structural malformations of the brain and nerves, intellectual disability, epilepsy, as well as some psychiatric conditions like autism and potentially schizophrenia. Ongoing gene identification reveals a great diversity of genetic causes underlying abnormal brain development, illuminating new biochemical pathways often not suspected based on genetic studies in other organisms. Our greater understanding of genetic disease also shows the complexity of �allelic diversity�, in which distinct mutations in a given gene can cause a wide range of distinct diseases or other phenotypes. These diverse alleles not only provide a platform for discovery of critical protein-protein interactions in a genetic fashion, but also illuminate the likely genetic architecture of as yet poorly characterized neurological disorders.
Walsh, Christopher A.; Engle, Elizabeth C.
NTP-CERHR monograph on the potential human reproductive and developmental effects of styrene.
The National Toxicology Program (NTP) Center for the Evaluation of Risks to Human Reproduction (CERHR) conducted an evaluation of the potential for styrene to cause adverse effects on reproduction and development in humans. Styrene was selected for evaluation because of (1) public concern about styrene exposure and (2) recently available exposure studies. Styrene (ethenylbenzene; CAS RN: 100-42-5) is a high production volume chemical (a million pounds or more produced each year) and is used in the production of polystyrene resins and as a co-polymer with acrylonitrile and 1,3-butadiene. Styrene is found in items such as foam cups, dental fillings, matrices for ion exchange filters, construction materials, and boats. It is also used in protective coatings, reinforced glass fiber, agricultural products, and as a food additive. The Food and Drug Administration regulates styrene for use as a synthetic flavoring substance and as a component of polymers in contact with dry food, and also regulates the amount of residual styrene monomer allowed in polystyrene intended for use in contact with food. The public can be exposed to styrene by ingesting food or drink that has been in contact with styrene polymers or through inhalation of polluted air and cigarette smoke. The results of this evaluation on styrene are published in a NTP-CERHR monograph that includes: (1) the NTP Brief, (2) the Expert Panel Report on the Reproductive and Developmental Toxicity of Styrene, and (3) public comments received on the expert panel report. The NTP reached its conclusion of negligible concern for adverse developmental and reproductive effects resulting from styrene exposures in humans based on information presented in the NTP-CERHR Expert Panel Report on the Reproductive and Developmental Toxicity of Styrene and the public comments on that report. This conclusion is based on estimated exposures in both the general population and in people whose occupation involves styrene exposure. The expert panel estimated styrene exposure in the general U.S. population to be less than 0.3 microg/kg body weight/day in nonsmokers and 3.51 and 2.86 microg/kg body weight/day in smokers ages 12-19 years and 20-70 years, respectively. Average occupational exposures are estimated to range from 1,400-52,000 microg/kg body weight/day. Studies in humans show no evidence that occupational exposures or exposure of the general population to styrene adversely affect reproduction or development. Further, data from experimental animal studies show no adverse reproductive or developmental effects at styrene doses far above human exposure levels. The NTP will transmit the NTP-CERHR monograph on styrene to federal and state agencies, interested parties, and the public and it will be available in electronic PDF format on the CERHR web site http://cerhr.niehs.nih.gov and in printed text or CD-ROM from the CERHR: M.D. Shelby, Ph.D., Director, CERHR, NIEHS, P.O. Box 12233, MD EC-32, Research Triangle Park, NC 27709, 919-541-3455 [phone], 919-316-4511 [fax], email@example.com [email]. PMID:17180169
Human Science for Human Freedom? Piaget's Developmental Research and Foucault's Ethical Truth Games
ERIC Educational Resources Information Center
The construction of the modern subject and the pursuit of human freedom and autonomy, as well as the practice of human science has been pivotal in the development of modern education. But for Foucault, the subject is only the effect of discourses and power-knowledge arrangements, and modern human science is part of the very arrangement that has�
Zhao, Guoping
Developmental changes in vasoactive intestinal polypeptide immunoreactivity in the human paravertebral ganglia.
Vasoactive intestinal polypeptide (VIP) belongs to the glucagon-secretin family of polypeptides and possesses numerous functions. Its existence in the mammalian central and peripheral nervous system has been widely documented. However, there are no reports on the developmental aspects of VIP-like immunoreactivity (VIP-IR) in the human postganglionic sympathetic neurons. In this study the availability and distribution of vasoactive intestinal polypeptide has been localized in human stellate ganglia neurons and nerve fibers from neonates, children and adults using the immunohistochemical method. In neonatal ganglia VIP-immunoreactive postganglionic neurons were revealed in a marked population compared to others age-groups. These nerve cells are both small and large in size and are distributed in small clusters or singly in the area of ganglia sections. In children, VIP-IR in ganglionic neurons decreases. In adult stellate ganglia, VIP-immunoreactive postganglionic neurons rarely occur. In ganglia of an individual human only varicosities of VIP-positive nerve fibers were observed. These results provide the age-dependent reduction of VIP-like immunoreactivity in human stellate ganglia neurons and suggest the different role of this peptide in the function of sympathetic ganglia neurons with age. PMID:10609054
Roudenok, V; K�hnel, W; Rogov, Y; Nerovnja, A
Building a Database of Developmental Neurotoxitants: Evidence from Human and Animal Studies
EPA?s program for the screening and prioritization of chemicals for developmental neurotoxicity (DNT) necessitates the generation of a list of chemicals that are known mammalian developmental neurotoxicants. This chemical list will be used to evaluate the sensitivity, reliability...
Crystal structure of human Mre11: understanding tumorigenic mutations.
Mre11 plays an important role in repairing damaged DNA by cleaving broken ends and by providing a platform for other DNA repair proteins. Various Mre11 mutations have been identified in several types of cancer. We have determined the crystal structure of the human Mre11 core (hMre11), which contains the nuclease and capping domains. hMre11 dimerizes through the interfaces between loop ?3-?3 from one Mre11 and loop ?4-?5 from another Mre11, and between loop ?2-?3 from one Mre11 and helices ?2 and ?3 from another Mre11, and assembles into a completely different dimeric architecture compared with bacterial or archaeal Mre11 homologs. Nbs1 binds to the region containing loop ?2-?3 which participates in dimerization. The hMre11 structure in conjunction with biochemical analyses reveals that many tumorigenic mutations are primarily associated with Nbs1 binding and partly with nuclease activities, providing a framework for understanding how mutations inactivate Mre11. PMID:22078559
Park, Young Bong; Chae, Jina; Kim, Young Chang; Cho, Yunje
NSDL National Science Digital Library
This set of videos, authored by Salman Khan of the Khan Academy, provides worked developmental math examples from the Monterey Institute. These start at a fairly basic level and would prepare a student for the set of Algebra I worked examples. After completion, students should gain a fundamental understanding of mathematics and future studies.
Khan, Salman
Measuring and Understanding Public Opinion on Human Evolution
NASA Astrophysics Data System (ADS)
The theory of evolution has long generated controversy in American society, but Americans' attitudes about human evolution are often neglected in studies of "culture wars" and the nature of mass belief systems more generally (Berkman and Plutzer 2010; Freeland and Houston 2009). Gallup and other survey organizations have polled about evolution, but offered limited response categories that mask complexity in public opinion (Bishop 2006; Moore 2008). The main problems concerning the leading survey questions about evolution are: first, questions measure only a single dimension, thus they ignore the potential for multidimensionality in people's attitudes. Second, depending on question wording and response options, the results of public opinion surveys vary by polling groups. This is an example of measurement error which misleads the interpretation and impression of American public opinion on the origin of humankind. A number of studies have analyzed Americans' beliefs about evolution and hypothesized about the influential effects of several factors (Deckman 2002; Mazur 2005; Mooney 2005; Miller et al. 2006; Newport 2006; Forrest 2007;Nisbet and Goidel 2007;Scott 2009). However, there remains a lack of complete understanding of what Americans know and believe about human evolution. Given the salience of this issue and the significant influence of public opinion on policy-making in America (Page and Shapiro 1992; Stimson 2004; Newport 2004), the measurement error and explanation of polling results on controversial issues related to this topic are in need of clarification. In this study, I address these deficiencies with analyses of data from a 2008 national survey by Harris Interactive (n= 4,626) that included numerous measures of factual knowledge and beliefs about evolution. The items offer more nuanced response options than the standard three-category question asked for decades by the Gallup poll. The Harris survey also had multiple measures of religiosity and the Right-Wing-Authoritarianism personality scale. Using this uniquely rich data set I develop a model of the nature and organization of these various attitude structures. Data analyses on explanation of public acceptance or rejection of evolution indicate that the Right-wing-authoritarianism and religious factors including beliefs in God's existence, views of the Bible, frequency of church attendance, and Evangelical Protestant affiliation are significant predictors across all measures. Scientific literacy, genetic science knowledge and familiarity, in general, are another contributor to prediction of public attitudes toward evolution. On measurement validity, consistency of measurement and responses are examined. The results from data analyses reveal the effect of question wording form and context is at play. In addition, public beliefs and knowledge about evolution are not consistent, rather contradictory, and are susceptible to framing effects. As scholars of public opinion warn, we should avoid the referendum view of polls on controversial issues (Schuman 2008; Moore 2008; Bishop 2005). Findings from this research lead to two key conclusions. First, great caution should be taken interpreting poll results on human evolution. Second, for better understanding of public opinion on this issue, a modified standard question should replace the current question.
Gwon, Misook
Myosin Va is developmentally regulated and expressed in the human cerebellum from birth to old age
Myosin Va functions as a processive, actin-based motor molecule highly enriched in the nervous system, which transports and/or tethers organelles, vesicles, and mRNA and protein translation machinery. Mutation of myosin Va leads to Griscelli disease that is associated with severe neurological deficits and a short life span. Despite playing a critical role in development, the expression of myosin Va in the central nervous system throughout the human life span has not been reported. To address this issue, the cerebellar expression of myosin Va from newborns to elderly humans was studied by immunohistochemistry using an affinity-purified anti-myosin Va antibody. Myosin Va was expressed at all ages from the 10th postnatal day to the 98th year of life, in molecular, Purkinje and granular cerebellar layers. Cerebellar myosin Va expression did not differ essentially in localization or intensity from childhood to old age, except during the postnatal developmental period. Structures resembling granules and climbing fibers in Purkinje cells were deeply stained. In dentate neurons, long processes were deeply stained by anti-myosin Va, as were punctate nuclear structures. During the first postnatal year, myosin Va was differentially expressed in the external granular layer (EGL). In the EGL, proliferating prospective granule cells were not stained by anti-myosin Va antibody. In contrast, premigratory granule cells in the EGL stained moderately. Granule cells exhibiting a migratory profile in the molecular layer were also moderately stained. In conclusion, neuronal myosin Va is developmentally regulated, and appears to be required for cerebellar function from early postnatal life to senescence.
Souza, C.C.R.; Dombroski, T.C.D.; Machado, H.R.; Oliveira, R.S.; Rocha, L.B.; Rodrigues, A.R.A.; Neder, L.; Chimelli, L.; Correa, V.M.A.; Larson, R.E.; Martins, A.R.
Myosin Va is developmentally regulated and expressed in the human cerebellum from birth to old age.
Myosin Va functions as a processive, actin-based motor molecule highly enriched in the nervous system, which transports and/or tethers organelles, vesicles, and mRNA and protein translation machinery. Mutation of myosin Va leads to Griscelli disease that is associated with severe neurological deficits and a short life span. Despite playing a critical role in development, the expression of myosin Va in the central nervous system throughout the human life span has not been reported. To address this issue, the cerebellar expression of myosin Va from newborns to elderly humans was studied by immunohistochemistry using an affinity-purified anti-myosin Va antibody. Myosin Va was expressed at all ages from the 10th postnatal day to the 98 th year of life, in molecular, Purkinje and granular cerebellar layers. Cerebellar myosin Va expression did not differ essentially in localization or intensity from childhood to old age, except during the postnatal developmental period. Structures resembling granules and climbing fibers in Purkinje cells were deeply stained. In dentate neurons, long processes were deeply stained by anti-myosin Va, as were punctate nuclear structures. During the first postnatal year, myosin Va was differentially expressed in the external granular layer (EGL). In the EGL, proliferating prospective granule cells were not stained by anti-myosin Va antibody. In contrast, premigratory granule cells in the EGL stained moderately. Granule cells exhibiting a migratory profile in the molecular layer were also moderately stained. In conclusion, neuronal myosin Va is developmentally regulated, and appears to be required for cerebellar function from early postnatal life to senescence. PMID:23558932
Souza, C C R; Dombroski, T C D; Machado, H R; Oliveira, R S; Rocha, L B; Rodrigues, A R A; Neder, L; Chimelli, L; Corr�a, V M A; Larson, R E; Martins, A R
Induced pluripotent stem cell-derived neuron as a human model for testing environmentally induced developmental neurotoxicity
Induced pluripotent stem cell-derived neurons as a human model for testing environmentally induced developmental neurotoxicity Ingrid L. Druwe1, Timothy J. Shafer2, Kathleen Wallace2, Pablo Valdivia3 ,and William R. Mundy2. 1University of North Carolina, Curriculum in Toxicology...
Impairments in Monkey and Human Face Recognition in 2-Year-Old Toddlers with Autism Spectrum Disorder and Developmental Delay
ERIC Educational Resources Information Center
Face recognition impairments are well documented in older children with Autism Spectrum Disorders (ASD); however, the developmental course of the deficit is not clear. This study investigates the progressive specialization of face recognition skills in children with and without ASD. Experiment 1 examines human and monkey face recognition in�
Chawarska, Katarzyna; Volkmar, Fred
Current testing methods for developmental neurotoxicity (DNT) make evaluation of the effects of large numbers of chemicals impractical and prohibitively expensive. As such, we are evaluating human neural progenitor cells (NPCs) as a screen for DNT. ReNcell CX (ReN CX) cells are a...
Human relevance framework evaluation of a novel rat developmental toxicity mode of action induced by sulfoxaflor.
Abstract Sulfoxaflor (CAS# 946578-00-3) is a novel active substance with insecticidal properties mediated via its agonism on the highly abundant insect nicotinic acetylcholine receptor (nAChR). In developmental and reproductive toxicity studies, gestational exposure caused fetal abnormalities (primarily limb contractures) and reduced neonatal survival in rats, but not rabbits, following high-dose dietary exposure. Sulfoxaflor induced these effects via a novel mode of action (MoA) mediated by the fetal-type muscle nAChR with the following key events: (1) binding to the receptor, (2) agonism on the receptor, causing (3) sustained muscle contracture in the near-term fetus and neonatal offspring. This sustained muscle contracture results in misshapen limbs, bent clavicles, and reduced diaphragm function, which compromises respiration in neonatal rats at birth, reducing their survival. This review evaluates the weight of evidence for this MoA based upon the Bradford Hill criteria, includes a cross-comparison of applied and internal doses in a variety of in vitro, ex vivo, and in vivo study designs, examines alternative MoAs, and applies a Human relevance framework (HRF) to ascertain human risk for this rat MoA. The review indicated, with a high level of confidence, that the sulfoxaflor-induced fetal abnormalities and neonatal death in rats occur via a single MoA comprising sustained activation of the rat fetal-type muscle nAChR resulting in a sustained muscle contracture. This MoA is considered not relevant to humans, given fundamental qualitative differences in sulfoxaflor agonism on the rat versus the human muscle nAChR. Specifically, sulfoxaflor does not cause agonism on either the human fetal- or adult-type muscle nAChR. PMID:24832553
Ellis-Hutchings, Robert G; Rasoulpour, Reza J; Terry, Claire; Carney, Edward W; Billington, Richard
NTP-CERHR monograph on the potential human reproductive and developmental effects of bisphenol A.
The National Toxicology Program (NTP) Center for the Evaluation of Risks to Human Reproduction (CERHR) conducted an evaluation of the potential for bisphenol A to cause adverse effects on reproduction and development in humans. The CERHR Expert Panel on Bisphenol A completed its evaluation in August 2007. CERHR selected bisphenol A for evaluation because of the: widespread human exposure; public concern for possible health effects from human exposures; high production volume; evidence of reproductive and developmental toxicity in laboratory animal studies Bisphenol A (CAS RN: 80-05-7) is a high production volume chemical used primarily in the production of polycarbonate plastics and epoxy resins. Polycarbonate plastics are used in some food and drink containers; the resins are used as lacquers to coat metal products such as food cans, bottle tops, and water supply pipes. To a lesser extent bisphenol A is used in the production of polyester resins, polysulfone resins, polyacrylate resins, and flame retardants. In addition, bisphenol A is used in the processing of polyvinyl chloride plastic and in the recycling of thermal paper. Some polymers used in dental sealants and tooth coatings contain bisphenol A. The primary source of exposure to bisphenol A for most people is assumed to occur through the diet. While air, dust, and water (including skin contact during bathing and swimming) are other possible sources of exposure, bisphenol A in food and beverages accounts for the majority of daily human exposure. The highest estimated daily intakes of bisphenol A in the general population occur in infants and children. The results of this bisphenol A evaluation are published in an NTP-CERHR Monograph that includes the (1) NTP Brief and (2) Expert Panel Report on the Reproductive and Developmental Toxicity of Bisphenol A. Additional information related to the evaluation process, including the peer review report for the NTP Brief and public comments received on the draft NTP Brief and the final expert panel report, are available on the CERHR website (http://cerhr.niehs.nih.gov/). See bisphenol A under "CERHR Chemicals" on the homepage or go directly to http://cerhr.niehs. nih.gov/chemicals/bisphenol/bisphenol.html). The NTP reached the following conclusions on the possible effects of exposure to bisphenol A on human development and reproduction. Note that the possible levels of concern, from lowest to highest, are negligible concern, minimal concern, some concern, concern, and serious concern. The NTP has some concern for effects on the brain, behavior, and prostate gland in fetuses, infants, and children at current human exposures to bisphenol A. The NTP has minimal concern for effects on the mammary gland and an earlier age for puberty for females in fetuses, infants, and children at current human exposures to bisphenol A. The NTP has negligible concern that exposure of pregnant women to bisphenol A will result in fetal or neonatal mortality, birth defects, or reduced birth weight and growth in their offspring. The NTP has negligible concern that exposure to bisphenol A will cause reproductive effects in non-occupationally exposed adults and minimal concern for workers exposed to higher levels in occupational settings. NTP will transmit the NTP-CERHR Monograph on Bisphenol A to federal and state agencies, interested parties, and the public and make it available in electronic PDF format on the CERHR web site (http://cerhr.niehs.nih.gov) and in printed text or CD from CERHR. PMID:19407859
Shelby, Michael D
Students' Understandings of Human Organs and Organ Systems.
ERIC Educational Resources Information Center
Discusses students' understandings of their own internal structure. Analysis shows the extent to which student understanding increases with age and the degree to which students know more about some organs and organ systems than others. Gender differences in the drawings were generally not large and there were some intriguing differences in the�
Reiss, Michael J.; Tunnicliffe, Sue Dale
CD16. Developmentally regulated IgG Fc receptors on cultured human monocytes
We have demonstrated that one Fc receptor for IgG (FcR) (CD16) on cultured human monocytes appears to be a developmentally regulated membrane protein. This receptor appears to contain less carbohydrate (if any) than does its counterpart on human neutrophils. Expression of CD16 on cultured monocytes increases with respect to both percentage of positive cells and numbers of sites per cell with length of time in culture. This was in contrast to expression of other types of FcRs that either decreased (CDw32) or did not change (FcRp72). Unlike an FcR that binds monomeric IgG (FcRp72), expression of CD16 on monocytes from most normal individuals was not influenced by IFN-gamma. After 14 d in culture, CD16 appeared to be the predominant FcR on cultured monocytes, and was capable of mediating both ligand attachment and phagocytosis. These findings support the hypothesis that CD16 plays an important role in mediating immunophagocytosis.
Relationship of Bender Gestalt Developmental Scores and Human Drawing Developmental Scores in a Sample of Turkish Preschool Children
ERIC Educational Resources Information Center
The Bender Gestalt test and Human Drawings are frequently utilized tests in assessing school readiness in children. This study was a pilot attempt to evaluate these two tests in a Turkish sample as they relate to first grade behaviour as measured by teacher ratings. One hundred and five children were evaluated at the end of kindergarten using the�
Ozer, Serap
Out of Sight Is Not Out of Mind: Developmental Changes in Infants' Understanding of Visual Perception During the Second Year
Three experiments investigated 14-, 18-, and 24- month-old infants' understanding of visual perception. Infants viewed films in which a protagonist was either able to view the location of a hidden object (Visual Access condition) or was blindfolded when the object location was revealed (No Visual Access condition). When requested to find the object, the protagonist pointed either at the correct
Diane Poulin-Dubois; Beate Sodian; Ulrike Metz; Joanne Tilden; Barbara Schoeppner
Cultural Understanding in Counterinsurgency: Analysis of the Human Terrain System.
National Technical Information Service (NTIS)
In the years following the invasion of Iraq, the United States military did not fully realize or understand the complexity of the situation faced by soldiers operating at the tactical and operational level. Coupled with the presence of multiple insurgent ...
G. S. Fawcett
Use of a mouse in vitro fertilization model to understand the developmental origins of health and disease hypothesis.
The Developmental Origins of Health and Disease hypothesis holds that alterations to homeostasis during critical periods of development can predispose individuals to adult-onset chronic diseases such as diabetes and metabolic syndrome. It remains controversial whether preimplantation embryo manipulation, clinically used to treat patients with infertility, disturbs homeostasis and affects long-term growth and metabolism. To address this controversy, we have assessed the effects of in vitro fertilization (IVF) on postnatal physiology in mice. We demonstrate that IVF and embryo culture, even under conditions considered optimal for mouse embryo culture, alter postnatal growth trajectory, fat accumulation, and glucose metabolism in adult mice. Unbiased metabolic profiling in serum and microarray analysis of pancreatic islets and insulin sensitive tissues (liver, skeletal muscle, and adipose tissue) revealed broad changes in metabolic homeostasis, characterized by systemic oxidative stress and mitochondrial dysfunction. Adopting a candidate approach, we identify thioredoxin-interacting protein (TXNIP), a key molecule involved in integrating cellular nutritional and oxidative states with metabolic response, as a marker for preimplantation stress and demonstrate tissue-specific epigenetic and transcriptional TXNIP misregulation in selected adult tissues. Importantly, dysregulation of TXNIP expression is associated with enrichment for H4 acetylation at the Txnip promoter that persists from the blastocyst stage through adulthood in adipose tissue. Our data support the vulnerability of preimplantation embryos to environmental disturbance and demonstrate that conception by IVF can reprogram metabolic homeostasis through metabolic, transcriptional, and epigenetic mechanisms with lasting effects for adult growth and fitness. This study has wide clinical relevance and underscores the importance of continued follow-up of IVF-conceived offspring. PMID:24684304
Feuer, Sky K; Liu, Xiaowei; Donjacour, Annemarie; Lin, Wingka; Simbulan, Rhodel K; Giritharan, Gnanaratnam; Piane, Luisa Delle; Kolahi, Kevin; Ameri, Kurosh; Maltepe, Emin; Rinaudo, Paolo F
Understanding Human Trafficking Origin: A Cross-Country Empirical Analysis
Feminist work on global human trafficking has highlighted the conceptual difficulty of differentiating between trafficking and migration. This contribution uses a cross-country United Nations Office on Crime and Drugs dataset on human trafficking from 2006 to empirically evaluate the socioeconomic characteristics of high-trafficking origin countries and compare them with patterns that have emerged in the literature on migration. In particular,
Smriti Rao; Christina Presenti
Developmentally-regulated extended domains of DNA hypomethylation encompass highly transcribed genes of the human ?-globin locus
Objective DNA methylation has long been implicated in developmental ?-globin gene regulation. However, the mechanism underlying this regulation is unclear, especially since these genes do not contain CpG islands. This has led us to propose and test the hypothesis that, just as for histone modifications, developmentally-specific changes in human ?-like globin gene expression are associated with long-range changes in DNA methylation. Methods Bisulfite sequencing was used to determine the methylation state of individual CpG dinucleotides across the ?-globin locus in uncultured primary human erythroblasts from fetal liver and bone marrow, and in primitive-like erythroid cells derived from human embryonic stem cells. Results ?-globin locus CpGs are generally highly methylated but domains of DNA hypomethylation spanning thousands of base pairs are established around the most highly expressed genes during each developmental stage. These large domains of DNA hypomethylation are found within domains of histone modifications associated with gene expression. We also find hypomethylation of a small proportion of ?-globin promoters in adult erythroid cells, suggesting a mechanism by which adult erythroid cells produce fetal hemoglobin. Conclusion This is one of the first reports to show that changes in DNA methylation patterns across large domains around non-CpG island genes correspond with changes in developmentally-regulated histone modifications and gene expression. This data supports a new model in which extended domains of DNA hypomethylation and active histone marks are coordinately established to achieve developmentally-specific gene expression of non-CpG island genes.
Lathrop, Melissa J.; Hsu, Mei; Richardson, Christine A.; Olivier, Emmanuel N.; Bouhassira, Eric E.; Fiering, Steven; Lowrey, Christopher H.
Understanding Human Culture as an Event in the Biota
ERIC Educational Resources Information Center
The role of human feelings as well as physiologicalfacts in ecological concerns is considered. New terms are proposed to facilitate thinking about the ecosystem - the entire system of relationships on which life is contingent. (LS)
Hartley, Peter E.
Developmental and reproductive toxicity of inorganic arsenic: Animal studies and human concerns
Information on the reproductive and developmental toxicity of inorganic arsenic is available primarily from studies in animals using arsenite and arsenate salts and arsenic trioxide. Inorganic arsenic has been extensively studied as a teratogen in animals. Data from animal studies demonstrate that arsenic can produce developmental toxicity, including malformation, death, and growth retardation, in four species (hamsters, mice, rats, rabbits).
Mari S. Golub; Michael S. Macintosh; Nikki Baumrind
High School Students� Understanding of the Human Body System
In this study, 120 tenth-grade students from 8 schools were examined to determine the extent of their ability to perceive\\u000a the human body as a system after completing the first stage in their biology curriculum - �The human body, emphasizing homeostasis�.\\u000a The students� systems thinking was analyzed according to the STH thinking model, which roughly divides it into three main
Orit Ben-Zvi Assaraf; Jeff Dodick; Jaklin Tripto
Targeting developmental regulators of zebrafish exocrine pancreas as a therapeutic approach in human pancreatic cancer
Summary Histone deacetylases (HDACs) and RNA polymerase III (POLR3) play vital roles in fundamental cellular processes, and deregulation of these enzymes has been implicated in malignant transformation. Hdacs and Polr3 are required for exocrine pancreatic epithelial proliferation during morphogenesis in zebrafish. We aim to test the hypothesis that Hdacs and Polr3 cooperatively control exocrine pancreatic growth, and combined inhibition of HDACs and POLR3 produces enhanced growth suppression in pancreatic cancer. In zebrafish larvae, combination of a Hdac inhibitor (Trichostatin A) and an inhibitor of Polr3 (ML-60218) synergistically prohibited the expansion of exocrine pancreas. In human pancreatic adenocarcinoma cells, combination of the HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) and ML-60218 produced augmented suppression of colony formation and proliferation, and induction of cell cycle arrest and apoptotic cell death. The enhanced cytotoxicity was associated with supra-additive upregulation of the pro-apoptotic regulator BAX and the cyclin-dependent kinase inhibitor p21CDKN1A. tRNAs have been shown to have pro-proliferative and anti-apoptotic roles, and SAHA-stimulated expression of tRNAs was reversed by ML-60218. These findings demonstrate that chemically targeting developmental regulators of exocrine pancreas can be translated into an approach with potential impact on therapeutic response in pancreatic cancer, and suggest that counteracting the pro-malignant side effect of HDAC inhibitors can enhance their anti-tumor activity.
Yee, Nelson S.; Zhou, Weiqiang; Chun, Stephen G.; Liang, I-Chau; Yee, Rosemary K.
Differential Developmental Trajectories of Magnetic Susceptibility in Human Brain Gray and White Matter Over the Lifespan
As indicated by several recent studies, magnetic susceptibility of the brain is influenced mainly by myelin in the white matter and by iron deposits in the deep nuclei. Myelination and iron deposition in the brain evolve both spatially and temporally. This evolution reflects an important characteristic of normal brain development and ageing. In this study, we assessed the changes of regional susceptibility in the human brain in vivo by examining the developmental and ageing process from 1 to 83 years of age. The evolution of magnetic susceptibility over this lifespan was found to display differential trajectories between the gray and the white matter. In both cortical and subcortical white matter, an initial decrease followed by a subsequent increase in magnetic susceptibility was observed, which could be fitted by a Poisson curve. In the gray matter, including the cortical gray matter and the iron-rich deep nuclei, magnetic susceptibility displayed a monotonic increase that can be described by an exponential growth. The rate of change varied according to functional and anatomical regions of the brain. For the brain nuclei, the age-related changes of susceptibility were in good agreement with the findings from R2* measurement. Our results suggest that magnetic susceptibility may provide valuable information regarding the spatial and temporal patterns of brain myelination and iron deposition during brain maturation and ageing.
Li, Wei; Wu, Bing; Batrachenko, Anastasia; Bancroft-Wu, Vivian; Morey, Rajendra A.; Shashi, Vandana; Langkammer, Christian; De Bellis, Michael D.; Ropele, Stefan; Song, Allen W.; Liu, Chunlei
PERT: A Method for Expression Deconvolution of Human Blood Samples from Varied Microenvironmental and Developmental Conditions
The cellular composition of heterogeneous samples can be predicted using an expression deconvolution algorithm to decompose their gene expression profiles based on pre-defined, reference gene expression profiles of the constituent populations in these samples. However, the expression profiles of the actual constituent populations are often perturbed from those of the reference profiles due to gene expression changes in cells associated with microenvironmental or developmental effects. Existing deconvolution algorithms do not account for these changes and give incorrect results when benchmarked against those measured by well-established flow cytometry, even after batch correction was applied. We introduce PERT, a new probabilistic expression deconvolution method that detects and accounts for a shared, multiplicative perturbation in the reference profiles when performing expression deconvolution. We applied PERT and three other state-of-the-art expression deconvolution methods to predict cell frequencies within heterogeneous human blood samples that were collected under several conditions (uncultured mono-nucleated and lineage-depleted cells, and culture-derived lineage-depleted cells). Only PERT's predicted proportions of the constituent populations matched those assigned by flow cytometry. Genes associated with cell cycle processes were highly enriched among those with the largest predicted expression changes between the cultured and uncultured conditions. We anticipate that PERT will be widely applicable to expression deconvolution strategies that use profiles from reference populations that vary from the corresponding constituent populations in cellular state but not cellular phenotypic identity.
Csaszar, Elizabeth; Yu, Mei; Morris, Quaid; Zandstra, Peter W.
Understanding actors and object-goals in the human brain
When another person takes �10 from your hand, it matters if they are a shopkeeper or a robber. That is, the meaning of a simple, goal-directed action can vary depending on the identity of the actors involved. Research examining action understanding has identified an action observation network (AON) that encodes action features such as goals and kinematics. However, it is
Richard Ramsey; Antonia F. de C. Hamilton
Which Aesthetic has the Greatest Effect on Human Understanding?
In the creation of graph drawing algorithms and systems, designers claim that by producing layouts that optimise certain aesthetic qualities, the graphs are easier to understand. Such aesthetics include maximise symmetry, minimise edge crosses and minimise bends. A previous study aimed to validate these claims with respect to three aesthetics, using paper-based experiments (11). The study reported here is superior
Helen C. Purchase
Human embryonic stem cell proliferation and differentiation as parameters to evaluate developmental toxicity.
In vitro models based on embryonic stem cells (ESC) are highly promising for improvement of predictive toxicology screening in humans. After the successful validation of embryonic stem cell test (EST) in 2001; concerns have been raised on the usage of mouse ESC and also the morphological evaluation of beating cell clusters. This requires specialized skill-sets and is highly prone to misjudgement and false positive results. To overcome these limitations, we undertook the present study incorporating improvisations over the conventional EST. Here, we explored the potential of a human ESC (hESC)-based assay to evaluate the potential toxicity of penicillin-G, caffeine, and hydroxyurea. Drug treatment inhibited hESC adhesion and substantially altered the morphology and viability (? 50%) of embryoid bodies (EBs). Flow cytometry analysis not only showed a significant increase of apoptotic cells in the highest doses but also induced a diverse pattern in DNA content and cell cycle distribution relative to control. Both semi-quantitative and quantitative RT-PCR studies revealed a selective down regulation of markers associated with stemness (Nanog, Rex1, SOX-2, and hTERT); cardiac mesoderm (Cripto1, MEF-2C, and Brachyury); hepatic endoderm (AFP, HNF-3?, HNF-4?, GATA-4, and SOX-17); and neuroectoderm (Nestin, SOX-1, NURR1, NEFH, Synaptophysin, TH, and Olig2) in a drug as well as dose dependent manner indicating abnormal differentiation. Furthermore, a decrease in the expression of AFP and GFAP proteins followed by a dose-dependent reduction in the levels of hCG-?, progesterone-II, and estradiol hormones was demonstrated by immunocytochemistry and ECLIA, respectively. This new and unique approach comprising of DNA cell cycle analysis, germ layer-specific marker expression and hormone levels as endpoints might offer a clinically relevant and commercially viable alternative for predicting in vivo developmental toxicity. PMID:20945368
Pal, Rajarshi; Mamidi, Murali Krishna; Das, Anjan Kumar; Bhonde, Ramesh
Developmental characteristics of neuronal nitric oxide synthase (nNOS) immunoreactive neurons in fetal to adolescent human brains
The developmental characteristics of the neuronal nitric oxide synthase (nNOS) immunoreactive neurons in the human brain were studied. In the frontal lobe, nNOS immunoreactive cells appeared as early as 18 gestational weeks (GW) in the subcortical plate and then increased predominantly in the subcortical white matter during the fetal period, while weakly immunoreactive neurons were found in the cortical II�IV
Junkou Ohyu; Sachio Takashima
Genital Measures: Comments on Their Role in Understanding Human Sexuality
ERIC Educational Resources Information Center
This paper discusses the use of genital measures in the study of both applied and basic work in human sexuality. Some of the advantages of psychophysiological measures are considered along with cautions concerning unwarranted assumptions. Some of the advances that are possible in both applied and basic work are examined. (Author)
Geer, James H.
Understanding Arts and Humanities Students' Experiences of Assessment and Feedback
ERIC Educational Resources Information Center
This article examines how undergraduate students on arts and humanities courses experience assessment and feedback. The research uses a detailed audit, a specially devised questionnaire (the Assessment Experience Questionnaire), and student focus group data, and the article examines results from 19 programmes, comparing those from "arts and�
Adams, Joelle; McNab, Nicole
Hemispheric Specialization and the Growth of Human Understanding.
ERIC Educational Resources Information Center
Connectionistic notions of hemispheric specialization and use are incompatible with the network organization of the human brain. Although brain organization has correspondence with phenomena at more complex levels of analysis, the correspondence is not categorical in nature, as has been claimed by the left-brain/right-brain theorists. (Author/GC)
Kinsbourne, Marcel
Comparative genomics: the key to understanding the human genome project
Summary The sequencing of the human genome is well underway. Technology has ad- vanced, such that the total genomic sequence is possible, along with an extensive catalogue of genes via comprehensive cDNA libraries. With the recent completion of the Saccharomyces cerevisiae sequencing project and the imminent comple- tion of that of Caenorhabditis elegans, the most frequently asked question is how
M. S. Clark
Education for International Understanding, Peace, and Human Rights.
ERIC Educational Resources Information Center
This 294-item annotated bibliography dealing with international education focuses on: general world problems and the new international economic order; education for peace, human rights, international cooperation, and comprehension; the system of associated schools; and reference works and teaching materials for teacher and classroom. Suggestions�
Montandon, Edmee, Ed.
Humanities in Dental Education: A Focus on Understanding the Child.
ERIC Educational Resources Information Center
Describes a seminar program at the University of Maryland Dental School, which uses books, short stories, and films that integrate human values into dental education, specifically in pediatric dentistry, for residents, clerks, and faculty. Results of initial evaluation and changes in the program over time are detailed. (DB)
Balis, Sophia A.; Rule, James T.
Modern air pollution regulation is first and foremost motivated by concerns about the effects of air pollutants on human health and secondarily by concerns about its effects on ecosystems, cultural artifacts, and quality of life values such as visibility. This order of priority ...
Targeted loss of Arx results in a developmental epilepsy mouse model and recapitulates the human phenotype in heterozygous females.
Mutations in the X-linked aristaless-related homeobox gene (ARX) have been linked to structural brain anomalies as well as multiple neurocognitive deficits. The generation of Arx-deficient mice revealed several morphological anomalies, resembling those observed in patients and an interneuron migration defect but perinatal lethality precluded analyses of later phenotypes. Interestingly, many of the neurological phenotypes observed in patients with various ARX mutations can be attributed, in part, to interneuron dysfunction. To directly test this possibility, mice carrying a floxed Arx allele were generated and crossed to Dlx5/6(CRE-IRES-GFP)(Dlx5/6(CIG)) mice, conditionally deleting Arx from ganglionic eminence derived neurons including cortical interneurons. We now report that Arx(-/y);Dlx5/6(CIG) (male) mice exhibit a variety of seizure types beginning in early-life, including seizures that behaviourally and electroencephalographically resembles infantile spasms, and show evolution through development. Thus, this represents a new genetic model of a malignant form of paediatric epilepsy, with some characteristics resembling infantile spasms, caused by mutations in a known infantile spasms gene. Unexpectedly, approximately half of the female mice carrying a single mutant Arx allele (Arx(-/+);Dlx5/6(CIG)) also developed seizures. We also found that a subset of human female carriers have seizures and neurocognitive deficits. In summary, we have identified a previously unrecognized patient population with neurological deficits attributed to ARX mutations that are recapitulated in our mouse model. Furthermore, we show that perturbation of interneuron subpopulations is an important mechanism underling the pathogenesis of developmental epilepsy in both hemizygous males and carrier females. Given the frequency of ARX mutations in patients with infantile spasms and related disorders, our data unveil a new model for further understanding the pathogenesis of these disorders. PMID:19439424
Marsh, Eric; Fulp, Carl; Gomez, Ernest; Nasrallah, Ilya; Minarcik, Jeremy; Sudi, Jyotsna; Christian, Susan L; Mancini, Grazia; Labosky, Patricia; Dobyns, William; Brooks-Kayal, Amy; Golden, Jeffrey A
The Dynamic Lift of Developmental Process
ERIC Educational Resources Information Center
What are the essential properties of human intelligence, currently unparalleled in its power relative to other biological forms and relative to artificial forms of intelligence? We suggest that answering this question depends critically on understanding developmental process. This paper considers three principles potentially essential to building�
Smith, Linda B.; Breazeal, Cynthia
Methods to identify and characterize developmental neurotoxicity for human health risk assessment. III: pharmacokinetic and pharmacodynamic considerations.
We review pharmacokinetic and pharmacodynamic factors that should be considered in the design and interpretation of developmental neurotoxicity studies. Toxicologic effects on the developing nervous system depend on the delivered dose, exposure duration, and developmental stage at which exposure occurred. Several pharmacokinetic processes (absorption, distribution, metabolism, and excretion) govern chemical disposition within the dam and the nervous system of the offspring. In addition, unique physical features such as the presence or absence of a placental barrier and the gradual development of the blood--brain barrier influence chemical disposition and thus modulate developmental neurotoxicity. Neonatal exposure may depend on maternal pharmacokinetic processes and transfer of the xenobiotic through the milk, although direct exposure may occur through other routes (e.g., inhalation). Measurement of the xenobiotic in milk and evaluation of biomarkers of exposure or effect following exposure can confirm or characterize neonatal exposure. Physiologically based pharmacokinetic and pharmacodynamic models that incorporate these and other determinants can estimate tissue dose and biologic response following in utero or neonatal exposure. These models can characterize dose--response relationships and improve extrapolation of results from animal studies to humans. In addition, pharmacologic data allow an experimenter to determine whether exposure to the test chemical is adequate, whether exposure occurs during critical periods of nervous system development, whether route and duration of exposure are appropriate, and whether developmental neurotoxicity can be differentiated from direct actions of the xenobiotic.
Dorman, D C; Allen, S L; Byczkowski, J Z; Claudio, L; Fisher, J E; Fisher, J W; Harry, G J; Li, A A; Makris, S L; Padilla, S; Sultatos, L G; Mileson, B E
High School Students' Understanding of the Human Body System
NASA Astrophysics Data System (ADS)
In this study, 120 tenth-grade students from 8 schools were examined to determine the extent of their ability to perceive the human body as a system after completing the first stage in their biology curriculum - "The human body, emphasizing homeostasis". The students' systems thinking was analyzed according to the STH thinking model, which roughly divides it into three main levels that are arranged "pyramid" style, in an ascending order of difficulty: 1. Analysis of system components�the ability to identify the components and processes existing in the human body system; 2. Synthesis of system components�ability to identify dynamic relations within the system; 3. Implementation�ability to generalize and identify patterns in the system, and to identify its hidden dimensions. The students in this study proved largely incapable of achieving systems thinking beyond the primary STH level of identifying components. An overwhelming majority if their responses corresponded to this level of the STH model, further indicating a pronounced favoring of structure over process, and of larger, macro elements over microscopic ones.
Assaraf, Orit Ben-Zvi; Dodick, Jeff; Tripto, Jaklin
Using animal models to understand cancer pain in humans.
Cancer pain is not a single entity but a complex pain state involving different pain syndromes, with inflammatory, neuropathic, compressive, and ischaemic mechanisms. Current therapeutic regimens are based largely on opioids, although opioid treatment can lead to many side effects. Studies using animal models of cancer pain are aimed at understanding cancer pain and developing novel therapies. The most frequently reported models are of bone cancer pain, predominantly modelling pain associated with tumour growth within bone marrow. Here we summarise recent findings from studies using animal models of cancer pain and discuss the methodological quality of these studies. PMID:24760492
Currie, Gillian L; Sena, Emily S; Fallon, Marie T; Macleod, Malcolm R; Colvin, Lesley A
Abstract Supernumerary or accessory ribs (SNR), either lumbar (LSNR) or cervical (CSNR) are a common finding in standard developmental toxicology bioassays. The biological significance of these anomalies within the regulatory arena has been problematic and the subject of some...
Understanding Human Glycosylation Disorders: Biochemistry Leads the Charge*
Nearly 70 inherited human glycosylation disorders span a breathtaking clinical spectrum, impacting nearly every organ system and launching a family-driven diagnostic odyssey. Advances in genetics, especially next generation sequencing, propelled discovery of many glycosylation disorders in single and multiple pathways. Interpretation of whole exome sequencing results, insights into pathological mechanisms, and possible therapies will hinge on biochemical analysis of patient-derived materials and animal models. Biochemical diagnostic markers and readouts offer a physiological context to confirm candidate genes. Recent discoveries suggest novel perspectives for textbook biochemistry and novel research opportunities. Basic science and patients are the immediate beneficiaries of this bidirectional collaboration.
Freeze, Hudson H.
Brain and Tissue Bank for Developmental Disorders
NSDL National Science Digital Library
The Brain and Tissue Bank at the University of Maryland at Baltimore is established to advance the research of developmental disorders and is in contract to the National Institute of Child Health and Human Development, National Institutes of Health. The objective of this human tissue repository is to systematically collect, store, and distribute brain and other tissue for research dedicated to the improved understanding, care and treatment of individuals with developmental disorders. A listing of disorders, tissues and request information is available, in addition to registry information for potential donors.
A chronology of human understanding of the nitrogen cycle.
Nitrogen over the ages! It was discovered in the eighteenth century. The following century, its importance in agriculture was documented and the basic components of its cycle were elucidated. In the twentieth century, a process to provide an inexhaustible supply of reactive N (Nr; all N species except N2) for agricultural, industrial and military uses was invented. This discovery and the extensive burning of fossil fuels meant that by the beginning of the twenty-first century, anthropogenic sources of newly created Nr were two to three times that of natural terrestrial sources. This caused a fundamental change in the nitrogen cycle; for the first time, there was the potential for enough food to sustain growing populations and changing dietary patterns. However, most Nr created by humans is lost to the environment, resulting in a cascade of negative earth systems impacts-including enhanced acid rain, smog, eutrophication, greenhouse effect and stratospheric ozone depletion, with associated impacts on human and ecosystem health. The impacts continue and will be magnified, as Nr is lost to the environment at an even greater rate. Thus, the challenge for the current century is how to optimize the uses of N while minimizing the negative impacts. PMID:23713118
Galloway, James N; Leach, Allison M; Bleeker, Albert; Erisman, Jan Willem
A chronology of human understanding of the nitrogen cycle�
Nitrogen over the ages! It was discovered in the eighteenth century. The following century, its importance in agriculture was documented and the basic components of its cycle were elucidated. In the twentieth century, a process to provide an inexhaustible supply of reactive N (Nr; all N species except N2) for agricultural, industrial and military uses was invented. This discovery and the extensive burning of fossil fuels meant that by the beginning of the twenty-first century, anthropogenic sources of newly created Nr were two to three times that of natural terrestrial sources. This caused a fundamental change in the nitrogen cycle; for the first time, there was the potential for enough food to sustain growing populations and changing dietary patterns. However, most Nr created by humans is lost to the environment, resulting in a cascade of negative earth systems impacts�including enhanced acid rain, smog, eutrophication, greenhouse effect and stratospheric ozone depletion, with associated impacts on human and ecosystem health. The impacts continue and will be magnified, as Nr is lost to the environment at an even greater rate. Thus, the challenge for the current century is how to optimize the uses of N while minimizing the negative impacts.
Galloway, James N.; Leach, Allison M.; Bleeker, Albert; Erisman, Jan Willem
Can human movement analysis contribute to usability understanding?
Nowadays human-machine interfaces are evaluated using different methodologies. These methodologies rarely consider the human movements involved in the interaction, and if so, the movements are considered in a simplistic manner. Another often neglected aspect is the relationship between the learning process and the use of the interface. Traditional approaches of cognitive modeling consider learning as just one continuous process. However there is some current evidence of concurrent processes on different time scales. This paper aims to answer, with experimental measurements, if learning actually implies a set of concurrent processes, if those processes are related to the coordinative aspects of hand movement, and how this can vary between young adult and elderly users. Two different interfaces, a washing machine and a domotic system, were analyzed with 23 and 20 people, respectively, classified as men or women and elderly (over 55) or adult (between 40 and 50). The results of the study provide support for the existence of different concurrent processes in learning, previously demonstrated for motor tasks. Moreover, the learning process is actually associated with changes in movement patterns. Finally, the results show that the progression of the learning process depends on age, although elderly people are equally capable of learning to use technological systems as young adults. PMID:20580455
Belda-Lois, Juan-Manuel; de-Rosario, Helios; Pons, Rom�; Poveda, Rakel; Mor�n, Ana; Porcar, Rosa; Garc�a, Ana-Cruz; G�mez, Amelia
Understanding mechanisms underlying human gene expression variation with RNA sequencing.
Understanding the genetic mechanisms underlying natural variation in gene expression is a central goal of both medical and evolutionary genetics, and studies of expression quantitative trait loci (eQTLs) have become an important tool for achieving this goal. Although all eQTL studies so far have assayed messenger RNA levels using expression microarrays, recent advances in RNA sequencing enable the analysis of transcript variation at unprecedented resolution. We sequenced RNA from 69 lymphoblastoid cell lines derived from unrelated Nigerian individuals that have been extensively genotyped by the International HapMap Project. By pooling data from all individuals, we generated a map of the transcriptional landscape of these cells, identifying extensive use of unannotated untranslated regions and more than 100 new putative protein-coding exons. Using the genotypes from the HapMap project, we identified more than a thousand genes at which genetic variation influences overall expression levels or splicing. We demonstrate that eQTLs near genes generally act by a mechanism involving allele-specific expression, and that variation that influences the inclusion of an exon is enriched within and near the consensus splice sites. Our results illustrate the power of high-throughput sequencing for the joint analysis of variation in transcription, splicing and allele-specific expression across individuals. PMID:20220758
Pickrell, Joseph K; Marioni, John C; Pai, Athma A; Degner, Jacob F; Engelhardt, Barbara E; Nkadori, Everlyne; Veyrieras, Jean-Baptiste; Stephens, Matthew; Gilad, Yoav; Pritchard, Jonathan K
Towards Better Human Robot Interaction: Understand Human Computer Interaction in Social Gaming Using a Video-Enhanced Diary Method
NASA Astrophysics Data System (ADS)
This paper presents findings from a descriptive research on social gaming. A video-enhanced diary method was used to understand the user experience in social gaming. From this experiment, we found that natural human behavior and gamer�s decision making process can be elicited and speculated during human computer interaction. These are new information that we should consider as they can help us build better human computer interfaces and human robotic interfaces in future.
See, Swee Lan; Tan, Mitchell; Looi, Qin En
Understanding the human health effects of chemical mixtures.
Most research on the effects of chemicals on biologic systems is conducted on one chemical at a time. However, in the real world people are exposed to mixtures, not single chemicals. Although various substances may have totally independent actions, in many cases two substances may act at the same site in ways that can be either additive or nonadditive. Many even more complex interactions may occur if two chemicals act at different but related targets. In the extreme case there may be synergistic effects, in which case the effects of two substances together are greater than the sum of either effect alone. In reality, most persons are exposed to many chemicals, not just one or two, and therefore the effects of a chemical mixture are extremely complex and may differ for each mixture depending on the chemical composition. This complexity is a major reason why mixtures have not been well studied. In this review we attempt to illustrate some of the principles and approaches that can be used to study effects of mixtures. By the nature of the state of the science, this discussion is more a presentation of what we do not know than of what we do know about mixtures. We approach the study of mixtures at three levels, using specific examples. First, we discuss several human diseases in relation to a variety of environmental agents believed to influence the development and progression of the disease. We present results of selected cellular and animal studies in which simple mixtures have been investigated. Finally, we discuss some of the effects of mixtures at a molecular level.
Carpenter, David O; Arcaro, Kathleen; Spink, David C
Has our understanding of calcification in human coronary atherosclerosis progressed?
Coronary artery calcification is a well-established predictor of future cardiac events; however, it is not a predictor of unstable plaque. The intimal calcification of the atherosclerotic plaques may begin with smooth muscle cell apoptosis and release of matrix vesicles and is almost always seen microscopically in pathological intimal thickening, which appears as microcalcification (?0.5 ?m, typically <15 ?m in diameter). Calcification increases with macrophage infiltration into the lipid pool in early fibroatheroma where they undergo apoptosis and release matrix vesicles. The confluence of calcified areas involves extracellular matrix and the necrotic core, which can be identified by radiography as speckled (?2 mm) or fragmented (>2, <5 mm) calcification. The calcification in thin-cap fibroatheromas and plaque rupture is generally less than what is observed in stable plaques and is usually speckled or fragmented. Fragmented calcification spreads into the surrounding collagen-rich matrix forming calcified sheets, the hallmarks of fibrocalcific plaques. The calcified sheets may break into nodules with fibrin deposition, and when accompanied by luminal protrusion, it is associated with thrombosis. Calcification is highest in fibrocalcific plaques followed by healed plaque rupture and is the least in erosion and pathological intimal thickening. The extent of calcification is greater in men than in women especially in the premenopausal period and is also greater in whites compared with blacks. The mechanisms of intimal calcification remain poorly understood in humans. Calcification often occurs in the presence of apoptosis of smooth muscle cells and macrophages with matrix vesicles accompanied by expression of osteogenic markers within the vessel wall. PMID:24558104
Otsuka, Fumiyuki; Sakakura, Kenichi; Yahagi, Kazuyuki; Joner, Michael; Virmani, Renu
The Emergence of Autobiographical Memory: A Social Cultural Developmental Theory
ERIC Educational Resources Information Center
The authors present a multicomponent dynamic developmental theory of human autobiographical memory that emerges gradually across the preschool years. The components that contribute to the process of emergence include basic memory abilities, language and narrative, adult memory talk, temporal understanding, and understanding of self and others. The�
Nelson, Katherine; Fivush, Robyn
Developmental Fate and Cellular Maturity Encoded in Human Regulatory DNA Landscapes
SUMMARY Cellular-state information between generations of developing cells may be propagated via regulatory regions. We report consistent patterns of gain and loss of DNase I-hypersensitive sites (DHSs) as cells progress from embryonic stem cells (ESCs) to terminal fates. DHS patterns alone convey rich information about cell fate and lineage relationships distinct from information conveyed by gene expression. Developing cells share a proportion of their DHS landscapes with ESCs; that proportion decreases continuously in each cell type as differentiation progresses, providing a quantitative benchmark of developmental maturity. Developmentally stable DHSs densely encode binding sites for transcription factors involved in autoregulatory feedback circuits. In contrast to normal cells, cancer cells extensively reactivate silenced ESC DHSs and those from developmental programs external to the cell lineage from which the malignancy derives. Our results point to changes in regulatory DNA landscapes as quantitative indicators of cell-fate transitions, lineage relationships, and dysfunction.
Reynolds, Alex; Humbert, Richard; Miller, Brady; Paige, Sharon L.; Vernot, Benjamin; Cheng, Jeffrey B.; Thurman, Robert E.; Sandstrom, Richard; Haugen, Eric; Heimfeld, Shelly; Murry, Charles E.; Akey, Joshua M.; Stamatoyannopoulos, John A.
Developmental processes in face perception.
Understanding the developmental origins of face recognition has been the goal of many studies of various approaches. Contributions of experience-expectant mechanisms (early component), like perceptual narrowing, and lifetime experience (late component) to face processing remain elusive. By investigating captive chimpanzees of varying age, a rare case of a species with lifelong exposure to non-conspecific faces at distinctive levels of experience, we can disentangle developmental components in face recognition. We found an advantage in discriminating chimpanzee above human faces in young chimpanzees, reflecting a predominant contribution of an early component that drives the perceptual system towards the conspecific morphology, and an advantage for human above chimpanzee faces in old chimpanzees, reflecting a predominant late component that shapes the perceptual system along the critical dimensions of the face exposed to. We simulate the contribution of early and late components using computational modeling and mathematically describe the underlying functions. PMID:23304435
Dahl, Christoph D; Rasch, Malte J; Tomonaga, Masaki; Adachi, Ikuma
Developmental processes in face perception
Understanding the developmental origins of face recognition has been the goal of many studies of various approaches. Contributions of experience-expectant mechanisms (early component), like perceptual narrowing, and lifetime experience (late component) to face processing remain elusive. By investigating captive chimpanzees of varying age, a rare case of a species with lifelong exposure to non-conspecific faces at distinctive levels of experience, we can disentangle developmental components in face recognition. We found an advantage in discriminating chimpanzee above human faces in young chimpanzees, reflecting a predominant contribution of an early component that drives the perceptual system towards the conspecific morphology, and an advantage for human above chimpanzee faces in old chimpanzees, reflecting a predominant late component that shapes the perceptual system along the critical dimensions of the face exposed to. We simulate the contribution of early and late components using computational modeling and mathematically describe the underlying functions.
Dahl, Christoph D.; Rasch, Malte J.; Tomonaga, Masaki; Adachi, Ikuma
Understanding and Assessing Risk of Intrastate Conflict: Human Development Theory and Practice.
National Technical Information Service (NTIS)
Understanding human development is perhaps more relevant today than at any other moment in history. Although the United States is very good at using destructive power against its adversaries, preventing conflict and reaching a desirable end state often el...
G. O. Renfrow
Developmental toxicology encompasses the study of developmental exposures, pharmacokinetics, mechanisms, pathogenesis, and outcomes potentially leading to adverse health effects. Manifestations of developmental toxicity include structural malformations, growth retardation, functi...
Critical review of the developmental toxicity and teratogenicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin: Recent advances toward understanding the mechanism
A specific teratogenic response is elicited in the mouse as a result of exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; dioxin). The characteristic spectrum of structural malformations induced in mice following exposure to TCDD and structurally-related congeners is highly reproducible and includes both hydronephrosis and cleft palate. In addition, prenatal exposure to TCDD has been shown to induce thymic hypoplasia. The three abnormalities occur at doses well below those producing maternal or embryo/fetal toxicity, and are among the most sensitive indicators of dioxin toxicity. In all other laboratory species tested, TCDD causes maternal and embryo/fetal toxicity, but does not induce a significant increase in the incidence of structural abnormalities even at toxic dose levels. Developmental toxicity occurs in a similar dose range across species, however, mice are particularly susceptible to development of TCDD-induced terata. Recent experiments using an organ culture were an attempt to address the issue of species and organ differences in sensitivity to TCDD. Human palatal shelves were examined in this in vitro system, and were found to approximate the rat in terms of sensitivity for induction of cleft palate.
Couture, L.A.; Abbott, B.D.; Birnbaum, L.S.
Facilitating conceptual change in ninth grade students' understanding of human circulatory system concepts
The purpose of this study was to investigate the effectiveness of the conceptual change text oriented instruction over traditionally designed instruction on ninth grade students� understanding of the human circulatory system concepts, and their retention of this understanding. The subjects of this study consist of 73 ninth grade female students from two classes of a basic school in Jordan. One
Salem A. Alkhawaldeh
Facilitating Conceptual Change in Ninth Grade Students' Understanding of Human Circulatory System Concepts
ERIC Educational Resources Information Center
The purpose of this study was to investigate the effectiveness of the conceptual change text oriented instruction over traditionally designed instruction on ninth grade students' understanding of the human circulatory system concepts, and their retention of this understanding. The subjects of this study consist of 73 ninth grade female students�
Alkhawaldeh, Salem A.
Developmental ability of chromosomally abnormal human embryos to develop to the blastocyst stage
BACKGROUND: A correlation between morphology, developmental competence and chromosome abnormalities is established. However, since absolute correlations are rare, embryo selection remains one of the most arduous tasks in assisted reproduction. This study was undertaken in order to determine which chromosomal abnormalities are compatible with development to the blastocyst stage. METHODS: Embryos diagnosed by preimplantation genetic diagnosis (PGD) as chromosomally abnormal
M. Sandalinas; S. Sadowy; M. Alikani; G. Calderon; J. Cohen
The induction of heritable mutations in germ cells represents a potential health concern. his paper will highlight several themes in the area of germ-cell mutagenesis and their implications in reproductive and developmental risk. dditionally, factors that influence the yield of g...
Developmental potential of human pronuclear zygotes in relation to their pronuclear orientation
BACKGROUND: Pronuclear zygote morphology has gained much attention recently due to its possible value in predicting implantation and pregnancy. The present study was performed to assess the developmental potential of zygotes with four different pronuclear orientations. METHODS: This prospective study involved 150 IVF and 190 ICSI patients seeking fertility treatment. Pronuclear zygotes were classified for orientation of the pronuclei in
Suresh Kattera; Christopher Chen
Non-Mendelian developmental defects: animal models and implications for research into human disease*
The major groups of malformations in man are polygenic in origin but this review deals only with defects due to non-Mendelian factors. Animal models that help in identifying the causes and in understanding the numerous and often subtle mechanisms of human malformations are of particular value. Many chemicals, physical agents, and nutritional deficiencies affect experimental species but few are teratogenic for domestic animals and even fewer for man. The known fetopathic viruses of animals and man cross the placenta to cause chronic, nonlethal fetal damage without harm to the mother. Ionizing radiations are teratogenic for all species and hyperthermia for many, but the role of the latter in human development is uncertain. The identification of more animal species with spontaneous or induced defects comparable to those found in man and of additional causative teratogens will increase the resources available for research into the causes and mechanisms of abnormal development in man. No animal species is ideal in teratological research but each has its virtues. This report comments on the present status of research in teratology and the trends that might profitably be followed in the future.
Developmental continuity and change in responses to social and nonsocial categories in human extrastriate visual cortex.
It is well known that adult human extrastriate visual cortex contains areas that respond in a selective fashion to specific categories of visual stimuli. Three regions have been identified with particular regularity: the fusiform face area (FFA), which responds to faces more than to other objects; the parahippocampal place area (PPA), which responds selectively to images of houses, places, and visual scenes; and the extrastriate body area (EBA), which responds specifically to images of bodies and body parts. While the presence of these regions in the mature human brain is well-established, the degree to which children possess these areas and the degree of functional specialization of these areas in children of various ages has thus far remained unclear. This functional magnetic resonance imaging study examined the development of the FFA, EBA, and PPA in healthy, typically developing 7- to 11-year-old children and adults. Our results revealed a right FFA and a bilateral EBA and PPA in the children that were localized in a way consistent with these same regions in adults. In addition, the response profiles of these regions were very similar in adults and children with comparable levels of functional specificity at all of the ages tested. We discuss the implications of this research for understanding abnormal regional specialization for social and nonsocial object categories in individuals with autism spectrum disorders. PMID:19826492
Pelphrey, Kevin A; Lopez, Juliana; Morris, James P
Automatic recognition and understanding of spoken language - a first step toward natural human-machine communication
The promise of a powerful computing device to help people in productivity as well as in recreation can only be realized with proper human-machine communication. Automatic recognition and understanding of spoken language is the first step toward natural human-machine interaction. Research in this field has produced remarkable results, leading to many exciting expectations and new challenges. We summarize the development
NTP-CERHR Monograph on the Potential Human Reproductive and Developmental Effects of Di-Isodecyl Phthalate (DIDP).
The National Toxicology Program (NTP) Center for the Evaluation of Risks to Human Reproduction (CERHR) conducted an evaluation of the potential for di-isodecyl phthalate (DIDP) to cause adverse effects on reproduction and development in humans. DIDP is one of 7 phthalate chemicals evaluated by the NTP CERHR Phthalates Expert Panel. These phthalates were selected for evaluation because of high production volume, extent of human exposures, use in children's products, and/or published evidence of reproductive or developmental toxicity. DIDP is a mixture of branched, C-10 phthalate isomers used to add flexibility to a wide variety of polyvinylchloride (PVC) plastic products such as artificial leather, toys, carpet backing, and pool liners. The results of this evaluation on DIDP are published in a NTP-CERHR monograph which includes: 1) the NTP Brief, 2) the Expert Panel Report on the Reproductive and Developmental Toxicity of Di-Isodecyl Phthalate, and 3) public comments received on the Expert Panel Report. As stated in the NTP Brief, the NTP reached the following conclusions regarding the possible effects of exposure to DIDP on human development and reproduction. First, although DIDP could possibly affect human development if exposures are sufficiently high, there is minimal concern for developmental effects in fetuses and children at current proposed/estimated exposure levels. There is no direct evidence that exposure of people to DIDP adversely affects reproduction or development, but show that oral exposure of pregnant rats to high doses (200 and 1000 mg/kg bodyweight/day) of DIDP can adversely affect fetal development. Human exposure information for DIDP was not available, but it was assumed that the general US population would be exposed to 3-30 mug/kg body weight/day, based upon the range of estimated exposures for DEHP, a more widely used phthalate. Second, there is negligible concern for reproductive toxicity in exposed adults. Studies evaluated showed that, at high exposure levels, there is no evidence of adverse reproductive effects in rats. NTP-CERHR monographs are transmitted to federal and state agencies, interested parties, and the public and are available electronically in PDF format on the CERHR web site (http://cerhr.niehs.nih.gov) and in printed text or CD-ROM from the CERHR (National Institute of Environmental Health Sciences, P.O. Box 12233, MD EC-32, Research Triangle Park, NC; fax: 919-316-4511). PMID:15995727
Isolation and functional characterization of human erythroblasts at distinct stages: implications for understanding of normal and disordered erythropoiesis in vivo.
Terminal erythroid differentiation starts from morphologically recognizable proerythroblasts that proliferate and differentiate to generate red cells. Although this process has been extensively studied in mice, its characterization in humans is limited. By examining the dynamic changes of expression of membrane proteins during in vitro human terminal erythroid differentiation, we identified band 3 and ?4 integrin as optimal surface markers for isolating 5 morphologically distinct populations at successive developmental stages. Functional analysis revealed that these purified cell populations have distinct mitotic capacity. Use of band 3 and ?4 integrin enabled us to isolate erythroblasts at specific developmental stages from primary human bone marrow. The ratio of erythroblasts at successive stages followed the predicted 1:2:4:8:16 pattern. In contrast, bone marrows from myelodysplastic syndrome patients exhibited altered terminal erythroid differentiation profiles. Thus, our findings not only provide new insights into the genesis of the red cell membrane during human terminal erythroid differentiation but also offer a means of isolating and quantifying each developmental stage during terminal erythropoiesis in vivo. Our findings should facilitate a comprehensive cellular and molecular characterization of each specific developmental stage of human erythroblasts and should provide a powerful means of identifying stage-specific defects in diseases associated with pathological erythropoiesis. PMID:23422750
Hu, Jingping; Liu, Jing; Xue, Fumin; Halverson, Gregory; Reid, Marion; Guo, Anqi; Chen, Lixiang; Raza, Azra; Galili, Naomi; Jaffray, Julie; Lane, Joseph; Chasis, Joel Anne; Taylor, Naomi; Mohandas, Narla; An, Xiuli
Isolation and functional characterization of human erythroblasts at distinct stages: implications for understanding of normal and disordered erythropoiesis in vivo
Terminal erythroid differentiation starts from morphologically recognizable proerythroblasts that proliferate and differentiate to generate red cells. Although this process has been extensively studied in mice, its characterization in humans is limited. By examining the dynamic changes of expression of membrane proteins during in vitro human terminal erythroid differentiation, we identified band 3 and ?4 integrin as optimal surface markers for isolating 5 morphologically distinct populations at successive developmental stages. Functional analysis revealed that these purified cell populations have distinct mitotic capacity. Use of band 3 and ?4 integrin enabled us to isolate erythroblasts at specific developmental stages from primary human bone marrow. The ratio of erythroblasts at successive stages followed the predicted 1:2:4:8:16 pattern. In contrast, bone marrows from myelodysplastic syndrome patients exhibited altered terminal erythroid differentiation profiles. Thus, our findings not only provide new insights into the genesis of the red cell membrane during human terminal erythroid differentiation but also offer a means of isolating and quantifying each developmental stage during terminal erythropoiesis in vivo. Our findings should facilitate a comprehensive cellular and molecular characterization of each specific developmental stage of human erythroblasts and should provide a powerful means of identifying stage-specific defects in diseases associated with pathological erythropoiesis.
Hu, Jingping; Liu, Jing; Xue, Fumin; Halverson, Gregory; Reid, Marion; Guo, Anqi; Chen, Lixiang; Raza, Azra; Galili, Naomi; Jaffray, Julie; Lane, Joseph; Chasis, Joel Anne; Taylor, Naomi; Mohandas, Narla
Genomic features and computational identification of human microRNAs under long-range developmental regulation
Background��Recent functional studies have demonstrated that many microRNAs (miRNAs) are expressed by RNA polymerase II in a specific\\u000a spatiotemporal manner during the development of organisms and play a key role in cell-lineage decisions and morphogenesis.\\u000a They are therefore functionally related to a number of key protein coding developmental genes, that form genomic regulatory\\u000a blocks (GRBs) with arrays of highly conserved
Ying Sheng; Christopher Previti
Unraveling the characteristics of microRNA regulation in the developmental and aging process of the human brain
Background Structure and function of the human brain are subjected to dramatic changes during its development and aging. Studies have demonstrated that microRNAs (miRNAs) play an important role in the regulation of brain development and have a significant impact on brain aging and neurodegeneration. However, the underling molecular mechanisms are not well understood. In general, development and aging are conventionally studied separately, which may not completely address the physiological mechanism over the entire lifespan. Thus, we study the regulatory effect between miRNAs and mRNAs in the developmental and aging process of the human brain by integrating miRNA and mRNA expression profiles throughout the lifetime. Methods In this study, we integrated miRNA and mRNA expression profiles in the human brain across lifespan from the network perspective. First, we chose the age-related miRNAs by polynomial regression models. Second, we constructed the bipartite miRNA-mRNA regulatory network by pair-wise correlation coefficient analysis between miRNA and mRNA expression profiles. At last, we constructed the miRNA-miRNA synergistic network from the miRNA-mRNA network, considering not only the enrichment of target genes but also GO function enrichment of co-regulated target genes. Results We found that the average degree of age-related miRNAs was significantly higher than that of non age-related miRNAs in the miRNA-mRNA regulatory network. The topological features between age-related and non age-related miRNAs were significantly different, and 34 reliable age-related miRNA synergistic modules were identified using Cfinder in the miRNA-miRNA synergistic network. The synergistic regulations of module genes were verified by reviewing miRNA target databases and previous studies. Conclusions Age-related miRNAs play a more important role than non age-related mrRNAs in the developmental and aging process of the human brain. The age-related miRNAs have synergism, which tend to work together as small modules. These results may provide a new insight into the regulation of miRNAs in the developmental and aging process of the human brain.
Pervasive Developmental Disorders in Girls
Pervasive developmental disorders are a group of conditions sharing as their common features impairment in social reciprocity,\\u000a developmental disturbances affecting communication, and manifestation of restricted and repetitive behaviors. Autism is the\\u000a prototypical pervasive developmental disorder, and others include Asperger's Disorder, Rett's Disorder, Childhood Disintegrative\\u000a Disorder, and Pervasive Developmental Disorder-Not Otherwise Specified (PDD-NOS). Critical to understanding these conditions\\u000a is appreciation of
Kathleen Koenig; Katherine D. Tsatsanis
Evaluation of Developmental Toxicants and Signaling Pathways in a Functional Test Based on the Migration of Human Neural Crest Cells
Background: Information on the potential developmental toxicity (DT) of the majority of chemicals is scarce, and test capacities for further animal-based testing are limited. Therefore, new approaches with higher throughput are required. A screening strategy based on the use of relevant human cell types has been proposed by the U.S. Environmental Protection Agency and others. Because impaired neural crest (NC) function is one of the known causes for teratologic effects, testing of toxicant effects on NC cells is desirable for a DT test battery. Objective: We developed a robust and widely applicable human-relevant NC function assay that would allow for sensitive screening of environmental toxicants and defining toxicity pathways. Methods: We generated NC cells from human embryonic stem cells, and after establishing a migration assay of NC cells (MINC assay), we tested environmental toxicants as well as inhibitors of physiological signal transduction pathways. Results: Methylmercury (50 nM), valproic acid (> 10 �M), and lead-acetate [Pb(CH3CO2)4] (1 �M) affected the migration of NC cells more potently than migration of other cell types. The MINC assay correctly identified the NC toxicants triadimefon and triadimenol. Additionally, it showed different sensitivities to various organic and inorganic mercury compounds. Using the MINC assay and applying classic pharmacologic inhibitors and large-scale microarray gene expression profiling, we found several signaling pathways that are relevant for the migration of NC cells. Conclusions: The MINC assay faithfully models human NC cell migration, and it reveals impairment of this function by developmental toxicants with good sensitivity and specificity.
Zimmer, Bastian; Lee, Gabsang; Balmer, Nina V; Meganathan, Kesavan; Sachinidis, Agapios; Studer, Lorenz
NTP-CERHR Monograph on the Potential Human Reproductive and Developmental Effects of Di-isononyl Phthalate (DINP).
The National Toxicology Program (NTP) Center for the Evaluation of Risks to Human Reproduction (CERHR) conducted an evaluation of the potential for di-isononyl phthalate (DINP) to cause adverse effects on reproduction and development in humans. DINP is one of 7 phthalate chemicals evaluated by the NTP CERHR Phthalates Expert Panel. These phthalates were selected for evaluation because of high production volume, extent of human exposures, use in children's products, and/or published evidence of reproductive or developmental toxicity. DINP is a mixture of branched, C-9 phthalate isomers used to add flexibility to a wide variety of plastic products such as toys, garden hoses, flooring tiles, tarps, and pool liners. The results of this evaluation on DINP are published in a NTP-CERHR monograph which includes: 1) the NTP Brief, 2) the Expert Panel Report on the Reproductive and Developmental Toxicity of Di-isononyl Phthalate, and 3) public comments received on the Expert Panel Report. As stated in the NTP Brief, the NTP reached the following conclusions regarding the possible effects of exposure to DINP on human development and reproduction. First, although DINP could possibly affect human development if exposures are sufficiently high, there is minimal concern for DINP causing adverse effects to human reproduction or fetal development. There is no direct evidence that exposure of people to DINP adversely affects reproduction or development, but studies show that oral exposure of pregnant rats to high doses (500 and 1000 mg/kg bodyweight/day) of DINP can adversely affect fetal development. Effects on pup growth were noted in a 2-generation reproductive toxicity study in rats at doses of 143-285 mg/kg body weight/day. Human exposure information for DINP was not available but it was assumed that the general US population would be exposed to 3-30 mug/kg body weight/day, based upon the range of estimated exposures for DEHP, a more widely used phthalate. Second, based on estimates of exposure of children to DINP from mouthing toys and other objects, the NTP has minimal concern for developmental effects in children. After the expert panel meeting, a US Consumer Products Safety Commission panel estimated that the majority of children exposed to DINP had a "minimum to non-existent risk of injury" from mouthing toys. Children's exposure was estimated at 70-280 mug/kg body weight/day, a level 1000-fold lower than exposures resulting in developmental effects in rats. NTP-CERHR monographs are transmitted to federal and state agencies, interested parties, and the public and are available electronically in PDF format on the CERHR web site (http://cerhr.niehs.nih.gov) and in printed text or CD-ROM from the CERHR (National Institute of Environmental Health Sciences, P.O. Box 12233, MD EC-32, Research Triangle Park, NC; fax: 919-316-4511). PMID:15995726
Developmental validation of a novel lateral flow strip test for rapid identification of human blood (Rapid Stain Identification--Blood).
Human blood is the body fluid most commonly encountered at crime scenes, and blood detection may aid investigators in reconstructing what occurred during a crime. In addition, blood detection can help determine which items of evidence should be processed for DNA-STR testing. Unfortunately, many common substances can cause red-brown stains that resemble blood. Furthermore, many current human blood detection methods are presumptive and prone to false positive results. Here, the developmental validation of a new blood identification test, Rapid Stain Identification--Blood (RSID--Blood), is described. RSID--Blood utilizes two anti-glycophorin A (red blood cell membrane specific protein) monoclonal antibodies in a lateral flow strip test format to detect human blood. We present evidence demonstrating that this test is accurate, reproducible, easy to use, and highly specific for human blood. Importantly, RSID--Blood does not cross-react with ferret, skunk, or primate blood and exhibits no high-dose hook effect. Also, we describe studies on the sensitivity, body fluid specificity, and species specificity of RSID--Blood. In addition, we show that the test can detect blood from a variety of forensic exhibits prior to processing for DNA-STR analysis. In conclusion, we suggest that RSID--Blood is effective and useful for the detection of human blood on forensic exhibits, and offers improved blood detection when compared to other currently used methods. PMID:19083828
Schweers, Brett A; Old, Jennifer; Boonlayangoor, P W; Reich, Karl A
Deconstructing Pancreas Developmental Biology
The relentless nature and increasing prevalence of human pancreatic diseases, in particular, diabetes mellitus and adenocarcinoma, has motivated further understanding of pancreas organogenesis. The pancreas is a multifunctional organ whose epithelial cells govern a diversity of physiologically vital endocrine and exocrine functions. The mechanisms governing the birth, differentiation, morphogenesis, growth, maturation, and maintenance of the endocrine and exocrine components in the pancreas have been discovered recently with increasing tempo. This includes recent studies unveiling mechanisms permitting unexpected flexibility in the developmental potential of immature and mature pancreatic cell subsets, including the ability to interconvert fates. In this article, we describe how classical cell biology, genetic analysis, lineage tracing, and embryological investigations are being complemented by powerful modern methods including epigenetic analysis, time-lapse imaging, and flow cytometry-based cell purification to dissect fundamental processes of pancreas development.
Benitez, Cecil M.; Goodyer, William R.
Gene expression profiles in the cerebellum and hippocampus following exposure to a neurotoxicant, Aroclor 1254: Developmental effects.
The developmental consequences of exposure to the polychlorinated biphenyls (PCBs) have been widely studied, making PCBs a unique model to understand issues related to environmental mixture of persistent chemicals. PCB exposure in humans adversely affects neurocognitive developm...
Understanding the meaning of human dignity in Korea: a content analysis
This study aims to understand the meaning of human dignity among adults in Korea. The authors utilized a qualitative study design. Data were collected with non-structured questions in a sample of 74 Korean adults and were then analyzed with qualitative content analysis. There were 4 categories, 31 themes and 106 theme clusters classified. The four categories that emerged were: fullness of dignity, loss of dignity, reinforcement of dignity, and enfeeblement of dignity. The results of this study may contribute to healthcare professionals� understanding of Korean adults� human dignity.
Jo, Kae-Hwa; Doorenbos, Ardith
A silly expression: Consultants' implicit and explicit understanding of Medical Humanities. A qualitative analysis.
The term Medical Humanities has still not been established in the wider medical, educational and academic communities. This qualitative study, conducted across three acute care trusts, is an exploration of whether clinicians were familiar with the term Medical Humanities, and if so, what the term meant to them and whether they considered the associated concepts relevant to medical practice and education. Reactions to the term Medical Humanities were varied: many clinicians had not heard of the term before, some were unsure what it meant, others displayed mistrust or contempt for it. Explicit definitions that were elicited were categorised (inductively) according to three main approaches to the understanding of Medical Humanities: Humanistic-holistic, Humanities-medicine seperate and Intellectual exercise. Findings indicate that the lack of clarity about the term Medical Humanities among experienced healthcare professionals, contrasts with their sophisticated implicit knowledge of key issues frequently associated with Medical Humanities. Thus, while some clinicians could not define Medical Humanities and some definitions separated humanities from medicine, all clinicians implicitly acknowledged the importance of Medical Humanities issues within their clinical and teaching practices during conversations prior to any mention of the term. It appears that clinicians as role models for medical students can inadvertently convey an ambivalent position towards the Medical Humanities that encompass the very values and attitudes they are trying to inculcate, sending out mixed messages to the novices. PMID:23673809
Knight, L V
Developmental origins of adult diseases
There is considerable evidence for the fact that early life environment in human beings are associated with future development of various metabolic diseases. Fetal programming and perinatal events appear to exert effects on later life that are independent of environmental risk factors in adults. Our understanding of the underlying mechanisms are limited and remains unclear. However several animal models and epidemiological studies have shown this association, and it is assumed secondary to the penalties of developmental plasticity. In this review, we amalgamate facts from several disciplines to support this hypothesis.
Mathew, Vivek; Ayyar, S. Vageesh
The Psychology of Isolated and Confined Environments: Understanding Human Behavior in Antarctica.
ERIC Educational Resources Information Center
Reviews lessons learned from research in Antarctica with relevance to understanding human behavior in other isolated and confined environments. Outlines four distinct characteristics of psychosocial adaptation to such environments and discusses some of the benefits for individuals seeking challenging experiences. (Contains references.) (SLD)
Palinkas, Lawrence A.
X Chromosome Abnormalities and Cognitive Development: Implications for Understanding Normal Human Development.
ERIC Educational Resources Information Center
Argues that knowledge from studies of individuals with sex chromosome abnormalities can further understanding of aspects of normal human development. Studies of XO girls, XXY boys, XXX girls, and males with a fragile X chromosome are summarized to demonstrate how results contribute to knowledge about normal cognitive development and about�
Walzer, Stanley
The Dolphin's (Tursiops truncatus) Understanding of Human Gazing and Pointing: Knowing What and Where
The authors tested whether the understanding by dolphins (Tursiops truncatus) of human pointing and head-gazing cues extends to knowing the identity of an indicated object as well as its location. In Experiment 1, the dolphins Phoenix and Akeakamai processed the identity of a cued object (of 2 that were present), as shown by their success in selecting a matching object
Adam A. Pack; Louis M. Herman
A Literature-Circles Approach to Understanding Science as a Human Endeavor
ERIC Educational Resources Information Center
The reading of science-related, historical nonfiction alone does not necessarily lead students to make personal connections to science or understand science as a human endeavor interdependent with culture, society, and history. Teachers must structure students' reading to ensure that they consider specific aspects of science while reading and�
Straits, William
Communicating Numerical Risk: Human Factors That Aid Understanding in Health Care
In this chapter, we review evidence from the human factors literature that verbal and visual formats can help increase the understanding of numerical risk information in health care. These visual representations of risk are grounded in empirically supported theory. As background, we first review research showing that people often have difficulty understanding numerical risks and benefits in health information. In particular, we discuss how understanding the meanings of numbers results in healthier decisions. Then, we discuss the processes that determine how communication of numerical risks can enhance (or degrade) health judgments and decisions. Specifically, we examine two different approaches to risk communication: a traditional approach and fuzzy-trace theory. Applying research on the complications of understanding and communicating risks, we then highlight how different visual representations are best suited to communicating different risk messages (i.e., their gist). In particular, we review verbal and visual messages that highlight gist representations that can better communicate health information and improve informed decision making. This discussion is informed by human factors theories and methods, which involve the study of how to maximize the interaction between humans and the tools they use. Finally, we present implications and recommendations for future research on human factors in health care.
Brust-Renck, Priscila G.; Royer, Caisa E.; Reyna, Valerie F.
The Circuit of Culture: A Strategy for Understanding the Evolving Human Dimensions of Wildland Fire
In this conceptual article, the authors explore the possibilities of another approach to examining the human dimensions of wildland fire. They argue that our understanding of this issue could be enhanced by considering a cultural studies construct known as the �circuit of culture.� This cross-disciplinary perspective provides increased analytic power by accounting for the meaningful role of 5 cultural processes
Joseph G. Champ; Jeffrey J. Brooks
Deletion of Porcn in Mice Leads to Multiple Developmental Defects and Models Human Focal Dermal Hypoplasia (Goltz Syndrome)
Background Focal Dermal Hypoplasia (FDH) is a genetic disorder characterized by developmental defects in skin, skeleton and ectodermal appendages. FDH is caused by dominant loss-of-function mutations in X-linked PORCN. PORCN orthologues in Drosophila and mice encode endoplasmic reticulum proteins required for secretion and function of Wnt proteins. Wnt proteins play important roles in embryo development, tissue homeostasis and stem cell maintenance. Since features of FDH overlap with those seen in mouse Wnt pathway mutants, FDH likely results from defective Wnt signaling but molecular mechanisms by which inactivation of PORCN affects Wnt signaling and manifestations of FDH remain to be elucidated. Results We introduced intronic loxP sites and a neomycin gene in the mouse Porcn locus for conditional inactivation. Porcn-ex3-7flox mice have no apparent developmental defects, but chimeric mice retaining the neomycin gene (Porcn-ex3-7Neo-flox) have limb, skin, and urogenital abnormalities. Conditional Porcn inactivation by EIIa-driven or Hprt-driven Cre recombinase results in increased early embryonic lethality. Mesenchyme-specific Prx-Cre-driven inactivation of Porcn produces FDH-like limb defects, while ectodermal Krt14-Cre-driven inactivation produces thin skin, alopecia, and abnormal dentition. Furthermore, cell-based assays confirm that human PORCN mutations reduce WNT3A secretion. Conclusions These data indicate that Porcn inactivation in the mouse produces a model for human FDH and that phenotypic features result from defective WNT signaling in ectodermal- and mesenchymal-derived structures.
Liu, Wei; Shaver, Timothy M.; Balasa, Alfred; Ljungberg, M. Cecilia; Wang, Xiaoling; Wen, Shu; Nguyen, Hoang; Van den Veyver, Ignatia B.
Developmental Expression of HERV-R (ERV3) and HERV-K in Human Tissue
The human endogenous retroviruses (HERVs), ERV3 (HERV-R) and HERV-K, are both known to be transcriptionally active in human placenta. In the case of ERV3 there is also indirect evidence for its participation in cellular differentiation. In this study we examined the expression of ERV3 (HERV-R) and HERV-K in human normal fetal tissues by in situ hybridization. The highest level of
Ann-Catrin Andersson; Patrick J. W Venables; Ralf R T�njes; J�rgen Scherer; Lars Eriksson; Erik Larsson
The Importance of Human Reliability Analysis in Human Space Flight: Understanding the Risks
NASA Technical Reports Server (NTRS)
HRA is a method used to describe, qualitatively and quantitatively, the occurrence of human failures in the operation of complex systems that affect availability and reliability. Modeling human actions with their corresponding failure in a PRA (Probabilistic Risk Assessment) provides a more complete picture of the risk and risk contributions. A high quality HRA can provide valuable information on potential areas for improvement, including training, procedural, equipment design and need for automation.
Hamlin, Teri L.
Global Developmental Gene Expression and Pathway Analysis of Normal Brain Development and Mouse Models of Human Neuronal Migration Defects
Heterozygous LIS1 mutations are the most common cause of human lissencephaly, a human neuronal migration defect, and DCX mutations are the most common cause of X-linked lissencephaly. LIS1 is part of a protein complex including NDEL1 and 14-3-3? that regulates dynein motor function and microtubule dynamics, while DCX stabilizes microtubules and cooperates with LIS1 during neuronal migration and neurogenesis. Targeted gene mutations of Lis1, Dcx, Ywhae (coding for 14-3-3?), and Ndel1 lead to neuronal migration defects in mouse and provide models of human lissencephaly, as well as aid the study of related neuro-developmental diseases. Here we investigated the developing brain of these four mutants and wild-type mice using expression microarrays, bioinformatic analyses, and in vivo/in vitro experiments to address whether mutations in different members of the LIS1 neuronal migration complex lead to similar and/or distinct global gene expression alterations. Consistent with the overall successful development of the mutant brains, unsupervised clustering and co-expression analysis suggested that cell cycle and synaptogenesis genes are similarly expressed and co-regulated in WT and mutant brains in a time-dependent fashion. By contrast, focused co-expression analysis in the Lis1 and Ndel1 mutants uncovered substantial differences in the correlation among pathways. Differential expression analysis revealed that cell cycle, cell adhesion, and cytoskeleton organization pathways are commonly altered in all mutants, while synaptogenesis, cell morphology, and inflammation/immune response are specifically altered in one or more mutants. We found several commonly dysregulated genes located within pathogenic deletion/duplication regions, which represent novel candidates of human mental retardation and neurocognitive disabilities. Our analysis suggests that gene expression and pathway analysis in mouse models of a similar disorder or within a common pathway can be used to define novel candidates for related human diseases.
Pramparo, Tiziano; Libiger, Ondrej; Jain, Sonia; Li, Hong; Youn, Yong Ha; Hirotsune, Shinji; Schork, Nicholas J.; Wynshaw-Boris, Anthony
Genomic features and computational identification of human microRNAs under long-range developmental regulation
Background Recent functional studies have demonstrated that many microRNAs (miRNAs) are expressed by RNA polymerase II in a specific spatiotemporal manner during the development of organisms and play a key role in cell-lineage decisions and morphogenesis. They are therefore functionally related to a number of key protein coding developmental genes, that form genomic regulatory blocks (GRBs) with arrays of highly conserved non-coding elements (HCNEs) functioning as long-range enhancers that collaboratively regulate the expression of their target genes. Given this functional similarity as well as recent zebrafish transgenesis assays showing that the miR-9 family is indeed regulated by HCNEs with enhancer activity, we hypothesized that this type of miRNA regulation is prevalent. In this paper, we therefore systematically investigate the regulatory landscape around conserved self-transcribed miRNAs (ST miRNAs), with their own known or computationally inferred promoters, by analyzing the hallmarks of GRB target genes. These include not only the density of HCNEs in their vicinity but also the presence of large CpG islands (CGIs) and distinct patterns of histone modification marks associated with developmental genes. Results Our results show that a subset of the conserved ST miRNAs we studied shares properties similar to those of protein-coding GRB target genes: they are located in regions of significantly higher HCNE/enhancer binding density and are more likely to be associated with CGIs. Furthermore, their putative promoters have both activating as well as silencing histone modification marks during development and differentiation. Based on these results we used both an elevated HCNE density in the genomic vicinity as well as the presence of a bivalent promoter to identify 29 putative GRB target miRNAs/miRNA clusters, over two-thirds of which are known to play a role during development and differentiation. Furthermore these predictions include miRNAs of the miR-9 family, which are the only experimentally verified GRB target miRNAs. Conclusions A subset of the conserved miRNA loci we investigated exhibits typical characteristics of GRB target genes, which may partially explain their complex expression profiles during development.
Recent Advances in Understanding the Role of Nutrition in Human Genome Evolution12
Dietary transitions in human history have been suggested to play important roles in the evolution of mankind. Genetic variations caused by adaptation to diet during human evolution could have important health consequences in current society. The advance of sequencing technologies and the rapid accumulation of genome information provide an unprecedented opportunity to comprehensively characterize genetic variations in human populations and unravel the genetic basis of human evolution. Series of selection detection methods, based on various theoretical models and exploiting different aspects of selection signatures, have been developed. Their applications at the species and population levels have respectively led to the identification of human specific selection events that distinguish human from nonhuman primates and local adaptation events that contribute to human diversity. Scrutiny of candidate genes has revealed paradigms of adaptations to specific nutritional components and genome-wide selection scans have verified the prevalence of diet-related selection events and provided many more candidates awaiting further investigation. Understanding the role of diet in human evolution is fundamental for the development of evidence-based, genome-informed nutritional practices in the era of personal genomics.
Ye, Kaixiong; Gu, Zhenglong
The early origins of human charity: developmental changes in preschoolers' sharing with poor and wealthy individuals
Recent studies have provided evidence that young children already engage in sharing behavior. The underlying social-cognitive mechanisms, however, are still under debate. In particular, it is unclear whether or not young children�s sharing is motivated by an appreciation of others� wealth. Manipulating the material needs of recipients in a sharing task (Experiment 1) and a resource allocation task (Experiment 2), we show that 5- but not 3-year-old children share more with poor than wealthy individuals. The 3-year-old children even showed a tendency to behave less selfishly towards the rich, yet not the poor recipient. This suggests that very early instances of sharing behavior are not motivated by a consideration of others� material needs. Moreover, the results show that 5-year-old children were rather inclined to give more to the poor individual than distributing the resources equally, demonstrating that their wish to support the poor overruled the otherwise very prominent inclination to share resources equally. This indicates that charity has strong developmental roots in preschool children.
Paulus, Markus
Spatial frequency discrimination learning in normal and developmentally impaired human vision
Perceptual learning effects demonstrate that the adult visual system retains neural plasticity. If perceptual learning holds any value as a treatment tool for amblyopia, trained improvements in performance must generalise. Here we investigate whether spatial frequency discrimination learning generalises within task to other spatial frequencies, and across task to contrast sensitivity. Before and after training, we measured contrast sensitivity and spatial frequency discrimination (at a range of reference frequencies 1, 2, 4, 8, 16�c/deg). During training, normal and amblyopic observers were divided into three groups. Each group trained on a spatial frequency discrimination task at one reference frequency (2, 4, or 8�c/deg). Normal and amblyopic observers who trained at lower frequencies showed a greater rate of within task learning (at their reference frequency) compared to those trained at higher frequencies. Compared to normals, amblyopic observers showed greater within task learning, at the trained reference frequency. Normal and amblyopic observers showed asymmetrical transfer of learning from high to low spatial frequencies. Both normal and amblyopic subjects showed transfer to contrast sensitivity. The direction of transfer for contrast sensitivity measurements was from the trained spatial frequency to higher frequencies, with the bandwidth and magnitude of transfer greater in the amblyopic observers compared to normals. The findings provide further support for the therapeutic efficacy of this approach and establish general principles that may help develop more effective protocols for the treatment of developmental visual deficits.
Astle, Andrew T.; Webb, Ben S.; McGraw, Paul V.
The Lutheran blood group glycoprotein, another member of the immunoglobulin superfamily, is widely expressed in human tissues and is developmentally regulated in human liver.
Glycoproteins expressing the Lutheran blood group antigens were isolated from human erythrocyte membranes and from human fetal liver. Amino acid sequence analyses allowed the design of redundant oligonucleotides that were used to generate a 459-bp, sequence-specific probe by PCR. A cDNA clone of 2400 bp was isolated from a human placental lambda gt 11 library and sequenced, and the deduced amino acid sequence was studied. The predicted mature protein is a type I membrane protein of 597 amino acids with five potential N-glycosylation sites. There are five disulfide-bonded, extracellular, immunoglobulin superfamily domains (two variable-region set and three constant-region set), a single hydrophobic, membrane-spanning domain, and a cytoplasmic domain of 59 residues. The overall structure is similar to that of the human tumor marker MUC 18 and the chicken neural adhesion molecule SC1. The extracellular domains and cytoplasmic domain contain consensus motifs for the binding of integrin and Src homology 3 domains, respectively, suggesting possible receptor and signal-transduction function. Immunostaining of human tissues demonstrated a wide distribution and provided evidence that the glycoprotein is under developmental control in liver and may also be regulated during differentiation in other tissues. Images Fig. 1
Parsons, S F; Mallinson, G; Holmes, C H; Houlihan, J M; Simpson, K L; Mawby, W J; Spurr, N K; Warne, D; Barclay, A N; Anstee, D J
Gut microbiota: next frontier in understanding human health and development of biotherapeutics
The gut microbiota is a remarkable asset for human health. As a key element in the development and prevention of specific diseases, its study has yielded a new field of promising biotherapeutics. This review provides comprehensive and updated knowledge of the human gut microbiota, its implications in health and disease, and the potentials and limitations of its modification by currently available biotherapeutics to treat, prevent and/or restore human health, and future directions. Homeostasis of the gut microbiota maintains various functions which are vital to the maintenance of human health. Disruption of the intestinal ecosystem equilibrium (gut dysbiosis) is associated with a plethora of human diseases, including autoimmune and allergic diseases, colorectal cancer, metabolic diseases, and bacterial infections. Relevant underlying mechanisms by which specific intestinal bacteria populations might trigger the development of disease in susceptible hosts are being explored across the globe. Beneficial modulation of the gut microbiota using biotherapeutics, such as prebiotics, probiotics, and antibiotics, may favor health-promoting populations of bacteria and can be exploited in development of biotherapeutics. Other technologies, such as development of human gut models, bacterial screening, and delivery formulations eg, microencapsulated probiotics, may contribute significantly in the near future. Therefore, the human gut microbiota is a legitimate therapeutic target to treat and/or prevent various diseases. Development of a clear understanding of the technologies needed to exploit the gut microbiota is urgently required.
Prakash, Satya; Rodes, Laetitia; Coussa-Charley, Michael; Tomaro-Duchesneau, Catherine
Eight Problems for the Mirror Neuron Theory of Action Understanding in Monkeys and Humans
The discovery of mirror neurons in macaque frontal cortex has sparked a resurgence of interest in motor/embodied theories of cognition. This critical review examines the evidence in support of one of these theories, namely that the mirror neurons provide the basis of action understanding. It is argued that there is no evidence from monkey data that directly tests this theory, and evidence from humans makes a strong case against the position.
Hickok, Gregory
A Literature-Circles Approach to Understanding Science as a Human Endeavor
NSDL National Science Digital Library
Unfortunately, the reading of science-related, historical nonfiction alone does not necessarily lead students to make personal connections to science or understand science as a human endeavor interdependent with culture, society, and history. Teachers must structure students' reading to ensure that they consider specific aspects of science while reading and discussing books. One way for teachers to focus their students' attention on components of the nature of science is through the use of literature circles.
Straits, William
Impairment of the Developmental Potential of Frozen-Thawed Human Zygotes Obtained After Intracytoplasmic Sperm Injection
Objective: To evaluate the effects of cryopreservation on the survival, cleavage, and morphology of embryos and on the implantation and embryonic loss rates of human zygotes obtained after ICSI compared with frozen-thawed zygotes obtained after traditional IVF. A further objective was to evaluate the same parameters in nonfrozen sibling ICSI and IVF zygotes and to compare them with corresponding frozen-thawed
Ervin Macas; Bruno Imthurn; Marika Borsos; Marinella Rosselli; Estilla Maurer-Major; Paul J Keller
Deletion of the c-kit protooncogene in the human developmental defect piebald trait
The protooncogene c-kit is critical for development of hematopoietic stem cells, germ cells, and melanoblasts in the mouse. Homozygous mutations of this gene in the mouse cause anemia, infertility, and albinism, whereas heterozygous mutant mice usually exhibit only a white forehead blaze and depigmentation of the ventral body, tail, and feet. The heterozygous mouse phenotype is very similar to human piebald trait, which is characterized by a congenital white hair forelock and ventral and extremity depigmentation. To investigate the possibility that alterations in the human c-kit gene may be a cause of piebald trait, DNA from seven unrelated affected individuals was examined by Southern blot analysis. One subject, although cytogenetically normal, has a heterozygous deletion of the c-kit protooncogene. This deletion encompasses the entire coding region for c-kit and also involves the closely linked gene for platelet-derived growth factor receptor {alpha}. These findings provide molecular evidence mapping piebald trait to the c-kit locus on chromosome 4. Although the authors cannot exclude the involvement of other closely linked genes, the demonstration of a genomic c-kit deletion in one subject with piebald trait and the marked concordance of the human and mouse phenotypes provide strong evidence for the role of c-kit in the development of human melanocytes and in the pathogenesis of piebald trait.
Fleischman, R.A.; Stastny, V.; Zneimer, S. (Univ. of Texas, Dallas (United States)); Saltman, D.L. (Genelabs, Inc., Redwood City, CA (United States))
Developmental Testing of Habitability and Human Factors Tools and Methods During Neemo 15
NASA Technical Reports Server (NTRS)
Currently, no established methods exist to collect real-time human factors and habitability data while crewmembers are living aboard the International Space Station (ISS), traveling aboard other space vehicles, or living in remote habitats. Currently, human factors and habitability data regarding space vehicles and habitats are acquired at the end of missions during postflight crew debriefs. These debriefs occur weeks or often longer after events have occurred, which forces a significant reliance on incomplete human memory, which is imperfect. Without a means to collect real-time data, small issues may have a cumulative effect and continue to cause crew frustration and inefficiencies. Without timely and appropriate reporting methodologies, issues may be repeated or lost. TOOL DEVELOPMENT AND EVALUATION: As part of a directed research project (DRP) aiming to develop and validate tools and methods for collecting near real-time human factors and habitability data, a preliminary set of tools and methods was developed. These tools and methods were evaluated during the NASA Extreme Environments Mission Operations (NEEMO) 15 mission in October 2011. Two versions of a software tool were used to collect observational data from NEEMO crewmembers that also used targeted strategies for using video cameras to collect observations. Space habitability observation reporting tool (SHORT) was created based on a tool previously developed by NASA to capture human factors and habitability issues during spaceflight. SHORT uses a web-based interface that allows users to enter a text description of any observations they wish to report and assign a priority level if changes are needed. In addition to the web-based format, a mobile Apple (iOS) format was implemented, referred to as iSHORT. iSHORT allows users to provide text, audio, photograph, and video data to report observations. iSHORT can be deployed on an iPod Touch, iPhone, or iPad; for NEEMO 15, the app was provided on an iPad2.
Thaxton, S. S.; Litaker, H. L., Jr.; Holden, K. L.; Adolf, J. A.; Pace, J.; Morency, R. M.
Developmental dyscalculia is a specific learning disability affecting the acquisition of arithmetic skills in an otherwise-normal child. Although poor teaching, environmental deprivation, and low intelligence have been implicated in the etiology of developmental dyscalculia, current data indicate that this learning disability is a brain-based disorder with a familial-genetic predisposition. The neurologic substrate of developmental dyscalculia is thought to involve both
Ruth S Shalev; Varda Gross-Tsur
The Extended Nutrigenomics - Understanding the Interplay between the Genomes of Food, Gut Microbes, and Human Host
Comprehensive investigation of nutritional health effects at the molecular level requires the understanding of the interplay between three genomes, the food, the gut microbial, and the human host genome. Food genomes are researched for discovery and exploitation of macro- and micronutrients as well as specific bioactives, with those genes coding for bioactive proteins and peptides being of central interest. The human gut microbiota encompasses a complex ecosystem in the intestine with profound impact on host metabolism. It is being studied at genomic and, more recently, also at proteomic and metabonomic level. Humans are being characterized at the level of genetic pre-disposition and inter-individual variability in terms of (i) response to nutritional interventions and direction of health trajectories; (ii) epigenetic, metabolic programming at certain life stages with health consequences later in life and even for subsequent generations; and (iii) acute genomic expression as a holistic response to diet, monitored at gene transcript, protein and metabolite level. Modern nutrition science explores health-related aspects of bioactive food components, thereby promoting health, preventing, or delaying the onset of disease, optimizing performance and assessing benefits and risks in individuals and subpopulations. Personalized nutrition means adapting food to individual needs, depending on the human host�s life stage, -style, and -situation. Traditionally, nutrigenomics and nutri(epi)genetics are seen as the key sciences to understand human variability in preferences and requirements for diet as well as responses to nutrition. This article puts the three nutrition and health-relevant genomes into perspective, namely the food, the gut microbial and the human host�s genome, and calls for an �extended nutrigenomics� approach in order to build the future tools for personalized nutrition, health maintenance, and disease prevention. We discuss examples of these genomes, proteomes, transcriptomes, and metabolomes under the definition of genomics as the overarching term covering essentially all Omics rather than the sole study of DNA and RNA.
Kussmann, Martin; Van Bladeren, Peter J.
The Extended Nutrigenomics - Understanding the Interplay between the Genomes of Food, Gut Microbes, and Human Host.
Comprehensive investigation of nutritional health effects at the molecular level requires the understanding of the interplay between three genomes, the food, the gut microbial, and the human host genome. Food genomes are researched for discovery and exploitation of macro- and micronutrients as well as specific bioactives, with those genes coding for bioactive proteins and peptides being of central interest. The human gut microbiota encompasses a complex ecosystem in the intestine with profound impact on host metabolism. It is being studied at genomic and, more recently, also at proteomic and metabonomic level. Humans are being characterized at the level of genetic pre-disposition and inter-individual variability in terms of (i) response to nutritional interventions and direction of health trajectories; (ii) epigenetic, metabolic programming at certain life stages with health consequences later in life and even for subsequent generations; and (iii) acute genomic expression as a holistic response to diet, monitored at gene transcript, protein and metabolite level. Modern nutrition science explores health-related aspects of bioactive food components, thereby promoting health, preventing, or delaying the onset of disease, optimizing performance and assessing benefits and risks in individuals and subpopulations. Personalized nutrition means adapting food to individual needs, depending on the human host's life stage, -style, and -situation. Traditionally, nutrigenomics and nutri(epi)genetics are seen as the key sciences to understand human variability in preferences and requirements for diet as well as responses to nutrition. This article puts the three nutrition and health-relevant genomes into perspective, namely the food, the gut microbial and the human host's genome, and calls for an "extended nutrigenomics" approach in order to build the future tools for personalized nutrition, health maintenance, and disease prevention. We discuss examples of these genomes, proteomes, transcriptomes, and metabolomes under the definition of genomics as the overarching term covering essentially all Omics rather than the sole study of DNA and RNA. PMID:22303317
Kussmann, Martin; Van Bladeren, Peter J
Large-scale gene expression profiling data for the model moss Physcomitrella patens aid understanding of developmental progression, culture and stress conditions.
The moss Physcomitrella patens is an important model organism for studying plant evolution, development, physiology and biotechnology. Here we have generated microarray gene expression data covering the principal developmental stages, culture forms and some environmental/stress conditions. Example analyses of developmental stages and growth conditions as well as abiotic stress treatments demonstrate that (i) growth stage is dominant over culture conditions, (ii) liquid culture is not stressful for the plant, (iii) low pH might aid protoplastation by reduced expression of cell wall structure genes, (iv) largely the same gene pool mediates response to dehydration and rehydration, and (v) AP2/EREBP transcription factors play important roles in stress response reactions. With regard to the AP2 gene family, phylogenetic analysis and comparison with Arabidopsis thaliana shows commonalities as well as uniquely expressed family members under drought, light perturbations and protoplastation. Gene expression profiles for P.�patens are available for the scientific community via the easy-to-use tool at https://www.genevestigator.com. By providing large-scale expression profiles, the usability of this model organism is further enhanced, for example by enabling selection of control genes for quantitative real-time PCR. Now, gene expression levels across a broad range of conditions can be accessed online for P.�patens. PMID:24889180
Hiss, Manuel; Laule, Oliver; Meskauskiene, Rasa M; Arif, Muhammad A; Decker, Eva L; Erxleben, Anika; Frank, Wolfgang; Hanke, Sebastian T; Lang, Daniel; Martin, Anja; Neu, Christina; Reski, Ralf; Richardt, Sandra; Schallenberg-R�dinger, Mareike; Sz�v�nyi, Peter; Tiko, Theodhor; Wiedemann, Gertrud; Wolf, Luise; Zimmermann, Philip; Rensing, Stefan A
Successful Entrepreneurship as Developmental Outcome: A Path Model From a Lifespan Perspective of Human Development
Applying a lifespan approach of human development, this study examined pathways to entrepreneurial success by analyzing retrospective and current data. Along the lines of McClelland�s ideas of early entrepreneurship development and Rauch and Frese�s Giessen-Amsterdam model on venture success, we investigated the roles of founders� adolescent years (early role models, authoritative parenting, and early entrepreneurial competence), personality traits (Big Five
Martin Obschonka; Rainer K. Silbereisen; Eva Schmitt-Rodermund
Species differences in developmental toxicity of epoxiconazole and its relevance to humans.
Epoxiconazole, a triazole-based fungicide, was tested in toxicokinetic, prenatal and pre-postnatal toxicity studies in guinea pigs, following oral (gavage) administration at several dose levels (high dose: 90 mg/kg body weight per day). Maternal toxicity was evidenced by slightly increased abortion rates and by histopathological changes in adrenal glands, suggesting maternal stress. No compound-related increase in the incidence of malformations or variations was observed in the prenatal study. In the pre-postnatal study, epoxiconazole did not adversely affect gestation length, parturition, or postnatal growth and development. Administration of epoxiconazole did not alter circulating estradiol levels. Histopathological examination of the placentas did not reveal compound-related effects. The results in guinea pigs are strikingly different to those observed in pregnant rats, in which maternal estrogen depletion, pathological alteration of placentas, increased gestation length, late fetal death, and dystocia were observed after administration of epoxiconazole. In the studies reported here, analysis of maternal plasma concentrations and metabolism after administration of radiolabeled epoxiconazole demonstrated that the different results in rats and guinea pigs were not due to different exposures of the animals. A comprehensive comparison of hormonal regulation of pregnancy and birth in murid rodents and primates indicates that the effects on pregnancy and parturition observed in rats are not applicable to humans. In contrast, the pregnant guinea pig shares many similarities to pregnant humans regarding hormonal regulation and is therefore considered to be a suitable species for extrapolation of related effects to humans. PMID:23630118
Schneider, Steffen; Hofmann, Thomas; Stinchcombe, Stefan; Moreno, Maria Cecilia Rey; Fegert, Ivana; Strauss, Volker; Gr�ters, Sibylle; Fabian, Eric; Thiaener, Jutta; Fussell, Karma C; van Ravenzwaay, Bennard
Towards a systems biology understanding of human health: interplay between genotype, environment and nutrition.
Sequencing of the human genome has opened the door to the most exciting new era for the holistic system description of human health. It is now possible to study the underlying mechanisms of human health in relation to diet and other environmental factors such as drugs and toxic pollutants. Technological advances make it feasible to envisage that in the future personalized drug treatment and dietary advice and possibly tailored food products can be used for promoting optimal health on an individual basis, in relation to genotype and lifestyle. Life-Science research has in the past very much focused on diseases and how to reestablish human health after illness. Today, the role of food and nutrition in human health and especially prevention of illness is gaining recognition. Diseases of modern civilization, such as diabetes, heart disease and cancer have been shown to be effected by dietary patterns. The risk of disease is often associated with genetic polymorphisms, but the effect is dependent on dietary intake and nutritional status. To understand the link between diet and health, nutritional-research must cover a broad range of areas, from the molecular level to whole body studies. Therefore it provides an excellent example of integrative biology requiring a systems biology approach. The current state and implications of systems biology in the understanding of human health are reviewed. It becomes clear that a complete mechanistic description of the human organism is not yet possible. However, recent advances in systems biology provide a trajectory for future research in order to improve health of individuals and populations. Disease prevention through personalized nutrition will become more important as the obvious avenue of research in life sciences and more focus will need to be put upon those natural ways of disease prevention. In particular, the new discipline of nutrigenomics, which investigates how nutrients interact with humans, taking predetermined genetic factors into account, will mediate new insights into human health that will finally have significant positive impact on our quality of life. PMID:15504703
Desiere, Frank
Amino acid turnover by human oocytes is influenced by gamete developmental competence, patient characteristics and gonadotrophin treatment
STUDY QUESTION Can amino acid profiling differentiate between human oocytes with differing competence to mature to metaphase II (MII) in vitro? SUMMARY ANSWER Oocytes which remained arrested at the germinal vesicle (GV) stage after 24 h of in vitro maturation (IVM) displayed differences in the depletion/appearance of amino acids compared with oocytes which progressed to MII and patient age, infertile diagnosis and ovarian stimulation regime significantly affected oocyte amino acid turnover during IVM. WHAT IS KNOWN ALREADY Amino acid profiling has been proposed as a technique which can distinguish between human pronucleate zygotes and cleavage stage embryos with the potential to develop to the blastocyst stage and implant to produce a pregnancy and those that arrest. Most recently, the amino acid turnover by individual bovine oocytes has been shown to be predictive of oocyte developmental competence as indicated by the gamete's capacity to undergo fertilization and early cleavage divisions in vitro. STUDY DESIGN, SIZE, DURATION The study was conducted between March 2005 and March 2010. A total of 216 oocytes which were at the GV or metaphase I (MI) stages at the time of ICSI were donated by 67 patients. PARTICIPANTS/MATERIALS, SETTINGS, METHODS The research was conducted in university research laboratories affiliated to a hospital-based infertility clinic. Oocytes were cultured for 24 h and the depletion/appearance of amino acids was measured during the final 6 h of IVM. Amino acid turnover was analysed in relation to oocyte meiotic progression, patient age, disease aetiology and controlled ovarian stimulation regime. MAIN RESULTS AND THE ROLE OF CHANCE The depletion/appearance of key amino acids was linked to the maturation potential of human oocytes in vitro. Oocytes which arrested at the GV stage (n = 9) depleted significantly more valine and isoleucine than those which progressed to MI (n = 32) or MII (n = 107) (P < 0.05). Glutamate, glutamine, arginine and valine depletion or appearance differed in MII versus degenerating oocytes (n = 20) (P < 0.05). Glutamine, arginine, methionine, phenylalanine, total depletion and total turnover all differed in oocytes from patients aged < 35 years versus patients ?35 years (P < 0.05). MII oocytes obtained following ovarian stimulation with recombinant FSH depleted more isoleucine (P < 0.05) and more alanine and lysine (P < 0.05) appeared than oocytes from hMG-stimulated cycles. MII oocytes from patients with a polycystic ovary (PCO) morphology (n = 33) depleted more serine (P < 0.05) than oocytes from women with normal ovaries (n = 61). LIMITATIONS, REASONS FOR CAUTION Immature oocytes collected at the time of ICSI were used as the model for human oocyte maturation. These oocytes have therefore failed to respond to the ovulatory hCG trigger in vivo (they are meiotically incompetent), and have limited capacity to support embryo development in vitro. The lack of cumulus cells and stress of the conditions in vitro may have influenced turnover of amino acids, and owing to the small sample sizes further studies are required to confirm these findings. WIDER IMPLICATIONS OF THE FINDINGS The findings provide support for the hypothesis that oocyte metabolism reflects oocyte quality. Longitudinal studies are required to link these functional metabolic indices of human oocyte quality with embryo developmental competence. Oocyte amino acid profiling may be a useful tool to quantify the impact of new assisted reproduction technologies (ART) on oocyte quality. STUDY FUNDING/COMPETING INTERESTS This project was funded by the UK Biology and Biotechnology Research Council (BB/C007395/1) and the Medical Research Council (G 0800250). K.E.H was in receipt of a British Fertility Society/Merck Serono studentship. H.J.L. is a shareholder in Novocellus Ltd, a company which seeks to devise a non-invasive biochemical test of embryo health.
Hemmings, K.E.; Maruthini, D.; Vyjayanthi, S.; Hogg, J.E.; Balen, A.H.; Campbell, B.K.; Leese, H.J.; Picton, H.M.
A Data-Driven Paradigm to Understand Multimodal Communication in Human-Human and Human-Robot Interaction
\\u000a Data-driven knowledge discovery is becoming a new trend in various scientific fields. In light of this, the goal of the present\\u000a paper is to introduce a novel framework to study one interesting topic in cognitive and behavioral studies � multimodal communication\\u000a between human-human and human-robot interaction. We present an overall solution from data capture, through data coding and\\u000a validation, to
Chen Yu; Thomas G. Smith; Shohei Hidaka; Matthias Scheutz; Linda B. Smith
To address the problem of developmental disabilities among children, CDC, the former Division of Birth Defects and Developmental Disabilities, which was funded by the Agency for Toxic Substances and Disease Registry (ATSDR), and the Georgia Department of Human Resources, initiate...
Chromatin structure and developmental expression of the human alpha-globin cluster.
The human alpha-like globins undergo a switch from the embryonic zeta-chain to the alpha-chain early in human development, at approximately the same time as the beta-like globins switch from the embryonic epsilon-to the fetal gamma-chains. We investigated the chromatin structure of the human alpha-globin gene cluster in fetal and adult erythroid cells. Our results indicate that DNase I-hypersensitive sites exist at the 5' ends of the alpha 1- and alpha 2-globin genes as well as at several other sites in the cluster in all erythroid cells examined. In addition, early and late fetal liver erythroid cells and adult bone marrow cells contain hypersensitive sites at the 5' end of the zeta gene, and in a purified population of 130-day-old fetal erythroid cells, the entire zeta-to alpha-globin region is sensitive to DNase I digestion. The presence of features of active chromatin in the zeta-globin region in fetal liver and adult bone marrow cells led us to investigate the transcription of zeta in these cells. By nuclear runoff transcription studies, we showed that initiated polymerases are present on the zeta-globin gene in these normal erythroid cells. Immunofluorescence with anti-zeta-globin antibodies also showed that late fetal liver cells contain zeta-globin. These findings demonstrate that expression of the embryonic zeta-globin continues at a low level in normal cells beyond the embryonic to fetal globin switch. Images
Yagi, M; Gelinas, R; Elder, J T; Peretz, M; Papayannopoulou, T; Stamatoyannopoulos, G; Groudine, M
Metalloproteinases in Drosophila to Humans That Are Central Players in Developmental Processes*
Many secreted proteins are synthesized as precursors with propeptides that must be cleaved to yield the mature functional form of the molecule. In addition, various growth factors occur in extracellular latent complexes with protein antagonists and are activated upon cleavage of such antagonists. Research in the separate fields of embryonic patterning and extracellular matrix formation has identified members of the BMP1/Tolloid-like family of metalloproteinases as key players in these types of biosynthetic processing events in species ranging from Drosophila to humans.
Muir, Alison; Greenspan, Daniel S.
Brief communication: Developmental versus functional three-dimensional geometric morphometric-based modularity of the human proximal humerus.
The proximal humerus is formed by three secondary ossification centers during the postnatal trajectory of the human infant. The ossification centers later grow into the structures of the articular surface, major tubercle, and minor tubercle. There is a purported functional division between the articular surface and the tubercles, with the articular surface mainly responsible for the range of movement of the shoulder joint, and the tubercles bearing the insertions of the rotator cuff muscles, mainly devoted to securing the joint against humeral displacement. Using three-dimensional geometric morphometrics, we tested the presence of such developmental and functional divisions in the proximal humerus, applying the RV coefficient of Escoufier to these a priori hypothesized modules. Our results indicate that the proximal humerus might be a generally integrated structure. However, a weak signal for modular configuration was present, with slightly stronger support for the two modules depicting the boundaries between the purported functional regions of the epiphysis: the articular surface and the tubercles. Am J Phys Anthropol 154:459-465, 2014. � 2014 Wiley Periodicals, Inc. PMID:24723325
Arias-Martorell, Julia; Potau, Josep Maria; Bello-Hellegouarch, Ga�lle; P�rez-P�rez, Alejandro
Developmental insights from early mammalian embryos and core signaling pathways that influence human pluripotent cell growth and differentiation.
Human pluripotent stem cells (hPSCs) have two potentially attractive applications: cell replacement-based therapies and drug discovery. Both require the efficient generation of large quantities of clinical-grade stem cells that are free from harmful genomic alterations. The currently employed colony-type culture methods often result in low cell yields, unavoidably heterogeneous cell populations, and substantial chromosomal abnormalities. Here, we shed light on the structural relationship between hPSC colonies/embryoid bodies and early-stage embryos in order to optimize current culture methods based on the insights from developmental biology. We further highlight core signaling pathways that underlie multiple epithelial-to-mesenchymal transitions (EMTs), cellular heterogeneity, and chromosomal instability in hPSCs. We also analyze emerging methods such as non-colony type monolayer (NCM) and suspension culture, which provide alternative growth models for hPSC expansion and differentiation. Furthermore, based on the influence of cell-cell interactions and signaling pathways, we propose concepts, strategies, and solutions for production of clinical-grade hPSCs, stem cell precursors, and miniorganoids, which are pivotal steps needed for future clinical applications. PMID:24603366
Chen, Kevin G; Mallon, Barbara S; Johnson, Kory R; Hamilton, Rebecca S; McKay, Ronald D G; Robey, Pamela G
Human behavior understanding for assisted living by means of hierarchical context free grammars
NASA Astrophysics Data System (ADS)
Human behavior understanding has attracted the attention of researchers in various fields over the last years. Recognizing behaviors with sufficient accuracy from sensors analysis is still an unsolved problem, because of many reasons, including the low accuracy of the data, differences in the human behaviors as well as the gap between low-level sensors data and high-level scene semantics. In this context, an application that is attracting the interest of both public and industrial entities is the possibility to allow elderly or physically impaired people conducting a normal life at home. Ambient intelligence (AmI) technologies, intended as the possibility of automatically detecting and reacting to the status of the environment and of the persons, is probably the major enabling factor for the achievement of such an ambitious objective. AmI technologies require suitable networks of sensors and actuators, as well as adequate processing and communication technologies. In this paper we propose a solution based on context free grammars for human behavior understanding with an application to assisted living. First, the grammars of the different actions performed by a person in his/her daily life are discovered. Then, a longterm analysis of the behavior is used to generate a control grammar, taking care of the context when an action is performed, and adding semantics. The proposed framework is tested on a dataset acquired in a real environment and compared with state of the art methods already available for the problem considered.
Rosani, A.; Conci, N.; De Natale, F. G. B.
Developmental Disabilities and Child Welfare.
ERIC Educational Resources Information Center
This monograph addresses common misconceptions about developmental disabilities, describes the conditions that child welfare workers are most likely to see, provides examples of effective interventions, and stresses the importance of early intervention to promote healthy development. Specific chapters include: (1) "Understanding Developmental�
Rycus, Judith S.; Hughes, Ronald C.
Thyrotropin acts as a T-cell developmental factor in mice and humans.
Using gene expression profiling, we detected differential thyrotropin receptor (TSH-R) expression during human T-cell development in the thymus. This expression pattern indicated a potential role for the TSH-R within the thymus, independent of its function in the thyroid gland. Here, we demonstrate that TSH-R expression is thymus-specific within the immune system. TSH was able to bind and activate the TSH-R present on thymocytes, thereby activating calcium signaling and cyclic adenosine monophosphate signaling pathways. Mice lacking functional TSH-R expression (hyt/hyt mice) were shown to have lower frequencies of DP and SP thymocytes compared to their heterozygous littermates. Moreover, addition of TSH to co-cultures of human thymocytes enhanced T-cell development. Thus, TSH acts as a previously unrecognized growth factor for developing T cells, with potential clinical use to enhance thymic output and thereby the functional T-cell repertoire in the periphery. The direct effects of TSH on thymocytes may also explain the thus far enigmatic thymic hyperplasia in Graves' disease. PMID:24635198
van der Weerd, Kim; van Hagen, P Martin; Schrijver, Benjamin; Heuvelmans, Sjanneke J W M; Hofland, Leo J; Swagemakers, Sigrid M A; Bogers, Ad J J C; Dik, Willem A; Visser, Theo J; van Dongen, Jacques J M; van der Lelij, Aart-Jan; Staal, Frank J T
What imitation tells us about social cognition: a rapprochement between developmental psychology and cognitive neuroscience
Both developmental and neurophysiological research suggest a common coding between perceived and generated actions. This shared representational network is innately wired in humans. We review psycho- logical evidence concerning the imitative behaviour of newborn human infants. We suggest that the mech- anisms involved in infant imitation provide the foundation for understanding that others are ' like me' and underlie the
Andrew N. Meltzoff; Jean Decety
Developmental effects of endocrine-disrupting chemicals in wildlife and humans
Large numbers and large quantities of endoncrine-disrupting chemicals have been released into the environment since World War II. Many of these chemicals can disturb development of the endocrine system and of the organs that respond to endocrine signals in organisms indirectly exposed during prenatal and/or early postnatal life; effects of exposure during development are permanent and irreversible. The risk to the developing organism can also stem from direct exposure of the offspring after birth or hatching. In addition, trangenerational exposure can result from the exposure of the mother to a chemical at any time throughout her life before producing offspring due to persistent of endocrine-disrupting chemicals in body fat, which is mobilized during egg laying or pregnancy and lactation. Mechanisms underlying the disruption of the development of vital systems, such as the endocrine, reproductive, and immune systems, are discussed with reference to wildlife, laboratory animals, and humans.
Colborn, T. (W. Alton Jones Foundation and World Wildlife Fund, Washington, DC (United States)); vom Saal, F.S. (Univ. of Missouri, Columbia, MO (United States)); Soto, A.M. (Tufts Univ., Boston, MA (United States))
Four decades of teaching developmental biology in Germany.
I have taught developmental biology in Essen for 30 years. Since my department is named Zoophysiologie (Zoophysiology), besides Developmental Biology, I also have to teach General Animal Physiology. This explains why the time for teaching developmental biology is restricted to a lecture course, a laboratory course and several seminar courses. However, I also try to demonstrate in the lecture courses on General Physiology the close relationship between developmental biology, physiology, morphology, anatomy, teratology, carcinogenesis, evolution and ecology (importance of environmental factors on embryogenesis). Students are informed that developmental biology is a core discipline of biology. In the last decade, knowledge about molecular mechanisms in different organisms has exponentially increased. The students are trained to understand the close relationship between conserved gene structure, gene function and signaling pathways, in addition to or as an extension of, classical concepts. Public reports about the human genome project and stem cell research (especially therapeutic and reproductive cloning) have shown that developmental biology, both in traditional view and at the molecular level, is essential for the understanding of these complex topics and for serious and non-emotional debate. PMID:12705670
Grunz, Horst
Understanding and Re-engineering Nucleoprotein Machines to Cure Human Disease
Summary The mammalian nucleus is filled with self-organizing, nanometer-scale nucleoprotein machines that carry out DNA replication, RNA biogenesis, and DNA repair. We discuss, as a model, the nonhomologous end-joining (NHEJ) machine, which repairs DNA double-strand breaks. The NHEJ machine consists of six core polypeptides and 10�20 ancillary polypeptides. A full understanding of its design principles will require measuring the behavior of single NHEJ complexes in living cells, using a Nano Toolbox that includes bright, stable, biocompatible fluorophores, efficient protein and nucleic acid tagging strategies, and sensitive, high-resolution imaging methods. Taking inspiration from natural examples, it may be possible to adapt and redesign the NHEJ machine to precisely correct mutations responsible for common human diseases, such as K-ras in lung cancer, or human papillomavirus E6 and E7 genes in cervical and oral cancers.
Dynan, William; Takeda, Yoshihiko; Roth, David; Bao, Gang
Towards understanding the dynamic behaviour of floodplains as human-water systems
NASA Astrophysics Data System (ADS)
This paper offers a conceptual approach to explore the complex dynamics of floodplains as fully coupled human-water systems. A number of hydrologists have recently investigated the impact of human activities (such as flood control measures, land-use changes, and settlement patterns) on the frequency and severity of floods. Meanwhile, social scientists have shown how interactions between society and waters in deltas and floodplain areas, including the frequency and severity of floods, have an impact on the ways in which social relations unfold (in terms of governance processes, policies, and institutions) and societies are organised (spatially, politically, and socially). However, we argue that the interactions and associated feedback mechanisms between hydrological and social processes remain largely unexplored and poorly understood. Thus, there is a need to better understand how the institutions and governance processes interact with hydrological processes in deltas and floodplains to influence the frequency and severity of floods, while (in turn) hydrological processes co-constitute the social realm and make a difference for how social relations unfold to shape governance processes and institutions. Our research goal, therefore, is not in identifying one or the other side of the cycle (hydrological or social), but in explaining the relationship between them: how, when, where, and why they interact, and to what result for both social relations and hydrological processes? We argue that long time series of hydrological and social data, along with remote sensing data, can be used to observe floodplain dynamics from unconventional approaches, and understand the complex interactions between water and human systems taking place in floodplain areas, across scales and levels of human impacts, and within different hydro-climatic conditions, socio-cultural settings, and modes of governance.
Di Baldassarre, G.; Kooy, M.; Kemerink, J. S.; Brandimarte, L.
Towards understanding the dynamic behaviour of floodplains as human-water systems
NASA Astrophysics Data System (ADS)
This paper offers a conceptual approach to explore the complex dynamics of floodplains as fully coupled human-water systems. A number of hydrologists have recently investigated the impact of human activities (such as flood control measures, land-use changes, and settlement patterns) on the frequency and severity of floods. Meanwhile, social scientists have shown how interactions between society and waters in floodplain areas, including the frequency and severity of floods, have an impact on the ways in which social relations unfold (in terms of governance processes, policies, and institutions) and societies are organised (spatially, politically, and socially). However, we argue that the interactions and associated feedback mechanisms between hydrological and social processes remain largely unexplored and poorly understood. Thus, there is a need to better understand how the institutions and governance processes interact with hydrological processes in floodplains to influence the frequency and severity of floods, while (in turn) hydrological processes co-constitute the social realm and make a difference for how social relations unfold to shape governance processes and institutions. Our research goal, therefore, is not in identifying one or the other side of the cycle (hydrological or social), but in explaining the relationship between them: how, when, where, and why they interact, and to what result for both social relations and hydrological processes? We argue that long time series of hydrological and social data, along with remote sensing data, can be used to observe floodplain dynamics from unconventional approaches, and understand the complex interactions between water and human systems taking place in floodplain areas, across scales and levels of human impacts, and within different hydro-climatic conditions, socio-cultural settings, and modes of governance.
Di Baldassarre, G.; Kooy, M.; Kemerink, J. S.; Brandimarte, L.
Male-mediated developmental toxicity.
Male-mediated developmental toxicity has been of concern for many years. The public became aware of male-mediated developmental toxicity in the early 1990s when it was reported that men working at Sellafield might be causing leukemia in their children. Human and animal studies have contributed to our current understanding of male-mediated effects. Animal studies in the 1980s and 1990s suggested that genetic damage after radiation and chemical exposure might be transmitted to offspring. With the increasing understanding that there is histone retention and modification, protamine incorporation into the chromatin and DNA methylation in mature sperm and that spermatozoal RNA transcripts can play important roles in the epigenetic state of sperm, heritable studies began to be viewed differently. Recent reports using molecular approaches have demonstrated that DNA damage can be transmitted to babies from smoking fathers, and expanded simple tandem repeats minisatellite mutations were found in the germline of fathers who were exposed to radiation from the Chernobyl nuclear power plant disaster. In epidemiological studies, it is possible to clarify whether damage is transmitted to the sons after exposure of the fathers. Paternally transmitted damage to the offspring is now recognized as a complex issue with genetic as well as epigenetic components. PMID:24369136
Anderson, Diana; Schmid, Thomas E; Baumgartner, Adolf
Male-mediated developmental toxicity
Male-mediated developmental toxicity has been of concern for many years. The public became aware of male-mediated developmental toxicity in the early 1990s when it was reported that men working at Sellafield might be causing leukemia in their children. Human and animal studies have contributed to our current understanding of male-mediated effects. Animal studies in the 1980s and 1990s suggested that genetic damage after radiation and chemical exposure might be transmitted to offspring. With the increasing understanding that there is histone retention and modification, protamine incorporation into the chromatin and DNA methylation in mature sperm and that spermatozoal RNA transcripts can play important roles in the epigenetic state of sperm, heritable studies began to be viewed differently. Recent reports using molecular approaches have demonstrated that DNA damage can be transmitted to babies from smoking fathers, and expanded simple tandem repeats minisatellite mutations were found in the germline of fathers who were exposed to radiation from the Chernobyl nuclear power plant disaster. In epidemiological studies, it is possible to clarify whether damage is transmitted to the sons after exposure of the fathers. Paternally transmitted damage to the offspring is now recognized as a complex issue with genetic as well as epigenetic components.
Anderson, Diana; Schmid, Thomas E; Baumgartner, Adolf
Developmental plasticity of murine and human Foxp3(+) regulatory T cells.
Murine and human CD4(+) regulatory T (Treg) cells expressing the Forkhead box p3 (Foxp3) transcription factor represent a distinct, highly differentiated CD4(+) T cell lineage that is programmed for dominant self-tolerance and control of immune responses against a variety of foreign antigens. Sustained Foxp3 expression in these cells drives the differentiation of a regulatory phenotype and ensures the stability of their suppressive functions under a variety of inflammatory settings. Some recent studies have challenged this premise and advanced the notion that Foxp3(+) Treg cells manifest a high degree of functional plasticity that enables them to adapt and reprogram into effector-like T cells in response to various inflammatory stimuli. The concept of Treg cell plasticity remains highly contentious, with a high degree of variation in measured plasticity potential observed under different experimental conditions. In this chapter, we propose a unifying model of Treg cell plasticity, which hypothesizes that the stable fates of regulatory and effector T (Teff) cell lineages allow transient plasticity into the alternative lineage under a discrete set of microenvironmental influences associated with, respectively, the initiation and resolution phases of infection. This model utilizes a theoretical framework consistent with the requirements for effective immune regulation and accounts for both the extraordinary long-term stability of Treg cells and the observed fate plasticity. PMID:23886065
Liston, Adrian; Piccirillo, Ciriaco A
A developmental study of sex and age interactions in the human corpus callosum.
Regional analysis of the corpus callosum (CC) has demonstrated that the development of this fiber tract is sexually dimorphic. Midsagittal CC tracings from magnetic resonance images (MRIs) of 73 pairs of age-matched (age 2-79 years) males and females were digitized using computer assisted software. Area, axis length, perimeter, and 99 widths were obtained. Widths were grouped into the following regions based upon prior factor analysis: widths 3-18 (W3-18), W22-39, W49-62, W65-74, W77-85, W89-94, and W95-99. Trend analyses were performed with Sex and Age (blocked into 10-year bins) as independent variables. Higher order Sex by Age interactions were significant in regions W3-18 and W22-39 and were marginal in W95-99. In all 3 regions, females did not attain maximum width until Age 41-50 whereas males had peaked at 20 years and declined thereafter. There were no significant interactions between Sex and Age in the remaining CC regions, nor were there any dramatic decreases once maximum width was reached in adulthood. These results suggest that sex differences may also exist in CC ultrastructure over the human lifespan. PMID:1606684
Cowell, P E; Allen, L S; Zalatimo, N S; Denenberg, V H
Developmental neurotoxicity of ortho-phthalate diesters: review of human and experimental evidence.
Ortho-phthalate diesters, or phthalates, are widely used synthetic chemicals found primarily in consumer products and polyvinyl chloride plastics. Experimental evidence suggests that several phthalates possess antiandrogenic properties and may disrupt endocrine pathways resulting in abnormal reproductive outcomes. Low-level exposure to phthalates has been well documented in humans, with higher levels found in children and women of childbearing age. Recent epidemiologic studies postulate that prenatal exposure to measurable urine phthalate concentrations may be associated with altered genital and pubertal development in infants and children. This review addresses the emerging evidence that some phthalates may have an adverse impact on the developing brain. The supporting animal studies and proposed mechanisms underlying the deleterious properties of phthalates in relation to neurodevelopmental outcomes are also discussed. While the observed associations are based on limited studies with a broad range of endpoints, the implications of such outcomes are of concern from a public health standpoint and merit further investigation given the widespread nature of the exposure. PMID:24486776
Miodovnik, Amir; Edwards, Andrea; Bellinger, David C; Hauser, Russ
Perfusion affects the tissue developmental patterns of human mesenchymal stem cells in 3D scaffolds.
Human mesenchymal stem cells (hMSCs) developed in three-dimensional (3D) scaffolds are significantly affected by culture conditions. We hypothesized that the hydrodynamic forces generated in perfusion bioreactors significantly affected hMSC functionality in 3D scaffolds by shaping the extracellular matrix (ECM) proteins. In this study, hMSCs were grown in 3D poly(ethylene terephthalate) (PET) scaffolds in static and a parallel perfusion system under similar initial conditions for up to 35 days. Results demonstrated that even at very low media velocities (O [10(-4) cm/sec]), perfusion cultures affected the ability of hMSCs to form an organized ECM network as illustrated by the immunostaining of collagen I and laminin fibrous structure. The change in the ECM microenvironment consequently influenced the nuclear shape. The hMSCs grown at the lower surface of static culture displayed a 15.2 times higher nuclear elongation than those at the upper surface, whereas cells grown in the perfusion bioreactor displayed uniform spherical nuclei on both surfaces. The difference in ECM organization and nuclear morphology associated with gene expression and differentiation characteristics of hMSCs. The cells exhibited lower CFU-F colony forming ability and decreased expressions of stem-cell genes of Rex-1 and Oct-4, implying a less primitive stem-cell phenotype was maintained in the perfusion culture relative to the static culture conditions. The significantly higher expression level of osteonectin gene in the perfusion culture at day 28 indicated an upregulation of osteogenic ability of hMSCs. The study highlights the critical role of dynamic culture conditions on 3D hMSC construct development and properties. PMID:19170078
Zhao, Feng; Grayson, Warren L; Ma, Teng; Irsigler, Andre
The Developmental Origins of Conversion Disorders
Attachment theory offers a novel developmental framework for understanding conversion reactions as having phylogenetic roots in two different innate animal defense behaviours: The `freeze response' and `appeasement defense behaviours'. From this perspective, conversion symptoms reflect two distinct, threat-elicited emotional responses, which are primed in context-dependent developmental experiences (pathways) and underpinned by different neurobiological mechanisms. The first of these two developmental
Kasia Kozlowska
This document presents an evaluation of the reproductive and developmental effects of lithium and reviews toxicologic information on several specific lithium salts: ithium carbonate, lithium chloride, lithium citrate, and lithium hypochlorite. ithium (Li), an alkali metal, is a n...
Meckel on developmental pathology.
Before Schleiden and Schwann, Darwin and Mendel there passed briefly a towering giant, Johann Friedrich Meckel the Younger (1781-1833), now glimpsed only fleetingly and obscurely through the mist of time and former controversies, who can nowadays easily and clearly be identified as the father of a "pre-modern" developmental biology. At his beginning this prodigiously gifted physician-scholar had, as one would say nowadays, an unfair advantage, his cradle having been rocked, as it were, by the preparators in his father's and grandfather's huge collection of normal and abnormal anatomical "specimens" in the home in which he was born and raised including his father's own skeleton (with two anatomical anomalies!). Initially reluctant to follow in the steps of his illustrious anatomist/physician grandfather and father, he nevertheless early demonstrated extraordinary gifts in anatomy and zootomy. Napoleon's conquest of his homeland notwithstanding, Meckel spent at least 2 extremely fruitful years in Paris, under the tutelage of Cuvier, but also in close contact with Geoffroy St. Hilaire (Etienne), Lamarck, and von Humboldt. He not only translated Cuvier's Le�ons d'anatomie compar�e into German but also greatly enriched this pivotal treatise with observations of embryonic and malformed fetuses and animals only of passing interest to his mentor. In his numerous publications, Meckel was the first to relate abnormal to normal development, define anomalies of incomplete differentiation (vestigia), but, most importantly, to relate those malformations known in humans to those that are normal adult developmental states in "lower" animals (atavisms). Thus, Meckel's three-fold parallelism of the scala naturae, normal ontogeny, and the malformations in humans and animals makes him a recapitulationist par excellence, however, without ever venturing into a fully articulated and explicit theory of descent. Today Meckel is remembered solely as the discoverer of the syndrome and cartilage named after him, and as having interpreted, correctly, the developmental nature of the "Meckel" diverticulum. It is virtually unknown that Meckel also first enuntiated the concept and distinction between primary and secondary malformations/anomalies, introduced the notion of heredity into the causal analysis of congenital anomalies, was the father of syndromology (the Meckel syndrome), had a clear understanding of pleiotropy and heterogeneity, and can unequivocally be regarded as the father of developmental pathology. In hindsight, and inspite of much professional success, Meckel emerges as a tragic figure in the history of biology, his life cut short at 52 without an ability to incorporate cell theory and the embryological insights of his younger contemporaries into his intellectual edifice which might have made it possible for him to finally and clearly see "analogy" (now homology), of which he was the greatest expert in his era, as incontrovertible evidence for descent. In that case, Darwin and Haeckel might have even had the courtesy of a tip-of-the-hat in Meckel's direction. PMID:16353245
Opitz, John M; Schultka, R�diger; G�bbel, Luminita
Editorial: 'What's up, (R)DoC?' - can identifying core dimensions of early functioning help us understand, and then reduce, developmental risk for mental disorders?
In the US the National Institute of Mental Health (NIMH), the main funder of mental health research in the world, has recently changed its funding model to promote a radically new perspective for mental health science. This bold, and for some controversial, initiative, termed the Research Diagnostic Criteria (or RDoC for short), intends to shift the focus of research, and eventually clinical practice, away from existing diagnostic categories, as recently updated in the DSM-5, towards 'new ways of classifying psychopathology based on dimensions of observable behavior and neurobiological measures.' This reorientation from discrete categorical disorder manifestations to underlying cross-cutting dimensions of individual functioning has generated considerable debate across the community of mental health researchers and clinicians (with strong views voiced both pro and con). Given its pivotal role in defining the research agenda globally, there is little doubt that this US science funding initiative will also have ramifications for researchers and clinicians worldwide. In this Editorial we focus specifically on the translational potential of the dimensional RDoC approach, properly extended to developmental models of early risk, in terms of its value as a potential driver of early intervention/prevention models; in the current issue of the JCPP this is exemplified by a number of papers thata address the mapping of underlying dimensions of core functioning to disorder risk, providing evidence for their potential predictive power as early markers of later disorder processes. PMID:25039570
Sonuga-Barke, Edmund J S
Animal models suggest that the immature immune system is more susceptible to xenobiotics than the fully mature system, and sequelae of developmental immunotoxicant exposure may be persistent well into adulthood. Immune maturation may be delayed by xenobiotic exposure and recover...
Evolutionary Developmental Psychology.
ERIC Educational Resources Information Center
Describes evolutionary developmental psychology as the study of the genetic and ecological mechanisms that govern the development of social and cognitive competencies common to all human beings and the epigenetic (gene-environment interactions) processes that adapt these competencies to local conditions. Outlines basic assumptions and domains of�
Geary, David C.; Bjorklund, David F.
Cognitive and Affective Components of Mental Workload: Understanding the Effects of Each on Human Decision Making Behavior.
National Technical Information Service (NTIS)
Human factors and ergonomics researchers have recognized for some time the increasing importance of understanding the role of the construct of mental workload in flight research. Current models of mental workload suggest that it is a multidimensional and ...
T. E. Nygren
Vitamin D Signaling in the Bovine Immune System: A Model for Understanding Human Vitamin D Requirements
The endocrine physiology of vitamin D in cattle has been rigorously investigated and has yielded information on vitamin D requirements, endocrine function in health and disease, general metabolism, and maintenance of calcium homeostasis in cattle. These results are relevant to human vitamin D endocrinology. The current debate regarding vitamin D requirements is centered on the requirements for proper intracrine and paracrine vitamin D signaling. Studies in adult and young cattle can provide valuable insight for understanding vitamin D requirements as they relate to innate and adaptive immune responses during infectious disease. In cattle, toll-like receptor recognition activates intracrine and paracrine vitamin D signaling mechanism in the immune system that regulates innate and adaptive immune responses in the presence of adequate 25-hydroxyvitamin D. Furthermore, experiments with mastitis in dairy cattle have provided in vivo evidence for the intracrine vitamin D signaling mechanism in macrophages as well as vitamin D mediated suppression of infection. Epidemiological evidence indicates that circulating concentrations above 32 ng/mL of 25-hydroxyvitamin D are necessary for optimal vitamin D signaling in the immune system, but experimental evidence is lacking for that value. Experiments in cattle can provide that evidence as circulating 25-hydroxyvitamin D concentrations can be experimentally manipulated within ranges that are normal for humans and cattle. Additionally, young and adult cattle can be experimentally infected with bacteria and viruses associated with significant diseases in both cattle and humans. Utilizing the bovine model to further delineate the immunomodulatory role of vitamin D will provide potentially valuable insights into the vitamin D requirements of both humans and cattle, especially as they relate to immune response capacity and infectious disease resistance.
Nelson, Corwin D.; Reinhardt, Timothy A.; Lippolis, John D.; Sacco, Randy E.; Nonnecke, Brian J.
Developmental regulated expression of anti- and pro-apoptotic BCL-2 family genes during human early embryonic development.
Apoptotic cell death has been reported in human oocytes and preimplantation embryos under in vivo and in vitro conditions. BCL-2 family proteins comprise both anti- and pro-apoptotic members, which are likely to play a key role in controlling oocyte and early embryo survival. However, very limited data are available on their expression kinetics during human early embryonic development. Using our DNA microarray data, we analyzed the expression pattern of 21 BCL-2 family genes in human mature MII oocytes, day 3 embryos and day 5/6 blastocysts from patients who underwent in vitro fertilization (IVF). Selected genes were further validated by qRT-PCR and their subcellular localization analyzed by immunofluorescence confocal microscopy. Our results suggest a switch from oocyte-inherited BCL-2 family transcripts, such as BCL2L10, to embryo-produced transcripts after embryonic genome activation, including BIK, BCL2L11 and NOXA. Moreover, the pro-apoptotic gene BCL2L13 was constitutively expressed throughout human early embryonic development. Remarkably, day 3 embryos expressed more BCL-2 pro-apoptotic genes than mature MII oocytes and day 5/6 blastocysts, suggesting that embryos at this stage are more prone to apoptosis. This is further supported by an absence of cleaved Caspase-3 in the oocyte and its presence in the embryo. Using a drug that induces apoptosis (gambogic acid), we were able to show activated Caspase-3 in the oocyte in addition to an alteration of BCL2L13 protein localization. Similarly BCL2L13 localization was altered in degenerated oocytes. This study opens new perspectives for understanding the molecular regulation of human oocyte and pre-implantation embryo survival and death. PMID:24083610
Boumela, I; Assou, S; Haouzi, D; D�chaud, H; A�t-Ahmed, O; Hamamah, S
The Contribution of Conceptual Change Texts Accompanied by Concept Mapping to Students' Understanding of the Human Circulatory System.
ERIC Educational Resources Information Center
Investigates the contribution of conceptual change texts accompanied by concept mapping instruction to 10th-grade students' understanding of the human circulatory system. Indicates that the conceptual change texts accompanied by concept mapping instruction produced a positive effect on students' understanding of concepts. Concludes that students�
Sungur, Semra; Tekkaya, Ceren; Geban, Omer
Understanding melatonin receptor pharmacology: Latest insights from mouse models, and their relevance to human disease.
Melatonin, the neuro-hormone synthesized during the night, has recently seen an unexpected extension of its functional implications toward type 2 diabetes development, visual functions, sleep disturbances, and depression. Transgenic mouse models were instrumental for the establishment of the link between melatonin and these major human diseases. Most of the actions of melatonin are mediated by two types of G protein-coupled receptors, named MT1 and MT2 , which are expressed in many different organs and tissues. Understanding the pharmacology and function of mouse MT1 and MT2 receptors, including MT1 /MT2 heteromers, will be of crucial importance to evaluate the relevance of these mouse models for future therapeutic developments. This review will critically discuss these aspects, and give some perspectives including the generation of new mouse models. PMID:24903552
Tosini, Gianluca; Owino, Sharon; Guillaume, Jean-Luc; Jockers, Ralf
On the Importance of Comparative Research for the Understanding of Human Behavior and Development: A Reply to Gottlieb & Lickliter (2004)
ERIC Educational Resources Information Center
Comparative behavioral research is important for a number of reasons and can contribute to the understanding of human behavior and development in many different ways. Research with animal models of human behavior and development can be a source not only of general principles and testable hypotheses but also of empirical information that may be�
Maestripieri, Dario
Models of conceptual understanding in human respiration and strategies for instruction
NASA Astrophysics Data System (ADS)
Prior research has indicated that students of all ages show little understanding of respiration beyond breathing in and out and the need for air to survive. This occurs even after instruction with alternative conceptions persisting into adulthood. Whether this is due to specific educational strategies or to the level of difficulty in understanding a complex system is an important question. The purpose of this study was to obtain a deeper understanding of middle school students' development of mental models of human respiration. The study was composed of two major parts, one concerned with documenting and analyzing how students learn, and one concerned with measuring the effect of teaching strategies. This was carried out through a pre-test, "learning aloud" case studies in which students engaged in one-on-one tutoring interviews with the researcher, and a post-test. Transcript data from the intervention and post-test indicates that all students in this study were successful in constructing mental models of a complex concept, respiration, and in successfully applying these mental models to transfer problems. Differences in the pretest and posttest means were on the order of two standard deviations in size. While findings were uncovered in the use of a variety of strategies, possibly most interesting are the new views of analogies as an instructional strategy. Some analogies appear to be effective in supporting construction of visual/spatial features. Providing multiple, simple analogies that allow the student to construct new models in small steps, using student generated analogies, and using analogies to determine prior knowledge may also increase the effectiveness of analogies. Evidence suggested that students were able to extend the dynamic properties of certain analogies to the dynamics of the target conception and that this, in turn, allowed students to use the new models to explain causal relationships and give new function to models. This suggests that construction of causal, dynamic mental models is supported by the use of analogies containing dynamic and causal relationships.
Rea-Ramirez, Mary Anne
Human Cytochrome P450 1A1 Structure and Utility in Understanding Drug and Xenobiotic Metabolism*
Cytochrome P450 (CYP) 1A1 is an extrahepatic monooxygenase involved in the metabolism of endogenous substrates and drugs, as well as the activation of certain toxins and environmental pollutants. CYP1A1 is particularly well known for its ability to biotransform polycyclic aromatic hydrocarbons, such as benzo[a]pyrene in tobacco smoke, into carcinogens. CYP1A1 possesses functional similarities and differences with human CYP1A2 and CYP1B1 enzymes, but the structural basis for this has been unclear. We determined a 2.6 ? structure of human CYP1A1 with the inhibitor ?-naphthoflavone. ?-Naphthoflavone binds within an enclosed active site, with the planar benzochromen-4-one core packed flat against the I helix that composes one wall of the active site, and the 2-phenyl substituent oriented toward the catalytic heme iron. Comparisons with previously determined structures of the related cytochrome P450 1A2 and 1B1 enzymes reveal distinct features among the active sites that may underlie the functional variability of these enzymes. Finally, docking studies probed the ability of CYP1A structures to assist in understanding their known in vitro interactions with several typical substrates and inhibitors.
Walsh, Agnes A.; Szklarz, Grazyna D.; Scott, Emily E.
Genomic Assessment of Human Cumulus Cell Marker Genes as Predictors of Oocyte Developmental Competence: Impact of Various Experimental Factors
Background Single embryo transfer (SET) is the most successful way to reduce the frequency of multiple pregnancies following in vitro fertilisation. However, selecting the embryo for SET with the highest chances of pregnancy remains a difficult challenge since morphological and kinetics criteria provide poor prediction of both developmental and implantation ability. Partly through the expression of specific genes, the oocyte-cumulus interaction helps the oocyte to acquire its developmental competence. Our aim was therefore to identify at the level of cumulus cells (CCs) genes related to oocyte developmental competence. Methodology/Principal Findings 197 individual CCs were collected from 106 patients undergoing an intra-cytoplasmic sperm injection procedure. Gene expression of CCs was studied using microarray according to the nuclear maturity of the oocyte (immature vs. mature oocyte) and to the developmental competence of the oocyte (ability to reach the blastocyst stage after fertilisation). Microarray study was followed by a meta-analysis of the behaviour of these genes in other datasets available in Gene Expression Omnibus which showed the consistency of this list of genes. Finally, 8 genes were selected according to oocyte developmental competence from the 308 differentially expressed genes (p<0.0001) for further validation by quantitative PCR (qPCR). Three of these 8 selected genes were validated as potential biomarkers (PLIN2, RGS2 and ANG). Experimental factors such as inter-patient and qPCR series variability were then assessed using the Generalised Linear Mixed Model procedure, and only the expression level of RGS2 was confirmed to be related to oocyte developmental competence. The link between biomarkers and pregnancy was finally evaluated and level of RGS2 expression was also correlated with clinical pregnancy. Conclusion/Significance RGS2, known as a regulator of G protein signalling, was the only gene among our 8 selected candidates biomarkers of oocyte competence to cover many factors of variability, including inter-patient factors and experimental conditions.
Chevalier, Catherine; Teusan, Raluca; Cadoret, Veronique; Guerif, Fabrice; Houlgatte, Remi; Royere, Dominique
Understanding the development of human bladder cancer by using a whole-organ genomic mapping strategy
The search for the genomic sequences involved in human cancers can be greatly facilitated by maps of genomic imbalances identifying the involved chromosomal regions, particularly those that participate in the development of occult preneoplastic conditions that progress to clinically aggressive invasive cancer. The integration of such regions with human genome sequence variation may provide valuable clues about their overall structure and gene content. By extension, such knowledge may help us understand the underlying genetic components involved in the initiation and progression of these cancers. We describe the development of a genome-wide map of human bladder cancer that tracks its progression from in situ precursor conditions to invasive disease. Testing for allelic losses using a genome-wide panel of 787 microsatellite markers was performed on multiple DNA samples, extracted from the entire mucosal surface of the bladder and corresponding to normal urothelium, in situ preneoplastic lesions, and invasive carcinoma. Using this approach, we matched the clonal allelic losses in distinct chromosomal regions to specific phases of bladder neoplasia and produced a detailed genetic map of bladder cancer development. These analyses revealed three major waves of genetic changes associated with growth advantages of successive clones and reflecting a stepwise conversion of normal urothelial cells into cancer cells. The genetic changes map to six regions at 3q22�q24, 5q22�q31, 9q21�q22, 10q26, 13q14, and 17p13, which may represent critical hits driving the development of bladder cancer. Finally, we performed high-resolution mapping using single nucleotide polymorphism markers within one region on chromosome 13q14, containing the model tumor suppressor gene RB1, and defined a minimal deleted region associated with clonal expansion of in situ neoplasia. These analyses provided new insights on the involvement of several non-coding sequences mapping to the region and identified novel target genes, termed forerunner (FR) genes, involved in early phases of cancer development.
Majewski, Tadeusz; Lee, Sangkyou; Jeong, Joon; Yoon, Dong-Sup; Kram, Andrzej; Kim, Mi-Sook; Tuziak, Tomasz; Bondaruk, Jolanta; Lee, Sooyong; Park, Weon-Seo; Tang, Kuang S; Chung, Woonbok; Shen, Lanlan; Ahmed, Saira S; Johnston, Dennis A; Grossman, H Barton; Dinney, Colin P; Zhou, Jain-Hua; Harris, R Alan; Snyder, Carrie; Filipek, Slawomir; Narod, Steven A; Watson, Patrice; Lynch, Henry T; Gazdar, Adi; Bar-Eli, Menashe; Wu, Xifeng F; McConkey, David J; Baggerly, Keith; Issa, Jean-Pierre; Benedict, William F; Scherer, Steven E; Czerniak, Bogdan
Developmental regulation of AMPA receptor subunit expression in forebrain and relationship to regional susceptibility to hypoxic/ischemic injury: Part II. Human cerebral white matter and cortex
This report is the second of a two-part evaluation of developmental differences in ?�amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor subunit expression in cell populations within white matter and cortex. In Part I, we report that in rat, developmental expression of Ca2+ permeable (GluR2-lacking) AMPARs correlated at the regional and cellular level with increased susceptibility to hypoxia/ischemia (H/I), suggesting an age-specific role of these receptors in the pathogenesis of brain injury. Part II examines the regional and cellular progression of AMPAR subunits in human white matter and cortex from midgestation through early childhood. Similar to the rodent, there is a direct correlation between selective vulnerability to H/I and expression of GluR2-lacking AMPARs in human brain. In midgestational cases aged 20-24 postconceptional weeks (PCW) and in premature infants (25-37 PCW), we found that radial glia, premyelinating oligodendrocytes and subplate neurons transiently expressed GluR2-lacking AMPARs. Notably, prematurity represents a developmental window of selective vulnerability for white matter injury, such as periventricular leukomalacia (PVL). During term (38-42 PCW) and post-term neonatal (43-46 PCW) periods, age windows characterized by increased susceptibility to cortical injury and seizures, GluR2 expression was low in the neocortex, specifically on cortical pyramidal and non-pyramidal neurons. This study indicates that Ca2+ permeable AMPAR blockade may represent an age-specific therapeutic strategy for potential use in humans. Furthermore, these data help validate specific rodent maturational stages as appropriate models for evaluation of H/I pathophysiology.
Talos, Delia M.; Follett, Pamela L.; Folkerth, Rebecca D.; Fishman, Rachel E.; Trachtenberg, Felicia L.; Volpe, Joseph J.; Jensen, Frances E.
Agency for Toxic Substances and Disease Registry's 1997 priority list of hazardous substances. Latent effects--carcinogenesis, neurotoxicology, and developmental deficits in humans and animals.
In support of Superfund re-authorization legislation, the Division of Toxicology of the Agency for Toxic Substances and Disease Registry (ATSDR) prepared a chemical-specific consultation document for Congress that identified those chemicals with carcinogenic, neurological, or developmental adverse effects having a latency period longer than 6 years. The review was limited to the top 50 substances listed on ATSDR's 1997 Priority List of Hazardous Substances (Priority List). Among the top 50 chemicals, a review of the technical literature indicated that 38 (76%) were classified as "reasonably anticipated," "possibly," or "probably" capable of causing cancer in humans, based either on human and animal data. Eight chemicals (16%) had well-established cancer latency periods in humans of 6 years or more following exposure. Three substances (6%)--arsenic, creosote, and benzidine--had data indicating latency periods longer than 6 years. The technical literature review likewise confirmed the potential for neurological and developmental effects with a latency of 6 years. Twenty-seven (54%) of the top 50 substances caused acute and/or chronic neurotoxic effects; a number of these also caused neurological effects that persisted beyond 6 years (or the equivalent in animal studies) such as: behavioral problems, neurological deficiencies, reduced psychomotor development, cognitive deficiencies, and reduced IQ. Twenty-eight substances (56%) caused adverse developmental effects in offspring of exposed individuals or animals including increased fetal and infant mortality, decreased birth weights and litter sizes, and growth delays. Latency periods for related chemicals are expected to be similar due to structural and toxicological similarities. PMID:10677885
Ostrowski, S R; Wilbur, S; Chou, C H; Pohl, H R; Stevens, Y W; Allred, P M; Roney, N; Fay, M; Tylenda, C A
The significance of human�animal relationships as modulators of trauma effects in children: a developmental neurobiological perspective
Emotional stress and trauma impacts the neurobiology of children. They are especially vulnerable given the developmental plasticity of the brain. The neural synaptic circular processes between the anterior cingulated cortex, prefrontal cortex, amygdala and the hypothalamus are altered. Trauma results in the release of the peptide glucocortisoid, or cortisol leading to an ongoing over?arousal of the anatomic nervous system. Kindling
Jan Yorke
The Significance of Human-Animal Relationships as Modulators of Trauma Effects in Children: A Developmental Neurobiological Perspective
ERIC Educational Resources Information Center
Emotional stress and trauma impacts the neurobiology of children. They are especially vulnerable given the developmental plasticity of the brain. The neural synaptic circular processes between the anterior cingulated cortex, prefrontal cortex, amygdala and the hypothalamus are altered. Trauma results in the release of the peptide glucocortisoid,�
Yorke, Jan
The human glutathione S-transferases: Developmental aspects of the GST1, GST2, and GST3 loci
The expression of the GST1, GST2, and GST3 loci in fetal, neonatal, and infant tissues has been studied using starch gel electrophoresis and chromatofocusing. Each locus demonstrated developmental changes in expression, some of which were specific to a single tissue while others occurred in several tissues. GST1 was not usually expressed in any of the tissues studied before 30 weeks
Richard C. Strange; Brian A. Davis; Charles G. Faulder; William Cotton; A. D. Bain; D. A. Hopkinson; Robert Hume
Folate metabolite profiling of different cell types and embryos suggests variation in folate one-carbon metabolism, including developmental changes in human embryonic brain.
Folates act as co-factors for transfer of one-carbon units for nucleotide production, methylation and other biosynthetic reactions. Comprehensive profiling of multiple folates can be achieved using liquid chromatography tandem mass spectrometry, enabling determination of their relative abundance that may provide an indication of metabolic differences between cell types. For example, cell lines exposed to methotrexate showed a dose-dependent elevation of dihydrofolate, consistent with inhibition of dihydrofolate reductase. We analysed the folate profile of E. coli sub-types as well as cell lines and embryonic tissue from both human and mouse. The folate profile of bacteria differed markedly from those of all the mammalian samples, most notably in the greater abundance of formyl tetrahydrofolate. The overall profiles of mouse and human fibroblasts and mid-gestation mouse embryos were broadly similar, with specific differences. The major folate species in these cell types was 5-methyl tetrahydrofolate, in contrast to lymphoblastoid cell lines in which the predominant form was tetrahydrofolate. Analysis of embryonic human brain revealed a shift in folate profile with increasing developmental stage, with a decline in relative abundance of dihydrofolate and increase in 5-methyl tetrahydrofolate. These cell type-specific and developmental changes in folate profile may indicate differential requirements for the various outputs of folate metabolism. PMID:23483428
Leung, Kit-Yi; De Castro, Sandra C P; Cabreiro, Filipe; Gustavsson, Peter; Copp, Andrew J; Greene, Nicholas D E
From 'human being' to 'social subject': "unfreezing" ergonomics and the implications for understanding and intervening health-disease process.
Ergonomics has been successful in increasing productivity and comfort in the work arena. It has also contributed to reducing occupational accidents. Despite this, ergonomics is frequently limited to understanding the health-disease process related to human-technology interactions, as this process is more complex than what can be understood from an ergonomic evaluation. Recognising this limit, this work ontologically and epistemologically contrasts the notions of 'human being' and 'social subject', and concludes that the study object of ergonomics, or human-technology interaction, greatly depends on social aspects that nowadays are not tackled explicitly: route (history), project, structure, agency, motivations and power. It also analyses how participatory ergonomics tacitly includes many of these aspects, including some implications that the change of notion, from 'human being' to 'social subject', brings to the understanding of the health-disease process and the reduction of associated risks during human activities. PMID:22317190
Morales, Karen Lange; Garc�a-Acosta, Gabriel
Developmental dyscalculia is a specific learning disability affecting the normal acquisition of arithmetic skills. Genetic, neurobiologic, and epidemiologic evidence indicates that dyscalculia, like other learning disabilities, is a brain-based disorder. However, poor teaching and environmental deprivation have also been implicated in its etiology. Because the neural network of both hemispheres comprises the substrate of normal arithmetic skills, dyscalculia can result
Ruth S. Shalev
ERIC Educational Resources Information Center
Available from: Journal of Pediatric Psychology, Child Study Cente, 1100 N.E. 13th Street, Oklahoma City, Oklahoma 73117. The author discusses the concept of developmental dyslexia and attributes the wide variation in estimates of prevalence to the use of conflicting definitions of the disorder. (IM)
Benton, Arthur
New Paradigm for Understanding In-Flight Decision Making Errors: a Neurophysiological Model Leveraging Human Factors
Human factors centered aviation accident analyses report that skill based errors are known to be cause of 80% of all accidents, decision making related errors 30% and perceptual errors 6%1. In-flight decision making error is a long time recognized major avenue leading to incidents and accidents. Through the past three decades, tremendous and costly efforts have been developed to attempt to clarify causation, roles and responsibility as well as to elaborate various preventative and curative countermeasures blending state of the art biomedical, technological advances and psychophysiological training strategies. In-flight related statistics have not been shown significantly changed and a significant number of issues remain not yet resolved. Fine Postural System and its corollary, Postural Deficiency Syndrome (PDS), both defined in the 1980's, are respectively neurophysiological and medical diagnostic models that reflect central neural sensory-motor and cognitive controls regulatory status. They are successfully used in complex neurotraumatology and related rehabilitation for over two decades. Analysis of clinical data taken over a ten-year period from acute and chronic post-traumatic PDS patients shows a strong correlation between symptoms commonly exhibited before, along side, or even after error, and sensory-motor or PDS related symptoms. Examples are given on how PDS related central sensory-motor control dysfunction can be correctly identified and monitored via a neurophysiological ocular-vestibular-postural monitoring system. The data presented provides strong evidence that a specific biomedical assessment methodology can lead to a better understanding of in-flight adaptive neurophysiological, cognitive and perceptual dysfunctional status that could induce in flight-errors. How relevant human factors can be identified and leveraged to maintain optimal performance will be addressed.
Souvestre, P A; Landrock, C K; Blaber, A P
Understanding human - bat interactions in NSW, Australia: improving risk communication for prevention of Australian bat lyssavirus
Background Australian bat lyssavirus (ABLV) infects a number of flying fox and insectivorous bats species in Australia. Human infection with ABLV is inevitably fatal unless prior vaccination and/or post-exposure treatment (PET) is given. Despite ongoing public health messaging about the risks associated with bat contact, surveillance data have revealed a four-fold increase in the number of people receiving PET for bat exposure in NSW between 2007 and 2011. Our study aimed to better understand these human � bat interactions in order to identify additional risk communication messages that could lower the risk of potential ABLV exposure. All people aged 18 years or over whom received PET for non-occupation related potential ABLV exposure in the Hunter New England Local Health District of Australia between July 2011 and July 2013 were considered eligible for the study. Eligible participants were invited to a telephone interview to explore the circumstances of their bat contact. Interviews were then transcribed and thematically analysed by two independent investigators. Results Of 21 eligible participants that were able to be contacted, 16 consented and participated in a telephone interview. Participants reported bats as being widespread in their environment but reported a general lack of awareness about ABLV, particularly the risk of disease from bat scratches. Participants who attempted to �rescue� bats did so because of a deep concern for the bat�s welfare. Participants reported a change in risk perception after the exposure event and provided suggestions for public health messages that could be used to raise awareness about ABLV. Conclusions Reframing the current risk messages to account for the genuine concern of people for bat welfare may enhance the communication. The potential risk to the person and possible harm to the bat from an attempted �rescue� should be promoted, along with contact details for animal rescue groups. The potential risk of ABLV from bat scratches merits greater emphasis.
Current understanding of the mechanism of benzene-induced leukemia in humans: implications for risk assessment
Benzene causes acute myeloid leukemia and probably other hematological malignancies. As benzene also causes hematotoxicity even in workers exposed to levels below the US permissible occupational exposure limit of 1 part per million, further assessment of the health risks associated with its exposure, particularly at low levels, is needed. Here, we describe the probable mechanism by which benzene induces leukemia involving the targeting of critical genes and pathways through the induction of genetic, chromosomal or epigenetic abnormalities and genomic instability, in a hematopoietic stem cell (HSC); stromal cell dysregulation; apoptosis of HSCs and stromal cells and altered proliferation and differentiation of HSCs. These effects modulated by benzene-induced oxidative stress, aryl hydrocarbon receptor dysregulation and reduced immunosurveillance, lead to the generation of leukemic stem cells and subsequent clonal evolution to leukemia. A mode of action (MOA) approach to the risk assessment of benzene was recently proposed. This approach is limited, however, by the challenges of defining a simple stochastic MOA of benzene-induced leukemogenesis and of identifying relevant and quantifiable parameters associated with potential key events. An alternative risk assessment approach is the application of toxicogenomics and systems biology in human populations, animals and in vitro models of the HSC stem cell niche, exposed to a range of levels of benzene. These approaches will inform our understanding of the mechanisms of benzene toxicity and identify additional biomarkers of exposure, early effect and susceptibility useful for risk assessment.
McHale, Cliona M.; Zhang, Luoping; Smith, Martyn T.
Ad cerebrum per scientia: Ira Hirsh, psychoacoustics, and new approaches to understanding the human brain
NASA Astrophysics Data System (ADS)
As Research Director of CID, Ira emphasized the importance of combining information from biology with rigorous studies of behavior, such as psychophysics, to better understand how the brain and body accomplish the goals of everyday life. In line with this philosophy, my doctoral dissertation sought to explain brain functional asymmetries (studied with dichotic listening) in terms of the physical dimensions of a library of test sounds designed to represent a speech-music continuum. Results highlighted individual differences plus similarities in terms of patterns of relative ear advantages, suggesting an organizational basis for brain asymmetries depending on physical dimensions of stimulus and gesture with analogs in auditory, visual, somatosensory, and motor systems. My subsequent work has employed a number of noninvasive methods (OAEs, EPs, qEEG, PET, MRI) to explore the neurobiological bases of individual differences in general and functional asymmetries in particular. This research has led to (1) the AXS test battery for assessing the neurobiology of human sensory-motor function; (2) the handshaking model of brain function, describing dynamic relations along all three body/brain axes; (3) the four-domain EPIC model of functional asymmetries; and (4) the trimodal brain, a new model of individual differences based on psychoimmunoneuroendocrinology.
Lauter, Judith
The GPCR genes have a variety of exon-intron structures even though their proteins are all structurally homologous. We have examined all human GPCR genes with at least two functional protein isoforms, totaling 199, aiming to gain an understanding of what may have contributed to the large diversity of the exon-intron structures of the GPCR genes. The 199 genes have a total of 808 known protein splicing isoforms with experimentally verified functions. Our analysis reveals that 1,301 (80.6%) adjacent exon-exon pairs out of the total of 1,613 in the 199 genes have either exactly one exon skipped or the intron in-between retained in at least one of the 808 protein splicing isoforms. This observation has a statistical significance p-value of 2.051762* e?09, assuming that the observed splicing isoforms are independent of the exon-intron structures. Our interpretation of this observation is that the exon boundaries of the GPCR genes are not randomly determined; instead they may be selected to facilitate specific alternative splicing for functional purposes.
Increasing our understanding of human cognition through the study of Fragile X Syndrome.
Fragile X Syndrome (FXS) is considered the most common form of inherited intellectual disability. It is caused by reductions in the expression level or function of a single protein, the Fragile X Mental Retardation Protein (FMRP), a translational regulator which binds to approximately 4% of brain messenger RNAs. Accumulating evidence suggests that FXS is a complex disorder of cognition, involving interactions between genetic and environmental influences, leading to difficulties in acquiring key life skills including motor skills, language, and proper social behaviors. Since many FXS patients also present with one or more features of autism spectrum disorders (ASDs), insights gained from studying the monogenic basis of FXS could pave the way to a greater understanding of underlying features of multigenic ASDs. Here we present an overview of the FXS and FMRP field with the goal of demonstrating how loss of a single protein involved in translational control affects multiple stages of brain development and leads to debilitating consequences on human cognition. We also focus on studies which have rescued or improved FXS symptoms in mice using genetic or therapeutic approaches to reduce protein expression. We end with a brief description of how deficits in translational control are implicated in FXS and certain cases of ASDs, with many recent studies demonstrating that ASDs are likely caused by increases or decreases in the levels of certain key synaptic proteins. The study of FXS and its underlying single genetic cause offers an invaluable opportunity to study how a single gene influences brain development and behavior. PMID:23723176
Cook, Denise; Nuro, Erin; Murai, Keith K
From competencies to human interests: ways of knowing and understanding in medical education.
When considering the teaching and learning of topics of social relevance in medicine, such as professionalism, medical ethics, the doctor-patient relationship, and issues of diversity and social justice, one is tempted to ask, are the ways of knowing in these fields different from that in the biomedical and clinical sciences? Furthermore, given that the competency approach is dominant in medical education, one might also ask, is the competency model truly appropriate for all of the types of knowledge necessary to become a good physician? These questions are not merely academic, for they are at the core of how these subjects are taught, learned, and assessed.The goal of this article is threefold: first, to explore the nature of knowing and the educational goals in different areas of medicine and, in particular, those areas that have social relevance; second, to critically review the concept of competencies when applied to education in these areas; and third, to explore alternative strategies for teaching, learning, and assessment. This discussion reflects a view that the goal of education in areas of social relevance in medicine should be the enhancement of an understanding of-a deep and abiding connection with-the social responsibilities of the physician. Moving beyond competencies, this approach aspires toward the development of practical wisdom (phronesis) which, when embodied in the physician, links the knowledge and skills of the biomedical and clinical sciences with a moral orientation and call to action that addresses human interests in the practice of medicine. PMID:24662200
Kumagai, Arno K
Understanding Social Complexity Within the Wildland-Urban Interface: A New Species of Human Habitation?
NASA Astrophysics Data System (ADS)
The lack of knowledge regarding social diversity in the Wildland Urban Interface (WUI) or an in-depth understanding of the ways people living there interact to address common problems is concerning, perhaps even dangerous, given that community action is necessary for successful wildland fire preparedness and natural resource management activities. In this article, we lay out the knowledge and preliminary case study evidence needed to begin systematically documenting the differing levels and types of adaptive capacity WUI communities have for addressing collective problems such as wildland fire hazard. In order to achieve this end, we draw from two theoretical perspectives encompassing humans' interactions with their environment, including (1) Kenneth Wilkinson's interactional approach to community, (2) and certain elements of place literature. We also present case study research on wildfire protection planning in two drastically different California communities to illustrate how social diversity influences adaptive capacity to deal with hazards such as wildland fire. These perspectives promote an image of the WUI not as a monolithic entity but a complex mosaic of communities with different needs and existing capacities for wildland fire and natural resource management.
Paveglio, Travis B.; Jakes, Pamela J.; Carroll, Matthew S.; Williams, Daniel R.
Understanding social complexity within the wildland-urban interface: a new species of human habitation?
The lack of knowledge regarding social diversity in the Wildland Urban Interface (WUI) or an in-depth understanding of the ways people living there interact to address common problems is concerning, perhaps even dangerous, given that community action is necessary for successful wildland fire preparedness and natural resource management activities. In this article, we lay out the knowledge and preliminary case study evidence needed to begin systematically documenting the differing levels and types of adaptive capacity WUI communities have for addressing collective problems such as wildland fire hazard. In order to achieve this end, we draw from two theoretical perspectives encompassing humans' interactions with their environment, including (1) Kenneth Wilkinson's interactional approach to community, (2) and certain elements of place literature. We also present case study research on wildfire protection planning in two drastically different California communities to illustrate how social diversity influences adaptive capacity to deal with hazards such as wildland fire. These perspectives promote an image of the WUI not as a monolithic entity but a complex mosaic of communities with different needs and existing capacities for wildland fire and natural resource management. PMID:19238478
Paveglio, Travis B; Jakes, Pamela J; Carroll, Matthew S; Williams, Daniel R
NTP-CERHR Monograph on the Potential Human Reproductive and Developmental Effects of Di-n-Octyl Phthalate (DnOP).
The National Toxicology Program (NTP) Center for the Evaluation of Risks to Human Reproduction (CERHR) conducted an evaluation of the potential for di-n-octyl phthalate (DnOP) to cause adverse effects on reproduction and development in humans. DnOP is one of 7 phthalate chemicals evaluated by the NTP CERHR Phthalates Expert Panel. These phthalates were selected for evaluation because of high production volume, extent of human exposures, use in children's products, and/or published evidence of repro- ductive or developmental toxicity. Available information indicates that there are no commercial uses of pure DnOP. However, DnOP comprises approximately 20% of the commercially important C6-10 phthalate mixture, which is used in flooring and carpet tiles, tarps, pool liners, and garden hoses. DnOP is approved by the FDA as an indirect food additive and is used in seam cements, bottle cap liners, and conveyor belts. The results of this evaluation on DnOP are published in an NTP-CERHR monograph which includes: 1) the NTP Brief, 2) the Expert Panel Report on the Reproductive and Developmental Toxicity of DnOP, and 3) public comments received on the Expert Panel Report. As stated in the NTP Brief, the NTP reached the following conclusions regarding the possible effects of exposure to DnOP on human development and reproduction. Limited studies in mice and rats show that high exposures to DnOP may cause adverse developmental effects, but no evidence of reproductive effects was observed. In a continuous breeding study, no adverse effects were observed in the treated parents or their offspring after dosed feed exposure of mice (approx. 1,800, 3,600, or 7,500 mg/kg body weight/day). Human exposure information for DnOP was not available but it was assumed that the general US population would be exposed to 3-30 mug/kg body weight/day, based upon the range of estimated exposures for DEHP. Based on this assumption, NTP concluded that there is negligible concern for effects on adult reproductive systems. Two developmental studies were evaluated by the panel. In the first study, pregnant rats were treated with 5,000 and 10,000 mg/kg body weight/day DnOP by intraperitoneal injection on gestational days 5, 10, and 15. Increased fetal malformations and reduced body weights were observed at both doses. In the second study, pregnant mice were treated by gavage with approx. 10,000 mg/kg bodyweight/day on gestational days 6-13 and were allowed to deliver the pups. The treated group had reduced litter size, but birth weights and pup survival to postnatal day 3 were not affected. These studies did not determine an exposure level at which no adverse effects occur. The NTP concluded that there is insufficient information on developmental toxicity to reach a conclusion regarding the potential for DnOP to adversely affect human development. NTP-CERHR monographs are transmitted to federal and state agencies, interested parties, and the public and are available in electronic PDF format on the CERHR web site (http://cerhr.niehs.nih.gov) and in printed text or CD-ROM from the CERHR (National Institute of Environmental Health Sciences, P.O. Box 12233, MD EC-32, Research Triangle Park, NC; fax: 919-316-4511). PMID:15995728
A novel X-linked disorder with developmental delay and autistic features
OBJECTIVE: Genomic duplications that lead to autism and other human diseases are interesting pathological lesions since the underlying mechanism almost certainly involves dosage sensitive genes. We aim to understand a novel genomic disorder with profound phenotypic consequences, most notably global developmental delay, autism, psychosis, and anorexia nervosa. METHODS: We evaluated the affected individuals, all maternally related, using childhood autism rating
N. Kaya; D. Colak; A. Albakheet; M. Al-Owain; N. Abu-Dheim; B. Al-Younes; J. Al-Zahrani; N. M. Mukaddes; A. Dervent; N. Al-Dosari; A. Al-Odaib; I. V. Kayaalp; M. Al-Sayed; Z. Al-Hassnan; M. J. Nester; M. Al-Dosari; H. Al-Dhalaan; A. Chedrawi; H. Gunoz; B. Karakas; N. Sakati; F. S. Alkuraya; G. G. Gascon; P. T. Ozand
Mixing Qualitative and Quantitative Research in Developmental Science: Uses and Methodological Choices
Multiple methods are vital to understanding development as a dynamic, transactional process. This article focuses on the ways in which quantitative and qualitative methodologies can be combined to enrich developmental science and the study of human development, focusing on the practical questions of \\
Hirokazu Yoshikawa; Thomas S. Weisner; Ariel Kalil
Understanding Historical Human Migration Patterns and Interbreeding (JGI Seventh Annual User Meeting 2012: Genomics of Energy and Environment)
Eske Willerslev from the University of Copenhagen on "Understanding Historical Human Migration Patterns and Interbreeding Using the Ancient Genomes of a Palaeo-Eskimo and an Aboriginal Australian" at the 7th Annual Genomics of Energy & Environment Meeting on March 21, 2012 in Walnut Creek, California.
Willerslev, Eske [University of Copenhagen
Understanding Historical Human Migration Patterns and Interbreeding (JGI Seventh Annual User Meeting 2012: Genomics of Energy and Environment)
Eske Willerslev from the University of Copenhagen on "Understanding Historical Human Migration Patterns and Interbreeding Using the Ancient Genomes of a Palaeo-Eskimo and an Aboriginal Australian" at the 7th Annual Genomics of Energy & Environment Meeting on March 21, 2012 in Walnut Creek, California.
Understanding Historical Human Migration Patterns and Interbreeding (JGI Seventh Annual User Meeting 2012: Genomics of Energy and Environment)
Eske Willerslev from the University of Copenhagen on "Understanding Historical Human Migration Patterns and Interbreeding Using the Ancient Genomes of a Palaeo-Eskimo and an Aboriginal Australian" at the 7th Annual Genomics of Energy & Environment Meeting on March 21, 2012 in Walnut Creek, California.
Willerslev, Eske [University of Copenhagen] [University of Copenhagen
Forensic Spoorology: Seeing and Understanding Human Behavior through Observation, Classification and Interpretation of Spoor Evidence.
National Technical Information Service (NTIS)
Humans have used traditional tracking 'skills' to follow a quarry (human or animal) since the beginning of existence. 'Visual Tracking' at its very basic level is the natural predatory hunting instinct of man.. Even with this history, the sophistication o...
T. J. Cunningham
RNA tumor viruses, oncogenes, human cancer and AIDS: On the frontiers of understanding
This book contains 31 papers divided into six sections. The section headings are: Molecular Genetics of the RNA Tumor Viruses, Endogenous Retrovirus Sequences in Human Cells, Molecular Biology of Human Cancers, HTLV/LAV, T-Cell Leukemia and AIDS, Experimental Model Systems for the Study of Human Neoplasia and Related Diseases, and Perspectives.
Furmanski, P.; Hager, J.C.; Rich, M.A.
Towards a systems biology understanding of human health: Interplay between genotype, environment and nutrition
Sequencing of the human genome has opened the door to the most exciting new era for the holistic system description of human health. It is now possible to study the underlying mechanisms of human health in relation to diet and other environmental factors such as drugs and toxic pollutants. Technological advances make it feasible to envisage that in the future
Frank Desiere
�A friend who understand fully�: notes on humanizing research in a multiethnic youth community
In this article, I conceptualize ethnographic, qualitative, and social language research with marginalized and oppressed communities as humanizing research. Humanizing research is a methodological stance, which requires that our inquiries involve dialogic consciousness?raising and the building of relationships of dignity and care for both researchers and participants. I offer evidence that such humanization is not only ethically necessary but also
Django Paris
Big thoughts in small brains? Dogs as am odel for understanding human social cognition
In this review we argued that dogs can provide a good model for both the evolution of human social-cognitive abilities and studying the underlying neural and genetic structures of these behavioural features. The key di�erence between the present and other approaches for modelling human social evolution lies in the assumption that there is a large overlap between the human and
J o?
Understanding Visual Metaphor: Developmental and Individual Differences.
ERIC Educational Resources Information Center
This monograph describes the development of the Metaphoric Triads Task (MTT), an instrument designed to assess metaphoric comprehension. Validity and reliability of the instrument are discussed and data for 12 samples of subjects are reported. Sex differences were negligible, but progressive improvement in MTT score with age was noted. Pictorial�
Kogan, Nathan; And Others
A biopsychosocial perspective on parenting and developmental psychopathology.
Although considerable research has examined the relations between parental behavior and a range of child developmental outcomes, much of this work has been conducted at a very broad level of behavioral analysis. A developmental psychopathology framework and recent research conducted within this framework point to the need for models of parenting and child psychopathology that offer greater specificity regarding processes that may be implicated in the effects of these relationships. In addition, recent animal work and some human work has focused more on the proximal biological and social mechanisms through which parenting affects child outcomes. Our conceptualization of parenting effects acknowledges that family and child factors are embedded in a dynamic biological and social context that is key to understanding developmental trajectories of child adjustment. In this paper, we review two areas of research that are illuminating the biological processes underlying links between parenting and child psychopathology: molecular genetics and psychophysiology. We adopt a biopsychosocial perspective on developmental psychopathology that implies that a set of hierarchically organized, but reciprocally interacting, processes, from the genetic to the environmental, provide the essential elements of both normative and nonnormative development (Gottlieb, 2007). New directions stimulated by this general approach are discussed, with an emphasis on the contextual and developmental issues and applications implied by such a perspective. PMID:24342847
Calkins, Susan D; Propper, Cathi; Mills-Koonce, W Roger
Resilience is the ability to adapt successfully in the face of stress and adversity. Stressful life events, trauma, and chronic adversity can have a substantial impact on brain function and structure, and can result in the development of posttraumatic stress disorder (PTSD), depression and other psychiatric disorders. However, most individuals do not develop such illnesses after experiencing stressful life events, and are thus thought to be resilient. Resilience as successful adaptation relies on effective responses to environmental challenges and ultimate resistance to the deleterious effects of stress, therefore a greater understanding of the factors that promote such effects is of great relevance. This review focuses on recent findings regarding genetic, epigenetic, developmental, psychosocial, and neurochemical factors that are considered essential contributors to the development of resilience. Neural circuits and pathways involved in mediating resilience are also discussed. The growing understanding of resilience factors will hopefully lead to the development of new pharmacological and psychological interventions for enhancing resilience and mitigating the untoward consequences.
Wu, Gang; Feder, Adriana; Cohen, Hagit; Kim, Joanna J.; Calderon, Solara; Charney, Dennis S.; Mathe, Aleksander A.
Developmental dyscalculia (DD) is a learning disorder affecting the acquisition of school level arithmetic skills present in approximately 3-6% of the population. At the behavioral level DD is characterized by poor retrieval of arithmetic facts from memory, the use of immature calculation procedures and counting strategies, and the atypical representation and processing of numerical magnitude. At the neural level emerging evidence suggests DD is associated with atypical structure and function in brain regions associated with the representation of numerical magnitude. The current state of knowledge points to a core deficit in numerical magnitude representation in DD, but further work is required to elucidate causal mechanisms underlying the disorder. PMID:23622170
Price, Gavin R; Ansari, Daniel
Cardiac vectors in the healthy human fetus: developmental changes assessed by magnetocardiography and realistic approximations of the volume conductor
This study sought to characterize the developmental changes of three measures used to describe the morphology of the fetal cardiac vector: QRS peak-amplitude, QRS duration and QRS time-amplitude integral. To achieve this objective, we rely on a recently developed methodology for fetal cardiac vector estimation, using multichannel fetal magnetocardiographic (fMCG) recordings and realistic approximations of the volume conductors obtained from free-hand ultrasound imaging. Fetal magnetocardiographic recordings and 3D ultrasound images were obtained from 23 healthy, uncomplicated pregnancies for a total of 77 recordings performed at gestational ages between 22 weeks and 37 weeks. We report the developmental changes of the cardiac vector parameters with respect to gestational age and estimated fetal weight, as well as their dependence on the estimated ventricular mass derived from cardiac dimensions measured with M-mode ultrasound. The normative values can be used along with the cardiac time intervals reported by previous fMCG studies to assist future clinical studies investigating conditions that affect fetal cardiac function.
Tao, R; Popescu, EA; Drake, WB; Popescu, M
Understanding our genetic inheritance: The US Human Genome Project, The first five years FY 1991--1995
The Human Genome Initiative is a worldwide research effort with the goal of analyzing the structure of human DNA and determining the location of the estimated 100,000 human genes. In parallel with this effort, the DNA of a set of model organisms will be studied to provide the comparative information necessary for understanding the functioning of the human genome. The information generated by the human genome project is expected to be the source book for biomedical science in the 21st century and will by of immense benefit to the field of medicine. It will help us to understand and eventually treat many of the more than 4000 genetic diseases that affect mankind, as well as the many multifactorial diseases in which genetic predisposition plays an important role. A centrally coordinated project focused on specific objectives is believed to be the most efficient and least expensive way of obtaining this information. The basic data produced will be collected in electronic databases that will make the information readily accessible on convenient form to all who need it. This report describes the plans for the U.S. human genome project and updates those originally prepared by the Office of Technology Assessment (OTA) and the National Research Council (NRC) in 1988. In the intervening two years, improvements in technology for almost every aspect of genomics research have taken place. As a result, more specific goals can now be set for the project.
Developmental alterations in molecular weights of proteins in the human central nervous system that react with antibodies against myelin-associated glycoprotein.
By the use of a rat IgG monoclonal antibody (mab), a mouse mab and human serum containing an IgM mab, all of which react with isolated human myelin-associated glycoprotein (MAG) on immunoblots and bind only to proteins with relative mobilities identical to MAG and dMAG on immunoblots of homogenates of adult human spinal cord, we demonstrated the following: in homogenates of central nervous system tissue from human fetuses of gestational ages that antedate myelination, the anti-MAG antibodies react only with proteins with molecular weights of 250,000 or larger. During myelination the molecular weights of proteins with which the anti-MAG antibodies react shift towards the lower molecular weights found in adult myelin. Amongst those central nervous system regions examined, the shift towards the low molecular weights occurred earliest in the region that is first to become myelinated and latest in the one that is the last to myelinate. Once myelination is completed, the antibodies react only with proteins with relative mobilities identical to those of MAG and dMAG. These developmental changes in molecular weights of "MAG-related proteins" may prove useful as an index of chemical processes on the basis of which myelination occurs. PMID:6208201
Marton, L S; Stefansson, K
Evolutionary conservation of the oocyte transcriptome among vertebrates and its implications for understanding human reproductive function.
Cross-phylum and cross-species comparative transcriptomic analyses provide an evolutionary perspective on how specific tissues use genomic information. A significant mRNA subset present in the oocytes of most vertebrates is stabilized or stored for post-LH surge use. Since transcription is arrested in the oocyte before ovulation, this RNA is important for completing maturation and sustaining embryo development until zygotic genome activation. We compared the human oocyte transcriptome with an oocyte-enriched subset of mouse, bovine and frog (Xenopus laevis) genes in order to evaluate similarities between species. Graded temperature stringency hybridization on a multi-species oocyte cDNA array was used to measure the similarity of preferentially expressed sequences to the human oocyte library. Identity analysis of 679 human orthologs compared with each identified official gene symbol found in the subtractive (somatic-oocyte) libraries comprising our array revealed that bovine/human similarity was greater than mouse/human or frog/human similarity. However, based on protein sequence, mouse/human similarity was greater than bovine/human similarity. Among the genes over-expressed in oocytes relative to somatic tissue in Xenopus, Mus and Bos, a high level of conservation was found relative to humans, especially for genes involved in early embryonic development. PMID:23340479
Sylvestre, Eve-Lyne; Robert, Claude; Pennetier, Sophie; Labrecque, R�mi; Gilbert, Isabelle; Dufort, Isabelle; L�veill�, Marie-Claude; Sirard, Marc-Andr�
Towards an understanding of the link between environmental emissions and human body burdens of PCBs using CoZMoMAN.
Different factors affect how organic contaminants released into the environment over time distribute and accumulate, enter various food-chains, and potentially cause toxic effects in wildlife and humans. A sound chemical risk assessment thus requires the determination of the quantitative relationship between emissions and human exposure. This study aimed to assess the extent of the quantitative and mechanistic understanding of the link between environmental emissions and human body burdens for polychlorinated biphenyls (PCBs) in the western part of the Baltic Sea drainage basin and to identify any remaining knowledge gaps. An integrated, non-steady state model calculating human body burden from environmental emissions (CoZMoMAN) was created by linking the multi-compartment environmental fate model CoZMo-POP 2 with the human food chain bioaccumulation model ACC-HUMAN. CoZMoMAN predicted concentrations of seven PCB congeners in 11 key model compartments to typically within a factor of 2 to 4 of measured values, although larger discrepancies are noted for soils and humans. We conclude that whereas the most important processes which link emissions of PCBs to human body burdens are quite well understood in this region, some critical knowledge gaps related to the time trend of historical emissions remain to be addressed. PMID:19913301
Breivik, Knut; Czub, Gertje; McLachlan, Michael S; Wania, Frank
A Developmental Approach to Gay and Lesbian Youth.
ERIC Educational Resources Information Center
Reviews the literature concerning homosexual identity development. Discusses at-risk issues (suicide, human immunodeficiency virus and Acquired Immune Deficiency Syndrome infection, school problems) and developmental difficulties for gay and lesbian youth (sensitization, identity confusion, identity assumption, commitment). Proposes developmental�
McFarland, William P.
Man Bites Mosquito: Understanding the Contribution of Human Movement to Vector-Borne Disease Dynamics
In metropolitan areas people travel frequently and extensively but often in highly structured commuting patterns. We investigate the role of this type of human movement in the epidemiology of vector-borne pathogens such as dengue. Analysis is based on a metapopulation model where mobile humans connect static mosquito subpopulations. We find that, due to frequency dependent biting, infection incidence in the
Ben Adams; Durrell D. Kapan
Human-Computer Interaction (HCI) in Educational Environments: Implications of Understanding Computers as Media
This article is a review of the literature in the field of Human Computer Interaction (HCI) as it may apply specifically to educational environments. The origin of HCI and its relation- ship to other areas of study such as human factors, usability, and computer interface design are examined. Additionally, the notion of computers as a medium was investigated in or-
A new approach to understanding the impact of circadian disruption on human health
BACKGROUND: Light and dark patterns are the major synchronizer of circadian rhythms to the 24-hour solar day. Disruption of circadian rhythms has been associated with a variety of maladies. Ecological studies of human exposures to light are virtually nonexistent, however, making it difficult to determine if, in fact, light-induced circadian disruption directly affects human health. METHODS: A newly developed field
Mark S Rea; Andrew Bierman; Mariana G Figueiro; John D Bullough
Transcending the Limitations of the Social Sciences: Insight, Understanding, and the Humanities in Educational Administration.
ERIC Educational Resources Information Center
Considers the role of the humanities in the study and practice of educational administration, offering significant insights into the human condition and the philosophical and moral aspects of education. Discusses the limitations of the subject-object dualism underpinning traditional social science. Explains how Slipperjack's "Honor the Sun,"�
Ryan, James
"A Friend Who Understand Fully": Notes on Humanizing Research in a Multiethnic Youth Community
ERIC Educational Resources Information Center
In this article, I conceptualize ethnographic, qualitative, and social language research with marginalized and oppressed communities as "humanizing research". Humanizing research is a methodological stance, which requires that our inquiries involve dialogic consciousness-raising and the building of relationships of dignity and care for both�
Paris, Django
Why Primates? The Importance of Nonhuman Primates for Understanding Human Infancy
ERIC Educational Resources Information Center
We introduce the thematic collection by noting some striking similarities in the cognitive abilities of human infants and nonhuman primates. What are the implications of these similarities for our comprehension of human infant cognition? After providing a brief historical and conceptual background on comparative behavioral research, we discuss how�
Weiss, Daniel J.; Santos, Laurie R.
Human-Computer Interaction (HCI) in Educational Environments: Implications of Understanding Computers as Media.
ERIC Educational Resources Information Center
Reviews literature in the field of human-computer interaction (HCI) as it applies to educational environments. Topics include the origin of HCI; human factors; usability; computer interface design; goals, operations, methods, and selection (GOMS) models; command language versus direct manipulation; hypertext; visual perception; interface�
Berg, Gary A.
Assessment of boric acid and borax using the IEHR evaluative process for assessing human developmental and reproductive toxicity of agents
This document presents an evaluation of the reproductive and developmental effects of boric acid, H3BO3 (CAS Registry No. 10043-35-3) and disodium tetraborate decahydrate or borax, Na2B4O2O(CAS Registry No. 1303-96-4). The element, boron, does not exist naturally. In dilute aqueous solution and at physiological pH (7.4), the predominant species in undissociated boric acid (greater than 98%), irrespective of whether the initial material was boric acid of borax. Therefore, it is both useful and correct to compare exposures and dosages to boric acid and borax in terms of `boron equivalents`, since both materials form equivalent species in dilute aqueous solution with similar systemic effects. In order to be clear in this document, the term `boron` will refer to `boron equivalents` or percent boron in boric acid and borax.
Moore, J.A.
BDE 49 and developmental toxicity in zebrafish
The polybrominated diphenyl ethers (PBDEs) are a group of brominated flame retardants. Human health concerns of these agents have largely centered upon their potential to elicit reproductive and developmental effects. Of the various congeners, BDE 49 (2,2�,4,5�-tetrabromodiphenyl ether) has been poorly studied, despite the fact that it is often detected in the tissues of fish and wildlife species. Furthermore, we have previously shown that BDE 49 is a metabolic debromination product of BDE 99 hepatic metabolism in salmon, carp and trout, underscoring the need for a better understanding of biological effects. In the current study, we investigated the developmental toxicity of BDE 49 using the zebrafish (Danio rerio) embryo larval model. Embryo and larval zebrafish were exposed to BDE 49 at either 5 hours post fertilization (hpf) or 24 hpf and monitored for developmental and neurotoxicity. Exposure to BDE 49 at concentrations of 4 �M- 32 �M caused a dose-dependent loss in survivorship at 6 days post fertilization (dpf). Morphological impairments were observed prior to the onset of mortality, the most striking of which included severe dorsal curvatures of the tail. The incidence of dorsal tail curvatures was dose and time dependent. Exposure to BDE 49 caused cardiac toxicity as evidenced by a significant reduction in zebrafish heart rates at 6 dpf but not earlier, suggesting that cardiac toxicity was non-specific and associated with physiological stress. Neurobehavioral injury from BDE 49 was evidenced by an impairment of touch-escape responses observed at 5 dpf. Our results indicate that BDE 49 is a developmental toxicant in larval zebrafish that can cause morphological abnormalities and adversely affect neurobehavior. The observed toxicities from BDE 49 were similar in scope to those previously reported for the more common tetrabrominated congener, BDE 47, and also for other lower brominated PBDEs, suggest that these compounds may share similarities in risk to aquatic species.
McClain, Valerie; Stapleton, Heather M.; Gallagher, Evan
Developmentally Appropriate Gardening for Young Children.
ERIC Educational Resources Information Center
Noting that the recent interest in gardening with young children has resulted in a variety of programs but little support to teachers or horticulturists on how to understand the developmental needs of children and how to adapt gardening activities to those needs, this paper presents principles and goals of developmentally appropriate gardening.�
Stoecklin, Vicki L.
Perceptions of Students in Developmental Classes
ERIC Educational Resources Information Center
The number of students enrolling in colleges and universities requiring remedial programs is increasing. Developmental courses are used to increase student academic skills. Understanding how students perceive their placement and experience in developmental courses can provide valuable insight for high schools, community colleges, and universities�
Koch, Bevan; Slate, John R.; Moore, George
Genetically-modified human pluripotent stem cells: new hopes for the understanding and the treatment of neurological diseases?
The fundamental inaccessibility of the human neural cell types affected by neurological disorders prevents their isolation for in vitro studies of disease mechanisms or for drug screening efforts. Pluripotent stem cells represent a new interesting way to generate models of human neurological disorders, explore the physiopathological mechanisms and develop new therapeutic strategies. Disease-specific human embryonic stem cells were the first source of material to be used to study certain disease states. The recent demonstration that human somatic cells, such as fibroblasts or blood cells, can be genetically converted to induced pluripotent stem cells (hiPSCs) together with the continuous improvement of methods to differentiate these cells into disease-affected neuronal subtypes opens new perspectives to model and understand a large number of human pathologies. This review focuses on the opportunities concerning the use disease-specific human pluripotent stem cells as well as the different challenges that still need to be overcome. We also discuss the recent improvements in the genetic manipulation of human pluripotent stem cells and the consequences of these on disease modeling and drug screening for neurological diseases. PMID:23444870
Nedelec, St�phane; Onteniente, Brigitte; Peschanski, Marc; Martinat, C�cile
Oversight on the Developmentally Disabled Assistance and Bill of Rights Act. Hearing Before the Subcommittee on the Handicapped of the Committee on Human Resources, U.S. Senate, 95th Congress, First Session.
ERIC Educational Resources Information Center
Presented is testimony given before the Subcommittee on the Handicapped of the Senate Committee on Human Resources regarding the Developmentally Disabled Assistance and Bill of Rights Act. Statements are included from representatives of such agencies and organizations as the National Association for Retarded Citizens, American Occupational Therapy�
Congress of the U.S., Washington, DC. Senate.
Interbeing and Mindfulness: A Bridge to Understanding Jean Watson's Theory of Human Caring.
ERIC Educational Resources Information Center
Explains and compares Thich Naht Hanh's concept of interbeing and mindfulness and Jean Watson's theory of human caring. Describes the application of mindful practices to holistic nursing and nursing education. (Contains 12 references.) (SK)
Sitzman, Kathleen L.
Experimental human exposure to air pollutants is essential to understand adverse health effects.
Air pollution has been found to cause significant global mortality, with 6.8 million excess deaths attributed to air pollution each year, and similarly large numbers of exacerbations of asthma, chronic obstructive pulmonary disease, and cardiovascular diseases. Epidemiological research has identified associations, and experimental human exposure has provided critical information on dose-response relationships of adverse effects caused by controlled human exposure to individual pollutants. Human exposures further enable examination of the relationship of adverse effects such as symptoms and pulmonary function changes to presumed mechanisms of disease revealed through analysis of bronchoalveolar lavage fluid obtained from the lower respiratory tract. In this Perspective, we analyze the ethics of human exposure, the importance of the information gained, and the risks of such exposure. We find that these studies appear to have been done with proper approval of institutional review boards, were done with informed consent from the participants, and have rarely been associated with serious adverse events. PMID:24024529
Rom, William N; Boushey, Homer; Caplan, Arthur
The nonhuman primate reproductive system provides an excellent model for studying basic physiological processes applicable to humans. This article reviews hormonal observations and experimental manipulations useful in the evaluation of ovarian events in various stages of the repr...
Structured Like A Monster: Understanding Human Difference Through A Legal Category
This article will argue that the legal idea of the monster offers to inform contemporary thinking in relation to outsiders.\\u000a Drawing on the work of Foucault it will be contended that the process, whereby at least some human beings are positioned as\\u000a outsiders, is structured like a monster. That is to say, at least some constructions or representations of human
Andrew N. Sharpe
Living systems theory as a paradigm for organizational behavior: understanding humans, organizations, and social processes.
Living systems theories have been used to model human, organization, and communication processes. This paper attempts to describe these models and to highlight the isomorphisms among the models. Particular emphasis is given to self-regulating properties of humans as a subsystem of social systems. Attention is given to the advantages of generalizing across levels and phenomena and integrating the middle-range theories that dominate the field of organizational behavior. Three broad recommendations for future research are discussed. PMID:8856949
Vancouver, J B
Remarriage: A Family Developmental Process.
ERIC Educational Resources Information Center
Outlines a developmental perspective for understanding the dynamics of remarried families. Uses case examples to illustrate the importance of adding to the current family situation both a view of critical points in a family's history, and expectation for its future paths. (RC)
Whiteside, Mary F.
... help the symptoms. Treatments include physical, speech, and occupational therapy. Special education classes and psychological counseling can also help. NIH: National Institute of Child Health and Human Development
Developmental dyspraxia and developmental coordination disorder
This article discusses the role developmental dyspraxia plays in developmental coordination disorder (DCD), based upon a review of literature on apraxia, developmental dyspraxia, and DCD. Apraxia and dyspraxia have often been equated with DCD. However, it is argued that apraxia and dyspraxia primarily refer to the problems of motor sequencing and selection, which not all children with DCD exhibit. The
Motohide Miyahara; Isabelle M�bs
Directly Comparing Computer and Human Performance in Language Understanding and Visual Reasoning.
ERIC Educational Resources Information Center
Evaluation models are being developed for assessing artificial intelligence (AI) systems in terms of similar performance by groups of people. Natural language understanding and vision systems are the areas of concentration. In simplest terms, the goal is to norm a given natural language system's performance on a sample of people. The specific�
Baker, Eva L.; And Others
Transcending the individual human mind�creating shared understanding through collaborative design
Complex design problems require more knowledge than any single person possesses because the knowledge relevant to a problem is usually distributed among stakeholders. Bringing different and often controversial points of view together to create a shared understanding among these stakeholders can lead to new insights, new ideas, and new artifacts. New media that allow owners of problems to contribute to
Ernesto Arias; Hal Eden; Gerhard Fischer; Andrew Gorman; Eric Scharff
Dynamic and Coordinated Epigenetic Regulation of Developmental Transitions in the Cardiac Lineage
SUMMARY Heart development is exquisitely sensitive to the precise temporal regulation of thousands of genes that govern developmental decisions during differentiation. However, we currently lack a detailed understanding of how chromatin and gene expression patterns are coordinated during developmental transitions in the cardiac lineage. Here, we interrogated the transcriptome and several histone modifications across the genome during defined stages of cardiac differentiation. We find distinct chromatin patterns that are coordinated with stage-specific expression of functionally related genes, including many human disease-associated genes. Moreover, we discover a novel pre-activation chromatin pattern at the promoters of genes associated with heart development and cardiac function. We further identify stage-specific distal enhancer elements and find enriched DNA binding motifs within these regions that predict sets of transcription factors that orchestrate cardiac differentiation. Together, these findings form a basis for understanding developmentally regulated chromatin transitions during lineage commitment and the molecular etiology of congenital heart disease.
Wamstad, Joseph A.; Alexander, Jeffrey M.; Truty, Rebecca M.; Shrikumar, Avanti; Li, Fugen; Eilertson, Kirsten E.; Ding, Huiming; Wylie, John N.; Pico, Alexander R.; Capra, John A.; Erwin, Genevieve; Kattman, Steven J.; Keller, Gordon M.; Srivastava, Deepak; Levine, Stuart S.; Pollard, Katherine S.; Holloway, Alisha K.; Boyer, Laurie A.; Bruneau, Benoit G.
A Developmental Perspective on Underage Alcohol Use
Underage alcohol use can be viewed as a developmental phenomenon because many kinds of developmental changes and expectations appear to influence this behavior and also because it has consequences for development. Data on alcohol use, abuse, and dependence show clear age-related patterns. Moreover, many of the effects that alcohol use has on the drinker, in both the short and long term, depend on the developmental timing of alcohol use or exposure. Finally, many developmental connections have been observed in the risk and protective factors that predict the likelihood of problem alcohol use in young people. Therefore, efforts to understand and address underage drinking would benefit from a developmental perspective, and the general principles of developmental psychopathology offer a useful conceptual framework for research and prevention concerned with underage drinking.
Masten, Ann S.; Faden, Vivian B.; Zucker, Robert A.; Spear, Linda P.
Analysis in Serum-Free Culture of the Targets of Recombinant Human Hemopoietic Growth Factors: Interleukin 3 and Granulocyte\\/Macrophage-Colony-Stimulating Factor are Specific for Early Developmental Stages
We have used a serum-free culture system for enriched human hemopoietic progenitors to analyze the developmental stages and lineage specificities of the human hemopoietic colony-stimulating factors. None of the individual factors alone efficiently supported hemopoietic colony formation. Neither interleukin 3 nor granulocyte\\/macrophage-colony-stimulating factor alone or in combination effectively supported proliferation of progenitor cells. However, when combined with granulocyte-colony-stimulating factor or
Yoshiaki Sonoda; Yu-Chung Yang; Gordon G. Wong; Steven C. Clark; Makio Ogawa
Reconciling Human Smoking Behavior and Machine Smoking Patterns: Implications for Understanding Smoking Behavior and the Impact on Laboratory Studies
Introduction Recent Food and Drug Administration legislation enables the mandating of product performance standards for cigarette smoke and the evaluation of manufacturers� health claims for modified tobacco products. Laboratory studies used for these evaluations, and also to understand tobacco smoke toxicology, use machines to generate smoke. The goal of this review is to critically evaluate methods to assess human smoking behavior and replicate this in the laboratory. Methods Smoking behavior and smoking machine studies were identified using PubMed and publically available databases for internal tobacco company documents. Results The smoking machine was developed to generate smoke to allow for comparing cigarette tar and nicotine yields. The intent was to infer relative human disease risk, but this concept was flawed because humans tailor their smoking to the product and chemical yields and toxicological effects change with different smoking profiles. While smoking machines also allow for mechanistic assessments of smoking-related diseases, the interpretations also are limited. However, available methods to assess how humans puff could be used to provide better laboratory assessments, but these need to be validated. Separately, the contribution of smoke mouth-holding and inhalation to dose need to be assessed, because these parts of smoking are not captured by the smoking machine. Better comparisons of cigarettes might be done by tailoring human puff profiles to the product based on human studies and comparing results across regimens. Conclusions There are major research gaps that limit the use of smoking machine studies for informing tobacco control regulation and mechanistic studies.
Marian, Catalin; O'Connor, Richard J.; Djordjevic, Mirjana; Rees, Vaughan W.; Hatsukami, Dorothy K.; Shields, Peter G.
Students' Participation in an Interdisciplinary, Socioscientific Issues Based Undergraduate Human Biology Major and Their Understanding of Scientific Inquiry
NASA Astrophysics Data System (ADS)
The purpose of this study was to examine whether Socioscientific Issues (SSI) based learning environments affect university students' epistemological understanding of scientific inquiry differently from traditional science educational contexts. We identify and compare conceptions of scientific inquiry of students participating in an interdisciplinary, SSI-focused undergraduate human biology major (SSI) and those participating in a traditional biology major (BIO). Forty-five SSI students and 50 BIO students completed an open-ended questionnaire examining their understanding of scientific inquiry. Eight general themes including approximately 60 subthemes emerged from questionnaire responses, and the numbers of students including each subtheme in their responses were statistically compared between groups. A subset of students participated in interviews, which were used to validate and triangulate questionnaire data and probe students' understanding of scientific inquiry in relation to their majors. We found that both groups provided very similar responses, differing significantly in only five subthemes. Results indicated that both groups held generally adequate understandings of inquiry, but also a number of misconceptions. Small differences between groups supported by both questionnaires and interviews suggest that the SSI context contributed to nuanced understandings, such as a more interdisciplinary and problem-centered conception of scientific inquiry. Implications for teaching and research are discussed.
Eastwood, Jennifer L.; Sadler, Troy D.; Sherwood, Robert D.; Schlegel, Whitney M.
The human PD1 gene: complete cDNA, genomic organization, and developmentally regulated expression in B cell progenitors
We report the complete cDNA sequence and the genomic structure of the human PD-1 homologue. An analysis of the expression pattern of the human PD-1 gene (hPD-1) and the murine PD-1 gene (mPD-1) in developing bone marrow B-lineage cells was also undertaken. The full length hPD-1 cDNA is 2106 nucleotides long and encodes a predicted protein of 288 amino acid
Lawrence R Finger; Jaiyu Pu; Robert Wasserman; Rajeev Vibhakar; Elaine Louie; Richard R Hardy; Peter D Burrows; Linda G Billips
Cardiomyopathy of Friedreich's Ataxia: Use of Mouse Models to Understand Human Disease and Guide Therapeutic Development
Friedreich�s ataxia is a multisystem disorder of mitochondrial function affecting primarily the heart and brain. Patients experience a severe cardiomyopathy that can progress to heart failure and death. Although the gene defect is known, the precise function of the deficient mitochondrial protein, frataxin, is not known and limits therapeutic development. Animal models have been valuable for understanding the basic events of this disease. A significant need exists to focus greater attention on the heart disease in Friedreich�s ataxia, to understand its long-term outcome, and to develop new therapeutic strategies using existing medications and approaches. This review discusses some key features of the cardiomyopathy in Friedreich�s ataxia and potential therapeutic developments.
Pride, P. Melanie; Babbey, Clifford M.
Grasping the Affordances, Understanding the Reasoning: Toward a Dialectical Theory of Human Tool Use
ERIC Educational Resources Information Center
One of the most exciting issues in psychology is, What are the psychological mechanisms underlying human tool use? The computational approach assumes that the use of a tool (e.g., a hammer) requires the extraction of sensory information about object properties (heavy, rigid), which can then be translated into appropriate motor outputs (grasping,�
Osiurak, Francois; Jarry, Christophe; Le Gall, Didier
Understanding Generational Diversity: Strategic Human Resource Management and Development across the Generational "Divide"
ERIC Educational Resources Information Center
There are more generations in today's workforce than ever before, which has the possibility to create challenges for Human Resource professionals. The purpose of this article is to interrogate existing stereotypes and generalities about the characteristics of different generations with respect to the workplace, and to offer suggestions for�
Amayah, Angela Titi; Gedro, Julie
Understanding Protein Synthesis: A Role-Play Approach in Large Undergraduate Human Anatomy and Physiology Classes
ERIC Educational Resources Information Center
This study investigated the effectiveness of role play in a large undergraduate science class. The targeted population consisted of 298 students enrolled in 2 sections of an undergraduate Human Anatomy and Physiology course taught by the same instructor. The section engaged in the role-play activity served as the study group, whereas the section�
Sturges, Diana; Maurer, Trent W.; Cole, Oladipo
Students' Understanding of Connections between Human Engineered and Natural Environmental Systems
ERIC Educational Resources Information Center
This research draws on developments in educational research where "learning progressions" are emerging as a strategy for synthesizing research on science learning and applying that research to policy and practice, and advances in the natural sciences, where "interdisciplinary research on coupled human and natural systems" has become increasingly�
Tsurusaki, Blakely K.; Anderson, Charles W.
Understanding Genetic Epidemiology: The Potential Benefits and Challenges of Genetics for Improving Human Health
Genetic epidemiology has the potential to significantly impact human health. Here, we examine the major developments in the field�s history and the current state of the field, including both promising avenues of research and potential challenges genetic epidemiologists face.
Seyerle, Amanda A; Avery, Christy L
Evolution of Humans: Understanding the Nature and Methods of Science through Cooperative Learning
ERIC Educational Resources Information Center
This article describes the use of an enquiry-based approach to the study of human evolution in a practical context, integrating role-playing, jigsaw cooperative learning and scientific argumentation. The activity seeks to unravel the evolutionary relationships of five hominids and one ape from rather "messy" evidence. This approach enhanced the�
Lee, Yeung Chung
Understanding and Modulating Mammalian-Microbial Communication for Improved Human Health
The fact that the bacteria in the human gastrointestinal (GI) tract play a symbiotic role was noted as early as 1885, well before we began to manage microbial infections using antibiotics. However, even with the first antimicrobial compounds used in humans, the sulfa drugs, microbes were recognized to be critically involved in the biotransformation of these therapeutics. Thus, the roles played by the microbiota in physiology and in the management of human health have long been appreciated. Detailed examinations of GI symbiotic bacteria that started in the early 2000s and the first phases of the Human Microbiome Project that were completed in 2012 have ushered in an exciting period of granularity with respect to the ecology, genetics, and chemistry of the mammalian-microbial axes of communication. Here we review aspects of the biochemical pathways at play between commensal GI bacteria and several mammalian systems, including both local-epithelia and nonlocal responses including inflammation, immunology, metabolism, and neurobiology. Finally, we discuss how the microbial biotransformation of therapeutic compounds, such as anticancer or nonsteroidal anti-inflammatory drugs, can be modulated to reduce toxicity and potentially improve therapeutic efficacy.
Mani, Sridhar; Boelsterli, Urs A.; Redinbo, Matthew R.
From Monsoons to Microbes: Understanding the Ocean's Role in Human Health
NSDL National Science Digital Library
This online book offers a deeper look into the oceans that surround us, exploring the links among physical oceanography, public health, epidemiology, marine biology, and medicine in understanding what the ocean has to offer. Chapters include: contains chapters about climate and weather, coastal hazards, and public health; oceans and infectious diseases, harmful algal blooms (HABs); marine-derived pharmaceuticals and related bioactive agents; and marine organisms as models for biomedical research. PDF versions of the chapters are available to skim or read.
Commission on Geosciences; Environment and Resources (CGER) Ocean Studies Board (OSB)
Understanding Causal Relationships in the Metabolic Syndrome: Recent Insights from Extreme Human Phenotypes
\\u000a Insulin resistance is often associated with metabolic dyslipidaemia, fatty liver, hypertension and a number of other metabolic\\u000a disorders clustered under the name �metabolic syndrome.� The associations are robust but our understanding of how they are\\u000a linked at a molecular level remains incomplete. Patients with monogenic defects in insulin action provide unique opportunities\\u000a to dissect out the molecular pathways underpinning these
David B. Savage
Understanding the role of representations of human-leopard conflict in Mumbai through media-content analysis.
Attempts to minimize the effects of human-wildlife conflict (HWC) on conservation goals require an understanding of the mechanisms by which such conflicts are caused and sustained. This necessitates looking beyond the natural sciences to the human dimensions of wildlife management. Public dissemination of information regarding HWC occurs largely through the mass media. We conducted a content analysis of print media articles on human-leopard conflict in Mumbai, India. We sought to understand the framing of HWC and the changes in media coverage over a 10-year period (2001-2011) during which a large number of attacks on people prior to 2005 were followed by a program of trapping and relocation. After 2005, when there was a decrease in the level of conflict, the tone of English-language media reports changed. The perpetrator framing was over 5 times more likely before 2005, whereas a neutral framing was twice as likely after 2005. English-language and non-English-language print media differed significantly in their framing of HWC and in the kinds of solutions advocated. Our results also suggest the print mass media in Mumbai could be an influential conduit for content that diminishes HWC. These media outlets seem attentive to human-leopard conflict, capable of correcting erroneous perceptions and facilitating mitigation and effective management. We believe better contact and mutual understanding between conservation professionals and the mass media could be an important component of managing HWC. We further suggest that in such interactions conservation professionals need to be aware of cultural and linguistic differences in reporting within the country. PMID:23530914
Bhatia, Saloni; Athreya, Vidya; Grenyer, Richard; MacDonald, David W
NSDL National Science Digital Library
The mission of Understanding Science is to provide a fun, accessible, and free resource that accurately communicates what science is and how it really works. The process of science is exciting, but standard explanations often miss its dynamic nature. Science affects us all everyday, but people often feel cut off from science. Science is an intensely human endeavor, but many portrayals gloss over the passion, curiosity, and even rivalries and pitfalls that characterize all human ventures. Understanding Science gives users an inside look at the general principles, methods, and motivations that underlie all of science.
An integrative framework for understanding cross-national human resource management practices
Currently, debate in the area of cross-national human resource management (HRM) suggests that both �culture-bound� and �culture-free� factors and variables are important determinants of HRM policies and practices. HRM is presented as being context-specific and it is argued that with the growth of new markets world-wide, and increased levels of competition and globalization of business, there is a strong need
Pawan S Budhwar; Paul R Sparrow
Understanding human interactions with track and body synergies (TBS) captured from multiple views
This paper presents a new two-stage multi-view framework for the analysis of human interactions and activities. The analysis is per- formed in a distributed multi-view vision system that synergistically integrates track- and body-level processing. The proposed frame- work is geared toward versatile and easily-deployable systems that do not require careful camera calibration. The main contributions of the paper are as
Sangho Park; Mohan M. Trivedi
Mechanistic understanding of time-dependent oral absorption based on gastric motor activity in humans
The relationship of gastric motor activity and gastric emptying of 0.7mm caffeine pellets with their absorption was investigated in the fed state in healthy human subjects by simultaneous monitoring of antral motility and plasma concentrations. A kinetic model for gastric emptying-dependent absorption yielded multiple phases of gastric emptying and rate constants (kg) with large inter-individual differences and large variability in
Kazutaka Higaki; Sally Y. Choe; Raimar L�benberg; Lynda S. Welage; Gordon L. Amidon
Human Adaptations for Mating: Frameworks for Understanding Patterns of Family Formation and Fertility
\\u000a Reproductive and mating systems vary substantially across modern and traditional human societies. A variety of conceptual\\u000a tools may be required to explain this variation. This chapter discusses an explanatory framework based on the notion of evoked\\u000a culture. Evoked cultural differences emerge when behavioral expression of an adaptation is contingent on environmental conditions,\\u000a such that the behavior of groups exposed to
Steven W. Gangestad
Oral sex and oral cancer in the context of human papillomavirus infection: lay public understanding
Human papillomavirus (HPV) is a risk factor for ano-genital and cervical cancers and has been associated with head and neck\\u000a malignancies in the context of oral sex for the transmission of the virus. However, the level of knowledge that lay people\\u000a have in terms of HPV transmission through oral sex and oral cancer development remains unknown. A pilot sample of
Mario A. BrondaniMario; Mario A. Cruz-Cabrera; Cheryle Colombe
Humans on the International Space Station-How Research, Operations, and International Collaboration are Leading to New Understanding of Human Physiology and Performance in Microgravity
NASA Technical Reports Server (NTRS)
As the International Space Station (ISS) nears completion, and full international utilization is achieved, we are at a scientific crossroads. ISS is the premier location for research aimed at understanding the effects of microgravity on the human body. For applications to future human exploration, it is key for validation, quantification, and mitigation of a wide variety of spaceflight risks to health and human performance. Understanding and mitigating these risks is the focus of NASA s Human Research Program. However, NASA s approach to defining human research objectives is only one of many approaches within the ISS international partnership (including Roscosmos, the European Space Agency, the Canadian Space Agency, and the Japan Aerospace Exploration Agency). Each of these agencies selects and implements their own ISS research, with independent but related objectives for human and life sciences research. Because the science itself is also international and collaborative, investigations that are led by one ISS partner also often include cooperative scientists from around the world. The operation of the ISS generates significant additional data that is not directly linked to specific investigations. Such data comes from medical monitoring of crew members, life support and radiation monitoring, and from the systems that have been implemented to protect the health of the crew (such as exercise hardware). We provide examples of these international synergies in human research on ISS and highlight key early accomplishments that derive from these broad interfaces. Taken as a whole, the combination of diverse research objectives, operational data, international sharing of research resources on ISS, and scientific collaboration provide a robust research approach and capability that no one partner could achieve alone.
Ronbinson, Julie A.; Harm, Deborah L.
ERIC Educational Resources Information Center
Understanding the pharmacokinetics and pharmacodynamics of drugs used in psychopharmacology across the pediatric age spectrum from infants to adolescents represents a major challenge for clinicians. In pediatrics, treatment protocols use either standard dose reductions for these drugs for children below a certain age or use less conventional�
van den Anker, Johannes N.
The Perception of Four Basic Emotions in Human and Nonhuman Faces by Children with Autism and Other Developmental Disabilities
ERIC Educational Resources Information Center
Children who experienced autism, mental retardation, and language disorders; and, children in a clinical control group were shown photographs of human female, orangutan, and canine (boxer) faces expressing happiness, sadness, anger, surprise and a neutral expression. For each species of faces, children were asked to identify the happy, sad, angry,�
Gross, Thomas F.
Future directions in the developmental science of addictions.
This article addresses important future directions for the study of addictions, emphasizing the incorporation of developmental perspectives into how we think about substance use and disorder as unfolding processes over time and context for a heterogeneous group of individuals. These perspectives articulate complexities in the developmental processes that underlie change and continuity in human behavior over time. We consider two key developmental concepts, namely, "time" and "heterogeneity." We argue that a lack of attention to time sampling creates ambiguity in the meaning of time-linked assessments, challenges in discerning which of multiple clocks may govern behavior, and the inability in some instances to distinguish which of multiple etiological processes may be driving behavior within our samples. Moreover, artificial divisions among disorders that commonly co-occur with substance use are a barrier to the further integration of the study and treatment of addictions with that of psychopathology. Similar to recent changes in the study of psychiatric disorders more broadly, we argue that identifying common deficits among commonly comorbid disorders, rather than patterns of comorbidity per se, is key to identifying early emerging risk factors for substance use and disorder, with important implications for identifying risk populations and developmental periods as well as potentially malleable intervention targets. Attention to time sampling in theory-driven research designs and attempts to identify more homogenous groups of individuals who use and eventually abuse substances over time are two examples of ways to better understand some of the complexity underlying the development of addictions. PMID:24156358
Hussong, Andrea M; Burns, Alison R; Solis, Jessica M; Rothenberg, W Andrew
Future Directions in the Developmental Science of Addictions
This essay addresses important future directions for the study of addictions, emphasizing the incorporation of developmental perspectives into how we think about substance use and disorder as unfolding processes over time and context for a heterogeneous group of individuals. These perspectives articulate complexities in the developmental processes that underlie change and continuity in human behavior over time. We consider two key developmental concepts, namely �time� and �heterogeneity�. We argue that a lack of attention to time sampling creates ambiguity in the meaning of time-linked assessments, challenges in discerning which of multiple clocks may govern behavior, and the inability in some instances to distinguish which of multiple etiological processes may be driving behavior within our samples. Moreover, artificial divisions among disorders that commonly co-occur with substance use are a barrier to the further integration of the study and treatment of addictions with that of psychopathology. Similar to recent changes in the study of psychiatric disorders more broadly, we argue that identifying common deficits among commonly comorbid disorders, rather than patterns of comorbidity per se, is key to identifying early emerging risk factors for substance use and disorder, with important implications for identifying risk populations and developmental periods as well as potentially malleable intervention targets. Attention to time sampling in theory-driven research designs and attempts to identify more homogenous groups of individuals who use and eventually abuse substances over time are two examples of ways to better understand some of the complexity underlying the development of addictions.
Hussong, Andrea M.; Burns, Alison R.; Solis, Jessica M.; Rothenberg, W. Andrew
Population Physiology: Leveraging Electronic Health Record Data to Understand Human Endocrine Dynamics
Studying physiology and pathophysiology over a broad population for long periods of time is difficult primarily because collecting human physiologic data can be intrusive, dangerous, and expensive. One solution is to use data that have been collected for a different purpose. Electronic health record (EHR) data promise to support the development and testing of mechanistic physiologic models on diverse populations and allow correlation with clinical outcomes, but limitations in the data have thus far thwarted such use. For example, using uncontrolled population-scale EHR data to verify the outcome of time dependent behavior of mechanistic, constructive models can be difficult because: (i) aggregation of the population can obscure or generate a signal, (ii) there is often no control population with a well understood health state, and (iii) diversity in how the population is measured can make the data difficult to fit into conventional analysis techniques. This paper shows that it is possible to use EHR data to test a physiological model for a population and over long time scales. Specifically, a methodology is developed and demonstrated for testing a mechanistic, time-dependent, physiological model of serum glucose dynamics with uncontrolled, population-scale, physiological patient data extracted from an EHR repository. It is shown that there is no observable daily variation the normalized mean glucose for any EHR subpopulations. In contrast, a derived value, daily variation in nonlinear correlation quantified by the time-delayed mutual information (TDMI), did reveal the intuitively expected diurnal variation in glucose levels amongst a random population of humans. Moreover, in a population of continuously (tube) fed patients, there was no observable TDMI-based diurnal signal. These TDMI-based signals, via a glucose insulin model, were then connected with human feeding patterns. In particular, a constructive physiological model was shown to correctly predict the difference between the general uncontrolled population and a subpopulation whose feeding was controlled.
Albers, D. J.; Hripcsak, George; Schmidt, Michael
Toxoplasma gondii infection, from predation to schizophrenia: can animal behaviour help us understand human behaviour?
Summary We examine the role of the protozoan Toxoplasma gondii as a manipulatory parasite and question what role study of infections in its natural intermediate rodent hosts and other secondary hosts, including humans, may elucidate in terms of the epidemiology, evolution and clinical applications of infection. In particular, we focus on the potential association between T. gondii and schizophrenia. We introduce the novel term �T. gondii�rat manipulation�schizophrenia model� and propose how future behavioural research on this model should be performed from a biological, clinical and ethically appropriate perspective.
Webster, Joanne P.; Kaushik, Maya; Bristow, Greg C.; McConkey, Glenn A.
PPAR involvement in PFAA developmental toxicity
Perfluoroalkyl acids (PFAAs) are found in the environment and in serum of wildlife and humans. Perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorooctane sulfonate (PFOS) are developmentally toxic in rodents. The effects of in utero exposure include increas...
Measurement of Androgen and Estrogen Concentrations in Cord Blood: Accuracy, Biological Interpretation, and Applications to Understanding Human Behavioral Development
Accurately measuring hormone exposure during prenatal life presents a methodological challenge and there is currently no �gold standard� approach. Ideally, circulating fetal hormone levels would be measured at repeated time points during pregnancy. However, it is not currently possible to obtain fetal blood samples without significant risk to the fetus, and therefore surrogate markers of fetal hormone levels must be utilized. Umbilical cord blood can be readily obtained at birth and largely reflects fetal circulation in late gestation. This review examines the accuracy and biological interpretation of the measurement of androgens and estrogens in cord blood. The use of cord blood hormones to understand and investigate human development is then discussed.
Hollier, Lauren P.; Keelan, Jeffrey A.; Hickey, Martha; Maybery, Murray T.; Whitehouse, Andrew J. O.
Understanding human visual systems and its impact on our intelligent instruments
NASA Astrophysics Data System (ADS)
We review the evolution of machine vision and comment on the cross-fertilization from the neural sciences onto flourishing fields of neural processing, parallel processing, and associative memory in optical sciences and computing. Then we examine how the intensive efforts in mapping the human brain have been influenced by concepts in computer sciences, control theory, and electronic circuits. We discuss two neural paths that employ the input from the vision sense to determine the navigational options and object recognition. They are ventral temporal pathway for object recognition (what?) and dorsal parietal pathway for navigation (where?), respectively. We describe the reflexive and conscious decision centers in cerebral cortex involved with visual attention and gaze control. Interestingly, these require return path though the midbrain for ocular muscle control. We find that the cognitive psychologists currently study human brain employing low-spatial-resolution fMRI with temporal response on the order of a second. In recent years, the life scientists have concentrated on insect brains to study neural processes. We discuss how reflexive and conscious gaze-control decisions are made in the frontal eye field and inferior parietal lobe, constituting the fronto-parietal attention network. We note that ethical and experiential learnings impact our conscious decisions.
Strojnik Scholl, Marija; P�ez, Gonzalo; Scholl, Michelle K.
Understanding the human factors contribution to railway accidents and incidents in Australia.
Forty rail safety investigation reports were reviewed and a theoretical framework (the Human Factors Analysis and Classification System; HFACS) adopted as a means of identifying errors associated with rail accidents/incidents in Australia. Overall, HFACS proved useful in categorising errors from existing investigation reports and in capturing the full range of relevant rail human factors data. It was revealed that nearly half the incidents resulted from an equipment failure, most of these the product of inadequate maintenance or monitoring programs. In the remaining cases, slips of attention (i.e. skilled-based errors), associated with decreased alertness and physical fatigue, were the most common unsafe acts leading to accidents and incidents. Inadequate equipment design (e.g. driver safety systems) was frequently identified as an organisational influence and possibly contributed to the relatively large number of incidents/accidents resulting from attention failures. Nearly all incidents were associated with at least one organisational influence, suggesting that improvements to resource management, organisational climate and organisational processes are critical for Australian accident and incident reduction. Future work will aim to modify HFACS to generate a rail-specific framework for future error identification, accident analysis and accident investigation. PMID:18760104
Baysari, Melissa T; McIntosh, Andrew S; Wilson, John R
The human premotor oculomotor brainstem system - can it help to understand oculomotor symptoms in Huntington's disease?
Recent progress in oculomotor research has enabled new insights into the functional neuroanatomy of the human premotor oculomotor brainstem network. In the present review, we provide an overview of its functional neuroanatomy and summarize the broad range of oculomotor dysfunctions that may occur in Huntington's disease (HD) patients. Although some of these oculomotor symptoms point to an involvement of the premotor oculomotor brainstem network in HD, no systematic analysis of this functional system has yet been performed in brains of HD patients. Therefore, its exact contribution to oculomotor symptoms in HD remains unclear. A possible strategy to clarify this issue is the use of unconventional 100-microm-thick serial tissue sections stained for Nissl substance and lipofuscin pigment (Nissl-pigment stain according to Braak). This technique makes it possible to identify the known nuclei of the premotor oculomotor brainstem network and to study their possible involvement in the neurodegenerative process. Studies applying this morphological approach and using the current knowledge regarding the functional neuroanatomy of this human premotor oculomotor brainstem network will help to elucidate the anatomical basis of the large spectrum of oculomotor dysfunctions that are observed in HD patients. This knowledge may aid clinicians in the diagnosis and monitoring of the disease. PMID:19187058
R�b, U; Heinsen, H; Brunt, E R; Landwehrmeyer, B; Den Dunnen, W F A; Gierga, K; Deller, T
Development of an Intelligent Digital Watershed to understand water-human interaction for a sustainable Agroeconomy in Midwest USA
NASA Astrophysics Data System (ADS)
Human activity is intricately linked to the quality and quantity of water resources. Although many studies have examined water-human interaction, the complexity of such coupled systems is not well understood largely because of gaps in our knowledge of water-cycle processes which are heavily influenced by socio-economic drivers. Considerable research has been performed to develop an understanding of the impact of local land use decisions on field and catchment processes at an annual basis. Still less is known about the impact of economic and environmental outcomes on decision-making processes at the local and national level. Traditional geographic information management systems lack the ability to support the modeling and analysis of complex spatial processes. New frameworks are needed to track, query, and analyze the massive amounts of data generated by ensembles of simulations produced by multiple models that couple socioeconomic and natural system processes. On this context, we propose to develop an Intelligent Digital Watershed (IDW) which fuses emerging concepts of Digital Watershed (DW). DW is a comprehensive characterization of the eco hydrologic systems based on the best available digital data generated by measurements and simulations models. Prototype IDW in the form of a cyber infrastructure based engineered system will facilitate novel insights into human/environment interactions through multi-disciplinary research focused on watershed-related processes at multiple spatio-temporal scales. In ongoing effort, the prototype IDW is applied to Clear Creek watershed, an agricultural dominating catchment in Iowa, to understand water-human processes relevant to management decisions by farmers regarding agro ecosystems. This paper would also lay out the database design that stores metadata about simulation scenarios, scenario inputs and outputs, and connections among these elements- essentially the database. The paper describes the cyber infrastructure and workflows developed for connecting the IDW modeling tools: ABM, Data-Driven Modeling, and SWAT.
Mishra, S. K.; Rapolu, U.; Ding, D.; Muste, M.; Bennett, D.; Schnoor, J. L.
Developmental regulation of granulocyte-macrophage colony-stimulating factor production during human monocyte-to-macrophage maturation
Summary Cells of the macrophage lineage are a major source of various cytokines and hematopoietic growth factors. With regard to the growth factors acting on cells of their own lineage, macrophage colony-stimulating factor (M-CSF) has been proven to be secreted by monocytes (MO) and macrophages (MAC), whereas the production of granulocyte-macrophage colony-stimulating factor (GM-CSF) by human MO\\/MAC is under debate.
S. W. Krause; M. Kreutz; G. Zenke; R. Andreesen
Overexpression of Human and Fly Frataxins in Drosophila Provokes Deleterious Effects at Biochemical, Physiological and Developmental Levels
Background Friedreich's ataxia (FA), the most frequent form of inherited ataxias in the Caucasian population, is caused by a reduced expression of frataxin, a highly conserved protein. Model organisms have contributed greatly in the efforts to decipher the function of frataxin; however, the precise function of this protein remains elusive. Overexpression studies are a useful approach to investigate the mechanistic actions of frataxin; however, the existing literature reports contradictory results. To further investigate the effect of frataxin overexpression, we analyzed the consequences of overexpressing human (FXN) and fly (FH) frataxins in Drosophila. Methodology/Principal Findings We obtained transgenic flies that overexpressed human or fly frataxins in a general pattern and in different tissues using the UAS-GAL4 system. For both frataxins, we observed deleterious effects at the biochemical, histological and behavioral levels. Oxidative stress is a relevant factor in the frataxin overexpression phenotypes. Systemic frataxin overexpression reduces Drosophila viability and impairs the normal embryonic development of muscle and the peripheral nervous system. A reduction in the level of aconitase activity and a decrease in the level of NDUF3 were also observed in the transgenic flies that overexpressed frataxin. Frataxin overexpression in the nervous system reduces life span, impairs locomotor ability and causes brain degeneration. Frataxin aggregation and a misfolding of this protein have been shown not to be the mechanism that is responsible for the phenotypes that have been observed. Nevertheless, the expression of human frataxin rescues the aconitase activity in the fh knockdown mutant. Conclusion/Significance Our results provide in vivo evidence of a functional equivalence for human and fly frataxins and indicate that the control of frataxin expression is important for treatments that aim to increase frataxin levels.
Soriano, Sirena; Botella, Jose A.; Schneuwly, Stephan; Martinez-Sebastian, Maria J.; Molto, Maria D.
Developmental Changes in the Expression ofLeishmania chagasigp63 and Heat Shock Proteins in a Human Macrophage Cell Line
The ability of the protozoanLeishmania chagasito infect a vertebrate host depends on its ability to survive intracellularly in a mammalian macrophage. Novel patterns of gene expression are probably important for conversion from the extracellular promastigote to the obligate intracellular amastigote parasite form. We found that the human macrophage-like cell line U937 provided an in vitro model of phagocytosis ofL. chagasi
Distinct T cell developmental consequences in humans and mice expressing identical mutations in the DLAARN motif of ZAP-70.
The protein tyrosine kinase, ZAP-70, is pivotally involved in transduction of Ag-binding signals from the TCR required for T cell activation and development. Defects in ZAP-70 result in SCID in humans and mice. We describe an infant with SCID due to a novel ZAP-70 mutation, comparable with that which arose spontaneously in an inbred mouse colony. The patient inherited a homozygous missense mutation within the highly conserved DLAARN motif in the ZAP-70 kinase domain. Although the mutation only modestly affected protein stability, catalytic function was absent. Despite identical changes in the amino acid sequence of ZAP-70, the peripheral T cell phenotypes of our patient and affected mice are distinct. ZAP-70 deficiency in this patient, as in other humans, is characterized by abundant nonfunctional CD4(+) T cells and absent CD8(+) T cells. In contrast, ZAP-70-deficient mice lack both major T cell subsets. Although levels of the ZAP-70-related protein tyrosine kinase, Syk, may be sufficiently increased in human thymocytes to rescue CD4 development, survival of ZAP-70-deficient T cells in the periphery does not appear to be dependent on persistent up-regulation of Syk expression. PMID:11123350
Elder, M E; Skoda-Smith, S; Kadlecek, T A; Wang, F; Wu, J; Weiss, A
Enhancing Understanding Of Coupled Human-Natural Systems Through Collaborative Learning
NASA Astrophysics Data System (ADS)
In the past decade, it has become clear that the dynamic nature of coupled human-natural systems must be better understood and incorporated into decision making. If the interactions between society and the rest of the ecosystem are poorly represented in system models, our ability to explore the potential consequences of feedbacks between the biophysical system and policy or management actions will be limited. Teams of researchers from three Oregon universities are collaborating with regional experts, water managers, and decision-makers to examine how climate change, population growth, and economic growth may alter the availability and use of water in the Willamette River Basin over the next one hundred years. A central project component is development of a version of the ENVISION modeling framework that will provide decision makers with a way to visualize the Willamette water system and evaluate the interaction of management choices with changing environmental and socioeconomic conditions. Key objectives of the project broader impacts team include: 1) assist with incorporating the human component of the system into the model, (2) fostering growth of the research team as an interdependent, interdisciplinary research community, and (3) communicating effectively with regional stakeholders. Through Learning-Action Networks we have been able to gather insightful, project-relevant knowledge on water use, management, policies and issues that impact water management in the region. We have identified the types of project outputs that managers and decision makers would find useful for anticipating water scarcity and informing integrative water systems responses. Events and processes used to accomplish our objectives began with field trips involving researchers, educators, and other stakeholders. Follow-up meetings and an all day symposium featured focus group interviews, plenary sessions on project progress, and interactive poster sessions in which participants could help identify water related policies and actions they would like to see modeled. Participants assisted in compiling an interactive table of potential policies and actions organized by water use sector and policy type (e.g., regulatory vs. incentive based). Involvement of K-12 educators and development of innovative interdisciplinary courses has enhanced the broader impacts of the project and helped us achieve multiple project objectives. We present plans to build on initial collaborative learning experiences to promote project outcomes that will advance coupled human-natural systems research and enhance the utility of model outcomes in water management.
Santelmann, M. V.; Chan, S.; Morzillo, A.; Stebbins, A.; Wright, M.
Understanding and exploiting dendritic cells in human immunodeficiency virus infection using the nonhuman primate model.
Dendritic cells (DC) are pivotal cells in the innate immune system. Recent interest in the role of DC in human immunodeficiency virus (HIV) pathogenesis has increased with the finding that both myeloid (mDC) and plasmacytoid DC (pDC) are lost from blood during infection, associated with progression to disease. DC are also being studied intensively for their capacity to stimulate robust virus-specific immunity as vaccines. Here we discuss our work in these contrasting fields of DC biology using the rhesus macaque nonhuman primate model. We focus on studies of DC dynamics in lymphoid tissues during pathogenic simian immunodeficiency virus (SIV) infection, DC trafficking in health and disease, DC-based vaccination and the use of autologous virus as antigen for stimulation of virus-specific T cells. PMID:17337787
Barratt-Boyes, Simon M; Brown, Kevin N; Melhem, Nada; Soloff, Adam C; Gleason, Sherrianne M
Towards an understanding of the role of Clostridium perfringens toxins in human and animal disease.
Clostridium perfringens uses its arsenal of >16 toxins to cause histotoxic and intestinal infections in humans and animals. It has been unclear why this bacterium produces so many different toxins, especially since many target the plasma membrane of host cells. However, it is now established that C. perfringens uses chromosomally encoded alpha toxin (a phospholipase C) and perfringolysin O (a pore-forming toxin) during histotoxic infections. In contrast, this bacterium causes intestinal disease by employing toxins encoded by mobile genetic elements, including C. perfringens enterotoxin, necrotic enteritis toxin B-like, epsilon toxin and beta toxin. Like perfringolysin O, the toxins with established roles in intestinal disease form membrane pores. However, the intestinal disease-associated toxins vary in their target specificity, when they are produced (sporulation vs vegetative growth), and in their sensitivity to intestinal proteases. Producing many toxins with diverse characteristics likely imparts virulence flexibility to C. perfringens so it can cause an array of diseases. PMID:24762309
Uzal, Francisco A; Freedman, John C; Shrestha, Archana; Theoret, James R; Garcia, Jorge; Awad, Milena M; Adams, Vicki; Moore, Robert J; Rood, Julian I; McClane, Bruce A
Understanding the role of NRF2-regulated miRNAs in human malignancies.
Nuclear factor (erythroid-derived 2)-like 2 (NRF2) is a key transcription factor that regulates the expression of over a hundred cytoprotective and antioxidant genes that provide cellular protection from reactive oxygen species. Chemotherapy resistance in several cancers has been linked to dysregulation of the NRF2 signalling pathway, moreover there is growing evidence that NRF2 may contribute to tumorigenesis. MicroRNA (miRNA) are small non-coding RNA sequences that post-transcriptionally regulate mRNA sequences. In cancer pathogenesis, aberrantly expressed miRNAs can act as either tumor suppressor or oncogenic miRNA. Recent evidence has been described that identifies a number of miRNA that can be regulated by NRF2. This review outlines the importance of NRF2 in regulating miRNA, and the functional role this may have in the tumorigenesis of human malignancies and their chemotherapy resistance. PMID:24029073
Shah, Niraj M; Rushworth, Stuart A; Murray, Megan Y; Bowles, Kristian M; MacEwan, David J
Understanding the role of NRF2-regulated miRNAs in human malignancies
Nuclear factor (erythroid-derived 2)-like 2 (NRF2) is a key transcription factor that regulates the expression of over a hundred cytoprotective and antioxidant genes that provide cellular protection from reactive oxygen species. Chemotherapy resistance in several cancers has been linked to dysregulation of the NRF2 signalling pathway, moreover there is growing evidence that NRF2 may contribute to tumorigenesis. MicroRNA (miRNA) are small non-coding RNA sequences that post-transcriptionally regulate mRNA sequences. In cancer pathogenesis, aberrantly expressed miRNAs can act as either tumor suppressor or oncogenic miRNA. Recent evidence has been described that identifies a number of miRNA that can be regulated by NRF2. This review outlines the importance of NRF2 in regulating miRNA, and the functional role this may have in the tumorigenesis of human malignancies and their chemotherapy resistance.
Shah, Niraj M; Rushworth, Stuart A; Murray, Megan Y; Bowles, Kristian M; MacEwan, David J
Understanding Alcoholism Through microRNA Signatures in Brains of Human Alcoholics
Advances in the fields of genomics and genetics in the last decade have identified a large number of genes that can potentially influence alcohol-drinking behavior in humans as well as animal models. Consequently, the task of identifying efficient molecular targets that could be used to develop effective therapeutics against the disease has become increasingly daunting. One of the reasons for this is the fact that each of the many alcohol-responsive genes only contributes a small effect to the overall mechanism and disease phenotype, as is characteristic of complex traits. Current research trends are hence shifting toward the analysis of gene networks rather than emphasizing individual genes. The discovery of microRNAs and their mechanisms of action on regulation of transcript level and protein translation have made evident the utility of these small non-coding RNA molecules that act as central coordinators of multiple cross-communicating cellular pathways. Cells exploit the fact that a single microRNA can target hundreds of mRNA transcripts and that a single mRNA transcript can be simultaneously targeted by distinct microRNAs, to ensure fine-tuned and/or redundant control over a large number of cellular functions. By the same token, we can use these properties of microRNAs to develop novel, targeted strategies to combat complex disorders. In this review, we will focus on recent discoveries of microRNA signatures in brain of human alcoholics supporting the hypothesis that changes in gene expression and regulation by microRNAs are responsible for long-term neuroadaptations occurring during development of alcoholism. We also discuss insights into the potential modulation of epigenetic regulators by a subset of microRNAs. Taken together, microRNA activity may be controlling many of the cellular mechanisms already known to be involved in the development of alcoholism, and suggests potential targets for the development of novel therapeutic interventions.
Nunez, Yury O.; Mayfield, R. Dayne
Long-term experiments to better understand soil-human interactions
NASA Astrophysics Data System (ADS)
Interactions between soils and people may be transforming global conditions, but the interactions are poorly understood. Changes in soils have proven difficult to quantify, especially in complex ecosystems manifesting large spatiotemporal variability. Long-term ecosystem experiments that evaluate soil change and demonstrate alternative choices are important to understanding changes, discovering new controls and drivers, and influencing decisions. Inspired by agriculture studies, like Rothamsted, the US Forest Service established in 1990 a network of operational-scale experiments across the Pacific Northwest to evaluate long-term effects of different forest management and disturbance regimes. With a strong experimental design, these experiments are now helping to better understand the long-term effects of managing tree harvesting (clearcutting and thinning), woody debris, and tree and understory species composition, and-serendipitously-the effects of fire. Initial results from the Southern Oregon experimental site indicate surprisingly rapid soil changes in some regimes but not others. We've also learned that rapid change presents challenges to repeat sampling. We present our sample-archive and comparable-layer approaches that seek to accommodate changes in surface elevation, aggregation and disaggregation, and mineral-soil exports. Thinning mature forest stands (80-100 yrs old) did not significantly change soil C in 11-yrs. A small upper-layer C increase was observed after thinning, but it was similar to the control. Significant increases in upper-layer soil N were observed with most treatments, but all increases were similar to the control. Leaving woody debris had little effect. The most remarkable change occurred when mature stands were clearcut and Douglas-firs were planted and tended. Associated with rapid growth of Douglas-fir, an average of 8 Mg C ha-1 was lost from weathered soil 4-18 cm deep. This contrasts with clearcuts where early-seral hardwoods and knobcone pines were established, that trended positively with 2 Mg C ha-1. Soil changes resulting from wild and prescribed fire were substantial. About 50% of the soil C (3-21 Mg ha-1) and 36% of soil N (41-650 kg ha-1) were lost from the upper profile (0-6.2 cm) compared to pre-fire conditions. Intense wildfire that killed most forest trees had about double the losses of C and N than forests burned at lower temperature with fewer trees killed. Average wildfire C losses were more than twice prescribed-fire losses. A long-term perspective is needed to compare episodic influences on soils, like harvesting and wildfire, to day-in, day-out effects of different species mixtures. Especially important is the effect of shrubs, that can rapidly achieve full leaf area but that lack the woody stem structure to store captured C as well as conifers. In theory, therefore, extending shrub cover will increase soil C. The annual profile soil C loss in Douglas-fir (-0.8 Mg ha-1yr-1), if continued beyond 11 yrs, would be similar to the effects of a fire-return interval of less than a third of the historical interval of about 100 years. National and regional soil-C monitoring would benefit from being grounded in existing experimental studies to help integrate large-scale changes with an unfolding understanding of processes in ways useful to decisionmakers.
Bormann, B. T.; Homann, P. S.
The Lutheran Blood Group Glycoprotein, Another Member of the Immunoglobulin Superfamily, is Widely Expressed in Human Tissues and is Developmentally Regulated in Human Liver
Glycoproteins expressing the Lutheran blood group antigens were isolated from human erythrocyte membranes and from human fetal liver. Amino acid sequence analyses allowed the design of redundant oligonucleotides that were used to generate a 459-bp, sequence-specific probe by PCR. A cDNA clone of 2400 bp was isolated from a human placental lambdagt11 library and sequenced, and the deduced amino acid
S. F. Parsons; G. Mallinson; C. H. Holmes; J. M. Houlihan; K. L. Simpson; W. J. Mawby; N. K. Spurr; D. Warne; A. N. Barclay; D. J. Anstee
Challenges of Interdisciplinary Research: Reconciling Qualitative and Quantitative Methods for Understanding Human-Landscape Systems
NASA Astrophysics Data System (ADS)
While interdisciplinary research is increasingly practiced as a way to transcend the limitations of individual disciplines, our concepts, and methods are primarily rooted in the disciplines that shape the way we think about the world and how we conduct research. While natural and social scientists may share a general understanding of how science is conducted, disciplinary differences in methodologies quickly emerge during interdisciplinary research efforts. This paper briefly introduces and reviews different philosophical underpinnings of quantitative and qualitative methodological approaches and introduces the idea that a pragmatic, realistic approach may allow natural and social scientists to work together productively. While realism assumes that there is a reality that exists independently of our perceptions, the work of scientists is to explore the mechanisms by which actions cause meaningful outcomes and the conditions under which the mechanisms can act. Our task as interdisciplinary researchers is to use the insights of our disciplines in the context of the problem to co-produce an explanation for the variables of interest. Research on qualities necessary for successful interdisciplinary researchers is also discussed along with recent efforts by funding agencies and academia to increase capacities for interdisciplinary research.
Lach, Denise
Developmental dyscalculia: a dysconnection syndrome?
Numerical understanding is important for everyday life. For children with developmental dyscalculia (DD), numbers and magnitudes present profound problems which are thought to be based upon neuronal impairments of key regions for numerical understanding. The aim of the present study was to investigate possible differences in white matter fibre integrity between children with DD and controls using diffusion tensor imaging. White matter integrity and behavioural measures were evaluated in 15 children with developmental dyscalculia aged around 10�years and 15 matched controls. The main finding, obtained by a whole brain group comparison, revealed reduced fractional anisotropy in the superior longitudinal fasciculus in children with developmental dyscalculia. In addition, a region of interest analysis exhibited prominent deficits in fibres of the superior longitudinal fasciculus adjacent to the intraparietal sulcus, which is thought to be the core region for number processing. To conclude, our results outline deficient fibre projection between parietal, temporal and frontal regions in children with developmental dyscalculia, and therefore raise the question of whether dyscalculia can be seen as a dysconnection syndrome. Since the superior longitudinal fasciculus is involved in the integration and control of distributed brain processes, the present results highlight the importance of considering broader domain-general mechanisms in the diagnosis and therapy of dyscalculia. PMID:23783231
Kucian, Karin; Ashkenazi, Simone Schwizer; H�nggi, J�rgen; Rotzer, Stephanie; J�ncke, Lutz; Martin, Ernst; von Aster, Michael
Developmental cues for the maturation of metabolic, electrophysiological and calcium handling properties of human pluripotent stem cell-derived cardiomyocytes
Human pluripotent stem cells (hPSCs), including embryonic and induced pluripotent stem cells, are abundant sources of cardiomyocytes (CMs) for cell replacement therapy and other applications such as disease modeling, drug discovery and cardiotoxicity screening. However, hPSC-derived CMs display immature structural, electrophysiological, calcium-handling and metabolic properties. Here, we review various biological as well as physical and topographical cues that are known to associate with the development of native CMs in vivo to gain insights into the development of strategies for facilitated maturation of hPSC-CMs.
The inducible tissue-specific expression of the human IL-3/GM-CSF locus is controlled by a complex array of developmentally regulated enhancers
The closely linked human IL-3 and GM-CSF genes are tightly regulated and are expressed in activated T cells and mast cells. Here we used transgenic mice to study the developmental regulation of this locus and to identify DNA elements required for its correct activity in vivo. Because these two genes are separated by a CTCF-dependent insulator, and the GM-CSF gene is regulated primarily by its own upstream enhancer, the main aim was to identify regions of the locus required for correct IL-3 gene expression. We initially found that the previously identified proximal upstream IL-3 enhancers were insufficient to account for the in vivo activity of the IL-3 gene. However, an extended analysis of DNase I hypersensitive sites (DHSs) spanning the entire upstream IL-3 intergenic region revealed the existence of a complex cluster of both constitutive and inducible DHSs spanning the ?34 to ?40 kb region. The tissue specificity of these DHSs mirrored the activity of the IL-3 gene, and included a highly inducible CyclosporinA-sensitive enhancer at ?37 kb which increased IL-3 promoter activity 40 fold. Significantly, inclusion of this region enabled correct in vivo regulation of IL-3 gene expression in T cells, mast cells and myeloid progenitor cells.
Baxter, Euan W.; Mirabella, Fabio; Bowers, Sarion R.; James, Sally R.; Bonavita, Aude-Marine; Bertrand, Elisabeth; Strogantsev, Ruslan; Hawwari, Abbas; Bert, Andrew G.; de Arce, Andrea Gonzalez; West, Adam G.; Bonifer, Constanze; Cockerill, Peter N.
Critical evaluation of current developmental toxicity testing strategies: a case of babies and their bathwater.
This review is the second in a series of four papers emanating from a workshop entitled "Developmental Toxicology-New Directions," which was sponsored by the ILSI Health and Environmental Sciences Institute's (HESI) Developmental and Reproductive Toxicology Technical Committee. The present review analyzes the strengths and weaknesses of current developmental safety testing approaches in an effort to identify those strengths that should be retained in the future versus the weaknesses that should be eliminated. Workshop participants considered the following to be key strengths of current testing approaches: the integrated biology of pregnant animal models including pharmacokinetic and pharmacodynamic processes, the ability to detect low incidence malformations as well as maternally mediated toxicity, and the long history of use coupled with extensive historical data. A number of weaknesses were related to the resource-intensive nature of developmental toxicity testing (e.g., large number of animals, high costs, low throughput, the inability to keep pace with the demand for more toxicity data). Other weaknesses included the use of very high dose levels that often far exceed human exposure levels, the confounding influence of maternal toxicity, sparse understanding of basic developmental mechanisms and genetics of standard animal models relative to mouse or lower organisms, difficulties interpreting low incidence findings, and issues surrounding the interpretation of minor skeletal variations. An appreciation of these strengths and weaknesses is critical for the design of new approaches to developmental toxicity testing in the 21st century. PMID:21770028
Carney, Edward W; Ellis, Amy L; Tyl, Rochelle W; Foster, Paul M D; Scialli, Anthony R; Thompson, Kary; Kim, James
Human development II: we need an integrated theory for matter, life and consciousness to understand life and healing.
For almost a decade, we have experimented with supporting the philosophical development of severely ill patients to induce recovery and spontaneous healing. Recently, we have observed a new pattern of extremely rapid, spontaneous healing that apparently can facilitate even the spontaneous remission of cancer and the spontaneous recovery of mental diseases like schizophrenia and borderline schizophrenia. Our working hypothesis is that the accelerated healing is a function of the patient's brain-mind and body-mind coming closer together due to the development of what we call "deep" cosmology. To understand and describe what happens at a biological level, we have suggested naming the process adult human metamorphosis, a possibility that is opened by the human genome showing full generic equipment for metamorphosis. To understand the mechanistic details in the complicated interaction between consciousness and biology, we need an adequate theory for biological information. In a series of papers, we propose what we call "holistic biology for holistic medicine". We suggest that a relatively simple model based on interacting wholenesses instead of isolated parts can shed a new light on a number of difficult issues that we need to explain and understand in biology and medicine in order to understand and use metamorphosis in the holistic medical clinic. We aim to give a holistic theoretical interpretation of biological phenomena at large, morphogenesis, evolution, immune system regulation (self-nonself discrimination), brain function, consciousness, and health in particular. We start at the most fundamental problem: what is biological information at the subcellular, cellular, and supracellular levels if we presume that it is the same phenomenon on all levels (using Occam's razor), and how can this be described scientifically? The problems we address are all connected to the information flow in the functioning, living organism: function of the brain and consciousness, the regulations of the immune system and cell growth, the dynamics of health and disease. We suggest that life utilizes an unseen fine structure of the physical energy of the universe at a subparticular or quantum level to give information-directed self-organization; we give a first sketch of a possible fractal structure of the energy able to both contain and communicate biological information and carry individual and collective consciousness. Finally, thorough our analysis, we put up a model for adult human metamorphosis. PMID:16830047
Ventegodt, S�ren; Hermansen, Tyge Dahl; Nielsen, Maj Lyck; Clausen, Birgitte; Merrick, Joav
Understanding effector selectivity in human posterior parietal cortex by combining information patterns and activation measures.
The posterior parietal cortex (PPC) has traditionally been viewed as containing separate regions for the planning of eye and limb movements, but recent neurophysiological and neuroimaging observations show that the degree of effector specificity is limited. This has led to the hypothesis that effector specificity in PPC is part of a more efficient than strictly modular organization, characterized by both distinct and common activations for different effectors. It is unclear, however, what differentiates the distinctions and commonalities in effector representations. Here, we used fMRI in humans to study the cortical representations involved in the planning of eye, hand, and foot movements. We used a novel combination of fMRI measures to assess the effector-related representational content of the PPC: a multivariate information measure, reflecting whether representations were distinct or common across effectors and a univariate activation measure, indicating which representations were actively involved in movement preparation. Active distinct representations were evident in areas previously reported to be effector specific: eye specificity in the posterior intraparietal sulcus (IPS), hand tuning in anterior IPS, and a foot bias in the anterior precuneus. Crucially, PPC regions responding to a particular effector also contained an active representation common across the other two effectors. We infer that rostral PPC areas do not code single effectors, but rather dichotomies of effectors. Such combinations of representations could be well suited for active effector selection, efficiently coding both a selected effector and its alternatives. PMID:24849346
Leon�, Frank T M; Heed, Tobias; Toni, Ivan; Medendorp, W Pieter
Understanding the formation of maxillary sinus in Japanese human foetuses using cone beam CT
The formation of the maxillary sinus (MS) is tied to the maturation of the craniofacial bones during development. The MS and surrounding bone matrices in Japanese foetal specimens were inspected using cone beam computed tomography relative to the nasal cavity (NC) and the surrounding bones, including the palatine bone, maxillary process, inferior nasal concha and lacrimal bone. The human foetuses analysed were 223.2���25.9�mm in crown-rump length (CRL) and ranged in estimated age from 20 to 30�weeks of gestation. The amount of bone in the maxilla surrounding the MS increased gradually between 20 and 30�weeks of gestation. Various calcified structures that formed the bone matrix were found in the cortical bone of the maxilla, and these calcified structures specifically surrounded the deciduous tooth germs. By 30�weeks of gestation, the uncinate process of the ethmoid bone formed a border with the maxilla. The distance from the midline to the maximum lateral surface border of the MS combined with the width from the midline to the maximum lateral surface border of the inferior nasal concha showed a high positive correlation with CRL in Japanese foetuses. There appears to be a complex correlation between the MS and NC formation during development in the Japanese foetus. Examination of the surrounding bone indicated that MS formation influences maturation of the maxilla and the uncinate process of the ethmoid bone during craniofacial bone development.
Asaumi, Rieko; Miwa, Yoko; Imura, Kosuke; Sunohara, Masataka; Kawai, Taisuke; Yosue, Takashi
Mechanistic understanding of time-dependent oral absorption based on gastric motor activity in humans.
The relationship of gastric motor activity and gastric emptying of 0.7 mm caffeine pellets with their absorption was investigated in the fed state in healthy human subjects by simultaneous monitoring of antral motility and plasma concentrations. A kinetic model for gastric emptying-dependent absorption yielded multiple phases of gastric emptying and rate constants (k(g)) with large inter-individual differences and large variability in onset of gastric emptying (50-175 min). The model suggests that 50% of the dose is emptied in 1-2h and over 90% emptied by 3.5h following dosing, in all subjects. The maximum values of k(g) (k(g)(max)) were much greater than those reported for emptying of liquids in the fasted state and were comparable to k(g) values in the late Phase II/III of the migrating motor complex (MMC). The model described the observed irregular absorption rate-time and plasma concentration-time profiles adequately but not in detail. The model was more successful at simulating double-peak phenomena in absorption rate profiles and onset of caffeine absorption. The results suggest that gastric emptying regulates drug absorption of small particles in the fed state. Further, estimates of k(a) derived using the time-dependent absorption model were closer to the intrinsic absorption rate constant for caffeine. PMID:18434110
Higaki, Kazutaka; Choe, Sally Y; L�benberg, Raimar; Welage, Lynda S; Amidon, Gordon L
Improving human health through understanding the complex structure of glucose polymers.
Two highly branched glucose polymers with similar structures--starch and glycogen--have important relations to human health. Slowly digestible and resistant starches have desirable health benefits, including the prevention and alleviation of metabolic diseases and prevention of colon cancer. Glycogen is important in regulating the use of glucose in the body, and diabetic subjects have an anomaly in their glycogen structure compared with that in healthy subjects. This paper reviews the biosynthesis-structure-property relations of these polymers, showing that polymer characterization produces knowledge which can be useful in producing healthier foods and new drug targets aimed at improving glucose storage in diabetic patients. Examples include mathematical modeling to design starch with better nutritional values, the effects of amylose fine structures on starch digestibility, the structure of slowly digested starch collected from in vitro and in vivo digestion, and the mechanism of the formation of glycogen ? particles from ? particles in healthy subjects. A new method to overcome a current problem in the structural characterization of these polymers using field-flow fractionation is also given, through a technique to calibrate evaporative light scattering detection with starch. PMID:23842899
Gilbert, Robert G; Wu, Alex C; Sullivan, Mitchell A; Sumarriva, Gonzalo E; Ersch, Natascha; Hasjim, Jovin
Use of Gene Ontology Annotation to understand the peroxisome proteome in humans
The Gene Ontology (GO) is the de facto standard for the functional description of gene products, providing a consistent, information-rich terminology applicable across species and information repositories. The UniProt Consortium uses both manual and automatic GO annotation approaches to curate UniProt Knowledgebase (UniProtKB) entries. The selection of a protein set prioritized for manual annotation has implications for the characteristics of the information provided to users working in a specific field or interested in particular pathways or processes. In this article, we describe an organelle-focused, manual curation initiative targeting proteins from the human peroxisome. We discuss the steps taken to define the peroxisome proteome and the challenges encountered in defining the boundaries of this protein set. We illustrate with the use of examples how GO annotations now capture cell and tissue type information and the advantages that such an annotation approach provides to users. Database URL: http://www.ebi.ac.uk/GOA/ and http://www.uniprot.org
Mutowo-Meullenet, Prudence; Huntley, Rachael P.; Dimmer, Emily C.; Alam-Faruque, Yasmin; Sawford, Tony; Jesus Martin, Maria; O'Donovan, Claire; Apweiler, Rolf
Developmental validation of RSID�-Semen: a lateral flow immunochromatographic strip test for the forensic detection of human semen.
Tests for the identification of semen commonly involve the microscopic visualization of spermatozoa or assays for the presence of seminal markers such as acid phosphatase (AP) or prostate-specific antigen (PSA). Here, we describe the rapid stain identification kit for the identification of semen (RSID�-Semen), a lateral flow immunochromatographic strip test that uses two antihuman semenogelin monoclonal antibodies to detect the presence of semenogelin. The RSID�-Semen strip is specific for human semen, detecting <2.5 nL of semen, and does not cross-react with other human or nonhuman tissues tested. RSID�-Semen is more sensitive with certain forensic evidence samples containing mixtures of vaginal secretions and semen than either of the commercially available PSA-based forensic semen detection tests or tests that measure AP activity that were tested in parallel. The RSID�-Semen kit also allows sampling a fraction of a questioned stain while retaining the majority of the sample for further processing through short tandem repeat analysis. PMID:22211796
Old, Jennifer; Schweers, Brett A; Boonlayangoor, Pravat W; Fischer, Brian; Miller, Kevin W P; Reich, Karl
Advances in understanding of mammalian penile evolution, human penile anatomy and human erection physiology: clinical implications for physicians and surgeons.
Recent studies substantiate a model of the tunica albuginea of the corpora cavernosa as a bi-layered structure with a 360� complete inner circular layer and a 300� incomplete outer longitudinal coat spanning from the bulbospongiosus and ischiocavernosus proximally and extending continuously into the distal ligament within the glans penis. The anatomical location and histology of the distal ligament invites convincing parallels with the quadrupedal os penis and therefore constitutes potential evidence of the evolutionary process. In the corpora cavernosa, a chamber design is responsible for facilitating rigid erections. For investigating its venous factors exclusively, hemodynamic studies have been performed on both fresh and defrosted human male cadavers. In each case, a rigid erection was unequivocally attainable following venous removal. This clearly has significant ramifications in relation to penile venous surgery and its role in treating impotent patients. One deep dorsal vein, 2 cavernosal veins and 2 pairs of para-arterial veins (as opposed to 1 single vein) are situated between Buck's fascia and the tunica albuginea. These newfound insights into penile tunical, venous anatomy and erection physiology were inspired by and, in turn, enhance clinical applications routinely encountered by physicians and surgeons, such as penile morphological reconstruction, penile implantation and penile venous surgery. PMID:22739749
Hsieh, Cheng-Hsing; Liu, Shih-Ping; Hsu, Geng-Long; Chen, Heng-Shuen; Molodysky, Eugen; Chen, Ying-Hui; Yu, Hong-Jeng
Advances in understanding of mammalian penile evolution, human penile anatomy and human erection physiology: Clinical implications for physicians and surgeons
Summary Recent studies substantiate a model of the tunica albuginea of the corpora cavernosa as a bi-layered structure with a 360� complete inner circular layer and a 300� incomplete outer longitudinal coat spanning from the bulbospongiosus and ischiocavernosus proximally and extending continuously into the distal ligament within the glans penis. The anatomical location and histology of the distal ligament invites convincing parallels with the quadrupedal os penis and therefore constitutes potential evidence of the evolutionary process. In the corpora cavernosa, a chamber design is responsible for facilitating rigid erections. For investigating its venous factors exclusively, hemodynamic studies have been performed on both fresh and defrosted human male cadavers. In each case, a rigid erection was unequivocally attainable following venous removal. This clearly has significant ramifications in relation to penile venous surgery and its role in treating impotent patients. One deep dorsal vein, 2 cavernosal veins and 2 pairs of para-arterial veins (as opposed to 1 single vein) are situated between Buck�s fascia and the tunica albuginea. These newfound insights into penile tunical, venous anatomy and erection physiology were inspired by and, in turn, enhance clinical applications routinely encountered by physicians and surgeons, such as penile morphological reconstruction, penile implantation and penile venous surgery.
Hsieh, Cheng-Hsing; Liu, Shih-Ping; Hsu, Geng-Long; Chen, Heng-Shuen; Molodysky, Eugen; Chen, Ying-Hui; Yu, Hong-Jeng
Linking soil forming processes, geomorphological dynamics and human activity to understand past and future patterns of landscape change
NASA Astrophysics Data System (ADS)
The interactions between soil formation, slope processes, human activities and changing climate are important in shaping landscapes. However, these aspects of landscape development have not often been combined in integrated quantitative analysis. This means that we cannot yet make accurate assessments of the sustainability of our land-based activities under changing climate and management conditions. In particular, important questions about the effects of human activity on soil formation and of erosion on soil formation remain unanswered. Models that can serve as a framework for the calculation of such interactions have recently become available, offering methods to rapidly and significantly increase our knowledge of the behaviour of the combined human-soil-landscape system under climatic influence. If quantitative data about interactions become available, these models can simulate landscape development and provide testable predictions. Recent exploratory work in this direction is promising. With diminishing computational limitations and increasing attention for parsimony in model building, Landscape Evolutin Models (LEMs) now allow quantitative incorporation of soil formation processes (e.g. LAPSUS) and recent soil formation models allow calculation of the evolution of soil properties in ways that are suited for such incorporation (e.g. SoilGen2). A major step forward is possible whereby landscape evolution and soil formation will be integrated through quantitative modelling, with possibilities to include dynamic feedback mechanisms between soil and landscape. Such a model will allow us to study the coupled human-environmental system and is a significant contribution to landscape change management. Our objective is to propose a model framework and platform for others to join or to be inspired. Altogether with the common goal to increase our understanding of the quantitative interaction between slope processes, soil formation and human activity through measurements and modelling.
Schoorl, J. M.; Finke, P. A.; Temme, A. J. A. M.; Sonneveld, M. P. W.
Isolation and fine mapping of 16 novel human zinc finger-encoding cDNAs identify putative candidate genes for developmental and malignant disorders
The authors have isolated and chromosomally fine-mapped 16 novel genes belonging to the human zinc finger Krueppel family (ZNF131-140, 142, 143, 148, 151, 154, and 155), including 1 of the GLI type (ZNF143) and 3 containing a KRAB (Krueppel-associated box) segment (ZNF133, 136, and 140). Based on their map position, several of these ZNF genes are putative candidate genes for both developmental and malignant disorders: ZNF138, ZNF139, and ZNF143 were localized to 7q11.2, 7q21.3-q22.1, and 11p15.3-p15.4, regions involved in deletions and/or translocations associated with Williams syndrome, split hand and foot disease (SHFD1), and Beckwith-Wiedemann syndrome, respectively. ZNF133 was localized to 20p11.2, close to, but probably distinct from, the region deleted in Alagille syndrome. Zinc finger genes mapping to regions commonly deleted in solid tumors included ZNF132, 134, 135, 137, 154, and 155, all located on 19q13 (thyroid adenoma), and ZNF151, at 1p36.1-p36.2 (neuroblastoma, colon cancer, and other tumors). In addition, several of the ZNFs mapped to regions implicated in recurrent chromosomal rearrangements in hematological malignancies (ZNF139, 7q21.3-q22.1; ZNF148, 3q21-q22; ZNF151, 1p36.1-p36.2). The study indicates that the number of ZNF genes in human is large and that systematic isolation and mapping of ZNF genes is a straightforward approach for the identification of novel candidate disease genes. 47 refs., 2 figs., 1 tab.
Tommerup, N. [John F. Kennedy Institute, Glostrup (Denmark)] [John F. Kennedy Institute, Glostrup (Denmark); Vissing, H. [Novo Nordisk, Bagsvaerd (Denmark)] [Novo Nordisk, Bagsvaerd (Denmark)
What Happened, and Why: Toward an Understanding of Human Error Based on Automated Analyses of Incident Reports. Volume 1
NASA Technical Reports Server (NTRS)
The objective of the Aviation System Monitoring and Modeling (ASMM) project of NASA s Aviation Safety and Security Program was to develop technologies that will enable proactive management of safety risk, which entails identifying the precursor events and conditions that foreshadow most accidents. This presents a particular challenge in the aviation system where people are key components and human error is frequently cited as a major contributing factor or cause of incidents and accidents. In the aviation "world", information about what happened can be extracted from quantitative data sources, but the experiential account of the incident reporter is the best available source of information about why an incident happened. This report describes a conceptual model and an approach to automated analyses of textual data sources for the subjective perspective of the reporter of the incident to aid in understanding why an incident occurred. It explores a first-generation process for routinely searching large databases of textual reports of aviation incident or accidents, and reliably analyzing them for causal factors of human behavior (the why of an incident). We have defined a generic structure of information that is postulated to be a sound basis for defining similarities between aviation incidents. Based on this structure, we have introduced the simplifying structure, which we call the Scenario as a pragmatic guide for identifying similarities of what happened based on the objective parameters that define the Context and the Outcome of a Scenario. We believe that it will be possible to design an automated analysis process guided by the structure of the Scenario that will aid aviation-safety experts to understand the systemic issues that are conducive to human error.
Maille, Nicolas P.; Statler, Irving C.; Ferryman, Thomas A.; Rosenthal, Loren; Shafto, Michael G.; Statler, Irving C.
A developmental examination of the conceptual structure of animal, artifact, and human social categories across two cultural contexts
Previous research indicates that the ontological status that adults attribute to categories varies systematically by domain. For example, adults view distinctions between different animal species as natural and objective, but view distinctions between different kinds of furniture as more conventionalized and subjective. The present work (N = 435; ages 5-18) examined the effects of domain, age, and cultural context on beliefs about the naturalness vs. conventionality of categories. Results demonstrate that young children, like adults, view animal categories as natural kinds, but artifact categories as more conventionalized. For human social categories (gender and race), beliefs about naturalness and conventionality were predicted by interactions between cultural context and age. Implications for the origins of social categories and theories of conceptual development will be discussed.
Rhodes, Marjorie; Gelman, Susan A.
Intoeing: a developmental norm.
Intoeing, often referred to as pigeon-toes, is a frequent reason for referral to the pediatric orthopaedic surgeon's practice. Parents and grandparents are concerned about the appearance of the legs and a history of frequent tripping and falling. Many of the "abnormalities" that these children present with are variations of normal development of the lower extremities and include flat footedness, and torsional or angular "deformity." The approach of the specialist team is to identify the source of the intoeing, to rule out neuromuscular dysfunction or other serious conditions, and to counsel the family on anticipatory guidance of the natural history of intoeing. The focus of this article is intoeing, associated examination techniques, and nursing considerations of education and treatment. An understanding of musculoskeletal developmental norms, the clinical examination for intoeing, and the current recommendations for treatment will enable the provider to educate and accurately inform families. PMID:12024629
Ryan, D J
Developmental prosopagnosia in childhood.
Developmental prosopagnosia (DP) is defined by severe face recognition problems resulting from a failure to develop the necessary visual mechanisms for processing faces. While there is a growing literature on DP in adults, little has been done to study this disorder in children. The profound impact of abnormal face perception on social functioning and the general lack of awareness of childhood DP can result in severe social and psychological consequences for children. This review discusses possible aetiologies of DP and summarizes the few cases of childhood DP that have been reported. It also outlines key objectives for the growth of this emerging research area and special considerations for studying DP in children. With clear goals and concerted efforts, the study of DP in childhood will be an exciting avenue for enhancing our understanding of normal and abnormal face perception for all age groups. PMID:23140142
Dalrymple, Kirsten A; Corrow, Sherryse; Yonas, Albert; Duchaine, Brad
Structural analysis on mutation residues and interfacial water molecules for human TIM disease understanding
Background Human triosephosphate isomerase (HsTIM) deficiency is a genetic disease caused often by the pathogenic mutation E104D. This mutation, located at the side of an abnormally large cluster of water in the inter-subunit interface, reduces the thermostability of the enzyme. Why and how these water molecules are directly related to the excessive thermolability of the mutant have not been investigated in structural biology. Results This work compares the structure of the E104D mutant with its wild type counterparts. It is found that the water topology in the dimer interface of HsTIM is atypical, having a "wet-core-dry-rim" distribution with 16 water molecules tightly packed in a small deep region surrounded by 22 residues including GLU104. These water molecules are co-conserved with their surrounding residues in non-archaeal TIMs (dimers) but not conserved across archaeal TIMs (tetramers), indicating their importance in preserving the overall quaternary structure. As the structural permutation induced by the mutation is not significant, we hypothesize that the excessive thermolability of the E104D mutant is attributed to the easy propagation of atoms' flexibility from the surface into the core via the large cluster of water. It is indeed found that the B factor increment in the wet region is higher than other regions, and, more importantly, the B factor increment in the wet region is maintained in the deeply buried core. Molecular dynamics simulations revealed that for the mutant structure at normal temperature, a clear increase of the root-mean-square deviation is observed for the wet region contacting with the large cluster of interfacial water. Such increase is not observed for other interfacial regions or the whole protein. This clearly suggests that, in the E104D mutant, the large water cluster is responsible for the subunit interface flexibility and overall thermolability, and it ultimately leads to the deficiency of this enzyme. Conclusions Our study reveals that a large cluster of water buried in protein interfaces is fragile and high-maintenance, closely related to the structure, function and evolution of the whole protein.
Developmental roles of brain histamine.
Histamine appears early during brain development, has been shown to regulate fetal and adult brain-derived stem cells in a receptor type-dependent manner, and has widespread actions on systems involved in arousal and movement. Developmental studies in both rodents and zebrafish have elucidated the spatiotemporal patterning of the histaminergic system and, in zebrafish, have revealed the mechanisms whereby histamine regulates the number of hypocretin/orexin (hcrt) neurons, which in turn may regulate the number of histaminergic cells. Recent demonstrations of increased numbers of histaminergic neurons in patients with narcolepsy highlight the importance, for our understanding of both normal and pathological brain function, of understanding these interactions. Here, we review recent research into the developmental roles of histamine and suggest key areas for future research. PMID:24486025
Panula, Pertti; Sundvik, Maria; Karlstedt, Kaj
Contemporary developmental toxicity testing focuses on the evaluation of a variety of adverse developmental effects which include structural malformations, intrauterine death, growth retardation, and deficits in postnatal function. n the extrapolation of information from animal s...
Effects of in vitro maturation of monkey oocytes on their developmental capacity
The study of in vitro maturation (IVM) of rhesus monkey oocytes has important implications for biomedical research and human infertility treatment. In vitro-matured rhesus monkey oocytes show much less developmental potential than IVM oocytes of other species. Since about 1980 when rhesus monkey IVM, in vitro fertilization (IVF) and in vitro embryo culture (IVC) systems were established, numerous efforts have been made to improve the developmental competence of oocytes and to understand the mechanisms regulating oocyte maturation. This review describes recent progress in this area, particularly the effects of factors such as steroid hormones, energy substrates, amino acids, ovarian follicle status, maternal age and breeding season on the developmental competence, gene expression patterns and genome integrity of rhesus IVM oocytes.
Zheng, P.
Effects of in vitro maturation of monkey oocytes on their developmental capacity.
The study of in vitro maturation (IVM) of rhesus monkey oocytes has important implications for biomedical research and human infertility treatment. In vitro-matured rhesus monkey oocytes show much less developmental potential than IVM oocytes of other species. Since about 1980 when rhesus monkey IVM, in vitro fertilization (IVF) and in vitro embryo culture (IVC) systems were established, numerous efforts have been made to improve the developmental competence of oocytes and to understand the mechanisms regulating oocyte maturation. This review describes recent progress in this area, particularly the effects of factors such as steroid hormones, energy substrates, amino acids, ovarian follicle status, maternal age and breeding season on the developmental competence, gene expression patterns and genome integrity of rhesus IVM oocytes. PMID:17081707
Zheng, P
Alimentary Epigenetics: A Developmental Psychobiological Systems View of the Perception of Hunger, Thirst and Satiety
Hunger, thirst and satiety have an enormous influence on cognition, behavior and development, yet we often take for granted that they are simply inborn or innate. Converging data and theory from both comparative and human domains, however, supports the conclusion that the phenomena hunger, thirst and satiety are not innate but rather emerge probabilistically as a function of experience during individual development. The metatheoretical perspective provided by developmental psychobiological systems theory provides a useful framework for organizing and synthesizing findings related to the development of the perception of hunger, thirst and satiety, or alimentary interoception. It is argued that neither developmental psychology nor the psychology of eating and drinking have adequately dealt with the ontogeny of alimentary interoception and that a more serious consideration of the species-typical developmental system of food and fluid intake and the many modifications that have been made therein is likely necessary for a full understanding of both alimentary and emotional development.
Harshaw, Christopher
Socio-hydrologic Modeling to Understand and Mediate the Competition for Water between Humans and Ecosystems: Murrumbidgee River Basin, Australia
NASA Astrophysics Data System (ADS)
Around the world the demand for water resources is growing in order to satisfy rapidly increasing human populations, leading to competition for water between humans and ecosystems. An entirely new and comprehensive quantitative framework is needed to establish a holistic understanding of that competition, thereby enabling development and evaluation of effective mediation strategies. We present a case study centered on the Murrumbidgee river basin in eastern Australia that illustrates the dynamics of the balance between water extraction and use for food production and efforts to mitigate and reverse consequent degradation of the riparian environment. Interactions between patterns of water resources management and climate driven hydrological variability within the prevailing socio-economic environment have contributed to the emergence of new whole system dynamics over the last 100 years. In particular, data analysis reveals a pendulum swing between an exclusive focus on agricultural development and food production in the initial stages of water resources development and its attendant socio-economic benefits, followed by the gradual realization of the adverse environmental impacts, efforts to mitigate these with the use of remedial measures, and ultimately concerted efforts and externally imposed solutions to restore environmental health and ecosystem services. A quasi-distributed coupled socio-hydrologic system model that explicitly includes the two-way coupling between human and hydrological systems, including evolution of human values/norms relating to water and the environment, is able to mimic broad features of this pendulum swing. The model consists of coupled nonlinear differential equations that include four state variables describing the co-evolution of storage capacity, irrigated area, human population, and ecosystem health, which are all connected by feedback mechanisms. The model is used to generate insights into the dominant controls of the trajectory of co-evolution of the coupled human-water system, to serve as the theoretical framework for more detailed analysis of the system, and to generate organizing principles that may be transferable to other systems in different climatic and socio-economic settings.
van Emmerik, Tim; Sivapalan, Murugesu; Li, Zheng; Pande, Saket; Savenije, Hubert
Imaging opioid analgesia in the human brain and its potential relevance for understanding opioid use in chronic pain.
Opioids play an important role for the management of acute pain and in palliative care. The role of long-term opioid therapy in chronic non-malignant pain remains unclear and is the focus of much clinical research. There are concerns regarding analgesic tolerance, paradoxical pain and issues with dependence that can occur with chronic opioid use in the susceptible patient. In this review, we discuss how far human neuroimaging research has come in providing a mechanistic understanding of pain relief provided by opioids, and suggest avenues for further studies that are relevant to the management of chronic pain with opioids. This article is part of the Special Issue Section entitled 'Neuroimaging in Neuropharmacology'. PMID:23891639
Lee, Michael C; Wanigasekera, Vishvarani; Tracey, Irene
The Schistosoma mansoni Tegumental-Allergen-Like (TAL) Protein Family: Influence of Developmental Expression on Human IgE Responses
Background A human IgE response to Sm22.6 (a dominant IgE target in Schistosoma mansoni) is associated with the development of partial immunity. Located inside the tegument, the molecule belongs to a family of proteins from parasitic platyhelminths, the Tegument-Allergen-Like proteins (TALs). In addition to containing dynein-light-chain domains, these TALs also contain EF-hand domains similar to those found in numerous EF-hand allergens. Methodology/Principal Findings S. mansoni genome searches revealed 13 members (SmTAL1-13) within the species. Recent microarray data demonstrated they have a wide range of life-cycle transcriptional profiles. We expressed SmTAL1 (Sm22.6), SmTAL2, 3, 4, 5 and 13 as recombinant proteins and measured IgE and IgG4 in 200 infected males (7�60 years) from a schistosomiasis endemic region in Uganda. For SmTAL1 and 3 (transcribed in schistosomula through adult-worms and adult-worms, respectively) and SmTAL5 (transcribed in cercariae through adult-worms), detectable IgE responses were rare in 7�9 year olds, but increased with age. At all ages, IgE to SmTAL2 (expressed constitutively), was rare while anti-SmTAL2 IgG4 was common. Levels of IgE and IgG4 to SmTAL4 and 13 (transcribed predominantly in the cercariae/skin stage) were all low. Conclusions We have not measured SmTAL protein abundance or exposure in live parasites, but the antibody data suggests to us that, in endemic areas, there is priming and boosting of IgE to adult-worm SmTALs by occasional death of long-lived worms, desensitization to egg SmTALs through continuous exposure to dying eggs and low immunogenicity of larval SmTALs due to immunosuppression in the skin by the parasite. Of these, it is the gradual increase in IgE to the worm antigens that parallels age-dependent immunity seen in endemic areas.
Fitzsimmons, Colin M.; Jones, Frances M.; Stearn, Alex; Chalmers, Iain W.; Hoffmann, Karl F.; Wawrzyniak, Jakub; Wilson, Shona; Kabatereine, Narcis B.; Dunne, David W.
Development and Validation of a Two-Tier Instrument to Examine Understanding of Internal Transport in Plants and the Human Circulatory System
ERIC Educational Resources Information Center
This study is intended to develop an assessment instrument to investigate students' understandings about internal transport in plants and human circulatory system. A refined process of a two-tier diagnostic test was used to develop the instrument. Finally, three versions of the Internal Transport in Plants and the Human Circulatory System test�
Wang, Jing-Ru