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Wnt Signaling in Cancer Stem Cell Biology
de Sousa e Melo, Felipe; Vermeulen, Louis
Aberrant regulation of Wnt signaling is a common theme seen across many tumor types. Decades of research have unraveled the epigenetic and genetic alterations that result in elevated Wnt pathway activity. More recently, it has become apparent that Wnt signaling levels identify stem-like tumor cells that are responsible for fueling tumor growth. As therapeutic targeting of these tumor stem cells is an intense area of investigation, a concise understanding on how Wnt activity relates to cancer stem cell traits is needed. This review attempts at summarizing the intricacies between Wnt signaling and cancer stem cell biology with a special emphasis on colorectal cancer. PMID:27355964
Plant Cell and Signaling Biology Blooms in the Wuyi Mountain
Institute of Scientific and Technical Information of China (English)
Jianping Hu
@@ INTRODUCTION The Eighth International Conference on Plant Biology Fron-tiers, organized by Zhenbiao Yang, Chentao Lin, and Xing-wang Deng, was convened in the Wuyi Mountain Yeohwa Resort in Fujian, China, 23-27 September 2010.The meeting's main theme was Cells and Signals, featuring four keynote speeches, 45 plenary talks, and over 40 poster presentations that covered a wide range of topics, from dynamic cellular structures to how developmental and environmental signals control various plant processes at the juncture of cells.
Role of Calcium Signaling in B Cell Activation and Biology.
Baba, Yoshihiro; Kurosaki, Tomohiro
Increase in intracellular levels of calcium ions (Ca2+) is one of the key triggering signals for the development of B cell response to the antigen. The diverse Ca2+ signals finely controlled by multiple factors participate in the regulation of gene expression, B cell development, and effector functions. B cell receptor (BCR)-initiated Ca2+ mobilization is sourced from two pathways: one is the release of Ca2+ from the intracellular stores, endoplasmic reticulum (ER), and other is the prolonged influx of extracellular Ca2+ induced by depleting the stores via store-operated calcium entry (SOCE) and calcium release-activated calcium (CRAC) channels. The identification of stromal interaction molecule 1(STIM1), the ER Ca2+ sensor, and Orai1, a key subunit of the CRAC channel pore, has now provided the tools to understand the mode of Ca2+ influx regulation and physiological relevance. Herein, we discuss our current understanding of the molecular mechanisms underlying BCR-triggered Ca2+ signaling as well as its contribution to the B cell biological processes and diseases. PMID:26369772
Role of inositol phospholipid signaling in natural killer cell biology
Gumbleton, Matthew; Kerr, William G.
Natural killer (NK) cells are important for host defense against malignancy and infection. At a cellular level NK cells are activated when signals from activating receptors exceed signaling from inhibitory receptors. At a molecular level NK cells undergo an education process to both prevent autoimmunity and acquire lytic capacity. Mouse models have shown important roles for inositol phospholipid signaling in lymphocytes. NK cells from mice with deletion in different members of the inositol ph...
Diffusion wave and signal transduction in biological live cells
Fan, Tian You
Transduction of mechanical stimuli into biochemical signals is a fundamental subject for cell physics. In the experiments of FRET signal in cells a wave propagation in nanoscope was observed. We here develop a diffusion wave concept and try to give an explanation to the experimental observation. The theoretical prediction is in good agreement to result of the experiment.
Mass spectrometry based proteomics in cell biology and signaling research
International Nuclear Information System (INIS)
Full text: Proteomics is one of the most powerful post-genomics technologies. Recently accomplishments include large scale protein-protein interaction mapping, large scale mapping of phosphorylation sites and the cloning of key signaling molecules. In this talk, current state of the art of the technology will be reviewed. Applications of proteomics to the mapping of multiprotein complexes will be illustrated with recent work on the spliceosome and the nucleolus. More than 300 proteins have been mapped to each of these complexes. Quantitative techniques are becoming more and more essential in proteomics. They are usually performed by the incorporation of stable isotopes - a light form in cell state 'A' and a heavy form in cell state 'E' - and subsequent comparison of mass spectrometric peak heights. A new technique called, SILAC for Stable isotope Incorporation by Amino acids in Cell culture, has been applied to studying cell differentiation and mapping secreted proteins from adipocytes. A number of known and novel proteins important in adipocyte differentiation have been identified by this technique. Some of these proved to be upregulated at the 1 mRNA level, too, whereas others appear to be regulated post-translationally. We have also applied the SILAC method to protein-protein interaction mapping. For example, we compared immunoprecipitates from stimulated and non-stimulated cells to find binding partners recruited to the bait due to the stimulus. Several novel substrates in the EGF pathway were found in this way. An important application of proteomics in the signaling field is the mapping of post-translational modifications. In particular, there are a number of techniques for phosphotyrosine phosphorylation mapping which have proven very useful. Making use of the mass deficiency of the phosphogroup, 'parent ion scans' con be performed, which selectively reveal phosphotyrosine peptides from complex peptides mixtures. This technique has been used to clone several
Biological signals as handicaps.
Grafen, A
An ESS model of Zahavi's handicap principle is constructed. This allows a formal exposition of how the handicap principle works, and shows that its essential elements are strategic. The handicap model is about signalling, and it is proved under fairly general conditions that if the handicap principle's conditions are met, then an evolutionarily stable signalling equilibrium exists in a biological signalling system, and that any signalling equilibrium satisfies the conditions of the handicap principle. Zahavi's major claims for the handicap principle are thus vindicated. The place of cheating is discussed in view of the honesty that follows from the handicap principle. Parallel signalling models in economics are discussed. Interpretations of the handicap principle are compared. The models are not fully explicit about how females use information about male quality, and, less seriously, have no genetics. A companion paper remedies both defects in a model of the handicap principle at work in sexual selection. PMID:2402153
Downregulation of RSK2 influences the biological activities of human osteosarcoma cells through inactivating AKT/mTOR signaling pathways.
Qiu, Quanhe; Jiang, Jing; Lin, Liangbo; Cheng, Si; Xin, Daqi; Jiang, Wei; Shen, Jieliang; Hu, Zhenming
RSK2 (90 kDa ribosomal S6 kinase) is a downstream effector of the Ras/ERK (extracellular signal-regulated kinase) signaling pathway that has major functions in cell biological activities, including regulating nuclear signaling, cell cycle progression, cell proliferation, cell growth, protein synthesis, cell migration and cell survival, and is expressed in most types of human malignant tumors, including lung cancer, prostate and breast tumors, skin cancer and osteosarcomas (OS). RSK2 was found to be essential for osteosarcoma formation. To investigate whether RSK2 is expressed at high levels in human osteosarcome tissues and whether its expression is correlated with the aggressive biological behavior of osteosarcoma cell line (OCLs), we assessed the association between RSK2 expression and OS cell progression, as well as the effects of RSK2 inhibition on the biological activities of osteosarcoma cells. We performed immunohistochemistry to analyze the expression of RSK2 in specimens from 30 humans with osteosarcoma, and 15 normal tissues. RSK2 gene expression levels in 30 specimens with osteosarcoma were significantly higher than those of normal tissues. We performed RNA interference on three OCLs to evaluate cell apoptosis, cell growth, cell proliferation, cell motility, chemosensitivity and oncogenicity. After transfection with RSK2 shRNA, increased cell apoptosis, cell growth inhibition, cell cycle progression, weaker cell proliferation, cell migration and weaker tumor formation were observed in all OCLs. These results suggested that RSK2 expression may mediate the biological activities of OS cells and RSK2 may be an effective therapeutic target for the treatment of osteosarcomas. The AKT/mTOR, MAPK/ERK/c-Fos and Bcl2/Bax pathways were analysed to clarify the mechanisms involved. PMID:27082640
Systems Biology Analysis of Heterocellular Signaling.
Tape, Christopher J
Tissues comprise multiple heterotypic cell types (e.g., epithelial, mesenchymal, and immune cells). Communication between heterotypic cell types is essential for biological cohesion and is frequently dysregulated in disease. Despite the importance of heterocellular communication, most systems biology techniques do not report cell-specific signaling data from mixtures of cells. As a result, our existing perspective of cellular behavior under-represents the influence of heterocellular signaling. Recent technical advances now permit the resolution of systems-level cell-specific signaling data. This review discusses how new physical, spatial, and isotopic resolving methods are facilitating unique systems biology studies of heterocellular communication. PMID:27087613
The biological networks in studying cell signal transduction complexity: The examples of sperm capacitation and of endocannabinoid system
Nicola Bernabò; Barbara Barboni; Mauro Maccarrone
Cellular signal transduction is a complex phenomenon, which plays a central role in cell surviving and adaptation. The great amount of molecular data to date present in literature, together with the adoption of high throughput technologies, on the one hand, made available to scientists an enormous quantity of information, on the other hand, failed to provide a parallel increase in the understanding of biological events. In this context, a new discipline arose, the systems biology, aimed to ma...
Illuminating Cell Signaling: Using "Vibrio harveyi" in an Introductory Biology Laboratory
Hrizo, Stacy L.; Kaufmann, Nancy
Cell signaling is an essential cellular process that is performed by all living organisms. Bacteria communicate with each other using a chemical language in a signaling pathway that allows bacteria to evaluate the size of their population, determine when they have reached a critical mass (quorum sensing), and then change their behavior in unison…
The biological networks in studying cell signal transduction complexity: The examples of sperm capacitation and of endocannabinoid system
Bernabò, Nicola; Barboni, Barbara; Maccarrone, Mauro
Cellular signal transduction is a complex phenomenon, which plays a central role in cell surviving and adaptation. The great amount of molecular data to date present in literature, together with the adoption of high throughput technologies, on the one hand, made available to scientists an enormous quantity of information, on the other hand, failed to provide a parallel increase in the understanding of biological events. In this context, a new discipline arose, the systems biology, aimed to manage the information with a computational modeling-based approach. In particular, the use of biological networks has allowed the making of huge progress in this field. Here we discuss two possible application of the use of biological networks to explore cell signaling: the study of the architecture of signaling systems that cooperate in determining the acquisition of a complex cellular function (as it is the case of the process of activation of spermatozoa) and the organization of a single specific signaling systems expressed by different cells in different tissues (i.e. the endocannabinoid system). In both the cases we have found that the networks follow a scale free and small world topology, likely due to the evolutionary advantage of robustness against random damages, fastness and specific of information processing, and easy navigability. PMID:25379139
Adaptive multiscale biological signal processing
Testoni, Nicola
Biological processes are very complex mechanisms, most of them being accompanied by or manifested as signals that reflect their essential characteristics and qualities. The development of diagnostic techniques based on signal and image acquisition from the human body is commonly retained as one of the propelling factors in the advancements in medicine and biosciences recorded in the recent past. It is a fact that the instruments used for biological signal and image rec...
Biological signals classification and analysis
Kiasaleh, Kamran
This authored monograph presents key aspects of signal processing analysis in the biomedical arena. Unlike wireless communication systems, biological entities produce signals with underlying nonlinear, chaotic nature that elude classification using the standard signal processing techniques, which have been developed over the past several decades for dealing primarily with standard communication systems. This book separates what is random from that which appears to be random, and yet is truly deterministic with random appearance. At its core, this work gives the reader a perspective on biomedical signals and the means to classify and process such signals. In particular, a review of random processes along with means to assess the behavior of random signals is also provided. The book also includes a general discussion of biological signals in order to demonstrate the inefficacy of the well-known techniques to correctly extract meaningful information from such signals. Finally, a thorough discussion of recently ...
3D-dynamic visualization of complex molecular cell biology processes : 1-year university students' understanding of visualizations of signal transduction
Jacobsson, Johan Lars Henrik
This study deals with the use of 3D-dynamic visualizations for teaching complex molecular cell biology concepts. The focus is on signal transduction, which is a concept that constitutes an important part of biological systems. 3D-dynamic visualizations (animations) were produced and shown for a total of 24 students attending a course in molecular cell biology at Karlstad University, Sweden. Data were collected by questionnaires and interviews which were structured around the understandability...
Energy Technology Data Exchange (ETDEWEB)
Abboud, Hanna E., E-mail: firstname.lastname@example.com
Mesangial cells originate from the metanephric mesenchyme and maintain structural integrity of the glomerular microvascular bed and mesangial matrix homeostasis. In response to metabolic, immunologic or hemodynamic injury, these cells undergo apoptosis or acquire an activated phenotype and undergo hypertrophy, proliferation with excessive production of matrix proteins, growth factors, chemokines and cytokines. These soluble factors exert autocrine and paracrine effects on the cells or on other glomerular cells, respectively. MCs are primary targets of immune-mediated glomerular diseases such as IGA nephropathy or metabolic diseases such as diabetes. MCs may also respond to injury that primarily involves podocytes and endothelial cells or to structural and genetic abnormalities of the glomerular basement membrane. Signal transduction and oxidant stress pathways are activated in MCs and likely represent integrated input from multiple mediators. Such responses are convenient targets for therapeutic intervention. Studies in cultured MCs should be supplemented with in vivo studies as well as examination of freshly isolated cells from normal and diseases glomeruli. In addition to ex vivo morphologic studies in kidney cortex, cells should be studied in their natural environment, isolated glomeruli or even tissue slices. Identification of a specific marker of MCs should help genetic manipulation as well as selective therapeutic targeting of these cells. Identification of biological responses of MCs that are not mediated by the renin–angiotensin system should help development of novel and effective therapeutic strategies to treat diseases characterized by MC pathology.
Institute of Scientific and Technical Information of China (English)
Aiming Lin; Zhenggang Liu
@@ Signal transduction is pivotal for many, if not all, fundamental cellular functions including proliferation, differentiation, transformation and programmed cell death. Deregulation of cell signaling may result in certain types of cancers and other human diseases.
Exposure to 3G mobile phone signals does not affect the biological features of brain tumor cells
Liu, Yu-Xiao; Li, Guo-Qing; Fu, Xiang-ping; Xue, Jing-hui; Ji, Shou-ping; Zhang, Zhi-Wen; Zhang, Yi; Li, An-Ming
Background The increase in mobile phone use has generated concerns about possible risks to human health, especially the development of brain tumors. Whether tumor patients should continue to use mobile telephones has remained unclear because of a paucity of information. Herein, we investigated whether electromagnetic fields from mobile phones could alter the biological features of human tumor cells and act as a tumor-promoting agent. Methods Human glioblastoma cell lines, U251-MG and U87-MG, ...
Lipidomics Investigations in Cell Biology
YU, Yang
Cell membrane is the biological barrier serving as both territorial defense and the communication hinge for the interior of cell from its surroundings. As building blocks of cellular membranes and also precursor for second messengers, a variety of lipids play essential roles in cellular membrane dynamics as well as important functions such as cell proliferation, apoptosis, signal transduction and membrane trafficking modulation. Lipidomics, representing the systematic and integrative studies ...
International Nuclear Information System (INIS)
This section contains summaries of research on mechanisms of lethality and radioinduced changes in mammalian cell properties, new cell systems for the study of the biology of mutation and neoplastic transformation, and comparative properties of ionizing radiations
Transcriptional Profiling of Hypoxic Neural Stem Cells Identifies Calcineurin-NFATc4 Signaling as a Major Regulator of Neural Stem Cell Biology
Directory of Open Access Journals (Sweden)
Marta Moreno
Full Text Available Neural stem cells (NSCs reside in a hypoxic microenvironment within the brain. However, the crucial transcription factors (TFs that regulate NSC biology under physiologic hypoxia are poorly understood. Here we have performed gene set enrichment analysis (GSEA of microarray datasets from hypoxic versus normoxic NSCs with the aim of identifying pathways and TFs that are activated under oxygen concentrations mimicking normal brain tissue microenvironment. Integration of TF target (TFT and pathway enrichment analysis identified the calcium-regulated TF NFATc4 as a major candidate to regulate hypoxic NSC functions. Nfatc4 expression was coordinately upregulated by top hypoxia-activated TFs, while NFATc4 target genes were enriched in hypoxic NSCs. Loss-of-function analyses further revealed that the calcineurin-NFATc4 signaling axis acts as a major regulator of NSC self-renewal and proliferation in vitro and in vivo by promoting the expression of TFs, including Id2, that contribute to the maintenance of the NSC state.
Stochastic processes in cell biology
Bressloff, Paul C
This book develops the theory of continuous and discrete stochastic processes within the context of cell biology. A wide range of biological topics are covered including normal and anomalous diffusion in complex cellular environments, stochastic ion channels and excitable systems, stochastic calcium signaling, molecular motors, intracellular transport, signal transduction, bacterial chemotaxis, robustness in gene networks, genetic switches and oscillators, cell polarization, polymerization, cellular length control, and branching processes. The book also provides a pedagogical introduction to the theory of stochastic process – Fokker Planck equations, stochastic differential equations, master equations and jump Markov processes, diffusion approximations and the system size expansion, first passage time problems, stochastic hybrid systems, reaction-diffusion equations, exclusion processes, WKB methods, martingales and branching processes, stochastic calculus, and numerical methods. This text is primarily...
Ardhanareeswaran, Karthikeyan; Mirotsou, Maria
Over the past few years new insights have been added to the study of stem cells in the adult lung. The exploration of the endogenous lung progenitors as well as the study of exogenously delivered stem cell populations holds promise for advancing our understanding of the biology of lung repair mechanisms. Moreover, it opens new possibilities for the use of stem cell therapy for the development of regenerative medicine approaches for the treatment of lung disease. Here, we discuss the main type...
Adaptive filtering in biological signal processing.
Iyer, V K; Ploysongsang, Y; Ramamoorthy, P A
The high dependence of conventional optimal filtering methods on the a priori knowledge of the signal and noise statistics render them ineffective in dealing with signals whose statistics cannot be predetermined accurately. Adaptive filtering methods offer a better alternative, since the a priori knowledge of statistics is less critical, real time processing is possible, and the computations are less expensive for this approach. Adaptive filtering methods compute the filter coefficients "on-line", converging to the optimal values in the least-mean square (LMS) error sense. Adaptive filtering is therefore apt for dealing with the "unknown" statistics situation and has been applied extensively in areas like communication, speech, radar, sonar, seismology, and biological signal processing and analysis for channel equalization, interference and echo canceling, line enhancement, signal detection, system identification, spectral analysis, beamforming, modeling, control, etc. In this review article adaptive filtering in the context of biological signals is reviewed. An intuitive approach to the underlying theory of adaptive filters and its applicability are presented. Applications of the principles in biological signal processing are discussed in a manner that brings out the key ideas involved. Current and potential future directions in adaptive biological signal processing are also discussed. PMID:2180633
Biologically synthesized silver nanoparticles induce neuronal differentiation of SH-SY5Y cells via modulation of reactive oxygen species, phosphatases, and kinase signaling pathways.
Dayem, Ahmed Abdal; Kim, BongWoo; Gurunathan, Sangiliyandi; Choi, Hye Yeon; Yang, Gwangmo; Saha, Subbroto Kumar; Han, Dawoon; Han, Jihae; Kim, Kyeongseok; Kim, Jin-Hoi; Cho, Ssang-Goo
Nano-scale materials are noted for unique properties, distinct from those of their bulk material equivalents. In this study, we prepared spherical silver nanoparticles (AgNPs) with an average size of about 30 nm and tested their potency to induce neuronal differentiation of SH-SY5Y cells. Human neuroblastoma SH-SY5Y cells are considered an ideal in vitro model for studying neurogenesis, as they can be maintained in an undifferentiated state or be induced to differentiate into neuron-like phenotypes in vitro by several differentiation-inducing agents. Treatment of SH-SY5Y cells by biologically synthesized AgNPs led to cell morphological changes and significant increase in neurite length and enhanced the expression of neuronal differentiation markers such as Map-2, β-tubulin III, synaptophysin, neurogenin-1, Gap-43, and Drd-2. Furthermore, we observed an increase in generation of intracellular reactive oxygen species (ROS), activation of several kinases such as ERK and AKT, and downregulation of expression of dual-specificity phosphatases (DUSPs) in AgNPs-exposed SH-SY5Y cells. Our results suggest that AgNPs modulate the intracellular signaling pathways, leading to neuronal differentiation, and could be applied as promising nanomaterials for stem cell research and therapy. PMID:24827677
Biologically synthesized silver nanoparticles induce neuronal differentiation of SH-SY5Y cells via modulation of reactive oxygen species, phosphatases, and kinase signaling pathwayss.
Dayem, Ahmed Abdal; Kim, Bongwoo; Gurunathan, Sangiliyandi; Choi, Hye Yeon; Yang, Gwangmo; Saha, Subbroto Kumar; Han, Dawoon; Han, Jihae; Kim, Kyeongseok; Kim, Jin-Hoi; Cho, Ssang-Goo
The relevant in vitro cellular model resembling functional neurons is important for the mechanistic research on various neuronal diseases. Human neuroblastoma SH-SY5Y cells may be considered one of the ideal in vitro models for studying neuroscience, as they can be maintained in an undifferentiated state or be induced to differentiate into neuron-like phenotypes in vitro by several differentiation-inducing agents. In this study, we prepared spherical silver nanoparticles (AgNPs) with an average size of about 30 nm and tested their potency to induce neuronal differentiation of SH-SY5Y cells. Treatment of SH-SY5Y cells by biologically synthesized AgNPs led to cell morphological changes and significant increase in neurite length and enhanced the expression of neuronal differentiation markers such as Map-2, β-tubulin III, synaptophysin, neurogenin-1, Gap-43, and Drd-2. Furthermore, we observed an increase in generation of intracellular reactive oxygen species (ROS), activation of several kinases such as ERK and AKT, and down-regulation of expression of dual-specificity phosphatases (DUSPs) in AgNPs-exposed SH-SY5Y cells. Our results suggest that AgNPs could modulate the intracellular signaling pathways to lead to neuronal differentiation, and could be applied as promising nanomaterials for stem cell research and therapy. PMID:24753441
Van Epps, Heather L.
In 1990, Charles Mackay and colleagues combined classical physiology with modern molecular biology to provide the first concrete evidence that naive and memory T cells follow distinct migratory routes out of the bloodstream— a discovery that helped invigorate the field of lymphocyte homing.
NASA's Ames Research Center awarded Ciencia, Inc., a Small Business Innovation Research contract to develop the Cell Fluorescence Analysis System (CFAS) to address the size, mass, and power constraints of using fluorescence spectroscopy in the International Space Station's Life Science Research Facility. The system will play an important role in studying biological specimen's long-term adaptation to microgravity. Commercial applications for the technology include diverse markets such as food safety, in situ environmental monitoring, online process analysis, genomics and DNA chips, and non-invasive diagnostics. Ciencia has already sold the system to the private sector for biosensor applications.
International Nuclear Information System (INIS)
Progress is reported on studies of the molecular biology and functional changes in cultured mammalian cells following exposure to x radiation, uv radiation, fission neutrons, or various chemical environmental pollutants alone or in combinations. Emphasis was placed on the separate and combined effects of polycyclic aromatic hydrocarbons released during combustion of fossil fuels and ionizing and nonionizing radiations. Sun lamps, which emit a continuous spectrum of near ultraviolet light of 290 nm to 315 nm were used for studies of predictive cell killing due to sunlight. Results showed that exposure to uv light (254 nm) may not be adequate to predict effects produced by sunlight. Data are included from studies on single-strand breaks and repair in DNA of cultured hamster cells exposed to uv or nearultraviolet light. The possible interactions of the polycyclic aromatic hydrocarbon 7,12-dimethylbenz(a)-anthracene (DmBA) alone or combined with exposure to x radiation, uv radiation (254 nm) or near ultraviolet simulating sunlight were compared for effects on cell survival
Networks in Cell Biology = Modelling cell biology with networks
Buchanan, Mark; Caldarelli, Guido; De Los Rios, Paolo; Rao, Francesco; Vendruscolo, M.
The science of complex biological networks is transforming research in areas ranging from evolutionary biology to medicine. This is the first book on the subject, providing a comprehensive introduction to complex network science and its biological applications. With contributions from key leaders in both network theory and modern cell biology, this book discusses the network science that is increasingly foundational for systems biology and the quantitative understanding of living systems. It ...
Ultrashort Phenomena in Biochemistry and Biological Signaling
International Nuclear Information System (INIS)
In biological phenomena there are indications that within the long pulse-length of the action potential on millisecond scale, there is additional ultrashort perturbation encoding that provides the brain with detailed information about the origin (location) and physiological characteristics. The objective is to identify the mechanism-of-action providing the potential for encoding in biological signal propagation. The actual molecular processes involved in the initiation of the action potential have been identified to be in the femtosecond and pico-second scale. The depolarization process of the cellular membrane itself, leading to the onset of the actionpotential that is transmitted to the brain, however is in the millisecond timeframe. One example of the femtosecond chemical interaction is the photoresponse of bacteriorhodopsin. No clear indication for the spatial encoding has so far been verified. Further research will be required on a cellular signal analysis level to confirm or deny the spatial and physiological encoding in the signal wave-trains of intercellular communications and sensory stimuli. The pathological encoding process for cardiac depolarization is however very pronounced and validated, however this electro-chemical process is in the millisecond amplitude and frequency modulation spectrum
Ultrashort Phenomena in Biochemistry and Biological Signaling
Splinter, Robert
In biological phenomena there are indications that within the long pulse-length of the action potential on millisecond scale, there is additional ultrashort perturbation encoding that provides the brain with detailed information about the origin (location) and physiological characteristics. The objective is to identify the mechanism-of-action providing the potential for encoding in biological signal propagation. The actual molecular processes involved in the initiation of the action potential have been identified to be in the femtosecond and pico-second scale. The depolarization process of the cellular membrane itself, leading to the onset of the actionpotential that is transmitted to the brain, however is in the millisecond timeframe. One example of the femtosecond chemical interaction is the photoresponse of bacteriorhodopsin. No clear indication for the spatial encoding has so far been verified. Further research will be required on a cellular signal analysis level to confirm or deny the spatial and physiological encoding in the signal wave-trains of intercellular communications and sensory stimuli. The pathological encoding process for cardiac depolarization is however very pronounced and validated, however this electro-chemical process is in the millisecond amplitude and frequency modulation spectrum.
TGF-β signaling in vascular biology and dysfunction
Institute of Scientific and Technical Information of China (English)
Marie-José Goumans; Zhen Liu; Peter ten Dijke
Transforming growth factor(TGF)-β family members are multifunctional cytokines that elicit their effects on cells,including endothelial and mural cells,via specific type I and type Ⅱ serine/threonine kinase receptors and intra-cellular Smad transcription factors.Knock-out mouse models for TGF-β family signaling pathway components have revealed their critical importance in proper yolk sac angiogenesis.Genefic studies in humans have linked mutations in these signaling components to specific cardiovascular syndromes such as hereditary hemorrhagic telangiectasia,primary pulmonary hypertension and Marfan syndrome.In this review,we present recent advances in our under-standing of the role of TGF-β receptor signaling in vascular biology and disease,and discuss how this may be appfied for therapy.
Multiscale entropy analysis of biological signals.
Costa, Madalena; Goldberger, Ary L; Peng, C-K
Traditional approaches to measuring the complexity of biological signals fail to account for the multiple time scales inherent in such time series. These algorithms have yielded contradictory findings when applied to real-world datasets obtained in health and disease states. We describe in detail the basis and implementation of the multiscale entropy (MSE) method. We extend and elaborate previous findings showing its applicability to the fluctuations of the human heartbeat under physiologic and pathologic conditions. The method consistently indicates a loss of complexity with aging, with an erratic cardiac arrhythmia (atrial fibrillation), and with a life-threatening syndrome (congestive heart failure). Further, these different conditions have distinct MSE curve profiles, suggesting diagnostic uses. The results support a general "complexity-loss" theory of aging and disease. We also apply the method to the analysis of coding and noncoding DNA sequences and find that the latter have higher multiscale entropy, consistent with the emerging view that so-called "junk DNA" sequences contain important biological information. PMID:15783351
Designer cell signal processing circuits for biotechnology
Bradley, Robert W.; Wang, Baojun
Microorganisms are able to respond effectively to diverse signals from their environment and internal metabolism owing to their inherent sophisticated information processing capacity. A central aim of synthetic biology is to control and reprogramme the signal processing pathways within living cells so as to realise repurposed, beneficial applications ranging from disease diagnosis and environmental sensing to chemical bioproduction. To date most examples of synthetic biological signal processing have been built based on digital information flow, though analogue computing is being developed to cope with more complex operations and larger sets of variables. Great progress has been made in expanding the categories of characterised biological components that can be used for cellular signal manipulation, thereby allowing synthetic biologists to more rationally programme increasingly complex behaviours into living cells. Here we present a current overview of the components and strategies that exist for designer cell signal processing and decision making, discuss how these have been implemented in prototype systems for therapeutic, environmental, and industrial biotechnological applications, and examine emerging challenges in this promising field. PMID:25579192
Designer cell signal processing circuits for biotechnology.
Bradley, Robert W; Wang, Baojun
Microorganisms are able to respond effectively to diverse signals from their environment and internal metabolism owing to their inherent sophisticated information processing capacity. A central aim of synthetic biology is to control and reprogramme the signal processing pathways within living cells so as to realise repurposed, beneficial applications ranging from disease diagnosis and environmental sensing to chemical bioproduction. To date most examples of synthetic biological signal processing have been built based on digital information flow, though analogue computing is being developed to cope with more complex operations and larger sets of variables. Great progress has been made in expanding the categories of characterised biological components that can be used for cellular signal manipulation, thereby allowing synthetic biologists to more rationally programme increasingly complex behaviours into living cells. Here we present a current overview of the components and strategies that exist for designer cell signal processing and decision making, discuss how these have been implemented in prototype systems for therapeutic, environmental, and industrial biotechnological applications, and examine emerging challenges in this promising field. PMID:25579192
Prostate cancer stem cell biology
Yu, Chunyan; Yao, Zhi; Jiang, Yuan; Keller, Evan T.
The cancer stem cell (CSC) model provides insights into pathophysiology of cancers and their therapeutic response. The CSC model has been both controversial, yet provides a foundation to explore cancer biology. In this review, we provide an overview of CSC concepts, biology and potential therapeutic avenues. We then focus on prostate CSC including (1) their purported origin as either basal-derived or luminal-derived cells; (2) markers used for prostate CSC identification; (3) alterations of s...
Defining Biological Networks for Noise Buffering and Signaling Sensitivity Using Approximate Bayesian Computation
Shuqiang Wang; Yanyan Shen; Changhong Shi; Tao Wang; Zhiming Wei; Hanxiong Li
Reliable information processing in cells requires high sensitivity to changes in the input signal but low sensitivity to random fluctuations in the transmitted signal. There are often many alternative biological circuits qualifying for this biological function. Distinguishing theses biological models and finding the most suitable one are essential, as such model ranking, by experimental evidence, will help to judge the support of the working hypotheses forming each model. Here, we employ the ...
International Nuclear Information System (INIS)
Studies of the action of N-ethylmaleimide (NEM), as an inhibitor of repair of x radioinduced injuries were extended from synchronous Chinese hamster cells to synchronous human HeLa cells. These studies showed a similar mode of action in both cell types lending support to the notion that conclusions may be extracted from such observations that are of fairly general applicability to mammalian cells. Radiation studies with NEM are being extended to hypoxic cells to inquire if NEM is effective relative to oxygen-independent damage. Observations relative to survival, DNA synthesis, and DNA strand elongation resulting from the addition products to DNA when cells were exposed to near uv in the presence of psoralen were extended. (U.S.)
Biological atomism and cell theory.
Nicholson, Daniel J
Biological atomism postulates that all life is composed of elementary and indivisible vital units. The activity of a living organism is thus conceived as the result of the activities and interactions of its elementary constituents, each of which individually already exhibits all the attributes proper to life. This paper surveys some of the key episodes in the history of biological atomism, and situates cell theory within this tradition. The atomistic foundations of cell theory are subsequently dissected and discussed, together with the theory's conceptual development and eventual consolidation. This paper then examines the major criticisms that have been waged against cell theory, and argues that these too can be interpreted through the prism of biological atomism as attempts to relocate the true biological atom away from the cell to a level of organization above or below it. Overall, biological atomism provides a useful perspective through which to examine the history and philosophy of cell theory, and it also opens up a new way of thinking about the epistemic decomposition of living organisms that significantly departs from the physicochemical reductionism of mechanistic biology. PMID:20934641
Alberts, Bruce; Lewis, Julian
Molecular Biology of the Cell is the classic in-dept text reference in cell biology. By extracting the fundamental concepts from this enormous and ever-growing field, the authors tell the story of cell biology, and create a coherent framework through which non-expert readers may approach the subject. Written in clear and concise language, and beautifully illustrated, the book is enjoyable to read, and it provides a clear sense of the excitement of modern biology. Molecular Biology of the Cell sets forth the current understanding of cell biology (completely updated as of Autumn 2001), and it explores the intriguing implications and possibilities of the great deal that remains unknown. The hallmark features of previous editions continue in the Fourth Edition. The book is designed with a clean and open, single-column layout. The art program maintains a completely consistent format and style, and includes over 1,600 photographs, electron micrographs, and original drawings by the authors. Clear and concise concept...
New Twists in Drosophila Cell Signaling.
Shilo, Ben-Zion
The discovery of a handful of conserved signaling pathways that dictate most aspects of embryonic and post-embryonic development of multicellular organisms has generated a universal view of animal development (Perrimon, N., Pitsouli, C., and Shilo, B. Z. (2012)Cold Spring Harb. Perspect. Biol.4, a005975). Although we have at hand most of the "hardware" elements that mediate cell communication events that dictate cell fate choices, we are still far from a comprehensive mechanistic understanding of these processes. One of the next challenges entails an analysis of developmental signaling pathways from the cell biology perspective. Where in the cell does signaling take place, and how do general cellular machineries and structures contribute to the regulation of developmental signaling? Another challenge is to examine these signaling pathways from a quantitative perspective, rather than as crude on/off switches. This requires more precise measurements, and incorporation of the time element to generate a dynamic sequence instead of frozen snapshots of the process. The quantitative outlook also brings up the issue of precision, and the unknown mechanisms that buffer variability in signaling between embryos, to produce a robust and reproducible output. Although these issues are universal to all multicellular organisms, they can be effectively tackled in theDrosophilamodel, by a combination of genetic manipulations, biochemical analyses, and a variety of imaging techniques. This review will present some of the recent advances that were accomplished by utilizing the versatility of theDrosophilasystem. PMID:26907691
Progesterone receptors - animal models and cell signalling in breast cancer: Diverse activation pathways for the progesterone receptor: possible implications for breast biology and cancer
International Nuclear Information System (INIS)
Progesterone and estradiol, and their nuclear receptors, play essential roles in the physiology of the reproductive tract, the mammary gland and the nervous system. Estrogens have traditionally been considered associated with an increased risk of breast cancer. There is, however, compelling evidence that progesterone plays an important role in breast cell proliferation and cancer. Herein, we review the possible role of progestins and the progesterone receptor-associated signaling pathways in the development of breast cancer, as well as the therapeutic possibilities arising from our growing knowledge of the activation of the progesterone receptor by other proliferative mechanisms
The biology of cancer stem cells.
Lobo, Neethan A; Shimono, Yohei; Qian, Dalong; Clarke, Michael F
Cancers originally develop from normal cells that gain the ability to proliferate aberrantly and eventually turn malignant. These cancerous cells then grow clonally into tumors and eventually have the potential to metastasize. A central question in cancer biology is, which cells can be transformed to form tumors? Recent studies elucidated the presence of cancer stem cells that have the exclusive ability to regenerate tumors. These cancer stem cells share many characteristics with normal stem cells, including self-renewal and differentiation. With the growing evidence that cancer stem cells exist in a wide array of tumors, it is becoming increasingly important to understand the molecular mechanisms that regulate self-renewal and differentiation because corruption of genes involved in these pathways likely participates in tumor growth. This new paradigm of oncogenesis has been validated in a growing list of tumors. Studies of normal and cancer stem cells from the same tissue have shed light on the ontogeny of tumors. That signaling pathways such as Bmi1 and Wnt have similar effects in normal and cancer stem cell self-renewal suggests that common molecular pathways regulate both populations. Understanding the biology of cancer stem cells will contribute to the identification of molecular targets important for future therapies. PMID:17645413
Cell signalling and phospholipid metabolism
Energy Technology Data Exchange (ETDEWEB)
Boss, W.F.
These studies explored whether phosphoinositide (PI) has a role in plants analogous to its role in animal cells. Although no parallel activity of PI in signal transduction was found in plant cells, activity of inositol phospholipid kinase was found to be modulated by light and by cell wall degrading enzymes. These studies indicate a major role for inositol phospholipids in plant growth and development as membrane effectors but not as a source of second messengers.
Cinnamaldehyde affects the biological behavior of human colorectal cancer cells and induces apoptosis via inhibition of the PI3K/Akt signaling pathway.
Li, Jiepin; Teng, Yuhao; Liu, Shenlin; Wang, Zifan; Chen, Yan; Zhang, Yingying; Xi, Songyang; Xu, Song; Wang, Ruiping; Zou, Xi
Cinnamaldehyde (CA) is a bioactive compound isolated from the stem bark of Cinnamomum cassia, that has been identified as an antiproliferative substance with pro-apoptotic effects on various cancer cell lines in vitro. In the present study, the effects of CA on human colon cancer cells were investigated at both the molecular and cellular levels. Three types of colorectal cancer cells at various stages of differentiation and invasive ability (SW480, HCT116 and LoVo) were treated with CA at final concentrations of 20, 40 and 80 µg/ml for 24 h. Compared with the control group, the proliferation inhibition rate of the human colorectal cancer cells following treatment with CA increased in a dose- and time-dependent manner. The invasion and adhesion abilities of the cells were significantly inhibited as indicated by Transwell and cell-matrix adhesion assays. Meanwhile, CA also upregulated the expression of E-cadherin and downregulated the expression of matrix metalloproteinase-2 (MMP-2) and MMP-9. CA also elevated the apoptotic rate. The levels of pro-apoptotic genes were upregulated while the levels of apoptosis inhibitory genes were decreased which further confirmed the pro-apoptotic effect of CA. In order to explore the mechanism of CA-induced apoptosis, insulin-like growth factor-1 (IGF-1) and PI3K inhibitor (LY294002) were used to regulate the phosphoinositide 3-kinase (PI3K)/AKT pathway. The transcription activity of PI3K/AKT was markedly inhibited by CA, as well as IGF-1 which functions as an anti-apoptotic factor. In conclusion, CA has the potential to be developed as a new antitumor drug. The mechanisms of action involve the regulation of expression of genes involved in apoptosis, invasion and adhesion via inhibition of the PI3K/Akt signaling pathway. PMID:26677144
Cell Biology and Pathology of Podocytes
Greka, Anna; Mundel, Peter
As an integral member of the filtration barrier in the kidney glomerulus, the podocyte is in a unique geographical position: It is exposed to chemical signals from the urinary space (Bowman's capsule), it receives and transmits chemical and mechanical signals to/from the glomerular basement membrane upon which it elaborates, and it receives chemical and mechanical signals from the vascular space with which it also communicates. As with every cell, the ability of the podocyte to receive signals from the surrounding environment and to translate them to the intracellular milieu is dependent largely on molecules residing on the cell membrane. These molecules are the first-line soldiers in the ongoing battle to sense the environment, to respond to friendly signals, and to defend against injurious foes. In this review, we take a membrane biologist's view of the podocyte, examining the many membrane receptors, channels, and other signaling molecules that have been implicated in podocyte biology. Although we attempt to be comprehensive, our goal is not to capture every membrane-mediated pathway but rather to emphasize that this approach may be fruitful in understanding the podocyte and its unique properties. PMID:22054238
Cohen, Paul; Spiegelman, Bruce M
The worldwide epidemic of obesity and type 2 diabetes has greatly increased interest in the biology and physiology of adipose tissues. Adipose (fat) cells are specialized for the storage of energy in the form of triglycerides, but research in the last few decades has shown that fat cells also play a critical role in sensing and responding to changes in systemic energy balance. White fat cells secrete important hormone-like molecules such as leptin, adiponectin, and adipsin to influence processes such as food intake, insulin sensitivity, and insulin secretion. Brown fat, on the other hand, dissipates chemical energy in the form of heat, thereby defending against hypothermia, obesity, and diabetes. It is now appreciated that there are two distinct types of thermogenic fat cells, termed brown and beige adipocytes. In addition to these distinct properties of fat cells, adipocytes exist within adipose tissue, where they are in dynamic communication with immune cells and closely influenced by innervation and blood supply. This review is intended to serve as an introduction to adipose cell biology and to familiarize the reader with how these cell types play a role in metabolic disease and, perhaps, as targets for therapeutic development. PMID:27528697
Syndecans, signaling, and cell adhesion
DEFF Research Database (Denmark)
Couchman, J R; Woods, A
structures within the heparan sulfate chains, leaving the roles of chondroitin sulfate chains and extracellular portion of the core proteins to be elucidated. Evidence that syndecans are a class of receptor involved in cell adhesion is mounting, and their small cytoplasmic domains may link with the...... transmembrane signaling from matrix to cytoskeleton, as proposed for other classes of adhesion receptors....
Stem cell biology meets systems biology
Roeder, I.; Radtke, F.
Stem cells and their descendents are the building blocks of life. How stem cell populations guarantee their maintenance and/or self-renewal, and how individual stem cells decide to transit from one cell stage to another to generate different cell types are long-standing and fascinating questions in the field. Here, we review the discussions that took place at a recent EMBO conference in Cambridge, UK, in which these questions were placed in the context of the latest advances in stem cell biol...
S-Nitrosothiol Signaling in Respiratory Biology
Gaston, Benjamin; Singel, David; Doctor, Allan; Stamler, Jonathan S.
Genetic and biochemical data demonstrate a pivotal role for S-nitrosothiols (SNOs) in mediating the actions of nitric oxide synthases (NOSs). SNOs serve to convey NO bioactivity and to regulate protein function. This understanding is of immediate interest to the pulmonary clinical and research communities. This article reviews the following: (1) biochemical and cellular evidence that SNOs in amino acids, peptides, and proteins elicit NOS-dependent signaling in the respiratory system and (2) s...
Biological fuel cells and their applications
Shukla, AK; Suresh, P; Berchmans, S; Rajendran, A.
One type of genuine fuel cell that does hold promise in the long-term is the biological fuel cell. Unlike conventional fuel cells, which employ hydrogen, ethanol and methanol as fuel, biological fuel cells use organic products produced by metabolic processes or use organic electron donors utilized in the growth processes as fuels for current generation. A distinctive feature of biological fuel cells is that the electrode reactions are controlled by biocatalysts, i.e. the biological redox-reac...
Wavelet-based detection of transients in biological signals
Mzaik, Tahsin; Jagadeesh, Jogikal M.
This paper presents two multiresolution algorithms for detection and separation of mixed signals using the wavelet transform. The first algorithm allows one to design a mother wavelet and its associated wavelet grid that guarantees the separation of signal components if information about the expected minimum signal time and frequency separation of the individual components is known. The second algorithm expands this idea to design two mother wavelets which are then combined to achieve the required separation otherwise impossible with a single wavelet. Potential applications include many biological signals such as ECG, EKG, and retinal signals.
Laboratory of Cell and Molecular Biology
Federal Laboratory Consortium — The Laboratory of Cell and Molecular Biology investigates the organization, compartmentalization, and biochemistry of eukaryotic cells and the pathology associated...
Short-time multifractal analysis: application to biological signals
International Nuclear Information System (INIS)
Some signals obtained from biological systems evince a great complexity. Recently, new tools which allow the extraction of information from them have been proposed. In particular, multifractal analysis gives a quantification of the degree and distribution of irregularities in a signal. A possible approach for this analysis is the one based on wavelet leaders. In this work, the use of wavelet leader based multifractal analysis in short-time windows is proposed in order to analyze the evolution of the multifractal behavior of biological signals. In particular, applications of this technique to the detection of ischemic episodes in heart rate variability signals and to voice activity detection are examined. It is shown that the study of the time evolution of indexes obtained with the proposed new method gives useful information hidden in the signals.
Multiway modeling and analysis in stem cell systems biology
Vandenberg Scott L; Bennett Kristin; Aguis Pheadra; Acar Evrim; Yener Bülent; Plopper George E
Abstract Background Systems biology refers to multidisciplinary approaches designed to uncover emergent properties of biological systems. Stem cells are an attractive target for this analysis, due to their broad therapeutic potential. A central theme of systems biology is the use of computational modeling to reconstruct complex systems from a wealth of reductionist, molecular data (e.g., gene/protein expression, signal transduction activity, metabolic activity, etc.). A number of deterministi...
Atomic force microscopy in cell biology
Institute of Scientific and Technical Information of China (English)
LU Zhexue; ZHANG Zhiling; PANG Daiwen
The history, characteristic, operation modes and coupling techniques of atomic force microscopy (AFM) are introduced. Then the application in cell biology is reviewed in four aspects: cell immobilization methods, cell imaging, force spectrum study and cell manipulation. And the prospect of AFM application in cell biology is discussed.
Automatic detection of biological cells
International Nuclear Information System (INIS)
The present research work has dealt with the analysis of biological cell images in general, and more specially with the cervical cells. This work was carried out in order to develop an automaton leading to a better prevention of cancer through automated mass screening. The device has been implemented on Motorola 68.000 microprocessor system. The automaton carries out cell nucleus analysis in several steps. The main steps are: - First: the automaton focuses on an individual cell nucleus among the smear's cell (about 10.000), - Second: it process each nucleus image. The digital processing yields geometrical of the nucleus (area and perimeter) for each cell. These data are stored in a local memory for further discriminant analysis by a microcomputer. In this way smears are classed in two groups: hale smears and uncertain smears. The automaton uses a wired logic for image acquisition and its software algorithms provide image reconstruction. The reconstruction algorithms are general purpose. Tests have proved that they can reconstruct any two dimensional images independently of its geometrical form. Moreover they can make the reconstruction of any image among the several images present in observation field. The processing times registered during the tests (for different cases) were situated, all of them, below three minutes for 10,000 images (each of them formed by an average of 450 pixels). The interest of the method is generality and speed. The only restriction is the primary device sensor (CCD linear array) length. Thus the automaton application can be extended beyond the biological image field. (author)
Biological Signal Processing with a Genetic Toggle Switch
Patrick Hillenbrand; Georg Fritz; Ulrich Gerland
Complex gene regulation requires responses that depend not only on the current levels of input signals but also on signals received in the past. In digital electronics, logic circuits with this property are referred to as sequential logic, in contrast to the simpler combinatorial logic without such internal memory. In molecular biology, memory is implemented in various forms such as biochemical modification of proteins or multistable gene circuits, but the design of the regulatory interface, ...
Biological Signal Processing with a Genetic Toggle Switch
Hillenbrand, Patrick; Fritz, Georg; Gerland, Ulrich
Complex gene regulation requires responses that depend not only on the current levels of input signals but also on signals received in the past. In digital electronics, logic circuits with this property are referred to as sequential logic, in contrast to the simpler combinatorial logic without such internal memory. In molecular biology, memory is implemented in various forms such as biochemical modification of proteins or multistable gene circuits, but the design of the regulatory interface, which processes the input signals and the memory content, is often not well understood. Here, we explore design constraints for such regulatory interfaces using coarse-grained nonlinear models and stochastic simulations of detailed biochemical reaction networks. We test different designs for biological analogs of the most versatile memory element in digital electronics, the JK-latch. Our analysis shows that simple protein-protein interactions and protein-DNA binding are sufficient, in principle, to implement genetic circuits with the capabilities of a JK-latch. However, it also exposes fundamental limitations to its reliability, due to the fact that biological signal processing is asynchronous, in contrast to most digital electronics systems that feature a central clock to orchestrate the timing of all operations. We describe a seemingly natural way to improve the reliability by invoking the master-slave concept from digital electronics design. This concept could be useful to interpret the design of natural regulatory circuits, and for the design of synthetic biological systems. PMID:23874595
Cancer systems biology: signal processing for cancer research
Institute of Scientific and Technical Information of China (English)
Olli Yli-Harja; Antti Ylip(a)(a); Matti Nykter; Wei Zhang
In this editorial we introduce the research paradigms of signal processing in the era of systems biology. Signal processing is a field of science traditionally focused on modeling electronic and communications systems, but recently it has turned to biological applications with astounding results. The essence of signal processing is to describe the natural world by mathematical models and then, based on these models, develop efficient computational tools for solving engineering problems. Here, we underline, with examples, the endless possibilities which arise when the battle-hardened tools of engineering are applied to solve the problems that have tormented cancer researchers. Based on this approach, a new field has emerged, called cancer systems biology. Despite its short history, cancer systems biology has already produced several success stories tackling previously impracticable problems. Perhaps most importantly, it has been accepted as an integral part of the major endeavors of cancer research, such as analyzing the genomic and epigenomic data produced by The Cancer Genome Atlas (TCGA) project. Finally, we show that signal processing and cancer research, two fields that are seemingly distant from each other, have merged into a field that is indeed more than the sum of its parts.
The universality and biological significance of signal molecules with intracellular-extracellular compatible functions
Institute of Scientific and Technical Information of China (English)
Generally,cell signal molecules are classified into the extracellular signal molecules (the first messengers) and the intracellular signal ones (the second messengers).Cyclic adenosine monophosphate (cAMP),calcium ions and calmodulin (CaM) are the traditional intracellular messengers,but they are also present in extracellular matrix (ECM).Some of them have been discovered to act as the first messengers through cell surface receptors.Other second messengers,such as cyclic guanosine monophosphate (cGMP),cyclic adenosine diphosphate ribose (cADPR) and annexin,are also found existing outside animal and plant cells.The existence of these messengers with intracellular-extracellular compatible functions in cells may be a regular biological phenomenon.These compatible messengers might be the communication factors between intracellular and extracellular regions or among the cell populations,and are also important in regulating cell development procedure.
HBpF-proBDNF: A New Tool for the Analysis of Pro-Brain Derived Neurotrophic Factor Receptor Signaling and Cell Biology.
Gaub, Perrine; de Léon, Andrès; Gibon, Julien; Soubannier, Vincent; Dorval, Geneviève; Séguéla, Philippe; Barker, Philip A
Neurotrophins activate intracellular signaling pathways necessary for neuronal survival, growth and apoptosis. The most abundant neurotrophin in the adult brain, brain-derived neurotrophic factor (BDNF), is first synthesized as a proBDNF precursor and recent studies have demonstrated that proBDNF can be secreted and that it functions as a ligand for a receptor complex containing p75NTR and sortilin. Activation of proBDNF receptors mediates growth cone collapse, reduces synaptic activity, and facilitates developmental apoptosis of motoneurons but the precise signaling cascades have been difficult to discern. To address this, we have engineered, expressed and purified HBpF-proBDNF, an expression construct containing a 6X-HIS tag, a biotin acceptor peptide (BAP) sequence, a PreScission™ Protease cleavage site and a FLAG-tag attached to the N-terminal part of murine proBDNF. Intact HBpF-proBDNF has activities indistinguishable from its wild-type counterpart and can be used to purify proBDNF signaling complexes or to monitor proBDNF endocytosis and retrograde transport. HBpF-proBDNF will be useful for characterizing proBDNF signaling complexes and for deciphering the role of proBDNF in neuronal development, synapse function and neurodegenerative disease. PMID:26950209
A Synthetic Biology Approach Reveals a CXCR4-G13-Rho Signaling Axis Driving Transendothelial Migration of Metastatic Breast Cancer Cells
Yagi, Hiroshi; Tan, Wenfu; Dillenburg-Pilla, Patricia; Armando, Sylvain; Amornphimoltham, Panomwat; Simaan, May; Weigert, Roberto; Molinolo, Alfredo A.; Bouvier, Michel; Gutkind, J. Silvio
Tumor cells can co-opt the pro-migratory activity of chemokines and their cognate G protein-coupled receptors (GPCRs) to metastasize to regional lymph nodes or distant organs. Indeed, the migration toward SDF-1 (stromal cell-derived factor-1) of tumor cells bearing CXCR4 [chemokine (C-X-C motif) receptor 4] has been implicated in the lymphatic and organ-specific metastasis of various human malignancies. Here, we used chimeric G proteins and GPCRs activated solely by artificial ligands to sele...
Evolutionary cell biology: two origins, one objective.
Lynch, Michael; Field, Mark C; Goodson, Holly V; Malik, Harmit S; Pereira-Leal, José B; Roos, David S; Turkewitz, Aaron P; Sazer, Shelley
All aspects of biological diversification ultimately trace to evolutionary modifications at the cellular level. This central role of cells frames the basic questions as to how cells work and how cells come to be the way they are. Although these two lines of inquiry lie respectively within the traditional provenance of cell biology and evolutionary biology, a comprehensive synthesis of evolutionary and cell-biological thinking is lacking. We define evolutionary cell biology as the fusion of these two eponymous fields with the theoretical and quantitative branches of biochemistry, biophysics, and population genetics. The key goals are to develop a mechanistic understanding of general evolutionary processes, while specifically infusing cell biology with an evolutionary perspective. The full development of this interdisciplinary field has the potential to solve numerous problems in diverse areas of biology, including the degree to which selection, effectively neutral processes, historical contingencies, and/or constraints at the chemical and biophysical levels dictate patterns of variation for intracellular features. These problems can now be examined at both the within- and among-species levels, with single-cell methodologies even allowing quantification of variation within genotypes. Some results from this emerging field have already had a substantial impact on cell biology, and future findings will significantly influence applications in agriculture, medicine, environmental science, and synthetic biology. PMID:25404324
Long-term depression: a cell biological view
Sheng, Morgan; Ertürk, Ali
Recent studies of the molecular mechanisms of long-term depression (LTD) suggest a crucial role for the signalling pathways of apoptosis (programmed cell death) in the weakening and elimination of synapses and dendritic spines. With this backdrop, we suggest that LTD can be considered as the electrophysiological aspect of a larger cell biological programme of synapse involution, which uses localized apoptotic mechanisms to sculpt synapses and circuits without causing cell death.
Cell Wall Integrity Signaling in Saccharomyces cerevisiae
Levin, David E.
The yeast cell wall is a highly dynamic structure that is responsible for protecting the cell from rapid changes in external osmotic potential. The wall is also critical for cell expansion during growth and morphogenesis. This review discusses recent advances in understanding the various signal transduction pathways that allow cells to monitor the state of the cell wall and respond to environmental challenges to this structure. The cell wall integrity signaling pathway controlled by the small...
Defining Biological Networks for Noise Buffering and Signaling Sensitivity Using Approximate Bayesian Computation
Directory of Open Access Journals (Sweden)
Shuqiang Wang
Full Text Available Reliable information processing in cells requires high sensitivity to changes in the input signal but low sensitivity to random fluctuations in the transmitted signal. There are often many alternative biological circuits qualifying for this biological function. Distinguishing theses biological models and finding the most suitable one are essential, as such model ranking, by experimental evidence, will help to judge the support of the working hypotheses forming each model. Here, we employ the approximate Bayesian computation (ABC method based on sequential Monte Carlo (SMC to search for biological circuits that can maintain signaling sensitivity while minimizing noise propagation, focusing on cases where the noise is characterized by rapid fluctuations. By systematically analyzing three-component circuits, we rank these biological circuits and identify three-basic-biological-motif buffering noise while maintaining sensitivity to long-term changes in input signals. We discuss in detail a particular implementation in control of nutrient homeostasis in yeast. The principal component analysis of the posterior provides insight into the nature of the reaction between nodes.
Micro/nano-fabrication technologies for cell biology
Qian, Tongcheng; Wang, Yingxiao
Micro/nano-fabrication techniques, such as soft lithography and electrospinning, have been well-developed and widely applied in many research fields in the past decade. Due to the low costs and simple procedures, these techniques have become important and popular for biological studies. In this review, we focus on the studies integrating micro/nano-fabrication work to elucidate the molecular mechanism of signaling transduction in cell biology. We first describe different micro/nano-fabricatio...
Cytotoxicity and mitogenicity assays with real-time and label-free monitoring of human granulosa cells with an impedance-based signal processing technology intergrating micro-electronics and cell biology.
Oktem, Ozgur; Bildik, Gamze; Senbabaoglu, Filiz; Lack, Nathan A; Akin, Nazli; Yakar, Feridun; Urman, Defne; Guzel, Yilmaz; Balaban, Basak; Iwase, Akira; Urman, Bulent
A recently developed technology (xCelligence) integrating micro-electronics and cell biology allows real-time, uninterrupted and quantitative analysis of cell proliferation, viability and cytotoxicity by measuring the electrical impedance of the cell population in the wells without using any labeling agent. In this study we investigated if this system is a suitable model to analyze the effects of mitogenic (FSH) and cytotoxic (chemotherapy) agents with different toxicity profiles on human granulosa cells in comparison to conventional methods of assessing cell viability, DNA damage, apoptosis and steroidogenesis. The system generated the real-time growth curves of the cells, and determined their doubling times, mean cell indices and generated dose-response curves after exposure to cytotoxic and mitogenic stimuli. It accurately predicted the gonadotoxicity of the drugs and distinguished less toxic agents (5-FU and paclitaxel) from more toxic ones (cisplatin and cyclophosphamide). This platform can be a useful tool for specific end-point assays in reproductive toxicology. PMID:26746109
Wearable System for Acquisition and Monitoring of Biological Signals
Piccinini, D. J.; Andino, N. B.; Ponce, S. D.; Roberti, MA; López, y. N.
This paper presents a modular, wearable system for acquisition and wireless transmission of biological signals. Configurable slaves for different signals (such as ECG, EMG, inertial sensors, and temperature) based in the ADS1294 Medical Analog Front End are connected to a Master, based in the CC3200 microcontroller, both from Texas Instruments. The slaves are configurable according to the specific application, providing versatility to the wearable system. The battery consumption is reduced, through a couple of Li-ion batteries and the circuit has also a battery charger. A custom made box was designed and fabricated in a 3D printer, preserving the requirements of low cost, low weight and safety recommendations.
Bone biology, signaling pathways, and therapeutic targets for osteoporosis.
Iñiguez-Ariza, Nicole M; Clarke, Bart L
Major advances have occurred recently in the treatment of osteoporosis in recent years. Most patients are currently treated with bisphosphonates, denosumab, raloxifene, or teriparatide, and in some countries, strontium ranelate. Strontium ranelate and calcitonin have recently had their use restricted due to cardiovascular concerns and malignancy, respectively. The available agents have generally provided excellent options that effectively reduce fracture risk. New targets are being sought based on appreciation of the bone biology and signaling pathways involved in bone formation and resorption. These agents will directly target these signaling pathways, and further expand the options available for treatment of osteoporosis. PMID:26255682
Microfluidic tools for cell biological research
Velve-Casquillas, Guilhem; Le Berre, Maël; Piel, Matthieu; Tran, Phong T.
Microfluidic technology is creating powerful tools for cell biologists to control the complete cellular microenvironment, leading to new questions and new discoveries. We review here the basic concepts and methodologies in designing microfluidic devices, and their diverse cell biological applications.
Systems Biology: The Role of Engineering in the Reverse Engineering of Biological Signaling
Iglesias, Pablo A.
One of the principle tasks of systems biology has been the reverse engineering of signaling networks. Because of the striking similarities to engineering systems, a number of analysis and design tools from engineering disciplines have been used in this process. This review looks at several examples including the analysis of homeostasis using control theory, the attenuation of noise using signal processing, statistical inference and the use of information theory to understand both binary decis...
Proteomes and Neural Stem Cells: cellular signalling during differentiation
Czech Academy of Sciences Publication Activity Database
Skalníková, Helena; Halada, Petr; Vodička, Petr; Motlík, Jan; Horning, O.; Jensen, O. N.; Gadher, S. J.; Pelech, S.; Kovářová, Hana
Cambridge : -, 2007, s. 1-1. [BSPR-EBI Meeting: Integrative Proteomics: From Molecules to Systems,. Cambridge (GB), 25.07.2007-27.07.2007] Institutional research plan: CEZ:AV0Z50450515; CEZ:AV0Z50200510 Keywords : neural stem cells * differentiation * signalling * proteome Subject RIV: EB - Genetics ; Molecular Biology
Quesenberry, Peter J.; Colvin, Gerald A; Lambert, Jean-Francois; Frimberger, Angela E.; Dooner, Mark S.; Mcauliffe, Christina I.; Miller, Caroline; Becker, Pamela; Badiavas, Evangelis; Falanga, Vincent J.; Elfenbein, Gerald; Lum, Lawrence G.
Recent studies have indicated that bone marrow stem cells are capable of generating muscle, cardiac, hepatic, renal, and bone cells. Purified hematopoietic stem cells have generated cardiac and hepatic cells and reversed disease manifestations in these tissues. Hematopoietic stem cells also alter phenotype with cell cycle transit or circadian phase. During a cytokine stimulated cell cycle transit, reversible alterations of differentiation and engraftment occur. Primitive hematopoietic stem ce...
Glycan Engineering for Cell and Developmental Biology
Griffin, Matthew E.; Hsieh-Wilson, Linda C.
Cell-surface glycans are a diverse class of macromolecules that participate in many key biological processes, including cell-cell communication, development, and disease progression. Thus, the ability to modulate the structures of glycans on cell surfaces provides a powerful means not only to understand fundamental processes but also to direct activity and elicit desired cellular responses. Here, we describe methods to sculpt glycans on cell surfaces and highlight recent successes in which artificially engineered glycans have been employed to control biological outcomes such as the immune response and stem cell fate. PMID:26933739
From high dilutions to digital biology: the physical nature of the biological signal.
Thomas, Yolène
The memory of water was a radical idea that arose in the laboratory of Jacques Benveniste in the late 1980s. Twenty-five years have passed and yet the often angry debate on its merits continues despite the increasing number of scientists who have reported confirmation of the basic results. One working hypothesis was that molecules can communicate with each other, exchanging information without being in physical contact and that at least some biological functions can be mimicked by certain energetic modes characteristics of a given molecule. These considerations informed exploratory research which led to the speculation that biological signaling might be transmissible by electromagnetic means. Around 1991, the transfer of specific molecular signals to sensitive biological systems was achieved using an amplifier and electromagnetic coils. In 1995, a more sophisticated procedure was established to record, digitize and replay these signals using a multimedia computer. From a physical and chemical perspective, these experiments pose a riddle, since it is not clear what mechanism can sustain such 'water memory' of the exposure to molecular signals. From a biological perspective, the puzzle is what nature of imprinted effect (water structure) can impact biological function. A parallel can be drawn between this debate on the memory of water, which presumes that the action of molecules is mediated by an electromagnetic phenomenon, and the often acrimonious debate on the transmission of nerve influxes via synaptic transfer of specific molecules, neurotransmitters. The latter debate began in 1921 with the first experiments by Loewi and was still active in 1949, 28 years later. A strong reluctance to accept research that questions basic aspects of long-accepted biochemical paradigms is to be expected. In this paper we will provide a brief summary of experiments relating to the memory of water: the earlier work on high dilutions (HD) and then the experiments, which followed and
Qualitative networks: a symbolic approach to analyze biological signaling networks
Directory of Open Access Journals (Sweden)
Henzinger Thomas A
Full Text Available Abstract Background A central goal of Systems Biology is to model and analyze biological signaling pathways that interact with one another to form complex networks. Here we introduce Qualitative networks, an extension of Boolean networks. With this framework, we use formal verification methods to check whether a model is consistent with the laboratory experimental observations on which it is based. If the model does not conform to the data, we suggest a revised model and the new hypotheses are tested in-silico. Results We consider networks in which elements range over a small finite domain allowing more flexibility than Boolean values, and add target functions that allow to model a rich set of behaviors. We propose a symbolic algorithm for analyzing the steady state of these networks, allowing us to scale up to a system consisting of 144 elements and state spaces of approximately 1086 states. We illustrate the usefulness of this approach through a model of the interaction between the Notch and the Wnt signaling pathways in mammalian skin, and its extensive analysis. Conclusion We introduce an approach for constructing computational models of biological systems that extends the framework of Boolean networks and uses formal verification methods for the analysis of the model. This approach can scale to multicellular models of complex pathways, and is therefore a useful tool for the analysis of complex biological systems. The hypotheses formulated during in-silico testing suggest new avenues to explore experimentally. Hence, this approach has the potential to efficiently complement experimental studies in biology.
Label-Free Biosensors for Cell Biology
Ye Fang
Label-free biosensors for studying cell biology have finally come of age. Recent developments have advanced the biosensors from low throughput and high maintenance research tools to high throughput and low maintenance screening platforms. In parallel, the biosensors have evolved from an analytical tool solely for molecular interaction analysis to powerful platforms for studying cell biology at the whole cell level. This paper presents historical development, detection principles, and applicat...
Shared signaling pathways in normal and breast cancer stem cells
Directory of Open Access Journals (Sweden)
Gautam K Malhotra
Full Text Available Recent advances in our understanding of breast cancer biology have led to the identification of a subpopulation of cells within tumors that appear to be responsible for initiating and propagating the cancer. These tumor initiating cells are not only unique in their ability to generate tumors, but also share many similarities with elements of normal adult tissue stem cells, and have therefore been termed cancer stem cells (CSCs. These CSCs often inappropriately use many of the same signaling pathways utilized by their normal stem cell counterparts which may present a challenge to the development of CSC specific therapies. Here, we discuss three major stem cell signaling pathways (Notch, Wnt, and Hedgehog; with a focus on their function in normal mammary gland development and their misuse in breast cancer stem cell fate determination.
Wnt signalling pathway parameters for mammalian cells.
Tan, Chin Wee; Gardiner, Bruce S; Hirokawa, Yumiko; Layton, Meredith J; Smith, David W; Burgess, Antony W
Wnt/β-catenin signalling regulates cell fate, survival, proliferation and differentiation at many stages of mammalian development and pathology. Mutations of two key proteins in the pathway, APC and β-catenin, have been implicated in a range of cancers, including colorectal cancer. Activation of Wnt signalling has been associated with the stabilization and nuclear accumulation of β-catenin and consequential up-regulation of β-catenin/TCF gene transcription. In 2003, Lee et al. constructed a computational model of Wnt signalling supported by experimental data from analysis of time-dependent concentration of Wnt signalling proteins in Xenopus egg extracts. Subsequent studies have used the Xenopus quantitative data to infer Wnt pathway dynamics in other systems. As a basis for understanding Wnt signalling in mammalian cells, a confocal live cell imaging measurement technique is developed to measure the cell and nuclear volumes of MDCK, HEK293T cells and 3 human colorectal cancer cell lines and the concentrations of Wnt signalling proteins β-catenin, Axin, APC, GSK3β and E-cadherin. These parameters provide the basis for formulating Wnt signalling models for kidney/intestinal epithelial mammalian cells. There are significant differences in concentrations of key proteins between Xenopus extracts and mammalian whole cell lysates. Higher concentrations of Axin and lower concentrations of APC are present in mammalian cells. Axin concentrations are greater than APC in kidney epithelial cells, whereas in intestinal epithelial cells the APC concentration is higher than Axin. Computational simulations based on Lee's model, with this new data, suggest a need for a recalibration of the model.A quantitative understanding of Wnt signalling in mammalian cells, in particular human colorectal cancers requires a detailed understanding of the concentrations of key protein complexes over time. Simulations of Wnt signalling in mammalian cells can be initiated with the parameters
Wnt signalling pathway parameters for mammalian cells.
Directory of Open Access Journals (Sweden)
Chin Wee Tan
Full Text Available Wnt/β-catenin signalling regulates cell fate, survival, proliferation and differentiation at many stages of mammalian development and pathology. Mutations of two key proteins in the pathway, APC and β-catenin, have been implicated in a range of cancers, including colorectal cancer. Activation of Wnt signalling has been associated with the stabilization and nuclear accumulation of β-catenin and consequential up-regulation of β-catenin/TCF gene transcription. In 2003, Lee et al. constructed a computational model of Wnt signalling supported by experimental data from analysis of time-dependent concentration of Wnt signalling proteins in Xenopus egg extracts. Subsequent studies have used the Xenopus quantitative data to infer Wnt pathway dynamics in other systems. As a basis for understanding Wnt signalling in mammalian cells, a confocal live cell imaging measurement technique is developed to measure the cell and nuclear volumes of MDCK, HEK293T cells and 3 human colorectal cancer cell lines and the concentrations of Wnt signalling proteins β-catenin, Axin, APC, GSK3β and E-cadherin. These parameters provide the basis for formulating Wnt signalling models for kidney/intestinal epithelial mammalian cells. There are significant differences in concentrations of key proteins between Xenopus extracts and mammalian whole cell lysates. Higher concentrations of Axin and lower concentrations of APC are present in mammalian cells. Axin concentrations are greater than APC in kidney epithelial cells, whereas in intestinal epithelial cells the APC concentration is higher than Axin. Computational simulations based on Lee's model, with this new data, suggest a need for a recalibration of the model.A quantitative understanding of Wnt signalling in mammalian cells, in particular human colorectal cancers requires a detailed understanding of the concentrations of key protein complexes over time. Simulations of Wnt signalling in mammalian cells can be initiated
Ku, Ja-Lok; Park, Jae-Gahb
SNU (Seoul National University) cell lines have been established from Korean cancer patients since 1982. Of these 109 cell lines have been characterized and reported, i.e., 17 colorectal carcinoma, 12 hepatocellular carcinoma, 11 gastric carcinoma, 12 uterine cervical carcinoma, 17 B-lymphoblastoid cell lines derived from cancer patients, 5 ovarian carcinoma, 3 malignant mixed Mllerian tumor, 6 laryngeal squamous cell carcinoma, 7 renal cell carcinoma, 9 brain tumor, 6 biliary tract, and 4 pa...
Hierarchical feedback modules and reaction hubs in cell signaling networks.
Directory of Open Access Journals (Sweden)
Jianfeng Xu
Full Text Available Despite much effort, identification of modular structures and study of their organizing and functional roles remain a formidable challenge in molecular systems biology, which, however, is essential in reaching a systematic understanding of large-scale cell regulation networks and hence gaining capacity of exerting effective interference to cell activity. Combining graph theoretic methods with available dynamics information, we successfully retrieved multiple feedback modules of three important signaling networks. These feedbacks are structurally arranged in a hierarchical way and dynamically produce layered temporal profiles of output signals. We found that global and local feedbacks act in very different ways and on distinct features of the information flow conveyed by signal transduction but work highly coordinately to implement specific biological functions. The redundancy embodied with multiple signal-relaying channels and feedback controls bestow great robustness and the reaction hubs seated at junctions of different paths announce their paramount importance through exquisite parameter management. The current investigation reveals intriguing general features of the organization of cell signaling networks and their relevance to biological function, which may find interesting applications in analysis, design and control of bio-networks.
Chemical approaches to studying stem cell biology
Institute of Scientific and Technical Information of China (English)
Wenlin Li; Kai Jiang; Wanguo Wei; Yan Shi; Sheng Ding
Stem cells,including both pluripotent stem cells and multipotent somatic stem cells,hold great potential for interrogating the mechanisms of tissue development,homeostasis and pathology,and for treating numerous devastating diseases.Establishment of in vitro platforms to faithfully maintain and precisely manipulate stem cell fates is essential to understand the basic mechanisms of stem cell biology,and to translate stem cells into regenerative medicine.Chemical approaches have recently provided a number of small molecules that can be used to control cell selfrenewal,lineage differentiation,reprogramming and regeneration.These chemical modulators have been proven to be versatile tools for probing stem cell biology and manipulating cell fates toward desired outcomes.Ultimately,this strategy is promising to be a new frontier for drug development aimed at endogenous stem cell modulation.
Micro and nanoplatforms for biological cell analysis
DEFF Research Database (Denmark)
Svendsen, Winnie Edith; Castillo, Jaime; Moresco, Jacob Lange;
while working in a biological environment maintaining the cells viability and adding analyte are addressed and discussed. An example of a cell culturing chamber useful for both adherent and non-adherent cells, with the capability of adding analyte is given, a small discussion of in vitro cellular......In this paper some of the technological platforms developed in our group for biological cell analysis will be highlighted. The paper first presents a short introduction pinpointing the advantages of using micro and nano technology in cellular studies. The issues of requiring transient analysis...... sorting cells using dielectrophoresis will be given, aiming at early cancer detection....
Photon emission and quantum signalling in biological systems
Mayburov, S. N.
Ultra-weak, non-termal photon emission is universal feature of living organisms and plants. In our experiment the fine structure of optical radiation emitted by the loach fish eggs is studied. It was shown earlier that such radiation performs the signaling between the distant fish egg samples, which result in significant correlations of their growth. The optical radiation of biological sample was measured by the cooled photomultiplier in photocurrent regime, it was found that the main bulk of radiation is produced in form of short-time quasi-periodic bursts. The analysis of radiation temporal structure indicates that the information about egg age and growth is encoded via the values of time intervals between neighbor bursts with the height higher than some fixed level. The applications of such biological radiation in medical diagnostics and biotechnology are considered.
Photon emission and quantum signalling in biological systems
Directory of Open Access Journals (Sweden)
Mayburov S.N.
Full Text Available Ultra-weak, non-termal photon emission is universal feature of living organisms and plants. In our experiment the fine structure of optical radiation emitted by the loach fish eggs is studied. It was shown earlier that such radiation performs the signaling between the distant fish egg samples, which result in significant correlations of their growth. The optical radiation of biological sample was measured by the cooled photomultiplier in photocurrent regime, it was found that the main bulk of radiation is produced in form of short-time quasi-periodic bursts. The analysis of radiation temporal structure indicates that the information about egg age and growth is encoded via the values of time intervals between neighbor bursts with the height higher than some fixed level. The applications of such biological radiation in medical diagnostics and biotechnology are considered.
DMPD: Lysophospholipid receptors: signaling and biology. [Dynamic Macrophage Pathway CSML Database
Lifescience Database Archive (English)
Full Text Available 15189145 Lysophospholipid receptors: signaling and biology. Ishii I, Fukushima N, Y...e X, Chun J. Annu Rev Biochem. 2004;73:321-54. (.png) (.svg) (.html) (.csml) Show Lysophospholipid receptors: signaling and bio...logy. PubmedID 15189145 Title Lysophospholipid receptors: signaling and biology. Authors
Use of Animation in Teaching Cell Biology
Stith, Bradley J.
To address the different learning styles of students, and because students can access animation from off-campus computers, the use of digital animation in teaching cell biology has become increasingly popular. Sample processes from cell biology that are more clearly presented in animation than in static illustrations are identified. The value of animation is evaluated on whether the process being taught involves motion, cellular location, or sequential order of numerous events. Computer progr...
The cell biology of T-dependent B cell activation
DEFF Research Database (Denmark)
Owens, T; Zeine, R
The requirement that CD4+ helper T cells recognize antigen in association with class II Major Histocompatibility Complex (MHC) encoded molecules constrains T cells to activation through intercellular interaction. The cell biology of the interactions between CD4+ T cells and antigen-presenting cells...
Analysis of single biological cells
International Nuclear Information System (INIS)
The extraction of elemental information from single cultured cells using nuclear microscopy is an area of great potential because it can provide both quantitative information on the uptake of elements by the cell, and also its elemental response to a wide variety of external stimuli. A recent technique based on nuclear physics technology enables the analysis of single cells down to the parts per million level to be achieved
Teaching Cell Biology in Primary Schools
Directory of Open Access Journals (Sweden)
Francele de Abreu Carlan
Full Text Available Basic concepts of cell biology are essential for scientific literacy. However, because many aspects of cell theory and cell functioning are quite abstract, students experience difficulties understanding them. In this study, we investigated whether diverse teaching resources such as the use of replicas of Leeuwenhoek's microscope, visualization of cells using an optical microscope, construction of three-dimensional cell models, and reading of a comic book about cells could mitigate the difficulties encountered when teaching cell biology to 8th-grade primary school students. The results suggest that these didactic activities improve students' ability to learn concrete concepts about cell biology, such as the composition of living beings, growth, and cicatrization. Also, the development of skills was observed, as, for example, the notion of cell size. However, no significant improvements were observed in students' ability to learn about abstract topics, such as the structures of subcellular organelles and their functions. These results suggest that many students in this age have not yet concluded Piaget's concrete operational stage, indicating that the concepts required for the significant learning of abstract subjects need to be explored more thoroughly in the process of designing programs that introduce primary school students to cell biology.
Lumpkin, Ellen A.; Marshall, Kara L.; Nelson, Aislyn M.
The sense of touch detects forces that bombard the body's surface. In metazoans, an assortment of morphologically and functionally distinct mechanosensory cell types are tuned to selectively respond to diverse mechanical stimuli, such as vibration, stretch, and pressure. A comparative evolutionary approach across mechanosensory cell types and genetically tractable species is beginning to uncover the cellular logic of touch reception.
Cell-to-cell variability in cell death: can systems biology help us make sense of it all?
Xia, X; Owen, M. S.; Lee, R E C; Gaudet, S
One of the most common observations in cell death assays is that not all cells die at the same time, or at the same treatment dose. Here, using the perspective of the systems biology of apoptosis and the context of cancer treatment, we discuss possible sources of this cell-to-cell variability as well as its implications for quantitative measurements and computational models of cell death. Many different factors, both within and outside of the apoptosis signaling networks, have been correlated...
Cell Science and Cell Biology Research at MSFC: Summary
The common theme of these research programs is that they investigate regulation of gene expression in cells, and ultimately gene expression is controlled by the macromolecular interactions between regulatory proteins and DNA. The NASA Critical Path Roadmap identifies Muscle Alterations and Atrophy and Radiation Effects as Very Serious Risks and Severe Risks, respectively, in long term space flights. The specific problem addressed by Dr. Young's research ("Skeletal Muscle Atrophy and Muscle Cell Signaling") is that skeletal muscle loss in space cannot be prevented by vigorous exercise. Aerobic skeletal muscles (i.e., red muscles) undergo the most extensive atrophy during long-term space flight. Of the many different potential avenues for preventing muscle atrophy, Dr. Young has chosen to study the beta-adrenergic receptor (betaAR) pathway. The reason for this choice is that a family of compounds called betaAR agonists will preferentially cause an increase in muscle mass of aerobic muscles (i.e., red muscle) in animals, potentially providing a specific pharmacological solution to muscle loss in microgravity. In addition, muscle atrophy is a widespread medical problem in neuromuscular diseases, spinal cord injury, lack of exercise, aging, and any disease requiring prolonged bedridden status. Skeletal muscle cells in cell culture are utilized as a model system to study this problem. Dr. Richmond's research ("Radiation & Cancer Biology of Mammary Cells in Culture") is directed toward developing a laboratory model for use in risk assessment of cancer caused by space radiation. This research is unique because a human model will be developed utilizing human mammary cells that are highly susceptible to tumor development. This approach is preferential over using animal cells because of problems in comparing radiation-induced cancers between humans and animals.
Articular cartilage stem cell signalling
Karlsson, Camilla; Lindahl, Anders
The view of articular cartilage as a non-regeneration organ has been challenged in recent years. The articular cartilage consists of distinct zones with different cellular and molecular phenotypes, and the superficial zone has been hypothesized to harbour stem cells. Furthermore, the articular cartilage demonstrates a distinct pattern regarding stem cell markers (that is, Notch-1, Stro-1, and vascular cell adhesion molecule-1). These results, in combination with the positive identification of...
Recent advances in hematopoietic stem cell biology
DEFF Research Database (Denmark)
Bonde, Jesper; Hess, David A; Nolta, Jan A
made recently in the field of stem cell biology, researchers now have improved tools to define novel populations of stem cells, examine them ex vivo using conditions that promote self-renewal, track them into recipients, and determine whether they can contribute to the repair of damaged tissues......PURPOSE OF REVIEW: Exciting advances have been made in the field of hematopoietic stem cell biology during the past year. This review summarizes recent progress in the identification, culture, and in vivo tracking of hematopoietic stem cells. RECENT FINDINGS: The roles of Wnt and Notch proteins...... in regulating stem cell renewal in the microenvironment, and how these molecules can be exploited in ex vivo stem cell culture, are reviewed. The importance of identification of stem cells using functional as well as phenotypic markers is discussed. The novel field of nanotechnology is then discussed...
Wnt signaling and stem cell control
Institute of Scientific and Technical Information of China (English)
Roel Nusse
Wnt signaling has been implicated in the control over various types of stem cells and may act as a niche factor to maintain stem cells in a self-renewing state.As currently understood,Wnt proteins bind to receptors of the Frizzled and LRP families on the cell surface.Through several cytoplasmic relay components,the signal is transduced to B-catenin,which then enters the nucleus and forms a complex with TCF to activate transcription of Wnt target genes.Wnts can also signal through tyrosine kinase receptors,in particular the ROR and RYK receptors,leading to alternative modes of Wnt signaling.During the growth of tissues,these ligands and receptors are dynamically expressed,often transcriptionally controlled by Wnt signals themselves,to ensure the right balance between proliferation and differentiation.Isolated Wnt proteins are active on a variety of stem cells,including neural,mammary and embryonic stem cells.In general,Wnt proteins act to maintain the undifferentiated state of stem cells,while other growth factors instruct the cells to proliferate.These other factors include FGF and EGF,signaling through tyrosine kinase pathways.
Interfacing nanostructures to biological cells
Energy Technology Data Exchange (ETDEWEB)
Chen, Xing; Bertozzi, Carolyn R.; Zettl, Alexander K.
Disclosed herein are methods and materials by which nanostructures such as carbon nanotubes, nanorods, etc. are bound to lectins and/or polysaccharides and prepared for administration to cells. Also disclosed are complexes comprising glycosylated nanostructures, which bind selectively to cells expressing glycosylated surface molecules recognized by the lectin. Exemplified is a complex comprising a carbon nanotube functionalized with a lipid-like alkane, linked to a polymer bearing repeated .alpha.-N-acetylgalactosamine sugar groups. This complex is shown to selectively adhere to the surface of living cells, without toxicity. In the exemplified embodiment, adherence is mediated by a multivalent lectin, which binds both to the cells and the .alpha.-N-acetylgalactosamine groups on the nanostructure.
An Audiovisual Program in Cell Biology
Fedoroff, Sergey; Opel, William
A subtopic of cell biology, the structure and function of cell membranes, has been developed as a series of seven self-instructional slide-tape units and tested in five medical schools. Organization of advisers, analysis and definition of objectives and content, and development and evaluation of scripts and storyboards are discussed. (Author/LBH)
BMP2 Transfer to Neighboring Cells and Activation of Signaling.
Alborzinia, Hamed; Shaikhkarami, Marjan; Hortschansky, Peter; Wölfl, Stefan
Morphogen gradients and concentration are critical features during early embryonic development and cellular differentiation. Previously we reported the preparation of biologically active, fluorescently labeled BMP2 and quantitatively analyzed their binding to the cell surface and followed BMP2 endocytosis over time on the level of single endosomes. Here we show that this internalized BMP2 can be transferred to neighboring cells and, moreover, also activates downstream BMP signaling in adjacent cells, indicated by Smad1/5/8 phosphorylation and activation of the downstream target gene id1. Using a 3D matrix to modulate cell-cell contacts in culture we could show that direct cell-cell contact significantly increased BMP2 transfer. Using inhibitors of vesicular transport, transfer was strongly inhibited. Interestingly, cotreatment with the physiological BMP inhibitor Noggin increased BMP2 uptake and transfer, albeit activation of Smad signaling in neighboring cells was completely suppressed. Our findings present a novel and interesting mechanism by which morphogens such as BMP2 can be transferred between cells and how this is modulated by BMP antagonists such as Noggin, and how this influences activation of Smad signaling by BMP2 in neighboring cells. PMID:27306974
Ceramide signaling in cancer and stem cells
Bieberich, Erhard
Most of the previous work on the sphingolipid ceramide has been devoted to its function as an apoptosis inducer. Recent studies, however, have shown that in stem cells, ceramide has additional nonapoptotic functions. In this article, ceramide signaling will be reviewed in light of 'systems interface biology': as an interconnection of sphingolipid metabolism, membrane biophysics and cell signaling. The focus will be on the metabolic interconversion of ceramide and sphingomyelin or sphingosine-...
New Modeling Approaches to Investigate Cell Signaling in Radiation Response
Plante, Ianik; Cucinotta, Francis A.; Ponomarev, Artem L.
Ionizing radiation damages individual cells and tissues leading to harmful biological effects. Among many radiation-induced lesions, DNA double-strand breaks (DSB) are considered the key precursors of most early and late effects [1] leading to direct mutation or aberrant signal transduction processes. In response to damage, a flow of information is communicated to cells not directly hit by the radiation through signal transduction pathways [2]. Non-targeted effects (NTE), which includes bystander effects and genomic instability in the progeny of irradiated cells and tissues, may be particularly important for space radiation risk assessment [1], because astronauts are exposed to a low fluence of heavy ions and only a small fraction of cells are traversed by an ion. NTE may also have important consequences clinical radiotherapy [3]. In the recent years, new simulation tools and modeling approaches have become available to study the tissue response to radiation. The simulation of signal transduction pathways require many elements such as detailed track structure calculations, a tissue or cell culture model, knowledge of biochemical pathways and Brownian Dynamics (BD) propagators of the signaling molecules in their micro-environment. Recently, the Monte-Carlo simulation code of radiation track structure RITRACKS was used for micro and nano-dosimetry calculations [4]. RITRACKS will be used to calculate the fraction of cells traversed by an ion and delta-rays and the energy deposited in cells in a tissue model. RITRACKS also simulates the formation of chemical species by the radiolysis of water [5], notably the .OH radical. This molecule is implicated in DNA damage and in the activation of the transforming growth factor beta (TGF), a signaling molecule involved in NTE. BD algorithms for a particle near a membrane comprising receptors were also developed and will be used to simulate trajectories of signaling molecules in the micro-environment and characterize autocrine
N-Acetylglucosamine Functions in Cell Signaling
Directory of Open Access Journals (Sweden)
James B. Konopka
Full Text Available The amino sugar N-acetylglucosamine (GlcNAc is well known for the important structural roles that it plays at the cell surface. It is a key component of bacterial cell wall peptidoglycan, fungal cell wall chitin, and the extracellular matrix of animal cells. Interestingly, recent studies have also identified new roles for GlcNAc in cell signaling. For example, GlcNAc stimulates the human fungal pathogen Candida albicans to undergo changes in morphogenesis and expression of virulence genes. Pathogenic E. coli responds to GlcNAc by altering the expression of fimbriae and CURLI fibers that promote biofilm formation and GlcNAc stimulates soil bacteria to undergo changes in morphogenesis and production of antibiotics. Studies with animal cells have revealed that GlcNAc influences cell signaling through the posttranslational modification of proteins by glycosylation. O-linked attachment of GlcNAc to Ser and Thr residues regulates a variety of intracellular proteins, including transcription factors such as NFκB, c-myc, and p53. In addition, the specificity of Notch family receptors for different ligands is altered by GlcNAc attachment to fucose residues in the extracellular domain. GlcNAc also impacts signal transduction by altering the degree of branching of N-linked glycans, which influences cell surface signaling proteins. These emerging roles of GlcNAc as an activator and mediator of cellular signaling in fungi, animals, and bacteria will be the focus of this paper.
Sec14-like phosphatidylinositol transfer proteins and the biological landscape of phosphoinositide signaling in plants.
Huang, Jin; Ghosh, Ratna; Bankaitis, Vytas A
Phosphoinositides and soluble inositol phosphates are essential components of a complex intracellular chemical code that regulates major aspects of lipid signaling in eukaryotes. These involvements span a broad array of biological outcomes and activities, and cells are faced with the problem of how to compartmentalize and organize these various signaling events into a coherent scheme. It is in the arena of how phosphoinositide signaling circuits are integrated and, and how phosphoinositide pools are functionally defined and channeled to privileged effectors, that phosphatidylinositol (PtdIns) transfer proteins (PITPs) are emerging as critical players. As plant systems offer some unique advantages and opportunities for study of these proteins, we discuss herein our perspectives regarding the progress made in plant systems regarding PITP function. We also suggest interesting prospects that plant systems hold for interrogating how PITPs work, particularly in multi-domain contexts, to diversify the biological outcomes for phosphoinositide signaling. This article is part of a Special Issue entitled: Plant Lipid Biology edited by Kent D. Chapman and Ivo Feussner. PMID:27038688
Janus kinases in immune cell signaling
Ghoreschi, Kamran; Laurence, Arian; O'Shea, John J.
The Janus family kinases (Jaks), Jak1, Jak2, Jak3, and Tyk2, form one subgroup of the non-receptor protein tyrosine kinases. They are involved in cell growth, survival, development, and differentiation of a variety of cells but are critically important for immune cells and hematopoietic cells. Data from experimental mice and clinical observations have unraveled multiple signaling events mediated by Jak in innate and adaptive immunity. Deficiency of Jak3 or Tyk2 results in defined clinical dis...
Prostate Cancer Stem Cells: Viewing Signaling Cascades at a Finer Resolution.
Lin, Xiukun; Farooqi, Ammad Ahmad; Qureshi, Muhammad Zahid; Romero, Mirna Azalea; Tabassum, Sobia; Ismail, Muhammad
It is becoming characteristically more understandable that within tumor cells, there lies a sub-population of tumor cells with "stem cell" like properties and remarkable ability of self-renewal. Many features of these self-renewing cells are comparable with normal stem cells and are termed as "cancer stem cells". Accumulating experimentally verified data has started to scratch the surface of spatio-temporally dysregulated intracellular signaling cascades in the biology of prostate cancer stem cells. We partition this multicomponent review into how different signaling cascades operate in cancer stem cells and how bioactive ingredients isolated from natural sources may modulate signaling network. PMID:26846602
Cell biology experiments conducted in space
Taylor, G. R.
A review of cell biology experiments conducted during the first two decades of space flight is provided. References are tabulated for work done with six types of living test system: isolated viruses, bacteriophage-host, bacteria, yeasts and filamentous fungi, protozoans, and small groups of cells (such as hamster cell tissue and fertilized frog eggs). The general results of studies involving the survival of cells in space, the effect of space flight on growing cultures, the biological effects of multicharged high-energy particles, and the effects of space flight on the genetic apparatus of microorganisms are summarized. It is concluded that cell systems remain sufficiently stable during space flight to permit experimentation with models requiring a fixed cell line during the space shuttle era.
Classification of biological signals using linear and nonlinear features
International Nuclear Information System (INIS)
This paper investigates the characterization ability of linear and nonlinear features and proposes combining such features in order to improve the classification of biological signals, in particular single-trial electroencephalogram (EEG) and electrocardiogram (ECG) data. For this purpose, three data sets composed of ECG, epileptic EEG and finger-movement EEG were utilized. The characterization ability of seven nonlinear features namely the approximate entropy, largest Lyapunov exponents, correlation dimension, nonlinear prediction error, Hurst exponent, higher order autocovariance and asymmetry due to time reversal are compared with two linear features namely the autoregressive (AR) reflection coefficients and AR model coefficients. The features were tested by their ability to differentiate between different classes of data using a linear discriminant analysis (LDA) method with tenfold cross-validation. The class separability of combined linear and nonlinear features was assessed using sequential floating forward search with linear discriminant analysis method (SFFS-LDA). The results demonstrated that linear and nonlinear features on their own provided comparable results for the ECG data set and the finger-movement EEG data set whilst the linear features provided a better class separability compared to nonlinear features for the epileptic EEG data set. Combining linear and nonlinear features demonstrated a significant improvement in the class separability for all of the data sets where an average improvement of 20.56% was obtained with the ECG data set, 7.45% with finger-movement data set and 6.62% with the epileptic EEG data set. Overall results suggest that the use of combined linear and nonlinear feature sets would be a better approach for the characterization and classification of biological signals such as EEG and ECG
Cell biology of mitotic recombination
DEFF Research Database (Denmark)
Lisby, Michael; Rothstein, Rodney
Homologous recombination provides high-fidelity DNA repair throughout all domains of life. Live cell fluorescence microscopy offers the opportunity to image individual recombination events in real time providing insight into the in vivo biochemistry of the involved proteins and DNA molecules as w...
DEFF Research Database (Denmark)
Disclosed is a system comprising: - a reconfigurable hardware platform; - a plurality of hardware units defined as cells adapted to be programmed to provide self-organization and self-maintenance of the system by means of implementing a program expressed in a programming language defined as DNA...
Measuring cell identity in noisy biological systems
Birnbaum, Kenneth D; Kussell, Edo
Global gene expression measurements are increasingly obtained as a function of cell type, spatial position within a tissue and other biologically meaningful coordinates. Such data should enable quantitative analysis of the cell-type specificity of gene expression, but such analyses can often be confounded by the presence of noise. We introduce a specificity measure Spec that quantifies the information in a gene's complete expression profile regarding any given cell type, and an uncertainty me...
Role of TAZ in cancer stem cells and Wnt signaling
Azzolin, Luca
The transcriptional co-activator TAZ, known Hippo transducer together with his paralogue YAP, has recently emerged as important player in processes like organ growth and tumorigenesis. Here we focused on two aspects of TAZ biology: the first regards the role of TAZ as molecular determinant of breast cancer stem cells (CSCs); the second is the characterization of TAZ as downstream mediator of Wnt signaling. Using a bioinformatic approach, we discovered that more-malignant/CSC-enriched prim...
Radioresistance-related signaling pathways in nasopharyngeal carcinoma cells
International Nuclear Information System (INIS)
Objective: To study the difference of gene expression profile between the radioresistant human nasopharyngeal carcinoma cell line CNE-2R and CNE-2, and to screen the signaling pathway associated with radioresistance of nasopharyngeal carcinoma. Methods: The radioresistant nasopharyngeal carcinoma cell line CNE-2R was constructed from the original cell line CNE-2. CNE-2R and CNE-2 cells were cultured and administered with 60Co γ-ray irradiation at the dose of 400 cGy for 15 times. Human-6v 3.0 whole genome expression profile was used to screen the differentially expressed genes. Bioinformatic analysis was used to identify the pathways related to radioresistance. Results: The number of the differentially expressed genes that were found in these 2 experiments was 374. The Kegg pathway and Biocarta pathway analysis of the differentially expressed genes showed the biological importance of Toll-like receptor signaling pathway and IL-1 R-mediated signal transduction pathway to the radioresistance of the CNE-2R cells and the significant differences of 13 genes in these 2 pathways,including JUN, MYD88, CCL5, CXCL10, STAT1, LY96, FOS, CCL3, IL-6, IL-8, IL-1α, IL-1β, and IRAK2 (t=13.47-66.57, P<0.05). Conclusions: Toll-like receptor signaling pathway and IL-1R-mediated signal transduction pathway might be related to the occurrence of radioresistance. (authors)
Signaling pathways regulating production of hyaluronic acid in pig oocyte-cumulus cell-complexes
Czech Academy of Sciences Publication Activity Database
Procházka, Radek; Nagyová, Eva
Luxembourg: Recherches Scientifiques Luxembourg, 2006. s. 647. [Cell Signaling World 2006, Signal Transduction Pathways therapeutic targets. 25.01.2006-28.01.2006, Luxembourg] R&D Projects: GA ČR GA523/04/0574 Institutional research plan: CEZ:AV0Z50450515 Keywords : signaling pathways Subject RIV: EB - Genetics ; Molecular Biology
Cell cycle and cell signal transduction in marine phytoplankton
Institute of Scientific and Technical Information of China (English)
LIU Jingwen; JIAO Nianzhi; CAI Huinong
As unicellular phytoplankton, the growth of a marine phytoplankton population results directly from the completion of a cell cycle, therefore, cell-environment communication is an important way which involves signal transduction pathways to regulate cell cycle progression and contribute to growth, metabolism and primary production and respond to their surrounding environment in marine phytoplankton. Cyclin-CDK and CaM/Ca2+ are essentially key regulators in control of cell cycle and signal transduction pathway, which has important values on both basic research and applied biotechnology. This paper reviews progress made in this research field, which involves the identification and characterization of cyclins and cell signal transduction system, cell cycle control mechanisms in marine phytoplankton cells, cell cycle proteins as a marker of a terminal event to estimate the growth rate of phytoplankton at the species level, cell cycle-dependent toxin production of toxic algae and cell cycle progression regulated by environmental factors.
Microsystems for biological cell characterization
Rissanen, Anna
This thesis describes three techniques for the characterization of living cells using micro-electro-mechanical systems (MEMS) based devices. The study of cellular function and structure is essential for bioprocess control, disease diagnosis, patient treatment and drug discovery. Microsystem technology enables characterization of very small samples, minimal use of expensive reagents, testing of multiple samples in parallel, and point-of-care testing, all of which increase throughput and reduce...
Signaling hierarchy regulating human endothelial cell development
Our present knowledge of the regulation of mammalian endothelial cell differentiation has been largely derived from studies of mouse embryonic development. However, unique mechanisms and hierarchy of signals that govern human endothelial cell development are unknown and, thus, explored in these stud...
The biology of hematopoietic stem cells.
Szilvassy, Stephen J
Rarely has so much interest from the lay public, government, biotechnology industry, and special interest groups been focused on the biology and clinical applications of a single type of human cell as is today on stem cells, the founder cells that sustain many, if not all, tissues and organs in the body. Granting organizations have increasingly targeted stem cells as high priority for funding, and it appears clear that the evolving field of tissue engineering and regenerative medicine will require as its underpinning a thorough understanding of the molecular regulation of stem cell proliferation, differentiation, self-renewal, and aging. Despite evidence suggesting that embryonic stem (ES) cells might represent a more potent regenerative reservoir than stem cells collected from adult tissues, ethical considerations have redirected attention upon primitive cells residing in the bone marrow, blood, brain, liver, muscle, and skin, from where they can be harvested with relative sociological impunity. Among these, it is arguably the stem and progenitor cells of the mammalian hematopoietic system that we know most about today, and their intense study in rodents and humans over the past 50 years has culminated in the identification of phenotypic and molecular genetic markers of lineage commitment and the development of functional assays that facilitate their quantitation and prospective isolation. This review focuses exclusively on the biology of hematopoietic stem cells (HSCs) and their immediate progeny. Nevertheless, many of the concepts established from their study can be considered fundamental tenets of an evolving stem cell paradigm applicable to many regenerating cellular systems. PMID:14734085
Signal transduction and chemotaxis in mast cells.
Draber, Petr; Halova, Ivana; Polakovicova, Iva; Kawakami, Toshiaki
Mast cells play crucial roles in both innate and adaptive arms of the immune system. Along with basophils, mast cells are essential effector cells for allergic inflammation that causes asthma, allergic rhinitis, food allergy and atopic dermatitis. Mast cells are usually increased in inflammatory sites of allergy and, upon activation, release various chemical, lipid, peptide and protein mediators of allergic reactions. Since antigen/immunoglobulin E (IgE)-mediated activation of these cells is a central event to trigger allergic reactions, innumerable studies have been conducted on how these cells are activated through cross-linking of the high-affinity IgE receptor (FcεRI). Development of mature mast cells from their progenitor cells is under the influence of several growth factors, of which the stem cell factor (SCF) seems to be the most important. Therefore, how SCF induces mast cell development and activation via its receptor, KIT, has been studied extensively, including a cross-talk between KIT and FcεRI signaling pathways. Although our understanding of the signaling mechanisms of the FcεRI and KIT pathways is far from complete, pharmaceutical applications of the knowledge about these pathways are underway. This review will focus on recent progresses in FcεRI and KIT signaling and chemotaxis. PMID:25941081
Keeping Signals Straight: How Cells Process Information and Make Decisions.
Laub, Michael T
As we become increasingly dependent on electronic information-processing systems at home and work, it's easy to lose sight of the fact that our very survival depends on highly complex biological information-processing systems. Each of the trillions of cells that form the human body has the ability to detect and respond to a wide range of stimuli and inputs, using an extraordinary set of signaling proteins to process this information and make decisions accordingly. Indeed, cells in all organisms rely on these signaling proteins to survive and proliferate in unpredictable and sometimes rapidly changing environments. But how exactly do these proteins relay information within cells, and how do they keep a multitude of incoming signals straight? Here, I describe recent efforts to understand the fidelity of information flow inside cells. This work is providing fundamental insight into how cells function. Additionally, it may lead to the design of novel antibiotics that disrupt the signaling of pathogenic bacteria or it could help to guide the treatment of cancer, which often involves information-processing gone awry inside human cells. PMID:27427909
Insights into biological information processing: structural and dynamical analysis of a human protein signalling network
International Nuclear Information System (INIS)
We present an investigation on the structural and dynamical properties of a 'human protein signalling network' (HPSN). This biological network is composed of nodes that correspond to proteins and directed edges that represent signal flows. In order to gain insight into the organization of cell information processing this network is analysed taking into account explicitly the edge directions. We explore the topological properties of the HPSN at the global and the local scale, further applying the generating function formalism to provide a suitable comparative model. The relationship between the node degrees and the distribution of signals through the network is characterized using degree correlation profiles. Finally, we analyse the dynamical properties of small sub-graphs showing high correlation between their occurrence and dynamic stability
Cell signalling and phospholipid metabolism. Final report
Energy Technology Data Exchange (ETDEWEB)
Boss, W.F.
These studies explored whether phosphoinositide (PI) has a role in plants analogous to its role in animal cells. Although no parallel activity of PI in signal transduction was found in plant cells, activity of inositol phospholipid kinase was found to be modulated by light and by cell wall degrading enzymes. These studies indicate a major role for inositol phospholipids in plant growth and development as membrane effectors but not as a source of second messengers.
Countercurrent distribution of biological cells
It is known that the addition of phosphate buffer to two polymer aqueous phase systems has a strong effect on the partition behavior of cells and other particles in such mixtures. The addition of sodium phosphate to aqueous poly(ethylene glycol) dextran phase systems causes a concentration-dependent shift in binodial on the phase diagram, progressively lowering the critical conditions for phase separation as the phosphate concentration is increased. Sodium chloride produces no significant shift in the critical point relative to the salt-free case. Accurate determinations of the phase diagram require measurements of the density of the phases; data is presented which allows this parameter to be calculated from polarimetric measurements of the dextran concentrations of both phases. Increasing polymer concentrations in the phase systems produce increasing preference of the phosphate for the dextran-rich bottom phase. Equilibrium dialysis experiments showed that poly(ethylene glycol) effectively rejected phosphate, and to a lesser extent chloride, but that dextran had little effect on the distribution of either salt. Increasing ionic strength via addition of 0.15 M NaCl to phase systems containing 0.01 M phosphate produces an increased concentration of phosphate ions in the bottom dextran-rich phase, the expected effect in this type of Donnan distribution.
The Biology of Allogeneic Hematopoietic Cell Resistance
Shizuru, Judith A.; Bhattacharya, Deepta; Cavazzana-Calvo, Marina
At the most basic level, success of an allogeneic hematopoietic cell transplantation (HCT) procedure relies upon the engraftment of recipients with donor hematopoietic stem cells (HSCs) that will generate blood formation for the life of that individual. The formula to achieve durable HSC engraftment involves multiple factors including the recipient conditioning regimen, the nature of the genetic disparity between donor and recipient, and the content of the hematopoietic graft. Animal and clinical studies have shown that the biology of host resistance is complex, involving both immune and nonimmune elements. In this article, we review the factors that contribute to host resistance, describe emerging concepts on the basic biology of resistance, and discuss hematopoietic resistance as it relates specifically to patients with severe combined immunodeficiencies (SCID)— disorders that bring unique insights into the dynamics of cell replacement by allogeneic HSCs and progenitor cells. PMID:19913629
Tracking hypoxic signaling within encapsulated cell aggregates.
Skiles, Matthew L; Sahai, Suchit; Blanchette, James O
In Diabetes mellitus type 1, autoimmune destruction of the pancreatic β-cells results in loss of insulin production and potentially lethal hyperglycemia. As an alternative treatment option to exogenous insulin injection, transplantation of functional pancreatic tissue has been explored. This approach offers the promise of a more natural, long-term restoration of normoglycemia. Protection of the donor tissue from the host's immune system is required to prevent rejection and encapsulation is a method used to help achieve this aim. Biologically-derived materials, such as alginate and agarose, have been the traditional choice for capsule construction but may induce inflammation or fibrotic overgrowth which can impede nutrient and oxygen transport. Alternatively, synthetic poly(ethylene glycol) (PEG)-based hydrogels are non-degrading, easily functionalized, available at high purity, have controllable pore size, and are extremely biocompatible. As an additional benefit, PEG hydrogels may be formed rapidly in a simple photo-crosslinking reaction that does not require application of non-physiological temperatures. Such a procedure is described here. In the crosslinking reaction, UV degradation of the photoinitiator, 1-[4-(2-Hydroxyethoxy)-phenyl]-2-hydroxy-2-methyl-1-propane-1-one (Irgacure 2959), produces free radicals which attack the vinyl carbon-carbon double bonds of dimethacrylated PEG (PEGDM) inducing crosslinking at the chain ends. Crosslinking can be achieved within 10 minutes. PEG hydrogels constructed in such a manner have been shown to favorably support cells, and the low photoinitiator concentration and brief exposure to UV irradiation is not detrimental to viability and function of the encapsulated tissue. While we methacrylate our PEG with the method described below, PEGDM can also be directly purchased from vendors such as Sigma. An inherent consequence of encapsulation is isolation of the cells from a vascular network. Supply of nutrients, notably oxygen
Biological cell as IR-optical resonator
Czech Academy of Sciences Publication Activity Database
Cifra, Michal
Recife : OSA, 2011, TuA2. ISBN 978-1-55752-903-9. ISSN 2162-2701. [Latin America Optics and Photonics Conference, LAOP 2010. Recife (BR), 27.09.2010-30.09.2010] R&D Projects: GA ČR GPP102/10/P454 Institutional research plan: CEZ:AV0Z20670512 Keywords : Biological cells * Eigen modes * Living cell Subject RIV: JA - Electronics ; Optoelectronics, Electrical Engineering
Towards systems thinking in cell biology education
Verhoeff, Roald Pieter
Students are taught a large variety of life structures and processes at the cellular level. The concepts used to describe them are mainly drawn from the sub-cellular level, but this knowledge seems to be fragmentary if its integration at the cellular and organismic level remains undone. As a consequence, many students fail to acquire coherent conceptual understanding of the cell as a basic and functional unit of the organism. To enhance the coherence in students' cell biological knowledge we ...
Wnt Signalling Pathway Parameters for Mammalian Cells
Tan, Chin Wee; Gardiner, Bruce S.; Hirokawa, Yumiko; Layton, Meredith J.; Smith, David W.; Burgess, Antony W.
Wnt/β-catenin signalling regulates cell fate, survival, proliferation and differentiation at many stages of mammalian development and pathology. Mutations of two key proteins in the pathway, APC and β-catenin, have been implicated in a range of cancers, including colorectal cancer. Activation of Wnt signalling has been associated with the stabilization and nuclear accumulation of β-catenin and consequential up-regulation of β-catenin/TCF gene transcription. In 2003, Lee et al. constructed a c...
Profiling Signaling Polarity in Chemotactic Cells
Energy Technology Data Exchange (ETDEWEB)
Wang, Yingchun; Ding, Shi-Jian; Wang, Wei; Jacobs, Jon M.; Qian, Weijun; Moore, Ronald J.; Yang, Feng; Camp, David G.; Smith, Richard D.; Klemke, Richard L.
While directional movement requires morphological polarization characterized by formation of a leading pseudopodium at the front and a trailing rear at the back, little is known about how protein networks are spatially integrated to regulate this process. Here, we utilize a unique pseudopodial purification system and quantitative proteomics and phosphoproteomics to map the spatial relationship of 3509 proteins and 228 distinct sites of phosphorylation in polarized cells. Networks of signaling proteins, metabolic pathways, actin regulatory proteins, and kinase-substrate cascades were found to partition to different poles of the cell including components of the Ras/ERK pathway. Also, several novel proteins were found to be differentially phosphorylated at the front or rear of polarized cells and to localize to distinct subcellular structures. Our findings provide insight into the spatial organization of signaling networks that control cell movement and provide a comprehensive profile of proteins and their sites of phosphorylation that control cell polarization.
Cytokine signalling in embryonic stem cells
DEFF Research Database (Denmark)
Kristensen, David Møbjerg; Kalisz, Mark; Nielsen, Jens Høiriis
Cytokines play a central role in maintaining self-renewal in mouse embryonic stem (ES) cells through a member of the interleukin-6 type cytokine family termed leukemia inhibitory factor (LIF). LIF activates the JAK-STAT3 pathway through the class I cytokine receptor gp130, which forms a trimeric...... pathways seem to converge on c-myc as a common target to promote self-renewal. Whereas LIF does not seem to stimulate self-renewal in human embryonic stem cells it cannot be excluded that other cytokines are involved. The pleiotropic actions of the increasing number of cytokines and receptors signalling...... via JAKs, STATs and SOCS exhibit considerable redundancy, compensation and plasticity in stem cells in accordance with the view that stem cells are governed by quantitative variations in strength and duration of signalling events known from other cell types rather than qualitatively different stem...
A special issue on cell signaling, disease, and stem cells
Institute of Scientific and Technical Information of China (English)
Dangsheng Li
As the basic unit of life,cells utilize signaling pathways to receive inputs from the environment and translate such information into appropriate cellular behaviors and responses.Cell signaling is also pivotal for multicellular organisms such as mammals,as cells need to communicate extensively among each other and with the environment in order to orchestrate appropriate actions,which are in turn integrated at the system level for the proper functioning and well-being of the organism.Thus,understanding the molecular mechanisms of cell signaling constitutes a fundamental quest of today's life science research.Not surprisingly,dysregulation of cell signaling causes many diseases such as cancer,and in such cases,a thorough understanding of the nature of cell signaling under disease states would provide an important basis to the efforts of developing novel therapeutic strategies.In this context,we are pleased to present this 2012 Cell Research Special Issue focusing on "Cell signaling,disease,and stem cells".
Advances in Retinal Stem Cell Biology
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Andrea S Viczian
Full Text Available Tremendous progress has been made in recent years to generate retinal cells from pluripotent cell sources. These advances provide hope for those suffering from blindness due to lost retinal cells. Understanding the intrinsic genetic network in model organisms, like fly and frog, has led to a better understanding of the extrinsic signaling pathways necessary for retinal progenitor cell formation in mouse and human cell cultures. This review focuses on the culture methods used by different groups, which has culminated in the generation of laminated retinal tissue from both embryonic and induced pluripotent cells. The review also briefly describes advances made in transplantation studies using donor retinal progenitor and cultured retinal cells.
An electrostatic model for biological cell division
Faraggi, Eshel
Probably the most fundamental processes for biological systems is their ability to create themselves through the use of cell division and cell differentiation. In this work a simple physical model is proposed for biological cell division. The model consists of a positive ionic gradient across the cell membrane, and concentration of charge at the nodes of the spindle and on the chromosomes. A simple calculation, based on Coulomb's Law, shows that under such circumstances a chromosome will tend to break up to its constituent chromatids and that the chromatids will be separated by a distance that is an order of thirty percent of the distance between the spindle nodes. Further repulsion between the nodes will tend to stretch the cell and eventually break the cell membrane between the separated chromatids, leading to cell division. The importance of this work is in continuing the understanding of the electromagnetic basis of cell division and providing it with an analytical model. A central implication of this and...
Lukic, Zana; Campbell, Edward M.
The tripartite motif (TRIM)–containing proteins are involved in many cellular functions such as cell signaling, apoptosis, cell differentiation, and immune modulation. TRIM5 proteins, including TRIM5α and TRIM-Cyp, are known to possess antiretroviral activity against many different retroviruses. Besides being retroviral restriction factors, TRIM5 proteins participate in other cellular functions that have recently emerged in the study of TRIM5α. In this review, we discuss properties of TRIM5α ...
Electron Tomography in Plant Cell Biology
Institute of Scientific and Technical Information of China (English)
This review focuses on the contribution of electron tomography-based techniques to our understanding of cellular processes in plant cells. Electron microscopy techniques have evolved to provide better three-dimensional resolution and improved preservation of the subcellular components. In particular, the combination of cryofixation/freeze substitution and electron tomography have allowed plant cell biologists to image organelles and macromolecular complexes in their native cellular context with unprecedented three-dimensional resolution (4-7 nm). Until now, electron tomography has been applied in plant cell biology for the study of cytokinesis, Golgi structure and trafficking, formation of plant endosome/prevacuolar compartments, and organization of photosynthetic membranes. We discuss in this review the new insights that these tomographic studies have brought to the plant biology field.
P2X and P2Y receptor signaling in red blood cells
Sluyter, Ronald
Purinergic signaling involves the activation of cell surface P1 and P2 receptors by extracellular nucleosides and nucleotides such as adenosine and adenosine triphosphate (ATP), respectively. P2 receptors comprise P2X and P2Y receptors, and have well-established roles in leukocyte and platelet biology. Emerging evidence indicates important roles for these receptors in red blood cells. P2 receptor activation stimulates a number of signaling pathways in progenitor red blood cells resulting in microparticle release, reactive oxygen species formation, and apoptosis. Likewise, activation of P2 receptors in mature red blood cells stimulates signaling pathways mediating volume regulation, eicosanoid release, phosphatidylserine exposure, hemolysis, impaired ATP release, and susceptibility or resistance to infection. This review summarizes the distribution of P2 receptors in red blood cells, and outlines the functions of P2 receptor signaling in these cells and its implications in red blood cell biology. PMID:26579528
Erythropoietin signaling promotes transplanted progenitor cell survival
Jia, Yi; Warin, Renaud; Yu, Xiaobing; Epstein, Reed; Noguchi, Constance Tom
We examine the potential for erythropoietin signaling to promote donor cell survival in a model of myoblast transplantation. Expression of a truncated erythropoietin receptor in hematopoietic stem cells has been shown to promote selective engraftment in mice. We previously demonstrated expression of endogenous erythropoietin receptor on murine myoblasts, and erythropoietin treatment can stimulate myoblast proliferation and delay differentiation. Here, we report that enhanced erythropoietin re...
A positive feedback cell signaling nucleation model of astrocyte dynamics
Directory of Open Access Journals (Sweden)
Gabriel A Silva
Full Text Available We constructed a model of calcium signaling in astrocyte neural glial cells that incorporates a positive feedback nucleation mechanism, whereby small microdomain increases in local calcium can stochastically produce global cellular and intercellular network scale dynamics. The model is able to simultaneously capture dynamic spatial and temporal heterogeneities associated with intracellular calcium transients in individual cells and intercellular calcium waves (ICW in spatially realistic networks of astrocytes, i.e. networks where the positions of cells were taken from real in vitro experimental data of spontaneously forming sparse networks, as opposed to artificially constructed grid networks or other non-realistic geometries. This is the first work we are aware of where an intracellular model of calcium signaling that reproduces intracellular dynamics inherently accounts for intercellular network dynamics. These results suggest that a nucleation type mechanism should be further investigated experimentally in order to test its contribution to calcium signaling in astrocytes and in other cells more broadly. It may also be of interest in engineered neuromimetic network systems that attempt to emulate biological signaling and information processing properties in synthetic hardwired neuromorphometric circuits or coded algorithms.
MAPK Cascades in Guard Cell Signal Transduction.
Lee, Yuree; Kim, Yun Ju; Kim, Myung-Hee; Kwak, June M
Guard cells form stomata on the epidermis and continuously respond to endogenous and environmental stimuli to fine-tune the gas exchange and transpirational water loss, processes which involve mitogen-activated protein kinase (MAPK) cascades. MAPKs form three-tiered kinase cascades with MAPK kinases and MAPK kinase kinases, by which signals are transduced to the target proteins. MAPK cascade genes are highly conserved in all eukaryotes, and they play crucial roles in myriad developmental and physiological processes. MAPK cascades function during biotic and abiotic stress responses by linking extracellular signals received by receptors to cytosolic events and gene expression. In this review, we highlight recent findings and insights into MAPK-mediated guard cell signaling, including the specificity of MAPK cascades and the remaining questions. PMID:26904052
Signaling involved in stem cell reprogramming and differentiation
Institute of Scientific and Technical Information of China (English)
Shihori; Tanabe
Stem cell differentiation is regulated by multiple signaling events. Recent technical advances have reve-aled that differentiated cells can be reprogrammed into stem cells. The signals involved in stem cell pro-gramming are of major interest in stem cell research. The signaling mechanisms involved in regulating stem cell reprogramming and differentiation are the subject of intense study in the field of life sciences. In this review,the molecular interactions and signaling pathways related to stem cell differentiation are discussed.
Multiway modeling and analysis in stem cell systems biology
Directory of Open Access Journals (Sweden)
Vandenberg Scott L
Full Text Available Abstract Background Systems biology refers to multidisciplinary approaches designed to uncover emergent properties of biological systems. Stem cells are an attractive target for this analysis, due to their broad therapeutic potential. A central theme of systems biology is the use of computational modeling to reconstruct complex systems from a wealth of reductionist, molecular data (e.g., gene/protein expression, signal transduction activity, metabolic activity, etc.. A number of deterministic, probabilistic, and statistical learning models are used to understand sophisticated cellular behaviors such as protein expression during cellular differentiation and the activity of signaling networks. However, many of these models are bimodal i.e., they only consider row-column relationships. In contrast, multiway modeling techniques (also known as tensor models can analyze multimodal data, which capture much more information about complex behaviors such as cell differentiation. In particular, tensors can be very powerful tools for modeling the dynamic activity of biological networks over time. Here, we review the application of systems biology to stem cells and illustrate application of tensor analysis to model collagen-induced osteogenic differentiation of human mesenchymal stem cells. Results We applied Tucker1, Tucker3, and Parallel Factor Analysis (PARAFAC models to identify protein/gene expression patterns during extracellular matrix-induced osteogenic differentiation of human mesenchymal stem cells. In one case, we organized our data into a tensor of type protein/gene locus link × gene ontology category × osteogenic stimulant, and found that our cells expressed two distinct, stimulus-dependent sets of functionally related genes as they underwent osteogenic differentiation. In a second case, we organized DNA microarray data in a three-way tensor of gene IDs × osteogenic stimulus × replicates, and found that application of tensile strain to a
[Neural stem cells and Notch signalling].
Traiffort, Elisabeth; Ferent, Julien
Development and repair of the nervous system are based on the existence of neural stem cells (NSCs) able to generate neurons and glial cells. Among the mechanisms that are involved in the control of embryo or adult NSCs, the Notch signalling plays a major role. In embryo, the pathway participates in the maintenance of NSCs during all steps of development of the central nervous system which starts with the production of neurons also called neurogenesis and continues with gliogenesis giving rise to astrocytes and oligodendrocytes. During the postnatal and adult period, Notch signalling is still present in the major neurogenic areas, the subventricular zone of the lateral ventricles and the subgranular zone of the hippocampus. In these regions, Notch maintains NSC quiescence, contributes to the heterogeneity of these cells and displays pleiotropic effects during the regeneration process occurring after a lesion. PMID:26672665
Intracellular Signals of T Cell Costimulation
Institute of Scientific and Technical Information of China (English)
Jianxun Song; Fengyang Tylan Lei; Xiaofang Xiong; Rizwanul Haque
Ligation of T cell receptor (TCR) alone is insufficient to induce full activation of T lymphocytes. Additional ligand-receptor interactions (costimulation) on antigen presenting cells (APCs) and T cells are required. T cell costimulation has been shown to be essential for eliciting efficient T cell responses, involving all phases during T cell development. However, the mechanisms by which costimulation affects the function of T cells still need to be elucidated. In recent years, advances have been made in studies of costimulation as potential therapies in cancer, infectious disease as well as autoimmune disease. In this review, we discussed intracellular costimulation signals that regulate T cell proliferation, cell cycle progression, cytokine production, survival, and memory development. In general, the pathway of phosphoinositide-3 kinase (PBK)/protein kinase B (PKB, also known as Akt)/nuclear factor κB (NF-κB) might be central to many costimulatory effects. Through these pathways, costimulation controls T-cell expansion and proliferation by maintenance of survivin and aurora B expression, and sustains long-term T-cell survival and memory development by regulating the expression of bci-2 family members. Cellular & Molecular Immunology.2008;5(4):239-247.
Cell–cell signaling drives the evolution of complex traits: introduction—lung evo-devo
Torday, John S.; Rehan, V.K.
Physiology integrates biology with the environment through cell–cell interactions at multiple levels. The evolution of the respiratory system has been "deconvoluted" (Torday and Rehan in Am J Respir Cell Mol Biol 31:8–12, 2004) through Gene Regulatory Networks (GRNs) applied to cell–cell communication for all aspects of lung biology development, homeostasis, regeneration, and aging. Using this approach, we have predicted the phenotypic consequences of failed signaling for lung development, ho...
The Kynurenine Pathway in Stem Cell Biology
Jones, Simon P; Guillemin, Gilles J; Bruce J Brew
The kynurenine pathway (KP) is the main catabolic pathway of the essential amino acid tryptophan. The KP has been identified to play a critical role in regulating immune responses in a variety of experimental settings. It is also known to be involved in several neuroinflammatory diseases including Huntington's disease, amyotrophic lateral sclerosis, and Alzheimer's disease. This review considers the current understanding of the role of the KP in stem cell biology. Both of these fundamental ar...
Biological cell manipulation by magnetic nanoparticles
Gertz, Frederick; Khitun, Alexander
We report a manipulation of biological cells (erythrocytes) by magnetite (Fe3O4) nanoparticles in the presence of a magnetic field. The experiment was accomplished on the top of a micro-electromagnet consisting of two magnetic field generating contours. An electric current flowing through the contour(s) produces a non-uniform magnetic field, which is about 1.4 mT/μm in strength at 100 mA current in the vicinity of the current-carrying wire. In responses to the magnetic field, magnetic nanoparticles move towards the systems energy minima. In turn, magnetic nanoparticles drag biological cells in the same direction. We present experimental data showing cell manipulation through the control of electric current. This technique allows us to capture and move cells located in the vicinity (10-20 microns) of the current-carrying wires. One of the most interesting results shows a periodic motion of erythrocytes between the two conducting contours, whose frequency is controlled by an electric circuit. The obtained results demonstrate the feasibility of non-destructive cell manipulation by magnetic nanoparticles with micrometer-scale precision.
Signaling involved in stem cell reprogramming and differentiation
Tanabe, Shihori
Stem cell differentiation is regulated by multiple signaling events. Recent technical advances have revealed that differentiated cells can be reprogrammed into stem cells. The signals involved in stem cell programming are of major interest in stem cell research. The signaling mechanisms involved in regulating stem cell reprogramming and differentiation are the subject of intense study in the field of life sciences. In this review, the molecular interactions and signaling pathways related to s...
Celebrating Plant Cells: A Special Issue on Plant Cell Biology
Institute of Scientific and Technical Information of China (English)
@@ A special issue on plant cell biology is long overdue for JIPB! In the last two decades or so, the plant biology community has been thrilled by explosive discoveries regarding the molecular and genetic basis of plant growth, development, and responses to the environment, largely owing to recent maturation of model systems like Arabidopsis thaliana and the rice Oryza sativa, as well as the rapid development of high throughput technologies associated with genomics and proteomics.
Mast cell chemotaxis - chemoattractants and signaling pathways
Czech Academy of Sciences Publication Activity Database
Hálová, Ivana; Dráberová, Lubica; Dráber, Petr
Roč. 3, May (2012), s. 119. ISSN 1664-3224 R&D Projects: GA MŠk LD12073; GA ČR GA301/09/1826; GA ČR GAP302/10/1759 Grant ostatní: ECST(XE) BM1007; AV ČR(CZ) MC200520901 Institutional support: RVO:68378050 Keywords : mast cell * IgE receptor * plasma membrane Subject RIV: EB - Genetics ; Molecular Biology
Inflammatory mediators: Parallels between cancer biology and stem cell therapy
Directory of Open Access Journals (Sweden)
A Patel
Full Text Available Shyam A Patel1,2,3, Andrew C Heinrich2,3, Bobby Y Reddy2, Pranela Rameshwar21Graduate School of Biomedical Sciences, University of Medicine and Dentistry of New Jersey, Newark, NJ, USA; 2Department of Medicine – Division of Hematology/Oncology, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, NJ, USA; 3These authors contributed equally to this workAbstract: Inflammation encompasses diverse molecular pathways, and it is intertwined with a wide array of biological processes. Recently, there has been an upsurge of interest in the interactions between mediators of inflammation and other cells such as stem cells and cancer cells. Since tissue injuries are associated with the release of inflammatory mediators, it would be difficult to address this subject without considering the implications of their systemic effects. In this review, we discuss the effects of inflammatory reactions on stem cells and extrapolate on information pertaining to cancer biology. The discussion focuses on integrins and cytokines, and identifies the transcription factor, nuclear factor-kappa B (NFκB as central to the inflammatory response. Since stem cell therapy has been proposed for type II diabetes mellitus, metabolic syndrome, pulmonary edema, these disorders are used as examples to discuss the roles of inflammatory mediators. We propose prospects for future research on targeting the NFκB signaling pathway. Finally, we explore the bridge between inflammation and stem cells, including neural stem cells and adult stem cells from the bone marrow. The implications of mesenchymal stem cells in regenerative medicine as pertaining to inflammation are vast based on their anti-inflammatory and immunosuppressive effects. Such features of stem cells offer great potential for therapy in graft-versus-host disease, conditions with a significant inflammatory component, and tissue regeneration.Keywords: mesenchymal stem cells, cancer, cytokines
Opposing Activities of Notch and Wnt Signaling Regulate Intestinal Stem Cells and Gut Homeostasis
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Hua Tian
Full Text Available Proper organ homeostasis requires tight control of adult stem cells and differentiation through the integration of multiple inputs. In the mouse small intestine, Notch and Wnt signaling are required both for stem cell maintenance and for a proper balance of differentiation between secretory and absorptive cell lineages. In the absence of Notch signaling, stem cells preferentially generate secretory cells at the expense of absorptive cells. Here, we use function-blocking antibodies against Notch receptors to demonstrate that Notch blockade perturbs intestinal stem cell function by causing a derepression of the Wnt signaling pathway, leading to misexpression of prosecretory genes. Importantly, attenuation of the Wnt pathway rescued the phenotype associated with Notch blockade. These studies bring to light a negative regulatory mechanism that maintains stem cell activity and balanced differentiation, and we propose that the interaction between Wnt and Notch signaling described here represents a common theme in adult stem cell biology.
Cell Signalling Through Covalent Modification and Allostery
Johnson, Louise N.
Phosphorylation plays essential roles in nearly every aspect of cell life. Protein kinases catalyze the transfer of the γ-phosphate of ATP to a serine, threonine or tyrosine residue in protein substrates. This covalent modification allows activation or inhibition of enzyme activity, creates recognition sites for other proteins and promotes order/disorder or disorder/order transitions. These properties regulate signalling pathways and cellular processes that mediate metabolism, transcription, cell cycle progression, differentiation, cytoskeleton arrangement and cell movement, apoptosis, intercellular communication, and neuronal and immunological functions. In this lecture I shall review the structural consequences of protein phosphorylation using our work on glycogen phosphorylase and the cell cycle cyclin dependent protein kinases as illustrations. Regulation of protein phosphorylation may be disrupted in the diseased state and protein kinases have become high profile targets for drug development. To date there are 11 compounds that have been approved for clinical use in the treatment of cancer.
Molecular signal transduction in vascular cell apoptosis
Institute of Scientific and Technical Information of China (English)
Apoptosis is a form of genetically programmed cell death, which plays a key role in regulation of cellularity in a variety of tissue and cell types including the cardiovascular tissues. Under both physiological and pathophysiological conditions, various biophysiological and biochemical factors, including mechanical forces, reactive oxygen and nitrogen species, cytokines, growth factors, oxidized lipoproteins, etc., may influence apoptosis of vascular cells. The Fas/Fas ligand/caspase death-signaling pathway, Bcl-2 protein family/mitochondria, the tumor suppressive gene p53, and the proto-oncogene c-myc may be activated in atherosclerotic lesions, and mediates vascular apoptosis during the development of atherosclerosis. Abnormal expression and dysfunction of these apoptosis-regulating genes may attenuate or accelerate vascular cell apoptosis and affect the integrity and stability of atherosclerotic plaques. Clarification of the molecular mechanism that regulates apoptosis may help design a new strategy for treatment of atherosclerosis and its major complication, the acute vascular syndromes.
Biology of primate relaxin: A paracrine signal in early pregnancy?
Directory of Open Access Journals (Sweden)
Hayes Eric S
Full Text Available Abstract Relaxin is a peptide hormone that exerts numerous effects in a variety of tissues across a broad range of species. Although first identified more than 75 years ago interest in relaxin biology has waxed and waned over the years consistent with peaks and troughs of new experimental data on its wide-ranging biological effects and advances in relaxin enabling technologies. Recent insights into species-dependent differences in relaxin biology during pregnancy have once again stimulated a relative surge of interest in the study of relaxin's reproductive biology. Identification and pharmacological characterization of orphaned relaxin receptors and exploration of its paracrine effects on pregnancy using genomic and proteomic technologies have succeeded in fueling current interest in relaxin research. Primates and non-primate vertebrates exhibit very disparate profiles of relaxin genomics, proteomics and functional biology. Non-human primates appear to exhibit a very close similarity to humans with respect to relaxin reproductive biology but the similarities and subtle differences are only just beginning to be understood. We, and others, have shown that relaxin produces significant changes to the non-human primate endometrium during the peri-implantation period that are consistent with relaxin's long perceived role as a paracrine modulator of pregnancy. The purpose of this review is to summarize the reproductive biology of relaxin in non-human primates with a specific emphasis on the paracrine role of ovarian and endometrial relaxin during embryo implantation and early pregnancy.
Lactation Biology Symposium: Lactocrine signaling and developmental programming
Lactocrine signaling is defined as transmission of bioactive factors from mother to offspring as a consequence of nursing. Lactocrine transmission of signaling molecules may be an evolutionarily conserved process through which bioactive factors necessary for support of neonatal development are deliv...
Detection, Characterization, and Biological Effect of Quorum-Sensing Signaling Molecules in Peanut-Nodulating Bradyrhizobia
Directory of Open Access Journals (Sweden)
Walter Giordano
Full Text Available Bacteria of the genus Bradyrhizobium are able to establish a symbiotic relationship with peanut (Arachis hypogaea root cells and to fix atmospheric nitrogen by converting it to nitrogenous compounds. Quorum sensing (QS is a cell-cell communication mechanism employed by a variety of bacterial species to coordinate behavior at a community level through regulation of gene expression. The QS process depends on bacterial production of various signaling molecules, among which the N-acylhomoserine lactones (AHLs are most commonly used by Gram-negative bacteria. Some previous reports have shown the production of QS signaling molecules by various rhizobia, but little is known regarding mechanisms of communication among peanut-nodulating strains. The aims of this study were to identify and characterize QS signals produced by peanut-nodulating bradyrhizobial strains and to evaluate their effects on processes related to cell interaction. Detection of AHLs in 53 rhizobial strains was performed using the biosensor strains Agrobacterium tumefaciens NTL4 (pZLR4 and Chromobacterium violaceum CV026 for AHLs with long and short acyl chains, respectively. None of the strains screened were found to produce AHLs with short acyl chains, but 14 strains produced AHLs with long acyl chains. These 14 AHL-producing strains were further studied by quantification of β-galactosidase activity levels (AHL-like inducer activity in NTL4 (pZLR4. Strains displaying moderate to high levels of AHL-like inducer activity were subjected to chemical identification of signaling molecules by high-performance liquid chromatography coupled to mass spectrometry (LC-MS/MS. For each AHL-producing strain, we found at least four different AHLs, corresponding to N-hexanoyl-DL-homoserine lactone (C6, N-(3-oxodecanoyl-L-homoserine lactone (3OC10, N-(3-oxododecanoyl-L-homoserine lactone (3OC12, and N-(3-oxotetradecanoyl-L-homoserine lactone (3OC14. Biological roles of 3OC10, 3OC12, and 3OC14 AHLs
Homotypic RANK signaling differentially regulates proliferation, motility and cell survival in osteosarcoma and mammary epithelial cells.
Beristain, Alexander G; Narala, Swami R; Di Grappa, Marco A; Khokha, Rama
RANKL (receptor activator of NF-κB ligand) is a crucial cytokine for regulating diverse biological systems such as innate immunity, bone homeostasis and mammary gland differentiation, operating through activation of its cognate receptor RANK. In these normal physiological processes, RANKL signals through paracrine and/or heterotypic mechanisms where its expression and function is tightly controlled. Numerous pathologies involve RANKL deregulation, such as bone loss, inflammatory diseases and cancer, and aberrant RANK expression has been reported in bone cancer. Here, we investigated the significance of RANK in tumor cells with a particular emphasis on homotypic signaling. We selected RANK-positive mouse osteosarcoma and RANK-negative preosteoblastic MC3T3-E1 cells and subjected them to loss- and gain-of-RANK function analyses. By examining a spectrum of tumorigenic properties, we demonstrate that RANK homotypic signaling has a negligible effect on cell proliferation, but promotes cell motility and anchorage-independent growth of osteosarcoma cells and preosteoblasts. By contrast, establishment of RANK signaling in non-tumorigenic mammary epithelial NMuMG cells promotes their proliferation and anchorage-independent growth, but not motility. Furthermore, RANK activation initiates multiple signaling pathways beyond its canonical target, NF-κB. Among these, biochemical inhibition reveals that Erk1/2 is dominant and crucial for the promotion of anchorage-independent survival and invasion of osteoblastic cells, as well as the proliferation of mammary epithelial cells. Thus, RANK signaling functionally contributes to key tumorigenic properties through a cell-autonomous homotypic mechanism. These data also identify the likely inherent differences between epithelial and mesenchymal cell responsiveness to RANK activation. PMID:22421365
Wnt signaling control of bone cell apoptosis
Institute of Scientific and Technical Information of China (English)
Peter V N Bodine
Wnts are a large family of growth factors that mediate essential biological processes like embryogenesis, morphogenesis and organogenesis. These proteins also play a role in oncogenesis, and they regulate apoptosis in many tissues. Wnts bind to a membrane receptor complex comprised of a frizzled (FZD) G-protein-coupled receptor and a low-density , lipoprotein (LDL) receptor-related protein (LRP). The formation of this ligand-receptor complex initiates a number of signaling cascades that include the canonical/beta-catenin pathway as well as several noncanonical pathways. In recent years, canonical Wnt signaling has been reported to play a significant role in the control of bone formation. Clinical studies have found that mutations in LRP-5 are associated with reduced bone mineral density (BMD) and fractures. Investigations of knockout and transgenic mouse models of Wnt pathway components have shown that canonical Wnt signaling modulates most aspects of osteoblast physiology including proliferation, differentiation, function and apoptosis. Transgenic mice expressing a gain of function mutant of LRP-5 in bone, or mice lacking the Wnt antagonist secreted frizzled-related protein-1, exhibit elevated BMD and suppressed osteoblast apoptosis. In addition, preclinical studies with pharmacologic compounds such as those that inhibit glycogen synthase kinase-3p support the importance of the canonical Wnt pathway in modulation of bone formation and osteoblast apoptosis.
Systems Biology for Organotypic Cell Cultures
Energy Technology Data Exchange (ETDEWEB)
Grego, Sonia [RTI International, Research Triangle Park, NC (United States); Dougherty, Edward R. [Texas A & M Univ., College Station, TX (United States); Alexander, Francis J. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Auerbach, Scott S. [National Inst. of Environmental Health Sciences, Research Triangle Park, NC (United States); Berridge, Brian R. [GlaxoSmithKline, Research Triangle Park, NC (United States); Bittner, Michael L. [Translational Genomics Research Inst., Phoenix, AZ (United States); Casey, Warren [National Inst. of Environmental Health Sciences, Research Triangle Park, NC (United States); Cooley, Philip C. [RTI International, Research Triangle Park, NC (United States); Dash, Ajit [HemoShear Therapeutics, Charlottesville, VA (United States); Ferguson, Stephen S. [National Inst. of Environmental Health Sciences, Research Triangle Park, NC (United States); Fennell, Timothy R. [RTI International, Research Triangle Park, NC (United States); Hawkins, Brian T. [RTI International, Research Triangle Park, NC (United States); Hickey, Anthony J. [RTI International, Research Triangle Park, NC (United States); Kleensang, Andre [Johns Hopkins Univ., Baltimore, MD (United States). Center for Alternatives to Animal Testing; Liebman, Michael N. [IPQ Analytics, Kennett Square, PA (United States); Martin, Florian [Phillip Morris International, Neuchatel (Switzerland); Maull, Elizabeth A. [National Inst. of Environmental Health Sciences, Research Triangle Park, NC (United States); Paragas, Jason [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Qiao, Guilin [Defense Threat Reduction Agency, Ft. Belvoir, VA (United States); Ramaiahgari, Sreenivasa [National Inst. of Environmental Health Sciences, Research Triangle Park, NC (United States); Sumner, Susan J. [RTI International, Research Triangle Park, NC (United States); Yoon, Miyoung [The Hamner Inst. for Health Sciences, Research Triangle Park, NC (United States); ScitoVation, Research Triangle Park, NC (United States)
Translating in vitro biological data into actionable information related to human health holds the potential to improve disease treatment and risk assessment of chemical exposures. While genomics has identified regulatory pathways at the cellular level, translation to the organism level requires a multiscale approach accounting for intra-cellular regulation, inter-cellular interaction, and tissue/organ-level effects. Tissue-level effects can now be probed in vitro thanks to recently developed systems of three-dimensional (3D), multicellular, "organotypic" cell cultures, which mimic functional responses of living tissue. However, there remains a knowledge gap regarding interactions across different biological scales, complicating accurate prediction of health outcomes from molecular/genomic data and tissue responses. Systems biology aims at mathematical modeling of complex, non-linear biological systems. We propose to apply a systems biology approach to achieve a computational representation of tissue-level physiological responses by integrating empirical data derived from organotypic culture systems with computational models of intracellular pathways to better predict human responses. Successful implementation of this integrated approach will provide a powerful tool for faster, more accurate and cost-effective screening of potential toxicants and therapeutics. On September 11, 2015, an interdisciplinary group of scientists, engineers, and clinicians gathered for a workshop in Research Triangle Park, North Carolina, to discuss this ambitious goal. Participants represented laboratory-based and computational modeling approaches to pharmacology and toxicology, as well as the pharmaceutical industry, government, non-profits, and academia. Discussions focused on identifying critical system perturbations to model, the computational tools required, and the experimental approaches best suited to generating key data. This consensus report summarizes the discussions held.
Skeletal Muscle Stem Cells from Animals I. Basic Cell Biology
Michael V. Dodson, Gary J. Hausman, LeLuo Guan, Min Du, Theodore P. Rasmussen, Sylvia P. Poulos, Priya Mir, Werner G. Bergen, Melinda E. Fernyhough, Douglas C. McFarland, Robert P. Rhoads, Beatrice Soret, James M. Reecy, Sandra G. Velleman, Zhihua Jiang
Skeletal muscle stem cells from food-producing animals are of interest to agricultural life scientists seeking to develop a better understanding of the molecular regulation of lean tissue (skeletal muscle protein hypertrophy) and intramuscular fat (marbling) development. Enhanced understanding of muscle stem cell biology and function is essential for developing technologies and strategies to augment the metabolic efficiency and muscle hypertrophy of growing animals potentially leading to grea...
Skeletal muscle stem cells from animals I. basic cell biology
Dodson, Michael V.; Hausman, Gary J.; Guan, Leluo; Du, Min; Rasmussen, Theodore P.; Poulos, Sylvia P; Mir, Priya; Bergen, Werner G.; Fernyhough, Melinda E.; McFarland, Douglas C.; Rhoads, Robert P.; Soret Lafraya, Beatriz; Reecy, James M.; Velleman, Sandra G; Jiang, Zhihua
Skeletal muscle stem cells from food-producing animals are of interest to agricultural life scientists seeking to develop a better understanding of the molecular regulation of lean tissue (skeletal muscle protein hypertrophy) and intramuscular fat (marbling) development. Enhanced understanding of muscle stem cell biology and function is essential for developing technologies and strategies to augment the metabolic efficiency and muscle hypertrophy of growing animals potentially leading to grea...
Lipid rafts: cell surface platforms for T cell signaling
Directory of Open Access Journals (Sweden)
Full Text Available The Src family tyrosine kinase Lck is essential for T cell development and T cell receptor (TCR* signaling. Lck is post-translationally fatty acylated at its N-terminus conferring membrane targeting and concentration in plasma membrane lipid rafts, which are lipid-based organisational platforms. Confocal fluorescence microscopy shows that Lck colocalises in rafts with GPI-linked proteins, the adaptor protein LAT and Ras, but not with non-raft membrane proteins including the protein tyrosine phosphatase CD45. The TCR also associates with lipid rafts and its cross-linking causes coaggregation of raft-associated proteins including Lck, but not of CD45. Cross-linking of either the TCR or rafts strongly induces specific tyrosine phosphorylation of the TCR in the rafts. Remarkably, raft patching alone induces signalling events analogous to TCR stimulation, with the same dependence on expression of key TCR signalling molecules. Our results indicate a mechanism whereby TCR engagement promotes aggregation of lipid rafts, which facilitates colocalisation of signaling proteins including Lck, LAT, and the TCR, while excluding CD45, thereby potentiating protein tyrosine phosphorylation and downstream signaling. We are currently testing this hypothesis as well as using imaging techniques such as fluorescence resonance energy transfer (FRET microscopy to study the dynamics of proteins and lipids in lipid rafts in living cells undergoing signaling events. Recent data show that the key phosphoinositide PI(4,5P2 is concentrated in T cell lipid rafts and that on stimulation of the cells it is rapidly converted to PI(3,4,5P3 and diacylglycerol within rafts. Thus rafts are hotspots for both protein and lipid signalling pathways.
Cell Biology Apps for Apple Devices
Stark, Louisa A.
Apps for touch-pad devices hold promise for guiding and supporting learning. Students may use them in the classroom or on their own for didactic instruction, just-in-time learning, or review. Since Apple touch-pad devices (i.e., iPad and iPhone) have a substantial share of the touch-pad device market (Campbell, 2012), this Feature will explore cell biology apps available from the App Store. My review includes iPad and iPhone apps available in June 2012, but does not include courses, lectures,...
Perturbation Biology: inferring signaling networks in cellular systems
Molinelli, Evan J.; Korkut, Anil; Wang, Weiqing; Miller, Martin L; Gauthier, Nicholas P.; Jing, Xiaohong; Kaushik, Poorvi; He, Qin; Mills, Gordon; Solit, David B.; Pratilas, Christine A.; Weigt, Martin; Braunstein, Alfredo; Pagnani, Andrea; Zecchina, Riccardo
Author Summary Drugs that target specific effects of signaling proteins are promising agents for treating cancer. One of the many obstacles facing optimal drug design is inadequate quantitative understanding of the coordinated interactions between signaling proteins. De novo model inference of network or pathway models refers to the algorithmic construction of mathematical predictive models from experimental data without dependence on prior knowledge. De novo inference is difficult because of...
Can molecular cell biology explain chromosome motions?
Directory of Open Access Journals (Sweden)
Gagliardi L
Full Text Available Abstract Background Mitotic chromosome motions have recently been correlated with electrostatic forces, but a lingering "molecular cell biology" paradigm persists, proposing binding and release proteins or molecular geometries for force generation. Results Pole-facing kinetochore plates manifest positive charges and interact with negatively charged microtubule ends providing the motive force for poleward chromosome motions by classical electrostatics. This conceptual scheme explains dynamic tracking/coupling of kinetochores to microtubules and the simultaneous depolymerization of kinetochore microtubules as poleward force is generated. Conclusion We question here why cells would prefer complex molecular mechanisms to move chromosomes when direct electrostatic interactions between known bound charge distributions can accomplish the same task much more simply.
JAK/STAT signaling regulates tissue outgrowth and male germline stem cell fate in Drosophila
Institute of Scientific and Technical Information of China (English)
Shree Ram SINGH; Xiu CHEN; Steven X.HOU
In multicellular organisms, biological activities are regulated by cell signaling. The various signal transduction pathways regulate cell fate, proliferation, migration, and polarity. Miscoordination of the communicative signals will lead to disasters like cancer and other fatal diseases. The JAK/STAT signal transduction pathway is one of the pathways, which was first identified in vertebrates and is highly conserved throughout evolution. Studying the JAK/STAT signal transduction pathway in Drosophila provides an excellent opportunity to understand the molecular mechanism of the cell regulation during development and tumor formation. In this review, we discuss the general overview of JAK/STAT signaling in Drosophila with respect to its functions in the eye development and stem cell fate determination.
Primary Cilia, Signaling Networks and Cell Migration
DEFF Research Database (Denmark)
Veland, Iben Rønn
controls directional cell migration as a physiological response. The ciliary pocket is a membrane invagination with elevated activity of clathrin-dependent endocytosis (CDE). In paper I, we show that the primary cilium regulates TGF-β signaling and the ciliary pocket is a compartment for CDE......-dependent regulation of signal transduction. Upon ligand-binding and activation in the cilium, TGFβ receptors accumulate and are internalized at the ciliary base together with Smad2/3 transcription factors that are phosphorylated here and translocated to the nucleus for target gene expression. These processes depend...... migration. A number of central Wnt components localize to the fibroblast primary cilium, including the Wnt5a-receptor, Fzd3, and Dvl proteins. Inversin-deficient MEFs have an elevated expression of canonical Wnt-associated genes and proteins, in addition to dysregulation of components in non-canonical Wnt...
Biology-oriented synthesis of a withanolide-inspired compound collection reveals novel modulators of hedgehog signaling.
Švenda, Jakub; Sheremet, Michael; Kremer, Lea; Maier, Lukáš; Bauer, Jonathan O; Strohmann, Carsten; Ziegler, Slava; Kumar, Kamal; Waldmann, Herbert
Biology-oriented synthesis employs the structural information encoded in complex natural products to guide the synthesis of compound collections enriched in bioactivity. The trans-hydrindane dehydro-δ-lactone motif defines the characteristic scaffold of the steroid-like withanolides, a plant-derived natural product class with a diverse pattern of bioactivity. A withanolide-inspired compound collection was synthesized by making use of three key intermediates that contain this characteristic framework derivatized with different reactive functional groups. Biological evaluation of the compound collection in cell-based assays that monitored biological signal-transduction processes revealed a novel class of Hedgehog signaling inhibitors that target the protein Smoothened. PMID:25736574
Lysyl oxidase propeptide inhibits smooth muscle cell signaling and proliferation
International Nuclear Information System (INIS)
Lysyl oxidase is required for the normal biosynthesis and maturation of collagen and elastin. It is expressed by vascular smooth muscle cells, and its increased expression has been previously found in atherosclerosis and in models of balloon angioplasty. The lysyl oxidase propeptide (LOX-PP) has more recently been found to have biological activity as a tumor suppressor, and it inhibits Erk1/2 Map kinase activation. We reasoned that LOX-PP may have functions in normal non-transformed cells. We, therefore, investigated its effects on smooth muscle cells, focusing on important biological processes mediated by Erk1/2-dependent signaling pathways including proliferation and matrix metalloproteinase-9 (MMP-9) expression. In addition, we investigated whether evidence for accumulation of LOX-PP could be found in vivo in a femoral artery injury model. Recombinant LOX-PP was expressed and purified, and was found to inhibit primary rat aorta smooth muscle cell proliferation and DNA synthesis by more than 50%. TNF-α-stimulated MMP-9 expression and Erk1/2 activation were both significantly inhibited by LOX-PP. Immunohistochemistry studies carried out with affinity purified anti-LOX-PP antibody showed that LOX-PP epitopes were expressed at elevated levels in vascular lesions of injured arteries. These novel data suggest that LOX-PP may provide a feedback control mechanism that serves to inhibit properties associated with the development of vascular pathology
Wnt/β-catenin signaling in T cell immunity and cancer immunotherapy
Gattinoni, Luca; Ji, Yun; Restifo, Nicholas P
Wnt ligands are lipid-modified secreted glycoproteins that regulate embryonic development, cell fate specification and the homeostasis of self-renewing adult tissues. In addition to its well established role in thymocyte development, recent studies have indicated that Wnt/β-catenin signaling is critical for the differentiation, polarization and survival of mature T lymphocytes. Here, we describe our current understanding of Wnt signaling in the biology of post-thymic T cells and discuss how h...
Cell Wall Biology: Perspectives from Cell Wall Imaging
Institute of Scientific and Technical Information of China (English)
Kieran J.D.Lee; Susan E.Marcus; J.Paul Knox
Polysaccharide-rich plant cell walls are important biomaterials that underpin plant growth,are major repositories for photosynthetically accumulated carbon,and,in addition,impact greatly on the human use of plants. Land plant cell walls contain in the region of a dozen major polysaccharide structures that are mostly encompassed by cellulose,hemicelluloses,and pectic polysaccharides. During the evolution of land plants,polysaccharide diversification appears to have largely involved structural elaboration and diversification within these polysaccharide groups. Cell wall chemistry is well advanced and a current phase of cell wall science is aimed at placing the complex polysaccharide chemistry in cellular contexts and developing a detailed understanding of cell wall biology. Imaging cell wall glycomes is a challenging area but recent developments in the establishment of cell wall molecular probe panels and their use in high throughput procedures are leading to rapid advances in the molecular understanding of the spatial heterogeneity of individual cell walls and also cell wall differences at taxonomic levels. The challenge now is to integrate this knowledge of cell wall heterogeneity with an understanding of the molecular and physiological mechanisms that underpin cell wall properties and functions.
Single cell analysis of signaling molecules
Czech Academy of Sciences Publication Activity Database
Klepárník, Karel; Luksch, Jaroslav; Adamová, Eva; Potáčová, Anna; Matalová, E.; Foret, František
Grupo VLS Print Solution, 2014 - (Guzman, N.; Taveres, M.). s. 49-49 [International Symposium on Electro- and Liquid Phase-Separation Techniques /21./ and Latin-American Symposium on Biotechnology, Biomedical, Biopharmaceutical, and Industrial Applications of Capillary Electrophoresis and Microchip Technology /21./. 04.10.2014-08.10.2014, Natal] R&D Projects: GA ČR(CZ) GA14-28254S Institutional support: RVO:68081715 ; RVO:67985904 Keywords : single cell analysis * signaling molecules * caspase Subject RIV: CB - Analytical Chemistry, Separation
Aberrant signaling pathways in medulloblastomas: a stem cell connection
Directory of Open Access Journals (Sweden)
Carolina Oliveira Rodini
Full Text Available Medulloblastoma is a highly malignant primary tumor of the central nervous system. It represents the most frequent type of solid tumor and the leading cause of death related to cancer in early childhood. Current treatment includes surgery, chemotherapy and radiotherapy which may lead to severe cognitive impairment and secondary brain tumors. New perspectives for therapeutic development have emerged with the identification of stem-like cells displaying high tumorigenic potential and increased radio- and chemo-resistance in gliomas. Under the cancer stem cell hypothesis, transformation of neural stem cells and/or granular neuron progenitors of the cerebellum are though to be involved in medulloblastoma development. Dissecting the genetic and molecular alterations associated with this process should significantly impact both basic and applied cancer research. Based on cumulative evidences in the fields of genetics and molecular biology of medulloblastomas, we discuss the possible involvement of developmental signaling pathways as critical biochemical switches determining normal neurogenesis or tumorigenesis. From the clinical viewpoint, modulation of signaling pathways such as TGFβ, regulating neural stem cell proliferation and tumor development, might be attempted as an alternative strategy for future drug development aiming at more efficient therapies and improved clinical outcome of patients with pediatric brain cancers.
Seeing Cells: Teaching the Visual/Verbal Rhetoric of Biology
Dinolfo, John; Heifferon, Barbara; Temesvari, Lesly A.
This pilot study obtained baseline information on verbal and visual rhetorics to teach microscopy techniques to college biology majors. We presented cell images to students in cell biology and biology writing classes and then asked them to identify textual, verbal, and visual cues that support microscopy learning. Survey responses suggest that…
Suofu Qin's work on studies of cell survival signaling in cancer and epithelial cells
Institute of Scientific and Technical Information of China (English)
Reactive oxygen species (ROS) encompass a variety of diverse chemical species including superoxide anions, hydrogen peroxide, hydroxyl radicals and peroxynitrite, which are mainly produced via mitochondrial oxidative metabolism, enzymatic reactions, and light-initiated lipid peroxidation. Over-production of ROS and/or decrease in the antioxidant capacity cause cells to undergo oxi- dative stress that damages cellular macromolecules such as proteins, lipids, and DNA. Oxidative stress is associated with ageing and the development of agerelated diseases such as cancer and age-related macular degeneration. ROS activate signaling pathways that promote cell survival or lead to cell death, depending on the source and site of ROS production, the specific ROS generated, the concentration and kinetics of ROS generation, and the cell types being challenged. However, how the nature and compartmentalization of ROS contribute to the pathogenesis of individual diseases is poorly understood. Consequently, it is crucial to gain a comprehensive understanding of the molecular bases of cell oxidative stress signaling, which will then provide novel therapeutic opportunities to interfere with disease progression via targeting specific signaling pathways.Currently, Dr. Qin's work is focused on inflammatory and oxidative stress responses using the retinal pigment epithelial (RPE) cells as a model. The study of RPE cell inflammatory and oxidative stress responses has successfully led to a better understanding of RPE cell biology and identification of potential therapeutic targets.
Suppressors of Cytokine Signaling (SOCS) in T cell differentiation, maturation, and function
Douglas C Palmer; Restifo, Nicholas P
Cytokines are key modulators of T cell biology but their influence can be attenuated by suppressors of cytokine signaling (SOCS), a family of proteins comprised of eight members, SOCS1-7 and CIS. SOCS proteins regulate cytokine signals that control the polarization of CD4+ T cells into Th1, Th2, Th17, and T regulatory cell lineages, the maturation of CD8+ T cells from naïve to "stem-cell memory" (Tscm), central memory (Tcm), and effector memory (Tem) states, and the activation of these lympho...
Thermodynamic and Kinetic Analysis of Sensitivity Amplification in Biological Signal Transduction
Qian, H
Based on a thermodynamic analysis of the kinetic model for the protein phosphorylation-dephosphorylation cycle, we study the ATP (or GTP) energy utilization of this ubiquitous biological signal transduction process. It was shown that the free energy from hydrolysis inside cells, Delta G (phosphorylation potential), controls the amplification and sensitivity of the switch-like cellular module; the response coefficient of the sensitivity amplification approaches the optimal 1 and the Hill coefficeint increases with increasing Delta G. Futhermore, we show the high amplification in zero-order ultrasensitivity is mechanistically related to the proofreading kinetics for protein biosynthesis. Both utilize multiple kinetic cycles in time to gain temporal cooperativity, in contrast to allosteric cooperativity that utilizes multiple subunits in a protein.
Chemokines: a new dendritic cell signal for T cell activation
Directory of Open Access Journals (Sweden)
Christoph A Thaiss
Full Text Available Dendritic cells (DCs are the main inducers and regulators of cytotoxic T lymphocyte (CTL responses against viruses and tumors. One checkpoint to avoid misguided CTL activation, which might damage healthy cells of the body, is the necessity for multiple activation signals, involving both antigenic as well as additional signals that reflect the presence of pathogens. DCs provide both signals when activated by ligands of pattern recognition receptors and licensed by helper lymphocytes. Recently, it has been established that such T cell licensing can be facilitated by CD4+ T helper cells (classical licensing or by NKT cells (alternative licensing. Licensing regulates the DC/CTL cross-talk at multiple layers. Direct recruitment of CTLs through chemokines released by licensed DCs has recently emerged as a common theme and has a crucial impact on the efficiency of CTL responses. Here, we discuss recent advances in our understanding of DC licensing for cross-priming and implications for the temporal and spatial regulation underlying this process. Future vaccination strategies will benefit from a deeper insight into the mechanisms that govern CTL activation.
Tritium and Autoradiography in Cell Biology
International Nuclear Information System (INIS)
Because tritium emits low energy beta radiation, it is the most useful isotope for high resolution autoradiography. The relative abundance of hydrogen in most biologically important substances combined with a relatively short half-life allows the labelling of cellular components at specific activities that can often be detected at intracellular dimensions by the use of nuclear emulsions. The cells are attached to glass by various cytological procedures and after fixation a -wet or fluid photographic emulsion is applied directly to the cell surface and allowed to dry. After exposure the emulsion is developed while still in contact with the biological specimen. The preparation, an autoradiogram, when viewed under the light microscope shows the cellular structures and the location of the isotope with a resolution of less than 1 pm. In this way the distribution of tritium-labelled deoxyribonucleic acid (DNA) of individual chromosomes has been traced through two to three cell divisions. These studies were made possible by the preparation of tritiated thymidine which is a highly selective label for DNA and is quickly depleted when the cell is removed from the environment containing the labelled thymidine. The technique has yielded information on the mechanism of DNA replication, structure and reproduction of chromosomes, kinetics of cell division and more recently on the patterns and time sequence in the reproduction of different chromosomes in the same nucleus and the different parts of a single chromosome. All chromosomes studied so far contain two functional sub-units of DNA which are distributed in a semi-conservative fashion during reproduction. The two sub-units are unlike in some structural sense that limits the type of exchanges that may occur among the four sub-units of a reproducing chromosome. Present evidence on sequences leads to the hypothesis that chromosomes reproduce in a genetically controlled sequence. Further evidence on the patterns and mechanism of
The biology of circulating tumor cells.
Pantel, K; Speicher, M R
Metastasis is a biologically complex process consisting of numerous stochastic events which may tremendously differ across various cancer types. Circulating tumor cells (CTCs) are cells that are shed from primary tumors and metastatic deposits into the blood stream. CTCs bear a tremendous potential to improve our understanding of steps involved in the metastatic cascade, starting from intravasation of tumor cells into the circulation until the formation of clinically detectable metastasis. These efforts were propelled by novel high-resolution approaches to dissect the genomes and transcriptomes of CTCs. Furthermore, capturing of viable CTCs has paved the way for innovative culturing technologies to study fundamental characteristics of CTCs such as invasiveness, their kinetics and responses to selection barriers, such as given therapies. Hence the study of CTCs is not only instrumental as a basic research tool, but also allows the serial monitoring of tumor genotypes and may therefore provide predictive and prognostic biomarkers for clinicians. Here, we review how CTCs have contributed to significant insights into the metastatic process and how they may be utilized in clinical practice. PMID:26050619
Categorization of biologically relevant chemical signals in the medial amygdala
Samuelsen, Chad L.; Meredith, Michael
Many species employ chemical signals to convey messages between members of the same species (conspecific), but chemosignals may also provide information to another species (heterospecific). Here, we found that conspecific chemosignals (male, female mouse urine) increased immediate early gene-protein (IEG) expression in both anterior and posterior medial amygdala of male mice, whereas most heterospecific chemosignals (e.g.: hamster vaginal fluid, steer urine) increased expression only in anter...
Cell biology apps for Apple devices.
Stark, Louisa A
Apps for touch-pad devices hold promise for guiding and supporting learning. Students may use them in the classroom or on their own for didactic instruction, just-in-time learning, or review. Since Apple touch-pad devices (i.e., iPad and iPhone) have a substantial share of the touch-pad device market (Campbell, 2012), this Feature will explore cell biology apps available from the App Store. My review includes iPad and iPhone apps available in June 2012, but does not include courses, lectures, podcasts, audiobooks, texts, or other books. I rated each app on a five-point scale (1 star = lowest; 5 stars = highest) for educational and production values; I also provide an overall score. PMID:22949420
A portable monitor system for biology signal based on singlechip
Tu, Qiaoling; Guo, Jianhua; He, Li; Xu, Xia
The objectives of the paper are to improve accuracy of the electrocardiogram and temperature signal, improve the system stability and the capability of dynamic response, and decrease power consumption and volume of the system. The basic method is making use of the inner resource of the singlechip, such as the exact constant-current source, hardware multiplier, ADC, etc. The model of singlechip is MSP430F449 of TI (Texas Instruments). A simple integral-coefficient band-rejection digital filter was designed for analyzing the electrocardiogram signal. The deviation of temperature coming from the degradation of battery voltage was compensated for. An automatic discharge access was designed in the circuit to improve the capability of dynamic response of circuit. The results indicate that the 50 Hz power frequency interfering and the baseline drift are filtered, the figure is clear, the accuracy of temperature is 0.03°C, and the consumption current is less than 1.3mA. The system can meet the requirement in ward monitor and surgery monitor.
Oncogenic KRAS Regulates Tumor Cell Signaling via Stromal Reciprocation.
Tape, Christopher J; Ling, Stephanie; Dimitriadi, Maria; McMahon, Kelly M; Worboys, Jonathan D; Leong, Hui Sun; Norrie, Ida C; Miller, Crispin J; Poulogiannis, George; Lauffenburger, Douglas A; Jørgensen, Claus
Oncogenic mutations regulate signaling within both tumor cells and adjacent stromal cells. Here, we show that oncogenic KRAS (KRAS(G12D)) also regulates tumor cell signaling via stromal cells. By combining cell-specific proteome labeling with multivariate phosphoproteomics, we analyzed heterocellular KRAS(G12D) signaling in pancreatic ductal adenocarcinoma (PDA) cells. Tumor cell KRAS(G12D) engages heterotypic fibroblasts, which subsequently instigate reciprocal signaling in the tumor cells. Reciprocal signaling employs additional kinases and doubles the number of regulated signaling nodes from cell-autonomous KRAS(G12D). Consequently, reciprocal KRAS(G12D) produces a tumor cell phosphoproteome and total proteome that is distinct from cell-autonomous KRAS(G12D) alone. Reciprocal signaling regulates tumor cell proliferation and apoptosis and increases mitochondrial capacity via an IGF1R/AXL-AKT axis. These results demonstrate that oncogene signaling should be viewed as a heterocellular process and that our existing cell-autonomous perspective underrepresents the extent of oncogene signaling in cancer. VIDEO ABSTRACT. PMID:27087446
Cyclopamine and hedgehog signaling: chemistry, biology, medical perspectives.
Heretsch, Philipp; Tzagkaroulaki, Lito; Giannis, Athanassios
When Odysseus left the devastated city of Troy after ten years of siege he could not foresee the perils he still had to face. The encounter with the cyclops, a giant with only one eye placed in the middle of its forehead, was doubtlessly one of the creepiest and most dangerous of his adventures. In the end, Odysseus could only escape with the help of a sheep. Whether Homers cyclops was inspired by the observation of terribly malformed neonates remains speculative. However, when sheep herders in Idaho in the middle of the 20th century faced an increasing number of cyclops-like sheep in their herds, a unique cascade of chemical, biological, and medicinal discoveries was initiated. This Minireview tells this story and shows its impact on modern biomedical research. PMID:20429080
Lessons learned about spaceflight and cell biology experiments
Hughes-Fulford, Millie
Conducting cell biology experiments in microgravity can be among the most technically challenging events in a biologist's life. Conflicting events of spaceflight include waiting to get manifested, delays in manifest schedules, training astronauts to not shake your cultures and to add reagents slowly, as shaking or quick injection can activate signaling cascades and give you erroneous results. It is important to select good hardware that is reliable. Possible conflicting environments in flight include g-force and vibration of launch, exposure of cells to microgravity for extended periods until hardware is turned on, changes in cabin gases and cosmic radiation. One should have an on-board 1-g control centrifuge in order to eliminate environmental differences. Other obstacles include getting your funding in a timely manner (it is not uncommon for two to three years to pass between notification of grant approval for funding and actually getting funded). That said, it is important to note that microgravity research is worthwhile since all terrestrial life evolved in a gravity field and secrets of biological function may only be answered by removing the constant of gravity. Finally, spaceflight experiments are rewarding and worth your effort and patience.
Oxygen in human health from life to death – An approach to teaching redox biology and signaling to graduate and medical students
Directory of Open Access Journals (Sweden)
Margaret M. Briehl
Full Text Available In the absence of oxygen human life is measured in minutes. In the presence of oxygen, normal metabolism generates reactive species (ROS that have the potential to cause cell injury contributing to human aging and disease. Between these extremes, organisms have developed means for sensing oxygen and ROS and regulating their cellular processes in response. Redox signaling contributes to the control of cell proliferation and death. Aberrant redox signaling underlies many human diseases. The attributes acquired by altered redox homeostasis in cancer cells illustrate this particularly well. This teaching review and the accompanying illustrations provide an introduction to redox biology and signaling aimed at instructors of graduate and medical students.
Cell-free biology: exploiting the interface between synthetic biology and synthetic chemistry
Harris, D. Calvin; Jewett, Michael C.
Just as synthetic organic chemistry once revolutionized the ability of chemists to build molecules (including those that did not exist in nature) following a basic set of design rules, cell-free synthetic biology is beginning to provide an improved toolbox and faster process for not only harnessing but also expanding the chemistry of life. At the interface between chemistry and biology, research in cell-free synthetic systems is proceeding in two different directions: using synthetic biology ...
Epigenetic disruption of cell signaling in nasopharyngeal carcinoma
Institute of Scientific and Technical Information of China (English)
Li-Li Li; Xing-Sheng Shu; Zhao-Hui Wang; Ya Cao; Qian Tao
Nasopharyngeal carcinoma (NPC) is a malignancy with remarkable ethnic and geographic distribution in southern China and Southeast Asia. Alternative to genetic changes, aberrant epigenetic events disrupt multiple genes involved in cell signaling pathways through DNA methylation of promoter CpG islands and/ or histone modifications. These epigenetic alterations grant cell growth advantage and contribute to the initiation and progression of NPC. In this review, we summariye the epigenetic deregulation of cell signaling in NPC tumorigenesis and highlight the importance of identifying epigenetic cell signaling regulators in NPC research. Developing pharmacologic strategies to reverse the epigenetic-silencing of cell signaling regulators might thus be useful to NPC prevention and therapy.
Genome Annotation in a Community College Cell Biology Lab
Beagley, C. Timothy
The Biology Department at Salt Lake Community College has used the IMG-ACT toolbox to introduce a genome mapping and annotation exercise into the laboratory portion of its Cell Biology course. This project provides students with an authentic inquiry-based learning experience while introducing them to computational biology and contemporary learning…
Van den Eynden, Jimmy
The central nervous system (CNS) is an integration center for signal processing, receiving signals from the different sensory systems and transmitting signals to the motor system. The main cells conducting signals are neurons, and for the largest part of the 20th century most attention of neuroscientist was focused on neurons. A role of glial cells, for a long time considered as passive connective tissue elements, in normal physiology and pathophysiology is now becoming increasingly appreciat...
A New Stem Cell Biology: The Continuum and Microvesicles
Quesenberry, Peter J.; Dooner, Mark S.; Goldberg, Laura R.; Aliotta, Jason M.; Pereira, Mandy; Amaral, Ashley; Del Tatto, Michael M.; Hixson, Douglas C.; Ramratnam, Bharat
The hierarchical models of stem cell biology have been based on work first demonstrating pluripotental spleen-colony-forming units, then showing progenitors with many differentiation fates assayed in in vitro culture; there followed the definition and separation of "stem cells" using monoclonal antibodies to surface epitopes and fluorescent-activated cell characterization and sorting (FACS). These studies led to an elegant model of stem cell biology in which primitive dormant G0 stem cells wi...
Wnt signaling in adult intestinal stem cells and cancer
Krausová, M. (Michaela); Kořínek, V. (Vladimír)
Signaling initiated by secreted glycoproteins of the Wnt family regulates many aspects of embryonic development and it is involved in homeostasis of adult tissues. In the gastrointestinal (GI) tract the Wnt pathway maintains the self-renewal capacity of epithelial stem cells. The stem cell attributes are conferred by mutual interactions of the stem cell with its local microenvironment, the stem cell niche. The niche ensures that the threshold of Wnt signaling in the stem cell is kept in physi...
Synthetic biology: programming cells for biomedical applications.
Hörner, Maximilian; Reischmann, Nadine; Weber, Wilfried
The emerging field of synthetic biology is a novel biological discipline at the interface between traditional biology, chemistry, and engineering sciences. Synthetic biology aims at the rational design of complex synthetic biological devices and systems with desired properties by combining compatible, modular biological parts in a systematic manner. While the first engineered systems were mainly proof-of-principle studies to demonstrate the power of the modular engineering approach of synthetic biology, subsequent systems focus on applications in the health, environmental, and energy sectors. This review describes recent approaches for biomedical applications that were developed along the synthetic biology design hierarchy, at the level of individual parts, of devices, and of complex multicellular systems. It describes how synthetic biological parts can be used for the synthesis of drug-delivery tools, how synthetic biological devices can facilitate the discovery of novel drugs, and how multicellular synthetic ecosystems can give insight into population dynamics of parasites and hosts. These examples demonstrate how this new discipline could contribute to novel solutions in the biopharmaceutical industry. PMID:23502560
A Diagnostic Assessment for Introductory Molecular and Cell Biology
Shi, Jia; Wood, William B.; Martin, Jennifer M.; Guild, Nancy A.; Vicens, Quentin; Knight, Jennifer K.
We have developed and validated a tool for assessing understanding of a selection of fundamental concepts and basic knowledge in undergraduate introductory molecular and cell biology, focusing on areas in which students often have misconceptions. This multiple-choice Introductory Molecular and Cell Biology Assessment (IMCA) instrument is designed…
Topography of plasma membrane microdomains and its consequences for mast cell signaling
Czech Academy of Sciences Publication Activity Database
Heneberg, Petr; Lebduška, Pavel; Dráberová, Lubica; Korb, Jan; Dráber, Petr
Roč. 36, č. 10 (2006), s. 2795-2806. ISSN 0014-2980 Institutional research plan: CEZ:AV0Z50520514 Keywords : Thy-1 * mast cell signaling * membrane microdomains Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.772, year: 2006
Hybrid modeling of cell signaling and transcriptional reprogramming and its application in C. elegans development
Directory of Open Access Journals (Sweden)
Elana J Fertig
Full Text Available Modeling of signal driven transcriptional reprogramming is critical for understanding of organism development, human disease, and cell biology. Many current modeling techniques discount key features of the biological sub-systems when modeling multi-scale, organism level processes. We present a mechanistic hybrid model, GESSA, which integrates a novel pooled probabilistic Boolean network model of cell signaling and a stochastic simulation of transcription and translation responding to a diffusion model of extra-cellular signals. We apply the model to simulate the well studied cell fate decision process of the vulval precursor cells (VPCs in C. elegans, using experimentally derived rate constants wherever possible and shared parameters to avoid overfitting. We demonstrate that GESSA recovers (1 the effects of varying scaffold protein concentration on signal strength, (2 amplification of signals in expression, (3 the relative external ligand concentration in a known geometry, and (4 feedback in biochemical networks. We demonstrate that setting model parameters based on wild-type and LIN-12 loss-of-function mutants in C. elegans leads to correct prediction of a wide variety of mutants including partial penetrance of phenotypes. Moreover, the model is relatively insensitive to parameters, retaining the wild-type phenotype for a wide range of cell signaling rate parameters.
Alternative Educational Approach to Introducing Cell Biology
Directory of Open Access Journals (Sweden)
Rosilane T. Silva
Full Text Available First year medical students usually have a great difficulty to visualize a three dimensional cell. They also present a series of misconceptions related to cell biology that seems to begin in the high school. An alternative educational approach is being tested with high school students in order to minimize these misconceptions, and also increase the pupils interest in the subject. The approach combines theoretical classes with experimental activities, the use of models, games, discussions, and oral presentations by the students at the end of the educational module. In short, the experimental activities are low-cost, easy-to-follow experiments that basically show a few properties of the living cells, such as membrane transport, enzyme action as well as the importance of the membrane integrity for life. A card game relates the functions of the organnels by matching pairs of cards. This game has one card without a matching pair that explains apoptosis; the player that ends up with this card loses the game. The pupils learn while they play the game. A 3D model of the membrane shows the major components and allows the observation of membrane assimetry. After comparing some panels of photomicrographs of cells and organnels, the students are presented to a 3D model of a cell as the teacher tries to relate the panels with a three dimensional visualization. They also have the opportunity to present their own models. The opinion of high school teachers about the different activities will be shown. The aim of this educational module is to promote learning while different abilities, according to Gardners Multiple Intelligences Theory, such as the visual-spatial, bodily-kinesthetic, interpersonal, and naturalistic are being developed. We believe that the diversity of approaches is one of the most important
A brief history of the Japan Society for Cell Biology.
Tashiro, Y; Okigaki, T
The Japan Society for Cell Biology (JSCB) was first founded in 1950 as the Japan Society for Cellular Chemistry under the vigorous leadership of Seizo Katsunuma, in collaboration with Shigeyasu Amano and Satimaru Seno. The Society was provisionally named as above simply because cell biology had not yet been coined at that time in Japan, although in prospect and reality the Society was in fact for the purpose of pursuing cell biology. Later in 1964, the Society was properly renamed as the Japan Society for Cell Biology. After this renaming, the JSCB made great efforts to adapt itself to the rapid progress being made in cell biology. For this purpose the Society's constitution was created in 1966 and revised in 1969. According to the revised constitution, the President, Executive Committee and Councils were to be determined by ballot vote. The style of the annual meetings was gradually modified to incorporate general oral and poster presentations in addition to Symposia (1969-1974). The publication of annual periodicals in Japanese called Symposia of the Japan Society for Cellular Chemistry (1951-1967) and later Symposia of the Japan Society for Cell Biology (1968-1974) was replaced by a new international journal called Cell Structure and Function initiated in 1975. This reformation made it possible for the Society to participate in the Science Council of Japan in 1975 and finally in 1993 to acquire its own study section of Cell Biology with grants-in-aid from the Ministry of Education and Science, Japan. The JSCB hosted the 3rd International Congress on Cell Biology (ICCB) in 1984 and the 3rd Asian-Pacific Organization for Cell Biology (APOCB) Congress in 1998, thus contributing to the international advancement of cell biology. Now the membership of JSCB stands at approximately 1,800 and the number of presentations per meeting is 300 to 400 annually. Although a good number of interesting and important findings in cell biology have been reported from Japan, the
Micro and nano-platforms for biological cell analysis
DEFF Research Database (Denmark)
Svendsen, Winnie Edith; Castillo, Jaime; Moresco, Jacob Lange;
In this paper some technological platforms developed for biological cell analysis will be presented and compared to existing systems. In brief, we present a novel micro cell culture chamber based on diffusion feeding of cells, into which cells can be introduced and extracted after culturing using...
Adhesion in the stem cell niche: biological roles and regulation
Chen, Shuyi; Lewallen, Michelle; Xie, Ting
Stem cell self-renewal is tightly controlled by the concerted action of stem cell-intrinsic factors and signals within the niche. Niche signals often function within a short range, allowing cells in the niche to self-renew while their daughters outside the niche differentiate. Thus, in order for stem cells to continuously self-renew, they are often anchored in the niche via adhesion molecules. In addition to niche anchoring, however, recent studies have revealed other important roles for adhe...
Learning Cell Biology as a Team: A Project-Based Approach to Upper-Division Cell Biology
Wright, Robin; Boggs, James
To help students develop successful strategies for learning how to learn and communicate complex information in cell biology, we developed a quarter-long cell biology class based on team projects. Each team researches a particular human disease and presents information about the cellular structure or process affected by the disease, the cellular…
Nuclear Receptor Signaling Atlas: Opening Access to the Biology of Nuclear Receptor Signaling Pathways.
Directory of Open Access Journals (Sweden)
Lauren B Becnel
Full Text Available Signaling pathways involving nuclear receptors (NRs, their ligands and coregulators, regulate tissue-specific transcriptomes in diverse processes, including development, metabolism, reproduction, the immune response and neuronal function, as well as in their associated pathologies. The Nuclear Receptor Signaling Atlas (NURSA is a Consortium focused around a Hub website (www.nursa.org that annotates and integrates diverse 'omics datasets originating from the published literature and NURSA-funded Data Source Projects (NDSPs. These datasets are then exposed to the scientific community on an Open Access basis through user-friendly data browsing and search interfaces. Here, we describe the redesign of the Hub, version 3.0, to deploy "Web 2.0" technologies and add richer, more diverse content. The Molecule Pages, which aggregate information relevant to NR signaling pathways from myriad external databases, have been enhanced to include resources for basic scientists, such as post-translational modification sites and targeting miRNAs, and for clinicians, such as clinical trials. A portal to NURSA's Open Access, PubMed-indexed journal Nuclear Receptor Signaling has been added to facilitate manuscript submissions. Datasets and information on reagents generated by NDSPs are available, as is information concerning periodic new NDSP funding solicitations. Finally, the new website integrates the Transcriptomine analysis tool, which allows for mining of millions of richly annotated public transcriptomic data points in the field, providing an environment for dataset re-use and citation, bench data validation and hypothesis generation. We anticipate that this new release of the NURSA database will have tangible, long term benefits for both basic and clinical research in this field.
Nuclear Receptor Signaling Atlas: Opening Access to the Biology of Nuclear Receptor Signaling Pathways
Becnel, Lauren B.; Darlington, Yolanda F.; Ochsner, Scott A.; Easton-Marks, Jeremy R.; Watkins, Christopher M.; McOwiti, Apollo; Kankanamge, Wasula H.; Wise, Michael W.; DeHart, Michael; Margolis, Ronald N.; McKenna, Neil J.
Signaling pathways involving nuclear receptors (NRs), their ligands and coregulators, regulate tissue-specific transcriptomes in diverse processes, including development, metabolism, reproduction, the immune response and neuronal function, as well as in their associated pathologies. The Nuclear Receptor Signaling Atlas (NURSA) is a Consortium focused around a Hub website (www.nursa.org) that annotates and integrates diverse 'omics datasets originating from the published literature and NURSA-funded Data Source Projects (NDSPs). These datasets are then exposed to the scientific community on an Open Access basis through user-friendly data browsing and search interfaces. Here, we describe the redesign of the Hub, version 3.0, to deploy "Web 2.0" technologies and add richer, more diverse content. The Molecule Pages, which aggregate information relevant to NR signaling pathways from myriad external databases, have been enhanced to include resources for basic scientists, such as post-translational modification sites and targeting miRNAs, and for clinicians, such as clinical trials. A portal to NURSA's Open Access, PubMed-indexed journal Nuclear Receptor Signaling has been added to facilitate manuscript submissions. Datasets and information on reagents generated by NDSPs are available, as is information concerning periodic new NDSP funding solicitations. Finally, the new website integrates the Transcriptomine analysis tool, which allows for mining of millions of richly annotated public transcriptomic data points in the field, providing an environment for dataset re-use and citation, bench data validation and hypothesis generation. We anticipate that this new release of the NURSA database will have tangible, long term benefits for both basic and clinical research in this field. PMID:26325041
The retinoblastoma tumor suppressor and stem cell biology
Sage, Julien
Stem cells play a critical role during embryonic development and in the maintenance of homeostasis in adult individuals. The retinoblastoma tumor suppressor RB controls the proliferation, differentiation, and survival of cells, and accumulating evidence points to a central role for RB activity in the biology of stem and progenitor cells. In this review by Sage, recent studies investigating the role of RB in embryonic stem cells, adult stem cells, and progenitor cells in plants and mammals is ...
Cytokine signaling in the differentiation of innate effector cells
Huang, Hua; Li, Yapeng; Qi, Xiaopeng
Innate effector cells, including innate effector cells of myeloid and lymphoid lineages, are crucial components of various types of immune responses. Bone marrow progenitors differentiate into many subsets of innate effector cells after receiving instructional signals often provided by cytokines. Signal transducer and activator of transcription (STATs) have been shown to be essential in the differentiation of various types of innate effector cells. In this review, we focus specifically on the...
Stem cell biology and neurodegenerative disease.
McKay, R D
The fundamental basis of our work is that organs are generated by multipotent stem cells, whose properties we must understand to control tissue assembly or repair. Central nervous system (CNS) stem cells are now recognized as a well-defined population of precursors that differentiate into cells that are indisputably neurons and glial cells. Work from our group played an important role in defining stem cells of the CNS. Embryonic stem (ES) cells also differentiate to specific neuron and glial ...
Wnt signaling and the control of human stem cell fate.
Van Camp, J K; Beckers, S; Zegers, D; Van Hul, W
Wnt signaling determines major developmental processes in the embryonic state and regulates maintenance, self-renewal and differentiation of adult mammalian tissue stem cells. Both β-catenin dependent and independent Wnt pathways exist, and both affect stem cell fate in developing and adult tissues. In this review, we debate the response to Wnt signal activation in embryonic stem cells and human, adult stem cells of mesenchymal, hematopoetic, intestinal, gastric, epidermal, mammary and neural lineages, and discuss the need for Wnt signaling in these cell types. Due to the vital actions of Wnt signaling in developmental and maintenance processes, deregulation of the pathway can culminate into a broad spectrum of developmental and genetic diseases, including cancer. The way in which Wnt signals can feed tumors and maintain cancer stem stells is discussed as well. Manipulation of Wnt signals both in vivo and in vitro thus carries potential for therapeutic approaches such as tissue engineering for regenerative medicine and anti-cancer treatment. Although many questions remain regarding the complete Wnt signal cell-type specific response and interplay of Wnt signaling with pathways such as BMP, Hedgehog and Notch, we hereby provide an overview of current knowledge on Wnt signaling and its control over human stem cell fate. PMID:24323281
Cytokine signaling for proliferation, survival, and death in hematopoietic cells.
Miyajima, A; Ito, Y; Kinoshita, T
The survival, proliferation, and differentiation of hematopoietic cells are regulated by cytokines. In the absence of cytokines, hematopoietic cells not only stop proliferation, but undergo apoptosis. This strict dependency of hematopoietic cells on cytokines is an important mechanism that maintains the homeostasis of blood cells. Cytokines induce various intracellular signaling pathways by activating the receptor-associated Janus kinases (Jaks), and distinct signals are responsible for cell cycle progression and cell survival. Induction of signals for cell cycle progression without suppressing apoptosis results in apoptotic cell death, indicating the essential role of anti-apoptotic signaling for cell growth. In hematopoietic cells, Ras, a cellular protooncogen product, and phosphatidylinositol 3 kinase are involved in the suppression of apoptosis. Cytokine depletion not only turns off anti-apoptotic signaling, but also actively induces cell death by activating caspases, a distinct family of cysteine proteases. Alterations in the mechanisms of cytokine signaling for cell cycle progression and anti-apoptotic function are implicated in hematological disorders. PMID:10222650
Excellence in cell signaling research recognized with major new award.
Feller, Stephan M
The newly installed Life Sciences Breakthrough Prize (http://www.breakthroughprizeinlifesciences.org/), which comes with more than double the financial reward of the Nobel Prize, has been awarded to several world-leaders in the field of cancer-related cell signaling and therapy research: Lewis C. Cantley (PI3 kinase), Hans Clevers (Wnt signaling), Charles L. Sawyers (signaling-targeted cancer therapy), Bert Vogelstein (colorectal cancer signaling) and Robert Weinberg (Ras & other cancer-relevant genes). They have all made remarkable contributions to our understanding of cell communication and malignancies over the last decades. Needless to say that virtually all other awardees of the 11 scientists honored in 2013 have also, in one way or another, touched upon signaling molecules, highlighting the fundamental interdisciplinarity and significance of signal transduction for living cells in general. For example, Shinya Yamanaka's exciting work was built on the four transcriptional signaling proteins, Oct3/4, Sox2, Klf4 and c-Myc. PMID:23497077
The effect of suppressor of cytokine signaling 3 on GH signaling in beta-cells
DEFF Research Database (Denmark)
Rønn, Sif G; Hansen, Johnny A; Lindberg, Karen;
. Furthermore, using Northern blot analysis it was shown that SOCS-3 can completely inhibit GH-induced insulin production in these cells. Finally, 5-bromodeoxyuridine incorporation followed by fluorescence-activated cell sorting analysis showed that SOCS-3 inhibits GH-induced proliferation of INS-1 cells. These......GH is an important regulator of cell growth and metabolism. In the pancreas, GH stimulates mitogenesis as well as insulin production in beta-cells. The cellular effects of GH are exerted mainly through activation of the Janus kinase-signal transducer and activator of transcription (STAT) pathway....... Recently it has been found that suppressors of cytokine signaling (SOCS) proteins are able to inhibit GH-induced signal transduction. In the present study, the role of SOCS-3 in GH signaling was investigated in the pancreatic beta-cell lines RIN-5AH and INS-1 by means of inducible expression systems. Via...
Calcium signals and calcium channels in osteoblastic cells
Duncan, R. L.; Akanbi, K. A.; Farach-Carson, M. C.
Calcium (Ca2+) channels are present in non-excitable as well as in excitable cells. In bone cells of the osteoblast lineage, Ca2+ channels play fundamental roles in cellular responses to external stimuli including both mechanical forces and hormonal signals. They are also proposed to modulate paracrine signaling between bone-forming osteoblasts and bone-resorbing osteoclasts at local sites of bone remodeling. Calcium signals are characterized by transient increases in intracellular Ca2+ levels that are associated with activation of intracellular signaling pathways that control cell behavior and phenotype, including patterns of gene expression. Development of Ca2+ signals is a tightly regulated cellular process that involves the concerted actions of plasma membrane and intracellular Ca2+ channels, along with Ca2+ pumps and exchangers. This review summarizes the current state of knowledge concerning the structure, function, and role of Ca2+ channels and Ca2+ signals in bone cells, focusing on the osteoblast.
Computational cell model based on autonomous cell movement regulated by cell-cell signalling successfully recapitulates the "inside and outside" pattern of cell sorting
Directory of Open Access Journals (Sweden)
Ajioka Itsuki
Full Text Available Abstract Background Development of multicellular organisms proceeds from a single fertilized egg as the combined effect of countless numbers of cellular interactions among highly dynamic cells. Since at least a reminiscent pattern of morphogenesis can be recapitulated in a reproducible manner in reaggregation cultures of dissociated embryonic cells, which is known as cell sorting, the cells themselves must possess some autonomous cell behaviors that assure specific and reproducible self-organization. Understanding of this self-organized dynamics of heterogeneous cell population seems to require some novel approaches so that the approaches bridge a gap between molecular events and morphogenesis in developmental and cell biology. A conceptual cell model in a computer may answer that purpose. We constructed a dynamical cell model based on autonomous cell behaviors, including cell shape, growth, division, adhesion, transformation, and motility as well as cell-cell signaling. The model gives some insights about what cellular behaviors make an appropriate global pattern of the cell population. Results We applied the model to "inside and outside" pattern of cell-sorting, in which two different embryonic cell types within a randomly mixed aggregate are sorted so that one cell type tends to gather in the central region of the aggregate and the other cell type surrounds the first cell type. Our model can modify the above cell behaviors by varying parameters related to them. We explored various parameter sets with which the "inside and outside" pattern could be achieved. The simulation results suggested that direction of cell movement responding to its neighborhood and the cell's mobility are important for this specific rearrangement. Conclusion We constructed an in silico cell model that mimics autonomous cell behaviors and applied it to cell sorting, which is a simple and appropriate phenomenon exhibiting self-organization of cell population. The model
The continuous Sir Philip Sidney game: a simple model of biological signalling.
Johnstone, R A; Grafen, A
An analysis of Maynard Smith's two-player, ESS model of biological signalling, the "Sir Philip Sidney game", is presented. The stable strategies of the players in this game are shown to satisfy the conditions of Zahavi's handicap principle. At equilibrium, signals are honest, costly, and costly in a way that is related to the true quality revealed. Further analysis reveals that the level of cost required to maintain stability is inversely related to the degree of relatedness between the players. It therefore seems likely that stable biological signalling systems will feature lower signalling costs when communication occurs between relatives. A three-player, extended version of the model is investigated, in which signals are passed via an intermediate, or "messenger". It is shown that this destabilizes the signalling system, and leads to increased signalling costs. This result suggests that "kin conflict" theories of the evolution of the endosperm in flowering plants require further refinement. The introduction of a novel resource acquisition tissue, which mediates parent-offspring interaction during development, cannot be assumed to limit parent-offspring conflict simply because it carries an extra copy of the maternally inherited genes. The ability to add such complications to the Sir Philip Sidney game and still obtain solutions makes it a very useful modelling tool. PMID:1640723
Industrial systems biology and its impact on synthetic biology of yeast cell factories
DEFF Research Database (Denmark)
Fletcher, Eugene; Krivoruchko, Anastasia; Nielsen, Jens
Engineering industrial cell factories to effectively yield a desired product while dealing with industrially relevant stresses is usually the most challenging step in the development of industrial production of chemicals using microbial fermentation processes. Using synthetic biology tools, micro...
Evolutionary cell biology: functional insight from "endless forms most beautiful".
Richardson, Elisabeth; Zerr, Kelly; Tsaousis, Anastasios; Dorrell, Richard G; Dacks, Joel B
In animal and fungal model organisms, the complexities of cell biology have been analyzed in exquisite detail and much is known about how these organisms function at the cellular level. However, the model organisms cell biologists generally use include only a tiny fraction of the true diversity of eukaryotic cellular forms. The divergent cellular processes observed in these more distant lineages are still largely unknown in the general scientific community. Despite the relative obscurity of these organisms, comparative studies of them across eukaryotic diversity have had profound implications for our understanding of fundamental cell biology in all species and have revealed the evolution and origins of previously observed cellular processes. In this Perspective, we will discuss the complexity of cell biology found across the eukaryotic tree, and three specific examples of where studies of divergent cell biology have altered our understanding of key functional aspects of mitochondria, plastids, and membrane trafficking. PMID:26668171
NMU signaling promotes endometrial cancer cell progression by modulating adhesion signaling.
Lin, Ting-Yu; Wu, Fang-Ju; Chang, Chia-Lin; Li, Zhongyou; Luo, Ching-Wei
Neuromedin U (NMU) was originally named based on its strong uterine contractile activity, but little is known regarding its signaling/functions in utero. We identified that NMU and one of its receptors, NMUR2, are not only present in normal uterine endometrium but also co-expressed in endometrial cancer tissues, where the NMU level is correlated with the malignant grades and survival of patients. Cell-based assays further confirmed that NMU signaling can promote cell motility and proliferation of endometrial cancer cells derived from grade II tumors. Activation of NMU pathway in these endometrial cancer cells is required in order to sustain expression of various adhesion molecules, such as CD44 and integrin alpha1, as well as production of their corresponding extracellular matrix ligands, hyaluronan and collagen IV; it also increased the activity of SRC and its downstream proteins RHOA and RAC1. Thus, it is concluded that NMU pathway positively controls the adhesion signaling-SRC-Rho GTPase axis in the tested endometrial cancer cells and that changes in cell motility and proliferation can occur when there is manipulation of NMU signaling in these cells either in vitro or in vivo. Intriguingly, this novel mechanism also explains how NMU signaling promotes the EGFR-driven and TGFβ receptor-driven mesenchymal transitions. Through the above axis, NMU signaling not only can promote malignancy of the tested endometrial cancer cells directly, but also helps these cells to become more sensitive to niche growth factors in their microenvironment. PMID:26849234
Modeling cell-in-cell structure into its biological significance
He, M-f; Wang, S.; Y Wang; Wang, X-n
Although cell-in-cell structure was noted 100 years ago, the molecular mechanisms of 'entering' and the destination of cell-in-cell remain largely unclear. It takes place among the same type of cells (homotypic cell-in-cell) or different types of cells (heterotypic cell-in-cell). Cell-in-cell formation affects both effector cells and their host cells in multiple aspects, while cell-in-cell death is under more intensive investigation. Given that cell-in-cell has an important role in maintainin...
Two distinct sites in sonic Hedgehog combine for heparan sulfate interactions and cell signaling functions
DEFF Research Database (Denmark)
Chang, Shu-Chun; Mulloy, Barbara; Magee, Anthony I;
Hedgehog (Hh) proteins are morphogens that mediate many developmental processes. Hh signaling is significant for many aspects of embryonic development, whereas dysregulation of this pathway is associated with several types of cancer. Hh proteins require heparan sulfate proteoglycans (HSPGs) for...... their normal distribution and signaling activity. Here, we have used molecular modeling to examine the heparin-binding domain of sonic hedgehog (Shh). In biochemical and cell biological assays, the importance of specific residues of the putative heparin-binding domain for signaling was assessed. It was...
Host-pathogen systems biology: logical modelling of hepatocyte growth factor and Helicobacter pylori induced c-Met signal transduction
Directory of Open Access Journals (Sweden)
Kähne Thilo
Full Text Available Abstract Background The hepatocyte growth factor (HGF stimulates mitogenesis, motogenesis, and morphogenesis in a wide range of tissues, including epithelial cells, on binding to the receptor tyrosine kinase c-Met. Abnormal c-Met signalling contributes to tumour genesis, in particular to the development of invasive and metastatic phenotypes. The human microbial pathogen Helicobacter pylori can induce chronic gastritis, peptic ulceration and more rarely, gastric adenocarcinoma. The H. pylori effector protein cytotoxin associated gene A (CagA, which is translocated via a type IV secretion system (T4SS into epithelial cells, intracellularly modulates the c-Met receptor and promotes cellular processes leading to cell scattering, which could contribute to the invasiveness of tumour cells. Using a logical modelling framework, the presented work aims at analysing the c-Met signal transduction network and how it is interfered by H. pylori infection, which might be of importance for tumour development. Results A logical model of HGF and H. pylori induced c-Met signal transduction is presented in this work. The formalism of logical interaction hypergraphs (LIH was used to construct the network model. The molecular interactions included in the model were all assembled manually based on a careful meta-analysis of published experimental results. Our model reveals the differences and commonalities of the response of the network upon HGF and H. pylori induced c-Met signalling. As another important result, using the formalism of minimal intervention sets, phospholipase Cγ1 (PLCγ1 was identified as knockout target for repressing the activation of the extracellular signal regulated kinase 1/2 (ERK1/2, a signalling molecule directly linked to cell scattering in H. pylori infected cells. The model predicted only an effect on ERK1/2 for the H. pylori stimulus, but not for HGF treatment. This result could be confirmed experimentally in MDCK cells using a specific
Ezrin Enhances EGFR Signaling and Modulates Erlotinib Sensitivity in Non–Small Cell Lung Cancer Cells
Directory of Open Access Journals (Sweden)
Yasemin Saygideğer-Kont
Full Text Available Ezrin is a scaffolding protein that is involved in oncogenesis by linking cytoskeletal and membrane proteins. Ezrin interacts with epidermal growth factor receptor (EGFR in the cell membrane, but little is known about the effects of this interaction on EGFR signaling pathway. In this study, we established the biological and functional significance of ezrin-EGFR interaction in non–small cell lung cancer (NSCLC cells. Endogenous ezrin and EGRF interaction was confirmed by co-immunoprecipitation and immunofluorescent staining. When expression of ezrin was inhibited, EGFR activity and phosphorylation levels of downstream signaling pathway proteins ERK and STAT3 were decreased. Cell fractionation experiments revealed that nuclear EGFR was significantly diminished in ezrin-knockdown cells. Consequently, mRNA levels of EGFR target genes AURKA, COX-2, cyclin D1, and iNOS were decreased in ezrin-depleted cells. A small molecule inhibitor of ezrin, NSC305787, reduced EGF-induced phosphorylation of EGFR and downstream target proteins, EGFR nuclear translocation, and mRNA levels of nuclear EGFR target genes similar to ezrin suppression. NSC305787 showed synergism with erlotinib in wild-type EGFR-expressing NSCLC cells, whereas no synergy was observed in EGFR-null cells. Phosphorylation of ezrin on Y146 was found as an enhancer of ezrin-EGFR interaction and required for increased proliferation, colony formation, and drug resistance to erlotinib. These findings suggest that ezrin-EGFR interaction augments oncogenic functions of EGFR and that targeting ezrin may provide a potential novel approach to overcome erlotinib resistance in NSCLC cells.
Biological cell controllable patch-clamp microchip
Penmetsa, Siva; Nagrajan, Krithika; Gong, Zhongcheng; Mills, David; Que, Long
A patch-clamp (PC) microchip with cell sorting and positioning functions is reported, which can avoid drawbacks of random cell selection or positioning for a PC microchip. The cell sorting and positioning are enabled by air bubble (AB) actuators. AB actuators are pneumatic actuators, in which air pressure is generated by microheaters within sealed microchambers. The sorting, positioning, and capturing of 3T3 cells by this type of microchip have been demonstrated. Using human breast cancer cells MDA-MB-231 as the model, experiments have been demonstrated by this microchip as a label-free technical platform for real-time monitoring of the cell viability.
Parallel analysis of individual biological cells using multifocal laser tweezers Raman spectroscopy.
Liu, Rui; Taylor, Douglas S; Matthews, Dennis L; Chan, James W
We report on the development and characterization of a multifocal laser tweezers Raman spectroscopy (M-LTRS) technique for parallel Raman spectral acquisition of individual biological cells. Using a 785-nm diode laser and a time-sharing laser trapping scheme, multiple laser foci are generated to optically trap single polystyrene beads and suspension cells in a linear pattern. Raman signals from the trapped objects are simultaneously projected through the slit of a spectrometer and spatially resolved on a charge-coupled device (CCD) detector with minimal signal crosstalk between neighboring cells. By improving the rate of single-cell analysis, M-LTRS is expected to be a valuable method for studying single-cell dynamics of cell populations and for the development of high-throughput Raman based cytometers. PMID:21073802
Progenitor cells in the kidney: biology and therapeutic perspectives
Rookmaaker, M.B.; Verhaar, M.C.; Zonneveld, A.J. van; Rabelink, T.J.
Progenitor cells in the kidney: Biology and therapeutic perspectives. The stem cell may be viewed as an engineer who can read the blue print and become the building. The role of this fascinating cell in physiology and pathophysiology has recently attracted a great deal of interest. The archetype of
Computational Systems Biology Analysis of Cell Reprogramming and Activation Dynamics
Fu, Yan
In the past two decades, molecular cell biology has transitioned from a traditional descriptive science into a quantitative science that systematically measures cellular dynamics on different levels of genome, transcriptome and proteome. Along with this transition emerges the interdisciplinary field of systems biology, which aims to unravel complex interactions in biological systems through integrating experimental data into qualitative or quantitative models and computer simulations. In th...
Stem cells: a plant biology perspective
Scheres, B.J.G.
A recent meeting at the Juan March Foundation in Madrid, Spain brought together plant biologists to discuss the characteristics of plant stem cells that are unique and those that are shared by stem cells from the animal kingdom
An approach to evolving cell signaling networks in silico
Decraene, James; Mitchell, George G.; Kelly, Ciaran; McMullin, Barry
Cell Signaling Networks(CSN) are complex bio-chemical networks which, through evolution, have become highly efficient for governing critical control processes such as immunological responses, cell cycle control or homeostasis. From a computational point of view, modeling Artificial Cell Signaling Networks (ACSNs) in silico may provide new ways to design computer systems which may have specialized application areas. To investigate these new opportunities, we review the key issues of mod...
Evaluation of the Redesign of an Undergraduate Cell Biology Course
McEwen, Laura April; Harris, dik; Schmid, Richard F.; Vogel, Jackie; Western, Tamara; Harrison, Paul
This article offers a case study of the evaluation of a redesigned and redeveloped laboratory-based cell biology course. The course was a compulsory element of the biology program, but the laboratory had become outdated and was inadequately equipped. With the support of a faculty-based teaching improvement project, the teaching team redesigned the…
Systems-biology dissection of eukaryotic cell growth
Andrews Justen; Przytycka Teresa M
Abstract A recent article in BMC Biology illustrates the use of a systems-biology approach to integrate data across the transcriptome, proteome and metabolome of budding yeast in order to dissect the relationship between nutrient conditions and cell growth. See research article http://jbiol.com/content/6/2/4 and http://www.biomedcentral.com/1741-7007/8/68
Modeling human liver biology using stem cell-derived hepatocytes
Sun, Pingnan; Zhou, XiaoLing; Farnworth, Sarah; Arvind H Patel; Hay, David C.
Stem cell-derived hepatocytes represent promising models to study human liver biology and disease. This concise review discusses the recent progresses in the field, with a focus on human liver disease, drug metabolism and virus infection.
Modeling Human Liver Biology Using Stem Cell-Derived Hepatocytes
Arvind H Patel; Hay, David C.; Farnworth, Sarah L.; Pingnan Sun; Xiaoling Zhou
Stem cell-derived hepatocytes represent promising models to study human liver biology and disease. This concise review discusses the recent progresses in the field, with a focus on human liver disease, drug metabolism and virus infection.
Adipocyte activation of cancer stem cell signaling in breast cancer
Institute of Scientific and Technical Information of China (English)
Benjamin; Wolfson; Gabriel; Eades; Qun; Zhou
Signaling within the tumor microenvironment has a critical role in cancer initiation and progression. Adipocytes, one of the major components of the breast microenvironment,have been shown to provide pro-tumorigenic signals that promote cancer cell proliferation and invasiveness in vitro and tumorigenicity in vivo. Adipocyte secreted factors such as leptin and interleukin-6(IL-6) have a paracrine effect on breast cancer cells. In adipocyte-adjacent breast cancer cells, the leptin and IL-6 signaling pathways activate janus kinase 2/signal transducer and activatorof transcription 5, promoting the epithelial-mesenchymal transition, and upregulating stemness regulators such as Notch, Wnt and the Sex determining region Y-box 2/octamer binding transcription factor 4/Nanog signaling axis. In this review we will summarize the major signaling pathways that regulate cancer stem cells in breast cancer and describe the effects that adipocyte secreted IL-6 and leptin have on breast cancer stem cell signaling. Finally we will introduce a new potential treatment paradigm of inhibiting the adipocyte-breast cancer cell signaling via targeting the IL-6 or leptin pathways.
Sphingolipid mediators in cardiovascular cell biology and pathology.
Levade, T; Augé, N; Veldman, R J; Cuvillier, O; Nègre-Salvayre, A; Salvayre, R
Sphingolipids have emerged as a new class of lipid mediators. In response to various extracellular stimuli, sphingolipid turnover can be stimulated in vascular cells and cardiac myocytes. Subsequent generation of sphingolipid molecules such as ceramide, sphingosine, and sphingosine-1-phosphate, is followed by regulation of ion fluxes and activation of various signaling pathways leading to smooth muscle cell proliferation, endothelial cell differentiation or apoptotic cell death, cell contraction, retraction, or migration. The importance of sphingolipids in cardiovascular signaling is illustrated by recent observations implicating them in physiological processes such as vasculogenesis as well as in frequent pathological conditions, including atherosclerosis and its complications. PMID:11717151
TRPM5, a taste-signaling transient receptor potential ion-channel, is a ubiquitous signaling component in chemosensory cells
Directory of Open Access Journals (Sweden)
Hofmann Thomas
Full Text Available Abstract Background A growing number of TRP channels have been identified as key players in the sensation of smell, temperature, mechanical forces and taste. TRPM5 is known to be abundantly expressed in taste receptor cells where it participates in sweet, amino acid and bitter perception. A role of TRPM5 in other sensory systems, however, has not been studied so far. Results Here, we systematically investigated the expression of TRPM5 in rat and mouse tissues. Apart from taste buds, where we found TRPM5 to be predominantly localized on the basolateral surface of taste receptor cells, TRPM5 immunoreactivity was seen in other chemosensory organs – the main olfactory epithelium and the vomeronasal organ. Most strikingly, we found solitary TRPM5-enriched epithelial cells in all parts of the respiratory and gastrointestinal tract. Based on their tissue distribution, the low cell density, morphological features and co-immunostaining with different epithelial markers, we identified these cells as brush cells (also known as tuft, fibrillovesicular, multivesicular or caveolated cells. In terms of morphological characteristics, brush cells resemble taste receptor cells, while their origin and biological role are still under intensive debate. Conclusion We consider TRPM5 to be an intrinsic signaling component of mammalian chemosensory organs, and provide evidence for brush cells being an important cellular correlate in the periphery.
Investigation on the role of IGF-1 signal transduction in the biological radiation responses
International Nuclear Information System (INIS)
Effects of γ-irradiation on the IGF-1 related gene expressions and activations in various cell lines - Various expression patterns of IGF-1 and IGF-1R following γ-irradiation were observed according to the cell lines - The increased expressions of IGF-1 and IGF-1R were observed in Balb/3T3 and NIH/3T3 cells - Among the IGF-1 downstream signaling molecules, the phosphorylated ERK5 were not changed by γ-irradiation in all three examined cell lines, whereas the phosphorylated p65 were increased by γ -irradiation in all cell lines. The role of IGF-1 and p38 signaling in γ-irradiated mouse embryonic fibroblast (MEF) cells - In MEF cells, IGF-1 signaling molecules were decreased and p21/phosphorylated p38 were increased by γ-irradiation - The experiments with IGF-1R inhibitor (AG1024) and p38 inhibitor (SB203580) revealed that IGF-1 signaling is involved but not essential in radiation-induced cell growth arrest and senescence and that p38 MAP kinase play a important role in this cellular radiation response. The role of IGF-1 and p38 signaling in γ-irradiated mouse fibroblast (NIH/3T3) cell - In NIH/3T3 cells, IGF-1 signaling molecules and p21/phosphorylated p38 were increased by γ -irradiation. - However, the experiments with IGF-1R inhibitor (AG1024) and p38 inhibitor (SB203580) revealed that IGF-1 and p38 signaling do not play a crucial role in radiation-induced cell growth arrest and senescence in NIH/3T3 cells. Effects of γ-irradiation on the expressions and activations on the genes related to the IGF-1 signaling in mouse tissues - In γ-irradiated mice, the increased expressions of IGF-1 and IGF-1R were observed in the lung and kidney at 2 months after irradiation, and in all the tissues examined (lung, liver and kidney) at 6 months after irradiation. - In the lung of γ-irradiated mice at 6 months after irradiation, the increases of IGF-1R, phosphorylated FOXO3a, p65, p38, p21 were observed. - The patterns of altered expressions showed significant
Nitric Oxide Prevents Mouse Embryonic Stem Cell Differentiation Through Regulation of Gene Expression, Cell Signaling, and Control of Cell Proliferation.
Tapia-Limonchi, Rafael; Cahuana, Gladys M; Caballano-Infantes, Estefania; Salguero-Aranda, Carmen; Beltran-Povea, Amparo; Hitos, Ana B; Hmadcha, Abdelkrim; Martin, Franz; Soria, Bernat; Bedoya, Francisco J; Tejedo, Juan R
Nitric oxide (NO) delays mouse embryonic stem cell (mESC) differentiation by regulating genes linked to pluripotency and differentiation. Nevertheless, no profound study has been conducted on cell differentiation regulation by this molecule through signaling on essential biological functions. We sought to demonstrate that NO positively regulates the pluripotency transcriptional core, enforcing changes in the chromatin structure, in addition to regulating cell proliferation, and signaling pathways with key roles in stemness. Culturing mESCs with 2 μM of the NO donor diethylenetriamine/NO (DETA/NO) in the absence of leukemia inhibitory factor (LIF) induced significant changes in the expression of 16 genes of the pluripotency transcriptional core. Furthermore, treatment with DETA/NO resulted in a high occupancy of activating H3K4me3 at the Oct4 and Nanog promoters and repressive H3K9me3 and H3k27me3 at the Brachyury promoter. Additionally, the activation of signaling pathways involved in pluripotency, such as Gsk3-β/β-catenin, was observed, in addition to activation of PI3 K/Akt, which is consistent with the protection of mESCs from cell death. Finally, a decrease in cell proliferation coincides with cell cycle arrest in G2/M. Our results provide novel insights into NO-mediated gene regulation and cell proliferation and suggest that NO is necessary but not sufficient for the maintenance of pluripotency and the prevention of cell differentiation. J. Cell. Biochem. 117: 2078-2088, 2016. © 2016 Wiley Periodicals, Inc. PMID:26853909
Quantum fluctuations of mesoscopic biological cell at finite temperature
Institute of Scientific and Technical Information of China (English)
LI Hong-qi; XU Xing-lei
On the basis of the quantization of mesoscopic biological cell equivalent circuit,we studied the quantum fluctuations of voltage and current of mesoscopic biological cell equivalent circuit as finite temperature by Bogoliuov transformation.The result shows that the quantum fluctuations of voltage and current not only relate with the parameters of equivalent circuit,temperature,but also decay with time.This result may have significant value on the design and application of the bio-electronic apparatus.
Mechanistic modeling confronts the complexity of molecular cell biology
Phair, Robert D.
Mechanistic modeling has the potential to transform how cell biologists contend with the inescapable complexity of modern biology. I am a physiologist–electrical engineer–systems biologist who has been working at the level of cell biology for the past 24 years. This perspective aims 1) to convey why we build models, 2) to enumerate the major approaches to modeling and their philosophical differences, 3) to address some recurrent concerns raised by experimentalists, and then 4) to imagine a fu...
The Effect of Hypoxia on Mesenchymal Stem Cell Biology
Mostafa Ejtehadifar; Karim Shamsasenjan; Aliakbar Movassaghpour; Parvin Akbarzadehlaleh; Nima Dehdilani; Parvaneh Abbasi; Zahra Molaeipour; Mahshid Saleh
Although physiological and pathological role of hypoxia have been appreciated in mammalians for decades however the cellular biology of hypoxia more clarified in the past 20 years. Discovery of the transcription factor hypoxia-inducible factor (HIF)-1, in the 1990s opened a new window to investigate the mechanisms behind hypoxia. In different cellular contexts HIF-1 activation show variable results by impacting various aspects of cell biology such as cell cycle, apoptosis, diff...
Regulation of hematopoiesis and the hematopoietic stem cell niche by Wnt signaling pathways
Institute of Scientific and Technical Information of China (English)
Michael J Nemeth; David M Bodine
Hematopoietic stem cells (HSCs) are a rare population of cells that are responsible for life-long generation of blood cells of all lineages. In order to maintain their numbers, HSCs must establish a balance between the opposing cell fates of self-renewal (in which the ability to function as HSCs is retained) and initiation of hematopoietic differentiation. Multiple signaling pathways have been implicated in the regulation of HSC cell fate. One such set of pathways are those activated by the Wnt family of ligands. Wnt signaling pathways play a crucial role during embryogenesis and deregulation of these pathways has been implicated in the formation of solid tumors. Wnt signaling also plays a role in the regulation of stem cells from multiple tissues, such as embryonic, epidermal, and intestinal stem cells. However, the function of Wnt signaling in HSC biology is still controversial. In this review, we will discuss the basic characteristics of the adult HSC and its regulatory microenvironment, the "niche", focusing on the regulation of the HSC and its niche by the Wnt signaling pathways.
Advancing Our Understanding of Osteocyte Cell Biology
Guo, Dayong; BONEWALD, LYNDA F.
Osteocytes were the forgotten bone cell until the bone community could become convinced that these cells do serve an important role in bone function and maintenance. In this review we trace the history of osteocyte characterization and present some of the major observations that are leading to the conclusion that these cells are not passive placeholders residing in the bone matrix, but are indeed, major orchestrators of bone remodeling.
Computational modelling of multi-cell migration in a multi-signalling substrate
International Nuclear Information System (INIS)
Cell migration is a vital process in many biological phenomena ranging from wound healing to tissue regeneration. Over the past few years, it has been proven that in addition to cell–cell and cell-substrate mechanical interactions (mechanotaxis), cells can be driven by thermal, chemical and/or electrical stimuli. A numerical model was recently presented by the authors to analyse single cell migration in a multi-signalling substrate. That work is here extended to include multi-cell migration due to cell–cell interaction in a multi-signalling substrate under different conditions. This model is based on balancing the forces that act on the cell population in the presence of different guiding cues. Several numerical experiments are presented to illustrate the effect of different stimuli on the trajectory and final location of the cell population within a 3D heterogeneous multi-signalling substrate. Our findings indicate that although multi-cell migration is relatively similar to single cell migration in some aspects, the associated behaviour is very different. For instance, cell–cell interaction may delay single cell migration towards effective cues while increasing the magnitude of the average net cell traction force as well as the local velocity. Besides, the random movement of a cell within a cell population is slightly greater than that of single cell migration. Moreover, higher electrical field strength causes the cell slug to flatten near the cathode. On the other hand, as with single cell migration, the existence of electrotaxis dominates mechanotaxis, moving the cells to the cathode or anode pole located at the free surface. The numerical results here obtained are qualitatively consistent with related experimental works. (paper)
Cell and molecular biology. 8th Edition
Energy Technology Data Exchange (ETDEWEB)
De Robertis
Extensively revised and reorganized, this edition can be considered a new book. The chapters on the cell membrane, cell interactions, cytoskeleton and cell motility, cell secretion, interphase nucleus, the genetic code and genetic engineering, transcription and processing of RNA, ribosomes and protein synthesis, gene regulation and differentiation are completely rewritten. More than half of the 504 illustrations are new. The discussions are concise and easy to read. Each chapter offers an introduction to the broad objectives of that chapter and concluding summary paragraphs which underscore the important points.
NK cell biology: An update and future directions
Campbell, Kerry S.; Hasegawa, Jun
Natural killer (NK) cells constitute a minor subset of normal lymphocytes that initiate innate immune responses toward tumor and virus-infected cells. They can mediate spontaneous cytotoxicity toward these abnormal cells and rapidly secrete numerous cytokines and chemokines to promote subsequent adaptive immune responses. Significant progress has been made in the past two decades to improve our understanding of NK cell biology. Here we review recent discoveries, including a better comprehensi...
Thrombopoietin stimulates migration and activates multiple signaling pathways in hepatoblastoma cells
DEFF Research Database (Denmark)
Romanelli, Roberto G; Petrai, Ilaria; Robino, Gaia;
Thrombopoietin (TPO), a cytokine that participates in the differentiation and maturation of megakaryocytes, is produced in the liver, but only limited information is available on the biological response of liver-derived cells to TPO. In this study, we investigated whether HepG2 cells express c-Mpl......, the receptor for TPO, and whether TPO elicits biological responses and intracellular signaling in this cell type. Specific transcripts for c-Mpl were detected in HepG2 cells by RT-PCR, and expression of the protein was demonstrated by Western blot analysis and immunofluorescence. Exposure of HepG2 cells to TPO...... members of the MAPK family, including ERK and JNK, as assessed using phosphorylation-specific antibodies and immune complex kinase assays. TPO also activated phosphatidylinositol 3-kinase (PI3K) and the downstream kinase Akt in a time-dependent manner. Finally, activation of c-Mpl was associated...
The biology of human innate lymphoid cells
J.H.J. Bernink
In this thesis I performed studies to investigate the contribution of human innate lymphoid cells (ILCs) in maintaining the mucosal homeostasis, initiating and/or propagating inflammatory responses, but also - when not properly regulated - how these cells contribute to immunopathology. First I descr
Cell-Autonomous Gβ Signaling Defines Neuron-Specific Steady State Serotonin Synthesis in Caenorhabditis elegans.
Xu, Lu; Choi, Sunju; Xie, Yusu; Sze, Ji Ying
Heterotrimeric G proteins regulate a vast array of cellular functions via specific intracellular effectors. Accumulating pharmacological and biochemical studies implicate Gβ subunits as signaling molecules interacting directly with a wide range of effectors to modulate downstream cellular responses, in addition to their role in regulating Gα subunit activities. However, the native biological roles of Gβ-mediated signaling pathways in vivo have been characterized only in a few cases. Here, we identified a Gβ GPB-1 signaling pathway operating in specific serotonergic neurons to the define steady state serotonin (5-HT) synthesis, through a genetic screen for 5-HT synthesis mutants in Caenorhabditis elegans. We found that signaling through cell autonomous GPB-1 to the OCR-2 TRPV channel defines the baseline expression of 5-HT synthesis enzyme tryptophan hydroxylase tph-1 in ADF chemosensory neurons. This Gβ signaling pathway is not essential for establishing the serotonergic cell fates and is mechanistically separated from stress-induced tph-1 upregulation. We identified that ADF-produced 5-HT controls specific innate rhythmic behaviors. These results revealed a Gβ-mediated signaling operating in differentiated cells to specify intrinsic functional properties, and indicate that baseline TPH expression is not a default generic serotonergic fate, but is programmed in a cell-specific manner in the mature nervous system. Cell-specific regulation of TPH expression could be a general principle for tailored steady state 5-HT synthesis in functionally distinct neurons and their regulation of innate behavior. PMID:26402365