A Japanese translation, cultural adaptation, and linguistic and content validity confirmation of the Scored Patient-Generated Subjective Global Assessment.
The Scored Patient-Generated Subjective Global Assessment (PG-SGA©) is a globally recognized and used nutritional screening, assessment, monitoring, and triaging tool. The aim of this study was to translate and culturally adapt the original English PG-SGA for the Japanese speaking populations and to assess its linguistic validity (i.e., comprehensibility, difficulty) and content validity, as perceived by Japanese patients and healthcare professionals. In accordance with methodology used in previous Dutch, Thai, German, and Norwegian PG-SGA studies, we followed the ten steps of the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) Principles of Good Practice for Translation and Cultural Adaptation for Patient-Reported Outcome Measures. The study enrolled 50 patients and 50 healthcare professionals (HCPs) to evaluate the comprehensibility and difficulty of the translated and culturally adapted PG-SGA. The HCPs also evaluated the content validity of the translation. We evaluated each item and quantified scale indices for content validity (item content validity index (I-CVI), scale content validity index (S-CVI)), comprehensibility (item comprehensibility index (I-CI), scale comprehensibility index (S-CI)), and difficulty (item difficulty index (I-DI), scale difficulty index (S-DI)). Patients evaluated the comprehensibility and difficulty of the patient component as excellent (S-CI = 0.97, S-DI = 0.96). The professionals rated the Japanese version of both components of the PG-SGA as very relevant (S-CVI = 0.94). The professionals evaluated the comprehensibility of the professional component as being acceptable (S-CI = 0.88) but difficult (S-DI = 0.69), based predominantly on items related to physical examination (I-DI = 0.33-0.67). The PG-SGA was systematically translated and culturally adapted for the Japanese setting according to the ISPOR process. The Japanese version of the PG-SGA was perceived as comprehensive, easy to use, and relevant. Perceived difficulty in professional components, specifically in the context of metabolic demand and physical examination, will require appropriate training for professionals in order to optimize implementation.


Attenuation of the pupillary response to luminance and color changes during interocular suppression.
The present study investigated the effects of interocular suppression on the pupillary constriction to luminance and color changes. Stable interocular suppression was produced by presenting a flickering high-contrast grating to one eye and a spatially homogeneous field to the other eye. The results showed that the pupillary responses to luminance as well as color changes were clearly attenuated during interocular suppression; the pupillary constriction to stimulus changes was delayed and reduced in amplitude when those changes occurred in the suppressed eye. The attenuation of the pupillary response was observed over a wide range of test contrast extending to well above the threshold level. Moreover, the properties of the suppressive effect were very similar to those assessed psychophysically using both detection thresholds for weak stimuli and reaction times for suprathreshold stimuli. Overall, the present study provided converging evidence that the pupillary response can be a useful objective probe of interocular suppression in humans. The results are discussed in view of possible differential involvements of subcortical and cortical visual processing in driving the pupillary response as well as in interocular suppression.


Repeat structure of the catfish genome: a genomic and transcriptomic assessment of Tc1-like transposon elements in channel catfish (Ictalurus punctatus).
We have assessed the distribution and diversity of members of the Tc1/mariner superfamily of transposable elements in the channel catfish (Ictalurus punctatus) genome as well as evaluating the extent of transcription of Tc1 transposases in the species. Through use of PCR amplification and sequencing, assessment of random BAC end sequences (BES) equivalent to 1.2% genome coverage, and screening of over 45,000 catfish ESTs, a significant proportion of Tc1-like elements and their associated transcripts were captured. Up to 4.2% of the catfish genome in base pairs appears to be composed of Tc1-like transposon-related sequences and a significant fraction of the catfish cellular mRNA, approximately 0.6%, was transcribed from transposon-related sequences in both sense and antisense orientations. Based on results of repeat-masking, as much as 10% of BAC end sequences from catfish, which is a random survey of the genome, contain some remnant of Tc1 elements, suggesting that these elements are present in the catfish genome as numerous, small remnants of the transposons. Phylogenetic analysis allowed comparison of catfish Tc1 transposase types with those found in other vertebrate and invertebrate species. In spite of the existence of many types of Tc1-like sequences that are not yet able to be placed in clades with strong statistical support, it is clear that multiple families of Tc1-like elements exist in channel catfish.


Relaxin treatment reverses insulin resistance in mice fed a high-fat diet.
The endogenous hormone relaxin increases vascular reactivity and angiogenesis. We demonstrate that acute relaxin infusion in lean C57BL/6J mice enhances skeletal muscle perfusion and augments muscle glucose uptake during a hyperinsulinemic-euglycemic clamp. However, an acute effect was absent in mice fed a high-fat (HF) diet for 13 weeks. In contrast, mice fed an HF diet for 13 weeks and continuously treated with relaxin for the final 3 weeks of the diet exhibited decreased fasting blood glucose. Insulin-stimulated whole-body glucose disappearance and percent suppression of hepatic glucose production are corrected by chronic relaxin. The increase in peripheral glucose utilization is a result of augmented in vivo skeletal muscle glucose uptake. Relaxin intervention improves endothelial-dependent vascular reactivity and induces a two-fold proliferation in skeletal muscle capillarity. The metabolic effects of the treatment are not attributed to changes in myocellular insulin signaling. Relaxin intervention reverses the accumulation of collagen III in the liver and collagen III and collagen IV in the heart; this is induced by HF feeding. These studies show the potential of relaxin in the treatment of diet-induced insulin resistance and vascular dysfunction. Relaxin provides a novel therapeutic approach targeting the extramyocellular barriers to insulin action, which are critical to the pathogenesis of insulin resistance.


Expanding the phenotype associated with 17q12 duplication: case report and review of the literature.
The routine use of molecular karyotyping in the evaluation of patients with idiopathic developmental delay with/without dysmorphic features, has led to the delineation of several submicroscopic deletion/duplication syndromes. De novo copy number variations are often presumed to be pathogenic and inherited ones from a healthy parent likely to be not relevant for the phenotype. However, it is difficult to draw such a conclusion for an inherited copy number variation not known to be a common variation. We report on a child with developmental delay, seizures, microcephaly, hypotonia, unusual stereotypical movements, and changes in the white matter who inherited a 17q12 tandem duplication of ~1.4 Mb from his healthy father. Copy number variations in this chromosomal region are thought to be pathogenic and associated with various phenotypes including developmental delay, growth retardation, seizures, renal disease, and diabetes mellitus. We review all reported cases with 17q12 duplication and discuss the novelty of the phenotype in the present case. We also share our thoughts on submicroscopic complexity that may underlie, at least in part, the wide range of phenotypes in patients with 17q12 duplication.


Cost-effective imaging of optoacoustic pressure, ultrasonic scattering, and optical diffuse reflectance with improved resolution and speed.
The idea of a method of cost-effective upgrades from an acoustic resolution photoacoustic microscope to a triple-modality imaging system is validated using phantoms. The newly developed experimental setup is based on a diode pumped solid state laser coupled to a fiber bundle with a spherically focused polyvinylidene fluoride detector integrated into the center of a ring shaped optical illuminator. Each laser pulse illuminating the sample performs two functions. While the photons absorbed by the sample provide a measurable optoacoustic (OA) signal, the photons absorbed by the detector provide the measurable diffuse reflectometry (DR) signal from the sample and the probing ultrasonic (US) pulse. At a 3 mm imaging depth, the axial resolution of the OA/US modalities is 38 μm/26 μm, while the lateral resolution of the DR/OA/US modalities is 3.5 mm/50 μm/35 μm. The maximum acquisition rate of the trimodal DR/OA/US A-scans is 2 kHz.


What's in a name: are menopausal "hot flashes" a symptom of menopause or a manifestation of neurovascular dysregulation?
Hot flashes have typically been classified as "symptoms of menopause" that should be tolerated or treated until they resolve. However, mounting evidence points to hot flashes as a manifestation of one or several underlying pathophysiological processes. Associations exist between the presence, timing of onset, severity, and duration of hot flashes, and the risk of several neurological (affecting sleep, mood, and cognition) and cardiovascular conditions. In addition, four consistent patterns of vasomotor disturbances have been identified across different countries, making it unlikely that these patterns are solely explained by socioeconomic or cultural factors. The changing hormonal environment of menopause may unmask differences in the autonomic neurovascular control mechanisms that put an individual woman at risk for chronic conditions of aging. These differences may have a genetic basis or may be acquired across the life span and are consistent with the variability of the clinical manifestations of aging observed in women after bilateral oophorectomy. It is time to investigate the pathophysiological mechanisms underlying the four patterns of vasomotor symptoms more closely, and to shift from describing hot flashes as symptoms to be tolerated to manifestations of an underlying autonomic neurovascular dysregulation that need to be addressed.


Photobiomodulation Suppresses Alpha-Synuclein-Induced Toxicity in an AAV-Based Rat Genetic Model of Parkinson's Disease.
Converging lines of evidence indicate that near-infrared light treatment, also known as photobiomodulation (PBM), may exert beneficial effects and protect against cellular toxicity and degeneration in several animal models of human pathologies, including neurodegenerative disorders. In the present study, we report that chronic PMB treatment mitigates dopaminergic loss induced by unilateral overexpression of human α-synuclein (α-syn) in the substantia nigra of an AAV-based rat genetic model of Parkinson's disease (PD). In this model, daily exposure of both sides of the rat's head to 808-nm near-infrared light for 28 consecutive days alleviated α-syn-induced motor impairment, as assessed using the cylinder test. This treatment also significantly reduced dopaminergic neuronal loss in the injected substantia nigra and preserved dopaminergic fibers in the ipsilateral striatum. These beneficial effects were sustained for at least 6 weeks after discontinuing the treatment. Together, our data point to PBM as a possible therapeutic strategy for the treatment of PD and other related synucleinopathies.


Solvent dependence of the electronic structure of I(-) and I3(-).
We present synchrotron-based I4d photoelectron spectroscopy experiments of solutions from LiI and LiI3 in water, ethanol, and acetonitrile. The experimentally determined solvent-induced binding energy shifts (SIBES) for the monatomic I(–) anion are compared to predictions from simple Born theory, PCM calculations, as well as multiconfigurational quantum chemical spectral calculations from geometries obtained through molecular dynamics of solvated clusters. We show that the SIBES for I(–) explicitly depend on the details of the hydrogen bonding configurations of the solvent to the I(–) and that static continuum models such as the Born model cannot capture the trends in the SIBES observed both in experiments and in higher-level calculations. To extend the discussion to more complex polyatomic anions, we also performed experiments on I3(–) and I(–)/I3(–) mixtures in different solvents and the results are analyzed in the perspective of SIBES. The experimental SIBES values indicate that the solvation effects even for such similar anions as I(–) and I3(–) can be rather different in nature.


Reversible acid activation of amniotic fluid inactive renin.
1. Inactive renin was isolated from human amniotic fluid by chromatography with DEAE-cellulose, pepstatin-aminobutyl-agarose, octylagarose and Cibacron Blue F3GA columns. 2. Before and after isolation from amniotic fluid, inactive renin could be activated by incubation with pepsin and by dialysis to pH 3.3, and the acid activation could be reversed by subsequent incubation at pH 7.4 and 37 degrees C. 3. Inactive renin was not activated by procedures expected to dissociate renin from an inhibitor. 4. The results suggest a pH-dependent conformational change as the mechanism of reversible acid activation of inactive renin in amniotic fluid. 5. There are chromatographic and activation similarities of inactive renin from human plasma, kidney and amniotic fluid.


Effect of combination fluticasone propionate and salmeterol or inhaled corticosteroids on asthma-related outcomes in a Medicare-eligible population.
National asthma treatment guidelines recommend either the use of inhaled corticosteroids (ICS) or ICS in combination with a long-acting bronchodilator for the treatment of moderate to severe asthma. Even though asthma is common among older adults, few studies have assessed the differences in effectiveness between these two recommended therapies in patients over 65 years of age. The aim of this study was to assess the association of the fluticasone-salmeterol combination (FSC) or ICS initiation on asthma-related events in Medicare-eligible asthma patients. This was a retrospective observational study using a large health claims database (July 1, 2001 to June 30, 2008). Subjects 65 to 79 years of age with 12-month preindex and 3- to 12-month postindex eligibility, an asthma diagnosis (ICD-493.xx), and with 1 or more FSC or ICS claims at index were included. Subjects with an FSC or ICS claim in the preindex and any claim for chronic obstructive pulmonary disease were excluded. Subjects were observed until they had an event (emergency department [ED] inpatient hospitalization [IP], combined IP/ED or oral corticosteroid [OCS] use) or were no longer eligible in the database, whichever came first. Cox proportional hazards regression was used to assess risk of an asthma-related event (IP, ED, or IP/ED). Baseline characteristics (age, sex, region, index season, comorbidities, preindex use of short-acting β-agonists, OCS, other asthma controllers, and asthma-related ED/IP visits) were independent covariates in the model. A total of 10,837 met the criteria (4843 ICS and 5994 FSC). Age (70.4 and 70.5 years, respectively) and the percentage of female subjects (65.5% and 64.8%, respectively) were similar. Asthma-related events were also similar at baseline. Postindex unadjusted rates occurring after >30 days were ED (1.8% vs 1.5%, P = 0.18), IP (2.7% vs 1.7%, P < 0.001), and ED/IP (4.1% vs 2.8%, P < 0.001) for ICS and FSC, respectively. Subjects who received FSC were associated with a 32% (adjusted HR = 0.68; 95% CI, 0.51-0.91) lower risk of experiencing an IP visit and a 22% (HR = 0.78; 95% CI, 0.62-0.98) lower risk of experiencing an ED/IP visit. No differences were observed for ED visits (HR = 0.94; 95% CI, 0.68-1.29). In Medicare-eligible asthma patients, FSC use was associated with lower rates of asthma-related serious exacerbations compared with ICS.


Neuron class-specific requirements for Fragile X Mental Retardation Protein in critical period development of calcium signaling in learning and memory circuitry.
Neural circuit optimization occurs through sensory activity-dependent mechanisms that refine synaptic connectivity and information processing during early-use developmental critical periods. Fragile X Mental Retardation Protein (FMRP), the gene product lost in Fragile X syndrome (FXS), acts as an activity sensor during critical period development, both as an RNA-binding translation regulator and channel-binding excitability regulator. Here, we employ a Drosophila FXS disease model to assay calcium signaling dynamics with a targeted transgenic GCaMP reporter during critical period development of the mushroom body (MB) learning/memory circuit. We find FMRP regulates depolarization-induced calcium signaling in a neuron-specific manner within this circuit, suppressing activity-dependent calcium transients in excitatory cholinergic MB input projection neurons and enhancing calcium signals in inhibitory GABAergic MB output neurons. Both changes are restricted to the developmental critical period and rectified at maturity. Importantly, conditional genetic (dfmr1) rescue of null mutants during the critical period corrects calcium signaling defects in both neuron classes, indicating a temporally restricted FMRP requirement. Likewise, conditional dfmr1 knockdown (RNAi) during the critical period replicates constitutive null mutant defects in both neuron classes, confirming cell-autonomous requirements for FMRP in developmental regulation of calcium signaling dynamics. Optogenetic stimulation during the critical period enhances depolarization-induced calcium signaling in both neuron classes, but this developmental change is eliminated in dfmr1 null mutants, indicating the activity-dependent regulation requires FMRP. These results show FMRP shapes neuron class-specific calcium signaling in excitatory vs. inhibitory neurons in developing learning/memory circuitry, and that FMRP mediates activity-dependent regulation of calcium signaling specifically during the early-use critical period.


A systematic review of feasibility studies promoting the use of mobile technologies in clinical research.
Mobile technologies, such as smart phone applications, wearables, ingestibles, and implantables, are increasingly used in clinical research to capture study endpoints. On behalf of the Clinical Trials Transformation Initiative, we aimed to conduct a systematic scoping review and compile a database summarizing pilot studies addressing mobile technology sensor performance, algorithm development, software performance, and/or operational feasibility, in order to provide a resource for guiding decisions about which technology is most suitable for a particular trial. Our systematic search identified 275 publications meeting inclusion criteria. From these papers, we extracted data including the medical condition, concept of interest captured by the mobile technology, outcomes captured by the digital measurement, and details regarding the sensors, algorithms, and study sample. Sixty-seven percent of the technologies identified were wearable sensors, with the remainder including tablets, smartphones, implanted sensors, and cameras. We noted substantial variability in terms of reporting completeness and terminology used. The data have been compiled into an online database maintained by the Clinical Trials Transformation Initiative that can be filtered and searched electronically, enabling a user to find information most relevant to their work. Our long-term goal is to maintain and update the online database, in order to promote standardization of methods and reporting, encourage collaboration, and avoid redundant studies, thereby contributing to the design and implementation of efficient, high-quality trials.


Assessing accuracy of GAP and LANDFIRE land cover datasets in winter habitats used by greater sage-grouse in Idaho and Wyoming, USA.
Remotely sensed land cover datasets have been increasingly employed in studies of wildlife habitat use. However, meaningful interpretation of these datasets is dependent on how accurately they estimate habitat features that are important to wildlife. We evaluated the accuracy of the GAP dataset, which is commonly used to classify broad cover categories (e.g., vegetation communities) and LANDFIRE datasets, which classifies narrower cover categories (e.g., plant species) and structural features of vegetation. To evaluate accuracy, we compared classification of cover types and estimates of percent cover and height of sagebrush (Artemisia spp.) derived from GAP and LANDFIRE datasets to field-collected data in winter habitats used by greater sage-grouse (Centrocercus urophasianus). Accuracy was dependent on the type of dataset used as well as the spatial scale (point, 500-m, and 1-km) and biological level (community versus dominant species) investigated. GAP datasets had the highest overall classification accuracy of broad sagebrush cover types (49.8%) compared to LANDFIRE datasets for narrower cover types (39.1% community-level; 31.9% species-level). Percent cover and height were not accurately estimated in the LANDFIRE dataset. Our results suggest that researchers must be cautious when applying GAP or LANDFIRE datasets to classify narrow categories of land cover types or to predict percent cover or height of sagebrush within sagebrush-dominated landscapes. We conclude that ground-truthing is critical for successful application of land cover datasets in landscape-scale evaluations and management planning, particularly when wildlife use relatively rare habitat types compared to what is available.


The cell-cycle regulator geminin inhibits Hox function through direct and polycomb-mediated interactions.
Embryonic development is tightly controlled. The clustered genes of the Hox family of homeobox proteins play an important part in regulating this development and also proliferation. They specify embryonic structures along the body axis, and are associated with normal and malignant cell growth. The cell-cycle regulator geminin controls replication by binding to the licensing factor Cdt1, and is involved in neural differentiation. Here, we show that murine geminin associates transiently with members of the Hox-repressing polycomb complex, with the chromatin of Hox regulatory DNA elements and with Hox proteins. Gain- and loss-of-function experiments in the chick neural tube demonstrate that geminin modulates the anterior boundary of Hoxb9 transcription, which suggests a polycomb-like activity for geminin. The interaction between geminin and Hox proteins prevents Hox proteins from binding to DNA, inhibits Hox-dependent transcriptional activation of reporter and endogenous downstream target genes, and displaces Cdt1 from its complex with geminin. By establishing competitive regulation, geminin functions as a coordinator of developmental and proliferative control.


Decreased vesicular somatodendritic dopamine stores in leptin-deficient mice.
An increasing number of studies indicate that leptin can regulate the activity of the mesolimbic dopamine system. The objective of this study was to examine the regulation of the activity of dopamine neurons by leptin. This was accomplished by examining the dopamine D2 receptor-mediated synaptic current that resulted from somatodendritic release of dopamine in brain slices taken from mice that lacked leptin (Lep(ob/ob) mice). Under control conditions, the amplitude and kinetics of the IPSC in wild-type and Lep(ob/ob) mice were not different. However, in the presence of forskolin or cocaine, the facilitation of the dopamine IPSC was significantly reduced in Lep(ob/ob) mice. The application of L-3,4-dihydroxyphenylalanine (L-DOPA) increased the IPSC in Lep(ob/ob) mice significantly more than in wild-type animals and fully restored the responses to both forskolin and cocaine. Treatment of Lep(ob/ob) mice with leptin in vivo fully restored the cocaine-induced increase in the IPSC to wild-type levels. These results suggest that there is a decrease in the content of somatodendritic vesicular dopamine in the Lep(ob/ob) mice. The release of dopamine from terminals may be less affected in the Lep(ob/ob) mice, because the cocaine-induced rise in dopamine in the ventral striatum was not statistically different between wild-type and Lep(ob/ob) mice. In addition, the relative increase in cocaine-induced locomotion was similar for wild-type and Lep(ob/ob) mice. These results indicate that, although basal release is not altered, the amount of dopamine that can be released is reduced in Lep(ob/ob) mice.


A DNA sequence containing the control sites for gene malT and for the malPQ operon.
The order of 802 base pairs was established in a DNA segment containing the promoter for malPQ which is one of the three maltose operons, and the promoter for malT, the positive regulator gene of the maltose regulon. The determination of the amino-terminal sequence of the MalT protein allowed us to identify the beginning of the malT gene on the sequence. The position of the malP gene was deduced from the published amino-terminal sequence of maltodextrin phosphorylase. A total of 611 base pairs separate the initiation codons for these two genes, which are transcribed in opposite directions. This large intergenic region does not code for any polypeptide of significant size. The main features of this sequence are discussed in terms of the regulation known to operate on malT and malPQ expression.


Aberrant mRNA transcripts and the nonsense-mediated decay proteins UPF2 and UPF3 are enriched in the Arabidopsis nucleolus.
The eukaryotic nucleolus is multifunctional and involved in the metabolism and assembly of many different RNAs and ribonucleoprotein particles as well as in cellular functions, such as cell division and transcriptional silencing in plants. We previously showed that Arabidopsis thaliana exon junction complex proteins associate with the nucleolus, suggesting a role for the nucleolus in mRNA production. Here, we report that the plant nucleolus contains mRNAs, including fully spliced, aberrantly spliced, and single exon gene transcripts. Aberrant mRNAs are much more abundant in nucleolar fractions, while fully spliced products are more abundant in nucleoplasmic fractions. The majority of the aberrant transcripts contain premature termination codons and have characteristics of nonsense-mediated decay (NMD) substrates. A direct link between NMD and the nucleolus is shown by increased levels of the same aberrant transcripts in both the nucleolus and in Up-frameshift (upf) mutants impaired in NMD. In addition, the NMD factors UPF3 and UPF2 localize to the nucleolus, suggesting that the Arabidopsis nucleolus is therefore involved in identifying aberrant mRNAs and NMD.


Living polymers: a tool in studies of ions and ion-pairs.
Studies of living polymers have greatly enriched our knowledge of the behavior of ions and ion-pairs in organic media. Future investigations will lead to more detailed knowledge of these interesting species. Especially, intramolecular associations or intramolecular solvation by the polymer chains provide promising field for additional studies, and one example of such phenomena was reported recently by Fisher and Szwarc (42).


Reanalysis of generalized sensitivity factors for optical-axis perturbation in nonplanar ring resonators.
By utilizing the novel coordinate system for Gaussian beam reflection and the generalized ray matrix for spherical mirror reflection, the generalized sensitivity factors SD1, ST1, SD2 and ST2 influenced by both the radial and axial displacements of a spherical mirror in a nonplanar ring resonator have been obtained. Besides, the singular points of different kinds of non-planar ring resonators under the conditions of incident angle A ranging from 0° to 45° or total coordinate rotation angle ρ ranging from 0° to 360° have also been obtained through the analysis of the determinant of the coefficient matrix of the linear equations. The analysis in this paper is important to the cavity design of non-planar ring resonators and it could be helpful to avoid the violent movement of the optical-axis to small misalignment of the mirrors in non-planar ring resonators.


Molecular genetic analysis of myoC, a Dictyostelium myosin I.
The protozoan myosin Is are widely expressed actin-based motors, yet their in vivo roles remain poorly understood. Molecular genetic studies have been carried out to determine their in vivo function in the simple eukaryote Dictyostelium, an organism that contains a family of four myosin Is. Here we report the characterization of myoC, a gene that encodes a fifth member of this family. Analysis of the deduced amino acid sequence reveals that the myoC gene encodes a myosin that is homologous to the well-described Acanthamoeba myosin Is as well as to Dictyostelium myoB and -D. The expression pattern of the myoC mRNA is similar to that of myoB and myoD, with a peak of expression at times of maximal cell migration, around 6 hours development. Deletion of the myoB gene has been previously shown to result in mutant cells that are defective in pseudopod extension and phagocytosis. However, no obvious differences in cell growth, development, phagocytosis or motility were detected in cells in which the myoC gene had been disrupted by homologous recombination. F-actin localization and ultrastructural organization also appeared unperturbed in myoC- cells. This apparent 'lack' of phenotype in a myosin I single knockout cannot be simply explained by redundancy of function. Our results rather suggest that the present means of assessing myosin I function in vivo are insufficient to identify the unique roles of these actin-based motors.


Positive regulation of ASK1-mediated c-Jun NH(2)-terminal kinase signaling pathway by the WD-repeat protein Gemin5.
Gemin5 is a 170-kDa WD-repeat-containing protein that was initially identified as a component of the survival of motor neurons (SMN) complex. We now show that Gemin5 facilitates the activation of apoptosis signal-regulating kinase 1 (ASK1) and downstream signaling. Gemin5 physically interacted with ASK1 as well as with the downstream kinases SEK1 and c-Jun NH(2)-terminal kinase (JNK1), and it potentiated the H(2)O(2)-induced activation of each of these kinases in intact cells. Moreover, Gemin5 promoted the binding of ASK1 to SEK1 and to JNK1, as well as the ASK1-induced activation of JNK1. In comparison, Gemin5 did not physically associate with MKK7, MKK3, MKK6, or p38. Furthermore, depletion of endogenous Gemin5 by RNA interference (RNAi) revealed that Gemin5 contributes to the activation of ASK1 and JNK1, and to apoptosis induced by H(2)O(2) and tumor necrosis factor-alpha (TNFalpha) in HeLa cells. Together, our results suggest that Gemin5 functions as a scaffold protein for the ASK1-JNK1 signaling module and thereby potentiates ASK1-mediated signaling events.


Promoting synergistic research and education in genomics and bioinformatics.
Bioinformatics and Genomics are closely related disciplines that hold great promises for the advancement of research and development in complex biomedical systems, as well as public health, drug design, comparative genomics, personalized medicine and so on. Research and development in these two important areas are impacting the science and technology.High throughput sequencing and molecular imaging technologies marked the beginning of a new era for modern translational medicine and personalized healthcare. The impact of having the human sequence and personalized digital images in hand has also created tremendous demands of developing powerful supercomputing, statistical learning and artificial intelligence approaches to handle the massive bioinformatics and personalized healthcare data, which will obviously have a profound effect on how biomedical research will be conducted toward the improvement of human health and prolonging of human life in the future. The International Society of Intelligent Biological Medicine (http://www.isibm.org) and its official journals, the International Journal of Functional Informatics and Personalized Medicine (http://www.inderscience.com/ijfipm) and the International Journal of Computational Biology and Drug Design (http://www.inderscience.com/ijcbdd) in collaboration with International Conference on Bioinformatics and Computational Biology (Biocomp), touch tomorrow's bioinformatics and personalized medicine throughout today's efforts in promoting the research, education and awareness of the upcoming integrated inter/multidisciplinary field. The 2007 international conference on Bioinformatics and Computational Biology (BIOCOMP07) was held in Las Vegas, the United States of American on June 25-28, 2007. The conference attracted over 400 papers, covering broad research areas in the genomics, biomedicine and bioinformatics. The Biocomp 2007 provides a common platform for the cross fertilization of ideas, and to help shape knowledge and scientific achievements by bridging these two very important disciplines into an interactive and attractive forum. Keeping this objective in mind, Biocomp 2007 aims to promote interdisciplinary and multidisciplinary education and research. 25 high quality peer-reviewed papers were selected from 400+ submissions for this supplementary issue of BMC Genomics. Those papers contributed to a wide-range of important research fields including gene expression data analysis and applications, high-throughput genome mapping, sequence analysis, gene regulation, protein structure prediction, disease prediction by machine learning techniques, systems biology, database and biological software development. We always encourage participants submitting proposals for genomics sessions, special interest research sessions, workshops and tutorials to Professor Hamid R. Arabnia (firstname.lastname@example.com) in order to ensure that Biocomp continuously plays the leadership role in promoting inter/multidisciplinary research and education in the fields. Biocomp received top conference ranking with a high score of 0.95/1.00. Biocomp is academically co-sponsored by the International Society of Intelligent Biological Medicine and the Research Laboratories and Centers of Harvard University--Massachusetts Institute of Technology, Indiana University--Purdue University, Georgia Tech--Emory University, UIUC, UCLA, Columbia University, University of Texas at Austin and University of Iowa etc. Biocomp--Worldcomp brings leading scientists together across the nation and all over the world and aims to promote synergistic components such as keynote lectures, special interest sessions, workshops and tutorials in response to the advances of cutting-edge research.


[Study on the roles of voltaged potassium channels in acute hypoxic pulmonary vasoconstriction].
To investigate the role of voltage-gated potassium channels in the acute hypoxic pulmonary vasoconstriction. Thirty Wistar rats were divided into two groups, namely the normoxic group and hypoxic group. The single smooth muscle cell was obtained from the pulmonary artery of Wistar rats with acute enzymatic digestion method. The conventional whole-cell patch clamp technique was used to record the resting membrane potential(Em) and the potassium currents of voltage-gated potassium channel (IKv) in rat pulmonary arterial smooth muscle cells(PASMC). Intracellular application of Kv1.2, Kv1.3, Kv1.5, and Kv2.1 antibodiesè1:125éwas conducted through the whole-cell patch clamp system. Em of PASMC was depolarized in hypoxia compared with that of control cells. The mixture of Kv1.2, Kv1.3, Kv1.5, and Kv2.1 antibodiesè1:125é depolarized Em and inhibited Ikv in PASMC from normoxic rat,whereas the mixture of Kv1.2, Kv1.3, Kv1.5, Kv2.1 antibodiesè1:125éhad no effects on Ikv and Em in hypoxic rats. Kv1.2, Kv1.3, Kv1.5, Kv2.1 might be oxygen sensitive potassium channels which mediated acute hypoxic pulmonary vasoconstriction.


Gene trees and the origins of inbred strains of mice.
Extensive data on genetic divergence among 24 inbred strains of mice provide an opportunity to examine the concordance of gene trees and species trees, especially whether structured subsamples of loci give congruent estimates of phylogenetic relationships. Phylogenetic analyses of 144 separate loci reproduce almost exactly the known genealogical relationships among these 24 strains. Partitioning these loci into structured subsets representing loci coding for proteins, the immune system and endogenous viruses give incongruent phylogenetic results. The gene tree based on protein loci provides an accurate picture of the genealogical relationships among strains; however, gene trees based upon immune and viral data show significant deviations from known genealogical affinities.


Association of upper trunk and visceral adipose tissue volume with insulin resistance in control and HIV-infected subjects in the FRAM study.
Visceral obesity is associated with insulin resistance, but the association of other regional adipose depots with insulin resistance is not understood. In HIV infection, buffalo hump (upper trunk fat) is associated, but the association of upper trunk fat with insulin resistance has not been examined in controls. To determine the independent association of adipose depots other than visceral with insulin resistance, we performed a cross-sectional analysis of controls and HIV-infected subjects in the Fat Redistribution and Metabolic Change in HIV Infection (FRAM) study, who had measurements of glucose, insulin, and adipose tissue volumes by whole-body magnetic resonance imaging. We studied 926 HIV-positive persons from 16 academic medical center clinics and trials units with demographic characteristics representative of US patients with HIV infection and 258 FRAM controls from the population-based Coronary Artery Risk Development in Young Adults study. We measured visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) volume in the legs, arms, lower trunk (back and abdomen), and upper trunk (back and chest) and assessed their association with the homeostasis model of assessment (HOMA) and HOMA >4 by stepwise multivariable analysis. The prevalence of HOMA >4 as a marker of insulin resistance was 28% among controls compared with 37% among HIV-infected subjects (P = 0.005). Among controls, those in the highest tertile of upper trunk SAT volume had an odds ratio (OR) of 9.0 (95% confidence interval [CI]: 2.4 to 34; P = 0.001) for having HOMA >4 compared with the lowest tertile, whereas in HIV-positive subjects, the OR was lower (OR = 2.09, 95% CI: 1.36 to 3.19; P = 0.001). Among controls, the highest tertile of VAT volume had an OR of 12.1 (95% CI: 3.2 to 46; P = 0.0002) of having HOMA >4 compared with the lowest tertile, whereas in HIV-positive subjects, the OR was 3.12 (95% CI: 2.0 to 4.8; P < 0.0001). After adjusting for VAT and upper trunk SAT, the association of other SAT depots with HOMA >4 did not reach statistical significance. Thus, VAT and upper trunk SAT are independently associated with insulin resistance in controls and in HIV-infected persons.


Ultrasound of colon diverticulitis.
Overall, the diagnosis of diverticulitis is more reliably made by computed tomography (CT) than by ultrasound (US). However, since US is often used as a first modality in acute abdomen, it is important to be aware of the US signs of diverticulitis. Besides, in not too obese patients, US may be superior to CT. US is most useful in early, uncomplicated diverticulitis. Daily, repeated US examinations in patients with diverticulitis have taught that diverticulitis, in the majority of cases, runs a predictable and benign course. Initially, there is local wall thickening of the colon with preservation of the US layer structure. Within the inflamed diverticulum, a fecolith is present, and the diverticulum is surrounded by hyperechoic, noncompressible tissue, which represents the inflamed mesentery and omentum 'sealing off' the imminent perforation. US follow-up shows evacuation of the fecolith to the colonic lumen, with or without the transient development of a small paracolic abscess, sometimes with disintegration of the fecolith. This process of spontaneous evacuation of pus and fecolith via local weakening of the colonic wall at the level of the original diverticular neck towards the colonic lumen takes place within 1 or 2 days, rarely longer. The residual inflammatory changes remain present for several days after the evacuation, and it is not uncommon to find an empty diverticulum at first presentation. If, in such cases, patients are specifically asked for their symptoms, they invariably declare that 'the worst pain is over'. Whenever diverticulitis takes a complicated course, CT is superior to US, especially in the detection of free air, fecal peritonitis and deeply located abscesses, and in general in obese patients. Finally, US, if necessary followed by CT, has an important role in the diagnosis of alternative conditions: ureterolithiasis, pyelonephritis, perforated peptic ulcer, appendicitis, Crohn's disease, epiploic appendagitis, gynecological conditions, colonic malignancy, pancreatitis, etc. Right-sided colonic diverticulitis in many respects differs from its left-sided cousin. Diverticula of the right colon are usually congenital, solitary, true diverticula containing all bowel wall layers. The fecoliths within these diverticula are larger and the diverticular neck is wider. There is no hypertrophy of the muscularis of the right colonic wall. My observations with US and CT in 110 patients with right colonic diverticulitis clearly show that it invariably has a favorable course and never leads to free perforation or large abscesses. Although relatively rare (left:right = 15:1), it is crucial to make a correct diagnosis since the clinical symptoms of acute right lower quadrant pain may lead to an unnecessary appendectomy or even right hemicolectomy.


Control of cell proliferation in the Drosophila eye by Notch signaling.
Cell proliferation in animals must be precisely controlled, but the signaling mechanisms that regulate the cell cycle are not well characterized. A regulated terminal mitosis, called the second mitotic wave (SMW), occurs during Drosophila eye development, providing a model for the genetic analysis of proliferation control. We report a cell cycle checkpoint at the G1-S transition that initiates the SMW, and we demonstrate that Notch signaling is required for cells to overcome this checkpoint. Notch triggers the onset of proliferation by multiple pathways, including the activation of dE2F1, a member of the E2F transcription factor family. Delta to Notch signaling derepresses the inhibition of dE2F1 by RBF, and Delta expression depends on the secreted proteins Hedgehog and Dpp. Notch is also required for the expression of Cyclin A in the SMW.


Current trends suggest most Asian countries are unlikely to meet future biodiversity targets on protected areas.
Aichi Target 11 committed governments to protect ≥17% of their terrestrial environments by 2020, yet it was rarely achieved, raising questions about the post-2020 Global Biodiversity Framework goal to protect 30% by 2030. Asia is a challenging continent for such targets, combining high biodiversity with dense human populations. Here, we evaluated achievements in Asia against Aichi Target 11. We found that Asia was the most underperforming continent globally, with just 13.2% of terrestrial protected area (PA) coverage, averaging 14.1 ± SE 1.8% per country in 2020. 73.1% of terrestrial ecoregions had <17% representation and only 7% of PAs even had an assessment of management effectiveness. We found that a higher agricultural land in 2015 was associated with lower PA coverage today. Asian countries also showed a remarkably slow average annual pace of 0.4 ± SE 0.1% increase of PA extent. These combined lines of evidence suggest that the ambitious 2030 targets are unlikely to be achieved in Asia unless the PA coverage to increase 2.4-5.9 times faster. We provided three recommendations to support Asian countries to meet their post-2020 biodiversity targets: complete reporting and the wider adoption "other effective area-based conservation measures"; restoring disturbed landscapes; and bolstering transboundary PAs.


Physicians' experiences with end-of-life decision-making: survey in 6 European countries and Australia.
In this study we investigated (a) to what extent physicians have experience with performing a range of end-of-life decisions (ELDs), (b) if they have no experience with performing an ELD, would they be willing to do so under certain conditions and (c) which background characteristics are associated with having experience with/or being willing to make such ELDs. An anonymous questionnaire was sent to 16,486 physicians from specialities in which death is common: Australia, Belgium, Denmark, Italy, the Netherlands, Sweden and Switzerland. The response rate differed between countries (39-68%). The experience of foregoing life-sustaining treatment ranged between 37% and 86%: intensifying the alleviation of pain or other symptoms while taking into account possible hastening of death between 57% and 95%, and experience with deep sedation until death between 12% and 46%. Receiving a request for hastening death differed between 34% and 71%, and intentionally hastening death on the explicit request of a patient between 1% and 56%. There are differences between countries in experiences with ELDs, in willingness to perform ELDs and in receiving requests for euthanasia or physician-assisted suicide. Foregoing treatment and intensifying alleviation of pain and symptoms are practiced and accepted by most physicians in all countries. Physicians with training in palliative care are more inclined to perform ELDs, as are those who attend to higher numbers of terminal patients. Thus, this seems not to be only a matter of opportunity, but also a matter of attitude.


Does colorectal endometriosis alter intestinal functions? A prospective manometric and questionnaire-based study.
To objectively evaluate using anorectal manometry whether endometriotic nodules influence intestinal function and to reveal subjective intestinal dysfunctions in patients with rectosigmoid deep infiltrating endometriosis. Prospective study. Tertiary care university hospital. Patients (n = 25) with a preoperative diagnosis of rectosigmoid endometriosis. Patients underwent anorectal manometry; after that, they filled a questionnaire about defecatory functions and ranked their pain symptoms. The parameters studied were resting pressure, maximum squeezing pressure, pushing, rectoanal inhibitory reflex, and rectal sensibility. We analyzed the responses to the defecatory function questionnaire and the scored the endometriosis pain symptoms using a Visual Analogue Scale. No alterations of the rectoanal inhibitory reflex were found. Hypertone of the internal anal sphincter was found in 20 of 25 patients. Almost half of the patients had an increase of the threshold of desire to defecate, and 7 patients had a reduction of the anal sphincter squeeze pressure. According to the responses to the defecatory function questionnaire, incomplete evacuation was the most common symptom. We did not find marked motility or sensitive dysfunctions at the anorectal manometry, whereas subjectively patients reported some defecatory disorders. We revealed the presence of hypertone of the internal anal sphincter in most of the patients. 74/2010/O/Sper.


Tornado1 and tornado2 are required for the specification of radial and circumferential pattern in the Arabidopsis root.
The cell layers of the Arabidopsis primary root are arranged in a simple radial pattern. The outermost layer is the lateral root cap and lies outside the epidermis that surrounds the ground tissue. The files of epidermal and lateral root cap cells converge on a ring of initials (lateral root cap/epidermis initial) from which the epidermal and lateral root cap tissues of the seedling are derived, once root growth is initiated after germination. Each initial gives rise to a clone of epidermal cells and a clone of lateral root cap cells. These initial divisions in the epidermal/lateral root cap initial are defective in tornado1 (trn1) and trn2 plants indicating a requirement for TRN1 and TRN2 for initial cell function. Furthermore, lateral root cap cells develop in the epidermal position in trn1 and trn2 roots indicating that TRN1 and TRN2 are required for the maintenance of the radial pattern of cell specification in the root. The death of these ectopic lateral root cap cells in the elongation zone (where lateral root cap cells normally die) results in the development of gaps in the epidermis. These observations indicate that TRN1 and TRN2 are required to maintain the distinction between the lateral root cap and epidermis and suggest that lateral root cap fate is the default state. It also suggests that TRN1 and TRN2 repress lateral root cap fate in cells in the epidermal location. Furthermore, the position-dependent pattern of root hair and non-root hair cell differentiation in the epidermis is defective in trn1 and trn2 mutants. Together these results indicate that TRN1 and TRN2 are required for the maintenance of both the radial pattern of tissue differentiation in the root and for the subsequent circumferential pattern within the epidermis.


Factors associated with self-reported first sexual intercourse in Scottish adolescents.
There is continuing concern about high pregnancy rates and increasing numbers of sexually transmitted infections being detected in Scottish adolescents. Consistent evidence about factors associated with risky sexual behaviours, including early first sexual intercourse, may help to identify adolescents at risk and help improve interventions. This study aimed to provide detailed analysis of the evidence of the associations between individual factors and early sexual intercourse using cross-sectional questionnaire data from 4,379 Scottish adolescents who participated in a sexual health intervention evaluation. Multivariate secondary analysis showed that aspects of family and school life such as decreasing parental monitoring (OR 1.45, 95% CI 1.24-1.70) and decreasing enjoyment of school (OR 2.55, 95% CI 2.15-3.03) were associated with reporting previous sexual intercourse. Furthermore, females were more likely to report previous sexual intercourse than males (OR 1.48, 95% CI 1.14-1.91). Several factors commonly used to inform sexual health intervention design, such as socioeconomic status, self-esteem and religion, were not independently associated. These results contribute to the evidence base for the association of several factors with early initiation of sexual activity. The findings suggest that interventions aiming to delay first intercourse may need to consider targeting aspects of individuals' connection to their school and family. Furthermore, the results do not support the need to consider socio-economic background, religion or self-esteem of the individuals in intervention design.


Anaphase onset does not require the microtubule-dependent depletion of kinetochore and centromere-binding proteins.
Spindle checkpoint proteins, such as Mad2 and BubR1, and the motors dynein/dynactin and CENP-E usually leave kinetochores prior to anaphase onset by microtubule-dependent mechanisms. Likewise, 'chromosome passenger proteins' including INCENP are depleted from the centromeres after anaphase onset and then move to the midzone complex, an event that is essential for cytokinesis. Here we test whether the cell cycle changes that occur at anaphase onset require or contribute to the depletion of kinetochore and centromere proteins independent of microtubules. This required the development of a novel non-antibody method to induce precocious anaphase onset in vivo by using a bacterially expressed fragment of the spindle checkpoint protein Mad1 capable of activating the APC/C, called GST-Mad1F10. By injecting PtK1 cells in nocodazole with GST-Mad1F10 and processing the cells for immunofluorescence microscopy after anaphase sister chromatid separation in nocodazole we found that Mad2, BubR1, cytoplasmic dynein, CENP-E and the 3F3/2 phosphoepitope remain on kinetochores. Thus depletion of these proteins (or phosphoepitope) at kinetochores is not required for anaphase onset and anaphase onset does not produce their depletion independent of microtubules. In contrast, both microtubules and anaphase onset are required for depletion of the 'chromosome passenger' protein INCENP from centromeres, as INCENP does not leave the chromosomes prior to anaphase onset in the presence or absence of microtubules, but does leave the centromeres after anaphase onset in the presence of microtubules.


p53 and bcl-2 expression in high-grade B-cell lymphomas: correlation with survival time.
B-cell high-grade lymphomas are heterogeneous in terms of histology, clinical presentation, treatment response and prognosis. As bcl-2 and p53 gene deregulations are frequently involved in several types of lymphoid malignancies, we aimed our investigation at the study of the relation between bcl-2 and p53 expression and survival probability in a group of 119 patients with B-cell high-grade lymphoma. These were obtained from the Virgen de la Salud Hospital, Toledo, Spain (73 cases), John Radcliffe Hospital, Oxford, UK (31 cases), and the Istituto Nazionale dei Tumori, Milan, Italy (15 cases). The relation between bcl-2 protein expression and survival was small, depending on the primary localisation of the tumour (in lymph node of mucosae), and lacked a significant correlation with overall survival. In contrast with this, p53 expression was related to survival probability in our series, this relation being both significant and independent of histological diagnosis. p53-positive patients showed a sudden decrease in life expectancy in the first months after diagnosis. Multivariant regression analysis confirmed that the only parameters significantly related with survival were extranodal origin, which is associated with a better prognosis, and p53 expression, which indicates a poor prognosis. Simultaneous expression of bcl-2 and p53 was associated with a poorer prognosis than p53 alone. This is particularly significant for large B-cell lymphomas presenting in lymph nodes. The cumulative poor effect of both p53 and bcl-2 in large B-cell lymphomas, which is more significant in nodal tumours, could confirm the existence of a multistep genetic deregulation in non-Hodgkin's lymphoma. This indicates that the genetic mechanisms controlling apoptosis and their disregulation are critical steps in the progression of lymphomas.


Phylogenetic and growth form variation in the scaling of nitrogen and phosphorus in the seed plants.
Plant biomass and nutrient allocation explicitly links the evolved strategies of plant species to the material and energy cycles of ecosystems. Allocation of nitrogen (N) and phosphorus (P) is of particular interest because N and P play pivotal roles in many aspects of plant biology, and their availability frequently limits plant growth. Here we present a comparative scaling analysis of a global data compilation detailing the N and P contents of leaves, stems, roots, and reproductive structures of 1,287 species in 152 seed plant families. We find that P and N contents (as well as N : P) are generally highly correlated both within and across organs and that differences exist between woody and herbaceous taxa. Between plant organs, the quantitative form of the scaling relationship changes systematically, depending on whether the organs considered are primarily structural (i.e., stems, roots) or metabolically active (i.e., leaves, reproductive structures). While we find significant phylogenetic signals in the data, similar scaling relationships occur in independently evolving plant lineages, which implies that both the contingencies of evolutionary history and some degree of environmental convergence have led to a common set of rules that constrain the partitioning of nutrients among plant organs.


Multielement trace determination in SiC powders: assessment of interlaboratory comparisons aimed at the validation and standardization of analytical procedures with direct solid sampling based on ETV ICP OES and DC arc OES.
The members of the committee NMP 264 "Chemical analysis of non-oxidic raw and basic materials" of the German Standards Institute (DIN) have organized two interlaboratory comparisons for multielement determination of trace elements in silicon carbide (SiC) powders via direct solid sampling methods. One of the interlaboratory comparisons was based on the application of inductively coupled plasma optical emission spectrometry with electrothermal vaporization (ETV ICP OES), and the other on the application of optical emission spectrometry with direct current arc (DC arc OES). The interlaboratory comparisons were organized and performed in the framework of the development of two standards related to "the determination of mass fractions of metallic impurities in powders and grain sizes of ceramic raw and basic materials" by both methods. SiC powders were used as typical examples of this category of material. The aim of the interlaboratory comparisons was to determine the repeatability and reproducibility of both analytical methods to be standardized. This was an important contribution to the practical applicability of both draft standards. Eight laboratories participated in the interlaboratory comparison with ETV ICP OES and nine in the interlaboratory comparison with DC arc OES. Ten analytes were investigated by ETV ICP OES and eleven by DC arc OES. Six different SiC powders were used for the calibration. The mass fractions of their relevant trace elements were determined after wet chemical digestion. All participants followed the analytical requirements described in the draft standards. In the calculation process, three of the calibration materials were used successively as analytical samples. This was managed in the following manner: the material that had just been used as the analytical sample was excluded from the calibration, so the five other materials were used to establish the calibration plot. The results from the interlaboratory comparisons were summarized and used to determine the repeatability and the reproducibility (expressed as standard deviations) of both methods. The calculation was carried out according to the related standard. The results are specified and discussed in this paper, as are the optimized analytical conditions determined and used by the authors of this paper. For both methods, the repeatability relative standard deviations were <25%, usually ~10%, and the reproducibility relative standard deviations were <35%, usually ~15%. These results were regarded as satifactory for both methods intended for rapid analysis of materials for which decomposition is difficult and time-consuming. Also described are some results from an interlaboratory comparison used to certify one of the materials that had been previously used for validation in both interlaboratory comparisons. Thirty laboratories (from eight countries) participated in this interlaboratory comparison for certification. As examples, accepted results are shown from laboratories that used ETV ICP OES or DC arc OES and had performed calibrations by using solutions or oxides, respectively. The certified mass fractions of the certified reference materials were also compared with the mass fractions determined in the interlaboratory comparisons performed within the framework of method standardization. Good agreement was found for most of the analytes.


Facilitators and barriers to adaptive implementation of the Meeting Centers Support Program (MCSP) in three European countries; the process evaluation within the MEETINGDEM study.
ABSTRACTBackground:In the MEETINGDEM project, the Meeting Centers Support Program (MCSP) was adaptively implemented and evaluated in three European countries: Italy, Poland, and the United Kingdom. The aim of this study was to investigate overall and country-specific facilitators and barriers to the implementation of MCSP in these European countries. A qualitative multiple case study design was used. Based on the theoretical model of adaptive implementation, a checklist was composed of potential facilitators and barriers to the implementation of MCSP. This checklist was administered among stakeholders involved in the implementation of MCSP to trace the experienced facilitators and barriers. Twenty-eight checklists were completed. Main similarities between countries were related to the presence of suitable staff, management, and a project manager, and the fact that the MCSP is attuned to needs and wishes of people with dementia and informal caregivers. Main differences between countries were related to: communication with potential referrers, setting up an inter-organizational collaboration network, receiving support of national organizations, having clear discharge criteria for the MCSP and continuous PR in the region. The results of this study provide insight into generic and country specific factors that can influence the implementation of MCSP in different European countries. This study informs further implementation and dissemination of MCSP in Europe and may also serve as an example for the dissemination and implementation of other effective psychosocial support interventions for people with dementia and their informal caregivers across and beyond Europe.


Pore-Spanning Plasma Membranes Derived from Giant Plasma Membrane Vesicles.
Giant plasma membrane vesicles (GPMVs) are a highly promising model system for the eukaryotic plasma membrane. The unresolved challenge, however, is a path to surface-based structures that allows accessibility to both sides of the plasma membrane through high-resolution techniques. Such an approach would pave the way to advanced chip-based technologies for the analysis of complex cell surfaces to study the roles of membrane proteins, host-pathogen interactions, and many other bioanalytical and sensing applications. This study reports the generation of planar supported plasma membranes and for the first-time pore-spanning plasma membranes (PSPMs) derived from pure GPMVs that are spread on activated solid and highly ordered porous silicon substrates. GPMVs were produced by two different vesiculation agents and were first investigated with respect to their growth behavior and phase separation. Second, these GPMVs were spread onto silicon substrates to form planar supported plasma membrane patches. PSPMs were obtained by spreading of pure GPMVs on oxygen-plasma activated porous substrates with pore diameters of 3.5 μm. Fluorescence micrographs unambiguously showed that the PSPMs partially phase separate in a mobile ordered phase surrounded by a disordered phase, which was supported by cholesterol extraction using methyl-β-cyclodextrin.


When research seems like clinical care: a qualitative study of the communication of individual cancer genetic research results.
Research ethicists have recently declared a new ethical imperative: that researchers should communicate the results of research to participants. For some analysts, the obligation is restricted to the communication of the general findings or conclusions of the study. However, other analysts extend the obligation to the disclosure of individual research results, especially where these results are perceived to have clinical relevance. Several scholars have advanced cogent critiques of the putative obligation to disclose individual research results. They question whether ethical goals are served by disclosure or violated by non-disclosure, and whether the communication of research results respects ethically salient differences between research practices and clinical care. Empirical data on these questions are limited. Available evidence suggests, on the one hand, growing support for disclosure, and on the other, the potential for significant harm. This paper explores the implications of the disclosure of individual research results for the relationship between research and clinical care through analysis of research-based cancer genetic testing in Ontario, Canada in the late 1990s. We analyze a set of 30 interviews with key informants involved with research-based cancer genetic testing before the publicly funded clinical service became available in 2000. We advance three insights: First, the communication of individual research results makes research practices seem like clinical services for our respondents. Second, while valuing the way in which research enables a form of clinical access, our respondents experience these quasi-clinical services as inadequate. Finally, our respondents recognize the ways in which their experience with these quasi-clinical services is influenced by research imperatives, but understand and interpret the significance and appropriateness of these influences in different ways. Our findings suggest that the hybrid state created through the disclosure of research results about individuals that are perceived to be clinically relevant may produce neither sufficiently adequate clinical care nor sufficiently ethical research practices. These findings raise questions about the extent to which research can, and should, be made to serve clinical purposes, and suggest the need for further deliberation regarding any ethical obligation to communicate individual research results.


Chemiluminescent detection of sequential DNA hybridizations to high-density, filter-arrayed cDNA libraries: a subtraction method for novel gene discovery.
A chemiluminescent approach for sequential DNA hybridizations to high-density filter arrays of cDNAs, using a biotin-based random priming method followed by a streptavidin/alkaline phosphatase/CDP-Star detection protocol, is presented. The method has been applied to the Brugia malayi genome project, wherein cDNA libraries, cosmid and bacterial artificial chromosome (BAC) libraries have been gridded at high density onto nylon filters for subsequent analysis by hybridization. Individual probes and pools of rRNA probes, ribosomal protein probes and expressed sequence tag probes show correct specificity and high signal-to-noise ratios even after ten rounds of hybridization, detection, stripping of the probes from the membranes and rehybridization with additional probe sets. This approach provides a subtraction method that leads to a reduction in redundant DNA sequencing, thus increasing the rate of novel gene discovery. The method is also applicable for detecting target sequences, which are present in one or only a few copies per cell; it has proven useful for physical mapping of BAC and cosmid high-density filter arrays, wherein multiple probes have been hybridized at one time (multiplexed) and subsequently "deplexed" into individual components for specific probe localizations.


Effects of prolonged standing on gait in children with spastic cerebral palsy.
The purpose of this study was to determine the effects of prolonged standing on gait characteristics in children with spastic cerebral palsy. Six children with spastic cerebral palsy participated in this study with an average age of 6.5 years (SD = 2.5, range = 4.0-9.8 years). A reverse baseline design (A-B-A) was used over a 9-week period. During phase A, the children received their usual physical therapy treatment. During phase B, children received the prolonged standing program three times per week, in addition to their usual physical therapy treatment. During phase A2, children received their usual physical therapy treatment. Gait analysis and clinical assessment of spasticity were performed before and after each phase. Analysis of variance (ANOVA) for repeated measurements was used to test for changes in gait measures across the four measurement sessions. Friedman's was used to test for changes in muscle tone (Modified Ashworth Scale) across the four measurement sessions. Stride length (p <.001), gait speed (p <.001), stride time (p <.001), stance phase time (p <.001), double support time (p <.003), muscle tone (p <.02), and peak dorsiflexion angle during midstance (p <.004) improved significantly following the intervention phase. The results of this study demonstrate that the gait pattern of children with cerebral palsy classified as level II or III on the Gross Motor Functional Classification System (GMFCS) improved by a prolonged standing program. However, these improvements were not maintained at 3 weeks. Further research is necessary with larger sample sizes to replicate these findings and determine specific "dosing" for standing programs to create long-lasting functional effects on gait.


Distinct contributions of rod, cone, and melanopsin photoreceptors to encoding irradiance.
Photoreceptive, melanopsin-expressing retinal ganglion cells (mRGCs) encode ambient light (irradiance) for the circadian clock, the pupillomotor system, and other influential behavioral/physiological responses. mRGCs are activated both by their intrinsic phototransduction cascade and by the rods and cones. However, the individual contribution of each photoreceptor class to irradiance responses remains unclear. We address this deficit using mice expressing human red cone opsin, in which rod-, cone-, and melanopsin-dependent responses can be identified by their distinct spectral sensitivity. Our data reveal an unexpectedly important role for rods. These photoreceptors define circadian responses at very dim "scotopic" light levels but also at irradiances at which pattern vision relies heavily on cones. By contrast, cone input to irradiance responses dissipates following light adaptation to the extent that these receptors make a very limited contribution to circadian and pupillary light responses under these conditions. Our data provide new insight into retinal circuitry upstream of mRGCs and optimal stimuli for eliciting irradiance responses.


Pseudopecoelus mccauleyi n. sp. and Podocotyle sp. (Digenea: Opecoelidae) from the deep waters off Oregon and British Columbia with an updated key to the species of Pseudopecoelus von Wicklen, 1946 and checklist of parasites from Lycodes cortezianus (Perciformes: Zoarcidae).
Pseudopecoelus mccauleyi n. sp. (Opecoelidae: Opecoelinae) is described from the intestine of the bigfin eelpout, Lycodes cortezianus (Gilbert, 1890) (Perciformes: Zoarcidae), collected at 200-800 m depths in the Northeastern Pacific Ocean off Oregon and Vancouver Island, British Columbia. The new species is distinguished by possessing a unique combination of the following diagnostic characters: vitelline fields that extend to the posterior margin of the ventral sucker; a slender, tubular and sinuous seminal vesicle that extends some distance into the hindbody; an unspecialized, protuberant ventral sucker; a genital pore at pharynx level; lobed to deeply multilobed testes; a lobed ovary; and an egg size of 68-80 μm × 30-46 μm. A single specimen of Podocotyle Dujardin, 1845 (Digenea: Plagioporinae) is also described from the intestine of an individual Coryphaenoides sp. (Gadiformes: Macrouridae) collected at 2,800 m depth off Oregon. A listing of parasites from the bigfin eelpout as well as observations of parasite diversity within relevant hosts are offered, new host and locality records are noted, and a brief discussion of Pseudopecoelus von Wicklen, 1946 in the deep sea is presented taking note of the low level of host specificity recorded (i.e. spp. of Pseudopecoelus are now known to parasitize deep-water fish from at least 20 piscine families). A new dichotomous key to the 39 recognized species of Pseudopecoelus is introduced.


Use of high-dose oral bisphosphonate therapy for symptomatic fibrous dysplasia of the skull.
Fibrous dysplasia of the bone in adults is a rare anomaly of skeletal development caused by a defect in differentiation of osteoblasts. This condition is associated with bone pain, bone deformity, and an increased incidence of fracture. Involvement of the skull is associated with headache along with dysmorphic features. Until recently, the principal treatment has been resection or fracture repair, although the latter is often palliative at best. However, new insight into the molecular mechanism of fibrous dysplasia has led to the use of bisphosphonates to treat this disease. The authors examined the effects of high-dose oral alendronate (40 mg daily) for 6 months on 3 adult patients with intractable headache due to fibrous dysplasia of the skull. Each patient had disease processes not amenable to surgery. The patients underwent clinical follow-up at 1, 3, and 6 months. Their pain levels were documented at each visit by using a visual analog scale. All 3 patients demonstrated a significant decrease in pain levels and became independent of scheduled analgesics. Tumor bulk did not progress during this interval in any patient. Overall, alendronate was tolerated well, although in 1 patient it was discontinued early due to esophagitis. High-dose oral bisphosphonate therapy is an alternative therapeutic option for the palliative treatment of patients with fibrous dysplasia of the skull.


Vestibular Response to Electrical Stimulation of the Otolith Organs. Implications in the Development of A Vestibular Implant for the Improvement of the Sensation of Gravitoinertial Accelerations.
Electrical stimulation of the utricular and saccular portions of the vestibular nerve improves stability in patients suffering from vestibular dysfunction. The main objective of this study was to evaluate a new technique, vestibular response telemetry (VRT), for measuring the electrically evoked vestibular compound action potential (saccular and utricular) after stimulating the otolith organ (saccular and utricular) in adults. This study used evidence that the otolith organ can be electrically stimulated in order to develop a new vestibular implant design to improve the sensation of gravitoinertial acceleration. Four adult patients were evaluated by using a variety of measurement procedures with novel VRT software. VRT values were obtained by stimulating with three full-band Nucleus CI24RE (ST) electrodes. Specific stimuli were used. Simultaneously, electrical ocular vestibular evoked myogenic potentials (eoVEMPs) were recorded in the contralateral side. Electrically evoked compound action potentials were obtained in 10 of the 12 electrodes tested, and eoVEMPs were recorded when VRT was present. In addition to the validation of this technique, a set of default clinical test parameters was established. The VRT response morphology consisted of a biphasic waveform with an initial negative peak (N1) followed by a positive peak (P1), and latencies were typically 400 μs for N1 and 800 μs for P1. The consequences for the development of a vestibular implant for the improvement of gravitoinertial acceleration sensation are also presented. The VRT measurement technique has been shown to be a useful tool to record neural response on the otolith organ, and thus it is a convenient tool to evaluate whether the implanted electrodes provide a neural response or not. This can be used for the early development of vestibular implants to improve gravitoinertial acceleration sensation.


A newt ribozyme: a catalytic activity in search of a function.
We analyzed the cleavage properties and the transcription regulation of the newt (Triturus vulgaris meridionalis) self-cleaving RNA. In vitro self-cleavage of model oligoribonucleotides occurs within a double hammerhead structure. In addition, an entire ribozyme molecule, as well as its catalytic domain, "trans-cleaves" in vitro appropriate oligoribonucleotide substrates. Signals encoded within the ribozyme DNA sequences regulate the ribozyme transcription, which is RNA polymerase II dependent. Finally, the deduced secondary structure of the self-cleaving RNA appears to be conserved in evolutionarily distant newt species. These features suggest that the newt ribozyme could play some role in the cell, possibly related to its cleavage properties.


Herbivore space use influences coral reef recovery.
Herbivores play an important role in marine communities. On coral reefs, the diversity and unique feeding behaviours found within this functional group can have a comparably diverse set of impacts in structuring the benthic community. Here, using a spatially explicit model of herbivore foraging, we explore how the spatial pattern of grazing behaviours impacts the recovery of a reef ecosystem, considering movements at two temporal scales-short term (e.g. daily foraging patterns) and longer term (e.g. monthly movements across the landscape). Model simulations suggest that more spatially constrained herbivores are more effective at conferring recovery capability by providing a favourable environment to coral recruitment and growth. Results also show that the composition of food available to the herbivore community is linked directly to the pattern of space use by herbivores. To date, most studies of variability among the impacts of herbivore species have considered the diversity of feeding modes and mouthparts. Our work provides a complementary view of spatial patterns of foraging, revealing that variation in movement behaviours alone can affect patterns of benthic change, and thus broadens our view of realized links between herbivore diversity and reef recovery.


Neuronal regulation: A mechanism for synaptic pruning during brain maturation.
Human and animal studies show that mammalian brains undergo massive synaptic pruning during childhood, losing about half of the synapses by puberty. We have previously shown that maintaining the network performance while synapses are deleted requires that synapses be properly modified and pruned, with the weaker synapses removed. We now show that neuronal regulation, a mechanism recently observed to maintain the average neuronal input field of a postsynaptic neuron, results in a weight-dependent synaptic modification. Under the correct range of the degradation dimension and synaptic upper bound, neuronal regulation removes the weaker synapses and judiciously modifies the remaining synapses. By deriving optimal synaptic modification functions in an excitatory-inhibitory network, we prove that neuronal regulation implements near-optimal synaptic modification and maintains the performance of a network undergoing massive synaptic pruning. These findings support the possibility that neural regulation complements the action of Hebbian synaptic changes in the self-organization of the developing brain.


Developments in the field of allergy in 2014 through the eyes of Clinical and Experimental Allergy.
The pathogenesis of asthma continues to be a major topic of interest to our authors with reviews and original papers on the role of viruses, mechanisms of inflammation, biomarkers, and phenotypes of asthma being major topics. A number of papers described new treatments for asthma focusing on blocking the Th2 response reflecting the fact that two decades of work in this area is finally bearing fruit. The pathogenesis of chronic rhinosinusitis is a growing area of interest, but there has been less on the genetics of airways disease than in previous years possibly reflecting the degree of rigour (and therefore a smaller body of work), with which these sorts of studies are now being undertaken. There continues to be a wide range of papers dealing with mechanisms of allergic disease ranging from clinical-based studies to basic research and the use of in vivo animal models especially mice. As before, mechanisms and new approaches to immunotherapy are common themes. Several were published in the allergens section investigating modification of allergens to increase their effectiveness and reduce the risk of adverse events. Risk factors for allergic disease was a common theme in the epidemiology section and food allergy a common theme in clinical allergy with papers on the development of protocols to induce tolerance and attempts to find biomarkers to distinguish sensitization from allergic disease. This was another exciting year for the editors, and we hope the readers of the journal.


Physical Activity, Sleep, and Nutrition Do Not Predict Cognitive Performance in Young and Middle-Aged Adults.
Biological lifestyle factors (BLFs) such as physical activity, sleep, and nutrition play a role in cognitive functioning. Research concerning the relation between BLFs and cognitive performance is scarce however, especially in young and middle-aged adults. Research has not yet focused on a multidisciplinary approach with respect to this relation in the abovementioned population, where lifestyle habits are more stable. The aim of this study was to examine the contribution of these BLFs to cognitive performance. Path analysis was conducted in an observational study in which 1131 adults were analyzed using a cross-validation approach. Participants provided information on physical activity, sedentary behavior, chronotype, sleep duration, sleep quality, and the consumption of breakfast, fish, and caffeine via a survey. Their cognitive performance was measured using objective digital cognitive tests. Exploration yielded a predictive cohesive model that fitted the data properly, χ(2) /df = 0.8, CFI = 1.00, RMSEA < 0.001, SRMR = 0.016. Validation of the developed model indicated that the model fitted the data satisfactorily, χ(2) /df = 2.75, CFI = 0.95, RMSEA < 0.056, SRMR = 0.035. None of the variables within the BLFs were predictive for any of the cognitive performance measures, except for sedentary behavior. Although sedentary behavior was positively predictive for processing speed its contribution was small and unclear. The results indicate that the variables within the BLFs do not predict cognitive performance in young and middle-aged adults.


Reinforcing effects of compounds lacking intrinsic efficacy at α1 subunit-containing GABAA receptor subtypes in midazolam- but not cocaine-experienced rhesus monkeys.
Benzodiazepines are prescribed widely but their utility is limited by unwanted side effects, including abuse potential. The mechanisms underlying the abuse-related effects of benzodiazepines are not well understood, although α1 subunit-containing GABAA receptors have been proposed to have a critical role. Here, we examine the reinforcing effects of several compounds that vary with respect to intrinsic efficacy at α2, α3, and α5 subunit-containing GABAA receptors but lack efficacy at α1 subunit-containing GABAA receptors ('α1-sparing compounds'): MRK-623 (functional selectivity for α2/α3 subunit-containing receptors), TPA023B (functional selectivity for α2/α3/α5 subunit-containing receptors), and TP003 (functional selectivity for α3 subunit-containing receptors). The reinforcing effects of the α1-sparing compounds were compared with those of the non-selective benzodiazepine receptor partial agonist MRK-696, and non-selective benzodiazepine receptor full agonists, midazolam and lorazepam, in rhesus monkeys trained to self-administer midazolam or cocaine, under a progressive-ratio schedule of intravenous (i.v.) drug injection. The α1-sparing compounds were self-administered significantly above vehicle levels in monkeys maintained under a midazolam baseline, but not under a cocaine baseline over the dose ranges tested. Importantly, TP003 had significant reinforcing effects, albeit at lower levels of self-administration than non-selective benzodiazepine receptor agonists. Together, these results suggest that α1 subunit-containing GABAA receptors may have a role in the reinforcing effects of benzodiazepine-type compounds in monkeys with a history of stimulant self-administration, whereas α3 subunit-containing GABAA receptors may be important mediators of the reinforcing effects of benzodiazepine-type compounds in animals with a history of sedative-anxiolytic/benzodiazepine self-administration.


Gli2, but not Gli1, is required for initial Shh signaling and ectopic activation of the Shh pathway.
The Shh signaling pathway is required in many mammalian tissues for embryonic patterning, cell proliferation and differentiation. In addition, inappropriate activation of the pathway has been implicated in many human tumors. Based on transfection assays and gain-of-function studies in frog and mouse, the transcription factor Gli1 has been proposed to be a major mediator of Shh signaling. To address whether this is the case in mouse, we generated a Gli1 null allele expressing lacZ. Strikingly, Gli1 is not required for mouse development or viability. Of relevance, we show that all transcription of Gli1 in the nervous system and limbs is dependent on Shh and, consequently, Gli1 protein is normally not present to transduce initial Shh signaling. To determine whether Gli1 contributes to the defects seen when the Shh pathway is inappropriately activated and Gli1 transcription is induced, Gli1;Ptc double mutants were generated. We show that Gli1 is not required for the ectopic activation of the Shh signaling pathway or to the early embryonic lethal phenotype in Ptc null mutants. Of significance, we found instead that Gli2 is required for mediating some of the inappropriate Shh signaling in Ptc mutants. Our studies demonstrate that, in mammals, Gli1 is not required for Shh signaling and that Gli2 mediates inappropriate activation of the pathway due to loss of the negative regulator Ptc.


Japanese cancer patient participation in and satisfaction with treatment-related decision-making: A qualitative study.
Over the last decade, patient involvement in treatment-related decision-making has been widely advocated in Japan, where patient-physician encounters are still under the influence of the long-standing tradition of paternalism. Despite this profound change in clinical practice, studies investigating the actual preferences of Japanese people regarding involvement in treatment-related decision-making are limited. The main objectives of this study were to (1) reveal the actual level of involvement of Japanese cancer patients in the treatment-related decision-making and their overall satisfaction with the decision-making process, and (2) consider the practical implications of increased satisfaction in cancer patients with regard to the decision-making process. We conducted semi-structured interviews with 24 Japanese cancer patients who were recruited from a cancer self-help group in Tokyo. The interviews were qualitatively analysed using the approach described by Lofland and Lofland. The analyses of the patients' interviews focused on 2 aspects: (1) who made treatment-related decisions (the physician or the patient), and (2) the informants' overall satisfaction with the decision-making process. The analyses revealed the following 5 categories of decision-making: 'patient as the active decision maker', 'doctor selection', 'wilfully entrusting the physician', 'compelled decision-making', and 'surrendering decision-making'. While the informants under the first 3 categories were fairly satisfied with the decision-making process, those under the latter 2 were extremely dissatisfied. Informants' views regarding their preferred role in the decision-making process varied substantially from complete physician control to complete patient control; the key factor for their satisfaction was the relation between their preferred involvement in decision-making and their actual level of involvement, irrespective of who the decision maker was. In order to increase patient satisfaction with regard to the treatment-related decision-making process, healthcare professionals in Japan must assess individual patient preferences and provide healthcare accordingly. Moreover, a better environment should be created in hospitals and in society to facilitate patients in expressing their preferences and appropriate resources need to be made available to facilitate their decision-making process.


Elevated aggression is associated with uncertainty in a network of dog dominance interactions.
Dominance hierarchies are widespread in animal societies and reduce the costs of within-group conflict over resources and reproduction. Variation in stability across a social hierarchy may result in asymmetries in the benefits obtained from hierarchy formation. However, variation in the stability and behavioural costs of dominance interactions with rank remain poorly understood. Previous theoretical models have predicted that the intensity of dominance interactions and aggression should increase with rank, but these models typically assume high reproductive skew, and so their generality remains untested. Here we show in a pack of free-living dogs with a sex-age-graded hierarchy that the central region of the hierarchy was dominated by more unstable social relationships and associated with elevated aggression. Our results reveal unavoidable costs of ascending a dominance hierarchy, run contrary to theoretical predictions for the relationship between aggression and social rank in high-skew societies, and widen our understanding of how heterogeneous benefits of hierarchy formation arise in animal societies.


Investigation of the interaction of amyloid β peptide (11-42) oligomers with a 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) membrane using molecular dynamics simulation.
Some amyloid related proteins/peptides are involved in aggregation and pore formation in phospholipid membranes (cell membranes), which result in a variety of neurological disorders such as Alzheimer's disease, Parkinson's disease and Huntington disease. In this research, the mechanism of pore formation by β amyloid (Aβ) peptides was investigated using molecular dynamics simulation by simulating the interaction of the Aβ(11-42) peptide, with a lipid membrane and the potential of the mean force of interaction was evaluated. A 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) membrane system with different cholesterol concentrations was used to simulate the neural cell membrane. The results indicated that Aβ(11-42) peptide oligomers with peptide numbers larger than two were more likely to lead to lipid deformation and water channels, and the free energy of penetration into the membrane decreased with the increasing number of peptides. Increasing the concentration of cholesterol leads to a higher energy barrier for the penetration of peptide into the lipid bilayer thereby protecting the membrane. The results of this research have potential application in the prevention of pore formation by Aβ aggregates on the lipid membrane.


A developmentally regulated and tissue-dependent transcription factor complexes with the retinoblastoma gene product.
DRTF1 is a cellular transcription factor which complexes with the retinoblastoma (Rb) gene product and cyclin A, an association modulated by certain viral oncogenes, such as adenovirus E1a. Complexed DRTF1, referred to as DRTF1a, has similar DNA binding specificity and DNA binding polypeptides to DRTF1b, which lacks Rb. DRTF1b is abundant in both F9 embryonal carcinoma (EC) stem cells and pluripotent embryonic stem (ES) cells and is strongly down-regulated during the differentiation of both cell types, suggestive of a stem cell E1a-like activity. In contrast, DRTF1a, which in F9 EC cells is much less abundant than the other activities, is induced as F9 cells begin to differentiate. Consistent with the relationship between EC, ES and inner cell mass cells, DRTF1b is present in blastocyst stage embryos although as embryogenesis progresses the levels of Rb-complexed DRTF1 increase. Certain tissues, such as liver and brain, contain high levels of DRTF1 during early embryonic stages but little in adult terminally differentiated tissue, in contrast to the thymus, which contains high levels of Rb-complexed DRTF1 but lacks associated cyclin A. These data show that DRTF1 is a group of transcription factors that share common DNA binding polypeptides and which complex with other non-DNA binding proteins, such as the Rb protein and cyclin A, in a developmentally regulated and tissue-dependent fashion.


Both seed germination and seedling mortality increase with experimental warming and fertilization in a subarctic tundra.
Climate change is expected to force many species in arctic regions to migrate and track their climatic niche. This requires recruitment from seed, which currently shows very low rates in arctic regions, where long-lived and vegetatively reproducing plants dominate. Therefore, we pose the question whether recruitment (germination and seedling establishment) in arctic regions will significantly improve in a warmer world, and thus allow species to follow their climatic niche. We used a full factorial experiment to examine if realistic warmer temperatures (+3 °C; infrared radiation) and increased nitrogen availability (+1.4 g N m-2 year-1) affected germination, seedling survival and above- and below-ground seedling biomass in five species common in subarctic regions (Anthoxanthum odoratum, Betula nana, Pinus sylvestris, Solidago virgaurea, Vaccinium myrtillus). We found that warming increased seedling emergence in all species, but that subsequent mortality also increased, resulting in no net warming effect on seedling establishment. Warming slightly increased above-ground seedling biomass. Fertilization, on the other hand, did not influence seedling biomass, but it increased seedling establishment in B. nana while it reduced establishment in V. myrtillus. This may help B. nana dominate over V. myrtillus in warmer tundra. Surprisingly, no interactive effects between warming and fertilization were found. The lack of a general positive response of seedling establishment to warmer and more nutrient-rich conditions suggests that (sub)arctic species may experience difficulties in tracking their climatic niche. Predictions of future species distributions in arctic regions solely based on abiotic factors may therefore overestimate species' ranges due to their poor establishment. Also, the opposite response to fertilization of two key (sub)arctic dwarf shrubs, i.e. B. nana and V. myrtillus, could have important implications for the future development of arctic plant communities and argues for more research into the role of fertilization for plant establishment.


Recovery of Food Intake after Gastrectomy for Gastric Cancer: Based on a Large-Scale Gastric Cancer Cohort.
This study was aimed at evaluating the food intake and nutritional status of patients who underwent gastrectomy for gastric cancer based on a large-scale gastric cancer cohort. An observational prospective cohort study for gastric cancer has been conducted since 2010. From the cohort data, we selected the data for patients who completed at least 2 days of 3-day diet diaries and who underwent subtotal gastrectomy (STG) or total gastrectomy (TG). As a control group, patients who underwent endoscopic submucosal dissection were also included. The collected diet data were converted to macro- and micronutrients using computerized software, and the nutrient intakes were compared. Among 6,556 patients who participated in the cohort study from 2011 to 2016, 1,289 patients who completed at least 2 days of 3-day diet diaries were included in this study. During the postoperative 3-month period, body weight was significantly decreased in the and TG groups. However, there was no difference in nutrient intake among the 3 groups except vitamin D and calcium intake. Similar results were observed during the postoperative 12 months period. Postoperative body weight loss and anemia might originate from altered absorptive function and metabolic change after gastrectomy rather than decreased nutrient intake.


[Characteristics of recidivism in patients with mental disorders: 156 cases analysis].
To analyze the characteristics of recidivism in patients with mental disorders, including criminology, clinic and guardianship, in order to provide references for preventing recidivism. Using the self-designed questionnaire, 156 psychotic patients who had repeated crimes were appraised by West China Forensic Science Center of Sichuan University from 2007 to 2011 and the data were collected and analyzed. In the majority of these cases, patients were male, 26-45 years old, junior high school or below diploma, unmarried, and farmers or jobless. Each patient broke law 3.26 times on average. The main crimes were intentional injury (34.6%) and murder (15.7%). Within 5 years after diagnosis with mental disorder, 56.4% of the patients committed first crime. Within 1 year after the first time breaking the law, 55.8% of them repeated crimes. The diagnoses of schizophrenia (63.5%) were in the majority. The assessment results were mostly irresponsibility (61.5%). Among the patients, 44.9% of them didn't receive treatment while 34.6% of them were out of supervision. After the first crime, 66.1% of them didn't receive criminal prosecution while only 7.1% of them went through the appraisement of forensic psychiatry. Most of the patients had low education and low income. Meanwhile, low outpatient rate and pool supervision occurred in this special crowd. A good system for care and treatment of these mental patients should be built to prevent them from recidivism.


Evolution of the topological properties of two-dimensional group IVA materials and device design.
Two-dimensional group IVA materials (graphene, silicene, germanene, stanene, and plumbene) are promising candidates for realization of the quantum spin Hall effect and for future device applications. We employ density functional theory, tight-binding models, and a Green's function method to systematically investigate their topological properties. From graphene to plumbene, the strength of spin-orbit coupling and the bulk gap increases with increasing atomic mass, and plumbene, as a normal insulator, is totally different from the other four materials, whose ground states are topological insulators. Through detailed analyses of orbital character weights and the evolution of low-energy states around the Γ point, we explain why plumbene is so different. Our quantum transport calculations also indicate that there exist electronic transport channels along edges within the bulk gap of topological insulators. By investigating the effects of external fields on the electronic structures of silicene, germanene, and stanene, we reveal a rich phase diagram and propose two filters with nearly 100% spin polarization. In addition, we present a theoretical design for a spin twister, based on curved two-dimensional topological insulators.