bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dose-dependent functions of SWI/SNF BAF in permitting and inhibiting cell proliferationin vivo
Authors: van der Vaart Aniek , Godfrey Molly , Portegijs Vincent , van den Heuvel Sander 
Published: May 2019

AbstractSWI/SNF complexes regulate transcription through chromatin remodeling and opposing gene silencing by Polycomb-group (PcG) proteins. Genes that encode SWI/SNF subunits are frequently mutated in human cancer. The selective advantage, subunit bias, and common heterozygosity of such mutations remains poorly understood. Here, we characterized how functional loss of various SWI/SNF subunits and PcG EZH2 affect proliferation-differentiation decisionsin vivo, making use of the reproducible development of the nematodeC. elegans.We applied a lineage-specific genetics strategy to create partial or complete SWI/SNF subunit loss, as well as double gene knockout with PcG EZH2. Our data show that a high SWI/SNF BAF dosage is needed to oppose Polycomb-mediated transcriptional repression and to arrest cell division during differentiation. In contrast, even in the absence of the PcG EZH2-related methyltransferase, a low level of the SWI/SNF BAF complex is necessary and sufficient to sustain cell proliferation and hyperplasia. Our data provide experimental support for the theory that during carcinogenesis partial SWI/SNF BAF loss-of-function mutations are selected because they eliminate a tumor suppressor activity while maintaining an essential transcription regulatory function.
Deep-learning enables proteome-scale identification of phase-separated protein candidates from immunofluorescence images
Authors: Yu Chunyu , Shen Boyan , Huang Qi , Shi Minglei , You Kaiqiang , Wu Congying , Chen Yang , Li Tingting 
Published: May 2019

AbstractIntrinsically disordered region (IDR) analysis has been widely used in the screening of phase-separated proteins. However, the precise sequences determining phase separation remain unclear. Furthermore, a large number of phase-separated proteins that exhibit relatively low IDR content remain uncharacterized. Phase-separated proteins appear as spherical droplet structures in immunofluorescence (IF) images, which renders them distinguishable from non-phase-separated proteins. Here, we transformed the problem of phase-separated protein recognition into a binary classification problem of image recognition. In addition, we established a method named IDeepPhase to identify IF images with spherical droplet structures based on convolutional neural networks. Using IDeepPhase on proteome-scale IF images from the Human Protein Atlas database, we generated a comprehensive list of phase-separated candidates which displayed spherical droplet structures in IF images, allowing nomination of proteins, antibodies and cell lines for subsequent phase separation study.
Genomic prediction including SNP-specific variance predictors
Authors: Mouresan E. F. , Selle M. , Rönnegård L. 
Published: May 2019

AbstractThe amount of available biological information on the markers is constantly increasing and provides valuable insight into the underlying biology of traits of interest. This information can also be used to inform the models applied for genomic selection to improve predictions. The objective of this study was to propose a general model for genomic selection using a link function approach within the hierarchical generalized linear model framework (hglm) that can include external information on the markers. These models can be fitted using the well-established hglm package in R. Furthermore, we also present an R package (CodataGS) to fit these models, which is significantly faster than the hglm package when the number of markers largely exceeds the number of individuals. Simulated data was used to validate the proposed model. Knowledge on the location of the QTLs on the genome, with varying degree of uncertainty, was used as external information on the markers. The proposed model showed improved accuracies from 3.8% up to 23.2% compared to the SNP-BLUP method, which assumes equal variances for all markers. The performance of the proposed models depended on the genetic architecture of the trait, as traits that deviate from the infinitesimal model benefited more from the external information. Also, the gain in accuracy depended on the degree of uncertainty of the external information provided to the model. The usefulness of these type of models is expected to increase with time as more accurate information on the markers becomes available.
Application of a novel force-field to manipulate the relationship between pelvis motion and step width in human walking
Authors: Heitkamp Lauren N. , Stimpson Katy H. , Dean Jesse C. 
Published: May 2019

AbstractMotion of the pelvis throughout a step predicts step width during human walking. This behavior is often considered an important component of ensuring bipedal stability, but can be disrupted in populations with neurological injuries. The purpose of this study was to determine whether a novel force-field that exerts mediolateral forces on the legs can manipulate the relationship between pelvis motion and step width, providing proof-of-concept for a future clinical intervention. We designed a force-field able to: 1) minimize the delivered mediolateral forces (Transparent mode); 2) apply mediolateral forces to assist the leg toward mechanically-appropriate step widths (Assistive mode); and 3) apply mediolateral forces to perturb the leg away from mechanically-appropriate step widths (Perturbing mode). Neurologically-intact participants were randomly assigned to either the Assistive group (n=12) or Perturbing group (n=12), and performed a series of walking trials in which they interfaced with the force-field. We quantified the step-by-step relationship between mediolateral pelvis displacement and step width using partial correlations. Walking in the Transparent force-field had a minimal effect on this relationship. However, force-field assistance directly strengthened the relationship between pelvis displacement and step width, whereas force-field perturbations weakened this relationship. Both assistance and perturbations were followed by short-lived effects during a wash-out period, in which the relationship between pelvis displacement and step width differed from the baseline value. The present results demonstrate that the link between pelvis motion and step width can be manipulated through mechanical means, which may be useful for retraining gait balance in clinical populations.
Fluorescent Sp3 Defect-Tailored Carbon Nanotubes Enable NIR-II Single Particle Imaging in Live Brain Slices at Ultra-Low Excitation Doses
Authors: Mandal Amit Kumar , Wu Xiaojian , Ferreira Joana S. , Kim Mijin , Powell Lyndsey R. , Kwon Hyejin , Groc Laurent , Wang YuHuang , Cognet Laurent 
Published: May 2019

AbstractCellular and tissue imaging in the second near-infrared window (NIR-II, ∼1000 - 1350 nm) is advantageous for in vivo studies because of low light extinction by biological constituents at these wavelengths. However, deep tissue imaging at the single molecule sensitivity has not been achieved in the NIR-II window due to lack of suitable bio-probes. Single-walled carbon nanotubes have emerged as promising near-infrared luminescent molecular bio-probes; yet, their inefficient photoluminescence (quantum yield ∼1%) drives requirements for sizeable excitation doses (∼1-10 kW/cm2) that are significantly blue-shifted from the NIR-II region (<850 nm) and may thus ultimately compromise live tissue. Here, we show that single nanotube imaging can be achieved in live brain tissue using ultralow excitation doses (∼100 W/cm2), an order of magnitude lower than those currently used. To accomplish this, we synthesized fluorescent sp3-defect tailored (6,5) carbon nanotubes which, when excited at their first order excitonic transition fluoresce brightly at ∼1160 nm. The biocompatibility of these functionalized nanotubes, which are wrapped by state-of-the-art encapsulation agents (phospholipid-polyethylene glycol), is demonstrated using standard cytotoxicity assays. Single molecule photophysical studies of these biocompatible nanotubes allowed us to identify the optimal luminescence properties in the context of biological imaging.
Bioresponsive Microspheres for On-demand Delivery of Anti-inflammatory Cytokines for Osteoarthritis
Authors: Park Eunjae , Hart Melanie , Rolauffs Bernd , Stegemann Jan P. , Annamalai Ramkumar T. 
Published: May 2019

AbstractDespite innovations in surgical interventions, treatment of cartilage injury in osteoarthritic joints remains a challenge due to concomitant inflammation. Obstructing a single dominant inflammatory cytokine have shown remarkable clinical benefits in rheumatoid arthritis, and similar strategies are being suggested to target inflammatory pathways in osteoarthritis (OA). Here we describe the utility of gelatin microspheres that are responsive to arthritic flares, resulting in on-demand, and spatiotemporally controlled release of anti-inflammatory cytokines for cartilage preservation and repair. These microspheres had net negative charge potential to sequester cationic anti-inflammatory cytokines, and the magnitude of the negative charge potential increased with increase in crosslinking density. The enzymatic degradation of the microcarriers was concentration dependent. Release of anti-inflammatory cytokines from the loaded microspheres was directly correlated with the degradation of the gelatin matrix. Exposure of the IL-4 and IL-13 loaded microspheres reduced the inflammation of chondrocytes up to 80%. Hence, the delivery of these microspheres in an osteoarthritic joint can attenuate the stimulation of chondrocytes to secrete catabolic factors including proteinases and nitric oxide. The microsphere format also allows for minimally invasive delivery and is less susceptible to mechanically-induced drug release and are conformant to the intra-articular space. Consequently, bioresponsive microspheres are an effective tool for OA prevention and treatment.
Cell-Fate Determination from Embryo to Cancer Development: Genomic Mechanism Elucidated
Authors: Tsuchiya Masa , Giuliani Alessandro , Yoshikawa Kenichi 
Published: May 2019

AbstractThe elucidation of the how and when of a cell-fate change asks for a physically reasonable mechanism allowing to achieve a coordinated switching of thousands of genes within a small and highly packed cell nucleus. We previously demonstrated that whole genome expression is dynamically self-organized through the emergence of a critical point. Furthermore, it has been confirmed that this happens at both the cell-population and single-cell level through the physical principle of self-organized criticality.In this paper, we further examine the genomic mechanism which determines cell-fate changes from embryo to cancer development. The state of the critical point, acting as the organizing center of cell-fate, determines whether the genome resides in a super- or sub-critical state. In the super-critical state, a specific stochastic perturbation can spread over the entire system through the ‘genome engine’ - an autonomous critical-control genomic system, whereas in the sub-critical state, the perturbation remains at a local level. We provide a consistent framework to develop a biological regulation transition theory demonstrating the cell-fate change.
The Pursuit of Pride: Outcomes achieved under Beliefs of Internal Control shape positive Affect and neural Dynamics in the vmPFC
Authors: Stolz David S , Müller-Pinzler Laura , Krach Sören , Paulus Frieder M 
Published: May 2019

AbstractExperiencing events as controllable and attributing positive outcomes to own contributions is essential for human well-being. Based on classic psychological theory we test how internal control beliefs impact the affective valuation of task outcomes, neural dynamics and ensuing behavioral preferences. In three consecutive studies with independent samples we show that dynamics in self-evaluative affect specifically increase when agents believe they caused a given task outcome. We demonstrate that these outcomes engage brain networks processing self-referential information in the cortical midline. Here, activity in the ventromedial prefrontal cortex tracks outcome valence regarding both success as well as internal control, and covaries with self-evaluative affect. These affective dynamics also relate to increased functional coupling between the ventral striatum and cortical midline structures. Finally, we show that self-evaluative affect promotes preferences for control, even at a monetary cost. Our investigations extend recent models of positive affect and well-being, and emphasize that control beliefs drive intrinsic motivation.
Improved single-cell ATAC-seq reveals chromatin dynamics of in vitro corticogenesis
Authors: Mulqueen Ryan M. , DeRosa Brooke A. , Thornton Casey A. , Sayar Zeynep , Torkenczy Kristof A. , Fields Andrew J. , Wright Kevin M. , Nan Xiaolin , Ramji Ramesh , Steemers Frank J. , O’Roak Brian J. , Adey Andrew C. 
Published: May 2019

AbstractDevelopment is a complex process that requires the precise modulation of regulatory gene networks controlled through dynamic changes in the epigenome. Single-cell-omic technologies provide an avenue for understanding the mechanisms of these processes by capturing the progression of epigenetic cell states during the course of cellular differentiation using in vitro or in vivo models1. However, current single-cell epigenomic methods are limited in the information garnered per individual cell, which in turn limits their ability to measure chromatin dynamics and state shifts. Single-cell combinatorial indexing (sci-) has been applied as a strategy for identifying single-cell-omic originating libraries and removes the necessity of single-cell, single-compartment chemistry2. Here, we report an improved sci-assay for transposase accessible chromatin by sequencing (ATAC-seq), which utilizes the small molecule inhibitor Pitstop 2™ (scip-ATAC-seq)3. We demonstrate that these improvements, which theoretically could be applied to any in situ transposition method for single-cell library preparation, significantly increase the ability of transposase to enter the nucleus and generate highly complex single-cell libraries, without altering biological signal. We applied sci-ATAC-seq and scip-ATAC-seq to characterize the chromatin dynamics of developing forebrain-like organoids, an in vitro model of human corticogenesis4. Using these data, we characterized novel putative regulatory elements, compared the epigenome of the organoid model to human cortex data, generated a high-resolution pseudotemporal map of chromatin accessibility through differentiation, and measured epigenomic changes coinciding with a neurogenic fate decision point. Finally, we combined transcription factor motif accessibility with gene activity (GA) scores to directly observe the dynamics of complex regulatory programs that regulate neurogenesis through developmental pseudotime. Overall, scip-ATAC-seq increases information content per cell and bolsters the potential for future single-cell studies into complex developmental processes.
Evaluation of radioprotective effect of chickpea (Cicer arietinum) in the survival of Lasioderma serricorne (Fabricius, 1792) (Coleoptera, Anobìidae) irradiated with 60Co
Authors: Barros Adilson C. , Okazaki Kayo , Arthur Valter 
Published: May 2019

ABSTRACTWe investigated the presence of natural radioprotectors in food using a new technical modality that utilizes the insect Lasioderma serricorne as a radiosensitivity bioindicator to check radioprotection properties in minimally processed chickpeas. The insects were obtained from the entomological biotherium of the Laboratory of Radiobiology and Environment of CENA-USP. They were fed with an experimental diet and just when the first generation hatched completely, the experiments were conducted. The randomly chosen control diet, consisted of three parts of wheat germ, one part of brewer’s yeast, and a slice of French bread toasted in an oven previously set up for humidity control. The diet of chickpeas consists only of whole grains crushed in a mechanical grinder to obtain flour. The result was significant for the survival of insects (p<0.0001) reared on a diet of chickpeas compared to those reared on control diet irradiated with gamma rays from 60Co in the range of 5.0 to 1500 Gy. We presented statistical evidence that the chickpea diet has radioprotective properties in the insect for gamma rays.SUMMARY STATEMENTThe study is important because it shows that chickpea has protective properties against ionizing radiation, how to act against its biological effects and minimize them.
Elaborate expansion of syntenic V1R hotspots correlates with high species diversity in nocturnal mouse and dwarf lemurs
Authors: Hunnicutt Kelsie E. , Tiley George P. , Williams Rachel C. , Larsen Peter A. , Blanco Marina B. , Rasoloarison Rodin M. , Campbell C. Ryan , Zhu Kevin , Weisrock David W. , Matsunami Hiroaki , Yoder Anne D. 
Published: May 2019

AbstractSensory gene families are of special interest, both for what they can tell us about molecular evolution, and for what they imply as mediators of social communication. The vomeronasal type-1 receptors (V1Rs) have often been hypothesized as playing a fundamental role in driving or maintaining species boundaries given their likely function as mediators of intraspecific mate choice, particularly in nocturnal mammals. Here, we employ a comparative genomic approach for revealing patterns of V1R evolution within primates, with a special focus on the small-bodied nocturnal mouse and dwarf lemurs of Madagascar (generaMicrocebusandCheirogaleus, respectively). By doubling the existing genomic resources for strepsirrhine primates (i.e., the lemurs and lorises), we find that the highly-speciose and morphologically-cryptic mouse lemurs have experienced an elaborate proliferation of V1Rs that we argue is functionally related to their capacity for rapid lineage diversification. Contrary to a previous study that found equivalent degrees of V1R diversity in diurnal and nocturnal lemurs, our study finds a strong correlation between nocturnality and V1R elaboration, with nocturnal lemurs showing elaborate V1R repertoires and diurnal lemurs showing less diverse repertoires. Recognized subfamilies among V1Rs show unique signatures of diversifying positive selection, as might be expected if they have each evolved to respond to specific stimuli. Further, a detailed syntenic comparison of mouse lemurs with mouse (genusMus) and other mammalian outgroups shows that orthologous mammalian subfamilies, predicted to be of ancient origin, tend to cluster in a densely populated region across syntenic chromosomes that we refer to as V1R “hotspots.”
Power-law behaviour of transcription factor dynamics at the single-molecule level implies a continuum affinity model
Authors: Garcia David A. , Fettweis Gregory , Presman Diego M. , Paakinaho Ville , Jarzynski Christopher , Upadhyaya Arpita , Hager Gordon L. 
Published: May 2019

ABSTRACTSingle-molecule tracking (SMT) allows the study of transcription factor (TF) dynamics in the nucleus, giving important information regarding the search and binding behaviour of these proteins in the nuclear environment. Dwell time distributions for most TFs have been described by SMT to follow bi-exponential behaviour. This is consistent with the existence of two discrete populations bound to chromatin in vivo, one non-specifically bound to chromatin (i.e. searching mode) and another specifically bound to target sites, as originally defined by decades of biochemical studies. However, alternative models have started to emerge, from multiple exponential components to power-law distributions. Here, we present an analytical pipeline with an unbiased model selection approach based on different statistical metrics to determine the model that best explains SMT data. We found that a broad spectrum of TFs (including glucocorticoid receptor, oestrogen receptor, FOXA1, CTCF) follow a power-law distribution, blurring the temporal line between non-specific and specific binding, and suggesting that productive binding may involve longer binding events than previously thought. We propose a continuum of affinities model to explain the experimental data, consistent with the movement of TFs through complex interactions with multiple nuclear domains as well as binding and searching on the chromatin template.
Interactions between the gut microbiome and mucosal immunoglobulins A, M and G in the developing infant gut
Authors: Janzon Anders , Goodrich Julia K. , Koren Omry ,   the TEDDY Study Group, Waters Jillian L. , Ley Ruth E. 
Published: May 2019

AbstractObjectiveInteractions between the gut microbiome and immunoglobulin (Ig) A in infancy are important for future health. IgM and IgG are also present, however, their interactions with the microbiome in the developing infant are less understood.DesignWe employed stool samples sampled 15 times in infancy from 32 healthy subjects at 4 locations in 3 countries (from the TEDDY study). We characterized patterns of microbiome development in relation to levels of IgA, IgG and IgM. For 8 infants from a single location, we FACS-sorted microbial cells from stool by Ig status. We used 16S rRNA gene profiling on full and sorted microbiomes to assess patterns of antibody coating in relation to age and other factors.ResultsAll antibodies decreased in concentration with age, but were augmented by breastmilk feeding regardless of infant age. Levels of IgA correlated with the relative abundances of OTUs belonging to the Bifidobacteria and Enterobacteriaceae, which dominated the early microbiome, and IgG levels correlated with Haemophilus. The diversity of Ig-coated microbiota was influenced by breastfeeding and age, but birth mode. IgA and IgM coated the same microbiota, while IgG targeted a different subset. Blautia generally evaded antibody coating, while members of the Bifidobacteria and Enterobacteriaceae were high in IgA/M.ConclusionIgA/M have similar dynamics with respect to microbiome development with age, and their interactions with the microbiome are influenced by breastfeeding status. IgG generally does not coat the commensal microbiota.SummaryWhat is already known on this subject?Secretory IgA coats ~50% of microbiota in the gutIgM and IgG are less prevalent and coat a lower fraction in the adult, dynamics in the infant gut are not well characterized.Breastmilk is a source of IgA to the infant gut and decreases with time.IgA coating of microbial cells in infant gut microbiome decreases over time.What are the new findings?Breastfeeding augments the IgA coating of the microbiome at all ages.IgA and IgM coat many of the same cells, whereas few are coated by IgG alone.Bifidobacteria, Enterobacteriaceae, Ruminococcus gnavus are enriched in IgA/M-coated cell fraction, Blautia is enriched in uncoated fraction.IgG levels correlated with Haemophilus.How might it impact on clinical practice in the foreseeable future?Ig-coated fraction of the gut microbiome could serve as a useful tool for tracking development of the infant gut microbiome, and/or identifying aberrations to immune sensing of the microbiome.