bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stem Cell–based Therapies for Sepsis
Authors: Keane Colm , Jerkic Mirjana , Laffey John G. 
Published: September 2017

Abstract
Sepsis is a life-threatening syndrome resulting in shock and organ dysfunction stemming from a microbial infection. Sepsis has a mortality of 40% and is implicated in half of all in-hospital deaths. The host immune response to microbial infection is critical, with early-phase sepsis characterized by a hyperinflammatory immune response, whereas the later phase of sepsis is often complicated by suppression. Sepsis has no treatment, and management remains supportive.
Stem cells constitute exciting potential therapeutic agents for sepsis. In this review, we examine the rationale for stem cells in sepsis, focusing on mesenchymal stem/stromal cells, which currently demonstrate the greatest therapeutic promise. We examine the preclinical evidence base and evaluate potential mechanisms of action of these cells that are important in the setting of sepsis. We discuss early-phase clinical trials and critically appraise translational barriers to the use of mesenchymal stem/stromal cells in patients with sepsis.
Climate change will lead to pronounced shifts in the diversity of soil microbial communities
Authors: Ladau Joshua , Shi Yu , Jing Xin , He Jin-Sheng , Chen Litong , Lin Xiangui , Fierer Noah , Gilbert Jack A , Pollard Katherine S , Chu Haiyan 
Published: September 2017

ABSTRACTSoil bacteria are key to ecosystem function and maintenance of soil fertility. Leveraging associations of current geographic distributions of bacteria with historic climate, we predict that soil bacterial diversity will increase across the majority (~75%) of the Tibetan Plateau and northern North America if bacterial communities equilibrate with existing climatic conditions. This prediction is possible because the current distributions of soil bacteria have stronger correlations with climate from ~50 years ago than with current climate. This lag is likely associated with the time it takes for soil properties to adjust to changes in climate. The predicted changes are location specific and differ across bacterial taxa, including some bacteria that are predicted to have reductions in their distributions. These findings demonstrate the widespread influence that climate change will have on belowground diversity and highlight the importance of considering bacterial communities when assessing climate impacts on terrestrial ecosystems.IMPORTANCEThere have been many studies highlighting how plant and animal communities lag behind climate change, causing extinction and diversity debts that will slowly be paid as communities equilibrate. By virtue of their short generation times and dispersal abilities, soil bacteria might be expected to respond to climate change quickly and to be effectively in equilibrium with current climatic conditions. We found strong evidence to the contrary in Tibet and North America. These findings could significantly improve understanding of climate impacts on soil microbial communities.
Alternative splicing links histone modifications to stem cell fate decision
Authors: Xu Yungang , Zhao Weiling , Olson Scott D. , Prabhakara Karthik S. , Zhou Xiaobo 
Published: September 2017

AbstractBackgroundUnderstanding the embryonic stem cell (ESC) fate decision between self-renewal and proper differentiation is important for developmental biology and regenerative medicine. Attention has focused on mechanisms involving histone modifications, alternative pre-mRNA splicing, and cell-cycle progression. However, their intricate interrelations and joint contributions to ESC fate decision remain unclear.ResultsWe analyze the transcriptomes and epigenomes of human ESC and five types of differentiated cells. We identify thousands of alternatively spliced exons and reveal their development and lineage-dependent characterizations. Several histone modifications show dynamic changes in alternatively spliced exons and three are strongly associated with 52.8% of alternative splicing events upon hESC differentiation. The histone modification-associated alternatively spliced genes predominantly function in G2/M phases and ATM/ATR-mediated DNA damage response pathway for cell differentiation, whereas other alternatively spliced genes are enriched in the G1 phase and pathways for self-renewal. These results imply a potential epigenetic mechanism by which some histone modifications contribute to ESC fate decision through the regulation of alternative splicing in specific pathways and cell-cycle genes. Supported by experimental validations and extended dataset from Roadmap/ENCODE projects, we exemplify this mechanism by a cell cycle-related transcription factor, PBX1, which regulates the pluripotency regulatory network by binding to NANOG. We suggest that the isoform switch from PBX1a to PBX1b links H3K36me3 to hESC fate determination through the PSIP1/SRSF1 adaptor, which results in the exon skipping of PBX1.ConclusionWe reveal the mechanism by which alternative splicing links histone modifications to stem cell fate decision.
Estimating the scale of biomedical data generation using text mining
Authors: Rosenfeld Gabriel , Lin Dawei 
Published: September 2017

AbstractWhile the impact of biomedical research has traditionally been measured using bibliographic metrics such as citation or journal impact factor, the data itself is an output which can be directly measured to provide additional context about a publication’s impact. Data are a resource that can be repurposed and reused providing dividends on the original investment used to support the primary work. Moreover, it is the cornerstone upon which a tested hypothesis is rejected or accepted and specific scientific conclusions are reached. Understanding how and where it is being produced enhances the transparency and reproducibility of the biomedical research enterprise. Most biomedical data are not directly deposited in data repositories and are instead found in the publication within figures or attachments making it hard to measure. We attempted to address this challenge by using recent advances in word embedding to identify the technical and methodological features of terms used in the free text of articles’ methods sections. We created term usage signatures for five types of biomedical research data, which were used in univariate clustering to correctly identify a large fraction of positive control articles and a set of manually annotated articles where generation of data types could be validated. The approach was then used to estimate the fraction of PLOS articles generating each biomedical data type over time. Out of all PLOS articles analyzed (n = 129,918), ~7%, 19%, 12%, 18%, and 6% generated flow cytometry, immunoassay, genomic microarray, microscopy, and high-throughput sequencing data. The estimate portends a vast amount of biomedical data being produced: in 2016, if other publishers generated a similar amount of data then roughly 40,000 NIH-funded research articles would produce ~56,000 datasets consisting of the five data types we analyzed.One Sentence SummaryApplication of a word-embedding model trained on the methods sections of research articles allows for estimation of the production of diverse biomedical data types using text mining.
Genomic sequencing identifies secondary findings in a cohort of parent study participants
Authors: Thompson Michelle L. , Finnila Candice R. , Bowling Kevin M. , Brothers Kyle B. , Neu Matthew B. , Amaral Michelle D. , Hiatt Susan M. , East Kelly M. , Gray David E. , Lawlor James M. J. , Kelley Whitley V. , Lose Edward J. , Rich Carla A. , Simmons Shirley , Levy Shawn E. , Myers Richard M. , Barsh Gregory S. , Bebin E. Martina , Cooper Gregory M. 
Published: September 2017

ABSTRACTPURPOSEClinically relevant secondary variants were identified in parents enrolled with a child with developmental delay and intellectual disability.METHODSExome/genome sequencing and analysis of 789 ‘unaffected’ parents was performed.RESULTSPathogenic/likely pathogenic variants were identified in 21 genes within 25 individuals (3.2%), with 11 (1.4%) participants harboring variation in a gene defined as clinically actionable by the ACMG. Of the 25 individuals, five carried a variant consistent with a previous clinical diagnosis, thirteen were not previously diagnosed but had symptoms or family history with probable association with the detected variant, and seven reported no symptoms or family history of disease. A limited carrier screen was performed yielding 15 variants in 48 (6.1%) parents. Parents were also analyzed as mate-pairs to identify cases in which both parents were carriers for the same recessive disease; this led to one finding inATP7B.Four participants had two findings (one carrier and one non-carrier variant). In total, 71 of the 789 enrolled parents (9.0%) received secondary findings.CONCLUSIONWe provide an overview of the rates and types of clinically relevant secondary findings, which may be useful in the design, and implementation of research and clinical sequencing efforts to identify such findings.
Functional redundancy of variant and canonical histone H3 lysine 9 modification inDrosophila
Authors: Penke Taylor J.R. , McKay Daniel J. , Strahl Brian D. , Matera A. Gregory , Duronio Robert J. 
Published: September 2017

ABSTRACTHistone post-translational modifications (PTMs) and differential incorporation of variant and canonical histones into chromatin are central modes of epigenetic regulation. Despite similar protein sequences, histone variants are enriched for different suites of PTMs compared to their canonical counterparts. For example, variant histone H3.3 occurs primarily in transcribed regions and is enriched for “active” histone PTMs like Lys9 acetylation (H3.3K9ac), whereas the canonical histone H3 is enriched for Lys9 methylation (H3K9me), which is found in transcriptionally silent heterochromatin. To determine the functions of K9 modification on variant versus canonical H3, we compared the phenotypes caused by engineeringH3.3K9RandH3K9Rmutant genotypes inDrosophila melanogaster. Whereas mostH3.3K9Rand a small number ofH3K9Rmutant animals are capable of completing development and do not have substantially altered protein coding transcriptomes, allH3.3K9RH3K9Rcombined mutants die soon after embryogenesis and display decreased expression of genes enriched for K9ac. These data suggest that the role of K9ac in gene activation during development can be provided by either H3 or H3.3. Conversely, we found that H3.3K9 is methylated at telomeric transposons, and this mark contributes to repressive chromatin architecture, supporting a role for H3.3 in heterochromatin that is distinct from that of H3. Thus, our genetic and molecular analyses demonstrate that K9 modification of variant and canonical H3 have overlapping roles in development and transcriptional regulation, though to differing extents in euchromatin and heterochromatin.
Evidence of sinks and sources in the PLC activated PIP2cycle
Authors: Suratekar Rohit , Raghu Padinjat , Krishna Sandeep 
Published: September 2017

AbstractIn many eukaryotic signalling cascades, receptor mediated phospholipase C (PLC) activity triggers phosphatidylinositol 4,5 bisphosphate (PIP2) hydrolysis leading to information transfer in cells. Coupled with PLC activation is a sequence of reactions spread across multiple compartments by which PIP2is resynthesized, a process essential to maintain PIP2levels and support sustained PLC signalling. The biochemical strategies to co-ordinate these reactions and support PIP2levels have remained poorly understood. In particular, the question of whether the PIP2cycle is a closed cycle with no net addition or loss of metabolites has not been addressed. Using mathematical modelling approaches, we find that a closed PIP2cycle cannot explain experimentally observed changes in the metabolic intermediates when changing enzyme activities in the PIP2cycle. Thus, we propose that the PIP2cycle likely includes at least one metabolic source and one sink whose net activity results in the experimentally observed regulation of this key signalling pathway.
An automated confocal micro-extensometer enables in vivo quantification of mechanical properties with cellular resolution
Authors: Robinson Sarah , Huflejt Michal , Barbier de Reuille Pierre , Braybrook Siobhan A. , Schorderet Martine , Reinhardt Didier , Kuhlemeier Cris 
Published: September 2017

AbstractHow complex developmental-genetic networks are translated into organs with specific 3D shapes remains an open question. This question is particularly challenging because the elaboration of specific shapes is in essence a question of mechanics. In plants, this means how the genetic circuitry affects the cell wall. The mechanical properties of the wall and their spatial variation are the key factors controlling morphogenesis in plants. However, these properties are difficult to measure and investigating their relation to genetic regulation is particularly challenging. To measure spatial variation of mechanical properties, one must determine the deformation of a tissue in response to a known force with cellular resolution. Here we present an automated confocal micro-extensometer (ACME), which greatly expands the scope of existing methods for measuring mechanical properties. Unlike classical extensometers, ACME is mounted on a confocal microscope and utilizes confocal images to compute the deformation of the tissue directly from biological markers, thus providing cellular scale information and improved accuracy. ACME is suitable for measuring the mechanical responses in live tissue. As a proof of concept we demonstrate that the plant hormone gibberellic acid induces a spatial gradient in mechanical properties along the length of the Arabidopsis hypocotyl.TermsStressis the force acting on the material per unit area.Strainthe relative increase in length of the material, and can be expressed as a percentage change in length.Mechanical propertiesdescribe the stress-strain relationship for a material. If we apply the same force to a material that is twice as thick/stiff? it will deform half as much, if the material is otherwise the same.Elasticelastic materials deform instantly and reversibly.Creepa time-dependent irreversible strain that occurs when a constant force is applied and maintained. Creep is measured using creep tests. A force is applied and maintained for a period of time. The force is removed to reveal the reversible and irreversible deformation.
A histone acetylome-wide association study of Alzheimer’s disease: neuropathology-associated regulatory variation in the human entorhinal cortex
Authors: Marzi Sarah J. , Ribarska Teodora , Smith Adam R. , Hannon Eilis , Poschmann Jeremie , Moore Karen , Troakes Claire , Al-Sarraj Safa , Beck Stephan , Newman Stuart , Lunnon Katie , Schalkwyk Leonard C. , Mill Jonathan 
Published: September 2017

AbstractAlzheimer’s disease (AD) is a chronic neurodegenerative disorder characterized by the progressive accumulation of amyloid-β (Aβ) plaques and neurofibrillary tangles in the neocortex. Recent studies have implicated a role for regulatory genomic variation in AD progression, finding widespread evidence for altered DNA methylation associated with neuropathology. To date, however, no study has systematically examined other types of regulatory genomic modifications in AD. In this study, we quantified genome-wide patterns of lysine H3K27 acetylation (H3K27ac) - a robust mark of active enhancers and promoters that is strongly correlated with gene expression and transcription factor binding - in entorhinal cortex samples from AD cases and matched controls (n = 47) using chromatin immunoprecipitation followed by highly parallel sequencing (ChIP-seq). Across ~182,000 robustly detected H3K27ac peak regions, we found widespread acetylomic variation associated with AD neuropathology, identifying 4,162 differential peaks (FDR < 0.05) between AD cases and controls. These differentially acetylated peaks are enriched in disease-specific biological pathways and include regions annotated to multiple genes directly involved in the progression of Aβ and tau pathology (e.g.APP,PSEN1,PSEN2,MAPT), as well as genomic regions containing variants associated with sporadic late-onset AD. This is the first study of variable H3K27ac yet undertaken in AD and the largest study investigating this modification in the entorhinal cortex. In addition to identifying molecular pathways associated with AD neuropathology, we present a framework for genome-wide studies of histone modifications in complex disease, integrating our data with results obtained from genome-wide association studies as well as other epigenetic marks profiled on the same samples.
Cell size control driven by the circadian clock and environment in cyanobacteria
Authors: Martins Bruno M. C. , Tooke Amy K. , Thomas Philipp , Locke James C. W. 
Published: September 2017

AbstractHow cells maintain their size has been extensively studied under constant conditions. In the wild, however, cells rarely experience constant environments. Here, we examine how the 24-hour circadian clock and environmental cycles modulate cell size control and division timings in the cyanobacteriumSynechococcus elongatususing single-cell time-lapse microscopy. Under constant light, wild type cells follow an apparent sizer-like principle. Closer inspection reveals that the clock generates two subpopulations, with cells born in the subjective day following different division rules from cells born in subjective night. A stochastic model explains how this behaviour emerges from the interaction of cell size control with the clock. We demonstrate that the clock continuously modulates the probability of cell division throughout day and night, rather than solely applying an on-off gate to division as previously proposed. Iterating between modelling and experiments, we go on to show that the combined effects of the environment and the clock on cell division are explained by an effective coupling function. Under naturally graded light-dark cycles, this coupling shifts cell division away from dusk and dawn, when light levels are low and cell growth is reduced. Our analysis allows us to disentangle, and predict the effects of, the complex interactions between the environment, clock, and cell size control.
Neurochondrin interacts with the SMN protein suggesting a novel mechanism for Spinal Muscular Atrophy pathology
Authors: Thompson Luke , Morrison Kim , Shirran Sally , Botting Catherine , Sleeman Judith 
Published: September 2017

AbstractSpinal Muscular Atrophy (SMA) is an inherited neurodegenerative condition caused by reduction in functional Survival Motor Neurones Protein (SMN). SMN has been implicated in transport of mRNA in neural cells for local translation. We previously identified microtubule-dependant mobile vesicles rich in SMN and the splicing factor SmB, a member of the Sm protein family, in neural cells. By comparing the proteome of SmB to that of SmN, a neural-specific Sm protein, we now show that the essential neural protein neurochondrin (NCDN) interacts with Sm proteins and SMN in the context of mobile vesicles in neurites. NCDN has roles in protein localisation in neural cells, and in maintenance of cell polarity. NCDN is required for the correct localisation of SMN, suggesting they may both be required for formation and transport of trafficking vesicles. NCDN provides a potential therapeutic target for SMA together with, or in place of, those targeting SMN expression.
Dynamic threat processing
Authors: Meyer Christian , Padmala Srikanth , Pessoa Luiz 
Published: September 2017

AbstractDuring real-life situations, multiple factors interact dynamically to determine threat level. In the current functional MRI study involving healthy adult human volunteers, we investigated interactions between proximity, direction (approach vs. retreat), and speed during a dynamic threat-of-shock paradigm. As a measure of threat-evoked physiological arousal, skin conductance responses were recorded during fMRI scanning. Whereas some brain regions tracked individual threat-related factors, others were also sensitive to combinations of these variables. In particular, signals in the anterior insula tracked the interaction between proximity and direction where approach vs. retreat responses were stronger when threat was closer compared to farther. A parallel proximity-by-direction interaction was also observed in physiological skin conductance responses. In the right amygdala, we observed a proximity by direction interaction, but intriguingly in the opposite direction as the anterior insula; retreat vs. approach responses were stronger when threat was closer compared to farther. In the right bed nucleus of the stria terminalis, we observed an effect of threat proximity, whereas in the right periaqueductal gray/midbrain we observed an effect of threat direction and a proximity by direction by speed interaction (the latter was detected in exploratory analyses but not in a voxelwise fashion). Together, our study refines our understanding of the brain mechanisms involved during aversive anticipation in the human brain. Importantly, it emphasizes that threat processing should be understood in a manner that is both context sensitive and dynamic.
Raspberry Pi Powered Imaging for Plant Phenotyping
Authors: Tovar Jose C. , Hoyer J. Steen , Lin Andy , Tielking Allison , Tessman Monica , Miller Michael , Callen Steven T. , Castillo S. Elizabeth , Fahlgren Noah , Carrington James C. , Nusinow Dmitri A. , Gehan Malia A. 
Published: September 2017

ABSTRACTPremise of the study: Image-based phenomics is a powerful approach to capture and quantify plant diversity. However, commercial platforms that make consistent image acquisition easy are often cost-prohibitive. To make high-throughput phenotyping methods more accessible, low-cost microcomputers and cameras can be used to acquire plant image data.Methods and Results: We used low-cost Raspberry Pi computers and cameras to manage and capture plant image data. Detailed here are three different applications of Raspberry Pi controlled imaging platforms for seed and shoot imaging. Images obtained from each platform were suitable for extracting quantifiable plant traits (shape, area, height, color)en masseusing open-source image processing software such as PlantCV.Conclusion: This protocol describes three low-cost platforms for image acquisition that are useful for quantifying plant diversity. When coupled with open-source image processing tools, these imaging platforms provide viable low-cost solutions for incorporating high-throughput phenomics into a wide range of research programs.