bluuebunny/crossref_metadata_2025_split huggingface dataset:
Point-of-Care Testing in Liver Disease and Liver Surgery
Authors: Abeysundara Lasitha , Mallett Susan , Clevenger Ben 
Published: March 2017

AbstractThe alterations in coagulation and hemostasis that accompany liver disease are complex, and while patients with this disease have traditionally been perceived as having a bleeding diathesis, it is now understood that in stable patients hemostasis is “re-balanced.” Hepatic surgery, and particularly liver transplantation, can be associated with large fluid shifts, massive bleeding, and coagulopathy, as well as postoperative thrombosis. Point-of-care tests (POCTs) of coagulation facilitate goal-directed treatments and hemostatic monitoring in dynamic environments where the coagulation status can alter rapidly and often unpredictably. POCTs reflect more accurately the re-balanced hemostatic system than do conventional coagulation tests (CCTs). Viscoelastic POCT-guided transfusion algorithms permit a reduction in blood product administration and are a key component of patient blood management programs. Moreover, viscoelastic POCTs are better able to identify patients with hypercoagulability than CCTs. With thrombosis increasingly recognized to be a problem in patients with liver disease, POCTs hold promise for both individualized bleeding and thrombosis management.
Influence of Body Image in Women Undergoing Treatment for Breast Cancer
Authors: Freitas-Junior Ruffo , Prates Mariana Ferreira Oliveira , Veloso Márcia de Faria , Barros Norami de Moura , Prates Ana Carolina Lagos 
Published: March 2017

Objective The objective of this study was to investigate the self-esteem of women with and without breast cancer regarding their body image.Methods A quantitative, case-control study in which 90 women with breast cancer were evaluated in the case group, and 77 women without breast cancer in the control group. For data collection, the body satisfaction scale (BSS), a scale adapted and validated in Brazil, and the Rosenberg self-esteem questionnaire were used. For the statistical analysis of the data, the Statistical Package for the Social Sciences software (IBM-SPSS, Chicago, Il, US), version 16.0 was used.Results Compared with the women without breast cancer, those with breast cancer were more dissatisfied with body image related to appearance. Women undergoing neoadjuvant chemotherapy were more dissatisfied with their appearance compared with those with cancer who were not undergoing this treatment. Mastectomy also accounted for more dissatisfaction concerning appearance among women who underwent the procedure compared with the women who were submitted to breast-conserving therapy.Conclusion Women with breast cancer were more dissatisfied with their body image compared with those without breast cancer, particularly following mastectomy or during chemotherapy. The self-esteem was found to be negatively affected in patients who were dissatisfied with their body image.
Imaging markers of multiple sclerosis prognosis
Authors: Louapre Céline , Bodini Benedetta , Lubetzki Catherine , Freeman Léorah , Stankoff Bruno 
Published: March 2017

Purpose of reviewStudies of large longitudinal cohorts of patients with multiple sclerosis (MS) have emphasized the prognostic value of conventional MRI markers, at least during early stages. Advanced imaging metrics derived from quantitative MRI and PET provide relevant information about microstructural damage within and outside visible lesions that may be more sensitive to predict long-term disability. Here, we summarize the most recent findings regarding the prognostic value of imaging markers throughout MS stages.Recent findingsIn clinically isolated syndrome, the presence of at least one brain or spinal cord T2 lesion strongly increases the risk of conversion to clinically definite MS (hazard ratio ranging from 5 to 11). Similarly, the occurrence of new white matter lesions is strongly predictive of subsequent relapse rate and response to current disease modifying therapies. Beyond white matter lesions, volumetric changes in the grey matter and normal-appearing tissue damage are more sensitive prognostic markers for physical and cognitive disability, especially in progressive MS.SummaryAlthough white matter lesion number and volume still remains the imaging metric used in daily clinical practice, further development of advanced imaging predictors of long-term disability should allow a better stratification of patients in future clinical trials aimed at promoting repair or neuroprotection.
Paternally inherited noncoding structural variants contribute to autism
Authors: Brandler William M. , Antaki Danny , Gujral Madhusudan , Kleiber Morgan L. , Maile Michelle S. , Hong Oanh , Chapman Timothy R. , Tan Shirley , Tandon Prateek , Pang Timothy , Tang Shih C. , Vaux Keith K. , Yang Yan , Harrington Eoghan , Juul Sissel , Turner Daniel J. , Kingsmore Stephen F. , Gleeson Joseph G. , Kakaradov Boyko , Telenti Amalio , Venter J Craig , Corominas Roser , Cormand Bru , Rueda Isabel , Messer Karen S. , Nievergelt Caroline M. , Arranz Maria J. , Courchesne Eric , Pierce Karen , Muotri Alysson R. , Iakoucheva Lilia M. , Hervas Amaia , Corsello Christina , Sebat Jonathan 
Published: March 2017

AbstractThe genetic architecture of autism spectrum disorder (ASD) is known to consist of contributions from gene-disrupting de novo mutations and common variants of modest effect. We hypothesize that the unexplained heritability of ASD also includes rare inherited variants with intermediate effects. We investigated the genome-wide distribution and functional impact of structural variants (SVs) through whole genome analysis (≥30X coverage) of 3,169 subjects from 829 families affected by ASD. Genes that are intolerant to inactivating variants in the exome aggregation consortium (ExAC) were depleted for SVs in parents, specifically within fetal-brain promoters, UTRs and exons. Rare paternally-inherited SVs that disrupt promoters or UTRs were over-transmitted to probands (P= 0.0013) and not to their typically-developing siblings. Recurrent functional noncoding deletions implicate the geneLEO1in ASD. Protein-coding SVs were also associated with ASD (P= 0.0025). Our results establish that rare inherited SVs predispose children to ASD, with differing contributions from each parent.
Dystroglycan Maintains Inner Limiting Membrane Integrity to Coordinate Retinal Development
Authors: Clements Reena , Turk Rolf , Campbell Kevin P. , Wright Kevin M. 
Published: March 2017

AbstractProper neural circuit formation requires the precise regulation of neuronal migration, axon guidance and dendritic arborization. Mutations affecting the function of the transmembrane glycoprotein dystroglycan cause a form of congenital muscular dystrophy that is frequently associated with neurodevelopmental abnormalities. Despite its importance in brain development, the role for dystroglycan in regulating retinal development remains poorly understood. Using a mouse model of dystroglycanopathy (ISPDL79*) and conditionaldystroglycanmutants of both sexes, we show that dystroglycan is critical for the proper migration, axon guidance and dendritic stratification of neurons in the inner retina. Using genetic approaches, we show that dystroglycan functions in neuroepithelial cells as an extracellular scaffold to maintain the integrity of the retinal inner limiting membrane (ILM). Surprisingly, despite the profound disruptions in inner retinal circuit formation, spontaneous retinal activity is preserved. These results highlight the importance of dystroglycan in coordinating multiple aspects of retinal development.Significance StatementThe extracellular environment plays a critical role in coordinating neuronal migration and neurite outgrowth during neural circuit development. The transmembrane glycoprotein dystroglycan functions as a receptor for multiple extracellular matrix proteins, and its dysfunction leads to a form of muscular dystrophy frequently associated with neurodevelopmental defects. Our results demonstrate that dystroglycan is required for maintaining the structural integrity of the inner limiting membrane (ILM) in the developing retina. In the absence of functional dystroglycan, ILM degeneration leads to defective migration, axon guidance and mosaic spacing of neurons, and a loss of multiple neuron types during retinal development. These results demonstrate that disorganization of retinal circuit development is a likely contributor to visual dysfunction in patients with dystroglycanopathy.
Steroid hormone induction of temporal gene expression in Drosophila brain neuroblasts generates neuronal and glial diversity
Authors: Syed Mubarak Hussain , Mark Brandon , Doe Chris Q. 
Published: March 2017

AbstractAn important question in neuroscience is how stem cells generate neuronal diversity. During Drosophila embryonic development, neural stem cells (neuroblasts) sequentially express transcription factors that generate neuronal diversity; regulation of the embryonic temporal transcription factor cascade is lineage-intrinsic. In contrast, larval neuroblasts generate longer ˜50 division lineages, and currently only one mid-larval molecular transition is known: Chinmo/Imp/Lin-28+ neuroblasts transition to Syncrip+ neuroblasts. Here we show that the hormone ecdysone is required to down-regulate Chinmo/Imp and activate Syncrip, plus two late neuroblast factors, Broad and E93. We show that Seven-up triggers Chinmo/Imp to Syncrip/Broad/E93 transition by inducing expression of the Ecdysone receptor in mid-larval neuroblasts, rendering them competent to respond to the systemic hormone ecdysone. Importantly, late temporal gene expression is essential for proper neuronal and glial cell type specification. This is the first example of hormonal regulation of temporal factor expression in Drosophila embryonic or larval neural progenitors.SummaryHormone induction of temporal gene expression in neural progenitors
Stem cell intrinsic, Seven-up-triggered temporal factor gradients diversify intermediate neural progenitors
Authors: Ren Qingzhong , Yang Ching-Po , Liu Zhiyong , Sugino Ken , Mok Kent , He Yisheng , Lee Tzumin 
Published: March 2017

SummaryDrosophilatype II neuroblasts produce numerous neurons and glia due to transiently amplifying, intermediate neural progenitors (INP). Consecutively born INPs produce morphologically distinct progeny, presumably due to temporal patterning in type II neuroblasts. We therefore profiled type II neuroblasts’ transcriptome across time. Our results reveal opposing temporal gradients of Imp and Syp RNA-binding proteins (descending and ascending, respectively). Maintaining Imp expression throughout brain development expands the number of neurons/glia with early temporal fate at the expense of cells with late fate. Conversely, precocious upregulation of Syp reduces the number of cells with early fate. Further, we reveal that the transcription factor, Seven-up initiates progression of the Imp/Syp gradients. Interestingly, genetic manipulations that fix Imp or Syp levels still yield progeny with a small range of early fates. We propose that the Seven-up-initiated Imp/Syp gradients create coarse temporal windows within type II neuroblasts to pattern INPs, which subsequently undergo fine-tuned subtemporal patterning.
SUPERmerge: ChIP-seq coverage island analysis algorithm for broad histone marks
Authors: Khomtchouk Bohdan B. , Van Booven Derek , Wahlestedt Claes 
Published: March 2017

AbstractSUPERmerge is a ChIP-seq read pileup analysis and annotation algorithm for investigating alignment (BAM) files of diffuse histone modification ChIP-seq datasets with broad chromatin domains at a single base pair resolution level. SUPERmerge allows flexible regulation of a variety of read pileup parameters, thereby revealing how read islands aggregate into areas of coverage across the genome and what annotation features they map to within individual biological replicates. SUPERmerge is especially useful for investigating low sample size ChIP-seq experiments in which epigenetic histone modifications (e.g., H3K9me1, H3K27me3) result in inherently broad peaks with a diffuse range of signal enrichment spanning multiple consecutive genomic loci and annotated features.
Neural computations underpinning the strategic management of influence in advice giving
Authors: Hertz Uri , Palminteri Stefano , Brunetti Silvia , Olesen Cecilie , Frith Chris D , Bahrami Bahador 
Published: March 2017

AbstractResearch on social influence has mainly focused on the target of influence (e.g., consumer, voter), while the cognitive and neurobiological underpinnings of the source of the influence (e.g., spin doctor, financial adviser) remain unexplored. Here, we introduce a 3-sided Advising Game consisting of a client and two advisers. Advisers managed their influence over the client strategically by modulating the confidence of their advice depending on their level of influence (i.e. which adviser had the client’s attention) and their relative merit (i.e. which adviser was more accurate). Functional magnetic resonance imaging showed that these sources of social information were computed in distinct cortical regions: relative merit prediction error was tracked in the medial-prefrontal cortex and selection by client in the right temporo-parietal junction. Trial-by-trial changes in both sources of social information modulated the activity in the ventral striatum. These results open a fresh avenue for exploration of human interactions and provide new insights on the neurobiology involved when we try to influence others.
Enhancing sensitivity and controlling false discovery rate in somatic indel discovery using a latent variable model
Authors: Dijkstra Louis J. , Köster Johannes , Marschall Tobias , Schönhuth Alexander 
Published: March 2017

AbstractCancer is a genetic disorder in the first place. Therefore, next-generation sequencing (NGS) based discovery of somatically acquired genetic variants has gained widespread attention. Computational prediction of somatic variants, however, is affected by a variety of confounding factors. In addition to the uncertainties that one commonly encounters also in germline variation prediction, such as misplaced and/or inaccurate read alignments, cancer heterogeneity and impure samples significantly add to the issues. Overall, this hampers state-of-the-art indel discovery tools to discover somatic indels at operable performance rates, although they perform excellently when calling germline indels. While affecting all size ranges, both common and cancer-specific problems interfere in particularly unfavorable ways in the prediction of somatic midsize (30-150 bp) insertions and deletions.Here, we present a latent variable model that can take the major confounding factors and uncertainties into a unifying account. Using this modeling framework, wefirstdemonstrate how toefficientlycompute the probability for a (putative) indel to be somatic, thereby resolving a principled computational runtime bottleneck in Bayesian uncertainty quantification.Second, we show how to reliably estimate the allele frequencies for a given list of indels.Third, we also present an intuitive and effective way to control the false discovery rate, an issue in genetic variant discovery that has been found notoriously hard to deal with. As a tool that implements all methodology developed, we present PROSIC (PROcessing Somatic Indel Calls). PROSIC achieves significant improvements in particular in terms of recall when applied to deletion call sheets, as provided by prevalent state-of-the-art tools, in comparison to their integrated somatic indel calling routines.The software is publicly available athttps://prosic.github.ioand can be easily installed viahttps://bioconda.github.io.
DrosophilaShort stop as a paradigm for the role and regulation of spectraplakins
Authors: Voelzmann Andre , Liew Yu-Ting , Qu Yue , Hahn Ines , Melero Cristina , Sánchez-Soriano Natalia , Prokop Andreas 
Published: March 2017

AbstractSpectraplakins are evolutionarily well conserved cytoskeletal linker molecules that are true members of three protein families: plakins, spectrins and Gas2-like proteins. Spectraplakin genes encode at least 7 characteristic functional domains which are combined in a modular fashion into multiple isoforms, and which are responsible for an enormous breadth of cellular functions. These functions are related to the regulation of actin, microtubules, intermediate filaments, intracellular organelles, cell adhesions and signalling processes during the development and maintenance of a wide variety of tissues. To gain a deeper understanding of this enormous functional diversity, invertebrate genetic model organisms, such as the fruit flyDrosophila, can be used to develop concepts and mechanistic paradigms that can inform the investigation in higher animals or humans. Here we provide a comprehensive overview of our current knowledge of theDrosophilaspectraplakin Short stop (Shot). We describe its functional domains and isoforms and compare them with those of the mammalian spectraplakins dystonin and MACF1. We then summarise its roles during the development and maintenance of the nervous system, epithelia, oocytes and muscles, taking care to compare and contrast mechanistic insights across these functions in the fly, but especially also with related functions of dystonin and MACF1 in mostly mammalian contexts. We hope that this review will improve the wider appreciation of how work onDrosophilaShot can be used as an efficient strategy to promote the fundamental concepts and mechanisms that underpin spectraplakin functions, with important implications for biomedical research into human disease.
Epigenetic analyses of planarian stem cells demonstrate conservation of bivalent histone modifications in animal stem cells
Authors: Dattani Anish , Kao Damian , Mihaylova Yuliana , Abnave Prasad , Hughes Samantha , Lai Alvina , Sahu Sounak , Aboobaker Aziz 
Published: March 2017

AbstractPlanarian flatworms have an indefinite capacity to regenerate missing or damaged body parts owing to a population of pluripotent adult stems cells called neoblasts (NBs). Currently, little is known about the importance of the epigenetic status of NBs and how histone modifications regulate homeostasis and cellular differentiation. We have developed an improved and optimized ChIP-seq protocol for NBs inSchmidtea mediterraneaand have generated genome-wide profiles for the active marks H3K4me3 and H3K36me3, and suppressive marks H3K4me1 and H3K27me3. The genome-wide profiles of these marks were found to correlate well with NB gene expression profiles. We found that genes with little transcriptional activity in the NB compartment but which switch on in post-mitotic progeny during differentiation are bivalent, being marked by both H3K4me3 and H3K27me3 at promoter regions. In further support of this hypothesis bivalent genes also have a high level of paused RNA Polymerase II at the promoter-proximal region. Overall, this study confirms that epigenetic control is important for the maintenance of a NB transcriptional program and makes a case for bivalent promoters as a conserved feature of animal stem cells and not a vertebrate specific innovation. By establishing a robust ChIP-seq protocol and analysis methodology, we further promote planarians as a promising model system to investigate histone modification mediated regulation of stem cell function and differentiation.
High-Throughput Characterization of Protein-Protein Interactions by Reprogramming Yeast Mating
Authors: Younger David , Berger Stephanie , Baker David , Klavins Eric 
Published: March 2017

AbstractHigh-throughput methods for screening protein-protein interactions enable the rapid characterization of engineered binding proteins and interaction networks. While existing approaches are powerful, none allow quantitative library-on-library characterization of protein interactions in a modifiable extracellular environment. Here, we show that sexual agglutination ofS. cerevisiaecan be reprogrammed to link interaction strength with mating efficiency using synthetic agglutination (SynAg). Validation of SynAg with 89 previously characterized interactions shows a log-linear relationship between mating efficiency and protein binding strength for interactions with KD’s ranging from below 500 pM to above 300 μM. Using induced chromosomal translocation to pair barcodes representing binding proteins, thousands of distinct interactions can be screened in a single pot. We demonstrate the ability to characterize protein interaction networks in a modifiable environment by introducing a soluble peptide that selectively disrupts a subset of interactions in a representative network by up to 800-fold. SynAg enables the high-throughput, quantitative characterization of protein-protein interaction networks in a fully-defined extracellular environment at a library-on-library scale.Significance StatementDe novoengineering of protein binders often requires experimental screening to select functional variants from a design library. We have achieved high-throughput, quantitative characterization of protein-protein binding interactions without requiring purified recombinant proteins, by linking interaction strength with yeast mating. Using a next-generation sequencing output, we have characterized protein networks consisting of thousands of pairwise interactions in a single tube and have demonstrated the effect of changing the binding environment. This approach addresses an existing bottleneck in protein binder design by enabling the high-throughput and quantitative characterization of binding strength between designed protein libraries and multiple target proteins in a fully defined environment.
Advances in abscission signaling
Authors: Patharkar O. Rahul , Walker John C. 
Published: March 2017

AbstractAbscission is a process in plants for shedding unwanted organs such as leaves, flowers, fruits, or floral organs. Shedding of leaves in the fall is the most visually obvious display of abscission in nature. The very shape plants take is forged by the processes of growth and abscission. Mankind manipulates abscission in modern agriculture to do things like prevent pre-harvest fruit drop prior to mechanical harvesting in fruit orchards. Abscission occurs specifically at abscission zones that are laid down as the organ that will one day abscise is developed. A sophisticated signaling network initiates abscission when it is time to shed the unwanted organ. In this article, we review recent advances in understanding the signaling mechanisms that activate abscission. Physiological advances and roles for hormones in abscission are also addressed. Finally, we discuss current avenues for basic abscission research and potentially lucrative future directions for its application to modern agriculture.