bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimising 3D scaffold for otic neural progenitor differentiation
Authors: Ngamkham Kamolchanok , Rivolta Marcelo N. , Battaglia Giuseppe 
Published: March 2017

ABSTRACTHearing loss is a condition highly prevalent worldwide. It affects people of a broad age range since the causes and risk factors are varied. At present, some types of hearing impairments have a palliative treatment whereas some, especially for those where otic neurons are damaged, cannot be properly treated. Recent findings had shown it possible to use human embryonic stem cell-derived otic neural progenitors (ONPs) as a new mode of treating hearing loss caused by damage to the spiral ganglion neurons (SGNs). To improve the efficiency and overcome some limitations of this potential treatment, we have applied principles of tissue engineering which involves an interaction between cells and an extracellular matrix –mimicking scaffold. Here, we describe the influence of poly(l-lactic acid)(PLLA) aligned fibres on ONP cell morphology, proliferation, neuronal differentiation and establishment of neural polarity under both progenitor and neuralising conditions. The results show that most of ONPs on aligned fibres exhibited bipolar morphology and extended their neurites along the major fibre axis. Their proliferation was lower than those in 2D culture but the differentiation of ONPs on aligned fibres was significantly enhanced in both progenitor and neuralising conditions as indicated by the fluorescence intensity and number of cells that were positive for neuronal markers (β-tubulin III and NF200) and the expression pattern of spiral ganglion molecular markers (MMP13, NPR2 and NTNG1). Moreover, axonal and dendritic markers (TAU and MAP2 respectively) were also induced after 14 days in culture.
STAR-Fusion: Fast and Accurate Fusion Transcript Detection from RNA-Seq
Authors: Haas Brian J. , Dobin Alex , Stransky Nicolas , Li Bo , Yang Xiao , Tickle Timothy , Bankapur Asma , Ganote Carrie , Doak Thomas G. , Pochet Nathalie , Sun Jing , Wu Catherine J. , Gingeras Thomas R. , Regev Aviv 
Published: March 2017

AbstractMotivationFusion genes created by genomic rearrangements can be potent drivers of tumorigenesis. However, accurate identification of functionally fusion genes from genomic sequencing requires whole genome sequencing, since exonic sequencing alone is often insufficient. Transcriptome sequencing provides a direct, highly effective alternative for capturing molecular evidence of expressed fusions in the precision medicine pipeline, but current methods tend to be inefficient or insufficiently accurate, lacking in sensitivity or predicting large numbers of false positives. Here, we describe STAR-Fusion, a method that is both fast and accurate in identifying fusion transcripts from RNA-Seq data.ResultsWe benchmarked STAR-Fusion’s fusion detection accuracy using both simulated and genuine Illumina paired-end RNA-Seq data, and show that it has superior performance compared to popular alternative fusion detection methods.Availability and implementationSTAR-Fusion is implemented in Perl, freely available as open source software athttp://star-fusion.github.io, and supported on Linux.Contactbhaas@broadinstitute.org
A personalized, multi-omics approach identifies genes involved in cardiac hypertrophy and heart failure
Authors: Santolini Marc , Romay Milagros C. , Yukhtman Clara L. , Rau Christoph D. , Ren Shuxun , Saucerman Jeffrey J. , Wang Jessica J. , Weiss James N. , Wang Yibin , Lusis Aldons J. , Karma Alain 
Published: March 2017

AbstractIdentifying genes underlying complex diseases remains a major challenge. Biomarkers are typically identified by comparing average levels of gene expression in populations of healthy and diseased individuals. However, genetic diversities may undermine the effort to uncover genes with significant but individual contribution to the spectrum of disease phenotypes within a population. Here we leverage the Hybrid Mouse Diversity Panel (HMDP), a model system of 100+ genetically diverse strains of mice exhibiting different complex disease traits, to develop a personalized differential gene expression analysis that is able to identify disease-associated genes missed by traditional population-wide methods. The population-level and personalized approaches are compared for isoproterenol(ISO)-induced cardiac hypertrophy and heart failure using pre- and post-ISO gene expression and phenotypic data. The personalized approach identifies 36 Fold-Change (FC) genes predictive of the severity of cardiac hypertrophy, and enriched in genes previously associated with cardiac diseases in human. Strikingly, these genes are either up- or down-regulated at the individual strain level, and are therefore missed when averaging at the population level. Using insights from the gene regulatory network and protein-protein interactome, we identifyHes1as a strong candidate FC gene. We validate its role by showing that even a mild knockdown of 20-40% ofHes1can induce a dramatic reduction of hypertrophy by 80-90% in rat neonatal cardiac cells. These findings emphasize the importance of a personalized approach to identify causal genes underlying complex diseases as well as to develop personalized therapies.SignificanceA traditional approach to investigate the genetic basis of complex diseases is to look for genes with a global change in expression between diseased and healthy individuals. Here, we investigate individual changes of gene expression by inducing heart failure in 100 strains of genetically distinct mice. We find that genes associated to the severity of the disease are either up- or down-regulated across individuals and are therefore missed by a traditional population level approach. However, they are enriched in human cardiac disease genes and form a coregulated module strongly interacting with a cardiac hypertrophic signaling network in the human interactome. Our analysis demonstrates that individualized approaches are crucial to reveal all genes involved in the development of complex diseases.
Sex-specific inhibition and stimulation of worker-reproductive transition in a termite
Authors: Sun Qian , Haynes Kenneth F. , Hampton Jordan D. , Zhou Xuguo 
Published: March 2017

AbstractIn social insects, the postembryonic development of individuals exhibits strong phenotypic plasticity in response to environment, thus generating the caste system. Different from eusocial Hymenoptera, in which queens dominate reproduction and inhibit worker fertility, the primary reproductive caste in termites (kings and queens) can be replaced by neotenic reproductives derived from functionally sterile individuals. Feedback regulation of nestmate differentiation into reproductives has been suggested, but the sex-specificity remains inconclusive. In the eastern subterranean termite,Reticulitermes flavipes, we tested the hypothesis that neotenic reproductives regulate worker-reproductive transition in a sex-specific manner. With thisR. flavipessystem, we demonstrate a sex-specific regulatory mechanism with both inhibitory and stimulatory functions. Neotenics inhibit workers of the same sex from differentiating into additional reproductives, but stimulate workers of the opposite sex to undergo this transition. Furthermore, this process is not affected by the presence of soldiers. Our results highlight the extraordinary reproductive plasticity of termites in response to social cues, and provide insights into the regulation of reproductive division of labour in a hemimetabolous social insect.
Neuronal brain region-specific DNA methylation and chromatin accessibility are associated with neuropsychiatric disease heritability
Authors: Rizzardi Lindsay F. , Hickey Peter F. , DiBlasi Varenka Rodriguez , Tryggvadóttir Rakel , Callahan Colin M. , Idrizi Adrian , Hansen Kasper D. , Feinberg Andrew P. 
Published: March 2017

AbstractEpigenetic modifications confer stable transcriptional patterns in the brain, and both normal and abnormal brain function involve specialized brain regions, yet little is known about brain region-specific epigenetic differences. Here, we compared prefrontal cortex, anterior cingulate gyrus, hippocampus and nucleus accumbens from 6 individuals, performing whole genome bisulfite sequencing for DNA methylation. In addition, we have performed ATAC-seq for chromatin accessibility, and RNA-seq for gene expression in the nucleus accumbens and prefrontal cortex from 6 additional individuals. We found substantial neuron- and brain region-specific differences in both DNA methylation and chromatin accessibility which were largely non-overlapping, and were greatest between nucleus accumbens and the other regions. In contrast, glial methylation and chromatin were relatively homogeneous across brain regions, although neuron/glia ratios varied greatly, demonstrating the necessity for cellular fractionation. Gene expression was also largely the same across glia from different brain regions and substantially different for neurons. Expression was correlated with methylation and accessibility across promoters and known enhancers. Several classes of transcription factor binding sites were enriched at regions of differential methylation and accessibility, including many that respond to synaptic activity. Finally, both regions of differential methylation and those of differential accessibility showed a surprising >10-fold enrichment of explained heritability associated with addictive behavior, as well as schizophrenia- and neuroticism-associated regions, suggesting that common psychiatric illness is mediated through brain region-specific epigenetic marks.
STAG-CNS: An Order-Aware Conserved Non-coding Sequences Discovery Tool For Arbitrary Numbers of Species
Authors: Lai Xianjun , Behera Sairam , Liang Zhikai , Lu Yanli , Deogun Jitender S , Schnable James C. 
Published: March 2017

ABSTRACTOne method for identifying noncoding regulatory regions of a genome is to quantify rates of divergence between related species, as functional sequence will generally diverge more slowly. Most approaches to identifying these conserved noncoding sequences (CNS) based on alignment have had relatively large minimum sequence lengths (⩾15 base pair) compared to the average length of known transcription factor binding sites. To circumvent this constraint, STAG-CNS integrates data from the promoters of conserved orthologous genes in three or more species simultaneously. Using data from up to six grass species made it possible to identify conserved sequences as short at 9 base pairs with FDP ⩽ 0.05. These CNS exhibit greater overlap with open chromatin regions identified using DNase I hypersensitivity, and are enriched in the promoters of genes involved in transcriptional regulation. STAG-CNS was further employed to characterize loss of conserved noncoding sequences associated with retained duplicate genes from the ancient maize polyploidy. Genes with fewer retained CNS show lower overall expression, although this bias is more apparent in samples of complex organ systems containing many cell types, suggesting CNS loss may correspond to a reduced number of expression contexts rather than lower expression levels across the entire ancestral expression domain.
Intersubject brain network organization during dynamic anxious anticipation
Authors: Najafi Mahshid , Kinnison Joshua , Pessoa Luiz 
Published: March 2017

AbstractHow do large-scale brain networks reorganize during the waxing and waning of anxious anticipation? Here, threat was dynamically modulated during functional MRI as two circles slowly meandered on the screen; if they touched, an unpleasant shock was delivered. We employed intersubject network analysis, which allows the investigation of network-level properties “across brains,” and sought to determine how network properties changed during periods of approach (circles moving closer) and periods of retreat (circles moving apart). Dynamic threat altered network cohesion across the salience, executive, and task-negative networks, as well as subcortical regions. Functional connections between subcortical regions and the salience network also increased during approach vs. retreat, including the putative periaqueductal gray, habenula, and amygdala, showing that the latter is involved under conditions of relatively prolonged and uncertain threat (the bed nucleus of the stria terminalis was observed during both approach and retreat). Together, our findings unraveled dynamic properties of large-scale networks across participants while threat levels varied continuously, and demonstrate the potential of characterizing emotional processing at the level of distributed networks.Significance StatementUnderstanding the brain basis of anxious anticipation is important not only from a basic research perspective, but because aberrant responding to uncertain future negative events is believed to be central to anxiety disorders. Although previous studies have investigated how brain responses are sensitive to threat proximity, little is known about how patterns of response co-activation change during dynamic manipulations of threat. To address these important gaps in the literature, we studied the dynamics of emotional processing at the level of large-scale brain networks by devising a manipulation in which threat was dynamically modulated during functional MRI scanning.
RNA viruses drove adaptive introgressions between Neanderthals and modern humans
Authors: Enard David , Petrov Dmitri A 
Published: March 2017

AbstractNeanderthals and modern humans came in contact with each other and interbred at least twice in the past 100,000 years. Such contact and interbreeding likely led both to the transmission of viruses novel to either species and to the exchange of adaptive alleles that provided resistance against the same viruses. Here, we show that viruses were responsible for dozens of adaptive introgressions between Neanderthals and modern humans. We identify RNA viruses—specifically lentiviruses and orthomyxoviruses—as likely drivers of introgressions from Neanderthals to Europeans. Our results imply that many introgressions between Neanderthals and modern humans were adaptive, and that host genetic variation can be used to understand ancient viral epidemics, potentially providing important insights regarding current and future epidemics.One Sentence SummaryOnce out of Africa, modern humans inherited from Neanderthals dozens of genes already adapted against viruses present in their new environment.
Adaptation, Specialization, and Coevolution within Phytobiomes
Authors: Baltrus David A. 
Published: March 2017

AbstractGrowth patterns of individual plants and evolutionary trajectories of plant communities are intimately linked with and are critically affected by host-associated microbiomes. Research across systems has begun to shed light on how these phytobiomes are established and under laboratory and natural conditions, and have cultivated hope that a better understanding of the governing principles for host-microbe interactions can guide attempts to engineer microbiomes to boost agricultural yields. One important, yet relatively understudied, parameter in regards to phytobiome membership is the degree to which specialization and coevolution between plant species and microbial strains structures these communities. In this article, I provide an broad overview about current knowledge concerning mechanisms enabling adaptation and specialization of phytobiome communties to host plants as well as the potential for plants themselves to recruit and cultivate interactions with beneficial microbes. I further explore the possibility of host-beneficial microbe coevolution and suggest interactions that could promote the evolution of such close-knit partnerships. It is my hope that this overview will encourage future experiments that can begin to fill in this black box of ecological and evolutionary interactions across phytobiomes.Abstract Figure
Competitive advantage
Authors: Kamukama Nixon , Kyomuhangi Diana Susan , Akisimire Richard , Orobia Laura A. 
Published: March 2017

PurposeThe purpose of this paper is to examine the mediating role of competitive advantage in the relationship between managerial competence and financial performance of commercial banks in Uganda.Design/methodology/approachA cross-sectional survey was employed using 22 fully licensed and operational commercial banks in Uganda. Data were analyzed using descriptive statistics, zero order correlation and hierarchical regression analyses. Further, the bootstrap method was used to test the mediation effect of competitive advantage. All the analyses were performed using SPSS v21.FindingsThe findings reinforce the important position of managerial competence on financial performance of commercial banks. First, managerial competence enhances firms’ competitive advantage. Second, managerial competence has an indirect effect on financial performance through competitive advantage. Overall, managerial competence and competitive advantage are strong predictors of financial performance of commercial banks.Research limitations/implicationsThe study employed only a single research methodological approach, therefore future research could be undertaken using a mixed approach and triangulate to compare findings. Furthermore, the findings from the present study are cross-sectional, considering the limitations there in, a longitudinal approach should be explored.Practical implicationsEmphasis should be put on improving the knowledge and skills of managers so as to attain a competitive edge in the market and thus register increased profits. This will help practitioners make legitimate decisions and conclusions that can foster business growth.Originality/valueA mediation effect of competitive advantage in the relationship between managerial competence and financial performance was tested; previous studies have tended to test the direct effects.
Research funding opportunities and challenges
Authors: Baro Ebikabowei Emmanuel , Bosah Gabriel Ejiobi , Obi Ifeyinwa Calista 
Published: March 2017

Purpose
The purpose of this study is to investigate the extent to which academic staff members in tertiary institutions in Nigeria access research grants, and to bring to light the factors that hinder their effort to accessing research grants.

Design/methodology/approach
An online questionnaire was designed using the SurveyMonkey software to collect the qualitative data from academic staff in tertiary institutions in Nigeria.

Findings
The study revealed that only a few number of academic staff members in the tertiary institutions in Nigeria have received research grants. The study also revealed that a large number of research works carried out by academic staff are funded by themselves from the meager salary they receive. It also emerged that Tertiary Education Trust Fund is the highest funding body that academic staff have received research grants from. Different research funding agencies/organizations both local and international that support studies in Nigeria were also mentioned to create awareness for others to utilize. Politics in the selection of research proposals, inadequate publicity/advertisement for research grants applications and lack of knowledge about funding agencies/organizations were identified as the most mentioned hindrances to accessing research grants in Nigeria.

Research limitations/implications
A limitation of this study is the low response rate obtained, considering the number of tertiary institutions in Nigeria which does not permit generalization. The low response rate suggests that responding to an online questionnaire is not high on the agenda of academic staff members in tertiary institutions in Nigeria, and this is a major challenge for researchers undertaking evidence-based research considering the number of institutions.

Practical/implications
The findings will provide academic staff with important data and insight into the various local and international research funding agencies/organizations that support research in Nigeria.

Social/implications
Academic staff members receiving research grants will enable them find a solution to societal problems through evidence-based research. The findings of this study will inform other academic staff of the various research funding agencies/organizations that support research in Nigeria. This will create awareness for them to access such grants.

Originality/value
The work is an original research work conducted by the researchers. The findings will add to the body of knowledge on the area of research funding in Nigeria.
Ownership concentration, earnings management and stock market liquidity: evidence from Malaysia
Authors: Al-Jaifi Hamdan Amer 
Published: March 2017

Purpose
This paper aims to examine whether ownership concentration and earnings management affect the stock market liquidity of Malaysian firms.

Design/methodology/approach
This study uses a sample of 2,020 yearly firm observations in Bursa Malaysia over the period 2009-2012. The ordinary least square regression is used to examine the relationships. The study undertakes a sensitivity test by regressing the main study variables by using different measurements. Another robustness test is then used, where a regression based on the change in variables and a one-year lag of the independent variables are used. Furthermore, to alleviate the concern of possible endogeneity, the simultaneity and reverse causality are checked using the lag of the dependent variable, fixed effect regression, two-stage least squares using the instrumental variables and the generalized method of moments using instrumental variables analysis.

Findings
The study finds that firms with a high level of ownership concentration have discrepancies in information between informed and uninformed traders, which impair the stock market liquidity. In addition, this study finds that firms with high earnings management experience greater liquidity. A possible explanation for this is that firms might manage earnings to convey private information to enhance the information content of the earnings. Overall, the evidence suggests that manipulating earnings signals information informatively, particularly in a country with a higher level of ownership concentration and a higher likelihood of expropriating minority shareholders.

Originality/value
This study enriches the limited empirical research devoted to the impact of earnings management and ownership concentration on stock market liquidity especially in the context of emerging economies. The findings of this study are robust to alternative liquidity measurements, to alternative estimation methods, and to endogeneity bias.