bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hybrid peeling for fast and accurate calling, phasing, and imputation with sequence data of any coverage in pedigrees
Authors: Whalen Andrew , Ros-Freixedes Roger , Wilson David L , Gorjanc Gregor , Hickey John M 
Published: December 2017

AbstractIn this paper we extend multi-locus iterative peeling to be a computationally efficient method for calling, phasing, and imputing sequence data of any coverage in small or large pedigrees. Our method, called hybrid peeling, uses multi-locus iterative peeling to estimate shared chromosome segments between parents and their offspring, and then uses single-locus iterative peeling to aggregate genomic information across multiple generations. Using a synthetic dataset, we first analysed the performance of hybrid peeling for calling and phasing alleles in disconnected families, families which contained only a focal individual and its parents and grandparents. Second, we analysed the performance of hybrid peeling for calling and phasing alleles in the context of the full pedigree. Third, we analysed the performance of hybrid peeling for imputing whole genome sequence data to the remaining individuals in the population. We found that hybrid peeling substantially increase the number of genotypes that were called and phased by leveraging sequence information on related individuals. The calling rate and accuracy increased when the full pedigree was used compared to a reduced pedigree of just parents and grandparents. Finally, hybrid peeling accurately imputed whole genome sequence information to non-sequenced individuals. We believe that this algorithm will enable the generation of low cost and high accuracy whole genome sequence data in many pedigreed populations. We are making this algorithm available as a standalone program called AlphaPeel.
Cytokine receptor-Eb1 interaction couples cell polarity and fate during asymmetric cell division
Authors: Chen Cuie , Cummings Ryan , Mordovanakis Aghapi , Hunt Alan J. , Mayer Michael , Sept David , Yamashita Yukiko M. 
Published: December 2017

AbstractAsymmetric stem cell division is a critical mechanism for balancing self-renewal and differentiation. Adult stem cells often orient their mitotic spindle to place one daughter inside the niche and the other outside of it to achieve asymmetric division. It remains unknown whether and how the niche may direct division orientation. Here we discover a novel and evolutionary conserved mechanism that couples cell polarity to cell fate. We show that the cytokine receptor homolog Dome, acting downstream of the niche-derived ligand Upd, directly binds to the microtubule-binding protein Eb1 to regulate spindle orientation in Drosophila male germline stem cells (GSCs). Dome’s role in spindle orientation is entirely separable from its known function in self-renewal mediated by the JAK-STAT pathway. We propose that integration of two functions (cell polarity and fate) in a single receptor is a key mechanism to ensure an asymmetric outcome following cell division.
Modifiable risk factors moderate the relationship between beta-amyloid and cognition in midlife
Authors: Clark Lindsay R. , Koscik Rebecca L. , Allison Samantha L. , Berman Sara E. , Carlsson Cynthia M. , Norton Derek , Bendlin Barbara B. , Asthana Sanjay , Betthauser Tobey , Christian Bradley T. , Johnson Sterling C. 
Published: December 2017

ABSTRACTAlthough evidence suggests a relationship between elevated beta-amyloid and cognitive decline, approximately 30% of older adults with positive markers of amyloid remain cognitively healthy. Our objective was to test if the presence of modifiable risk factors (i.e., central obesity, hypertension, and depressive symptoms) moderated the relationship between amyloid and longitudinal cognitive performance. Data were from 207 adults (140 females; age range=40-70) enriched for Alzheimer’s disease risk (73% parental history of Alzheimer’s disease) enrolled in the Wisconsin Registry for Alzheimer’s Prevention study. Participants completed at least three neuropsychological evaluations and one biomarker visit ([C11]Pittsburgh Compound B PET scan or lumbar puncture). Participants were characterized as high or low on beta-amyloid using cutoffs developed for [C11]Pittsburgh Compound B-PET distribution volume ratio or CSF amyloid beta 1-42 values. Participants were also coded as high or low risk on obesity (waist circumference > 102 cm for males or 88 cm for females), hypertension (systolic blood pressure ≥ 140 mm Hg or diastolic blood pressure ≥ 90 mm Hg), and depressive symptoms (Center for Epidemiologic Studies of Depression scale ≥ 16). Linear mixed effects regression models examined three-way interactions between modifiable risk factor status x beta-amyloid status x visit age on longitudinal Verbal Learning & Memory and Speed & Flexibility factor scores. Results indicated that the relationship between beta-amyloid and Verbal Learning & Memory decline was moderated by the presence of hypertension at baseline (p = .02), presence of hypertension at all visits (p = .001), and presence of obesity at all visits (p = .049). Depressive symptoms did not moderate the association between beta-amyloid and longitudinal Verbal Learning & Memory (p = .62) or Speed & Flexibility (p = .15) performances. In this at-risk for Alzheimer’s disease cohort, modifiable risk factors of hypertension and obesity moderated the relationship between beta-amyloid and cognitive decline. Identification and modification of these risk factors in late middle age may slow the effect of amyloid on the progression of cognitive symptoms.
Personalized modeling of the human gut microbiome reveals distinct bile acid deconjugation and biotransformation potential in healthy and IBD individuals
Authors: Heinken Almut , Ravcheev Dmitry A. , Baldini Federico , Heirendt Laurent , Fleming Ronan M.T. , Thiele Ines 
Published: December 2017

AbstractThe human gut microbiome performs important functions human health and disease. Intestinal microbes are capable of deconjugation and biotransformation of human primary bile acids to secondary bile acids. Alterations of the bile acid pool as a result of microbial dysbiosis have been linked to multifactorial diseases, such as inflammatory bowel disease (IBD).Constraint-based modeling is a powerful approach for the mechanistic, systems-level analysis of metabolic interactions in microbial communities. Recently, we constructed a resource of 773 curated genome-scale reconstructions of human gut microbes, AGORA. Here, we performed a comparative genomic analysis of bile acid deconjugation and biotransformation pathways in 693 human gut microbial genomes to expand these AGORA reconstructions accordingly (available athttp://vmh.life).To elucidate the metabolic potential of individual microbiomes, publicly available metagenomic data from a cohort of healthy Western individuals, as well as two cohorts of IBD patients and healthy controls, were mapped onto the reference set of AGORA genomes. We constructed for each individual a large-scale personalized microbial community model that take strain-level abundances into account. Using flux balance analysis, we found that distinct potential to deconjugate and tranform primary bile acids between the gut microbiomes of healthy individuals. Moreover, the microbiomes of pediatric IBD patients were significantly depleted in their bile acid production potential compared with controls. The contributions of each strain to overall bile acid production potential across individuals were found to be distinct between IBD patients and controls. IBD microbiomes were depleted in contributions of Bacteroidetes strains but enriched in contributions of Proteobacteria. Finally, bottlenecks limiting secondary bile acid production potential were identified in each microbiome model. For ursodeoxycholate, the abundance of strains producing the precursor rather than of strains directly producing this secondary bile acid was synthesis-limiting in certain microbiomes.In summary, we integrated for the first-time metagenomics data with large-scale personalized metabolic modeling of microbial communities. We provided mechanistic insight into the link between dysbiosis and metabolic potential in IBD microbiomes. This large-scale modeling approach provides a novel way of analyzing metagenomics data to accelerate our understanding of the metabolic interactions between human host and gut microbiomes in health and diseases states.
Laws of concatenated perception: Vision goes for novelty, Decisions for perseverance
Authors: Pascucci D. , Mancuso G. , Santandrea E. , Della Libera C. , Plomp G. , Chelazzi L. 
Published: December 2017

AbstractEvery instant of perception depends on a cascade of brain processes calibrated to the history of sensory and decisional events. In the present work, we show that human visual perception is constantly shaped by two contrasting forces, exerted by sensory adaptation and past decisions. In a series of experiments, we used multilevel modelling and cross-validation approaches to investigate the impact of previous stimuli and responses on current errors in adjustment tasks. Our results revealed that each perceptual report is permeated by opposite biases from a hierarchy of serially dependent processes: low-level adaptation repels perceptionawayfrom previous stimuli; high-level, decisional traces attract perceptual reportstowardprevious responses. Contrary to recent claims, we demonstrated that positive serial dependence does not result fromcontinuity fieldsoperating at the level of early visual processing, but arises from the inertia of decisional templates. This finding is consistent with a Two-process model of serial dependence in which the persistence of read-out weights in a decision unit compensates for sensory adaptation, leading to attractive biases in sequential responses. We propose the first unified account of serial dependence in which functionally distinct mechanisms, operating at different stages, promote the differentiation and integration of visual information over time.
TIMELINE OF BRAIN ALTERATIONS IN ALZHEIMER’S DISEASE ACROSS THE ENTIRE LIFESPAN
Authors: Coupé Pierrick , Manjón José Vicente , Lanuza Enrique , Catheline Gwenaelle ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: December 2017

AbstractBrain imaging studies have shown that progressive cerebral atrophy characterized the development of Alzheimer’s Disease (AD). The key question is how long before the diagnosis of AD the neurodegenerative process started leading to these structural alterations. To answer this question, we proposed an innovative way by inferring brain structure volume trajectories across the entire lifespan using massive number of MRI (N=4714). Our study provides evidences of early divergence of the AD model from the control model for the hippocampus before 40 years, followed by the lateral ventricles and the amygdala around 40 years for the AD model. Moreover, our lifespan investigation reveals the dynamic of the evolution of these biomarkers and suggest close abnormality trajectories for the hippocampus and the amygdala. Finally, our results highlight that the temporal lobe atrophy, a key biomarker in AD, is a very early pathophysiological event potentially associated to early life exposures to risk factors.
Regionalization of the nervous system requires axial allocation prior to neural lineage commitment
Authors: Metzis Vicki , Steinhauser Sebastian , Pakanavicius Edvinas , Gouti Mina , Stamataki Despina , Lovell-Badge Robin , Luscombe Nicholas M , Briscoe James 
Published: December 2017

SummaryNeural induction in vertebrates generates a central nervous system that extends the rostral-caudal length of the body. The prevailing view is that neural cells are initially induced with anterior (forebrain) identity, with caudalising signals then converting a proportion to posterior fates (spinal cord). To test this model, we used chromatin accessibility assays to define how cells adopt region-specific neural fates. Together with genetic and biochemical perturbations this identified a developmental time window in which genome-wide chromatin remodeling events preconfigure epiblast cells for neural induction. Contrary to the established model, this revealed that cells commit to a regional identity before acquiring neural identity. This “primary regionalization” allocates cells to anterior or posterior regions of the nervous system, explaining how cranial and spinal neurons are generated at appropriate axial positions. These findings prompt a revision to models of neural induction and support the proposed dual evolutionary origin of the vertebrate central nervous system.
A Multi-Species Functional Embedding Integrating Sequence and Network Structure
Authors: Fan Jason , Cannistra Anthony , Fried Inbar , Lim Tim , Schaffner Thomas , Crovella Mark , Hescott Benjamin , Leiserson Mark D.M. 
Published: December 2017

AbstractA key challenge to transferring knowledge between species is that different species have fundamentally different genetic architectures. Initial computational approaches to transfer knowledge across species have relied on measures of heredity such as genetic homology, but these approaches suffer from limitations. First, only a small subset of genes have homologs, limiting the amount of knowledge that can be transferred, and second, genes change or repurpose functions, complicating the transfer of knowledge. Many approaches address this problem by expanding the notion of homology by leveraging high-throughput genomic and proteomic measurements, such as through network alignment.In this work, we take a new approach to transferring knowledge across species by expanding the notion of homology through explicit measures of functional similarity between proteins in different species. Specifically, our kernel-based method, Handl(Homology Assessment across Networks using Diffusion and Landmarks), integrates sequence and network structure to create a functional embedding in which proteins from different species are embedded in the same vector space. We show that inner products in this space capture functional similarity across species, and the vectors themselves are useful for a variety of cross species tasks. We perform the first whole-genome method for predicting phenologs, generating many that were previously identified, but also predicting new phenologs supported from the biological literature. We also demonstrate the Handl-embedding captures pairwise gene function, in that gene pairs with synthetic lethal interactions are co-located in Handl-space both within and across species. Software for the Handl algorithm is available at http://github.com/lrgr/HANDL.
Optogenetics reprogramming of planktonic cells for biofilm formation
Authors: Xia Aiguo , Yang Shuai , Huang Yajia , Jin Zhenyu , Ni Lei , Pu Lu , Yang Guang , Jin Fan 
Published: December 2017

AbstractSingle-cell behaviors play essential roles during early-stage biofilms formation. In this study, we evaluated whether biofilm formation could be guided by precisely manipulating single cells behaviors. Thus, we established an illumination method to precisely manipulate the type IV pili (TFP) mediated motility and microcolony formation of Pseudomonas aeruginosa by using a combination of a high-throughput bacterial tracking algorithm, optogenetic manipulation and adaptive microscopy. We termed this method as Adaptive Tracking Illumination (ATI). We reported that ATI enables the precise manipulation of TFP mediated motility and microcolony formation during biofilm formation by manipulating bis-(3′-5′)-cyclic dimeric guanosine monophosphate (c-di-GMP) levels in single cells. Moreover, we showed that the spatial organization of single cells in mature biofilms can be controlled using ATI. Thus, the established method (i.e., ATI) can markedly promote ongoing studies of biofilms.
Researching the financial abuse of individuals lacking mental capacity
Authors: Dalley Gillian , Gilhooly Mary Lynn , Gilhooly Kenneth , Levi Michael , Harries Priscilla 
Published: December 2017

Purpose
The purpose of this paper is to report on the aspects of an exploratory investigation into the scale and nature of the financial abuse of adults lacking mental capacity.

Design/methodology/approach
It uses mixed-methods study which comprises of: a review of safeguarding adults’ statistics; analysis of court case findings; classification of types of financial abuse, victims and perpetrators; qualitative exploration of professional views of the nature of financial abuse of those lacking mental capacity; and a consideration of policy implications.

Findings
It demonstrates the significance of financial abuse within the spectrum of abuse experienced by adults at risk; the wide range of both victims lacking capacity being abused and type of financial abuse; its often hidden nature embedded within the family; and the limitations of processes designed to protect.

Research limitations/implications
The investigation reveals the paucity of statistical data available on the nature of financial abuse and the outcomes of official investigations into reported cases, both of which limit analysis and understanding of the phenomenon.

Practical implications
It demonstrates the need for greater transparency and consistency in the reporting of safeguarding and legal processes to enable practitioners and policymakers to fully understand the nature and significance of this abuse for both victims and society.

Social implications
It questions the extent to which existing protective processes are sufficient in terms of safeguarding victims and deterring perpetrators.

Originality/value
It involves original research that brings together data from a range of sources involved in the protection of a particular hard-to-reach group of individuals (those lacking capacity) from a particular type of risk (financial abuse) of increasing social significance.
Distributed leadership and teacher job satisfaction in Singapore
Authors: García Torres Darlene 
Published: December 2017

PurposeSingapore is a country with low teacher attrition rates and high performance on international assessments (TIMSS 2011/2015 and PISA 2012/2015). Consequently, its education system is often considered as a model for other nations. The purpose of this paper is to extend research on teacher job satisfaction in Singapore and provide comparative information for other education systems.Design/methodology/approachThis paper presents a secondary analysis of data from the Organization for Economic Cooperation and Development’s 2013 Teaching and Learning International Survey with a focus on relationships among teacher and principal perceptions of distributed leadership and teachers’ job satisfaction in Singapore. Hierarchical linear modeling is applied to investigate teacher job satisfaction with principal perceptions and aggregate teacher perceptions of distributed leadership as school-level (level 2) variables and individual teacher perceptions of distributed leadership as a level 1 variable.FindingsResults indicated that distributed leadership significantly predicted teachers’ work and professional satisfaction; higher distributed leadership scores were associated with higher satisfaction scores.Originality/valueThe significant positive relationship between distributed leadership and both dimensions of job satisfaction after accounting for individual teacher characteristics is a new finding in the Singapore schooling context.
The financial services industry and society
Authors: Murray Noel , Manrai Ajay K. , Manrai Lalita Ajay 
Published: December 2017

Purpose
This paper aims to present an analysis of the role of financial incentives, moral hazard and conflicts of interests leading up to the 2008 financial crisis.

Design/methodology/approach
The study’s analysis has identified common structural flaws throughout the securitization food chain. These structural flaws include inappropriate incentives, the absence of punishment, moral hazard and conflicts of interest. This research sees the full impact of these structural flaws when considering their co-occurrence throughout the financial system. The authors address systemic defects in the securitization food chain and examine the inter-relationships among homeowners, mortgage originators, investment banks and investors. The authors also address the role of exogenous factors, including the SEC, AIG, the credit rating agencies, Congress, business academia and the business media.

Findings
The study argues that the lack of criminal prosecutions of key financial executives has been a key factor in creating moral hazard. Eight years after the Great Recession ended in the USA, the financial services industry continues to suffer from a crisis of trust with society.

Practical implications
An overwhelming majority of Americans, 89 per cent, believe that the federal government does a poor job of regulating the financial services industry (Puzzanghera, 2014). A study argues that the current corporate lobbying framework undermines societal expectations of political equality and consent (Alzola, 2013). The authors believe the Singapore model may be a useful starting point to restructure regulatory agencies so that they are more responsive to societal concerns and less responsive to special interests. Finally, the widespread perception is that the financial services sector, in particular, is ethically challenged (Ferguson, 2012); perhaps there would be some benefit from the implementation of ethical climate monitoring in firms that have been subject to deferred prosecution agreements for serious ethical violations (Arnaud, 2010).

Originality/value
The authors believe the paper makes a truly original contribution. They provide new insights via their analysis of the role of financial incentives, moral hazard and conflicts of interests leading up to the 2008 financial crisis.
Actual and intended growth in family firms and non-family-owned firms: are they different?
Authors: Saridakis George , Lai Yanqing , Muñoz Torres Rebeca I. , Mohammed Anne-Marie 
Published: December 2017

PurposeDrawing on the motivation theory and family business literature, the purpose of this paper is to investigate the influence of family effect in growth behaviour of small-and-medium-sized enterprises (SMEs) in the UK.Design/methodology/approachThe authors first compare the actual and expected growth of family and non-family-owned SMEs. The authors then compare the growth behaviour of small family firms managed by owner-directors and small family businesses co-managed by family and non-family directors with the non-family-owned SMEs.FindingsThe authors find a negative effect of family ownership on actual and intended small business growth behaviours. In addition, the findings also suggest that small family firms co-managed by non-family and family directors are no different from non-family-owned firms, in terms of reporting past actual growth in employment size and turnover as well as expecting growth in workforce size and turnover. The authors also observe a significant difference in anticipating sales growth between family-controlled and non-family-controlled firms. However, this difference is not explained by the heterogeneity of a top management team.Practical implicationsThe study has important implications for managerial practice to family firms and on policies that improve the growth of SMEs. Specifically, the competence of managers and decision makers matters considerably in evaluating the efficient operation of the business and maximising the economic growth in SMEs.Originality/valueThe study makes two important theoretical contributions to small business growth literature. First, the findings underline a negative family effect in the actual and expected growth behaviour of SMEs. Second, the mode of family ownership alone may not sufficiently capture family effect and offer a thorough understanding of growth behaviour in SMEs.