bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mosaic deletion patterns of the human antibody heavy chain gene locus as revealed by Bayesian haplotyping
Authors: Gidoni Moriah , Snir Omri , Peres Ayelet , Polak Pazit , Lindeman Ida , Mikocziova Ivana , Sarna Vikas Kumar , Lundin Knut E. A. , Clouser Christopher , Vigneault Francois , Collins Andrew M. , Sollid Ludvig M. , Yaari Gur 
Published: May 2018

AbstractAnalysis of antibody repertoires by high-throughput sequencing is of major importance in understanding adaptive immune responses. Our knowledge of variations in the genomic loci encoding antibody genes is incomplete, mostly due to technical difficulties in aligning short reads to these highly repetitive loci. The partial knowledge results in conflicting V-D-J gene assignments between different algorithms, and biased genotype and haplotype inference. Previous studies have shown that haplotypes can be inferred by taking advantage of IGHJ6 heterozygosity, observed in approximately one third of the population. Here, we propose a robust novel method for determining V-D-J haplotypes by adapting a Bayesian framework. Our method extends haplotype inference to IGHD- and IGHV-based analysis, thereby enabling inference of complex genetic events like deletions and copy number variations in the entire population. We generated the largest multi individual data set, to date, of naïve B-cell repertoires, and tested our method on it. We present evidence for allele usage bias, as well as a mosaic, tiled pattern of deleted and present IGHD and IGHV nearby genes, across the population. The inferred haplotypes and deletion patterns may have clinical implications for genetic predispositions to diseases. Our findings greatly expand the knowledge that can be extracted from antibody repertoire sequencing data.
Polarity sorting drives remodeling of actin-myosin networks
Authors: Wollrab Viktoria , Belmonte Julio M. , Leptin Maria , Nédeléc François , Koenderink Gijsje H. 
Published: May 2018

AbstractCytoskeletal networks of actin filaments and myosin motors drive many dynamic cell processes. A key characteristic of these networks is their contractility. Despite intense experimental and theoretical efforts, it is not clear what mechanism favors network contraction over expansion. Recent work points to a dominant role for the nonlinear mechanical response of actin filaments, which can withstand stretching but buckle upon compression. Here we present an alternative mechanism. We study how interactions between actin and myosin-2 at the single filament level translate into contraction at the network scale by performing time-lapse imaging on reconstituted quasi-2D-networks mimicking the cell cortex. We observe myosin end-dwelling after it runs processively along actin filaments. This leads to transport and clustering of actin filament ends and the formation of transiently stable bipolar structures. Further we show that myosin-driven polarity sorting leads to polar actin aster formation, which act as contractile nodes that drive contraction in crosslinked networks. Computer simulations comparing the roles of the end-dwelling mechanism and a buckling-dependent mechanism show that the relative contribution of end-dwelling contraction increases as the network mesh-size decreases.
Defective DNA damage repair leads to frequent catastrophic genomic events in murine and human tumors
Authors: Ratnaparkhe Manasi , Wong John , Wei Pei-Chi , Hlevnjak Mario , Kolb Thorsten , Haag Daniel , Paul Yashna , Devens Frauke , Northcott Paul , Jones David TW , Kool Marcel , Jauch Anna , Pastorczak Agata , Mlynarski Wojciech , Korshunov Andrey , Kumar Rajiv , Downing Susanna M. , Pfister Stefan M , Zapatka Marc , McKinnon Peter J , Alt Frederick W , Lichter Peter , Ernst Aurélie 
Published: May 2018

AbstractChromothripsis and chromoanasynthesis are catastrophic events leading to clustered genomic rearrangements. Whole-genome sequencing revealed frequent chromothripsis or chromoanasynthesis (n= 16/26) in brain tumors developing in mice deficient for factors involved in homologous-recombination-repair or non-homologous-end-joining. Catastrophic events were tightly linked to Myc/Mycn amplification, with increased DNA damage and inefficient apoptotic response already observable at early postnatal stages. Inhibition of repair processes and comparison of the mouse tumors with human medulloblastomas (n=68) and glioblastomas (n=32) identified chromothripsis as associated with MYC/MYCN gains and with DNA repair deficiencies, pointing towards therapeutic opportunities to target DNA repair defects in tumors with complex genomic rearrangements.
CRISPR-Cas9 interference in cassava linked to the evolution of editing-resistant geminiviruses
Authors: Mehta Devang , Stürchler Alessandra , Hirsch-Hoffmann Matthias , Gruissem Wilhelm , Vanderschuren Hervé 
Published: May 2018

ABSTRACTWe used CRISPR-Cas9 in the staple food crop cassava with the aim of engineering resistance to African cassava mosaic virus, a member of a widespread and important family of plant-pathogenic DNA viruses. We found that between 33 and 48% of edited virus genomes evolved a conserved single-nucleotide mutation that confers resistance to CRISPR-Cas9 cleavage. Our study highlights the potential for virus escape from this technology. Care should be taken to design CRISPR-Cas9 experiments that minimize the risk of virus escape.
Selfish mutations dysregulating RAS-MAPK signaling are pervasive in aged human testes
Authors: Maher Geoffrey J. , Ralph Hannah K. , Ding Zhihao , Koelling Nils , Mlcochova Hana , Giannoulatou Eleni , Dhami Pawan , Paul Dirk S. , Stricker Stefan H. , Beck Stephan , McVean Gilean , Wilkie Andrew OM , Goriely Anne 
Published: May 2018

ABSTRACTMosaic mutations present in the germline have important implications for reproductive risk and disease transmission. We previously demonstrated a phenomenon occurring in the male germline, whereby specific mutations arising spontaneously in stem cells (spermatogonia) lead to clonal expansion, resulting in elevated mutation levels in sperm over time. This process, termed selfish spermatogonial selection, explains the high spontaneous birth prevalence and strong paternal age-effect of disorders such as achondroplasia, Apert, Noonan and Costello syndromes, with direct experimental evidence currently available for specific positions of six genes (FGFR2, FGFR3, RET, PTPN11, HRAS and KRAS). We present a discovery screen to identify novel mutations and genes showing evidence of positive selection in the male germline, by performing massively parallel simplex PCR using RainDance technology to interrogate mutational hotspots in 67 genes (51.5 kb in total) in 276 biopsies of testes from 5 men (median age: 83 years). Following ultra-deep sequencing (~16,000x), development of a low-frequency variant prioritization strategy and targeted validation, we identified 61 distinct variants present at frequencies as low as 0.06%, including 54 variants not previously directly associated with selfish selection. The majority (80%) of variants identified have previously been implicated in developmental disorders and/or oncogenesis and include mutations in six newly associated genes (BRAF, CBL, MAP2K1, MAP2K2, RAF1 and SOS1), all of which encode components of RAS-MAPK pathway and activate signaling. Our findings extend the link between mutations dysregulating the RAS-MAPK pathway and selfish selection, and show that the ageing male germline is a repository for such deleterious mutations.
Rapid olfactory discrimination learning in adult zebrafish
Authors: Namekawa Iori , Moenig Nila R. , Friedrich Rainer W. 
Published: May 2018

AbstractThe zebrafish is a model organism to study olfactory information processing but efficient behavioral procedures to analyze olfactory discrimination and memory are lacking. We devised an automated odor discrimination task for adult zebrafish based on olfactory conditioning of feeding behavior. Presentation of a conditioned odor (CS+), but not a neutral odor (CS-), was followed by food delivery at a specific location. Fish developed differential behavioral responses to CS+ and CS- within a few trials even when odors were similar. The behavioral response to the CS+ was complex and included components reminiscent of food search such as increased swimming speed and water surface sampling. Appetitive behavior was therefore quantified by a composite score that combined measurements of multiple behavioral parameters. Discrimination behavior was robust in different strains and learned preferences could overcome innate odor preferences. These results confirm that zebrafish can rapidly learn to make fine odor discriminations. The procedure is efficient and provides novel opportunities to dissect the neural mechanisms underlying olfactory discrimination and memory.
The suppressive cap-binding-complex factor 4EIP is required for normal differentiation
Authors: Terrao Monica , Kamanyi Marucha Kevin , Mugo Elisha , Droll Dorothea , Minia Ihor , Egler Franziska , Braun Johanna , Clayton Christine 
Published: May 2018

Summary/AbstractTrypanosoma brucei live in mammals as bloodstream forms and in the Tsetse midgut as procyclic forms. Differentiation from one form to the other proceeds via a growth-arrested stumpy form with low mRNA content and translation. The parasites have six eIF4Es and five eIF4Gs. EIF4E1 pairs with the mRNA-binding protein 4EIP but not with any EIF4G. EIF4E1 and 4EIP each inhibit expression when tethered to a reporter mRNA. The 4E-binding motif in 4EIP is required for the interaction with EIF4E1 both in vivo and in a 2-hybrid assay, but not for the suppressive activity of 4EIP when tethered. However, the suppressive activity of EIF4E1 when tethered requires 4EIP. Correspondingly, in growing bloodstream forms, 4EIP is preferentially associated with unstable mRNAs. Trypanosomes lacking 4EIP have a marginal growth disadvantage as cultured bloodstream or procyclic forms. Bloodstream forms without 4EIP cannot make differentiation-competent stumpy forms, but the defect can be complemented by a truncated 4EIP that does not interact with EIF4E1. Bloodstream forms lacking EIF4E1 have a growth defect but can differentiate. We suggest that 4EIP and EIF4E1 fine-tune mRNA levels in growing cells, and that 4EIP is required for mRNA suppression during differentiation to the stumpy form.
Polymeric perfluorocarbon nanoemulsions are ultrasound-activated wireless drug infusion catheters
Authors: Zhong Q , Yoon BC , Aryal M , Wang JB , Karthik A , Airan RD 
Published: May 2018

ABSTRACTCatheter-based intra-arterial drug therapies have proven effective for a range of oncologic, neurologic, and cardiovascular applications. However, these procedures are limited by their invasiveness, as well as the relatively broad drug spatial distribution that is achievable with selective arterial catheterization. The ideal technique for local pharmacotherapy would be noninvasive and would flexibly deliver a given drug to any region of the body. Combining polymeric perfluorocarbon nanoemulsions with existent clinical focused ultrasound systems could in principle enable noninvasive targeted drug delivery, but it has not been clear whether these nanoparticles could provide the necessary drug loading, stability, and generalizability across a range of drugs to meet these needs, beyond a few niche applications. Here, we directly address all of those challenges and fully develop polymeric perfluorocarbon nanoemulsions into a generalized platform for ultrasound-targeted drug delivery with high potential for clinical translation. We demonstrate that a wide variety of drugs may be effectively uncaged with ultrasound using these nanoparticles, with drug loading increasing with hydrophobicity. We also set the stage for clinical translation by delineating production protocols that hew to clinical standards and yield stable and optimized ultrasound-activated drug-loaded nanoemulsions. Finally, as a new potential clinical application for these nanoemulsions, we exhibit their in vivo efficacy and performance for cardiovascular applications, by achieving local vasodilation in the highest flow vessel of the body, the aorta. This work establishes the power of polymeric perfluorocarbon nanoemulsions as a clinically-translatable platform for effective noninvasive ultrasonic drug uncaging for myriad targets in the brain and body.
ShinyGO: a graphical enrichment tool for ani-mals and plants
Authors: Ge Steven Xijin , Jung Dongmin 
Published: May 2018

AbstractMotivationGene lists are routinely produced from various genome-wide studies. Enrichment analysis can link these gene lists with underlying molecular pathways by using functional categories such as gene ontology (GO).ResultsTo complement existing tools, we developed ShinyGO with several features: (1) large annotation database from GO and many other sources for over 200 plant and animal species, (2) graphical visualization of enrichment results and gene characteristics, and (3) application program interface (API) access to KEGG and STRING for the retrieval of pathway diagrams and protein-protein interaction networks. ShinyGO is an intuitive, graphical web application that can help researchers gain actionable insights from gene lists.Availabilityhttp://ge-lab.org/go/Contactgexijin@gmail.comSupplementary informationSupplementary data are available at Bioinformatics online.
Lipid composition but not curvature is a determinant of a low molecular mobility within HIV-1 lipid envelope
Authors: Urbančič Iztok , Brun Juliane , Shrestha Dilip , Waithe Dominic , Eggeling Christian , Chojnacki Jakub 
Published: May 2018

AbstractHuman Immunodeficiency Virus type-1 (HIV-1) acquires its lipid membrane from the plasma membrane of the infected cell from where it buds out. Previous studies have shown that the HIV-1 envelope is a very low mobility environment with the diffusion of incorporated proteins two orders of magnitude slower than in plasma membrane. One of the reasons for this difference is thought to be due to HIV-1 membrane composition that is characterised by a high degree of rigidity and lipid packing. To further refine the model of the molecular mobility on HIV-1 surface, we here investigated the relative importance of membrane composition and curvature in Large Unilamellar Vesicles of different composition and size (0.2–1 μm) by super-resolution STED microscopy-based fluorescence correlation spectroscopy (STED-FCS) analysis. We find that lipid composition and its rigidity but not membrane curvature play an important role in the decreased molecular mobility on vesicle surface thus confirming that this factor is an essential determinant of HIV-1 low surface mobility. Our results provide further insight into the dynamic properties of the surface of individual HIV-1 particles.
Detection of Multidimensional Co-Exclusion Patterns in Microbial Communities
Authors: Albayrak Levent , Khanipov Kamil , Golovko George , Fofanov Yuriy 
Published: May 2018

AbstractMotivationIdentification of complex relationships among members of microbial communities is key to understand and control the microbiota. Co-exclusion is arguably one of the most important patterns reflecting microorganisms’ intolerance to each other’s presence. Knowing these relations opens an opportunity to manipulate microbiotas, personalize anti-microbial and probiotic treatments as well as guide microbiota transplantation. The co-exclusion pattern however, cannot be appropriately described by a linear function nor its strength be estimated using covariance or (negative) Pearson and Spearman correlation coefficients. This manuscript proposes a way to quantify the strength and evaluate the statistical significance of co-exclusion patterns between two, three or more variables describing a microbiota and allows one to extend analysis beyond microorganism abundance by including other microbiome associated measurements such as, pH, temperature etc., as well as estimate the expected numbers of false positive co-exclusion patterns in a co-exclusion network.ResultsThe implemented computational pipeline (CoEx) tested against 2,380 microbial profiles (samples) from The Human Microbiome Project resulted in body-site specific pairwise co-exclusion patterns.AvailabilityC++ source code for calculation of the score and p-value for 2, 3, and 4 dimensional co-exclusion patterns as well as source code and executable files for the CoEx pipeline are available athttps://scsb.utmb.edu/labgroups/fofanov/co-exclusion_in_microbial_communities.aspContactlealbayr@utmb.eduSupplementary informationSupplementary data are available atbiorxivonline.
The good teacher for the twenty-first century: a “mentoring teacher” with heutagogical skills
Authors: Levy-Feldman Irit 
Published: May 2018

Purpose
The purpose of this paper is to propose a new conception of the “good teacher” – that of the teacher-as-mentor, or, as the author refer to it, the “mentoring teacher,” who is equipped with heutagogical skills aimed at promoting self-determined learning through dialogic teaching. This conception appears to be better suited than current conceptions for the twenty-first century and the postmodern era.

Design/methodology/approach
The conception is based on an interpretative textual analysis of western educational philosophies and of the nature of postmodernity.

Findings
The mentoring teacher, presented to be the “good teacher” for the new era, is provided with skills associated with heutagogy: a pedagogical approach that emphasizes the individual’s need to learn autonomously and independently and that regards the capacity to do so as a basic skill for living and lifelong learning in the changing world. Using dialogic teaching, mentoring teachers equipped with heutagogical skills can navigate their teaching to promote the self-learning abilities of different learners and better prepare them to navigate the challenges of the current era.

Research limitations/implications
This paper presents one perspective on looking at the changes that have occurred in the conception of the good teacher in western society and offers one point of view of the image of the new good teacher, hoping it might stimulate new thinking on the need to reconsider the role of the teacher in contemporary western society.

Originality/value
Placing the focus on teachers’ skills as opposed to students’ needs, which is much more common, invites discussion regarding the image of the good teacher and teacher education.
Stand Up to Work: assessing the health impact of adjustable workstations
Authors: Garland Elizabeth , Watts Abigail , Doucette John , Foley Mary , Senerat Araliya , Sanchez Sadie 
Published: May 2018

PurposeSedentary behavior is linked to health risks, and prolonged sitting is prevalent among office workers. Adjustable workstations (AWS) promote health by allowing transitions between sitting and standing. Stand Up to Work compares workers with AWS to traditional desks (TD). The paper aims to discuss these issues.Design/methodology/approachEmployees were randomly selected from one office floor to receive AWS, two identical floors maintained TD. Participants received workplace wellness and ergonomic training, completed self-administered questionnaires, and responded to repeated micropolling at baseline (T0), 3 (T1), 6 (T2), and 12 (T3) months in Atlanta, 2015-2016. Groups were compared using two-samplet-tests and nonparametric Wilcoxon tests.FindingsCompared to TD (n= 24), participants with AWS (n= 24) reported significantly less sedentary behavior at T1 and T2 after AWS installation (p<0.05), with a retention rate at T2 of 80 and 65 percent for the AWS and TD group, respectively. In all, 47 percent of participants with AWS reported decline in upper back, shoulder, and neck discomfort (p=0.04); 88 percent of AWS participants reported convenience to use, 65 percent reported increased productivity, and 65 percent reported positive impact outside the workplace. Individuals with normal or underweight body mass index (BMI) reported a significantly greater decline in percent of time sitting compared to participants with overweight or obese BMI at all three time points.Originality/valueAWS are beneficial in reducing sedentary behavior in and outside the workplace. Behavioral changes were sustained over time and associated with less self-reported muscle pain, more self-reported energy, and awareness of standing. When considering total worker health, employers should include options for AWS to promote reducing sedentary behavior.
Perceptions of control legitimacy in information systems development
Authors: Cram W. Alec , Wiener Martin 
Published: May 2018

PurposeExisting studies of information systems development (ISD) control commonly examine controller-centric considerations, such as the antecedents and performance impacts of control mode choices. In contrast, little is known about the controllee-centric factors that may influence the effectiveness of control activities. Drawing on institutional theory, the purpose of this paper is to introduce the concept of control legitimacy to the ISD literature – a concept that past organizational research has linked to outcomes such as employee commitment and performance. Specifically, the authors explore how different dimensions of control activities (mode, degree, style) relate to controllee perceptions of control legitimacy in terms of justice, autonomy, group identification, and competence development.Design/methodology/approachInterviews were conducted with 20 practitioners across three companies. A structured data coding approach was employed and analysis was conducted within and across each case study.FindingsThe authors find that the control degree and control style can help explain control legitimacy perceptions better than control modes alone. For example, the results suggest that formal controls enacted in a bilateral style correspond with higher perceptions of justice and autonomy, when compared to formal controls enacted in a unilateral style.Originality/valueThe study results imply that ISD managers should be increasingly mindful of enacting controls in a way that is perceived to be legitimate by subordinates, thereby potentially enhancing both staff well-being and ISD performance.
The unintended emergence of a greed-led economic system
Authors: Andreff Wladimir 
Published: May 2018

Purpose
This paper aims to propose a new model of economic behaviour in which activities are led by greed rather than by the traditional formal rules of capitalism.

Design/methodology/approach
This paper relies on the empirical observation of bad practices that developed in synchrony during the collapse of the former communist economic system and the rise of global financial capitalism. Both were fuelled by greedy behaviour of asset grabbing, and paved the way to an emerging greed-led economic system.

Findings
First, microeconomic individual greedy behaviours that drive asset grabbing are identified, such as rigged or corrupt privatisation drives, subprime mortgage loans, Ponzi schemes, lending to insolvent clients, bad loan securitisation, stock options, fraudulent accounting and online betting on fixed matches. Then systematic changes in the traditional formal rules of capitalism that favour those having adopted a greedy strategy are pointed at; greedy behaviour is institutionalised when these capture the state and successfully lobby for rules change. Contrary to capitalism, systemic greed uses asset grabbing, instead of capital accumulation, as its major means for wealth maximisation without constraint, in a winner-take-all economy beneficial to oligarchs.

Research limitations/implications
The implications of this new systemic behaviour have implications for further economic modelling.

Practical implications
The emergence of systemic greed will have implications for the design of regulatory systems.

Originality/value
This paper proposes that a greed-controlled economy is replacing the traditional capitalist economy.