bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bayesian meta-analysis across genome-wide association studies of diverse phenotypes
Authors: Trochet Holly , Pirinen Matti , Band Gavin , Jostins Luke ,   Wellcome Trust Case-Control Consortium 2, McVean Gilean , Spencer Chris C. A. 
Published: November 2018

AbstractGenome-wide association studies (GWAS) are a powerful tool for understanding the genetic basis of diseases and traits, but most studies have been conducted in isolation, with a focus on either a single or a set of closely related phenotypes. We describe MetABF, a simple Bayesian framework for performing integrative meta-analysis across multiple GWAS using summary statistics. The approach is applicable across a wide range of study designs and can increase the power by 50% compared to standard frequentist tests when only a subset of studies have a true effect. We demonstrate its utility in a meta-analysis of 20 diverse GWAS which were part of the Wellcome Trust Case-Control Consortium 2. The novelty of the approach is its ability to explore, and assess the evidence for, a range of possible true patterns of association across studies in a computationally efficient framework.
DEAH-box helicase 37 (DHX37) defects are a novel molecular etiology of 46,XY gonadal dysgenesis spectrum
Authors: Silva Thatiana E. da , Gomes Nathalia L. , Lerario Antonio M. , Keegan Catherine E. , Nishi Mirian Y. , Carvalho Filomena M. , Vilain Eric , Barseghyan Hayk , Martinez-Aguayo Alejandro , Forclaz María V. , Papazian Regina , Carvalho Luciani R. , Costa Elaine M. F. , Mendonca Berenice B. , Domenice Sorahia 
Published: November 2018

ABSTRACT46,XY gonadal dysgenesis is a heterogeneous disorder of sex development (DSD) that features abnormal gonadal development and varying degrees of undervirilization of the external genitalia, ranging from micropenis to female-like genitalia. Embryonic testicular regression syndrome (ETRS; MIM: 273250) is considered part of the clinical spectrum of 46,XY gonadal dysgenesis. Most ETRS patients present micropenis or atypical genitalia associated with a complete absence of gonadal tissue in one or both sides. In most patients with gonadal dysgenesis, the genetic diagnosis is unclear. We performed whole exome sequencing in ETRS patients and identified a rare variant, the p.Arg308Gln, in DEAH (Asp-Glu-Ala-His) box polypeptide 37 (DHX37) in 5 affected individuals from three unrelated families. We expanded the analysis of DHX37 coding region to additional 71 patients with 46,XY gonadal dysgenesis and identified the p.Arg308Gln and three other DHX37 missense variants (p.Arg151Trp, p.Thr304Met and p.Arg674Trp) in 11 affected members from eight distinct families (8 patients with ETRS, two with partial gonadal dysgenesis and one 46,XY DSD female patient previously gonadectomized). The p.Arg308Gln and p.Arg674Trp recurrent variants were identified in six and three families, respectively. Segregation analysis revealed sex-limited autosomal dominant inheritance in 4 families, autosomal dominant with incomplete penetrance in one family and autosomal recessive in another family. Immunohistochemical analysis of normal testes revealed that DHX37 is expressed in germ cells at different stages of maturation.This study demonstrates an expressive frequency of rare predicted to be deleterious DHX37 variants in 46,XY gonadal dysgenesis group, particularly those individuals exhibiting the ETRS phenotype (25% and 50%, respectively).Our findings indicate that DHX37 is a new player in the complex cascade of male gonadal differentiation and maintenance, thus establishing a novel and frequent molecular etiology for 46,XY gonadal dysgenesis spectrum, mainly for embryonic testicular regression syndrome.
Lack of detectable neoantigen depletion in the untreated cancer genome
Authors: Eynden Jimmy Van den , Jiménez-Sánchez Alejandro , Miller Martin L. , Larsson Erik 
Published: November 2018

ABSTRACTSomatic mutations in cancer can result in the presentation of mutated peptides on the cell surface, eliciting an immune response. Mutant peptides are presented via HLA molecules and are known as neoantigens. It has been suggested that selection acts against the underlying mutations, leading to neoantigen depletion. Knowing the extent of this specific form of immunoediting may provide fundamental insights into tumour-immune interactions during tumour evolution. Here, we quantified the extent of neoantigen depletion in a wide range of human cancers by studying somatic mutations in the HLA-binding annotated exome, i.e. genomic regions that can be translated into presented peptides. We initially observed reduced non-synonymous mutation rates in presented regions, suggestive of neoantigen depletion. However, when compared to the expected mutation rates from a trinucleotide-based mutational signature model, depletion signals were negligible. This is explained by correlative relationships between the likelihood of mutagenesis in different nucleotide sequences and predicted HLA affinities for corresponding peptides. Our results suggest that signals of immunogenic negative selection are weak or absent in cancer genomics data and that other mechanisms to escape immune responses early during tumour evolution might be more efficient.
TRPC3 is essential for functional heterogeneity of cerebellar Purkinje cells
Authors: Wu Bin , Blot Francois G.C. , Wong Aaron B. , Osório Catarina , Adolfs Youri , Pasterkamp R. Jeroen , Hartmann Jana , Becker Esther B. E. , Boele Henk-Jan , Zeeuw Chris I. De , Schonewille Martijn 
Published: November 2018

AbstractDespite the canonical homogenous character of its organization, the cerebellum plays differential computational roles in distinct types of sensorimotor behaviors. However, the molecular and cell physiological underpinnings are unclear. Here we determined the contribution of transient receptor potential cation channel type C3 (TRPC3) to signal processing in different cerebellar modules. Using gain-of-function and loss-of-function mouse models, we found that TRPC3 controls the simple spike activity of zebrin-negative (Z–), but not of zebrin-positive (Z+), Purkinje cells. Moreover,in vivoTRPC3 also regulated complex spike firing and its interaction with simple spikes exclusively in Z– Purkinje cells. Finally, we found that eyeblink conditioning, related to Z– modules, but not compensatory eye movement adaptation, linked to Z+ modules, was affected in TRPC3 loss-of-function mice. Together, our results indicate that TRPC3 is essential for the cellular heterogeneity that introduces distinct physiological properties in an otherwise homogeneous population of Purkinje cells, conjuring functional heterogeneity in cerebellar sensorimotor integration.
Development of the Brief Personal Values Inventory for sense of values in the Japanese general population
Authors: Ozawa Sachiyo , Iijima Yudai , Ando Shuntaro , Okada Naohiro , Kawashima Tomoko , Ohta Kazusa , Yamasaki Syudo , Kasai Kiyoto , Nishida Atsushi , Nakatani Hironori , Koike Shinsuke 
Published: November 2018

AbstractThe Portrait Values Questionnaire (PVQ) is a widely used questionnaire for assessing sense of values; however, it has limitations, especially for children. Therefore, the present study aims to develop a questionnaire for sense of values, called the Brief Personal Values Inventory (BPVI), consisting of simple questions and a smaller number of items compared to the PVQ. We first created 12 items for the BPVI and then tested their validity and reliability in 167 Japanese general population (81 males, mean age (SD) [range]: 23.4 (8.2) [15-57] years). Each of these items was correlated with one or more values in the PVQ-57. The BPVI items covered all higher-order values in Schwartz’s theory (Openness to Change, Self-Enhancement, Conservation, and Self-Transcendence). In sum, the BPVI has an acceptable criterion-related validity and corresponds to higher-order values in Schwartz’s value theory. The BPVI is suitable for a reliable and direct comparison of sense of values between children and adults, which may be useful for elucidating the developmental pathway of personal sense of values.
Homeostatic versus pathological functions of Dual Leucine Zipper Kinase in the adult mouse brain
Authors: Goodwani Sunil , Hamby Mary E , Buggia-Prevot Virginie , Acton Paul , Fernandez Celia , Al-Ouran Rami , Jiang Yongying , Soth Michael , Jones Philip , Ray William J. 
Published: November 2018

AbstractDual Leucine Zipper Kinase (DLK, Map3k12), is an injury-induced axonal protein that governs the balance between degeneration and regeneration through its downstream effectors c-jun N-terminal kinase (JNK) and phosphorylated c-jun (p-c-Jun). DLK is generally considered to be inactive in healthy neurons until induced by injury. However we report that DLK in the cerebellum appears constitutively active and drives nuclear p-c-Jun in cerebellar granule neurons in the absence of injury. In contrast the adult hippocampus expresses similar levels of apparently constitutively active DLK, but p-c-Jun is lower and does not accumulate in the nucleus. Injury is required there for p-c-jun nuclear expression, because in the rTg4510 model of tauopathy, where there is extensive hippocampal pathology, nuclear p-c-Jun is induced in a DLK-dependent manner. This context-specific regulation of DLK signaling could relate to availability of JNK scaffolding proteins, as the cerebellum preferentially expresses JNK-interacting protein-1 (JIP-1) whereas the hippocampus contains more JIP-3 and Plenty of SH3 (POSH). To understand how DLK signaling differs between the hippocampus and cerebellum, we selectively blocked DLK and measured changes in protein and mRNA expression. In the cerebellum, p-c-Jun levels correlated with synaptophysin, suggesting a link between DLK activity and synaptic maintenance. In rTg4510 mice, hippocampal p-c-Jun instead correlated with markers of neuronal injury and gliosis (Iba1 and GFAP). RNA sequencing revealed that in both brain regions DLK inhibition reduced expression of JNK/c-Jun pathway components and a novel set of co-regulated genes. In the cerebellum, Jun mRNA levels were co-regulated with genes mapping to metabolic pathways, while in the rTg4510 hippocampus, Jun-correlated mRNAs correspond primarily to neuroinflammation. These data suggest that in the uninjured cerebellum, DLK/p-c-Jun signaling is linked to synaptic regulation, but in the hippocampus, pathologically activated DLK/p-c-Jun signaling regulates genes associated with the injury response.
Hippocampal connectivity with sensorimotor cortex during volitional finger movements I. Laterality and relationship to motor learning
Authors: Burman Douglas D. 
Published: November 2018

AbstractHippocampal interactions with the motor system are often assumed to reflect the role of memory in motor learning. Here, we examine hippocampal connectivity with sensorimotor cortex during two tasks requiring paced movements, one with a mnemonic component (sequence learning) and one without (repetitive tapping). Functional magnetic resonance imaging activity was recorded from thirteen right-handed subjects; connectivity was identified from sensorimotor cortex (SMC) correlations with psychophysiological interactions in hippocampal activity between motor and passive visual tasks. Finger movements in both motor tasks anticipated the timing of the metronome, reflecting cognitive control, yet evidence of motor learning was limited to the sequence learning task; nonetheless, hippocampal connectivity was observed during both tasks. Connectivity from corresponding regions in the left and right hippocampus overlapped extensively, with improved sensitivity resulting from their conjunctive (global) analysis. The cortical laterality of SMC connectivity depended both on the hippocampal source and the task.Functionally-defined seeds produced bilateral connectivity within the hand representation, regardless of whether finger movements were uni- or bimanual; these seeds were located midlateral within the hippocampus, whereas structural seeds were located in the posterior hippocampus and produced unilateral connectivity. Results implicate the hippocampus in volitional finger movements even in the absence of motor learning or recall.
Immunological female role tested on artificial plugs in three scorpion species
Authors: Oviedo-Diego Mariela A. , Mattoni Camilo I. , Peretti Alfredo V. 
Published: November 2018

AbstractWithin arachnids, genital plugs are morphologically diverse, and they can be formed by male, female or be a contribution of both sexes. Although several species of scorpions with genital plugs are known, the physiological effects on the female after being plugged have not been well studied yet. This work compares three scorpion species, two with genital plugs and one without. We first describe the genital plugs morphology of twoUrophoniusspecies. Second, through the placement of artificial genital plugs in the female genital atrium, we tested 1) whether there are interspecific differences in the immune encapsulation response on the artificial genital plug, 2) if there are an effect in the hemocyte load in the hemolymph, and 3) if individual’s immunological parameters and body weight are correlated. Additionally, we describe and quantify the hemocytes in these species. In both species ofUrophonius, genital plugs were found covering the female genital aperture and blocking the genital atrium. The plugs consist of three zones that are distinct in morphology and coloration. We found different patterns of encapsulation and melanization on the artificial plug according to the species, with a greater and more specific response in females of plug producing species. Also, these species showed a decrease in the hemocyte load one month after the placement of the artificial plug, possibly due to the recirculation of the hemocytes into the genital area. In addition, correlations were found between the body weight and the immunological parameters, as well as between different immunological parameters. Our results suggest that females contribute to the formation of genital plugs by adding material and generating the darkening of the genital plugs in certain zones. This comparative study can help to provide a wider framework of different physiological consequences related to a particular postcopulatory mechanism such as the genital plugs.
A population of bang-bang switches of defective interfering particles makes within-host dynamics of dengue virus controllable
Authors: Mapder Tarunendu , Clifford Sam , Aaskov John , Burrage Kevin 
Published: November 2018

AbstractThe titre of virus in a dengue patient and the duration of this viraemia has a profound effect on whether or not a mosquito will become infected when it feeds on the patient and this, in turn is a key driver of the magnitude of a dengue outbreak. As mosquitoes require 100-1000 times more virus to become infected than a patient, the transmission of dengue virus from a patient to a mosquito is a vulnerability that may be able to be targeted to improve disease control. The intrinsic variability in the within-host dynamics of viraemias is explored for a population of patients using the method of population of models (POMs). A dataset from 207 patients is used to calibrate 20,000 models for the infection kinetics for each of the four dengue virus serotypes. The effect of adding defective dengue virus interfering particles to patients as a therapeutic is evaluated using the calibrated POMs in a bang-bang optimal control setting.Author summaryDengue virions with deletions or defects in their genomes can be recovered from dengue patients. These defective viruses can only replicate with the assistance of fully functional viruses and they reduce the yield of the fully functional viruses. They are known as defective interfering (DI) particles. By administering additional, defined, DI particles to patients it may be possible to reduce the titre and duration of their viraemia. This, in turn may reduce the severity of the disease and the likelihood that dengue virus will be passed from the patient to a mosquito vector. This study estimates the number of DI particles that would need to be administered, and over what period, to have a significant effect on patient viraemia and subsequent dengue fever severity.
The factors of consumer confidence recovery after scandals in food supply chain safety
Authors: Wang Shuhui , Alexander Paul 
Published: November 2018

Purpose
Viewing consumer confidence as a set of static factors has informed previous research and underpinned strategies used in recovering from food safety quality failures, but this approach has not delivered reliable and quick recovery from large-scale food safety scandals. The purpose of this paper is to examine extant models and the factors they are composed of, and suggest an extended model that has a better potential for consumer confidence. The paper focuses on food products where supply chains are visible, and use these features to group the findings.

Design/methodology/approach
In this study principal components and logit analyses are used to assess the role of 30 variables operating in a consumer confidence model constructed from several existing in the literature. This combined model considers emotional, cognitive, trust and sociodemographic factors. In total, 14 independent factors are identified. The authors examine the factors, and from these, the decision-making mechanisms before and after the Sanlu Infant Milk Formula (IMF) scandal of 2008.

Findings
The authors find that the factors considered by consumers are different for different IMF supply chains, and different again before and after the scandal. The authors develop the argument for an extension to the existing models, incorporating a dynamic consumer confidence system.

Research limitations/implications
The paper uses a single survey after the focus event to establish “before” and “after” decision-making factors. Since the IMF scandal is recent and of very high profile, this is likely valid even if it carries memory bias effects. The study is directly applicable to food safety scandals in a Chinese context. Deductive reasoning extends our assertions to a wider context. They are logically validated but have not been formally tested.

Practical implications
Using this system as a framework a checklist for recovery from a similar food safety scandal is suggested. The authors also suggest more general use for use where supply chains features are visible to consumers.

Originality/value
Models for food safety consumer confidence recovery have previously focused on identifying models and the static factors they consist of. These do represent a reflection of how this phenomenon operates, but using the principals of this model nevertheless does not result in good recovery from extreme food safety failures. This paper contributes by extending these models to one that can be applied for better recovery.
Decisional factors driving farmers to adopt organic farming in India: a cross-sectional study
Authors: Azam Md Sikandar , Shaheen Musarrat 
Published: November 2018

PurposeThe purpose of this paper is to carry out an empirical investigation of the role of various factors such as economics, social, marketing, cultivation and government in adoption of organic farming. Further, this study examines the factors that influence farmers’ choice of adopting organic farming, based on their demographic classification such as education level, farm size, farming experiences and land ownership of the organic farmers.Design/methodology/approachTo address the research objectives, the primary data were collected with the help of a structured questionnaire from 200 respondents. In this study, the QUAL–QUAN sequence of mixed method design was used. Four focus groups were conducted to identify the factors of organic farming adoption. Further, multinomial regression analysis was applied to analyze the differential impact of these factors in relation to the farmers’ demographic classification.FindingsThe study found five major factors that affect the adoption of organic farming (economic, social, marketing, cultivation, government policy) in India. The study also observed that marketing and government policy factors were most crucial in influencing all types of farmers irrespective of their educational level. The farmers with more farming experience were more concerned about social factors. Similarly, the farmers using lease farms were found to be concerned about the economic viability of organic farming.Social implicationsThis study suggests that without government support, the adoption of organic agriculture seems to be a highly challenging task in a situation, where majority of the farmers fall under the small and marginal category. Hence, to promote organic farming in a developing country like India, the government has to invest more in schemes where farmers should get exclusive training and support to strengthen their intention behind the adoption of the organic farming.Originality/valueBased on the collective insights from the studies, the different stakeholders with interest in organic agriculture may frame necessary strategies to promote organic farming.
Sport volunteer service performance, image formation, and service encounters
Authors: Lee Younghan , Kim Mi-Lyang , Koo Jakeun , Won Hyung-Joong 
Published: November 2018

PurposeThe purpose of this paper is to examine the link between sport event volunteer service performance and sport spectator experience that leads to future intentions.Design/methodology/approachSubjects were the international visitors at a mega sporting event in South Korea (n=431). The sample was randomly drawn based on convenience sampling method. Partial least squares structural equation modeling was utilized to test the hypotheses. The adequacy and statistical significance of the path models were confirmed by individual indicator loadings, average variance explained, bootstrapt-statistics and convergent validity.FindingsVolunteer service performance significantly predicted event satisfaction, event image, and host city image and indirectly influenced intentions to revisit the event and host city. Event image predicted host city image, event satisfaction and intention to revisit the event. Host city image predicted event satisfaction and intention to revisit the host city. Event satisfaction predicted both intentions to revisit the event and the host city.Originality/valueSport event volunteers are in direct contact with spectators; therefore the performance of volunteers’ service may have an impact on establishing event and host city images perceived by visitors at the event. The research findings suggest that sport event volunteer performance positively affects image formation and further induce international visitors to revisit both the event and the host city. One of the key findings includes the important role of event satisfaction in the association between volunteer performance, image formation and future behavior.