bluuebunny/crossref_metadata_2025_split huggingface dataset:
An Adhesive Interface for the Non-Clustered δ1 Protocadherin-1 Involved in Respiratory Diseases
Authors: Modak Debadrita , Sotomayor Marcos 
Published: December 2018

ABSTRACTCadherins form a large family of calcium-dependent adhesive proteins involved in morphogenesis, cell differentiation, and neuronal connectivity. Non-clustered δ1 protocadherins form a cadherin subgroup of proteins with seven extracellular cadherin (EC) repeats and cytoplasmic domains distinct from those of classical cadherins. The non-clustered δ1 protocadherins mediate homophilic adhesion and have been implicated in various diseases including asthma, autism, and cancer. Here we present X-ray crystal structures of Protocadherin-1 (PCDH1), a δ1-protocadherin member essential for New World hantavirus infection that is typically expressed in the brain, airway epithelium, skin keratinocytes, and lungs. The structures suggest a binding mode that involves antiparallel overlap of repeats EC1 to EC4. Mutagenesis combined with binding assays and biochemical experiments validated this mode of adhesion. Overall, these results reveal the molecular mechanism underlying adhesiveness of PCDH1 and δ1-protocadherins, also shedding light on PCDH1’s role in maintaining airway epithelial integrity, the loss of which causes respiratory diseases.
Sphingosine-1-Phosphate (S1P) analogue Phyto-sphingosine-1-Phosphate (P1P) improves thein vitromaturation efficiency of porcine oocytes via regulation of oxidative stress and apoptosis
Authors: Park Kyu-Mi , Wang Jae Woong , Yoo Yeong-Min , Jang Ji Eun , Choi Myeong Jun , Hyun Sang Hwan , Hwang Kyu Chan , Jeung Eui-Bae , Jeong Yeon Woo , Hwang Woo Suk 
Published: December 2018

AbstractPhytosphingosine-1-Phosphate (P1P) is a signaling sphingolipid regulating various physiological activities. Yet, little is known of the effect of P1P in the context of reproduction. As such, we aimed to investigate the influence of P1P on oocyte maturation during porcinein vitromaturation (IVM). Here we report the expression of S1PR1-3 among P1P receptors (S1PR1-4) in cumulus cells and oocytes. When P1P was treated by concentrations 10 nM, 50 nM, 100 nM, and 1000 nM during IVM, Metaphase II rate was significantly increased in 1000 nM (=1 μM) P1P treatment group. Maturation rate improvement by P1P supplementation was only observed in the presence of EGF. Oocytes under the influence of P1P decreased intracellular ROS levels yet did not show significant differences in GSH levels. In our molecular studies, P1P treatment up-regulated gene expressions involved in cumulus expansion (Has2andEGF), antioxidant enzyme (SOD3andCat), and developmental competence (Oct4) while activating ERK1/2 and Akt signaling. P1P treatment also influenced oocyte survival by shifting the ratio ofBcl-2toBax, while inactivating JNK signaling. We further demonstrated that oocytes matured with P1P significantly displayed not only higher developmental competence (cleavage and blastocyst formation rate), but also greater blastocyst quality (total cell number and the ratio of apoptotic cells) when activated via parthenogenetic activation (PA) andin vitrofertilization (IVF). Despite low levels of endogenous P1P found in animals, exogenous P1P was able to influence animal reproduction as shown by increased porcine oocyte maturation as well as preimplantation embryo development.
Schizophrenia polygenic risk scores, urbanicity and treatment-resistant schizophrenia
Authors: Gasse Christiane , Wimberley Theresa , Wang Yungpeng , Horsdal Henriette Thisted 
Published: December 2018

AbstractIntroductionTo investigate the impact of a polygenic risk score for schizophrenia (PRS-SZ) and urbanicity on the risk of treatment-resistant schizophrenia in people with a diagnosis of schizophrenia and to evaluate the association between PRS-SZ and TRS across areas of urbanicity.MethodsCohort study of people born after 1981 with a first time diagnosis of schizophrenia between 1996 and 2012 using Danish population registry data. Through linkage to genome-wide data, we calculated PRS-SZ based on a Psychiatric Genomics Consortium meta-analysis. We assessed urbanicity at birth (capital, provincial and rural areas). TRS was defined using prescription and hospital data. Performing Cox regression analysis, we calculated hazard rate ratios (HRs) and 95% confidence intervals (CI).ResultsAmong 4,475 people with schizophrenia, we identified 593 (13.3%) with TRS during 17 558 person years of follow-up. The adjusted HR for TRS associated with 1 standard deviation (SD) increase in the PRS-SZ was 1.11 (95% CI: 1.00–1.24). The adjusted HRs for urbanicity and TRS were 1.20 (95% CI: 0.98–1.47) for provincial areas and 1.19 (95% CI 0.96–1.47) for rural areas compared with the capital area. Across strata of urbanicity, the adjusted HR for TRS was 1.39 (95% CI: 1.14–1.70) in the capital area with 1 SD increase in the PRS-SZ, 0.99 (95% CI 0.84–1.17) in provincial areas, and 1.03 (95% CI: 0.86–1.25) in rural areas.ConclusionThe risk of TRS associated with genetic liability varied across urbanicity areas and was highest in people with schizophrenia who resided in the capital areas at birth.
The validity and consistency of continuous joystick response in perceptual decision-making
Authors: Szul Maciej J. , Bompas Aline , Sumner Petroc , Zhang Jiaxiang 
Published: December 2018

AbstractA computer joystick is an efficient and cost-effective response device for recording continuous movements in psychological experiments. Movement trajectories and other measures from continuous responses have expanded the insights gained from discrete responses (e.g. button presses) by providing unique information on how cognitive processes unfold over time. However, few studies have evaluated the validity of joystick responses with reference to conventional key presses, and response modality can affect cognitive processes. Here, we systematically compared human participants’ behavioural performance of perceptual decision-making when they responded with either joystick movements or key presses in a four-alternative motion discrimination task. We found evidence that the response modality did not affect raw behavioural measures including decision accuracy and mean reaction time (RT) at the group level. Furthermore, to compare the underlying decision processes between the two response modalities, we fitted a drift-diffusion model of decision-making to individual participant’s behavioural data. Bayesian analyses of the model parameters showed no evidence that switching from key presses to continuous joystick movements modulated the decision-making process. These results supported continuous joystick actions as a valid apparatus for continuous movements, although we highlighted the need for caution when conducting experiments with continuous movement responses.
Sensory Cue Combination in Children Under 10 Years of Age
Authors: Negen James , Chere Brittney , Bird Laura , Taylor Ellen , Roome Hannah E. , Keenaghan Samantha , Thaler Lore , Nardini Marko 
Published: December 2018

ABSTRACTCue combination occurs when two independent noisy perceptual estimates are merged together as a weighted average, creating a unified estimate that is more precise than either single estimate alone. Surprisingly, this effect has not been demonstrated compellingly in children under the age of 10 years, in contrast with the array of other multisensory skills that children show even in infancy. Instead, across a wide variety of studies, precision with both cues is no better than the best single cue – and sometimes worse. Here we provide the first consistent evidence of cue combination in children from 7–10 years old. Across three experiments, participants showed evidence of a bimodal precision advantage (Experiments 1a and 1b) and the majority were best-fit by a combining model (Experiment 2). The task was to localize a target horizontally with a binaural audio cue and a noisy visual cue in immersive virtual reality. Feedback was given as well, which could both (a) help participants judge how reliable each cue is and (b) help correct between-cue biases that might prevent cue combination. A feedback effect was found in Experiment 2, with children who were given single-cue feedback showing the highest rate of cue combination. Given this, we suggest that children at 7–10 years old are capable of cue combination in principle, but must have sufficient representations of reliabilities and biases in their own perceptual estimates as relevant to the task, which can be facilitated through task-specific feedback.
Trichoderma asperelloides enhances local and systemic acquired resistance response under low nitrate nutrition in Arabidopsis
Authors: Wany Aakanksha , Pathak Pradeep K. , Fernie Alisdair R , Gupta Kapuganti Jagadis 
Published: December 2018

AbstractNitrogen (N) is essential for growth, development and defense but, how low N affects defense and the role of Trichoderma in enhancing defense under low nitrate is not known. Low nitrate fed Arabidopsis plants displayed reduced growth and compromised local and systemic acquired resistance responses when infected with both avirulent and virulent Pseudomonas syringae DC3000. These responses were enhanced in the presence of Trichoderma. The mechanism of increased local and systemic acquired resistance mediated by Trichoderma involved increased N uptake and enhanced protein levels via modulation of nitrate transporter genes. The nrt2.1 mutant is compromised in local and systemic acquired resistance responses suggesting a link between enhanced N transport and defense. Enhanced N uptake was mediated by Trichoderma elicited nitric oxide (NO). Low NO producing nia1,2 mutant and nsHb+ over expressing lines were unable to induce nitrate transporters and thereby compromised defense in the presence of Trichoderma under low N suggesting a signaling role of Trichoderma elicited NO. Trichoderma also induced SA and defense gene expression under low N. The SA deficient NahG transgenic line and the npr1 mutant were also compromised in Trichoderma-mediated local and systemic acquired resistance responses. Collectively our results indicated that the mechanism of enhanced plant defense under low N mediated by Trichoderma involves NO, ROS, SA production as well as the induction of NRT and marker genes for systemic acquired resistance.One-sentence summaryTrichoderma enhances local and systemic acquired resistance under low nitrate nutrition
Prophages and satellite prophages are widespread amongStreptococcusspecies and may play a role in pneumococcal pathogenesis
Authors: Javan Reza Rezaei , Ramos-Sevillano Elisa , Akter Asma , Brown Jeremy , Brueggemann Angela B 
Published: December 2018

AbstractProphages (viral genomes integrated within a host bacterial genome) are abundant within the bacterial world and are of interest because they often confer various phenotypic traits to their hosts, such as by encoding genes that increase pathogenicity. Satellite prophages are ‘parasites of parasites’ that rely on the bacterial host and another helper prophage for survival. We analysed >1,300 genomes of 70 differentStreptococcusspecies for evidence of prophages and identified nearly 800 prophages and satellite prophages, the majority of which are reported here for the first time. We show that prophages and satellite prophages were widely distributed among streptococci, were two clearly different entities and each possessed a structured population. There was convincing evidence that cross-species transmission of prophages is not uncommon. Furthermore,Streptococcus pneumoniae(pneumococcus) is a leading human pathogen worldwide, but the genetic basis for its pathogenicity and virulence is not yet fully understood. Here we report that over one-third of pneumococcal genomes possessed satellite prophages and demonstrate for the first time that a satellite prophage was associated with virulence in a murine model of infection. Overall, our findings demonstrate that prophages are widespread components ofStreptococcusspecies and suggest that they play a role in pneumococcal pathogenesis.
Genome-wide Association Study of Multisite Chronic Pain in UK Biobank
Authors: Johnston Keira J.A. , Adams Mark J. , Nicholl Barbara I. , Ward Joey , Strawbridge Rona J , Ferguson Amy , McIntosh Andrew , Bailey Mark E.S. , Smith Daniel J. 
Published: December 2018

AbstractChronic pain is highly prevalent worldwide, contributing a significant socioeconomic and public health burden. Several aspects of chronic pain, for example back pain and a severity-related phenotype, chronic pain grade, have been shown to be complex, heritable traits with a polygenic component. Additional pain-related phenotypes capturing aspects of an individual’s overall sensitivity to experiencing and reporting chronic pain have also been suggested. We have here made use of a measure of the number of sites of chronic pain in individuals within the general UK population. This measure, termed Multisite Chronic Pain (MCP), is also a complex trait, but its genetic architecture has not previously been investigated. To address this, a large-scale genome-wide association study (GWAS) of MCP was carried out in ~380,000 UK Biobank participants to identify associated genetic variants. Findings were consistent with MCP having a significant polygenic component with a SNP heritability of 10.2%, and 76 independent lead single nucleotide polymorphisms (SNPs) at 39 risk loci were identified. Additional gene-level association analyses identified neurogenesis, synaptic plasticity, nervous system development, cell-cycle progression and apoptosis genes as being enriched for genetic association with MCP. Genetic correlations were observed between MCP and a range of psychiatric, autoimmune and anthropometric traits including major depressive disorder (MDD), asthma and BMI. Furthermore, in Mendelian randomisation (MR) analyses a bi-directional causal relationship was observed between MCP and MDD. A polygenic risk score (PRS) for MCP was found to significantly predict chronic widespread pain (pain all over the body), indicating the existence of genetic variants contributing to both of these pain phenotypes. These findings support the proposition that chronic pain involves a strong nervous system component and have implications for our understanding of the physiology of chronic pain and for the development of novel treatment strategies.
Pre-Clinical Blocking of PD-L1 molecule, which expression is down regulated by NF-κB, JAK1/JAK2 and BTK inhibitors, induces regression of activated B-cell lymphoma
Authors: Vincent-Fabert Christelle , Roland Lilian , Zimber-Strobl Ursula , Feuillard Jean , Faumont Nathalie 
Published: December 2018

AbstractEscape from immune control must be important in the natural course of B-cell lymphomas, especially for those with activation of NF-κB. The pre-clinical L.CD40 transgenic mouse model is characterized by B-cell specific CD40 signaling responsible for NF-κB continuous activation with a spleen monoclonal B-cell tumor after one year in 60% of cases. L.CD40 tumors B-cells expressed high levels of PD-L1. This expression was dependent on activation of either NF-κB, JAK1/JAK2 or BTK pathways since ex vivo treatment with the inhibitory molecules PHA-408, ruxolitinib and ibrutinib led to decrease of its expression. Treatment of L.CD40 lymphomatous mice with an anti-PD-L1 monoclonal antibody induced tumor regression with decreased spleen content, activation and proliferation rate of B-cells as well as a marked increase in T cell activation, as assessed by CD62L and CD44 expression. These results highlight the interest of therapies targeting the PD-1/PD-L1 axis in activated lymphomas with PD-L1 expression, with possible synergies with tyrosine kinase inhibitors.
Professional skills development for mathematics undergraduates
Authors: Russell Ewan , Rowlett Peter 
Published: December 2018

Purpose
The purpose of this paper is to describe the design and development of a final year undergraduate mathematics module designed to address professional skills development at a UK university, including via input to curriculum and assessment from employers, and to investigate student acquisition of skills from this module.

Design/methodology/approach
Literature on skills development in mathematics informs module design and development. Students optionally completed Likert-style competency questionnaires before and after the taught module content, and reflected on skills development via an end of module questionnaire. Data collection took place over three academic years.

Findings
Several key competencies exhibit median increases over the course of the module in each academic year, indicating a perceived skills development. Problem solving and presentation skills are particularly highlighted.

Research limitations/implications
Numbers of students were small, though the study is repeated with three different cohorts. Some students study mathematics jointly with another discipline and hence may have experience in skills development from the other subject.

Practical implications
This study indicates that innovations in teaching style and assessment in mathematics modules can enhance student confidence and competence with key professional skills.

Originality/value
Undergraduate modules in mathematics which have a focus on professional skills development are still fairly rare in UK universities. Often such modules do not embed the professional skills development activities with subject-specific technical tasks and projects as this module does. There are few formal studies of the effectiveness of this style of module, especially longitudinal studies covering several academic years.
Volatility in frontier markets: a Multivariate GARCH analysis
Authors: Seth Neha , Singhania Monica 
Published: December 2018

PurposeThe purpose of this paper is to analyze the existence of volatility spillover effect in frontier markets. This study also examines whether any linkages exist among these markets or not.Design/methodology/approachMonthly data of regional frontier markets, from 2009 to 2016, are analyzed using Multivariate GARCH (BEKK and Dynamic Conditional Correlation (DCC)) models.FindingsThe result of cointegration test shows that the sample frontier markets are not linked in long run, and Granger causality test reveals that the markets under consideration do not cause each other even in the short run. BEKK test says that the effect of the arrival of shock from the own market does not last for longer, whereas shock from other markets lasts with the stronger persistence, and according to DCC test, the volatility spillover exists for all the markets.Practical implicationsThe results of present study suggest that the frontier markets are not cointegrated in the long run as well as in the short run, which opens the doors for long-term investments in these markets in future, which may lead to decent returns. Long-term investors may draw the benefits from including the financial assets in their portfolios from these non-integrated frontier markets; nevertheless, they have to consider and implement diversification and hedging strategies during the period of financial turmoil, so as to protect themselves against economic and financial distress.Originality/valueSignificant work has been done on developed, developing and emerging markets but frontier markets are not explored much so far. This paper is an attempt to see the status of frontier stock markets as potential financial markets for diversification benefits.
Analysis of patients with drug‐induced pemphigoid using the Japanese Adverse Drug Event Report database
Authors: Tanaka Hiroyuki , Ishii Toshihiro 
Published: December 2018

AbstractTo clarify the incidence of drug‐induced pemphigoid in Japan, we conducted a database search and analysis using the Japanese Adverse Drug Event Report database (JADER). Among the cases recorded in JADER between April 2004 and November 2017, we targeted “pemphigoid” and analyzed the patients’ backgrounds, drug involvement, time of pemphigoid onset, outcomes and year reported. For cases where three or more drugs were reportedly involved, the signal index was calculated using the reporting odds ratio (ROR) method. The total number of reported pemphigoid cases was 769. Males accounted for 58% (446 cases) and patients over the age of 60 years accounted for 82% (630 cases). The most frequently reported causative drug was vildagliptin (288 cases), followed in order by sitagliptin phosphate hydrate (102 cases), teneligliptin hydrobromide hydrate (86 cases), linagliptin (64 cases) and furosemide (46 cases). For the 27 causative drugs, the safety signal was detected by the ROR method. The median time to onset tended to be long for these drugs. For vildagliptin with the largest reported number, the value was 508 days (range, 2–1871). Analysis of outcomes demonstrated recovery or improvement in 66.3% of cases. Analysis of the years in which reports had been published revealed that the number of pemphigoid cases has increased rapidly in recent years. Our survey was able to reveal useful data on the incidence of drug‐induced pemphigoid. We expect that these results will aid the early detection and treatment of this condition.
Cascading effects of forested area and isolation on seed dispersal effectiveness of rodents on subtropical islands
Authors: Zeng Di , Swihart Robert K. , Zhao Yuhao , Si Xingfeng , Ding Ping 
Published: December 2018

Abstract

Habitat loss and fragmentation often leads to defaunation of large‐bodied mammals, and their loss could trigger release from top‐down control or food resource competition for small mammal seed dispersers, which in turn may affect the effectiveness of seed dispersal by altering the number of dispersed seeds or the manner in which they are dispersed. Although rodents are primary seed dispersers in habitat subjected to defaunation, changes in seed dispersal effectiveness of rodents along mammalian defaunation gradients, and empirical support for mechanisms underlying alteration of this ecological process, are unclear.

We assessed the direct and indirect effects of forested area and isolation on seed dispersal effectiveness of rodents on 21 study islands with varying levels of defaunation in the Thousand Island Lake, China. We used camera sampling, live traps and semi‐quantitative acorn counts to assess occurrence of large‐bodied mammal species, relative abundance of small rodent species and seed crop size respectively. Seed dispersal, post‐dispersal seed survival, seedling emergence, and seedling survival were estimated by tracking fates of tagged acorns and by planting acorns in exclosures.

Forested area had positive indirect effects on seed dispersal effectiveness through defaunation and rodent competition for acorns, whereas isolation had negative direct and weaker positive indirect effects on seed dispersal effectiveness mediated by loss of large‐bodied mammals and rodent competition for acorns. Loss of large‐bodied mammals negatively affected seed dispersal effectiveness indirectly by virtue of its impact on rodent competition for acorns. Seed dispersal effectiveness exhibited a unimodal relationship with intensity of rodent competition for acorns, peaking at intermediate levels.

Synthesis. Indirect effects of island attributes mediated by defaunation of large‐bodied mammals on small or isolated islands appear to drive altered competition for food among rodents and decreased seed dispersal effectiveness. Altered interactions between acorns and their rodent consumers/dispersers can substantially affect oak population demography in the Thousand Island Lake system. More broadly, our findings highlight the importance to the seed dispersal process of multiple interwoven effects between habitat fragmentation and defaunation of large‐bodied mammals.