bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ex vivo 1H-MRS brain metabolic profiling in a two-hit model of schizophrenia-related alterations: effects of prenatal immune activation and peripubertal stress
Authors: Capellán Roberto , Moreno Mario , Orihuel Javier , Roura-Martínez David , Ucha Marcos , Ambrosio Emilio , Higuera-Matas Alejandro 
Published: May 2019

ABSTRACTPrenatal infections are environmental risk factors for neurodevelopmental disorders. In addition, traumatic experiences during adolescence in individuals exposed to infections during gestation could increase the risk of schizophrenia. Given the tremendous burden that these diseases pose on societies when they fully manifest, it is of the most crucial importance to discover potential markers of the disease in its early stages or even before its onset, so that therapeutic strategies may be implemented. In the present study, we combined a well-characterized two-hit model of schizophrenia-related symptoms with proton magnetic resonance spectroscopy to discover potential biomarkers. To this end, we i.p. injected 100 μg/kg/ml of lipopolysaccharide (LPS) or saline on gestational days 15 and 16 to pregnant rats. Their male offspring were then subjected to five episodes of stress or handling on alternate days during postnatal days (PND) 28 to 38. Once the animals reached adulthood (PND70), we evaluated prepulse inhibition (PPI). At PND90, we performed an ex vivo proton magnetic resonance spectroscopy study in the cortex and striatum. While we did not detect alterations in PPI at the age tested, we found neurochemical disturbances induced by LPS, stress or (more interestingly) their interaction. LPS decreased glucose levels in the cortex and striatum and altered glutamate, glutamine and N-acetylaspartate levels. Glutamate and glutamine levels in the left (but not right) striatum were differentially affected by prenatal LPS exposure in a manner that depended on stress experiences. These results suggest that alterations in the glutamate cycle in the striatum may predate the full emergence of disorders of the schizophrenic spectrum and could be used as early markers of the disease.
Competition among host-specific lineages ofPoecilochirus carabimites influences the extent of co-adaptation with theirNicrophorus vespilloidesburying beetle hosts
Authors: Sun Syuan-Jyun , Kilner Rebecca M. 
Published: May 2019

AbstractReciprocal selection between symbiotic organisms and their hosts can generate variations in local adaptation between them. Symbionts often form species complexes with lineages partially adapted to various hosts. However, it is unclear how interactions among these lineages influences geographic variation in host-symbiont local adaptation. We addressed this shortcoming with experiments on burying beetlesNicrophorus vespilloidesand their specialist phoretic mitePoecilochirus carabiin two adjacent woodlands. Burying beetles transport these mites to vertebrate carrion upon which they both reproduce.P. carabiappears to be a species complex, with distinct lineages that specialise on breeding alongside differentNicrophorusspecies. We found that in one wood (Gamlingay Woods),N. vespilloidescarries a mixture of mite lineages, with each lineage corresponding to one of the fourNicrophorusspecies that inhabits this wood. However, two burying beetle species coexist in neighbouring Waresley Woods and hereN. vespilloidespredominantly carries the mite lineage that favoursN. vespilloides. Mite lineage mixing alters the degree of local adaptation for bothN. vespilloidesand theP. carabimites, affecting reproductive success variably across different woodlands. In Gamlingay, mite lineage mixing reducedN. vespilloidesreproductive success, while experimentally purifying mites lineage enhanced it. The near pure lineage ofvespilloidesmites negligibly impacted WaresleyN. vespilloides. Mite reproductive success varied with host specificity: Gamlingay mites had greatest reproductive success on Gamlingay beetles, and performed less well with Waresley beetles. By contrast, Waresley mites had consistent reproductive success, regardless of beetle’s woodland of origin. We conclude that there is some evidence thatN. vespilloidesand its specific mite lineage have co-adapted. However, neitherN. vespilloidesnor its mite lineage adapted to breed alongside other mite lineages. This, we suggest, causes variation between Waresley and Gaminglay Woods in the extent of local adaptation betweenN. vespilloidesbeetles and theirP. carabimites.
Comparative analysis of neuroinvasion by Japanese encephalitis virulent and vaccine strains in anin cellulomodel of human blood-brain barrier
Authors: Khou Cécile , Díaz-Salinas Marco Aurelio , da Costa Anaelle , Préhaud Christophe , Jeannin Patricia , Afonso Philippe V. , Vignuzzi Marco , Lafon Monique , Pardigon Nathalie 
Published: May 2019

ABSTRACTJapanese encephalitis virus (JEV) is the major cause of viral encephalitis in South East Asia. It has been suggested that JEV gets access to the central nervous system (CNS) as a consequence of a preceding inflammatory process which leads to the blood-brain barrier (BBB) disruption and viral neuroinvasion. However, what happens at early times of JEV contact with the BBB is poorly understood. In the present work, we evaluated the ability of both a virulent and a vaccine strain of JEV (JEV RP9 and SA14-14-2, respectively) to cross anin cellulohuman BBB model consisting of hCMEC/D3 human endothelial cells cultivated on permeable inserts above SK-N-SH human neuroblastoma cells. Using this system, we demonstrated that both JEV RP9 and SA14-14-2 are able to cross the BBB without disrupting it at early times post-addition. Furthermore, this BBB model was able to discriminate between the virulent RP9 and the vaccine SA14-14-2 strains, as demonstrated by the presence of almost 10 times more RP9 infectious particles that crossed the BBB than SA14-14 particles at a high MOI. Besides contributing to the understanding of early events in JEV neuroinvasion, thisin celluloBBB model represents a suitable and useful system to study the viral determinants of JEV neuroinvasiveness and the molecular mechanisms by which this flavivirus crosses the BBB at early times of neuroinvasion.
Knowledge-guided analysis of ‘omics’ data using the KnowEnG cloud platform
Authors: Blatti Charles , Emad Amin , Berry Matthew J. , Gatzke Lisa , Epstein Milt , Lanier Daniel , Rizal Pramod , Ge Jing , Liao Xiaoxia , Sobh Omar , Lambert Mike , Post Corey S. , Xiao Jinfeng , Groves Peter , Epstein Aidan T. , Chen Xi , Srinivasan Subhashini , Lehnert Erik , Kalari Krishna R. , Wang Liewei , Weinshilboum Richard M. , Song Jun S. , Jongeneel C. Victor , Han Jiawei , Ravaioli Umberto , Sobh Nahil , Bushell Colleen B. , Sinha Saurabh 
Published: May 2019

AbstractWe present KnowEnG, a free-to-use computational system for analysis of genomics data sets, designed to accelerate biomedical discovery. It includes tools for popular bioinformatics tasks such as gene prioritization, sample clustering, gene set analysis and expression signature analysis. The system offers ‘knowledge-guided’ data-mining and machine learning algorithms, where user-provided data are analyzed in light of prior information about genes, aggregated from numerous knowledge-bases and encoded in a massive ‘Knowledge Network’. KnowEnG adheres to ‘FAIR’ principles: its tools are easily portable to diverse computing environments, run on the cloud for scalable and cost-effective execution of compute-intensive and data-intensive algorithms, and are interoperable with other computing platforms. They are made available through multiple access modes including a web-portal, and include specialized visualization modules. We present use cases and re-analysis of published cancer data sets using KnowEnG tools and demonstrate its potential value in democratization of advanced tools for the modern genomics era.
Tightly regulated, yet flexible, directional switching mechanism of a rotary motor
Authors: Afanzar Oshri , Di Paolo Diana , Eisenstein Miriam , Levi Kohava , Plochowietz Anne , Kapanidis Achillefs N. , Berry Richard Michael , Eisenbach Michael 
Published: May 2019

SummaryBiological switches are wide spread in many biological systems. Among them, the switch of the bacterial flagellar motor has generated much interest because it affects a mechanical process rather than a chemical reaction, it controls the direction of rotation of a rotary motor rather than being an on/off switch, and it is exceptionally ultrasensitive. Yet, the molecular mechanism underlying its function has remained unknown. Here we resolved unique features of this mechanism: On the one hand, it is tightly regulated by multiple means, involving three binding sites and two different covalent modifications, with the binding specificity being dictated by the type of covalent modification and by a strict binding sequence. On the other hand, it endows the motor with flexibility as it involves an intermediate stage of brief switches that provides a “go/no go” situation, in which the motor can either proceed to a stable rotation in the new direction or shift back to the original direction. This intermediate stage appears to be a means of the cell to produce angular deflection of swimming while maintaining directional persistence. Furthermore, we show by mathematical modeling that such a switching mechanism can provide ultrasensitivity. This unique combination of tight regulation, flexibility, and ultrasensitivity makes this switching mechanism of special interest.
Unique axon-to-soma signaling pathways mediate dendritic spine loss and hyper-excitability post-axotomy
Authors: Nagendran Tharkika , Taylor Anne Marion 
Published: May 2019

AbstractAxon damage may cause axon regeneration, retrograde synapse loss, and hyper-excitability, all of which affect recovery following acquired brain injury. While axon regeneration is studied extensively, less is known about signaling mediating retrograde synapse loss and hyper-excitability, especially in long projection pyramidal neurons. To investigate intrinsic injury signaling within neurons, we use anin vitromicrofluidic platform that models dendritic spine loss and delayed hyper-excitability following remote axon injury. Our data show that sodium influx and reversal of sodium calcium exchangers (NCXs) at the site of axotomy, mediate dendritic spine loss following axotomy. In contrast, sodium influx and NCX reversal alone are insufficient to cause retrograde hyper-excitability. We found that calcium release from axonal ER is critical for the induction of hyper-excitability and inhibition loss. These data suggest that synapse loss and hyper-excitability are uncoupled responses following axon injury. Further, axonal ER may play a critical and underappreciated role in mediating retrograde hyper-excitability within the CNS.
In the presence of population structure: From genomics to candidate genes underlying local adaptation
Authors: Price Nicholas , Lopez Lua , Platts Adrian E. , Lasky Jesse R. , McKay John K. 
Published: May 2019

AbstractUnderstanding the genomic signatures, genes, and traits underlying local adaptation of organisms to heterogeneous environments is of central importance to the field evolutionary biology. Mixed linear mrsodels that identify allele associations to environment, while controlling for genome-wide variation at other loci, have emerged as the method of choice when studying local adaptation. Despite their importance, it is unclear whether this approach performs better than identifying environmentally-associated SNPs without accounting for population structure. To examine this, we first use the mixed linear model GEMMA, and simple Spearman correlations, to identify SNPs showing significant associations to climate with and without accounting for population structure. Subsequently, using Italy and Sweden populations, we compare evidence of allele frequency differentiation (FST), linkage disequilibrium (LD), fitness variation, and functional constraint, underlying these SNPs. Using a lenient cut-off for significance, we find that SNPs identified by both approaches, and SNPs uniquely identified by Spearman correlations, were enriched at sites showing genomic evidence of local adaptation and function but were limited across Quantitative Trait Loci (QTL) explaining fitness variation. SNPs uniquely identified by GEMMA, showed no direct or indirect evidence of local adaptation, and no enrichment along putative functional sites. Finally, SNPs that showed significantly highFSTand LD, were enriched along fitness QTL peaks and cis-regulatory/nonsynonymous sites showing significant functional constraint. Using these SNPs, we identify genes underlying fitness QTL, and genes linking flowering time to local adaptation. These include a regulator of abscisic-acid (FLDH) and flowering time genesPIF3, FIO1, andCOL5.
Direct prediction of regulatory elements from partial data without imputation
Authors: Zhang Yu , Mahony Shaun 
Published: May 2019

ABSTRACTGenome segmentation approaches allow us to characterize regulatory states in a given cell type using combinatorial patterns of histone modifications and other regulatory signals. In order to analyze regulatory state differences across cell types, current genome segmentation approaches typically require that the same regulatory genomics assays have been performed in all analyzed cell types. This necessarily limits both the numbers of cell types that can be analyzed and the complexity of the resulting regulatory states, as only a small number of histone modifications have been profiled across many cell types. Data imputation approaches that aim to estimate missing regulatory signals have been applied before genome segmentation. However, this approach is computationally costly and propagates any errors in imputation to produce incorrect genome segmentation results downstream.We present an extension to the IDEAS genome segmentation platform which can perform genome segmentation on incomplete regulatory genomics dataset collections without using imputation. Instead of relying on imputed data, we use an expectation-maximization approach to estimate marginal density functions within each regulatory state. We demonstrate that our genome segmentation results compare favorably with approaches based on imputation or other strategies for handling missing data. We further show that our approach can accurately impute missing data after genome segmentation, reversing the typical order of imputation/genome segmentation pipelines. Finally, we present a new 2D genome segmentation analysis of 127 human cell types studied by the Roadmap Epigenomics Consortium. By using an expanded set of chromatin marks that have been profiled in subsets of these cell types, our new segmentation results capture a more complex picture of combinatorial regulatory patterns that appear on the human genome.
Japanese surgical resource utilization in 2016
Authors: Nakata Yoshinori , Watanabe Yuichi , Narimatsu Hiroto , Yoshimura Tatsuya , Otake Hiroshi , Sawa Tomohiro 
Published: May 2019

Purpose
The purpose of this paper is to examine from the viewpoint of resource utilization the Japanese surgical payment system which was revised in April 2016.

Design/methodology/approach
The authors collected data from surgical records in the Teikyo University electronic medical record system from April 1 till September 30, 2016. The authors defined the decision-making unit as a surgeon with the highest academic rank in the surgery. Inputs were defined as the number of medical doctors who assisted surgery, and the time of operation from skin incision to closure. An output was defined as the surgical fee. The authors calculated each surgeon’s efficiency score using output-oriented Charnes–Cooper–Rhodes model of data envelopment analysis. The authors compared the efficiency scores of each surgical specialty using the Kruskal–Wallis and the Steel method.

Findings
The authors analyzed 2,558 surgical procedures performed by 109 surgeons. The difference in efficiency scores was significant (p = 0.000). The efficiency score of neurosurgery was significantly greater than obstetrics and gynecology, general surgery, orthopedics, emergency surgery, urology, otolaryngology and plastic surgery (p<0.05).

Originality/value
The authors demonstrated that the surgeons’ efficiency was significantly different among their specialties. This suggests that the Japanese surgical reimbursement scales fail to reflect resource utilization despite the revision in 2016.
Nursing staff and patients’ length of stay
Authors: Moisoglou Ioannis , Galanis Petros , Meimeti Evangelia , Dreliozi Angeliki , Kolovos Petros , Prezerakos Panagiotis 
Published: May 2019

Purpose
The purpose of this paper is to investigate the effect of nurse staffing, nurse education and work experience on patients’ length of stay (LOS) in the Greek public hospitals.

Design/methodology/approach
A cross-sectional study, with retrospective administrative data, was implemented. From all seven Regional Health Authorities of Greece, 25 general surgical units in 17 public hospitals participated in the study.

Findings
All over the hospitals were studied, 32,287 patients ⩾17 years old and 203 nursing staff, who were working in the study units, were included in the analysis. According to the multivariate linear regression model, increased years of experience as a nurse (b= −0.04, 95% CI= −0.06 to −0.02, p=0.001) and increased percentage of registered nurse to the total nursing staff (b= −1.18, CI= −1.88 to −0.47, p=0.03) were associated with decreased patient LOS.

Originality/value
This was the first extended study in Greece, which explored the relationship between nurse staffing, nurse education, work experience and the LOS. The role that nurse staffing play together with its characteristics in the provision toward the quality healthcare services has already been recognized worldwide. The findings revealed the great shortage of nursing staff and the significant correlation between the work experience and educational level to patients’ LOS.
An open source solution to a common collection problem: the Africa image and map portal
Authors: Partlow Mia , Quill Theresa , Djenno Mireille 
Published: May 2019

Purpose
The purpose of this paper is to provide an overview of the Africa image and map portal (AIMP) project’s origins and development, along with its applications to date. This paper includes methods and a step-by-step appendix so that the project can be reproduced at other institutions.

Design/methodology/approach
AIMP was created with a suite of free and open source software, including QGIS, Mapbox.js and GitHub. Built around the concept of an interactive index map, AIMP allows for geographic searching of maps, posters and images from Indiana University’s (IU) African Studies collections. This paper presents a case study for the use of this geographic discovery tool at an academic library.

Findings
AIMP has allowed comparison of collection strengths with research interests of IU African Studies affiliates and to make strategic collection development decisions that will best serve the authors’ patrons. The instruction applications of AIMP are also full of potential. To date, the Librarian for African Studies has used the portal to familiarize faculty, as well as undergraduate and graduate students, with the range of image and map resources available to them, in a variety of settings.

Social implications
AIMP allows researchers around the world to discover materials through a geographic search, dramatically connecting and increasing access to and discoverability of these important collections. The use of free and open source geospatial software (foss4g) means that the interface does not rely on an institution’s proprietary software-licensing agreements, making it replicable for other institutions. This use of foss4g widens access to maps, spatial data, images and posters of Africa held by IUL to a global audience.

Originality/value
While interactive index maps are popular among map libraries, AIMP uniquely acts as a discovery portal for a variety of media, including images and posters. In this way, AIMP works to overcome institutional silos and increase discoverability of these important collections to a global audience.
Identification of a small RNA that directly controls the translation of the quorum sensing signal synthase gene rhlI in Pseudomonas aeruginosa
Authors: Chen Ronghao , Wei Xueying , Li Zhenpeng , Weng Yuding , Xia Yushan , Ren WenRan , Wang Xiangxiang , Jin Yongxin , Bai Fang , Cheng Zhihui , Jin Shouguang , Wu Weihui 
Published: May 2019

SummaryThe biofilm formation by Pseudomonas aeruginosa highly increases the bacterial resistance to antimicrobial agents and host immune clearance. The biofilm formation is positively regulated by two small RNAs, RsmY and RsmZ. Previously, we reported that mutation in the polynucleotide phosphorylase (PNPase) coding gene pnp increases the levels of RsmY/Z. However, in this study, we found that the biofilm formation is decreased in the pnp mutant, which is due to a defect in rhamnolipids production. The rhamnolipids production is regulated by the RhlI‐RhlR quorum sensing system. We found that PNPase influences the translation of RhlI through its 5′‐untranslated region (UTR) and identified that the sRNA P27 is responsible for the translational repression. In vitro translation experiments demonstrated that P27 directly represses the translation of the rhlI mRNA through its 5′UTR in an Hfq‐dependent manner. Point mutations in the rhlI 5′UTR or P27, which abolish the pairing between the two RNAs restore the rhlI expression and rhamnolipids production as well as the biofilm formation in the pnp mutant. Overall, our results reveal a novel layer of regulation of the Rhl quorum sensing system by the sRNA P27.
Subordinate reactions to ethical leaders’ abusive behavior: a multiple‐wave study
Authors: Wang Rong , Chan Darius K‐S 
Published: May 2019

This paper examines the role of ethical leadership in mitigating the effects of abusive supervision and subsequent impact on employee outcomes including interaction justice, job attitudes and well‐being. We examined two sets of moderated mediating models to link positive and negative leader behaviors together by taking on a subordinate‐centric perspective. The first set stipulates that prior ethical leadership, as a moral licence, will reduce the negative impact of subsequent abusive supervision on interactional justice, which, in turn, will enhance subordinates’ job‐related attitudes and well‐being. The second set hypothesizes that prior ethical leadership will accentuate the importance of interactional justice, making subordinates more easily influenced by subsequent abusive supervision. Data were obtained from full‐time Chinese employees by using a three‐wave time lagged design (n = 223). The results generally supported our second hypothesized model. Specifically, interactional justice mediated the relations between abusive supervision and work outcomes. Moreover, prior ethical leadership moderated the interactional justice–work outcome relations as well as the indirect effect of abusive supervision on work outcomes via interactional justice.