bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fitness-related traits are maximized in recently introduced, slow-growing populations of a global invasive clam
Authors: Hünicken Leandro A. , Sylvester Francisco , Bonel Nicolás 
Published: April 2019

ABSTRACTMany species are shifting their ranges being forced to rapidly respond to novel stressful environmental conditions. Colonizing individuals experience strong selective forces that favor the expression of life history traits notably affecting dispersal and reproductive rates in newly invaded habitats. Limited information is currently available on trait variation within the invasive range despite being critical for understanding ecological and evolutionary factors that drive the process of range expansion of invasive species. Here we evaluated life history shifts of the widely introduced Asian clam Corbicula, within its invaded range. Through an exhaustive literature search, we obtained data for 17 invasive Corbicula populations from different ecosystems worldwide. We tested the relationship between population and individual parameters relevant to the process of range expansion. Our main results are that recently introduced Corbicula populations were characterized by (i) low density and low rate of population increase, (ii) clams reproduced earlier in slow-growing populations, and (iii) density had no effect on population increase. All Corbicula populations analyzed in this study, which are fixed for one genotype (lineage Form A/R), experienced different selective environments in the introduced range. These findings support the perspective that adaptive phenotypic plasticity favored the expression of traits that maximize fitness in recently established populations, which faced stronger r-selective forces relative to long-established ones. We discuss the role of plasticity in facilitating rapid adaptation and increasing the likelihood of populations to overcome difficulties associated with low densities and low population increase in newly invaded areas.
An antisense oligonucleotide leads to suppressed transcriptional elongation ofHdac2and long-term memory enhancement
Authors: Poplawski Shane G. , Garbett Krassimira A. , McMahan Rebekah L. , Kordasiewicz Holly B. , Zhao Hien , Kennedy Andrew J. , Goleva Slavina B. , Sanders Teresa H. , Motley S. Timothy , Swayze Eric E. , Ecker David J. , Sweatt J. David , Michael Todd P. , Greer Celeste B. 
Published: April 2019

ABSTRACTRepression of the memory suppressor genehistonedeacetylase 2 (Hdac2) in mice elicits cognitive enhancement, and drugs that block HDAC2 catalytic activity are being investigated for treating disorders affecting memory. Currently available compounds that target HDAC2 are not specific to the HDAC2 isoform, and have short half-lives. Antisense oligonucleotides (ASOs) are a class of drugs that base pair with RNA targets and exhibit extremely long-lasting, specific inhibition relative to small molecule drugs. We utilized an ASO to reduceHdac2messenger RNA (mRNA) quantities, and explored its longevity, specificity, and mechanism of repression. A single injection of theHdac2-targeted ASO in the central nervous system diminishedHdac2mRNA levels for at least 4 months in the brain, and knockdown of this factor resulted in significant memory enhancement for 8 weeks in mice. RNA-seq analysis of brain tissues revealed that the ASO repression was specific to theHdac2isoform relative to other classicalHdacgenes, and caused alterations in levels of other memory-associated mRNAs. In cultured neurons, we observed that theHdac2-targeted ASO suppressedHdac2mRNA and anHdac2non-coding regulatory extra-coding RNA (ecRNA). The ASO not only triggered a reduction in mRNA levels, but also elicited direct transcriptional suppression of theHdac2gene through blocking RNA polymerase II elongation. These findings suggest transcriptional suppression of the target gene as a novel mechanism of action of ASOs, and opens up the possibility of using ASOs to achieve lasting gene silencing in the brain without altering the nucleotide sequence of a gene.
NK cells force cytomegalovirus to use hematopoietic cells and immune evasion for dissemination after mucosal infection
Authors: Zhang Shunchuan , Grey Finn , Snyder Christopher M. 
Published: April 2019

AbstractCytomegalovirus (CMV) infects most people in the world and causes clinically important disease in immune compromised and immune immature individuals. How the virus disseminates from the initial site of infection is poorly understood. We used an innovative approach, involving insertion of target sites for the haematopoietic specific miRNA miR-142-3p into an essential viral gene in murine cytomegalovirus. This virus was unable to disseminate to the salivary gland following intranasal infection, demonstrating a strict need for hematopoietic cells for dissemination from the natural site of infection. Viral immune evasion genes that modulate MHC-I expression and NKG2D activation were also required in this setting, as MCMV lacking these genes exhibited impaired dissemination of the viral genome to the salivary gland, and there was no detectable viral replication in the salivary gland. Depletion of T cells rescued the replication of this evasion-deficient virus in the salivary gland. Surprisingly however, the early dissemination to the salivary gland of this evasion-deficient virus, could be rescued by depletion of NK cells, but not T cells. These data are the first to show a profound loss of MCMV fitness in the absence of its MHC-I evasion genes and suggest that they protect the virus from NK cells during hematopoietic dissemination to the salivary gland, where they continued to need the three evasion genes to avoid T cell responses. Remarkably, we found that depletion of NK cells also freed the virus from the need to infect hematopoietic cells in order to reach the salivary gland. Thus, our data show that MCMV adapts to NK cell pressure after intranasal infection by using hematopoietic cells for dissemination while immune evasion genes protect the virus from NK cells during dissemination and from T cells within mucosal tissues.
An association between the gut microbiota and immune cell dynamics in humans
Authors: Schluter Jonas , Peled Jonathan U. , Taylor Bradford P. , Smith Melody , Markey Kate A. , Taur Ying , Niehus Rene , Staffas Anna , Dai Anqi , Fontana Emily , Amoretti Luigi A. , Wright Roberta J. , Morjaria Sejal , Fenelus Maly , Pessin Melissa S. , Chao Nelson J. , Lew Meagan , Bohannon Lauren , Bush Amy , Sung Anthony D. , Hohl Tobias M. , Perales Miguel-Angel , van den Brink Marcel R.M. , Xavier Joao B. 
Published: April 2019

ABSTRACTThe gut microbiota influences development and homeostasis of the mammalian immune system1–3, can alter immune cell compositions in mice4–7, and is associated with responses to immunotherapy that rely on the activity of peripheral immune cells8–12. Still, our understanding of how the microbiota modulates immune cells dynamics remains limited, particularly in humans where a lack of deliberate manipulations makes inference challenging. Here we study hundreds of hospitalized—and closely monitored—patients receiving hematopoietic cell transplantation as they recover from chemotherapy and stem cell engraftment. This aggressive treatment causes large shifts in both circulatory immune cell and microbiota populations, allowing the relationships between the two to be studied simultaneously. We analyzed daily changes in white blood cells from 2,235 patients, and 10,680 longitudinal microbiota samples to identify bacteria associated with those changes. Bayesian inference and validation across patient cohorts revealed consistent associations between gut bacteria and white blood cell dynamics in the context of immunomodulatory medications, clinical metadata and homeostatic feedbacks. We contrasted the potency of fermentatively active, obligate anaerobic bacteria with that of medications with known immunomodulatory mechanism to estimate the potential of the microbiota to influence peripheral immune cell dynamics. Our analysis establishes and quantifies the link between the gut microbiota and the human immune system, with implications for microbiota-driven modulation of immunity.
Alterations of the pulmonary immunity are independent of spontaneous pneumonia in an experimental model of ischemic stroke
Authors: Farris Breanne Y. , Monaghan Kelly L. , Amend Courtney D. , Zheng Wen , Hu Heng , Coad James E. , Ren Xuefang , Wan Edwin C.K. 
Published: April 2019

AbstractStroke-associated pneumonia (SAP) is a major cause of mortality in patients who have suffered from severe ischemic stroke. Although multi-factorial in nature, stroke-induced immunosuppression plays a key role in the development of SAP. Previous studies of focal ischemic stroke induction, using a murine model of transient middle cerebral artery occlusion (tMCAO) have shown that severe brain damage results in massive apoptosis and functional defects of lymphocytes in the spleen, thymus, and peripheral blood. However, how immune alternations in remote tissues lead to a greater susceptibility to lung infections is not well-understood. Importantly, how ischemic stroke alters immune-cell fates, and the expression of cytokines and chemokines in the lungs that directly impact pulmonary immunity, has not been characterized. We report here that ischemic stroke increases the percentage of alveolar macrophages, neutrophils, and CD11b+ dendritic cells (DCs), but reduces the percentage of CD4+ T cells, CD8+ T cells, B cells, natural killer (NK) cells, and eosinophils in the lungs. The depletion of immune cells in the lungs is not caused by apoptosis, cell infiltration to the brain, or spontaneous pneumonia following ischemic stroke as previously described, but correlates with a significant reduction in the levels of multiple chemokines in the lungs, including: CCL3, CCL4, CCL5, CCL17, CCL20, CCL22, CXCL5, CXCL9, and CXCL10. These findings suggest that ischemic stroke negatively impacts pulmonary immunity to become more susceptible for SAP development. Further investigation into the mechanisms that control pulmonary immune alternations following ischemic stroke may identify novel diagnostic or therapeutic targets for SAP.
Gephebase, a Database of Genotype-Phenotype Relationships for natural and domesticated variation in Eukaryotes
Authors: Courtier-Orgogozo Virginie , Arnoult Laurent , Prigent Stéphane R. , Wiltgen Séverine , Martin Arnaud 
Published: April 2019

AbstractGephebase is a manually-curated database compiling our accumulated knowledge of the genes and mutations that underlie natural, domesticated and experimental phenotypic variation in all Eukaryotes — mostly animals, plants and yeasts. Gephebase aims to compile studies where the genotype-phenotype association (based on linkage mapping, association mapping or a candidate gene approach) is relatively well supported or understood. Human disease and aberrant mutant phenotypes in laboratory model organisms are not included in Gephebase and can be found in other databases (eg. OMIM, OMIA, Monarch Initiative). Gephebase contains more than 1700 entries. Each entry corresponds to an allelic difference at a given gene and its associated phenotypic change(s) between two species or between two individuals of the same species, and is enriched with molecular details, taxonomic information, and bibliographic information. Users can easily browse entries for their topic of interest and perform searches at various levels, whether phenotypic, genetic, taxonomic or bibliographic (eg. transposable elements, cis-regulatory mutations, snakes, carotenoid content, an author name). Data can be searched using keywords and boolean operators and is exportable in spreadsheet format. This database allows to perform meta-analysis to extract general information and global trends about evolution, genetics, and the field of evolutionary genetics itself. Gephebase should also help breeders, conservationists and others to identify the most promising target genes for traits of interest, with potential applications such as crop improvement, parasite and pest control, bioconservation, and genetic diagnostic. It is freely available at www.gephebase.org.
Collective intelligence defines biological functions in Wikipedia as communities in the hidden protein connection network
Authors: Zinovyev Andrei , Czerwinska Urszula , Cantini Laura , Barillot Emmanuel , Frahm Klaus M. , Shepelyansky Dima L. 
Published: April 2019

AbstractEnglish Wikipedia, containing more than five millions articles, has approximately eleven thousands web pages devoted to proteins or genes most of which were generated by the Gene Wiki project. These pages contain information about interactions between proteins and their functional relationships. At the same time, they are interconnected with other Wikipedia pages describing biological functions, diseases, drugs and other topics curated by independent, not coordinated collective efforts. Therefore, Wikipedia contains a directed network of protein functional relations or physical interactions embedded into the global network of the encyclopedia terms, which defines hidden (indirect) functional proximity between proteins. We applied the recently developed reduced Google Matrix (REGOMAX) algorithm in order to extract the network of hidden functional connections between proteins in Wikipedia. In this network we discovered tight communities which reflect areas of interest in molecular biology or medicine. Moreover, by comparing two snapshots of Wikipedia graph (from years 2013 and 2017), we studied the evolution of the network of direct and hidden protein connections. We concluded that the hidden connections are more dynamic compared to the direct ones and that the size of the hidden interaction communities grows with time. We recapitulate the results of Wikipedia protein community analysis and annotation in the form of an interactive online map, which can serve as a portal to the Gene Wiki project.
Superficial bound of the depth limit of 2-photon imaging in mouse brain
Authors: Takasaki Kevin , Abbasi-Asl Reza , Waters Jack 
Published: April 2019

ABSTRACT2-photon fluorescence microscopy has been used extensively to probe the structure and functions of cells in living biological tissue. 2-photon excitation generates fluorescence from the focal plane, but also from outside the focal plane, with out-of-focus fluorescence increasing as the focus is pushed deeper into tissue. It has been suggested that the 2-photon depth limit, beyond which results become inaccurate, is where in- and out-of-focus fluorescence are equal. We found the depth limit of 2-photon excitation in mice with GCaMP6 indicator expression in all layers of visual cortex, by comparing near-simultaneous 2- and 3-photon excitation. 2-photon results were accurate only superficial to 450 μm, matching the depth at which in-and out-of-focus fluorescence were equal. The expected depth limit is deeper in tissue with fewer fluorophores outside the plane of interest. Our results, from tissue with a largely homogenous distribution of fluorophores, establish a superficial bound on the 2-photon depth limit in the mouse visual cortex.
Single-cell imaging reveals unexpected heterogeneity of TERT expression across cancer cell lines
Authors: Rowland Teisha J. , Dumbović Gabrijela , Hass Evan P. , Rinn John L. , Cech Thomas R. 
Published: April 2019

AbstractTelomerase is pathologically reactivated in most human cancers, where it maintains chromosomal telomeres and allows immortalization. Because telomerase reverse transcriptase (TERT) is usually the limiting component for telomerase activation, numerous studies have measured TERT mRNA levels in populations of cells or in tissues. However, little is known about TERT expression at the single-cell and single-molecule level. Here we analyzed TERT expression across 10 human cancer lines using single-molecule RNA FISH and made several unexpected findings. First, there was substantial cell-to-cell variation in number of transcription sites and ratio of transcription sites to gene copies. Second, previous classification of lines as having monoallelic or biallelic TERT expression was found to be inadequate for capturing the TERT gene expression patterns. Finally, TERT mRNA had primarily nuclear localization in cancer cells and induced pluripotent stem cells (iPSCs), in stark contrast to the expectation that mature mRNA should be predominantly cytoplasmic. These data reveal unappreciated heterogeneity, complexity, and unconventionality in TERT expression across human cancer cells.
An In-Silico Investigation of Menthol Metabolism
Authors: Limpanuparb Taweetham , Lorpaiboon Wanutcha , Chinsukserm Kridtin 
Published: April 2019

ABSTRACTPrevalence of mentholated products for consumption has brought great importance to studies on menthol’s metabolic pathways to ensure safety, design more potent derivatives, and identify therapeutic benefits. Proposed pathways of (-)-menthol metabolism based on metabolites found experimentally in previous works by Yamaguchi, Caldwell & Farmer, Madyastha & Srivatsan and Hiki et al. were not in agreement. This in silico approach is based on the three in vivo studies and aims to resolve the discrepancies. Reactions in the pathways are conjugation with glucuronic acid/sulfate, oxidation to alcohol, aldehyde & carboxylic acid, and formation of a four-membered/five-membered ring. Gas-phase structures, standard Gibbs energies and SMD solvation energies at B3LYP/6-311++G(d,p) level were obtained for 102 compounds in the pathways. This study provides a more complete picture of menthol metabolism by combining information from three experimental studies and filling missing links in previously published pathways.
Childhood conditions, pathways to entertainment work and current practices of female entertainment workers in Cambodia: Baseline findings from the Mobile Link trial
Authors: Brody Carinne , Chhoun Pheak , Tuot Sovannary , Swendeman Dallas , Yi Siyan 
Published: April 2019

AbstractBackgroundEntertainment venues have been identified as an important location for HIV prevention due to the increasing number of young female entertainment and sex workers at these venues. The purpose of this report is to increase understanding of the childhood conditions, pathways to entertainment work and current practices of female entertainment workers (FEWs) in Cambodia.MethodsData used for this study were collected in April 2018 as part of the baseline survey of the Mobile Link, a randomized controlled trial to improve sexual and reproductive health of FEWs in Cambodia. We used a stratified random sampling method to recruit 600 FEWs for face-to-face interviews using a structured questionnaire. Descriptive analyses were performed.ResultsMost participants came from childhood homes without electricity (82.0%) or running water (87.0%). Most women moved to the city in the last ten years (80.5%) for economic reasons (43.7%). About a third worked in the garment industry prior to the entertainment industry (36.7%). Participation in transactional sex in the past three months was reported by 36.0%. Women reported low condom use practices with non-paying partners (23.4% used condom with partner at last sex), excessive and forced alcohol use at work (33.1% reported being forced to drink alcohol at work more than once a month), low modern contraception use (31.4% was using modern contraception), and experiences of gender-based violence (23.3% reported verbal threats, physical abuse or forced sex in the past six months).ConclusionsThis information will help to support the development of future individual and structural level interventions for the safety and support of FEWs. In addition, these results may contribute to an evidence base that can inform policy level changes intended to support the realization of full human rights for entertainment works in Cambodia including the rights to health, safety, and respectful employment.
Intrauterine exposure to hyperglycaemia in pregnancy and risk of adiposity in the offspring at 10 years of age – A community based retrospective cohort study in Sri Lanka
Authors: Herath Himali , Herath Rasika , Wickremasinghe Rajitha 
Published: April 2019

AbstractBackgroundIntrauterine exposure to a hyperglycemic environment can cause long term changes in body composition resulting in increased adiposity and cardio metabolic risk in the offspring. The aim of this study was to determine the association between hyperglycaemia in pregnancy (HIP) and risk of adiposity in the offspring at 10-11 years of age.MethodsA retrospective cohort study was conducted in the Colombo district, Sri Lanka. 7205 children who were born in 2005 were identified through schools and Public Health Midwives in the community. Mothers of these children still possessing antenatal records were interviewed and relevant data were extracted from medical records to identify eligible participants. Exposure status (hyperglycaemia in pregnancy) was ascertained based on client held antenatal records. 159 children of mothers with HIP (exposed) and 253 children of mothers with no HIP (non-exposed) were recruited. Height, weight, waist circumference and triceps skin fold thickness (TSFT) of participants were measured to ascertain outcome status.ResultsThe mean ages (SD) of exposed and non-exposed groups were 10.9 (0.3) and 10.8 (0.3) years respectively. The median BMI (17.6 vs 16.1, p<0.001), waist circumference (63cm vs 59.3 cm, p<0.001) and triceps skinfold thickness (13.7mm vs 11.2mm, p< 0.001) were significantly higher in the exposed group than in the non-exposed group.Children who were exposed to intrauterine hyperglycaemia were more likely to be overweight (aOR=2.5, 95% CI 1.3-4.7), have abdominal obesity (aOR=2.9, 95% CI 1.2-6.8) and high TSFT > 70thcentile (aOR=2.1, 95% CI 1.2-3.9) at 10-11 years of age than children who were not exposed after adjusting for maternal BMI, birth weight and birth order.ConclusionsIntrauterine exposure to HIP is associated with significantly higher risk of adiposity in the offspring at 10 years of age.
The role of HR in leadership development
Authors: Maheshwari Shilpa Kabra , Yadav Jaya 
Published: April 2019

Purpose
Business environments have become more complex, dynamic, and uncertain in the past few decades. To navigate this complexity, organizations need to enhance their competitiveness, improve performance, and build leadership. Though leadership contributes to strategic advantage, the challenge for human resources (HR) to build the next generation of leaders remains. This has sparked the need for practitioners to understand the role of HR in enhancing leadership capability.

Design/methodology/approach
Using qualitative analysis and practitioner insights, this paper contributes to the understanding of the role of HR in leadership development.

Findings
The study proposes the HR PACE model for the role of HR in leadership development.

Practical implications
This study has potentially significant implications for HR, leadership development scholars, and practitioners while designing and implementing leadership development in organizations.

Originality/value
While empirical studies on how HR practices of recruitment, performance management, training, and development impact organizations exist, there are rare studies assessing the role of HR in leadership development. This study examines the role of HR in leadership development.