bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estradiol Protects Against Cardiorespiratory Dysfunctions and Oxidative Stress in Intermittent Hypoxia
Authors: Laouafa Sofien , Ribon-Demars Alexandra , Marcouiller François , Roussel Damien , Bairam Aida , Pialoux Vincent , Joseph Vincent 
Published: June 2017

Abstract

Study Objectives
We tested the hypothesis that estradiol (E2) protects against cardiorespiratory disorders and oxidative stress induced by chronic intermittent hypoxia (CIH) in adult female rats.

Methods
Sprague-Dawley female rats (230–250 g) were ovariectomized and implanted with osmotic pumps delivering vehicle or E2 (0.5 mg/kg/d). After 14 days of recovery, the rats were exposed to CIH (21%–10% O2: 8 h/d, 10 cycles per hour) or room air (RA). After 7 days of CIH or RA exposure, we measured arterial pressures (tail cuff), metabolic rate (indirect calorimetry), minute ventilation, the frequency of sighs and apneas at rest, and ventilatory responses to hypoxia and hypercapnia (whole body plethysmography). We collected the cerebral cortex, brainstem, and adrenal glands to measure the activity of NADPH and xanthine oxidase (pro-oxidant enzymes), glutathione peroxidase, and the mitochondrial and cytosolic superoxide dismutase (antioxidant enzymes) and measured lipid peroxidation and advanced oxidation protein products (markers of oxidative stress).

Results
CIH increased arterial pressure, the frequency of apnea at rest, and the hypoxic and hypercapnic ventilatory responses and reduced metabolic rate. CIH also increased oxidant enzyme activities and decreased antioxidant activity in the cortex. E2 treatment reduced body weight and prevented the effects of CIH.

Conclusions
E2 prevents cardiorespiratory disorders and oxidative stress induced by CIH. These observations may help to better understand the underlying mechanisms linking menopause and occurrence of sleep apnea in women and highlight a potential advantage of hormone therapy.
Embryonic Exposure to Valproic Acid Disrupts Social Predispositions in Newly-Hatched Chicks
Authors: Sgadò Paola , Rosa-Salva Orsola , Versace Elisabetta , Vallortigara Giorgio 
Published: June 2017

AbstractBiological predispositions to attend to visual cues, such as those associated with face-like stimuli or with biological motion, guide social behavior from the first moments of life and have been documented in human neonates, infant monkeys and newly-hatched domestic chicks. In human neonates at high familial risk of Autism Spectrum Disorder (ASD), a lack of such predispositions has been recently reported. Prompted by these observations, we modeled ASD behavioral deficit in newborn chicks, using embryonic exposure to valproic acid (VPA), the histone deacetylases (HDACs) inhibitor that in humans is associated with an increased risk for developing ASD. We assessed spontaneous predispositions in newly-hatched, visually-naïve chicks, by comparing responses to a stuffed henvs.a scrambled version of it. We found that social predispositions were abolished in VPAtreated chicks. In contrast, experience-dependent learning mechanisms associated with filial imprinting were not affected. Our results indicate a specific effect of VPA on the development of biologically-predisposed social orienting mechanisms, opening new perspectives to investigate the molecular and neurobiological mechanisms involved in early ASD symptoms.
A statistical framework for the robust detection of hidden variation in single cell transcriptomes
Authors: Lee Donghyung , Cheng Anthony , Bolisetty Mohan , Ucar Duygu 
Published: June 2017

AbstractSingle cell RNA-sequencing (scRNA-seq) precisely characterize gene expression levels and dissect variation in expression associated with the state (technical or biological) and the type of the cell, which is averaged out in bulk measurements. Multiple and correlated sources contribute to gene expression variation in single cells, which makes their estimation difficult with the existing methods developed for bulk measurements (e.g., surrogate variable analysis (SVA)) that estimate orthogonal transformations of these sources. We developed iteratively adjusted surrogate variable analysis (IA-SVA) that can estimate hidden and correlated sources of variation by identifying a set of genes affected with each hidden factor in an iterative manner. Analysis of scRNA-seq data from human cells showed that IA-SVA could accurately capture hidden variation arising from technical (e.g., stacked doublet cells) or biological sources (e.g., cell type or cell-cycle stage). Furthermore, IA-SVA delivers a set of genes associated with the detected hidden source to be used in downstream data analyses. As a proof of concept, IA-SVA recapitulated known marker genes for islet cell subsets (e.g., alpha, beta), which improved the grouping of subsets into distinct clusters. Taken together, IA-SVA is an effective and novel method to dissect multiple and correlated sources of variation in scRNA-seq data.
High Frequency Actionable Pathogenic Exome Mutations in an Average-Risk Cohort
Authors: Rego Shannon , Dagan-Rosenfeld Orit , Zhou Wenyu , Reza Sailani M. , Limcaoco Patricia , Colbert Elizabeth , Avina Monika , Wheeler Jessica , Craig Colleen , Salins Denis , Röst Hannes L. , Dunn Jessilyn , McLaughlin Tracey , Steinmetz Lars M. , Bernstein Jonathan A. , Snyder Michael P. 
Published: June 2017

AbstractWhole exome sequencing (WES) is increasingly utilized in both clinical and non-clinical settings, but little is known about the utility of WES in healthy individuals. In order to determine the frequency of both medically actionable and non-actionable but medically relevant exome findings in the general population we assessed the exomes of 70 participants who have been extensively characterized over the past several years as part of a longitudinal integrated multi-omics profiling study at Stanford University. We assessed exomes for rare likely pathogenic and pathogenic variants in genes associated with Mendelian disease in the Online Mendelian Inheritance in Man (OMIM) database. We used American College of Medical Genetics (ACMG) guidelines were used for the classification of rare sequence variants, and additionally we assessed pharmacogenetic variants. Twelve out of 70 (17%) participants had medically actionable findings in Mendelian disease genes, including 6 (9%) with mutations in genes not currently included in the ACMG’s list of 59 actionable genes. This number is higher than that reported in previous studies and suggests added benefit from utilizing expanded gene lists and manual curation to assess actionable findings. A total of 60 participants (89%) had non-actionable findings identified including 57 who were found to be mutation carriers for recessive diseases and 21 who have increased Alzheimer’s disease risk due to heterozyg ous or homozygousAPOEe4 alleles (18 participants had both). These results suggest that exome sequencing may have considerably more utility for health management in the general population than previously thought.
The coalescent for prokaryotes with homologous recombination from external source
Authors: Akita Tetsuya , Takuno Shohei , Innan Hideki 
Published: June 2017

ABSTRACTThe coalescent process for prokaryote species is theoretically considered. Prokaryotes undergo homologous recombination not only with other individuals within the same species (intra-specific recombination) but also with other species (inter-specific recombination). This work particularly focuses the latter because the former has been well incorporated in the framework of the coalescent. We here developed a simulation framework for generating patterns of SNPs (single nucleotide polymorphisms) allowing integration of external DNA out of the focal species, and a simulator namedmsProwas developed. We found that the joint work of intra- and inter-specific recombination creates a complex pattern of SNPs. The direct effect of inter-specific recombination is to increase the amount of polymorphism. Because inter-specific recombination is very rare in general, it creates a regions with an exceptionally high level of polymorphisms. Following an inter-specific recombination event, intra-specific recombination chop the integrated foreign DNA into small pieces, making a complicated pattern of SNPs that looks as if foreign DNAs were integrated multiple times. This work with themsProsimulator would be useful to understand and evaluate the relative contribution of intra- and inter specific recombination to creating complicated patterns of SNPs in prokaryotes.
Moment-to-moment fluctuations in neuronal excitability bias subjective perception rather than decision-making
Authors: Iemi Luca , Busch Niko A 
Published: June 2017

AbstractPerceiving an external stimulus not only depends on the physical features of the stimulus, but also fundamentally on the current state of neuronal excitability, indexed by the power of ongoing alpha oscillations. Recent studies suggest that heightened excitability does not improve perceptual acuity, but biases observers to report the presence of a stimulus regardless of its physical presence. It is unknown whether this bias is due to changes in observers’ subjective perceptual experience (perceptual bias) or their perception-independent decision-making strategy (decision bias). We tested these alternative interpretations in an EEG experiment in which human participants performed two-interval forced choice (2IFC) detection and discrimination. According to signal detection theory, perceptual bias only affects 2IFC detection, but not discrimination, while interval decision bias should be task-independent. We found that detection was optimal in trials in which excitability before the stimulus-present interval exceeded that before the stimulus-absent interval, consistent with an effect of excitability on perceptual bias. By contrast, discrimination accuracy was unaffected by excitability fluctuations between intervals, ruling out an effect on interval decision bias. We conclude that the current state of neuronal excitability biases the perceptual experience itself, rather than the decision process.
A resource-rational theory of set size effects in visual working memory
Authors: van den Berg Ronald , Ma Wei Ji 
Published: June 2017

AbstractEncoding precision in visual working memory decreases with the number of encoded items. Here, we propose a normative theory for such set size effects: the brain minimizes a weighted sum of an error-based behavioral cost and a neural encoding cost. We construct a model from this theory and find that it predicts set size effects. Notably, these effects are mediated by probing probability, which aligns with previous empirical findings. The model accounts well for effects of both set size and probing probability on encoding precision in nine delayed-estimation experiments. Moreover, we find support for the prediction that the total amount of invested resource can vary non-monotonically with set size. Finally, we show that it is sometimes optimal to encode only a subset or even none of the relevant items in a task. Our findings raise the possibility that cognitive “limitations” arise from rational cost minimization rather than from constraints.
Impairment of mitochondrial respiratory function as an early biomarker of apoptosis induced by growth factor removal
Authors: Lemieux Hélène , Subarsky Patrick , Doblander Christine , Wurm Martin , Troppmair Jakob , Gnaiger Erich 
Published: June 2017

AbstractIntracellular signaling pathways not only control cell proliferation and survival, but also regulate the provision of cellular energy and building blocks through mitochondrial and non-mitochondrial metabolism. Wild-type and oncogenic RAF kinases have been shown to prevent apoptosis following the removal of interleukin 3 (IL-3) from mouse pro-myeloid 32D cells by reducing mitochondrial reactive oxygen species production. To study primary effects of RAF on mitochondrial energy metabolism, we applied high-resolution respirometry after short-term IL-3 deprivation (8 h), before 32D cells show detectable signs of cell death. Respiration in intact 32D cells was suppressed as an early event following removal of IL-3, but remained more stable in 32D cells expressing the v-RAF oncogene. In permeabilized 32D cells deprived of IL-3, respiratory capacities of the NADH-pathway, the convergent NADH&succinate-pathway, and Complex IV activity were decreased compared to cells grown in the presence of IL-3, whereas succinate-supported respiration remained unchanged, consistent with control by Complex IV. The apparent Complex IV excess capacity was zero above NADH&succinate-pathway capacity reconstituting tricarboxylic acid cycle function. In comparison, electron flow reached only 60% when supported by succinate alone through Complexes II, III and IV, and was therefore relatively insensitive to Complex IV injuries up to a threshold of 40% inhibition. A slight increase in respiration following addition of cytochromec, a marker of mitochondrial outer membrane leakage, was present after IL-3 depletion, indicating mitochondrial fragility. Our results highlight a novel link between the key mitogenic and survival kinase CRAF and mitochondrial energy homeostasis.
Effects of Human-Animal Interaction on Dog Salivary and Plasma Oxytocin and Vasopressin
Authors: MacLean Evan L. , Gesquiere Laurence R. , Gee Nancy , Levy Kerinne , Lance Martin W. , Sue Carter C. 
Published: June 2017

AbstractOxytocin (OT) and Vasopressin (AVP) are neuropeptides with diverse effects on social behavior, cognition and stress responses. Recent studies suggest that OT facilitates and responds to affiliative forms of human-animal interaction (HAI). However, previous studies measuring OT and AVP in dogs have been limited to measures from blood or urine, which present concerns related to the invasiveness of sample collection, the potential for matrix interference in immunoassays, and whether samples can be collected at precise time points to assess event-linked endocrine responses. Previous studies from our laboratory validated salivary measures of OT and AVP in dogs, however, it is currently unknown whether these measures respond dynamically to aspects of HAI. Here, we investigated the effects of affiliative forms of HAI on both plasma and salivary OT and AVP in dogs. We employed a between-subjects design with a group of Labrador retrievers and Labrador retriever X golden retriever crosses (23 females, 15 males). Half of the dogs engaged in 10 minutes of free-form friendly interaction with a human experimenter (HAI condition), and the other half rested quietly in the same environment, without human interaction (control condition). We collected blood and saliva samples before, and immediately following both experimental conditions, and all samples were analyzed using enzyme-linked immunosorbent assays (ELISAs) following previously validated protocols. Dogs participating in HAI exhibited a significant increase in both salivary OT (+39%) and plasma OT (+5.7%) whereas dogs in the control group did not. Salivary AVP showed no change in the HAI group but increased significantly (+33%) in the control group. Plasma AVP decreased significantly following HAI (-13%) but did not change across time in the control condition. Within the dogs exposed to HAI, increases in salivary OT, and decreases in plasma AVP, were predicted by the extent of affiliative behaviour between the dog and human (indexed by scores from a principal components analysis of social behaviours between the dog and human). Collectively our results suggest that measures of salivary OT and AVP provide useful biomarkers in studies of HAI, and afford a flexible and noninvasive toolkit than can be employed in diverse research contexts.
Bridging the dynamics and organization of chromatin domains by mathematical modeling
Authors: Shinkai Soya , Nozaki Tadasu , Maeshima Kazuhiro , Togashi Yuichi 
Published: June 2017

AbstractThe genome is three-dimensionally organized in the cell, and the mammalian genome DNA is partitioned into submegabase-sized chromatin domains. Genome functions are regulated within and across the domains according to their organization, whereas the chromatin itself is highly dynamic. However, the details of such dynamic organization of chromatin domains in living cells remain unclear. To unify chromatin dynamics and organization, we recently demonstrated that structural information of chromatin domains in living human cells can be extracted from analyses of the subdiffusive nucleosome movement using mathematical modeling. Our mathematical analysis suggested that as the chromatin domain becomes smaller and more compact, nucleosome movement becomes increasingly restricted. Here, we show the implication of these results for bridging the gap between chromatin dynamics and organization, and provide physical insight into chromatin domains as efficient units to conduct genome functions in the thermal noisy environment of the cell.Extra View toShinkai S, Nozaki T, Maeshima K, Togashi Y. Dynamic Nucleosome Movement Provides Structural Information of Topological Chromatin Domains in Living Human Cells. PLoS Comput Biol. 2016;12(10):e1005136. doi: 10.1371/journal.pcbi.1005136. PubMed PMID: 27764097; PubMed Central PMCID: PMCPMC5072619.FundingThis work was supported by Platform Project for Supporting in Drug Discovery and Life Science Research (Platform for Dynamic Approaches to Living System) from MEXT and AMED; KAKENHI under Grant JP16H01408, JP23115007, JP23115005, JP16H04746; CREST grant (JPMJCR15G2) from JST; and Research Fellowship for Young Scientists under Grant JP13J04821, JP16J07205.DisclosureNo potential conflicts of interest were disclosed.AcknowledgementsWe would like to thank Dr. Takashi Toda for comments regarding the manuscript.
IFNα, a potential biomarker for stress vitiligo risk
Authors: Wu Huali , Wang Ting , Cai Minxuan , Fu Mengsi , Ping Fengfeng , He Ling , An Xiaohong , Shi Zhixiang , Xia Zhenjiang , Shang Jing 
Published: June 2017

AbstractNeural hypothesis has become an important aspect of vitiligo, yet without corresponding diagnostic indicators. We preliminarily found 32 cases of vitiligo patients with certain aggregation of mental factors. In peripheral blood mononuclear cells (PBMCs) of these patients, transcriptome analyses revealed that the circulation expression of a type I interferon (IFN-I)-dependent genes was induced. Also, serum IFNα was elevated in vitiligo patients with depression. Therefore, our hypothesis is whether IFNα levels predict the occurrence of psychiatric vitiligo. Through the establishment of stress-induced depigmentation model, serum IFNα also showed increase. Intracerebroventricular and subcutaneous IFNα injection can both elicit not only depressive behavior but also vitiligo-like characteristics. Mechanistically, central IFNα induces the release of dorsal root ganglion (DRG) substance P (SP) to inhibit melanogenesis. Peripheral IFNα disturbs cutaneous-neuro-endocrine microenvironment. Type I IFN (IFNα) pathway-related genes in stress vitiligo were significantly discriminating from non-stress vitiligo, while that of type II IFN pathway was not.
Fibroblast Growth Factor Signaling Instructs Ensheathing Glia Wrapping ofDrosophilaOlfactory Glomeruli
Authors: Wu Bing , Li Jiefu , Chou Ya-Hui , Luginbuhl David , Luo Liqun 
Published: June 2017

AbstractThe formation of complex yet highly organized neural circuits requires interactions between neurons and glia. During the assembly of theDrosophilaolfactory circuit, 50 olfactory receptor neuron (ORN) classes and 50 projection neuron (PN) classes form synaptic connections in 50 glomerular compartments in the antennal lobe, each of which represents a discrete olfactory information processing channel. Each compartment is separated from the adjacent compartments by membranous processes from ensheathing glia. Here we show that Thisbe, a fibroblast growth factor (FGF) released from olfactory neurons, particularly local interneurons, instructs ensheathing glia to wrap each glomerulus. The Heartless FGF receptor acts cell-autonomously in ensheathing glia to regulate process extension so as to insulate each neuropil compartment. Overexpressing Thisbe in ORNs or PNs causes over-wrapping of glomeruli to which their axons or dendrites target. Failure to establish the FGF-dependent glia structure disrupts precise ORN axon targeting and discrete glomerular formation.Significance StatementThis research reports that reciprocal interactions betweenDrosophilaolfactory neurons and ensheathing glia mediate the formation of neuronal compartments—groups of synapses that are packed into discrete structures called glomeruli that carry specific olfactory information. Ensheathing glia respond to a neuronal cue, the fibroblast growth factor (FGF) Thisbe, to pattern the boundaries of the nascent compartments. Neural compartments in turn require such glial barriers to separate themselves from neighboring compartments, so as to ensure the correct organization of the olfactory circuit. These findings highlight the importance of glia in the assembly and maintenance of neural circuits and the functions of FGF signaling in these processes.
Ownership structure and the choice of SEO issue method in the UK
Authors: Andrikopoulos Panagiotis , Sun Ji , Guo Jie 
Published: June 2017

PurposeThe purpose of this paper is to analyse the role of ownership characteristics in a firm’s choice of alternative seasoned equity offering (SEO) methods, offer price discounts, and market reactions to such announcements within the UK setting.Design/methodology/approachThe study examines 697 SEO events of firms traded in the UK during the period 1998 to 2012 using multivariate and binomial logistic regression models. Ordinary least square models are also used to examine how ownership variables affect offer price discounts and stock market performance during the announcement of such corporate events.FindingsThe authors show that placings and open offers (OOs) are the preferred methods for issuing equity by firms with higher managerial ownership. Thus, the evidence strongly supports the prediction of the entrenched management hypothesis. Moreover, the probability of choosing a combination of placings and OOs is also found to be significantly related to issue size, offer discount, leverage, and previous stock performance. The results show that pre-issue market conditions have a significant effect on the choice of issue method with rights offers (ROs) and the combination of placings and OOs primarily utilised by firms for issuing equity during hot market periods.Originality/valueUnlike prior SEOs’ studies in the UK that predominantly concentrate on the use of ROs and placings, this study examines, for the first time, the link between OOs and the combination of placings and OOs with ownership concentration. The authors also investigate how offer price discounts are related to the firms’ ownership structure, various company micro-characteristics and the wider market conditions.