bluuebunny/crossref_metadata_2025_split huggingface dataset:
HIPPO signaling resolves embryonic cell fate conflicts during establishment of pluripotencyin vivo
Authors: Frum Tristan , Murphy Tayler , Ralston Amy 
Published: May 2018

AbstractDuring mammalian development, the challenge for the embryo is to override intrinsic cellular plasticity to drive cells to distinct fates. Here, we unveil novel roles for the HIPPO signaling pathway segregates pluripotent and extraembryonic fates by controlling cell positioning as well as expression ofSox2,the first marker of pluripotency in the mouse early embryo. We show that maternal and zygotic YAP1 and WWTR1 repressSox2while promoting expression of the trophectoderm geneCdx2in parallel. Yet,Sox2is more sensitive thanCdx2toYap1/Wwtr1dosage, leading cells to a state of conflicted cell fate when YAP1/WWTR1 activity is moderate. Remarkably, HIPPO signaling activity resolves conflicted cell fate by repositioning cells to the interior of the embryo, independent of its role in regulatingSox2expression. Rather, HIPPO antagonizes apical localization of Par complex components PARD6B and aPKC. Thus, negative feedback between HIPPO and Par complex components ensure robust lineage segregation.
Robust Reference Powered Association Test of genome-wide association studies
Authors: Wang Yi , Li Yi , Hao Meng , Liu Xiaoyu , Zhang Menghan , Xiong Momiao , Wang Jiucun , Shugart Yin Yao , Jin Li 
Published: May 2018

ABSTRACTGenome-wide association studies (GWAS) have identified abundant genetic susceptibility loci, although they are far less from meeting the previous expectations due to low statistical power and false positive results. Effective statistical methods are required to further improve the analyses of massive GWAS data. Here we presented a new statistic (Robust Reference Powered Association Test,http://drwang.top/gwas.html) to use large public database as reference to reduce concern of potential population stratification. To evaluate the performance of this statistic for various situations, we simulated multiple sets of sample size and frequencies to compute statistical power. Furthermore, we applied our method to several real datasets (psoriasis genome-wide association datasets and schizophrenia genome-wide association dataset) to evaluate the performance. Careful analyses indicated that our newly developed statistic outperformed several previously developed GWAS applications. Importantly, this statistic is more robust than naive merging method in the presence of small control-reference differentiation, therefore likely to detect more association signals.
Frequency and synchrony of actomyosin oscillation during PCP-dependent convergent extension
Authors: Shindo Asako , Inoue Yasuhiro , Kinoshita Makoto , Wallingford John B. 
Published: May 2018

AbstractOscillatory actomyosin flows play a key role in single cell migration and in collective cell movements that shape invertebrates embryos, but the role of such oscillations in vertebrate morphogenesis remains poorly defined. Here, data from mathematical modeling andin vivo4D imaging of actomyosin in theXenopusgastrula suggest that oscillatory actomyosin contractions are a general feature of convergent extension by junction shrinking. We show that synchronous intracellular flows link two spatially distinct populations of actomyosin within individual cells, but that oscillations are asynchronousbetweenneighboring cells that share a shrinking cell-cell junction. We also show that the core PCP protein Prickle2 displays a parallel oscillatory behavior and is required for tuning the frequency of actomyosin contractions, indicating that PCP signaling controls not only the orientation of actomyosin contractions, but also their frequency. Together, these data provide new insights into the function and control of oscillatory actomyosin contractions in collective cell movement.
Anti-Microbial Resistance in Agents Causing Urinary Tract Infections
Authors: Rizvi Zuhair Ali , Jamal Ali Murad , Malik Ali Hassan , Ullah Naimat , Arshad Daneyal 
Published: May 2018

ABSTRACTBACKGROUNDUrinary Tract Infections are usually treated with empirical therapy by physicians based on previous knowledge of predictability of causative agents and their antimicrobial susceptibilities.OBJECTIVEThe objective of this study was to determine the frequency of various pathogens causing urinary tract infections and their antimicrobial susceptibility in patients presenting in out-patient department of a tertiary care hospital.MATERIALS AND METHODSThis descriptive cross sectional study was conducted in Out-Patient department of Urology of Benazir Bhutto Hospital during a period of 6 months from January 2017 to June 2017 after ethical approval from institutional research forum of Rawalpindi Medical University. 1000 patients (12 years old or above) that were clinically suspected for urinary tract infections were included in this study. Patients with co-morbidities like diabetes mellitus, renal pathologies, Immunodeficiency disorders, malignancies and congenital urogenital disorders were also excluded. Recipients of corticosteroid therapy or with a history of intake of broad spectrum antibiotics in previous 15 days were also excluded. Modified Kirby-Bauer disc diffusion method was used for determining the antimicrobial resistance against various antimicrobials.RESULTSA total of 530 (53%) isolates were found to be culture positive for E.coli(77.4%),Klebsiella (6.4%), Enterobacter (6.0%), Pseudomonas (3.8%), Staphylococcus saprophyticus (3.4%), Citrobacter (1.1%) and Morganella (0.4%).Antimicrobial resistance against commonly used antimicrobials was alarmingly highCONCLUSIONSurveillance of trends of antimicrobial susceptibility pattern is highly important.
Cellular Adaptive Response and Regulation of HIF after Low Dose Gamma-radiation Exposure
Authors: Gandhi Nitin Motilal 
Published: May 2018

AbstractPurposeCellular damage due to low dose of γ-radiation (≤0.1 Gy) is generally extrapolated from observing the effects at higher doses. These estimations are not accurate. This has led to uncertainties while assessing the radiation risk factors at low doses. Although there are reports on the radiation induced adaptive response, the mechanism of action is not fully elucidated, leading to the uncertainties. One of the outcomes of low dose radiation exposure is believed to be adaptive response. The mechanism of adaptive response is not fully understood. Therefore, the study was undertaken to understand the role of hypoxia inducible factor (HIF) on radiation induced adaptive response.Materials and methodsMCF-7 cells pre-exposed to low dose γ-radiation (0.1 Gy; Priming dose) were exposed to 2 Gy (challenging dose) 8 hrs after the priming dose and studied for the adaptive response. Cell death was measured by MTT assay, and apoptosis was measured by FACS analysis. DNA damage was measures by alkaline comet assay. HIF transcription activity was assayed using transiently transfected plasmid having HIF consensus sequence and luciferase as the reporter gene.ResultsCells when exposed to 0.1 Gy priming dose 8 hrs prior to the higher dose (2 Gy; Challenging dose) results in lower amount of radiation induced damages compared to the cells exposed to 2 Gy alone. Cobalt chloride treatment in place of priming dose also results in the protection to cells when exposed to challenging dose. There was up-regulation of HIF activity when cells were exposed to priming dose, indicating the role of HIF in radiation induced response.ConclusionResults indicate the γ-radiation induced adaptive response. One of the mechanism proposed is up-regulation of HIF after low dose exposure, which protects the cells from damages when they are exposed to challenging dose of 2 Gy radiation dose.
PID1 alters antilipolytic action of insulin and increases lipolysis via Inhibited the activation of AKT/PKA Pathway
Authors: Yin Chunyan , Jin Yan , Liu Yuesheng , Wang Li , Xiao Yanfeng 
Published: May 2018

ABSTRACTPurposeThe aim was to investigate the mechanism for impaired control of lipolysis in obesity by investigating the effect of PID1 on insulin-induced activation of AKT/PKA/HSL pathway and lipolysis.MethodsFirst, PID1 expression was detected in adipose tissue and blood insulin and glycerol levels were measured in high-fat diet-induced obese rats. Next, we examined the effect of different concentrations of insulin on lipolysis and AKT/PKA/HSL pathway in 3T3-L1cells. We also investigated the role of PID1 in regulating AKT/PKA/HSL cascade and lipolysis after insulin treatment and lipofectamine over-expression.ResultsPID1 expression is increased in adipose tissue from HFD rat and positive correlation with insulin levels and lipolysis. In 3T3-L1 adipocytes, we found that antilipolytic effect of insulin is mediated by AKT and AKT activated by insulin can results in phosphorylation of PKA and HSL and suppresses glycerol release. However, over-expression of PID1 counteracts insulin action as indicated by glycerol releaseand reduced level of Akt phosphorylation in accordance with a decrease in the activity of insulin-dependent PKA/HSLsignaling cascade.ConclusionsAll together, these data showed that activation of PID1 in adipose tissue increases lipolysis by altering the antilipolytic action of insulin. This suggests that PID1 may constitute a new strategy to ameliorate adipocyte lipolysis and hence to improve insulin sensitivity.
Human personality reflects spatio-temporal and time-frequency EEG structure
Authors: Runnova Anastasia E. , Maksimenko Vladimir A. , Zhuravlev Maksim O. , Protasov Pavel , Kulanin Roman , Khramova Marina V. , Pisarchik Alexander N. , Khramov Alexander E. 
Published: May 2018

AbstractThe brain controls all physiological processes in the organism and regulates its interaction with the external environment. The way the brain solves mental tasks is determined by individual human features, which are reflected in neuronal network dynamics, and therefore can be detected in neurophysiological data. Every human action is associated with a unique brain activity (motor-related, cognitive, etc.) represented by a specific oscillatory pattern in a multichannel electroencephalogram (EEG). The connection between neurophysiological processes and personal mental characteristics is manifested when using simple psycho-diagnostic tests (Schulte tables) in order to study the attention span. The analysis of spatio-temporal and time-frequency structures of the multichannel EEG using the Schulte tables allows us to divide subjects into three groups depending on their neural activity. The personality multi-factor profile of every participant can be individually described based on both the Sixteen Personality Factor Questionnaire (16PF) and a personal interview with an experienced psychologist. The correlation of the EEG-based personality classification with individual multi-factor profiles provides a possibility to identify human personality by analyzing electrical brain activity. The obtained results are of great interest for testing human personality and creating automatized intelligent programs that employ simple tests and EEG measurements for an objective estimation of human personality features.
Escherichia coliBcteriuria in pregnant women in Ghana: Antibiotic resistance pattern, Virulence Factors and Resistant genetic markers
Authors: Akua Forson Obeng , Bright Wilson , Nana-Adjei David , Quarchie Marjorie Ntiwaa , Obeng-Nkuramah Noah 
Published: May 2018

AbstractThe relevance ofEscherichia coliassociated bacteriuria infection in pregnant women is poorly understood, despite these strains sharing a similar virulence profile with other extra intestinal pathogenicE. coliproducing severe obstetric and neonatal infections. We characterized and determined the antimicrobial susceptibility, resistant genes and virulence profiles of 82E. coliisolates associated with asymptomatic bacteriuria in some pregnant in five very distinct hospitals in the Volta region from January, 2016 to April, 2016 using Kirby-Bauer disc diffusion and polymerase chain reaction.High levels of antimicrobial resistance was observed to Ampicillin (79.3%), Tetracycline (70.7%) and Cotrimoxazole (59.8%), except for Cefuroxime (32.9%). Resistant genes analyses revealed 58.5% were positive forBlaTEMand 14.6% foraph(3)-Ia(aphA2). Virulence factors (VFs) was more widespread in pregnant women in the 2ndand 3rdtrimesters than 1sttrimester. VFs relating to adhesion (papC andiha), Protectins (traT), aerobactin acquisition (iutA) and iron acquisition systems (fyuA andirp2) were more prevalent in the resistantE. coliisolates. This study provides additional evidence for a link in bacteriuria and transmission of extra-intestinalE. coliin pregnant women to cause multi-resistant severe obstetric or neonatal infections. Considering the involvement of extra-intestinalE. coliin infections, our results may be helpful to develop strategies to prevent maternal and/ neonatal infections. In addition continuous surveillance is required to guide appropriate antibiotic usage in pregnant women.
Elucidating the roles of Alzheimer disease-associated proteases and the signal-peptide peptidase-like 3 (SPPL3) in the shedding of glycosyltransferases
Authors: El-Battari Assou , Mathieu Sylvie , Sigaud Romain , Prorok-Hamon Maëlle , Ouafik L’Houcine , Jeanneau Charlotte 
Published: May 2018

ABSTRACTThe Golgi resident glycosyltransferases (GTs) are membrane-bound glycoproteins but are frequently found as soluble proteins in biological fluids where their function remains largely unknown. Previous studies have established that the release of these proteins involved Alzheimer disease-associated proteases such as β-secretases (BACE1 and BACE2) and the intramembrane-cleaving aspartyl proteases Presenilins 1 and 2. Recent studies have involved another intramembrane-cleaving enzyme, the signal peptide peptidese-like-3 (SPPL3). Except for the latter, the two former studies mostly addressed particular cases of GTs, namely ST6Gal-I (BACEs) or GnT-V (Presenilins). Therefore the question still remains as which of these secretases is truly responsible for the cleavage and secretion of GTs. We herein combined the 3 proteases in a single study with respect to their abilities to release 3 families of GTs encompassing three N-acetylglucosaminyltransferases, two fucosyltransferases and two sialyltransferases. Green fluorescent protein (gfp)-fused versions of these GTs were virally transduced in mouse embryonic fibroblasts devoid of BACEs, Presenilins or SPPL3. We found that neither BACE nor Presenilins are involved in the shedding of these glycosyltransferases, while SPPL3 was involved in the cleavage and release of some but not all GTs. Notably, the γ- secretase inhibitor DFK-167 was the only molecule capable of significantly decreasing glycosyltransferase secretion, suggesting the involvement of γ-secretase(s), yet different from Presenilins but comprising SPPL3 among other proteases still to be identified. Using confocal microscopy, we show that SPPL3 selectivity towards GTs relays not only on sequence specificity but also depends on how GTs distribute in the cell with respect SPPL3 during their cycling within and outside the Golgi.
Heterogeneity of Long-History Migration Predicts Smiling, Laughter and Positive Emotion Across the Globe and Within the United States
Authors: Niedenthal Paula M. , Rychlowska Magdalena , Wood Adrienne , Zhao Fangyun 
Published: May 2018

AbstractRecent findings demonstrate that heterogeneity of long-history migration predicts present-day emotion behaviors and norms. Residents of countries characterized by high ancestral diversity display emotion expressions that are easier to decode by observers, endorse norms of higher emotion expressivity, and smile more in response to certain stimuli than residents of countries that lack ancestral diversity. We build on the extant findings and investigate historical heterogeneity as a predictor of daily smiling, laughter, and positive emotion across the world’s countries and the states of the United States. Study 1 finds that historical heterogeneity is positively associated with self-reports of smiling, laughter, and positive emotions in the Gallup World Poll when controlling for GDP and current present-day population diversity. Study 2 extends the findings to effects of long-history migration within the United States. We estimated the average percentage of foreign-born citizens in each state between 1850 and 2010 based on US Census information as an indicator of historical heterogeneity. Consistent with the world findings of Study 1, historical heterogeneity predicted smiling, laughter, and positive, but not negative, emotion. The relationships remained significant when controlling for per capita income and present-day diversity of population of each state. Together, the findings further demonstrate the important role of long-history migration in shaping emotion cultures of countries and states, which persist beyond the original socio-ecological conditions, and open promising avenues for cross-cultural research.
BK channel inhibition by strong extracellular acidification
Authors: Zhou Yu , Xia Xiao-Ming , Lingle Christopher J. 
Published: May 2018

AbstractBK-type voltage- and Ca2+-dependent K+ channels are found in a wide range of cells and intracellular organelles. Among different loci, the composition of the extracellular microenvironment, including pH, may differ substantially. For example, it has been reported that BK channels are expressed in lysosomes with their extracellular side facing the strongly acidified lysosomal lumen (pH ~ 4.5). Here we show that BK activation is strongly and reversibly inhibited by extracellular H+, with its conductance-voltage relationship shifted by more than +100 mV at pHO 4. Our results reveal that this inhibition is mainly caused by H+ inhibition of BK voltage-sensor (VSD) activation through three acidic residues on the extracellular side of BK VSD. Given that these key residues (D133, D147, D153) are highly conserved among members in the voltage-dependent cation channel superfamily, the mechanism underlying BK inhibition by extracellular acidification might also be applicable to other members in the family.
Robust Design for Coalescent Model Inference
Authors: Parag Kris V , Pybus Oliver G 
Published: May 2018

Abstract—The coalescent process describes how changes in the size of a population influence the genealogical patterns of sequences sampled from that population. The estimation of population size changes from genealogies that are reconstructed from these sequence samples, is an important problem in many biological fields. Often, population size is characterised by a piecewise-constant function, with each piece serving as a population size parameter to be estimated. Estimation quality depends on both the statistical coalescent inference method employed, and on the experimental protocol, which controls variables such as the sampling of sequences through time and space, or the transformation of model parameters. While there is an extensive literature devoted to coalescent inference methodology, there is surprisingly little work on experimental design. The research that does exist is largely simulation based, precluding the development of provable or general design theorems. We examine three key design problems: temporal sampling of sequences under the skyline demographic coalescent model, spatio-temporal sampling for the structured coalescent model, and time discretisation for sequentially Markovian coalescent models. In all cases we prove that (i) working in the logarithm of the parameters to be inferred (e.g. population size), and (ii) distributing informative coalescent events uniformly among these log-parameters, is uniquely robust. ‘Robust’ means that the total and maximum uncertainty of our estimates are minimised, and are also insensitive to their unknown (true) parameter values. Given its persistence among models, this formally derived two-point theorem may form the basis of an experimental design paradigm for coalescent inference.
Regulation of trophic architecture across spatial scales in a major river network
Authors: Harvey Eric , Altermatt Florian 
Published: May 2018

AbstractMoving beyond species count data is an essential step to better understand the effects of environmental perturbations on biodiversity and ecosystem functions, and to eventually better predict the strength and direction of those effects. Here, coupling an integrative path analysis approach with data from an extensive countrywide monitoring program, we tested the main spatial, environmental and anthropogenic drivers of change in stream macroinvertebrate trophic structure along the entire Swiss Rhine river catchment. Trophic structure was largely driven by inherent altitudinal variation influencing and cascading to regional scaled factors such as land use change and position in the riverine network, which, in turn, transformed local habitat structure variables. Those cascading effects across scales propagated through the biotic community, first affecting preys and, in turn, predators. Our results illustrate how seemingly less important factors can act as essential transmission belts, propagating through direct and indirect pathways across scales to generate the specific context in which each trophic group will strive or not, leading to characteristic landscape wide variations in trophic community structure.
Tropical forest refuge in peripheral soils of slags in Caatinga
Authors: de Souza José João Lelis Leal , de Souza Bartolomeu Israel , de Queiroz Rubens Teixeira , Lunguinho Rony Lopes , de Medeiros Joseilson Ramos , Cardoso Eini Celly Morais , de Melo e Silva Pedro André , de Oliveira Helder Cavalcante 
Published: May 2018

AbstractThe influence of environmental factors on the structure and composition of plant communities in the Caatinga is complex and poorly explored. Spatial variation of biodiversity in Caatinga is poorly know and strictly attributed to climatic conditions. We investigated the influence of slags on floristic composition and structure of a shrubby-arboreal community in one of the driest region in Brazil. Chemical and physical analyses of soils were performed in samples of seven plots from savannic formations and from forest formations. Vegetation was characterized floristically and structurally in all plots. Habitats were structurally distinct, and diversity differed between peripheral and non-peripheral areas of slags. Nine of the ninety-seven species identified are reported to (sub)humid biomes. Soils are dominantly shallow, eutrophic and sandy loam. However, soils in the periphery of slags are more developed once paludization, melanization and bioturbation were verified. Our results suggest that soil fertility did not influence vegetable cover in Caatinga. The cover of plant species considered exclusive of (sub)humid biomes in Brazil extends beyond highlands in the semiarid, associated with high soil organic carbon content and water retention capacity of more developed soils than the typical of the Caatinga.