bluuebunny/crossref_metadata_2025_split huggingface dataset:
The histone demethylase KDM5 is essential for larval growth inDrosophila
Authors: Drelon Coralie , Belalcazar Helen M. , Secombe Julie 
Published: April 2018

AbstractRegulated gene expression is necessary for developmental and homeostatic processes. The KDM5 family of proteins are histone H3 lysine 4 demethylases that can regulate transcription through both demethylase-dependent and independent mechanisms. While loss and overexpression of KDM5 proteins are linked to intellectual disability and cancer, respectively, their normal developmental functions remain less characterized.Drosophila melanogasterprovides an ideal system to investigate KDM5 function, as it encodes a single ortholog in contrast to the four paralogs found in mammalian cells. To examine the consequences of complete loss of KDM5, we generated a null allele ofDrosophila kdm5, also known aslittle imaginal discs(lid), and show that it is essential for development. Animals lacking KDM5 die during late pupal development but show a dramatically delayed larval development that coincides with decreased proliferation and increased cell death in imaginal discs. Interestingly, this developmental delay is independent of the well-characterized Jumonji C (JmjC) domain-encoded histone demethylase activity and plant homedomain (PHD) motif-mediated chromatin binding activities of KDM5, suggesting key functions for less characterized domains. Consistent with the phenotypes observed, transcriptome analyses ofkdm5null mutant wing imaginal discs revealed the dysregulation of genes involved in several cellular processes, including cell cycle progression and DNA repair. Together, our data provide the first description of complete loss of KDM5 function in a metazoan and offer an invaluable tool for defining the biological activities of KDM5 family proteins.
C. elegansRAP-1 reinforces LET-60/Ras induction of cell fate
Authors: Rasmussen Neal R. , Dickinson Daniel J. , Reiner David J. 
Published: April 2018

AbstractThe notoriety of the small GTPase Ras as the most mutated oncoprotein has led to a well-characterized signaling network largely conserved across metazoans. Yet the role of its close relative Rap1 (Ras Proximal), which shares 100% identity between their core effector binding sequences, remains unclear. A long-standing controversy in the field is whether Rap1 also functions to activate the canonical Ras effector, the S/T kinase Raf. We used the developmentally simplerCaenorhabditis elegans, which lacks the extensive paralog redundancy of vertebrates, to examine the role of RAP-1 in two distinct LET-60/Ras-dependent cell fate patterning events: induction of 1˚ vulval precursor cell (VPC) fate and of the excretory duct cell. Fluorescently tagged endogenous RAP-1 is localized to plasma membranes and is expressed ubiquitously, with even expression levels across the VPCs. RAP-1 and its activating GEF PXF-1 function cell autonomously and are necessary for maximal induction of 1˚ VPCs. Critically, mutationally activated endogenous RAP-1 is sufficient both to induce ectopic 1˚s and duplicate excretory duct cells. Like endogenous RAP-1, before induction GFP expression from thepxf-1promoter is uniform across VPCs. However, unlike endogenous RAP-1, after induction GFP expression is increased in presumptive 1˚s and decreased in presumptive 2˚s. We conclude that RAP-1 is a positive regulator that promotes Ras-dependent inductive fate decisions. We hypothesize that PXF-1 activation of RAP-1 serves as a minor parallel input into the major LET-60/Ras signal through LIN-45/Raf.
Specific miRNA-GPCR networks regulate Sox9a/Sox9b activities to promote gonadal renewal in zebrafish
Authors: Du Xinlu , Guo Huiping , Zhang Ying , Wu Jiacheng , Li Minyou , Hua Xianxian , Yan Jizhou 
Published: April 2018

AbstractFertility and endocrine function rely on a tightly regulated synchronicity within the hypothalamic-pituitary gonadal (HPG) axis. FSH/cAMP/MAPK/ Sox9 axis signaling and its regulated specific miRNAs are thought to regulate vertebrate gonadal development and sex differentiation, and yet the regulatory networks are largely unknown. Here we construct small RNA and mRNA libraries from sexually matured ovary and testis of zebrafish to identify specific miRNA-target pairs. Integration of Targetscan prediction and in vivo induced gene expression highlight four specific miRNAs that conditionally target three G protein–coupled receptor (GPCR) x-Sox9 signaling genes, and implicate two regulatory circuits of miR430a-Sox9a in the testis and miR218a-Sox9b in the ovary. Co-injected Sox9a-miR430a mixture increases the proportion of spermatogonia but degenerates primary oocyte, while Sox9b-miR218a mixture induces renewal of ovarian follicles. Co-immunoprecipitation and mass-spectrometry analyses further reveal that miR430a and Sox9a synergistically activate testicular PKC/Rock1 signals while miR218a and Sox9b constrict ovary PKC/PI3K/Rock1 signaling. These results clarify specific miRNAs-GPCR regulatory networks of Sox9a/Sox9b switch, and also provide mechanistic insight into gonadal rejuvenation and plasticity.
Interferon Alpha and Kinase Inhibitor Nilotinib Increase Cell Adhesion and Tunneling Nanotubes in CML
Authors: Omsland Maria , Andresen Vibeke , Ayuda-Durán Pilar , Gullaksen Stein-Erik , Hovland Randi , Enserink Jorrit , Gjertsen Bjørn Tore 
Published: April 2018

Summary statementThis study describes the effects of tyrosine kinase inhibitors on tunneling nanotube formation via increased adhesion through β-integrin in chronic myeloid leukemia cells.AbstractThe actin-containing cell-to-cell communicator tunneling nanotube (TNT) is involved in regulation of cell death threshold of leukemic cells, while the mechanism of TNT regulation is mostly unknown. We have investigated TNT formation and its response to treatment in chronic myeloid leukemia (CML) cells with the pathognomonic chimeric fusion kinase BCR-ABL1 after treatment with the tyrosine kinase inhibitor nilotinib and interferon-α. Bone marrow cells of chronic phase CML patients and the CML cell line Kcl-22 formed few or no TNTs. Nilotinib and interferon-α treatment induced TNT formation in Kcl-22 cells and were found to be linked to increased adherence to fibronectin coated surfaces by restoration of β1-integrin function. This suggests modulation of TNT cell-cell communication in CML as a novel mechanism in kinase inhibitor therapy of CML.
Heteromeric RNP assembly at LINEs controls lineage-specific RNA processing
Authors: Attig Jan , Agostini Federico , Gooding Clare , Singh Aarti , Chakrabarti Anob M , Haberman Nejc , Emmett Warren , Smith Christopher WJ , Luscombe Nicholas M , Ule Jernej 
Published: April 2018

ABSTRACTIt is challenging for RNA processing machineries to select exons within long intronic regions. We find that intronic LINE repeat sequences (LINEs) contribute to this selection by recruiting dozens of RNA-binding proteins (RBPs). This includes MATR3, which promotes binding of PTBP1 to multivalent binding sites in LINEs. Both RBPs repress splicing and 3’ end processing within and around LINEs, as demonstrated in cultured human cells and mouse brain. Notably, repressive RBPs preferentially bind to evolutionarily young LINEs, which are confined to deep intronic regions. These RBPs insulate both LINEs and surrounding regions from RNA processing. Upon evolutionary divergence, gradual loss of insulation diversifies the roles of LINEs. Older LINEs are located closer to exons, are a common source of tissue-specific exons, and increasingly bind to RBPs that enhance RNA processing. Thus, LINEs are hubs for assembly of repressive RBPs, and contribute to evolution of new, lineage-specific transcripts in mammals.
Multidimensional Scaling and Relatedness Research
Authors: Graffelman Jan , Femenía Iván Galván , de Cid Rafael , Barceló-i-Vidal Carles 
Published: April 2018

AbstractMultidimensional scaling is a well-known multivariate technique, that is often used in genetics for studying population substructure. In this paper we show that multidimensional scaling of marker data is of relevance for relatedness research. Relatedness is usually investigated by estimating and plotting identity-by-state and identity-by-descent allele-sharing statistics. We show that outlying individuals in a map obtained by multidimensional scaling of genetic variables do not necessarily stem from a different human population, but can be the consequence of relatedness. We propose a method for classifying pairs of individuals into the standard relationship categories that combines genetic bootstrapping, multidimensional scaling and discriminant analysis. We validate our method with simulation studies. Given the variant filtering procedures, our method classifies relationships up to and including the fourth degree with high accuracy (96-97%), using only identity by state. The usefulness of the method is illustrated with data from the 1,000 genomes and the GCAT projects.
A high-throughput technique to quantify pathogens’ virulence on the insect model Galleria mellonella
Authors: Parthuisot Nathalie , Rouquette Jacques , Ferdy Jean-Baptiste 
Published: April 2018

AbstractWe combined spectrophotometry and an original statistical approach to infer bacteria virulence, using the lepidoptera Galleria mellonella as a host model. With this method, it is possible to use a microplate reader to automatize data collection on both pathogens multiplication and host survival on batches of 96 samples.
Functional Quantitative Trait Loci (QTL) analysis for adaptive traits in a three-generation Scots pine pedigree
Authors: Calleja-Rodriguez A , Li Z , Hallingbäck H R , Sillanpää M J , Wu H X , Abrahamsson S , García-Gil MR 
Published: April 2018

AbstractIn forest tree breeding, QTL identification aims to accelerate the breeding cycle and increase the genetic gain of traits with economical and ecological value. In our study, both phenotypic data and predicted breeding values were used in the identification QTL linked to the adaptive value in a three-generation pedigree population, for the first time in a conifer species (Pinus sylvestrisL.). A total of 11 470 open pollinated F2-progeny trees established at three different locations, were measured for growth and adaptive traits. Breeding values were predicted for their 360 mothers, originating from a single cross of two parents. A multilevel LASSO association analysis was conducted to detect QTL using genotypes of the mothers with the corresponding phenotypes and estimated breeding values (EBVs). Different levels of genotype-by-environment (G×E) effects among sites and ages were detected for survival and height. Moderate-to-low narrow sense heritabilities and EBVs accuracies were found for all traits and all sites. We identified 18 AFLPs and 12 SNPs to be associated with QTL for one or more traits. 62 QTL were significant with percentages of variance explained ranging from 1.7 to 18.9%, mostly for traits based on phenotypic data. Two SNP-QTL showed pleiotropic effects for traits related with survival, seed and flower production. Furthermore, we detected several QTL with significant effects across multiple ages, which could be considered as strong candidate loci for early selection. The lack of reproducibility of some QTL detected across sites may be due to environmental heterogeneity and QTL-by-environment effects.
CD4+ T cell fate decisions are stochastic, precede cell division, depend on GITR co-stimulation, and are associated with uropodium development
Authors: Cobbold Stephen P. , Adams Elizabeth , Howie Duncan , Waldmann Herman 
Published: April 2018

AbstractDuring an immune response, naïve CD4+ T cells proliferate and generate a range of effector, memory and regulatory T cell subsets, but how these processes are co-ordinated remains unclear. A traditional model suggests that memory cells use mitochondrial respiration and are survivors from a pool of previously proliferating and glycolytic, but short-lived effector cells. A more recent model proposes a binary commitment to either a memory or effector cell lineage during a first, asymmetric cell division, with each lineage able to undergo subsequent proliferation and differentiation. We used improved fixation and staining methods with imaging flow cytometry in an optimised in vitro system that indicates a third model. We found that cell fates result from stochastic decisions that depend on GITR co-stimulation and which take place before any cell division. Effector cell commitment is associated with mTORC2 signalling leading to uropodium development, while developing memory cells lose mitochondria, have a nuclear localization of NFκB and depend on TGFβ for their survival. Induced, T helper subsets and foxp3+ regulatory T cells were found in both the effector and memory cell lineages. This in vitro model of T cell differentiation is well suited to testing how manipulation of cytokine, nutrient other components of the microenvironment might be exploited for therapeutic purposes.
Mitochondria promote neuropeptide secretion inCaenorhabditis elegansby preventing activation of hypoxia inducible factor
Authors: Zhao Tongtong , Kaplan Joshua M 
Published: April 2018

ABSTRACTNeurons are highly dependent on mitochondrial function, and mitochondrial damage has been implicated in many neurological and neurodegenerative diseases. Relatively little is known about how mitochondria regulate neuronal function. Here we show that axonal mitochondria are necessary for neuropeptide secretion inCaenorhabditis elegans, and that oxidative phosphorylation, but not mitochondrial calcium uptake, is required for secretion. Oxidative phosphorylation produces cellular ATP, reactive oxygen species, and consumes oxygen. Disrupting any of these functions could inhibit neuropeptide secretion. We show that blocking mitochondria transport into axons inhibits neuropeptide secretion through activation of the hypoxia inducible factor HIF-1. Our results suggest that axonal mitochondria modulate neuropeptide secretion by regulating transcriptional responses induced by metabolic stress.
Effect of selection on bias and accuracy in genomic prediction of breeding values
Authors: Gowane G. R. , Lee Sang Hong , Clark Sam , Moghaddar Nasir , Al-Mamun Hawlader A , van der Werf Julius H. J. 
Published: April 2018

AbstractReference populations for genomic selection (GS) usually involve highly selected individuals, which may result in biased prediction of estimated genomic breeding values (GEBV). In the present study, bias and accuracy of GEBV were explored for various genetic models and prediction methods when using selected individuals for a reference. Data were simulated for an animal breeding program to compare Best Linear Unbiased Prediction of breeding values using pedigree based relationships (PBLUP), genomic relationships for genotyped animals only (GBLUP) and a Single Step approach (SSGBLUP), where information on genotyped individuals was used to infer a matrix H with relationships among all available genotyped and non-genotyped individuals that were linked through pedigree. In SSGBLUP, various weights (α=0.95, 0.80, 0.50) for the genomic relationship matrix (G) relative to the numerator relationship matrix (A) were applied to construct H and in another version (SSGBLUP_F), inbreeding was accounted for while computing A-1. With GBLUP, accuracy of GEBV prediction increased linearly with an increase in the number of animals selected in reference. For the scenario with no-selection and random mating (RR) prediction was unbiased. For GBLUP, lower accuracy and bias observed in the scenarios with selection and random mating (SR) or selection and positive assortative mating (SA), in which prediction bias increased when a smaller and highly selected proportion genotyped. Bias disappeared when all individuals were genotyped. SSGBLUP_F showed higher accuracy compared to GBLUP and bias of prediction was negligible even with selective genotyping. However, PBLUP and SSGBLUP showed bias in SA owing to not fully accounting for allele frequency changes because of selection of quantitative trait loci (QTL) with larger effects and also due to high inbreeding rate. In genetic models with fewer QTL but each with larger effect, predictions were less accurate and more biased for selection scenarios. Results suggest that prediction accuracy and bias is affected by the genetic architecture of the trait. Selective genotyping lead to significant bias in GEBV prediction. SSGBLUP with appropriate scaling of A and G matrices can provide accurate and less biased prediction but scaling requires careful consideration in populations under selection and with high levels of inbreeding.
Confounding factors in algal phosphorus limitation experiments
Authors: Beck Whitney S. , Hall Ed K. 
Published: April 2018

AbstractAssessing algal nutrient limitation is critical for understanding the interaction of primary production and nutrient cycling in streams, and nutrient diffusing substrate (NDS) experiments are often used to determine limiting nutrients such as nitrogen (N) and phosphorus (P). Unexpectedly, many experiments have also shown decreased algal biomass on NDS P treatments compared to controls. To address whether inhibition of algal growth results from direct P toxicity, NDS preparation artifacts, or environmental covariates, we first quantified the frequency of nutrient inhibition in published experiments. We also conducted a meta-analysis to determine whether heterotrophic microbial competition or selective grazing could explain decreases in algal biomass with P additions. We then deployed field experiments to determine whether P-inhibition of algal growth could be explained by P toxicity, differences in phosphate cation (K vs. Na), differences in phosphate form (monobasic vs. dibasic), or production of H2O2during NDS preparation. We found significant inhibition of algal growth in 12.9% of published NDS P experiments as compared to 4.7% and 3.6% of N and NP experiments. The meta-analysis did not show enhanced heterotrophy on NDS P treatments or selective grazing of P-rich algae. Our field experiments did not show inhibition of autotrophic growth with P additions, but we found significantly lower gross primary productivity (GPP) and biomass-specific GPP of benthic algae on monobasic phosphate salts as compared to dibasic phosphate salts, likely because of reduced pH levels. Additionally, we note that past field experiments and meta-analyses support the plausibility of direct P toxicity or phosphate form (monobasic vs. dibasic) leading to inhibition of algal growth, particularly when other resources such as N or light are limiting. Given that multiple mechanisms may be acting simultaneously, we recommend practical, cost-effective steps to minimize the potential for P-inhibition of algal growth as an artifact of NDS experimental design.
Timeline of engagement research and future research directions
Authors: Kunte Manjiri , Rungruang Parisa 
Published: April 2018

PurposeStudies suggest that engagement is related with organizationally desired outcomes, including performance, productivity, profitability, employee retention, organization citizenship behavior and employee well-being. Despite its practical relevance in the workplace, the concept of engagement has been theoretically dispersed. Therefore, this study aims to present a conceptual review of engagement studies leading to the development of a nomological framework and an evolution timeline for the concept.Design/methodology/approachThe present study is divided into three sections. The first section elicits the nomological framework based on the comparison between engagement, its predecessors and its contemporary concepts such as motivation theories, job design theories, burnout theories and positive psychology. A review of related theories and concepts highlights the similarities and differences vis-a-vis engagement. In the second section, the study depicts the evolution of the engagement concept based on the nomological framework. The evolution is discussed through the decades of before 1990, 1990-2000, 2000-2010 and 2010 onwards. To consolidate the theories and concepts, the authors covered studies that defined engagement as role engagement, personal engagement, work engagement and employee engagement. The third section presents the future research directions based on the framework and evolution.FindingsThe literature review reveals future research directions. These include the addition of new antecedents and theoretical frameworks to enrich the explanatory power and practical relevance of the antecedents of engagement, exploring the context of work with qualitative and mixed method designs, exploring the unit of “role” in engagement studies and the need for more replication studies in this field.Originality/valueThe key contributions of this paper are the nomological framework and the timeline of the evolution of engagement concept.
The association between immunoexpression levels of oxidant and antioxidant enzymes and lip squamous cell carcinoma
Authors: Tseng Hui‐Wen , Tseng Hui‐Hwa , Liou Huei‐Han , Tsai Kuo‐Wang , Ger Luo‐Ping , Shiue Yow‐Ling 
Published: April 2018

The aim of this study was to investigate the associations among the immunoexpression levels of manganese superoxide dismutase (Mn‐SOD), glutathione peroxidase (GPx), and myeloperoxidase (MPO) in lip squamous cell carcinoma (LSCC) tissues and the clinicopathological characteristics, and prognostic factors in patients with LSCC. The immunoexpression levels of Mn‐SOD, GPx, and MPO were examined in 76 LSCC tissue samples using immunohistochemical staining on tissue microarray slides, and compared to those in normal lip mucosa adjacent to venous lakes (normal controls), normal tissue adjacent to corresponding tumors (NTACT), and recurrent tumors. Associations between immunoexpression levels and clinicopathological characteristics were analyzed using the Student's t‐test. The prognostic factors were analyzed using Cox regression. The immunoexpression levels of Mn‐SOD, GPx, and MPO were significantly different among the normal controls, NTACTs, tumors, and recurrent tumors (Mn‐SOD: p = 0.001, GPx: p < 0.001, MPO: p < 0.001). Lower lip cancer was associated with higher Mn‐SOD immunoexpression levels (p = 0.04) and probably indicated higher oxidative stress. Lymph node involvement with a lower immunoexpression level of MPO (p = 0.007) indicated compensatory mechanism to attenuate oxidative damage. A low Mn‐SOD immunoexpression level was borderline significantly associated with a worse prognosis for disease‐specific survival, and it was probably related to a lower capacity for coping with oxidative stress.
Labor pain in women with and without severe fear of childbirth: A population‐based, longitudinal study
Authors: Junge Carolin , von Soest Tilmann , Weidner Kerstin , Seidler Andreas , Eberhard‐Gran Malin , Garthus‐Niegel Susan 
Published: April 2018

AbstractBackgroundThis prospective study aims to investigate whether severe fear of childbirth increases pain perceptions during birth and whether co‐occurring maternal health and birth factors as well as length and weight of the child explain the association.MethodsThe study sample comprised women with a vaginal delivery and was drawn from the Akershus Birth Cohort. Data from the hospital birth's record and questionnaires at weeks 17‐19 and 32 of pregnancy and 8 weeks postpartum were used (n = 1649). Analysis of variance and analysis of covariance were conducted to examine whether ratings of labor pain differed significantly between women with and without severe fear of childbirth and which factors explained the difference.ResultsWomen with severe fear of childbirth experienced significantly more labor pain than women without severe fear of childbirth (P < .01). However, when controlling for symptoms of maternal depression and anxiety, use of epidural/spinal anesthetic or nitrous oxide gas, and menstrual pain, this difference was no longer significant (P = .09).DiscussionAlthough the results show that labor pain is related to multiple physiological and psychological factors in a complex manner, symptoms of maternal depression and anxiety seem to play a central role for the experience of labor pain, and should therefore be focused on by health practitioners.