7,724 results match your criteria PLoS Genetics [Journal]


Anti-inflammatory microRNA-146a protects mice from diet-induced metabolic disease.

PLoS Genet 2019 Feb 15;15(2):e1007970. Epub 2019 Feb 15.

Department of Pathology, University of Utah, Salt Lake City, Utah, United States of America.

Identifying regulatory mechanisms that influence inflammation in metabolic tissues is critical for developing novel metabolic disease treatments. Here, we investigated the role of microRNA-146a (miR-146a) during diet-induced obesity in mice. miR-146a is reduced in obese and type 2 diabetic patients and our results reveal that miR-146a-/- mice fed a high-fat diet (HFD) have exaggerated weight gain, increased adiposity, hepatosteatosis, and dysregulated blood glucose levels compared to wild-type controls. Read More

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http://dx.doi.org/10.1371/journal.pgen.1007970DOI Listing
February 2019

Parental legacy, demography, and admixture influenced the evolution of the two subgenomes of the tetraploid Capsella bursa-pastoris (Brassicaceae).

PLoS Genet 2019 Feb 15;15(2):e1007949. Epub 2019 Feb 15.

Plant Ecology and Evolution, Department of Ecology and Genetics, Evolutionary Biology Centre and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.

Allopolyploidy is generally perceived as a major source of evolutionary novelties and as an instantaneous way to create isolation barriers. However, we do not have a clear understanding of how two subgenomes evolve and interact once they have fused in an allopolyploid species nor how isolated they are from their relatives. Here, we address these questions by analyzing genomic and transcriptomic data of allotetraploid Capsella bursa-pastoris in three differentiated populations, Asia, Europe, and the Middle East. Read More

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http://dx.doi.org/10.1371/journal.pgen.1007949DOI Listing
February 2019

Modular epistasis and the compensatory evolution of gene deletion mutants.

PLoS Genet 2019 Feb 15;15(2):e1007958. Epub 2019 Feb 15.

Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, Massachusetts, United States of America.

Screens for epistatic interactions have long been used to characterize functional relationships corresponding to protein complexes, metabolic pathways, and other functional modules. Although epistasis between adaptive mutations is also common in laboratory evolution experiments, the functional basis for these interactions is less well characterized. Here, we quantify the extent to which gene function (as determined by a genome-wide screen for epistasis among deletion mutants) influences the rate and genetic basis of compensatory adaptation in a set of 37 gene deletion mutants nested within 16 functional modules. Read More

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http://dx.doi.org/10.1371/journal.pgen.1007958DOI Listing
February 2019

An African-specific haplotype in MRGPRX4 is associated with menthol cigarette smoking.

PLoS Genet 2019 Feb 15;15(2):e1007916. Epub 2019 Feb 15.

National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland, United States of America.

In the U.S., more than 80% of African-American smokers use mentholated cigarettes, compared to less than 30% of Caucasian smokers. Read More

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http://dx.plos.org/10.1371/journal.pgen.1007916
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February 2019
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BMP signaling is required for nkx2.3-positive pharyngeal pouch progenitor specification in zebrafish.

PLoS Genet 2019 Feb 14;15(2):e1007996. Epub 2019 Feb 14.

State Key Laboratory of Membrane Biology, Institute of Zoology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing, China.

Pharyngeal pouches, a series of outpocketings that bud from the foregut endoderm, are essential to the formation of craniofacial skeleton as well as several important structures like parathyroid and thymus. However, whether pharyngeal pouch progenitors exist in the developing gut tube remains unknown. Here, taking advantage of cell lineage tracing and transgenic ablation technologies, we identified a population of nkx2. Read More

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http://dx.doi.org/10.1371/journal.pgen.1007996DOI Listing
February 2019

Evolutionary rate covariation analysis of E-cadherin identifies Raskol as a regulator of cell adhesion and actin dynamics in Drosophila.

PLoS Genet 2019 Feb 14;15(2):e1007720. Epub 2019 Feb 14.

Department of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.

The adherens junction couples the actin cytoskeletons of neighboring cells to provide the foundation for multicellular organization. The core of the adherens junction is the cadherin-catenin complex that arose early in the evolution of multicellularity to link actin to intercellular adhesions. Over time, evolutionary pressures have shaped the signaling and mechanical functions of the adherens junction to meet specific developmental and physiological demands. Read More

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http://dx.doi.org/10.1371/journal.pgen.1007720DOI Listing
February 2019

Assessing effects of germline exposure to environmental toxicants by high-throughput screening in C. elegans.

PLoS Genet 2019 Feb 14;15(2):e1007975. Epub 2019 Feb 14.

Department of Genetics, Harvard Medical School, Boston, MA, United States of America.

Chemicals that are highly prevalent in our environment, such as phthalates and pesticides, have been linked to problems associated with reproductive health. However, rapid assessment of their impact on reproductive health and understanding how they cause such deleterious effects, remain challenging due to their fast-growing numbers and the limitations of various current toxicity assessment model systems. Here, we performed a high-throughput screen in C. Read More

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http://dx.doi.org/10.1371/journal.pgen.1007975DOI Listing
February 2019

Emerging RAS superfamily conditions involving GTPase function.

Authors:
Joseph T C Shieh

PLoS Genet 2019 Feb 14;15(2):e1007870. Epub 2019 Feb 14.

Division of Medical Genetics, Department of Pediatrics, Institute for Human Genetics, University of California San Francisco, UCSF Benioff Children's Hospital, San Francisco, California, United States of America.

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http://dx.doi.org/10.1371/journal.pgen.1007870DOI Listing
February 2019

Paternal age at conception effects on offspring telomere length across species-What explains the variability?

PLoS Genet 2019 Feb 14;15(2):e1007946. Epub 2019 Feb 14.

Department of Anthropology, University of Washington, Seattle, Washington, United States of America.

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http://dx.doi.org/10.1371/journal.pgen.1007946DOI Listing
February 2019

Epigenetic inheritance of telomere length in wild birds.

PLoS Genet 2019 Feb 14;15(2):e1007827. Epub 2019 Feb 14.

Groningen Institute for Evolutionary Life Sciences, University of Groningen, Groningen, The Netherlands.

Telomere length (TL) predicts health and survival across taxa. Variation in TL between individuals is thought to be largely of genetic origin, but telomere inheritance is unusual, because zygotes already express a TL phenotype, the TL of the parental gametes. Offspring TL changes with paternal age in many species including humans, presumably through age-related TL changes in sperm, suggesting an epigenetic inheritance mechanism. Read More

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http://dx.doi.org/10.1371/journal.pgen.1007827DOI Listing
February 2019

Sumoylation of DNA-bound transcription factor Sko1 prevents its association with nontarget promoters.

PLoS Genet 2019 Feb 14;15(2):e1007991. Epub 2019 Feb 14.

Department of Biology, York University, Toronto, Ontario, Canada.

Sequence-specific transcription factors (TFs) represent one of the largest groups of proteins that is targeted for SUMO post-translational modification, in both yeast and humans. SUMO modification can have diverse effects, but recent studies showed that sumoylation reduces the interaction of multiple TFs with DNA in living cells. Whether this relates to a general role for sumoylation in TF binding site selection, however, has not been fully explored because few genome-wide studies aimed at studying such a role have been reported. Read More

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http://dx.doi.org/10.1371/journal.pgen.1007991DOI Listing
February 2019

Evolution as a guide for experimental cell biology.

PLoS Genet 2019 Feb 14;15(2):e1007937. Epub 2019 Feb 14.

Department of Biological Sciences, University of Denver, Denver, Colorado, United States of America.

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http://dx.doi.org/10.1371/journal.pgen.1007937DOI Listing
February 2019

The Wilms' tumor suppressor gene regulates pancreas homeostasis and repair.

PLoS Genet 2019 Feb 14;15(2):e1007971. Epub 2019 Feb 14.

Department of Animal Biology, Faculty of Science, University of Málaga, Málaga, Spain.

The Wilms' tumor suppressor gene (Wt1) encodes a zinc finger transcription factor that plays an essential role in the development of kidneys, gonads, spleen, adrenals and heart. Recent findings suggest that WT1 could also be playing physiological roles in adults. Systemic deletion of WT1 in mice provokes a severe deterioration of the exocrine pancreas, with mesothelial disruption, E-cadherin downregulation, disorganization of acinar architecture and accumulation of ascitic transudate. Read More

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http://dx.doi.org/10.1371/journal.pgen.1007971DOI Listing
February 2019

Spatio-temporal regulation of nuclear division by Aurora B kinase Ipl1 in Cryptococcus neoformans.

PLoS Genet 2019 Feb 14;15(2):e1007959. Epub 2019 Feb 14.

Molecular Mycology Laboratory, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bangalore, India.

The nuclear division takes place in the daughter cell in the basidiomycetous budding yeast Cryptococcus neoformans. Unclustered kinetochores gradually cluster and the nucleus moves to the daughter bud as cells enter mitosis. Here, we show that the evolutionarily conserved Aurora B kinase Ipl1 localizes to the nucleus upon the breakdown of the nuclear envelope during mitosis in C. Read More

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http://dx.plos.org/10.1371/journal.pgen.1007959
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February 2019
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Maternal and zygotic gene regulatory effects of endogenous RNAi pathways.

PLoS Genet 2019 Feb 13;15(2):e1007784. Epub 2019 Feb 13.

Biology of Non-coding RNA Group, Institute of Molecular Biology, Ackermannweg 4, Mainz, Germany.

Endogenous small RNAs (sRNAs) and Argonaute proteins are ubiquitous regulators of gene expression in germline and somatic tissues. sRNA-Argonaute complexes are often expressed in gametes and are consequently inherited by the next generation upon fertilization. In Caenorhabditis elegans, 26G-RNAs are primary endogenous sRNAs that trigger the expression of downstream secondary sRNAs. Read More

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http://dx.doi.org/10.1371/journal.pgen.1007784DOI Listing
February 2019

A systematic genetic screen identifies essential factors involved in nuclear size control.

PLoS Genet 2019 Feb 13;15(2):e1007929. Epub 2019 Feb 13.

Cell Cycle Laboratory, The Francis Crick Institute, London, United Kingdom.

Nuclear size correlates with cell size, but the mechanism by which this scaling is achieved is not known. Here we screen fission yeast gene deletion mutants to identify essential factors involved in this process. Our screen has identified 25 essential factors that alter nuclear size, and our analysis has implicated RNA processing and LINC complexes in nuclear size control. Read More

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http://dx.doi.org/10.1371/journal.pgen.1007929DOI Listing
February 2019

Stress response, behavior, and development are shaped by transposable element-induced mutations in Drosophila.

PLoS Genet 2019 Feb 12;15(2):e1007900. Epub 2019 Feb 12.

Institute of Evolutionary Biology (IBE), CSIC-Universitat Pompeu Fabra, Barcelona, Spain.

Most of the current knowledge on the genetic basis of adaptive evolution is based on the analysis of single nucleotide polymorphisms (SNPs). Despite increasing evidence for their causal role, the contribution of structural variants to adaptive evolution remains largely unexplored. In this work, we analyzed the population frequencies of 1,615 Transposable Element (TE) insertions annotated in the reference genome of Drosophila melanogaster, in 91 samples from 60 worldwide natural populations. Read More

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http://dx.doi.org/10.1371/journal.pgen.1007900DOI Listing
February 2019

A genome-wide association study reveals a novel regulator of ovule number and fertility in Arabidopsis thaliana.

PLoS Genet 2019 Feb 11;15(2):e1007934. Epub 2019 Feb 11.

Department of Botany and Plant Pathology, Purdue University, West Lafayette, Indiana United States of America.

Ovules contain the female gametophytes which are fertilized during pollination to initiate seed development. Thus, the number of ovules that are produced during flower development is an important determinant of seed crop yield and plant fitness. Mutants with pleiotropic effects on development often alter the number of ovules, but specific regulators of ovule number have been difficult to identify in traditional mutant screens. Read More

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http://dx.doi.org/10.1371/journal.pgen.1007934DOI Listing
February 2019

The CIN-TCP transcription factors promote commitment to differentiation in Arabidopsis leaf pavement cells via both auxin-dependent and independent pathways.

PLoS Genet 2019 Feb 11;15(2):e1007988. Epub 2019 Feb 11.

Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, India.

Cells in organ primordia undergo active proliferation at an early stage to generate sufficient number, before exiting proliferation and entering differentiation. However, how the actively proliferating cells are developmentally reprogrammed to acquire differentiation potential during organ maturation is unclear. Here, we induced a microRNA-resistant form of TCP4 at various developmental stages of Arabidopsis leaf primordium that lacked the activity of TCP4 and its homologues and followed its effect on growth kinematics. Read More

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http://dx.doi.org/10.1371/journal.pgen.1007988DOI Listing
February 2019

Mitochondrial proline catabolism activates Ras1/cAMP/PKA-induced filamentation in Candida albicans.

PLoS Genet 2019 Feb 11;15(2):e1007976. Epub 2019 Feb 11.

Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.

Amino acids are among the earliest identified inducers of yeast-to-hyphal transitions in Candida albicans, an opportunistic fungal pathogen of humans. Here, we show that the morphogenic amino acids arginine, ornithine and proline are internalized and metabolized in mitochondria via a PUT1- and PUT2-dependent pathway that results in enhanced ATP production. Elevated ATP levels correlate with Ras1/cAMP/PKA pathway activation and Efg1-induced gene expression. Read More

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http://dx.plos.org/10.1371/journal.pgen.1007976
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February 2019
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Broad antifungal resistance mediated by RNAi-dependent epimutation in the basal human fungal pathogen Mucor circinelloides.

PLoS Genet 2019 Feb 11;15(2):e1007957. Epub 2019 Feb 11.

Department of Molecular Genetics and Microbiology, Duke University, Duke University Medical Center, Durham, North Carolina, United States of America.

Mucormycosis-an emergent, deadly fungal infection-is difficult to treat, in part because the causative species demonstrate broad clinical antifungal resistance. However, the mechanisms underlying drug resistance in these infections remain poorly understood. Our previous work demonstrated that one major agent of mucormycosis, Mucor circinelloides, can develop resistance to the antifungal agents FK506 and rapamycin through a novel, transient RNA interference-dependent mechanism known as epimutation. Read More

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http://dx.doi.org/10.1371/journal.pgen.1007957DOI Listing
February 2019

Spatial soft sweeps: Patterns of adaptation in populations with long-range dispersal.

PLoS Genet 2019 Feb 11;15(2):e1007936. Epub 2019 Feb 11.

Department of Physics, University of California, Berkeley, Berkeley, California, United States of America.

Adaptation in extended populations often occurs through multiple independent mutations responding in parallel to a common selection pressure. As the mutations spread concurrently through the population, they leave behind characteristic patterns of polymorphism near selected loci-so-called soft sweeps-which remain visible after adaptation is complete. These patterns are well-understood in two limits of the spreading dynamics of beneficial mutations: the panmictic case with complete absence of spatial structure, and spreading via short-ranged or diffusive dispersal events, which tessellates space into distinct compact regions each descended from a unique mutation. Read More

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http://dx.doi.org/10.1371/journal.pgen.1007936DOI Listing
February 2019

The AGC protein kinase UNICORN controls planar growth by attenuating PDK1 in Arabidopsis thaliana.

PLoS Genet 2019 Feb 11;15(2):e1007927. Epub 2019 Feb 11.

Entwicklungsbiologie der Pflanzen, Wissenschaftszentrum Weihenstephan, Technische Universität München, Freising, Germany.

Tissue morphogenesis critically depends on the coordination of cellular growth patterns. In plants, many organs consist of clonally distinct cell layers, such as the epidermis, whose cells undergo divisions that are oriented along the plane of the layer. The developmental control of such planar growth is poorly understood. Read More

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http://dx.doi.org/10.1371/journal.pgen.1007927DOI Listing
February 2019

mRNA dynamics and alternative conformations adopted under low and high arginine concentrations control polyamine biosynthesis in Salmonella.

PLoS Genet 2019 Feb 11;15(2):e1007646. Epub 2019 Feb 11.

Department of Microbiology and Molecular Genetics, IMRIC, The Hebrew University-Hadassah Medical School, Jerusalem, Israel.

Putrescine belongs to the large group of polyamines, an essential class of metabolites that exists throughout all kingdoms of life. The Salmonella speF gene encodes an inducible ornithine decarboxylase that produces putrescine from ornithine. Putrescine can be also synthesized from arginine in a parallel metabolic pathway. Read More

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http://dx.doi.org/10.1371/journal.pgen.1007646DOI Listing
February 2019

Tissue- and sex-specific small RNAomes reveal sex differences in response to the environment.

PLoS Genet 2019 Feb 8;15(2):e1007905. Epub 2019 Feb 8.

Department of Ecology and Evolution, University of Lausanne, Lausanne, Switzerland.

RNA interference (RNAi) related pathways are essential for germline development and fertility in metazoa and can contribute to inter- and trans-generational inheritance. In the nematode Caenorhabditis elegans, environmental double-stranded RNA provided by feeding can lead to heritable changes in phenotype and gene expression. Notably, transmission efficiency differs between the male and female germline, yet the underlying mechanisms remain elusive. Read More

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http://dx.doi.org/10.1371/journal.pgen.1007905DOI Listing
February 2019

Comprehensive structural variation genome map of individuals carrying complex chromosomal rearrangements.

PLoS Genet 2019 Feb 8;15(2):e1007858. Epub 2019 Feb 8.

Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.

Complex chromosomal rearrangements (CCRs) are rearrangements involving more than two chromosomes or more than two breakpoints. Whole genome sequencing (WGS) allows for outstanding high resolution characterization on the nucleotide level in unique sequences of such rearrangements, but problems remain for mapping breakpoints in repetitive regions of the genome, which are known to be prone to rearrangements. Hence, multiple complementary WGS experiments are sometimes needed to solve the structures of CCRs. Read More

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http://dx.doi.org/10.1371/journal.pgen.1007858DOI Listing
February 2019

Dual role of DMXL2 in olfactory information transmission and the first wave of spermatogenesis.

PLoS Genet 2019 Feb 8;15(2):e1007909. Epub 2019 Feb 8.

UMR BDR, INRA, ENVA, Université Paris Saclay, Jouy-en-Josas, France.

Gonad differentiation is a crucial step conditioning the future fertility of individuals and most of the master genes involved in this process have been investigated in detail. However, transcriptomic analyses of developing gonads from different animal models have revealed that hundreds of genes present sexually dimorphic expression patterns. DMXL2 was one of these genes and its function in mammalian gonads was unknown. Read More

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http://dx.doi.org/10.1371/journal.pgen.1007909DOI Listing
February 2019

Rescue of collapsed replication forks is dependent on NSMCE2 to prevent mitotic DNA damage.

PLoS Genet 2019 Feb 8;15(2):e1007942. Epub 2019 Feb 8.

Department of Cellular and Molecular Medicine, University of Arizona, Tucson, Arizona, United States of America.

NSMCE2 is an E3 SUMO ligase and a subunit of the SMC5/6 complex that associates with the replication fork and protects against genomic instability. Here, we study the fate of collapsed replication forks generated by prolonged hydroxyurea treatment in human NSMCE2-deficient cells. Double strand breaks accumulate during rescue by converging forks in normal cells but not in NSMCE2-deficient cells. Read More

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http://dx.doi.org/10.1371/journal.pgen.1007942DOI Listing
February 2019

Marine environmental DNA biomonitoring reveals seasonal patterns in biodiversity and identifies ecosystem responses to anomalous climatic events.

PLoS Genet 2019 Feb 8;15(2):e1007943. Epub 2019 Feb 8.

Trace and Environmental DNA (TrEnD) Laboratory, School of Molecular and Life Sciences, Curtin University, Bentley, Western Australia.

Marine ecosystems are changing rapidly as the oceans warm and become more acidic. The physical factors and the changes to ocean chemistry that they drive can all be measured with great precision. Changes in the biological composition of communities in different ocean regions are far more challenging to measure because most biological monitoring methods focus on a limited taxonomic or size range. Read More

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http://dx.plos.org/10.1371/journal.pgen.1007943
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February 2019
2 Reads

Fast and flexible linear mixed models for genome-wide genetics.

PLoS Genet 2019 Feb 8;15(2):e1007978. Epub 2019 Feb 8.

Department of Biostatistics, Brown University, Providence, Rhode Island, United States of America.

Linear mixed effect models are powerful tools used to account for population structure in genome-wide association studies (GWASs) and estimate the genetic architecture of complex traits. However, fully-specified models are computationally demanding and common simplifications often lead to reduced power or biased inference. We describe Grid-LMM (https://github. Read More

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http://dx.doi.org/10.1371/journal.pgen.1007978DOI Listing
February 2019
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A genetic variant associated with multiple sclerosis inversely affects the expression of CD58 and microRNA-548ac from the same gene.

PLoS Genet 2019 Feb 7;15(2):e1007961. Epub 2019 Feb 7.

University of Rostock, Department of Neurology, Division of Neuroimmunology, Rostock, Germany.

Genome-wide association studies have identified more than 200 genetic variants to be associated with an increased risk of developing multiple sclerosis (MS). Still, little is known about the causal molecular mechanisms that underlie the genetic contribution to disease susceptibility. In this study, we investigated the role of the single-nucleotide polymorphism (SNP) rs1414273, which is located within the microRNA-548ac stem-loop sequence in the first intron of the CD58 gene. Read More

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http://dx.plos.org/10.1371/journal.pgen.1007961
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February 2019
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The Drosophila fussel gene is required for bitter gustatory neuron differentiation acting within an Rpd3 dependent chromatin modifying complex.

PLoS Genet 2019 Feb 7;15(2):e1007940. Epub 2019 Feb 7.

Department of Developmental Biology, Institute of Zoology, University of Regensburg, Regensburg, Bavaria, Germany.

Members of the Ski/Sno protein family are classified as proto-oncogenes and act as negative regulators of the TGF-ß/BMP-pathways in vertebrates and invertebrates. A newly identified member of this protein family is fussel (fuss), the Drosophila homologue of the human functional Smad suppressing elements (fussel-15 and fussel-18). We and others have shown that Fuss interacts with SMAD4 and that overexpression leads to a strong inhibition of Dpp signaling. Read More

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http://dx.doi.org/10.1371/journal.pgen.1007940DOI Listing
February 2019
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Subunits of the mechano-electrical transduction channel, Tmc1/2b, require Tmie to localize in zebrafish sensory hair cells.

PLoS Genet 2019 Feb 6;15(2):e1007635. Epub 2019 Feb 6.

Oregon Hearing Research Center and Vollum Institute, Oregon Health & Science University, Portland, Oregon, United States of America.

Mutations in transmembrane inner ear (TMIE) cause deafness in humans; previous studies suggest involvement in the mechano-electrical transduction (MET) complex in sensory hair cells, but TMIE's precise role is unclear. In tmie zebrafish mutants, we observed that GFP-tagged Tmc1 and Tmc2b, which are subunits of the MET channel, fail to target to the hair bundle. In contrast, overexpression of Tmie strongly enhances the targeting of Tmc1-GFP and Tmc2b-GFP to stereocilia. Read More

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http://dx.doi.org/10.1371/journal.pgen.1007635DOI Listing
February 2019

Genes encoding SATB2-interacting proteins in adult cerebral cortex contribute to human cognitive ability.

PLoS Genet 2019 Feb 6;15(2):e1007890. Epub 2019 Feb 6.

Institute for Neuroscience, Medical University of Innsbruck, Innsbruck, Austria.

During CNS development, the nuclear protein SATB2 is expressed in superficial cortical layers and determines projection neuron identity. In the adult CNS, SATB2 is expressed in pyramidal neurons of all cortical layers and is a regulator of synaptic plasticity and long-term memory. Common variation in SATB2 locus confers risk of schizophrenia, whereas rare, de novo structural and single nucleotide variants cause severe intellectual disability and absent or limited speech. Read More

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http://dx.doi.org/10.1371/journal.pgen.1007890DOI Listing
February 2019

Nr2f-dependent allocation of ventricular cardiomyocyte and pharyngeal muscle progenitors.

PLoS Genet 2019 Feb 5;15(2):e1007962. Epub 2019 Feb 5.

Division of Molecular Cardiovascular Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States of America.

Multiple syndromes share congenital heart and craniofacial muscle defects, indicating there is an intimate relationship between the adjacent cardiac and pharyngeal muscle (PM) progenitor fields. However, mechanisms that direct antagonistic lineage decisions of the cardiac and PM progenitors within the anterior mesoderm of vertebrates are not understood. Here, we identify that retinoic acid (RA) signaling directly promotes the expression of the transcription factor Nr2f1a within the anterior lateral plate mesoderm. Read More

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http://dx.doi.org/10.1371/journal.pgen.1007962DOI Listing
February 2019

Dual functions for the ssDNA-binding protein RPA in meiotic recombination.

PLoS Genet 2019 Feb 4;15(2):e1007952. Epub 2019 Feb 4.

Department of Biomedical Sciences, University of Pennsylvania School of Veterinary Medicine, Philadelphia, Pennsylvania, United States of America.

Meiotic recombination permits exchange of genetic material between homologous chromosomes. The replication protein A (RPA) complex, the predominant ssDNA-binding complex, is required for nearly all aspects of DNA metabolism, but its role in mammalian meiotic recombination remains unknown due to the embryonic lethality of RPA mutant mice. RPA is a heterotrimer of RPA1, RPA2, and RPA3. Read More

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http://dx.doi.org/10.1371/journal.pgen.1007952DOI Listing
February 2019

Conformational regulation of Escherichia coli DNA polymerase V by RecA and ATP.

PLoS Genet 2019 Feb 4;15(2):e1007956. Epub 2019 Feb 4.

Department of Biological Sciences, University of Southern California, Los Angeles, California, United States of America.

Mutagenic translesion DNA polymerase V (UmuD'2C) is induced as part of the DNA damage-induced SOS response in Escherichia coli, and is subjected to multiple levels of regulation. The UmuC subunit is sequestered on the cell membrane (spatial regulation) and enters the cytosol after forming a UmuD'2C complex, ~ 45 min post-SOS induction (temporal regulation). However, DNA binding and synthesis cannot occur until pol V interacts with a RecA nucleoprotein filament (RecA*) and ATP to form a mutasome complex, pol V Mut = UmuD'2C-RecA-ATP. Read More

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http://dx.plos.org/10.1371/journal.pgen.1007956
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February 2019
4 Reads

Strand break-induced replication fork collapse leads to C-circles, C-overhangs and telomeric recombination.

PLoS Genet 2019 Feb 4;15(2):e1007925. Epub 2019 Feb 4.

MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, P. R. China.

Telomerase-independent ALT (alternative lengthening of telomeres) cells are characterized by high frequency of telomeric homologous recombination (HR), C-rich extrachromosomal circles (C-circles) and C-rich terminal 5' overhangs (C-overhangs). However, underlying mechanism is poorly understood. Here, we show that both C-circle and C-overhang form when replication fork collapse is induced by strand break at telomeres. Read More

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http://dx.plos.org/10.1371/journal.pgen.1007925
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February 2019
5 Reads

Genomic insights into neonicotinoid sensitivity in the solitary bee Osmia bicornis.

PLoS Genet 2019 Feb 4;15(2):e1007903. Epub 2019 Feb 4.

College of Life and Environmental Sciences, Biosciences, University of Exeter, Penryn Campus, Penryn, Cornwall, United Kingdom.

The impact of pesticides on the health of bee pollinators is determined in part by the capacity of bee detoxification systems to convert these compounds to less toxic forms. For example, recent work has shown that cytochrome P450s of the CYP9Q subfamily are critically important in defining the sensitivity of honey bees and bumblebees to pesticides, including neonicotinoid insecticides. However, it is currently unclear if solitary bees have functional equivalents of these enzymes with potentially serious implications in relation to their capacity to metabolise certain insecticides. Read More

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http://dx.doi.org/10.1371/journal.pgen.1007903DOI Listing
February 2019
2 Reads

A specialized MreB-dependent cell wall biosynthetic complex mediates the formation of stalk-specific peptidoglycan in Caulobacter crescentus.

PLoS Genet 2019 Feb 1;15(2):e1007897. Epub 2019 Feb 1.

Faculty of Biology, Philipps-Universität, Marburg, Germany.

Many bacteria have complex cell shapes, but the mechanisms producing their distinctive morphologies are still poorly understood. Caulobacter crescentus, for instance, exhibits a stalk-like extension that carries an adhesive holdfast mediating surface attachment. This structure forms through zonal peptidoglycan biosynthesis at the old cell pole and elongates extensively under phosphate-limiting conditions. Read More

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February 2019

Mammalian Hbs1L deficiency causes congenital anomalies and developmental delay associated with Pelota depletion and 80S monosome accumulation.

PLoS Genet 2019 Feb 1;15(2):e1007917. Epub 2019 Feb 1.

Division of Newborn Medicine, Boston Children's Hospital, Boston, Massachusetts, United States of America.

Hbs1 has been established as a central component of the cell's translational quality control pathways in both yeast and prokaryotic models; however, the functional characteristics of its human ortholog (Hbs1L) have not been well-defined. We recently reported a novel human phenotype resulting from a mutation in the critical coding region of the HBS1L gene characterized by facial dysmorphism, severe growth restriction, axial hypotonia, global developmental delay and retinal pigmentary deposits. Here we further characterize downstream effects of the human HBS1L mutation. Read More

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February 2019

Transcription-driven chromatin repression of Intragenic transcription start sites.

PLoS Genet 2019 Feb 1;15(2):e1007969. Epub 2019 Feb 1.

University of Copenhagen, Department of Plant and Environmental Sciences, Copenhagen Plant Science Centre, Frederiksberg, Denmark.

Progression of RNA polymerase II (RNAPII) transcription relies on the appropriately positioned activities of elongation factors. The resulting profile of factors and chromatin signatures along transcription units provides a "positional information system" for transcribing RNAPII. Here, we investigate a chromatin-based mechanism that suppresses intragenic initiation of RNAPII transcription. Read More

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February 2019
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Molecular predictors of brain metastasis-related microRNAs in lung adenocarcinoma.

PLoS Genet 2019 Feb 1;15(2):e1007888. Epub 2019 Feb 1.

Department of Radiation Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Brain metastasis (BM) is a major complication of lung adenocarcinoma (LAD). An investigation of the pathogenic mechanisms of BM, as well as the identification of appropriate molecular markers, is necessary. The aim of this study was to determine the expression patterns of microRNAs (miRNAs) in LAD with BM, and to investigate the biological role of these miRNAs during tumorigenesis. Read More

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February 2019

Global survey of mobile DNA horizontal transfer in arthropods reveals Lepidoptera as a prime hotspot.

PLoS Genet 2019 Feb 1;15(2):e1007965. Epub 2019 Feb 1.

Laboratoire de Biométrie et Biologie Evolutive, Université Lyon 1, CNRS, UMR 5558, Villeurbanne, France.

More than any other genome components, Transposable Elements (TEs) have the capacity to move across species barriers through Horizontal Transfer (HT), with substantial evolutionary consequences. Previous large-scale surveys, based on full-genomes comparisons, have revealed the transposition mode as an important predictor of HT rates variation across TE superfamilies. However, host biology could represent another major explanatory factor, one that needs to be investigated through extensive taxonomic sampling. Read More

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February 2019

Searching for the causal effects of body mass index in over 300 000 participants in UK Biobank, using Mendelian randomization.

PLoS Genet 2019 Feb 1;15(2):e1007951. Epub 2019 Feb 1.

MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, United Kingdom.

Mendelian randomization (MR) has been used to estimate the causal effect of body mass index (BMI) on particular traits thought to be affected by BMI. However, BMI may also be a modifiable, causal risk factor for outcomes where there is no prior reason to suggest that a causal effect exists. We performed a MR phenome-wide association study (MR-pheWAS) to search for the causal effects of BMI in UK Biobank (n = 334 968), using the PHESANT open-source phenome scan tool. Read More

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February 2019
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O-GlcNAcylation of PERIOD regulates its interaction with CLOCK and timing of circadian transcriptional repression.

PLoS Genet 2019 Jan 31;15(1):e1007953. Epub 2019 Jan 31.

Department of Entomology and Nematology, College of Agricultural and Environmental Sciences, University of California, Davis, Davis, CA, United States of America.

Circadian clocks coordinate time-of-day-specific metabolic and physiological processes to maximize organismal performance and fitness. In addition to light and temperature, which are regarded as strong zeitgebers for circadian clock entrainment, metabolic input has now emerged as an important signal for clock entrainment and modulation. Circadian clock proteins have been identified to be substrates of O-GlcNAcylation, a nutrient sensitive post-translational modification (PTM), and the interplay between clock protein O-GlcNAcylation and other PTMs is now recognized as an important mechanism by which metabolic input regulates circadian physiology. Read More

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January 2019

Exposure of Candida albicans β (1,3)-glucan is promoted by activation of the Cek1 pathway.

PLoS Genet 2019 Jan 31;15(1):e1007892. Epub 2019 Jan 31.

Department of Microbiology, University of Tennessee, Knoxville, TN, United States of America.

Candida albicans is among the most common causes of human fungal infections and is an important source of mortality. C. albicans is able to diminish its detection by innate immune cells through masking of β (1,3)-glucan in the inner cell wall with an outer layer of heavily glycosylated mannoproteins (mannan). Read More

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January 2019
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Early girl is a novel component of the Fat signaling pathway.

PLoS Genet 2019 Jan 30;15(1):e1007955. Epub 2019 Jan 30.

Waksman Institute and Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, New Jersey.

The Drosophila protocadherins Dachsous and Fat regulate growth and tissue polarity by modulating the levels, membrane localization and polarity of the atypical myosin Dachs. Localization to the apical junctional membrane is critical for Dachs function, and the adapter protein Vamana/Dlish and palmitoyl transferase Approximated are required for Dachs membrane localization. However, how Dachs levels are regulated is poorly understood. Read More

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January 2019