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Plos Genetics : Glucocorticoid Receptor-dependent Gene Regulatory ...

By: Greg Gibson

Description : While the molecular mechanisms of glucocorticoid regulation of transcription have been studied in detail, the global networks regulated by the glucocorticoid receptor (GR) remain unknown. To address this question, we performed an orthogonal analysis to identify direct targets of the GR. First, we analyzed the expression profile of mouse livers in the presence or absence of exogenous glucocorticoid, resulting in over 1,300 differentially expressed genes. We ...

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Plos Genetics : Mutations in Slc29A3, Encoding an Equilibrative Nu...

By: Marshall S. Horwitz

Description : The histiocytoses are a heterogeneous group of disorders characterised by an excessive number of histiocytes. In most cases the pathophysiology is unclear and treatment is nonspecific. Faisalabad histiocytosis (FHC) (MIM 602782) has been classed as an autosomal recessively inherited form of histiocytosis with similarities to Rosai-Dorfman disease (RDD) (also known as sinus histiocytosis with massive lymphadenopathy (SHML)). To elucidate the molecular basis ...

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Plos Genetics : Sex-specific Signaling in the Blood–brain Barrier ...

By: Claude Desplan

Description : Soluble circulating proteins play an important role in the regulation of mating behavior in Drosophila melanogaster. However, how these factors signal through the blood–brain barrier (bbb) to interact with the sex-specific brain circuits that control courtship is unknown. Here we show that male identity of the blood–brain barrier is necessary and that malespecific factors in the bbb are physiologically required for normal male courtship behavior. Feminizati...

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Plos Genetics : Guidelines for Genome-wide Association Studies, Vo...

By: Gregory S. Barsh
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Plos Genetics : Primary Coenzyme Q Deficiency in Pdss2Mutant Mice ...

By: David Beier

Description : Coenzyme Q (CoQ) is an essential electron carrier in the respiratory chain whose deficiency has been implicated in a wide variety of human mitochondrial disease manifestations. Its multi-step biosynthesis involves production of polyisoprenoid diphosphate in a reaction that requires the enzymes be encoded by PDSS1 and PDSS2. Homozygous mutations in either of these genes, in humans, lead to severe neuromuscular disease, with nephrotic syndrome seen in PDSS2 d...

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Plos Genetics : Rpos Plays a Central Role in the Sos Induction by ...

By: Diarmaid Hughes

Description : Bacteria encounter sub-inhibitory concentrations of antibiotics in various niches, where these low doses play a key role for antibiotic resistance selection. However, the physiological effects of these sub-lethal concentrations and their observed connection to the cellular mechanisms generating genetic diversification are still poorly understood. It is known that, unlike for the model bacterium Escherichia coli, sub-minimal inhibitory concentrations (sub-MI...

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Plos Genetics : a Cholinergic-regulated Circuit Coordinates the Ma...

By: Miriam B. Goodman

Description : Penetration of a male copulatory organ into a suitable mate is a conserved and necessary behavioral step for most terrestrial matings: however, the detailed molecular and cellular mechanisms for this distinct social interaction have not been elucidated in any animal. During mating, the Caenorhabditis elegans male cloaca is maintained over the hermaphrodite’s vulva as he attempts to insert his copulatory spicules. Rhythmic spicule thrusts cease when insertio...

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Plos Genetics : Bmp and Nodal Independently Regulate Lefty1 Expres...

By: Mary C. Mullins

Description : In vertebrates, left-right (LR) axis specification is determined by a ciliated structure in the posterior region of the embryo. Fluid flow in this ciliated structure is responsible for the induction of unilateral left-sided Nodal activity in the lateral plate mesoderm, which in turn regulates organ laterality. Bmp signalling activity has been implied in repressing Nodal expression on the right side, however its mechanism of action has been controversial. In...

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Plos Genetics : Ciliary Beating Recovery in Deficient Human Airway...

By: Nicholas Katsanis

Description : Primary Ciliary Dyskinesia is a heterogeneous genetic disease that is characterized by cilia dysfunction of the epithelial cells lining the respiratory tracts, resulting in recurrent respiratory tract infections. Despite lifelong physiological therapy and antibiotics, the lungs of affected patients are progressively destroyed, leading to respiratory insufficiency. Recessive mutations in Dynein Axonemal Intermediate chain type 1 (DNAI1) gene have been descri...

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Plos Genetics : Learning a Prior on Regulatory Potential from Eqtl...

By: Alan M. Moses

Description : Genome-wide RNA expression data provide a detailed view of an organism’s biological state: hence, a dataset measuring expression variation between genetically diverse individuals (eQTL data) may provide important insights into the genetics of complex traits. However, with data from a relatively small number of individuals, it is difficult to distinguish true causal polymorphisms from the large number of possibilities. The problem is particularly challenging...

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Plos Genetics : a Dominant Mutation in Mediator of Paramutation2, ...

By: Gregory P. Copenhaver

Description : Paramutation involves homologous sequence communication that leads to meiotically heritable transcriptional silencing. We demonstrate that mop2 (mediator of paramutation2), which alters paramutation at multiple loci, encodes a gene similar to Arabidopsis NRPD2/E2, the second-largest subunit of plant-specific RNA polymerases IV and V. In Arabidopsis, Pol-IV and Pol-V play major roles in RNA–mediated silencing and a single second-largest subunit is shared bet...

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Plos Genetics : Bacterial Communities of Diverse Drosophila Specie...

By: Harmit S. Malik

Description : Drosophila melanogaster is emerging as an important model of non-pathogenic host–microbe interactions. The genetic and experimental tractability of Drosophila has led to significant gains in our understanding of animal–microbial symbiosis. However, the full implications of these results cannot be appreciated without the knowledge of the microbial communities associated with natural Drosophila populations. In particular, it is not clear whether laboratory cu...

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Plos Genetics : Assumption-free Estimation of Heritability from Ge...

By: Trudy MacKay

Description : The study of continuously varying, quantitative traits is important in evolutionary biology, agriculture, and medicine. Variation in such traits is attributable to many, possibly interacting, genes whose expression may be sensitive to the environment, which makes their dissection into underlying causative factors difficult. An important population parameter for quantitative traits is heritability, the proportion of total variance that is due to genetic fact...

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Plos Genetics : Tgf-ß Sma, Volume 5

By: Stuart K. Kim

Description : Female reproductive cessation is one of the earliest age-related declines humans experience, occurring in mid-adulthood. Similarly, Caenorhabditis elegans’ reproductive span is short relative to its total life span, with reproduction ceasing about a third into its 15–20 day adulthood. All of the known mutations and treatments that extend C. elegans’ reproductive period also regulate longevity, suggesting that reproductive span is normally linked to life spa...

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Plos Genetics : Myc Oncogene-induced Genomic Instability ; Dna Pal...

By: Hung Y. Fan

Description : Genetic instability plays a key role in the formation of naturally occurring cancer. The formation of long DNA palindromes is a rate-limiting step in gene amplification, a common form of tumor-associated genetic instability. Genome-wide analysis of palindrome formation (GAPF) has detected both extensive palindrome formation and gene amplification, beginning early in tumorigenesis, in an experimental Myc-induced model tumor system in the chicken bursa of Fab...

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Plos Genetics : Gwas of Diabetic Nephropathy ; is the Genie Out of...

By: Greg Gibson
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Plos Genetics : Repeat Associated Non-atg Translation Initiation ;...

By: Gregory P. Copenhaver

Description : Diseases associated with unstable repetitive elements in the DNA, RNA, and amino acids have consistently revealed scientific surprises. Most diseases are caused by expansions of trinucleotide repeats, which ultimately lead to diseases like Huntington’s disease, myotonic dystrophy, fragile X syndrome, and a series of spinocerebellar ataxias. These repeat mutations are dynamic, changing through generations and within an individual, and the repeats can be bi-d...

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Plos Genetics : Specificity of the Stat4Genetic Association for Se...

By: Goncalo Abecasis

Description : Systemic lupus erythematosus (SLE) is a genetically complex disease with heterogeneous clinical manifestations. A polymorphism in the STAT4 gene has recently been established as a risk factor for SLE, but the relationship with specific SLE subphenotypes has not been studied. We studied 137 SNPs in the STAT4 region genotyped in 4 independent SLE case series (total n = 1398) and 2560 healthy controls, along with clinical data for the cases. Using conditional ...

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Plos Genetics : Targeted Induction of Endoplasmic Reticulum Stress...

By: Matthew L. Warman

Description : Pathologies caused by mutations in extracellular matrix proteins are generally considered to result from the synthesis of extracellular matrices that are defective. Mutations in type X collagen cause metaphyseal chondrodysplasia type Schmid (MCDS), a disorder characterised by dwarfism and an expanded growth plate hypertrophic zone. We generated a knock-in mouse model of an MCDS–causing mutation (COL10A1 p.Asn617Lys) to investigate pathogenic mechanisms link...

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Plos Genetics : Tinkering Evolution of Post-transcriptional Rna Re...

By: Jianzhi Zhang

Description : Genome-wide studies of post-transcriptional mRNA regulation in model organisms indicate a ‘‘post-transcriptional RNA regulon’’ model, in which a set of functionally related genes is regulated by mRNA–binding RNAs or proteins. One wellstudied post-transcriptional regulon by Puf3p functions in mitochondrial biogenesis in budding yeast. The evolution of the Puf3p regulon remains unclear because previous studies have shown functional divergence of Puf3p regulon...

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