The tau tubulin kinases TTBK1/2 promote accumulation of pathological TDP-43.

abstract：:Heterozygous mutations in the PRPF31 gene cause autosomal dominant retinitis pigmentosa (adRP), a hereditary disorder leading to progressive blindness. In some cases, such mutations display incomplete penetrance, implying that certain carriers develop retinal degeneration while others have no symptoms at all. Asymptom...

journal_title：PLoS genetics

authors： Venturini G,Rose AM,Shah AZ,Bhattacharya SS,Rivolta C

更新日期：2012-01-01 00:00:00

abstract：:Endoplasmic reticulum (ER) stress occurs when misfolded proteins accumulate in the ER. The cellular response to ER stress involves complex transcriptional and translational changes, important to the survival of the cell. ER stress is a primary cause and a modifier of many human diseases. A first step to understanding ...

journal_title：PLoS genetics

authors： Chow CY,Wang X,Riccardi D,Wolfner MF,Clark AG

更新日期：2015-02-04 00:00:00

abstract：:Obesity is defined by excessive lipid accumulation. However, the active mechanistic roles that lipids play in its progression are not understood. Accumulation of ceramide, the metabolic hub of sphingolipid metabolism, has been associated with metabolic syndrome and obesity in humans and model systems. Here, we use Dro...

journal_title：PLoS genetics

authors： Walls SM Jr,Attle SJ,Brulte GB,Walls ML,Finley KD,Chatfield DA,Herr DR,Harris GL

更新日期：2013-01-01 00:00:00

abstract：:Rare individuals with inactivating mutations in the Huntington's disease gene (HTT) exhibit variable abnormalities that imply essential HTT roles during organ development. Here we report phenotypes produced when increasingly severe hypomorphic mutations in the murine HTT orthologue Htt, (HdhneoQ20, HdhneoQ50, HdhneoQ1...

journal_title：PLoS genetics

authors： Murthy V,Tebaldi T,Yoshida T,Erdin S,Calzonetti T,Vijayvargia R,Tripathi T,Kerschbamer E,Seong IS,Quattrone A,Talkowski ME,Gusella JF,Georgopoulos K,MacDonald ME,Biagioli M

更新日期：2019-03-21 00:00:00

abstract：:MicroRNAs (miRNAs) play important roles in normal cellular differentiation and oncogenesis. microRNA93 (mir-93), a member of the mir106b-25 cluster, located in intron 13 of the MCM7 gene, although frequently overexpressed in human malignancies may also function as a tumor suppressor gene. Using a series of breast canc...

journal_title：PLoS genetics

authors： Liu S,Patel SH,Ginestier C,Ibarra I,Martin-Trevino R,Bai S,McDermott SP,Shang L,Ke J,Ou SJ,Heath A,Zhang KJ,Korkaya H,Clouthier SG,Charafe-Jauffret E,Birnbaum D,Hannon GJ,Wicha MS

更新日期：2012-01-01 00:00:00

abstract：:Most genetic variants associated with disease occur within regulatory regions of the genome, underscoring the importance of defining the mechanisms underlying differences in regulation of gene expression between individuals. We discovered a pair of co-regulated, divergently oriented transcripts, AQY2 and ncFRE6, that ...

journal_title：PLoS genetics

authors： Read T,Richmond PA,Dowell RD

更新日期：2016-01-11 00:00:00

abstract：:For many decades, Salmonella enterica has been subdivided by serological properties into serovars or further subdivided for epidemiological tracing by a variety of diagnostic tests with higher resolution. Recently, it has been proposed that so-called eBurst groups (eBGs) based on the alleles of seven housekeeping gene...

journal_title：PLoS genetics

authors： Alikhan NF,Zhou Z,Sergeant MJ,Achtman M

更新日期：2018-04-05 00:00:00

abstract：:In metazoan germlines, the piRNA pathway acts as a genomic immune system, employing small RNA-mediated silencing to defend host DNA from the harmful effects of transposable elements (TEs). Expression of genomic TEs is proposed to initiate self regulation by increasing the production of repressive piRNAs, thereby "adap...

journal_title：PLoS genetics

authors： Wang L,Barbash DA,Kelleher ES

更新日期：2020-06-11 00:00:00

abstract：:Endoplasmic reticulum (ER) stress activates the Unfolded Protein Response, a compensatory signaling response that is mediated by the IRE-1, PERK/PEK-1, and ATF-6 pathways in metazoans. Genetic studies have implicated roles for UPR signaling in animal development and disease, but the function of the UPR under physiolog...

journal_title：PLoS genetics

authors： Richardson CE,Kinkel S,Kim DH

更新日期：2011-11-01 00:00:00

abstract：:Genomic resources for the domestic dog have improved with the widespread adoption of a 173k SNP array platform and updated reference genome. SNP arrays of this density are sufficient for detecting genetic associations within breeds but are underpowered for finding associations across multiple breeds or in mixed-breed ...

journal_title：PLoS genetics

authors： Hayward JJ,White ME,Boyle M,Shannon LM,Casal ML,Castelhano MG,Center SA,Meyers-Wallen VN,Simpson KW,Sutter NB,Todhunter RJ,Boyko AR

更新日期：2019-09-16 00:00:00

abstract：:Variation in DNA methylation is being increasingly associated with health and disease outcomes. Although DNA methylation is hypothesized to be a mechanism by which both genetic and non-genetic factors can influence the regulation of gene expression, little is known about the extent to which DNA methylation at specific...

journal_title：PLoS genetics

authors： Hannon E,Knox O,Sugden K,Burrage J,Wong CCY,Belsky DW,Corcoran DL,Arseneault L,Moffitt TE,Caspi A,Mill J

更新日期：2018-08-09 00:00:00

abstract：:Lethal recessive alleles cause pre- or postnatal death in homozygous affected individuals, reducing fertility. Especially in small size domestic and wild populations, those alleles might be exposed by inbreeding, caused by matings between related parents that inherited the same recessive lethal allele from a common an...

journal_title：PLoS genetics

authors： Derks MFL,Gjuvsland AB,Bosse M,Lopes MS,van Son M,Harlizius B,Tan BF,Hamland H,Grindflek E,Groenen MAM,Megens HJ

更新日期：2019-03-15 00:00:00

abstract：:Elevated proteasome activity extends lifespan in model organisms such as yeast, worms and flies. This pro-longevity effect might be mediated by improved protein homeostasis, as this protease is an integral module of the protein homeostasis network. Proteasomes also regulate cellular processes through temporal and spat...

journal_title：PLoS genetics

authors： Yao Y,Tsuchiyama S,Yang C,Bulteau AL,He C,Robison B,Tsuchiya M,Miller D,Briones V,Tar K,Potrero A,Friguet B,Kennedy BK,Schmidt M

更新日期：2015-01-28 00:00:00

abstract：:Genomic instability is a hallmark of human cancer cells. To prevent genomic instability, chromosomal DNA is faithfully duplicated in every cell division cycle, and eukaryotic cells have complex regulatory mechanisms to achieve this goal. Here, we show that untimely activation of replication origins during the G1 phase...

journal_title：PLoS genetics

authors： Tanaka S,Araki H

更新日期：2011-06-01 00:00:00

abstract：:Arsenic is a well-established human carcinogen of poorly understood mechanism of genotoxicity. It is generally accepted that arsenic acts indirectly by generating oxidative DNA damage that can be converted to replication-dependent DNA double-strand breaks (DSBs), as well as by interfering with DNA repair pathways and ...

journal_title：PLoS genetics

authors： Litwin I,Bocer T,Dziadkowiec D,Wysocki R

更新日期：2013-01-01 00:00:00

abstract：:The mammalian Y chromosome plays a critical role in spermatogenesis. However, the exact functions of each gene in the Y chromosome have not been completely elucidated, partly owing to difficulties in gene targeting analysis of the Y chromosome. Zfy was first proposed to be a sex determination factor, but its function ...

journal_title：PLoS genetics

authors： Nakasuji T,Ogonuki N,Chiba T,Kato T,Shiozawa K,Yamatoya K,Tanaka H,Kondo T,Miyado K,Miyasaka N,Kubota T,Ogura A,Asahara H

更新日期：2017-01-23 00:00:00

abstract：:Among the rare colonizers of heavy-metal rich toxic soils, Arabidopsis halleri is a compelling model extremophile, physiologically distinct from its sister species A. lyrata, and A. thaliana. Naturally selected metal hypertolerance and extraordinarily high leaf metal accumulation in A. halleri both require Heavy Metal...

journal_title：PLoS genetics

authors： Hanikenne M,Kroymann J,Trampczynska A,Bernal M,Motte P,Clemens S,Krämer U

更新日期：2013-01-01 00:00:00

abstract：:Microbial populations founded by a single clone and propagated under resource limitation can become polymorphic. We sought to elucidate genetic mechanisms whereby a polymorphism evolved in Escherichia coli under glucose limitation and persisted because of cross-feeding among multiple adaptive clones. Apart from a 29 k...

journal_title：PLoS genetics

authors： Kinnersley MA,Holben WE,Rosenzweig F

更新日期：2009-11-01 00:00:00

abstract：:Despite strong vetting for disease activity, only 10% of candidate new molecular entities in early stage clinical trials are eventually approved. Analyzing historical pipeline data, Nelson et al. 2015 (Nat. Genet.) concluded pipeline drug targets with human genetic evidence of disease association are twice as likely t...

journal_title：PLoS genetics

authors： King EA,Davis JW,Degner JF

更新日期：2019-12-12 00:00:00

abstract：:Sodalis glossinidius, a maternally inherited endosymbiont of the tsetse fly, maintains genes encoding homologues of the PhoP-PhoQ two-component regulatory system. This two-component system has been extensively studied in facultative bacterial pathogens and is known to serve as an environmental magnesium sensor and a r...

journal_title：PLoS genetics

authors： Pontes MH,Smith KL,De Vooght L,Van Den Abbeele J,Dale C

更新日期：2011-11-01 00:00:00

abstract：:The cytoplasmic peptide:N-glycanase (Ngly1 in mammals) is a de-N-glycosylating enzyme that is highly conserved among eukaryotes. It was recently reported that subjects harboring mutations in the NGLY1 gene exhibited severe systemic symptoms (NGLY1-deficiency). While the enzyme obviously has a critical role in mammals,...

journal_title：PLoS genetics

authors： Fujihira H,Masahara-Negishi Y,Tamura M,Huang C,Harada Y,Wakana S,Takakura D,Kawasaki N,Taniguchi N,Kondoh G,Yamashita T,Funakoshi Y,Suzuki T

更新日期：2017-04-20 00:00:00

abstract：:Hereditary cystatin C amyloid angiopathy (HCCAA) is an autosomal dominant disease with high penetrance, manifest by brain hemorrhages in young normotensive adults. In Iceland, this condition is caused by the L68Q mutation in the cystatin C gene, with contemporary carriers reaching an average age of only 30 years. Here...

journal_title：PLoS genetics

authors： Palsdottir A,Helgason A,Palsson S,Bjornsson HT,Bragason BT,Gretarsdottir S,Thorsteinsdottir U,Olafsson E,Stefansson K

更新日期：2008-06-20 00:00:00

abstract：:Bases within DNA are frequently damaged, producing obstacles to efficient and accurate DNA replication by replicative polymerases. Translesion synthesis (TLS) polymerases, via their ability to catalyze nucleotide additions to growing DNA chains across DNA lesions, promote replication of damaged DNA, thus preventing ch...

journal_title：PLoS genetics

authors： van Bostelen I,van Schendel R,Romeijn R,Tijsterman M

更新日期：2020-04-24 00:00:00

abstract：:The cell envelope of Gram-negative bacteria is a formidable barrier that is difficult for antimicrobial drugs to penetrate. Thus, the list of treatments effective against these organisms is small and with the rise of new resistance mechanisms is shrinking rapidly. New therapies to treat Gram-negative bacterial infecti...

journal_title：PLoS genetics

authors： Paradis-Bleau C,Kritikos G,Orlova K,Typas A,Bernhardt TG

更新日期：2014-01-01 00:00:00

abstract：:The Yorkie/Yap transcriptional coactivator is a well-known regulator of cellular proliferation in both invertebrates and mammals. As a coactivator, Yorkie (Yki) lacks a DNA binding domain and must partner with sequence-specific DNA binding proteins in the nucleus to regulate gene expression; in Drosophila, the develop...

journal_title：PLoS genetics

authors： Slattery M,Voutev R,Ma L,Nègre N,White KP,Mann RS

更新日期：2013-01-01 00:00:00

abstract：:A universal Tree of Life (TOL) has long been a goal of molecular phylogeneticists, but reticulation at the level of genes and possibly at the levels of cells and species renders any simple interpretation of such a TOL, especially as applied to prokaryotes, problematic. ...

journal_title：PLoS genetics

authors： Doolittle WF,Brunet TD

更新日期：2016-04-14 00:00:00

abstract：:Synonymous mutations do not alter the specified amino acid but may alter the structure or function of an mRNA in ways that impact fitness. There are few examples in the literature, however, in which the effects of synonymous mutations on microbial growth rates have been measured, and even fewer for which the underlyin...

journal_title：PLoS genetics

authors： Kristofich J,Morgenthaler AB,Kinney WR,Ebmeier CC,Snyder DJ,Old WM,Cooper VS,Copley SD

更新日期：2018-08-27 00:00:00

abstract：:There is increasing evidence that non-coding macroRNAs are major elements for silencing imprinted genes, but their mechanism of action is poorly understood. Within the imprinted Gnas cluster on mouse chromosome 2, Nespas is a paternally expressed macroRNA that arises from an imprinting control region and runs antisens...

journal_title：PLoS genetics

authors： Williamson CM,Ball ST,Dawson C,Mehta S,Beechey CV,Fray M,Teboul L,Dear TN,Kelsey G,Peters J

更新日期：2011-03-01 00:00:00

abstract：:In multicellular organisms, tight regulation of gene expression ensures appropriate tissue and organismal growth throughout development. Reversible phosphorylation of the RNA Polymerase II (RNAPII) C-terminal domain (CTD) is critical for the regulation of gene expression states, but how phosphorylation is actively mod...

journal_title：PLoS genetics

authors： Ciurciu A,Duncalf L,Jonchere V,Lansdale N,Vasieva O,Glenday P,Rudenko A,Vissi E,Cobbe N,Alphey L,Bennett D

更新日期：2013-10-01 00:00:00

abstract：:Genetic variants in genome-wide association studies (GWAS) are tested for disease association mostly using simple regression, one variant at a time. Standard approaches to improve power in detecting disease-associated SNPs use multiple regression with Bayesian variable selection in which a sparsity-enforcing prior on ...

journal_title：PLoS genetics

authors： Banerjee S,Zeng L,Schunkert H,Söding J

更新日期：2018-12-31 00:00:00