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排序方式: 共有168条查询结果,搜索用时 15 毫秒
81.
Hatchell EC Colley SM Beveridge DJ Epis MR Stuart LM Giles KM Redfern AD Miles LE Barker A MacDonald LM Arthur PG Lui JC Golding JL McCulloch RK Metcalf CB Wilce JA Wilce MC Lanz RB O'Malley BW Leedman PJ 《Molecular cell》2006,22(5):657-668
Steroid receptor RNA activator (SRA), the only known RNA coactivator, augments transactivation by nuclear receptors (NRs). We identified SLIRP (SRA stem-loop interacting RNA binding protein) binding to a functional substructure of SRA, STR7. SLIRP is expressed in normal and tumor tissues, contains an RNA recognition motif (RRM), represses NR transactivation in a SRA- and RRM-dependent manner, augments the effect of Tamoxifen, and modulates association of SRC-1 with SRA. SHARP, a RRM-containing corepressor, also binds STR7, augmenting repression with SLIRP. SLIRP colocalizes with SKIP (Chr14q24.3), another NR coregulator, and reduces SKIP-potentiated NR signaling. SLIRP is recruited to endogenous promoters (pS2 and metallothionein), the latter in a SRA-dependent manner, while NCoR promoter recruitment is dependent on SLIRP. The majority of the endogenous SLIRP resides in the mitochondria. Our data demonstrate that SLIRP modulates NR transactivation, suggest it may regulate mitochondrial function, and provide mechanistic insight into interactions between SRA, SLIRP, SRC-1, and NCoR. 相似文献
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84.
Jemma L. Geoghegan Peter J. Walker Jean-Bernard Duchemin Isabelle Jeanne Edward C. Holmes 《PLoS neglected tropical diseases》2014,8(11)
Arthropod-borne viruses are a major cause of emerging disease with significant public health and economic impacts. However, the factors that determine their activity and seasonality are not well understood. In Australia, a network of sentinel cattle herds is used to monitor the distribution of several such viruses and to define virus-free regions. Herein, we utilize these serological data to describe the seasonality, and its drivers, of three economically important animal arboviruses: bluetongue virus, Akabane virus and bovine ephemeral fever virus. Through epidemiological time-series analyses of sero-surveillance data of 180 sentinel herds between 2004–2012, we compared seasonal parameters across latitudes, ranging from the tropical north (−10°S) to the more temperate south (−40°S). This analysis revealed marked differences in seasonality between distinct geographic regions and climates: seasonality was most pronounced in southern regions and gradually decreased as latitude decreased toward the Equator. Further, we show that both the timing of epidemics and the average number of seroconversions have a strong geographical component, which likely reflect patterns of vector abundance through co-varying climatic factors, especially temperature and rainfall. Notably, despite their differences in biology, including insect vector species, all three viruses exhibited very similar seasonality. By revealing the factors that shape spatial and temporal distributions, our study provides a more complete understanding of arbovirus seasonality that will enable better risk predictions. 相似文献
85.
Pankratz N Dumitriu A Hetrick KN Sun M Latourelle JC Wilk JB Halter C Doheny KF Gusella JF Nichols WC Myers RH Foroud T DeStefano AL;PSG-PROGENI GenePD Investigators Coordinators Molecular Genetic Laboratories 《PloS one》2011,6(8):e20988
Copy number variants (CNVs) are known to cause Mendelian forms of Parkinson disease (PD), most notably in SNCA and PARK2. PARK2 has a recessive mode of inheritance; however, recent evidence demonstrates that a single CNV in PARK2 (but not a single missense mutation) may increase risk for PD. We recently performed a genome-wide association study for PD that excluded individuals known to have either a LRRK2 mutation or two PARK2 mutations. Data from the Illumina370Duo arrays were re-clustered using only white individuals with high quality intensity data, and CNV calls were made using two algorithms, PennCNV and QuantiSNP. After quality assessment, the final sample included 816 cases and 856 controls. Results varied between the two CNV calling algorithms for many regions, including the PARK2 locus (genome-wide p = 0.04 for PennCNV and p = 0.13 for QuantiSNP). However, there was consistent evidence with both algorithms for two novel genes, USP32 and DOCK5 (empirical, genome-wide p-values<0.001). PARK2 CNVs tended to be larger, and all instances that were molecularly tested were validated. In contrast, the CNVs in both novel loci were smaller and failed to replicate using real-time PCR, MLPA, and gel electrophoresis. The DOCK5 variation is more akin to a VNTR than a typical CNV and the association is likely caused by artifact due to DNA source. DNA for all the cases was derived from whole blood, while the DNA for all controls was derived from lymphoblast cell lines. The USP32 locus contains many SNPs with low minor allele frequency leading to a loss of heterozygosity that may have been spuriously interpreted by the CNV calling algorithms as support for a deletion. Thus, only the CNVs within the PARK2 locus could be molecularly validated and associated with PD susceptibility. 相似文献
86.
Sebastiani P Solovieff N Dewan AT Walsh KM Puca A Hartley SW Melista E Andersen S Dworkis DA Wilk JB Myers RH Steinberg MH Montano M Baldwin CT Hoh J Perls TT 《PloS one》2012,7(1):e29848
Like most complex phenotypes, exceptional longevity is thought to reflect a combined influence of environmental (e.g., lifestyle choices, where we live) and genetic factors. To explore the genetic contribution, we undertook a genome-wide association study of exceptional longevity in 801 centenarians (median age at death 104 years) and 914 genetically matched healthy controls. Using these data, we built a genetic model that includes 281 single nucleotide polymorphisms (SNPs) and discriminated between cases and controls of the discovery set with 89% sensitivity and specificity, and with 58% specificity and 60% sensitivity in an independent cohort of 341 controls and 253 genetically matched nonagenarians and centenarians (median age 100 years). Consistent with the hypothesis that the genetic contribution is largest with the oldest ages, the sensitivity of the model increased in the independent cohort with older and older ages (71% to classify subjects with an age at death>102 and 85% to classify subjects with an age at death>105). For further validation, we applied the model to an additional, unmatched 60 centenarians (median age 107 years) resulting in 78% sensitivity, and 2863 unmatched controls with 61% specificity. The 281 SNPs include the SNP rs2075650 in TOMM40/APOE that reached irrefutable genome wide significance (posterior probability of association = 1) and replicated in the independent cohort. Removal of this SNP from the model reduced the accuracy by only 1%. Further in-silico analysis suggests that 90% of centenarians can be grouped into clusters characterized by different “genetic signatures” of varying predictive values for exceptional longevity. The correlation between 3 signatures and 3 different life spans was replicated in the combined replication sets. The different signatures may help dissect this complex phenotype into sub-phenotypes of exceptional longevity. 相似文献
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DeStefano AL Latourelle J Lew MF Suchowersky O Klein C Golbe LI Mark MH Growdon JH Wooten GF Watts R Guttman M Racette BA Perlmutter JS Marlor L Shill HA Singer C Goldwurm S Pezzoli G Saint-Hilaire MH Hendricks AE Gower A Williamson S Nagle MW Wilk JB Massood T Huskey KW Baker KB Itin I Litvan I Nicholson G Corbett A Nance M Drasby E Isaacson S Burn DJ Chinnery PF Pramstaller PP Al-Hinti J Moller AT Ostergaard K Sherman SJ Roxburgh R Snow B Slevin JT Cambi F Gusella JF Myers RH 《Human genetics》2008,124(1):95-99
Genetic variants in embryonic lethal, abnormal vision, Drosophila-like 4 (ELAVL4) have been reported to be associated with onset age of Parkinson disease (PD) or risk for PD affection in Caucasian populations.
In the current study we genotyped three single nucleotide polymorphisms in ELAVL4 in a Caucasian study sample consisting of 712 PD patients and 312 unrelated controls from the GenePD study. The minor allele of rs967582 was associated with increased risk of PD (odds ratio = 1.46, nominal P value = 0.011) in the GenePD population. The minor allele of rs967582 was also the risk allele for PD affection or earlier onset age in the previously
studied populations. This replication of association with rs967582 in a third cohort further implicates ELAVL4 as a PD susceptibility gene. 相似文献
89.
Johnson N Black C Smith J Un H McElhinney LM Aylan O Fooks AR 《Journal of wildlife diseases》2003,39(2):262-270
Sixteen rabies isolates recently collected from mainland Turkey and two isolates held within a British archive were used to form a representative cohort from a range of vectors, and were analyzed to identify potential causes for an increase of rabies within the fox (Vulpes vulpes) population in Turkey. Each isolate was characterized by sequence analysis of the nucleoprotein gene and compared phylogenetically to the cohort, to isolates from neighboring countries and to isolates from continental Europe and Russia. From this analysis the isolates could be divided into three groups associated with geographic location. This included a western group, an eastern group, and one isolate that did not group with any other Turkish isolate. This observation was also found using the heteroduplex mobility assay as an alternative method for typing rabies virus isolates. Further comparison with isolates from neighboring countries suggests that this isolate was related to viruses present in Georgia and could represent a recent import to Turkey from that country. Within the two larger groups, sequence data were obtained from both infected dogs and foxes suggesting that there has been transmission of virus between these two species. The direction of transmission could not be identified by the phylogenetic analysis, although absence of rabies within the fox population in previous years suggests that this could represent a recent spillover from the domestic dog to the fox. 相似文献
90.
Morreale G Lanckriet H Miller JC Middelberg AP 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2003,786(1-2):237-246
In this study we develop the components of an integrated process for the continuous extraction and purification of a histidine-tagged fusion protein expressed as an inclusion body in Escherichia coli. Lac21 was selected as a model peptide and was expressed as a fusion to ketosteroid isomerase. A purification strategy was developed on a 1-ml batch column before successful scale-up and transfer to a continuous purification system, having a bed volume of 240 ml. Preliminary experiments proved cleavage of the fusion protein. The use of chemical extraction and continuous chromatography gives a flowsheet far superior to the traditional methods for inclusion body processing. 相似文献