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1.
Comparison of statistics for candidate-gene association studies using cases and parents. 总被引:17,自引:5,他引:12
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Studies of association between candidate genes and disease can be designed to use cases with disease, and in place of nonrelated controls, their parents. The advantage of this design is the elimination of spurious differences due to ethnic differences between cases and nonrelated controls. However, several statistical methods of analysis have been proposed in the literature, and the choice of analysis is not always clear. We review some of the statistical methods currently developed and present two new statistical methods aimed at specific genetic hypotheses of dominance and recessivity of the candidate gene. These new methods can be more powerful than other current methods, as demonstrated by simulations. The basis of these new statistical methods is a likelihood approach. The advantage of the likelihood framework is that regression models can be developed to assess genotype-environment interactions, as well as the relative contribution that alleles at the candidate-gene locus make to the relative risk (RR) of disease. This latter development allows testing of (1) whether interactions between alleles exist, on the scale of log RR, and (2) whether alleles originating from the mother or father of a case impart different risks, i.e., genomic imprinting. 相似文献
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3.
Vincent Anquetil Caroline Le Sommer Agn��s M��reau Sandra Hamon Hubert Lerivray Serge Hardy 《The Journal of biological chemistry》2009,284(47):32370-32383
Alternative splicing of 3′-terminal exons plays a critical role in gene expression by producing mRNA with distinct 3′-untranslated regions that regulate their fate and their expression. The Xenopus α-tropomyosin pre-mRNA possesses a composite internal/3′-terminal exon (exon 9A9′) that is differentially processed depending on the embryonic tissue. Exon 9A9′ is repressed in non-muscle tissue by the polypyrimidine tract binding protein, whereas it is selected as a 3′-terminal or internal exon in myotomal cells and adult striated muscles, respectively. We report here the identification of an intronic regulatory element, designated the upstream terminal exon enhancer (UTE), that is required for the specific usage of exon 9A9′ as a 3′-terminal exon in the myotome. We demonstrate that polypyrimidine tract binding protein prevents the activity of UTE in non-muscle cells, whereas a subclass of serine/arginine rich (SR) proteins promotes the selection of exon 9A9′ in a UTE-dependent way. Morpholino-targeted blocking of UTE in the embryo strongly reduced the inclusion of exon 9A9′ as a 3′-terminal exon in the endogenous mRNA, demonstrating the function of UTE under physiological circumstances. This strategy allowed us to reveal a splicing pathway that generates a mRNA with no in frame stop codon and whose steady-state level is translation-dependent. This result suggests that a non-stop decay mechanism participates in the strict control of the 3′-end processing of the α-tropomyosin pre-mRNA. 相似文献
4.
Antoine Wystrach Sebastian Schwarz Patrick Schultheiss Guy Beugnon Ken Cheng 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》2011,197(2):167-179
The Australian desert ant Melophorus bagoti often follows stereotypical routes through a cluttered landscape containing both distant panoramic views and obstacles (plants)
to navigate around. We created an artificial obstacle course for the ants between a feeder and their nest. Landmarks comprised
natural objects in the landscape such as logs, branches, and tussocks. Many ants travelled stereotypical routes home through
the obstacle course in training, threading repeatedly the same gaps in the landmarks. Manipulations altering the relations
between the landmarks and the surrounding panorama, however, affected the routes in two major ways. Both interchanging the
positions of landmarks (transpositions) and displacing the entire landmark set along with the starting position of the ants
(translations) (1) reduced the stereotypicality of the route, and (2) increased turns and meanders during travel. The ants
might have used the entire panorama in view-based travel, or the distal panorama might prime the identification and use of
landmarks en route. Despite the large data set, both options (not mutually exclusive) remain viable. 相似文献
5.
Production and characterization of human basic fibroblast growth factor from Escherichia coli 总被引:7,自引:0,他引:7
C H Squires J Childs S P Eisenberg P J Polverini A Sommer 《The Journal of biological chemistry》1988,263(31):16297-16302
6.
zge Karayel Francesca Tonelli Sebastian Virreira Winter Phillip E. Geyer Ying Fan Esther M. Sammler Dario R. Alessi Martin Steger Matthias Mann 《Molecular & cellular proteomics : MCP》2020,19(9):1546-1560
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- •MS-based clinical assay that accurately determines phospho Rab10 occupancy.
- •Stable isotope labeled phosphopeptide injected as a standard with endogenous tryptic phospho Rab peptide for accurate ratio determination.
- •Determination of pRab levels in neutrophils of Parkinson disease patients.
- •Relevance of pRab levels as marker of PD.
7.
Volker Sommer 《Animal behaviour》2011,82(5):1213-1214
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Krzysztof J. Gorgolewski Dan Lurie Sebastian Urchs Judy A. Kipping R. Cameron Craddock Michael P. Milham Daniel S. Margulies Jonathan Smallwood 《PloS one》2014,9(5)
Although neural activity often reflects the processing of external inputs, intrinsic fluctuations in activity have been observed throughout the brain. These may relate to patterns of self-generated thought that can occur while not performing goal-driven tasks. To understand the relationship between self-generated mental activity and intrinsic neural fluctuations, we developed the New York Cognition Questionnaire (NYC-Q) to assess the content and form of an individual''s experiences during the acquisition of resting-state fMRI data. The data were collected as a part of the Nathan Kline Rockland Enhanced sample. We decomposed NYC-Q scores using exploratory factor analysis and found that self-reported thoughts clustered into distinct dimensions of content (future related, past related, positive, negative, and social) and form (words, images, and specificity). We used these components to perform an individual difference analysis exploring how differences in the types of self-generated thoughts relate to whole brain measures of intrinsic brain activity (fractional amplitude of low frequency fluctuations, regional homogeneity, and degree centrality). We found patterns of self-generated thoughts related to changes that were distributed across a wide range of cortical areas. For example, individuals who reported greater imagery exhibited greater low frequency fluctuations in a region of perigenual cingulate cortex, a region that is known to participate in the so-called default-mode network. We also found certain forms of thought were associated with other areas, such as primary visual cortex, the insula, and the cerebellum. For example, individuals who reported greater future thought exhibited less homogeneous neural fluctuations in a region of lateral occipital cortex, a result that is consistent with the claim that particular types of self-generated thought depend on processes that are decoupled from sensory processes. These data provide evidence that self-generated thought is a heterogeneous category of experience and that studying its content can be helpful in understanding brain dynamics. 相似文献
9.
Sebastian Kalamajski Dominique Bihan Arkadiusz Bonna Kristofer Rubin Richard W. Farndale 《The Journal of biological chemistry》2016,291(15):7951-7960
The hallmark of fibrotic disorders is a highly cross-linked and dense collagen matrix, a property driven by the oxidative action of lysyl oxidase. Other fibrosis-associated proteins also contribute to the final collagen matrix properties, one of which is fibromodulin. Its interactions with collagen affect collagen cross-linking, packing, and fibril diameter. We investigated the possibility that a specific relationship exists between fibromodulin and lysyl oxidase, potentially imparting a specific collagen matrix phenotype. We mapped the fibromodulin-collagen interaction sites using the collagen II and III Toolkit peptide libraries. Fibromodulin interacted with the peptides containing the known collagen cross-linking sites and the MMP-1 cleavage site in collagens I and II. Interestingly, the interaction sites are closely aligned within the quarter-staggered collagen fibril, suggesting a multivalent interaction between fibromodulin and several collagen helices. Furthermore, we detected an interaction between fibromodulin and lysyl oxidase (a major collagen cross-linking enzyme) and mapped the interaction site to 12 N-terminal amino acids on fibromodulin. This interaction also increases the activity of lysyl oxidase. Together, the data suggest a fibromodulin-modulated collagen cross-linking mechanism where fibromodulin binds to a specific part of the collagen domain and also forms a complex with lysyl oxidase, targeting the enzyme toward specific cross-linking sites. 相似文献
10.
Murine histocompatibility antigens were solubilized from the spleens and lungs of C57BL/6 (H-2b) animals with hypertonic salt (3 M KC1). Aggregate-free soluble antigens were incubated with nonadherent lymph node cells from BALB/c (H-2d) mice for 18 hr prior to their use as responder cells in the mixed-lymphocyte reaction (MLR). It was found that the generation of cytotoxic cells was suppressed while the proliferative response was not affected. The observed suppression was not due to a shift in the kinetics of the generation of cytotoxicity as determined throughout a 10-day culture period. The suppression was specific in that the response in MLR to unrelated H-2f stimulator cells and the subsequent generation of cytotoxic cells were unchanged. Using various H-2 recombinant strains as target cells in the assay of cell-mediated lympholysis, suppression of cytotoxicity was observed when the D end, but not the K end, was shared with the C57BL/6 strain from which the antigens were derived. 相似文献