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141.
Pathogen genetics is already a mainstay of public health investigation and control efforts; now advances in technology make it possible to investigate the role of human genetic variation in the epidemiology of infectious diseases. To describe trends in this field, we analyzed articles that were published from 2001 through 2010 and indexed by the HuGE Navigator, a curated online database of PubMed abstracts in human genome epidemiology. We extracted the principal findings from all meta-analyses and genome-wide association studies (GWAS) with an infectious disease-related outcome. Finally, we compared the representation of diseases in HuGE Navigator with their contributions to morbidity worldwide. We identified 3,730 articles on infectious diseases, including 27 meta-analyses and 23 GWAS. The number published each year increased from 148 in 2001 to 543 in 2010 but remained a small fraction (about 7%) of all studies in human genome epidemiology. Most articles were by authors from developed countries, but the percentage by authors from resource-limited countries increased from 9% to 25% during the period studied. The most commonly studied diseases were HIV/AIDS, tuberculosis, hepatitis B infection, hepatitis C infection, sepsis, and malaria. As genomic research methods become more affordable and accessible, population-based research on infectious diseases will be able to examine the role of variation in human as well as pathogen genomes. This approach offers new opportunities for understanding infectious disease susceptibility, severity, treatment, control, and prevention. 相似文献
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Julian Little Julian P.T Higgins John P.A Ioannidis David Moher France Gagnon Erik von Elm Muin J Khoury Barbara Cohen George Davey-Smith Jeremy Grimshaw Paul Scheet Marta Gwinn Robin E Williamson Guang Yong Zou Kim Hutchings Candice Y Johnson Valerie Tait Miriam Wiens Jean Golding Cornelia van Duijn John McLaughlin Andrew Paterson George Wells Isabel Fortier Matthew Freedman Maja Zecevic Richard King Claire Infante-Rivard Alex Stewart Nick Birkett 《PLoS medicine》2009,6(2)
146.
Gwinn WM Damsker JM Falahati R Okwumabua I Kelly-Welch A Keegan AD Vanpouille C Lee JJ Dent LA Leitenberg D Bukrinsky MI Constant SL 《Journal of immunology (Baltimore, Md. : 1950)》2006,177(7):4870-4879
Extracellular cyclophilins have been well described as chemotactic factors for various leukocyte subsets. This chemotactic capacity is dependent upon interaction of cyclophilins with the cell surface signaling receptor CD147. Elevated levels of extracellular cyclophilins have been documented in several inflammatory diseases. We propose that extracellular cyclophilins, via interaction with CD147, may contribute to the recruitment of leukocytes from the periphery into tissues during inflammatory responses. In this study, we examined whether extracellular cyclophilin-CD147 interactions might influence leukocyte recruitment in the inflammatory disease allergic asthma. Using a mouse model of asthmatic inflammation, we show that 1) extracellular cyclophilins are elevated in the airways of asthmatic mice; 2) mouse eosinophils and CD4+ T cells express CD147, which is up-regulated on CD4+ T cells upon activation; 3) cyclophilins induce CD147-dependent chemotaxis of activated CD4+ T cells in vitro; 4) in vivo treatment with anti-CD147 mAb significantly reduces (by up to 50%) the accumulation of eosinophils and effector/memory CD4+ T lymphocytes, as well as Ag-specific Th2 cytokine secretion, in lung tissues; and 5) anti-CD147 treatment significantly reduces airway epithelial mucin production and bronchial hyperreactivity to methacholine challenge. These findings provide a novel mechanism whereby asthmatic lung inflammation may be reduced by targeting cyclophilin-CD147 interactions. 相似文献
147.
Jouvin-Marche E; Cuddihy A; Butler S; Hansen JN; Fitch WM; Rudikoff S 《Molecular biology and evolution》1988,5(5):500-511
The immunoglobulin kappa light-chain constant region gene (C kappa) has
been cloned and sequenced from five wild mouse species. Analysis of these
data has permitted an assessment of single-copy gene evolution during a
limited time period as defined by the genus Mus. Sequence conservation was
found to be as high (or higher) in the 5' and enhancer regions as in the
coding region. The pattern of substitutions throughout these genes suggests
that parallel evolution has occurred frequently and that substitutions at
replacement sites have not decreased significantly, owing to saturation
during this period of approximately 10 Myr. Phylogenetic relationships have
been determined among these wild species as well as among members of the
genus Rattus.
相似文献
148.
Evidence from nuclear sequences that invariable sites should be considered when sequence divergence is calculated 总被引:3,自引:1,他引:2
It has long been known, from the distribution of multiple amino acid
replacements, that not all amino acids of a sequence are replaceable. More
recently, the phenomenon was observed at the nucleotide level in
mitochondrial DNA even after allowing for different rates of transition and
transversion substitutions. We have extended the search to globin gene
sequences from various organisms, with the following results: (1) Nearly
every data set showed evidence of invariable nucleotide positions. (2) In
all data sets, substitution rates of transversions and transitions were
never in the ratio of 2/1, and rarely was the ratio even constant. (3) Only
rarely (e.g., the third codon position of beta hemoglobins) was it possible
to fit the data set solely by making allowance for the number of invariable
positions and for the relative rates of transversion and transition
substitutions. (4) For one data set (the second codon position of beta
hemoglobins) we were able to simulate the observed data by making the
allowance in (3) and having the set of covariotides (concomitantly variable
nucleotides) be small in number and be turned over in a stochastic manner
with a probability that was appreciable. (5) The fit in the latter case
suggests, if the assumptions are correct and at all common, that current
procedures for estimating the total number of nucleotide substitutions in
two genes since their divergence from their common ancestor could be low by
as much as an order of magnitude. (6) The fact that only a small fraction
of the nucleotide positions differ is no guarantee that one is not
seriously underestimating the total amount of divergence (substitutions).
(7) Most data sets are so heterogeneous in their number of transition and
transversion differences that none of the current models of nucleotide
substitution seem to fit them even after (a) segregation of coding from
noncoding sequences and (b) splitting of the codon into three subsets by
codon position. (8) These frequently occurring problems cannot be seen
unless several reasonably divergent orthologous genes are examined
together.
相似文献
149.
Interlimb Coordination During Locomotion 总被引:1,自引:0,他引:1
SYNOPSIS. Studies of interlimb control during cat locomotionare directed at four different levels of organization. Interlimbstepping patterns are described from studies of the timing ofelectromyographic activity of muscles of different limbs. Patternsof coordination are based on the frequency of occurrence ofthe phasing of step cycles of the different limbs. Selectivespinal cord lesions are used to perturb those patterns of coordinationand have implicated two ascending spinal systems in interlimbcontrol: long ascending propriospinal neurons (LAPNs) and neuronsof the ventral spinocerebellar tract (VSCT). The results ofneuroanatomical tract tracing experiments indicate that twodifferent populations of LAPNs exist which might provide directconnection between cervical and lumbosacral locomotor centersbut that neurons of the VSCT do not make such connections. Theseresults imply that the role of the VSCT in interlimb controlis by way of the cerebellum. Unit recordings made from axonsof the VSCT during treadmill locomotion are consistent withthe VSCT carrying information about the timing of both hindlimbstep cycles. 相似文献
150.