排序方式: 共有27条查询结果,搜索用时 31 毫秒
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Justin M. Richner Grzegorz B. Gmyrek Jennifer Govero Yizheng Tu Gerritje J. W. van der Windt Talibah U. Metcalf Elias K. Haddad Johannes Textor Mark J. Miller Michael S. Diamond 《PLoS pathogens》2015,11(7)
Impaired immune responses in the elderly lead to reduced vaccine efficacy and increased susceptibility to viral infections. Although several groups have documented age-dependent defects in adaptive immune priming, the deficits that occur prior to antigen encounter remain largely unexplored. Herein, we identify novel mechanisms for compromised adaptive immunity that occurs with aging in the context of infection with West Nile virus (WNV), an encephalitic flavivirus that preferentially causes disease in the elderly. An impaired IgM and IgG response and enhanced vulnerability to WNV infection during aging was linked to delayed germinal center formation in the draining lymph node (DLN). Adoptive transfer studies and two-photon intravital microscopy revealed a decreased trafficking capacity of donor naïve CD4+ T cells from old mice, which manifested as impaired T cell diapedesis at high endothelial venules and reduced cell motility within DLN prior to antigen encounter. Furthermore, leukocyte accumulation in the DLN within the first few days of WNV infection or antigen-adjuvant administration was diminished more generally in old mice and associated with a second aging-related defect in local cytokine and chemokine production. Thus, age-dependent cell-intrinsic and environmental defects in the DLN result in delayed immune cell recruitment and antigen recognition. These deficits compromise priming of early adaptive immune responses and likely contribute to the susceptibility of old animals to acute WNV infection. 相似文献
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Marie GB Hansen Mette Christoffersen Line R Thuesen Morten R Petersen Anders M Bojesen 《Acta veterinaria Scandinavica》2010,52(1):3
Background
Borrelia burgdorferi sensu lato and Anaplasma phagocytophilum are able to infect horses. However, the extend to which Danish horses are infected and seroconvert due to these two bacteria is unknown. The aim of the present study was to evaluate the seroprevalence of B. burgdorferi sensu lato and A. phagocytophilum in Danish horses.Methods
A total of 390 blood samples collected from all major regions of Denmark and with a geographical distribution corresponding to the density of the Danish horse population were analyzed. All samples were examined for the presence of antibodies against B. burgdorferi sensu lato and A. phagocytophilum by the use of the SNAP®4DX ® ELISA test.Results
Overall, 29.0% of the horses were seropositive for B. burgdorferi sensu lato whereas 22.3% were seropositive for A. phagocytophilum.Conclusions
Antibodies against B burgdorferi sensu lato and A. phagocytophilum are commonly found among Danish horses thus showing that Danish horses are frequently infected by these organisms.5.
Gmyrek GB 《Postepy biochemii》2005,51(4):379-381
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Estimates of DNA and protein sequence divergence: an examination of some assumptions 总被引:5,自引:3,他引:2
Some of the assumptions underlying estimates of DNA and protein sequence
divergence are examined. A solution for the variance of these estimates
that allows for different mutation rates and different population sizes in
each species and for an arbitrary structure in the initial population is
obtained. It is shown that these conditions do not strongly affect
estimates of divergence. In general, they cause the variance of divergence
to be smaller than a binomial variance. Thus, the binomial variance that is
usually assumed for these estimates is safely conservative. It is shown
that variability in the mutation rate among sites can have an effect as
large as or larger than variability in the mutation rate among bases.
Variability in the mutation rate among bases and among sites causes the
number of substitutions between two sequences to be underestimated. Protein
and DNA sequences from several species are collected to estimate the
variability in mutation rates among sites. When many homologous sequences
are known, standard methods to estimate this variability can be used. The
estimates of this variability show that this factor is important when
considering the spectrum of spontaneous mutations and is strongly reflected
in the divergence of sequences. Smaller variability is found for the third
position of codons than for the first and second codon positions. This may
be because of less selective constraints on this position or because the
third position has been saturated with mutations for the sequences
examined.
相似文献
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Streelman JT Gmyrek SL Kidd MR Kidd C Robinson RL Hert E Ambali AJ Kocher TD 《Molecular ecology》2004,13(8):2471-2479
Rapidly evolving systems offer the chance to observe genetic and phenotypic change in real time. We exploit a well-characterized introduction of cichlid fish into Lake Malawi National Park to document a short history of habitat colonization and the evolution of genes and colour pattern. In the early 1960s, a fish exporter introduced individuals of Cynotilapia afra to a single site (Mitande Point) of Thumbi West Island and, as late as 1983, the species was confined to this location. In 2001, C. afra had colonized the entire perimeter of Thumbi West. In July of that year, we sampled C. afra individuals from six sites around the island and scored variation in dorsal fin colour as well as allelic diversity at six microsatellite loci. We found that, in two decades, C. afra had diverged into genetically distinct, phenotypically different northern and southern populations. We observed a high proportion of hybrids between the introduced C. afra and the native Metriaclima zebra on the southern coast of Thumbi West, and speculate that hybridization is facilitated by low water clarity at these windward sites. The short history of C. afra at Thumbi West is a microcosm of contemporary evolutionary divergence and may provide the opportunity to study the process from start to finish in genetic detail. 相似文献
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Functional interactions of the Escherichia coli PriA helicase 181N-terminal domain with the DNA and nucleotide cofactors have been quantitatively examined. The isolated 181N-terminal domain forms a stable dimer in solution, most probably reflecting the involvement of the domain in specific cooperative interactions of the intact PriA protein--double-stranded DNA (dsDNA) complex. Only one monomer of the domain dimer binds the DNA; i.e., the dimer has one effective DNA-binding site. Although the total site size of the dimer--single-stranded DNA (ssDNA) complex is ~13 nucleotides, the DNA-binding subsite engages in direct interactions with approximately five nucleotides. A small number of interacting nucleotides indicates that the DNA-binding subsites of the PriA helicase, i.e., the strong subsite on the helicase domain and the weak subsite on the N-terminal domain, are spatially separated in the intact enzyme. Contrary to current views, the subsite has an only slight preference for the 3'-end OH group of the ssDNA and lacks any significant base specificity, although it has a significant dsDNA affinity. Unlike the intact helicase, the DNA-binding subsite of the isolated domain is in an open conformation, indicating the presence of the direct helicase domain--N-terminal domain interactions. The discovery that the 181N-terminal domain possesses a nucleotide-binding site places the allosteric, weak nucleotide-binding site of the intact PriA on the N-terminal domain. The specific effect of ADP on the domain DNA-binding subsite indicates that in the intact helicase, the bound ADP not only opens the DNA-binding subsite but also increases its intrinsic DNA affinity. 相似文献
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Martin Kolisko Ivan Cepicka Vladimir Hampl Jessica Leigh Andrew J Roger Jaroslav Kulda Alastair GB Simpson Jaroslav Flegr 《BMC evolutionary biology》2008,8(1):205