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排序方式: 共有398条查询结果,搜索用时 15 毫秒
71.
Joseph S. Johnson DeeAnn M. Reeder James W. McMichael III Melissa B. Meierhofer Daniel W. F. Stern Shayne S. Lumadue Lauren E. Sigler Harrison D. Winters Megan E. Vodzak Allen Kurta Joseph A. Kath Kenneth A. Field 《PloS one》2014,9(11)
An estimated 5.7 million or more bats died in North America between 2006 and 2012 due to infection with the fungus Pseudogymnoascus destructans (Pd) that causes white-nose syndrome (WNS) during hibernation. The behavioral and physiological changes associated with hibernation leave bats vulnerable to WNS, but the persistence of bats within the contaminated regions of North America suggests that survival might vary predictably among individuals or in relation to environmental conditions. To investigate variables influencing WNS mortality, we conducted a captive study of 147 little brown myotis (Myotis lucifugus) inoculated with 0, 500, 5 000, 50 000, or 500 000 Pd conidia and hibernated for five months at either 4 or 10°C. We found that female bats were significantly more likely to survive hibernation, as were bats hibernated at 4°C, and bats with greater body condition at the start of hibernation. Although all bats inoculated with Pd exhibited shorter torpor bouts compared to controls, a characteristic of WNS, only bats inoculated with 500 conidia had significantly lower survival odds compared to controls. These data show that host and environmental characteristics are significant predictors of WNS mortality, and that exposure to up to 500 conidia is sufficient to cause a fatal infection. These results also illustrate a need to quantify dynamics of Pd exposure in free-ranging bats, as dynamics of WNS produced in captive studies inoculating bats with several hundred thousand conidia may differ from those in the wild. 相似文献
72.
Nicholas M. Chesarino Temet M. McMichael Jocelyn C. Hach Jacob S. Yount 《The Journal of biological chemistry》2014,289(17):11986-11992
Interferon-inducible transmembrane protein 3 (IFITM3) is essential for innate defense against influenza virus in mice and humans. IFITM3 localizes to endolysosomes where it prevents virus fusion, although mechanisms controlling its trafficking to this cellular compartment are not fully understood. We determined that both mouse and human IFITM3 are phosphorylated by the protein-tyrosine kinase FYN on tyrosine 20 (Tyr20) and that mouse IFITM3 is also phosphorylated on the non-conserved Tyr27. Phosphorylation led to a cellular redistribution of IFITM3, including plasma membrane accumulation. Mutation of Tyr20 caused a similar redistribution of IFITM3 and resulted in decreased antiviral activity against influenza virus, whereas Tyr27 mutation of mouse IFITM3 showed minimal effects on localization or activity. Using FYN knockout cells, we also found that IFITM3 phosphorylation is not a requirement for its antiviral activity. Together, these results indicate that Tyr20 is part of an endocytosis signal that can be blocked by phosphorylation or by mutation of this residue. Further mutagenesis narrowed this endocytosis-controlling region to four residues conforming to a YXXΦ (where X is any amino acid and Φ is Val, Leu, or Ile) endocytic motif that, when transferred to CD4, resulted in its internalization from the cell surface. Additionally, we found that phosphorylation of IFITM3 by FYN and mutagenesis of Tyr20 both resulted in decreased IFITM3 ubiquitination. Overall, these results suggest that modification of Tyr20 may serve in a cellular checkpoint controlling IFITM3 trafficking and degradation and demonstrate the complexity of posttranslational regulation of IFITM3. 相似文献
73.
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75.
McMichael GL Gibson CS Goldwater PN Haan EA Priest K Dekker GA MacLennan AH;South Australian Cerebral Palsy Research Group 《Human genetics》2008,124(4):411-416
Apolipoprotein E (APOE) plays a significant role in lipid metabolism and has been implicated in the growth and repair of injured
neurons. Two small studies have suggested an association between APOE genotype and cerebral palsy. We investigated if APOE
genotype is associated with an increased risk for cerebral palsy, influences the type of cerebral palsy or interacts with
prenatal viral infection to influence risk of cerebral palsy. The population-based case-control study comprised newborn screening
cards of 443 Caucasian patients with cerebral palsy and 883 Caucasian matched controls. APOE genotyping was performed on DNA
extracted from dried blood spots. Allelic and genotypic frequencies did not differ between cases and controls and combined
frequencies were 0.10 (ε2), 0.76 (ε3), 0.14 (ε4), 0.03 (ε2/ε2), 0.10 (ε2/ε3), 0.03 (ε2/ε4), 0.02 (ε4/ε4), 0.21 (ε3/ε4), 0.61
(ε3/ε3). APOE genotype was correlated with cerebral palsy, type of cerebral palsy, gestation at birth and the presence of
viral nucleic acids detected in previous work. Analysis by gestational age (all gestational ages, ≥37, 32–36 and <32 weeks)
and type of cerebral palsy (all types, diplegia, hemiplegia and quadriplegia) showed no association between APOE genotype
and cerebral palsy in this Caucasian population. An association between prenatal viral infection, APOE genotype and cerebral
palsy was not demonstrated. These results did not confirm an association between APOE genotype, cerebral palsy, type of cerebral
palsy and prenatal infection in a Caucasian population. Given the low frequency of APOE ε2 and some of the heterozygote and
homozygote combinations in this study, a larger study is assessing this further. 相似文献
76.
Dendritic cells are less susceptible to human immunodeficiency virus type 2 (HIV-2) infection than to HIV-1 infection 总被引:1,自引:0,他引:1
Duvall MG Loré K Blaak H Ambrozak DA Adams WC Santos K Geldmacher C Mascola JR McMichael AJ Jaye A Whittle HC Rowland-Jones SL Koup RA 《Journal of virology》2007,81(24):13486-13498
Human immunodeficiency virus type 1 (HIV-1) infection of dendritic cells (DCs) has been documented in vivo and may be an important contributor to HIV-1 transmission and pathogenesis. HIV-1-specific CD4+ T cells respond to HIV antigens presented by HIV-1-infected DCs and in this process become infected, thereby providing a mechanism through which HIV-1-specific CD4+ T cells could become preferentially infected in vivo. HIV-2 disease is attenuated with respect to HIV-1 disease, and host immune responses are thought to be contributory. Here we investigated the susceptibility of primary myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) to infection by HIV-2. We found that neither CCR5-tropic primary HIV-2 isolates nor a lab-adapted CXCR4-tropic HIV-2 strain could efficiently infect mDCs or pDCs, though these viruses could infect primary CD4+ T cells in vitro. HIV-2-exposed mDCs were also incapable of transferring virus to autologous CD4+ T cells. Despite this, we found that HIV-2-specific CD4+ T cells contained more viral DNA than memory CD4+ T cells of other specificities in vivo. These data suggest that either infection of DCs is not an important contributor to infection of HIV-2-specific CD4+ T cells in vivo or that infection of DCs by HIV-2 occurs at a level that is undetectable in vitro. The frequent carriage of HIV-2 DNA within HIV-2-specific CD4+ T cells, however, does not appear to be incompatible with preserved numbers and functionality of HIV-2-specific CD4+ T cells in vivo, suggesting that additional mechanisms contribute to maintenance of HIV-2-specific CD4+ T-cell help in vivo. 相似文献
77.
Rates and patterns of evolution in partial sequences of five mitochondrial
genes (cytochrome b, ATPase 6, NADH dehydrogenase subunit 5, tRNA(Glu), and
the control region) were compared among taxa in the passerine bird genera
Fringilla and Carduelis. Rates of divergence do not vary significantly
among genes, even in comparisons with the control region. Rate variation
among lineages is significant only for the control region and NADH
dehydrogenase subunit 5, and patterns of variation are consistent with the
expectations of neutral theory. Base composition is biased in all genes but
is stationary among lineages, and there is evidence for directional
mutation pressure only in the control region. Despite these similarities,
patterns of substitution differ among genes, consistent with alternative
regimes of selective constraint. Rates of nonsynonymous substitution are
higher in NADH dehydrogenase subunit 5 than in other protein-coding genes,
and transitions exist in elevated proportions relative to transversions.
Transitions appear to accumulate linearly with time in tRNA(Glu), and
despite exhibiting the highest overall rate of divergence among species,
there are no transversional changes in this gene. Finally, for resolving
phylogenetic relationships among Fringilla taxa, the combined
protein-coding data are broadly similar to those of the control region in
terms of phylogenetic informativeness and statistical support.
相似文献
78.
Benjamin M Good Benjamin J Ainscough Josh F McMichael Andrew I Su Obi L Griffith 《Genome biology》2014,15(8)
Interpretation of the clinical significance of genomic alterations remains the most severe bottleneck preventing the realization of personalized medicine in cancer. We propose a knowledge commons to facilitate collaborative contributions and open discussion of clinical decision-making based on genomic events in cancer. 相似文献
79.
Michael J. Fiske Ross A. Fredenburg Karl R. VanDerMeid John C. McMichael Rasappa Arumugham 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2001,753(2)
The UspA2 protein from the bacterium Moraxella catarrhalis is a potential vaccine candidate for preventing human diseases caused by this organism. Before a vaccine can be administered parentally, the level of endotoxin must be reduced as much as possible. However, in this case the endotoxin was very tightly complexed with the UspA2 protein and could not be dissociated with Triton X-100. It was found that it dissociated from the protein with the zwitterionic detergents Zwittergent 3-12 and Zwittergent 3-14. The endotoxin could then be separated from the protein by either ion-exchange or gel filtration chromatography. Using the limulus amoebocyte lysate assay for quantitation, the endotoxin was reduced approximately 20 000-fold. The removal of residual endotoxin from UspA2 preparations had no detrimental effect on the immunological properties of the protein. Mouse antisera raised against UspA2 prior to, and following endotoxin reduction exhibited comparable antibody and bactericidal titers against the tested strains. Further, mice immunized with both preparations, followed by pulmonary challenge with either a homologous or a heterologous isolate, exhibited comparable levels of clearance. 相似文献
80.
Alexander J. Bridges Donna R. Cody Hairong Zhou Amy McMichael David W. Fry 《Bioorganic & medicinal chemistry》1995,3(12)
4-Benzylaminoquinazolines can be potent reversible inhibitors of the EGFR tyrosine kinase at the ATP binding site. Examination of benzylic methylation reveals that an (R)-methyl group is four- to six-fold activating, with an optimal Ki of 630 pM for compound II. In sharp contrast, (S)-methylation causes a > 30 to 500-fold loss of inhibitory activity, showing that the ATP-binding site of the receptor has very low tolerance for even moderate out-of-plane bulk in certain directions. It is suggested that the best of these inhibitors can induce a conformation of the kinase not available to poorer inhibitors. 相似文献