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71.
Q fever is an infectious disease caused by Coxiella burnetii, which may become chronic when cytokine network and cell-mediated immune responses are altered. Chemokines, such as Regulated upon Activation, Normal T cell Expressed and Secreted (RANTES, CCL5) and Monocyte Chemoattractant Protein-1 (MCP-1, CCL2), are specialized in the trafficing of peripheral blood mononuclear cells (PBMC), and are associated with T cell polarization that is essential for intracellular survival of C. burnetii. The present study investigated whether or not the infection status (no infection and acute or chronic infection with C. burnetii) of donors, affected the production of the two chemokines by PBMC with or without stimulation with virulent and avirulent C. burnetii. Our findings indicate that in vitro exposure to virulent or avirulent C. burnetii stimulated the production of RANTES and MCP-1 in PBMC obtained from healthy adults. The co-cultivation of endothelial cells and human PBMC resulted in an increased production of MCP-1 and the up-regulation of RANTES, which were contact-dependent. Unstimulated PBMC from patients with acute or chronic Q fever overproduced MCP-1. Interestingly, the addition of C. burnetii resulted in an increased production of RANTES and MCP-1 by PBMC obtained from patients with chronic Q fever, and the co-cultivation of PBMC with endothelial cells amplified increased production of chemokines. Circulating levels of RANTES and MCP-1 were also increased in chronic Q fever. We suggest that the overproduction of RANTES and MCP-1 secondary to the contact of PBMC with endothelium may perpetuate exaggerated inflammatory responses leading to inappropriate PBMC trafficking and to the pathogenesis of Q fever. 相似文献
72.
C Allard V Desgagné J Patenaude M Lacroix L Guillemette MC Battista M Doyon J Ménard JL Ardilouze P Perron L Bouchard MF Hivert 《Epigenetics》2015,10(4):342-351
Leptin is an adipokine that acts in the central nervous system and regulates energy balance. Animal models and human observational studies have suggested that leptin surge in the perinatal period has a critical role in programming long-term risk of obesity. In utero exposure to maternal hyperglycemia has been associated with increased risk of obesity later in life. Epigenetic mechanisms are suspected to be involved in fetal programming of long term metabolic diseases. We investigated whether DNA methylation levels near LEP locus mediate the relation between maternal glycemia and neonatal leptin levels using the 2-step epigenetic Mendelian randomization approach. We used data and samples from up to 485 mother-child dyads from Gen3G, a large prospective population-based cohort. First, we built a genetic risk score to capture maternal glycemia based on 10 known glycemic genetic variants (GRS10) and showed it was an adequate instrumental variable (β = 0.046 mmol/L of maternal fasting glucose per additional risk allele; SE = 0.007; P = 7.8 × 10−11; N = 467). A higher GRS10 was associated with lower methylation levels at cg12083122 located near LEP (β = −0.072 unit per additional risk allele; SE = 0.04; P = 0.05; N = 166). Direction and effect size of association between the instrumental variable GRS10 and methylation at cg12083122 were consistent with the negative association we observed using measured maternal glycemia. Lower DNA methylation levels at cg12083122 were associated with higher cord blood leptin levels (β = −0.17 log of cord blood leptin per unit; SE = 0.07; P = 0.01; N = 170). Our study supports that maternal glycemia is part of causal pathways influencing offspring leptin epigenetic regulation. 相似文献
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74.
Chimpanzee fetal G gamma and A gamma globin gene nucleotide sequences provide further evidence of gene conversions in hominine evolution 总被引:5,自引:0,他引:5
The fetal globin genes G gamma and A gamma from one chromosome of a
chimpanzee (Pan troglodytes) were sequenced and found to be closely similar
to the corresponding genes of man and the gorilla. These genes contain
identical promoter and termination signals and have exons 1 and 2 separated
by the conserved short intron 1 (122 bp) and exons 2 and 3 separated by the
more rapidly evolving, larger intron 2 (893 bp and 887 bp in chimpanzee G
gamma and A gamma, respectively). Each intron 2 has a stretch of simple
sequence DNA (TG)n serving possibly as a "hot spot" for recombination. The
two chimpanzee genes encode polypeptide chains that differ only at position
136 (glycine in G gamma and alanine in A gamma) and that are identical to
the corresponding human chains, which have aspartic acid at position 73 and
lysine at 104 in contrast to glycine and arginine at these respective
positions of the gorilla A gamma chain. Phylogenetic analysis by the
parsimony method revealed four silent (synonymous) base substitutions in
evolutionary descent of the chimpanzee G gamma and A gamma codons and none
in the human and gorilla codons. These Homininae (Pan, Homo, Gorilla)
coding sequences evolved at one-tenth the average mammalian rate for
nonsynonymous and one-fourth that for synonymous substitutions. Three
sequence regions that were affected by gene conversions between chimpanzee
G gamma and A gamma loci were identified: one extended 3' of the hot spot
with G gamma replaced by the A gamma sequence, another extended 5' of the
hot spot with A gamma replaced by G gamma, and the third conversion
extended from the 5' flanking to the 5' end of intron 2, with G gamma
replaced here by the A gamma sequence. A conversion similar to this third
one has occurred independently in the descent of the gorilla genes. The
four previously identified conversions, labeled C1-C4 (Scott et al. 1984),
were substantiated with the addition of the chimpanzee genes to our
analysis (C1 being shared by all three hominines and C2, C3, and C4 being
found only in humans). Thus, the fetal genes from all three of these
hominine species have been active in gene conversions during the descent of
each species.
相似文献
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77.
Esther Heikens Masja Leendertse Lucas M Wijnands Miranda van Luit-Asbroek Marc JM Bonten Tom van der Poll Rob JL Willems 《BMC microbiology》2009,9(1):19-7
Background
Enterococcus faecium has globally emerged as a cause of hospital-acquired infections with high colonization rates in hospitalized patients. The enterococcal surface protein Esp, identified as a potential virulence factor, is specifically linked to nosocomial clonal lineages that are genetically distinct from indigenous E. faecium strains. To investigate whether Esp facilitates bacterial adherence and intestinal colonization of E. faecium, we used human colorectal adenocarcinoma cells (Caco-2 cells) and an experimental colonization model in mice. 相似文献78.
79.
80.
Multiple forms of tubulin in the cytoskeletal and flagellar microtubules of polytomella 总被引:14,自引:9,他引:5 下载免费PDF全文
The alga polytomella contains several organelles composed of microtubules, including four flagella and hundreds of cytoskeletal microtubules. Brown and co-workers have shown (1976. J. Cell Biol. 69:6-125; 1978, Exp. Cell Res. 117: 313-324) that the flagella could be removed and the cytoskeletans dissociated, and that both structures could partially regenerate in the absence of protein synthesis. Because of this, and because both the flagella and the cytoskeletons can be isolated intact, this organism is particularly suitable for studying tubulin heterogeneity and the incorporation of specific tubulins into different microtubule-containing organelles in the same cell. In order to define the different species of tubulin in polytonella cytoplasm, a (35)S- labeled cytoplasmic fraction was subjected to two cycles of assembly and disassembly in the presence of unlabeled brain tubulin. Comparison of the labeled polytomella cytoplasmic tubulin obtained by this procedure with the tubulin of isolated polytomella flagella by two-dimensional gel electrophoresis showed that, whereas the β-tubulin from both cytoplasmic and flagellar tubulin samples comigrated, the two α-tubulins had distinctly different isoelectic points. As a second method of isolating tubulin from the cytoplasm, cells were gently lysed with detergent and intact cytoskeletons obtained. When these cytoskeletons were exposed to cold temperature, the proteins that were released were found to be highly enriched in tubulin; this tubulin, by itself, could be assembled into microtubules in vitro. The predominant α-tubulin of this in vitro- assembled cytoskeletal tubulin corresponded to the major cytoplasmic α-tubulin obtained by coassembly of labeled polytomella cytoplasmic extract with brain tubulin and was quite distinct from the α-tubulin of purified flagella. These results clearly show that two different microtubule-containing organelles from the same cell are composed of distinct tubulins. 相似文献