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121.
Phylogenetic analysis of the outer-membrane-protein genes of Chlamydiae, and its implication for vaccine development 总被引:9,自引:0,他引:9
Examination of 18 complete and 6 partial sequences of the major outer-
membrane protein from 24 chlamydiae isolates was used to reconstruct their
evolutionary relationships. From this analysis, assuming that the clades
with 100% bootstrap support are correct, come the following conclusions:
(1) The tree of these sequences is not congruent with the phylogeny of the
hosts, and thus host switching would seem to have occurred, thereby
limiting the extent to which there has been coevolution of parasite and
host. (2) The tree is also noncongruent with clustering by type of cell
infected, thereby limiting the extent to which there has been coevolution
of parasite and the cell type that it infects. (3) The tree is also
noncongruent with clustering by the organ infected (eyes or genitalia),
thereby limiting the extent to which there has been coevolution of parasite
and the organ that it infects. (4) The tree is also noncongruent with
genital strains arising from lymphogranuloma venereum strains. (5) The tree
is also noncongruent with the geographic site at which the isolates were
obtained, thereby limiting the extent of divergence explained by geographic
separation. (6) There are estimated to be 185 amino acid positions that are
invariable (as opposed to unvaried) in the major outer-membrane protein.
There are 10 unvaried positions in the variable domains, of which 9 appear
to be invariable, giving some reason to hope that development of a vaccine
might be possible. (7) The rate of change of this protein is too small to
see increased divergence over the time span of isolation of these genes,
giving hope to any vaccine having longevity. Bootstrapping supports those
portions of the tree on which the first five conclusions above depend. The
picture that these results provide is more one of pathogen versatility than
one of coevolutionary constraints. In addition, we examined 10 60-KDa,
outer-membrane protein- 2 genes, all but one of which were from these same
strains. The tree was not, among the trachomatis strains, congruent with
the major-outer- membrane protein tree, suggesting that gene exchange could
be occurring among strains. Moreover, there is an apparent slowdown in
divergence in this gene, among the trachomatis strains.
相似文献
122.
Angelika Wientzek María‐José Tormo Díaz Jose Maria Huerta Castaño Pilar Amiano Larraitz Arriola Kim Overvad Jane Nautrup Østergaard Marie‐Aline Charles Guy Fagherazzi Domenico Palli Benedetta Bendinelli Guri Skeie Kristin Benjaminsen Borch Wanda Wendel‐Vos Ellen de Hollander Anne M. May Marjolein EM den Ouden Antonia Trichopoulou Elissavet Valanou Stefan Söderberg Paul W. Franks Soren Brage Matthäus Vigl Heiner Boeing Ulf Ekelund 《Obesity (Silver Spring, Md.)》2014,22(5):E127-E134
123.
124.
Acidophilic activation of steroid hormone receptors 总被引:4,自引:0,他引:4
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128.
Maxwell CA Benítez J Gómez-Baldó L Osorio A Bonifaci N Fernández-Ramires R Costes SV Guinó E Chen H Evans GJ Mohan P Català I Petit A Aguilar H Villanueva A Aytes A Serra-Musach J Rennert G Lejbkowicz F Peterlongo P Manoukian S Peissel B Ripamonti CB Bonanni B Viel A Allavena A Bernard L Radice P Friedman E Kaufman B Laitman Y Dubrovsky M Milgrom R Jakubowska A Cybulski C Gorski B Jaworska K Durda K Sukiennicki G Lubiński J Shugart YY Domchek SM Letrero R Weber BL Hogervorst FB Rookus MA 《PLoS biology》2011,9(11):e1001199
Differentiated mammary epithelium shows apicobasal polarity, and loss of tissue organization is an early hallmark of breast carcinogenesis. In BRCA1 mutation carriers, accumulation of stem and progenitor cells in normal breast tissue and increased risk of developing tumors of basal-like type suggest that BRCA1 regulates stem/progenitor cell proliferation and differentiation. However, the function of BRCA1 in this process and its link to carcinogenesis remain unknown. Here we depict a molecular mechanism involving BRCA1 and RHAMM that regulates apicobasal polarity and, when perturbed, may increase risk of breast cancer. Starting from complementary genetic analyses across families and populations, we identified common genetic variation at the low-penetrance susceptibility HMMR locus (encoding for RHAMM) that modifies breast cancer risk among BRCA1, but probably not BRCA2, mutation carriers: n = 7,584, weighted hazard ratio (wHR) = 1.09 (95% CI 1.02–1.16), ptrend = 0.017; and n = 3,965, wHR = 1.04 (95% CI 0.94–1.16), ptrend = 0.43; respectively. Subsequently, studies of MCF10A apicobasal polarization revealed a central role for BRCA1 and RHAMM, together with AURKA and TPX2, in essential reorganization of microtubules. Mechanistically, reorganization is facilitated by BRCA1 and impaired by AURKA, which is regulated by negative feedback involving RHAMM and TPX2. Taken together, our data provide fundamental insight into apicobasal polarization through BRCA1 function, which may explain the expanded cell subsets and characteristic tumor type accompanying BRCA1 mutation, while also linking this process to sporadic breast cancer through perturbation of HMMR/RHAMM. 相似文献
129.
Moringa oleifera is a pantropical tree of the family Moringaceae. A previously undescribed property of an aqueous extract from the seeds of this plant is the modulation of ruminal fermentation patterns, especially protein degradation, as demonstrated in a short-term batch incubation system. Gas, short chain fatty acids (SCFA) and cellulolytic enzyme activities were determined as general fermentation parameters. A dot blot assay able to directly detect true protein in rumen fluid samples was used to quantify protein degradation. For complex substrates the interpretation of protein degradation profiles was amended by polyacrylamide gel electrophoresis (PAGE) of the samples. When incubated with pure carbohydrates at a concentration of 1 mg ml–1, the extract reduced microbial degradation of the model protein, bovine serum albumin (BSA), such that its concentration was at least 40% above the control after 12 h of incubation. Total protein degradation was thus delayed by approximately 9 h. When fermented along with wheat straw, leaf protein (Rubisco) was almost entirely protected during 12 h of fermentation. The degradation of soy proteins was retarded by at least 4- 6 h, depending on the protein band. There were strong side effects on the fermentation of pure cellulose (SCFA yield -60% after 12 h), whereas cellobiose and starch fermentation were less affected (-18 and -8%, respectively). When the complex substrates were fermented, SCFA yield was reduced by approximately 30% after 12 h. In our work we clearly demonstrate the efficacy of the new substance, which is neither a tannin nor a saponin, in an in vitro system, using pure as well as complex substrates. The properties shown in vitro for the crude extract suggest that it could have a positive effect on the protein metabolism of ruminants under intensive management and that negative side effects can be overcome by an optimized dosage. If the chemical nature of the active substance and its mechanism of action can be clarified, it may provide an alternative to replace critical synthetic feed additives (such as antibiotics) for high yielding dairy cows. 相似文献
130.
Rohola Hosseini Gerda EM Lamers Zlatan Hodzic Annemarie H Meijer Marcel JM Schaaf Herman P Spaink 《Autophagy》2014,10(10):1844-1857
High-resolution imaging of autophagy has been used intensively in cell culture studies, but so far it has been difficult to visualize this process in detail in whole animal models. In this study we present a versatile method for high-resolution imaging of microbial infection in zebrafish larvae by injecting pathogens into the tail fin. This allows visualization of autophagic compartments by light and electron microscopy, which makes it possible to correlate images acquired by the 2 techniques. Using this method we have studied the autophagy response against Mycobacterium marinum infection. We show that mycobacteria during the progress of infection are frequently associated with GFP-Lc3-positive vesicles, and that 2 types of GFP-Lc3-positive vesicles were observed. The majority of these vesicles were approximately 1 μm in size and in close vicinity of bacteria, and a smaller number of GFP-Lc3-positive vesicles was larger in size and were observed to contain bacteria. Quantitative data showed that these larger vesicles occurred significantly more in leukocytes than in other cell types, and that approximately 70% of these vesicles were positive for a lysosomal marker. Using electron microscopy, it was found that approximately 5% of intracellular bacteria were present in autophagic vacuoles and that the remaining intracellular bacteria were present in phagosomes, lysosomes, free inside the cytoplasm or occurred as large aggregates. Based on correlation of light and electron microscopy images, it was shown that GFP-Lc3-positive vesicles displayed autophagic morphology. This study provides a new approach for injection of pathogens into the tail fin, which allows combined light and electron microscopy imaging in vivo and opens new research directions for studying autophagy process related to infectious diseases. 相似文献