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81.
Barrionuevo P Delpino MV Velásquez LN García Samartino C Coria LM Ibañez AE Rodríguez ME Cassataro J Giambartolomei GH 《Microbes and infection / Institut Pasteur》2011,13(3):239-250
The strategies that allow Brucella abortus to persist for years inside macrophages subverting host immune responses are not completely understood. Immunity against this bacterium relies on the capacity of IFN-γ to activate macrophages, endowing them with the ability to destroy intracellular bacteria. We report here that infection with B. abortus down-modulates the expression of the type I receptor for the Fc portion of IgG (FcγRI, CD64) and FcγRI-restricted phagocytosis regulated by IFN-γ in human monocytes/macrophages. Both phenomena were not dependent on bacterial viability, since they were also induced by heat-killed B. abortus (HKBA), suggesting that they were elicited by a structural bacterial component. Accordingly, a prototypical B. abortus lipoprotein (L-Omp19), but not its unlipidated form, inhibited both CD64 expression and FcγRI-restricted phagocytosis regulated by IFN-γ. Moreover, a synthetic lipohexapeptide that mimics the structure of the protein lipid moiety also inhibited CD64 expression, indicating that any Brucella lipoprotein could down-modulate CD64 expression and FcγRI-restricted phagocytosis. Pre-incubation of monocytes/macrophages with anti-TLR2 mAb blocked the inhibition of the CD64 expression mediated by HKBA and L-Omp19. These results, together with our previous observations establish that B. abortus utilizes its lipoproteins to inhibit the monocytes/macrophages activation mediated by IFN-γ and to subvert host immunonological responses. 相似文献
82.
Rendal Vázquez ME Díaz Román TM Rodríguez Cabarcos M Zavanella Botta C Domenech García N González Cuesta M Sánchez Dopico MJ Pértega Díaz S Andión Núñez C 《Cell and tissue banking》2008,9(2):101-107
To analyse the influence of cold ischemic time (CIT) (2–24 h) and of cryopreservation (liquid phase) on the viability of the
valvular fibroblasts and in the presence of apoptosis. Cardiac valves from 10 pigs were evaluated by anatomo-pathological
study of the wall, muscle and leaflet. At the same time, the presence of cellular death due to apoptosis was investigated
in two ways; directly on tissue by Apodetec system and by two-colour flow cytometry assay analyzing a suspension of fibroblast
from valve leaflets using Anexina V and propidium iodure (PI). We established three groups of samples to compare different
experimental conditions: 2 h of ischemia (group 1), 24 h of ischemia (group 2), and a programme of cryopreservation (−1°C/min)
after 2 h of ischemia, followed by storage in liquid nitrogen during a week and thawing was performed (group 3). The analysis
of viabilities showed slight differences between all three groups. The results indicated CIT of 24 h undergoing more structural
affectation than CIT of 2 h. Flow cytometry analysis did not show important differences between groups; however cryopreserved
samples (group 3) slightly less viability and a higher percentage of death by apoptosis than group 1 and 2 using flow cytometry.
Apoptosis was confirmed on tissue from all valves but mainly in samples of group 2 and group 3. In summary, the viability
of the valves in the case of ischemic times of 2 h, 24 h or after cryopreservation/thawing differs slightly. The death of
the cells is mainly mediated by necrosis and not by apoptosis. 相似文献
83.
Rausell F Pertusa JF Gómez-Piquer V Hermenegildo C García-Pérez MA Cano A Tarín JJ 《Molecular reproduction and development》2007,74(7):860-869
We analyzed the effect of in vitro aging of mouse oocytes in the presence of dithiothreitol (DTT) on relative levels of glutathione S-transferase (GST) activity and thiols in oocytes, and cell number, DNA fragmentation and cellular allocation to the inner cell mass (ICM) and trophectoderm (TE) lineage at the blastocyst stage. Ovulated oocytes from gonadotropin primed hybrid female mice of 6-8 weeks of age were aged in vitro in the presence of 0, 5, 50, or 500 microM DTT for 6 hr prior to insemination. Relative levels of GST activity and thiols in oocytes were determined by confocal laser scanning microscopy, DNA fragmentation using a single-step TUNEL method, and cell allocation to the ICM and TE lineage by blastocyst staining with propidium iodide and Hoechst 33258. Non-aged oocytes exhibited higher relative levels of GST activity and thiols when compared to oocytes aged in the presence of 0, 5, and 50 microM DTT. Day 5 blastocysts from the 5, 50, and 500 microM DTT groups exhibited higher total number of cells, number of ICM cells, and ICM/TE ratio, but lower percentage of number of nuclei with DNA fragmentation/number of ICM cells than blastocyst from the 0 microM DTT group. These data show that DTT counteracts the negative effects of a post-ovulatory aging of mouse oocytes in vitro on relative levels of GST activity and thiols in oocytes, and percentage of number of nuclei with DNA fragmentation/number of ICM cells, total number of cells, number of ICM cells and ICM/TE ratio in Day 5 blastocysts. 相似文献
84.
Genetic determinants of bone mass. 总被引:14,自引:0,他引:14
A genetic contribution to bone mass determination was first described in the early 70s. Elucidation of gene contribution to this has since been attempted through studies analyzing associations between bone mass acquisition and/or maintenance and polymorphic variations of several genes. The first to be described was the vitamin D receptor gene (VDR), initially claimed to contribute to almost 75% of the genetic variation in bone mineral density (BMD) in twin and general population studies. Not all of the studies published to date conclude that a clear relationship exists between polymorphic VDR alleles and BMD, and the molecular basis for the VDR gene polymorphisms influence on bone mineralization has not yet been clarified. Since then, other genes with a significant role in bone metabolism such as estradiol receptor, collagen type 1alpha1, TGF-beta1, interleukin-6, calcitonin receptor, alpha2-HS-glycoprotein, osteocalcin, calcium-sensing receptor, interleukin-1 receptor antagonist, beta3-adrenergic receptor, apolipoprotein E, PTH, IGF-I and glucocorticoid receptor have been analyzed. Some polymorphic variations in these genes have been associated in some works with significant differences in BMD, with even more significant contributions when associations of different gene polymorphisms were analyzed. Again, the molecular basis for the contribution of these alleles to bone mass determination has not yet been described. A different approach has been attempted by linkage analysis of loci involved in bone density in pedigrees with low BMD using BMD as a quantitative trait. Recent results do not confirm, in these families, any association with any of the previously reported genes, but rather with other as yet unidentified genes. The genetic contribution to mild variations in the general population, as a result of environmental and endogenous individual influences, probably differs completely from that providing a pathologic BMD. 相似文献
85.
Background
To compare the characteristics and prognostic features of ischemic stroke in patients with diabetes and without diabetes, and to determine the independent predictors of in-hospital mortality in people with diabetes and ischemic stroke. 相似文献86.
87.
88.
Alberto Zambrano Verónica García-Carpizo María Esther Gallardo Raquel Villamuera Maria Ana Gómez-Ferrería Angel Pascual Nicolas Buisine Laurent M. Sachs Rafael Garesse Ana Aranda 《The Journal of cell biology》2014,204(1):129-146
There is increasing evidence that the thyroid hormone (TH) receptors (THRs) can play a role in aging, cancer and degenerative diseases. In this paper, we demonstrate that binding of TH T3 (triiodothyronine) to THRB induces senescence and deoxyribonucleic acid (DNA) damage in cultured cells and in tissues of young hyperthyroid mice. T3 induces a rapid activation of ATM (ataxia telangiectasia mutated)/PRKAA (adenosine monophosphate–activated protein kinase) signal transduction and recruitment of the NRF1 (nuclear respiratory factor 1) and THRB to the promoters of genes with a key role on mitochondrial respiration. Increased respiration leads to production of mitochondrial reactive oxygen species, which in turn causes oxidative stress and DNA double-strand breaks and triggers a DNA damage response that ultimately leads to premature senescence of susceptible cells. Our findings provide a mechanism for integrating metabolic effects of THs with the tumor suppressor activity of THRB, the effect of thyroidal status on longevity, and the occurrence of tissue damage in hyperthyroidism. 相似文献
89.
Nuria Lauzurica Luis García-García José A. Fuentes Mercedes Delgado 《Journal of physiology and biochemistry》2013,69(1):69-74
Serotonin (5-HT) is one of the regulators of feeding in humans. Drugs acting on the serotoninergic system are used to treat bulimia nervosa and to enhance the effect of hypocaloric diets in overweight subjects. They act rapidly to normalise feeding when used to treat eating-related problems. To explore the role of the 5-HT transporter (serotonin transporter (SERT)) in the short-term action of serotonin selective reuptake inhibitor fluoxetine, rats were i.p. given the drug for five consecutive days. Acute administration of fluoxetine in male and female rats produced a strong reduction in food intake, an effect that held up when daily treatment was maintained for five consecutive days. This reduction translated into a diminution of body weight that was statistically significant in the case of the males. As a reflection of the body weight change in rats killed after the fifth daily drug injection, retroperitoneal fat pad also decreased; a diminution that was statistically significant in the case of male rats. In these conditions, plasma leptin levels of both male and female rats were lower than in untreated animals. While acute fluoxetine administration did not modify SERT gene expression, subchronic drug treatment increased the content of SERT mRNA in the midbrain raphe complex of both rat genders. These findings may contribute to explain the role of SERT in fluoxetine action on binging and as an adjunct to hypocaloric diets. 相似文献
90.
Guillermo López Marcos López-Parra Germán Garrote Leonardo Fernández Teresa del Rey-Wamba Rafael Arenas-Rojas Maribel García-Tardío Gema Ruiz Irene Zorrilla Manuel Moral Miguel A. Simón 《European Journal of Wildlife Research》2014,60(2):359-366
The conservation of endangered species requires accurate data, and knowledge of cause-specific mortality rates is one of the most important issues. In recent years, conservation programs for the critically endangered Iberian lynx Lynx pardinus have been developed on the basis of mortality data derived 30 years ago from the small Doñana population. Thus, there is an urgent need for an update of mortality rates and causes in both populations (Sierra Morena and Doñana). Here we use radio-tracking information from the whole range of the Iberian lynx to quantify mortality rates and identify their causes. Between 2006 and 2011, we radio-tagged 78 Iberian lynxes from its two remaining populations (39 from Sierra Morena and 39 from Doñana). Mortality events were evaluated to identify causes, and cause-specific annual mortality rates (AMR) were obtained using the nonparametric cumulative incidence function estimator. Overall, AMR was estimated at 0.16?±?0.05 (0.19?±?0.09 in Sierra Morena and 0.12?±?0.07 in Doñana). Disease was the main cause of mortality both for the whole population and the Doñana population. Poaching was the main cause of mortality in Sierra Morena. Our results suggest that the best strategy for conserving this species is to focus action on decreasing the fatal effect of disease and poaching. Given the possible existence of an underlying inbreeding-mediated immunosuppression, genetic management aimed at increasing the genetic diversity of this population is also recommended. 相似文献