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201.
Distinct human immunodeficiency virus type 1 subtype A virus circulating in West Africa: sub-subtype A3 下载免费PDF全文
Meloni ST Kim B Sankalé JL Hamel DJ Tovanabutra S Mboup S McCutchan FE Kanki PJ 《Journal of virology》2004,78(22):12438-12445
Phylogenetic analyses demonstrate significant diversity in worldwide circulating strains of human immunodeficiency virus type 1 (HIV-1). Detailed studies have revealed a complex pattern of intersubtype recombinations, as well as evidence of sub-subtypes circulating in various populations. In this study, we characterized an HIV-1 strain that had previously been identified as a distinct subcluster within the subtype A radiation based on partial sequence data. These viruses were of particular interest given that we recently found that their prevalence was significantly higher in dually infected individuals compared to women who were singly infected with HIV-1. Five viruses isolated from commercial sex workers in Dakar, Senegal, were full-length PCR amplified and sequenced. Phylogenetic analyses indicated that, whereas three of these viruses were closely related and clustered overall within the HIV-1 subtype A radiation, they were distinct from previously characterized sub-subtype A1 and A2 viruses. The clustering pattern was maintained in the individual gag, pol, and env regions of the genome. Distance calculations between these viruses, which we termed A3, and other reference sub-subtype A1 and A2 viruses fell in the range of distances between previously characterized sub-subtype groups. In addition, we found evidence of two A3-containing recombinants in our cohort. These recombinants are mosaics composed of sequence from both sub-subtype A3 and CRF02_AG, the major circulating recombinant form in this West African population. Based on phylogenetic analyses, we propose that the group of viruses found in the Dakar sex worker cohort, previously referred to as HIV-1 A subcluster 2, be referred to as HIV-1 sub-subtype A3. 相似文献
202.
Bertrand L Ginion A Beauloye C Hebert AD Guigas B Hue L Vanoverschelde JL 《American journal of physiology. Heart and circulatory physiology》2006,291(1):H239-H250
Diabetic hearts are known to be more susceptible to ischemic disease. Biguanides, like metformin, are known antidiabetic drugs that lower blood glucose concentrations by decreasing hepatic glucose production and increasing glucose disposal in muscle. Part of these metabolic effects is thought to be mediated by the activation of AMP-activated protein kinase (AMPK). In this work, we studied the relationship between AMPK activation and glucose uptake stimulation by biguanides and oligomycin, another AMPK activator, in both insulin-sensitive and insulin-resistant cardiomyocytes. In insulin-sensitive cardiomyocytes, insulin, biguanides and oligomycin were able to stimulate glucose uptake with the same efficiency. Stimulation of glucose uptake by insulin or biguanides was correlated to protein kinase B (PKB) or AMPK activation, respectively, and were additive. In insulin-resistant cardiomyocytes, where insulin stimulation of glucose uptake was greatly reduced, biguanides or oligomycin, in the absence of insulin, induced a higher stimulation of glucose uptake than that obtained in insulin-sensitive cells. This stimulation was correlated with the activation of both AMPK and PKB and was sensitive to the phosphatidylinositol-3-kinase/PKB pathway inhibitors. Finally, an adenoviral-mediated expression of a constitutively active form of AMPK increased both PKB phosphorylation and glucose uptake in insulin-resistant cardiomyocytes. We concluded that AMPK activators, like biguanides and oligomycin, are able to restore glucose uptake stimulation, in the absence of insulin, in insulin-resistant cardiomyocytes via the additive activation of AMPK and PKB. Our results suggest that AMPK activation could restore normal glucose metabolism in diabetic hearts and could be a potential therapeutic approach to treat insulin resistance. 相似文献
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Phosphorylation of the agonist-activated form of G-protein-coupled receptors (GPCRs) by a protein kinase from the G-protein-coupled receptor kinase (GRK) family initiates, with arrestin proteins, a negative feedback process known as desensitization. Because these receptors are involved in so many vital functions, it seems likely that disorders affecting GRK- or arrestin-mediated regulation of GPCRs would contribute to, if not engender, disease. Traditionally, it is believed that the desensitization process protects the cell against an overstimulation; however, in certain situations, this process is maladjusted and participes in disease progression. For example, in Oguchi disease, excessive rhodopsin stimulation due to a functional loss of GRK1 or arrestin 1 leads to light sensitization and stationary night blindness. Also, transgenic mice with vascular smooth muscle-targeted overexpression of GRK2 showed an elevated resting blood pressure, suggesting that increase in GRK2 level in humans is involved in hypertension associated with a decreased effect of beta-adrenergic receptor-mediated vasorelaxation. The restoration of normal GPCR function in modulating the desensitization process has been successfully demonstrated in animal models of heart failure, which indicates that targeting GRKs or arrestins may open a novel therapeutic strategy in human diseases with GPCR dysregulation. However, the few effective pharmacological compounds in this domain currently preclude human clinical tests. 相似文献
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Heating oils and fats may lead to cyclization of polyunsaturated fatty acids, as for example linolenic acid. Cyclohexenyl and cyclopentenyl fatty acids are subsequently present in some edible oils and these are suspected to induce metabolic disorders. In a previous experiment using [1-14C] labeled molecules, we published that these cyclic fatty acids are beta oxidized to the same extent as linolenic acid, at least for the first cycle of beta oxidation. However, it is possible that the presence of a ring could alter the ability of the organism to fully oxidize the molecule. In order to test this hypothesis, we assessed the oxidative metabolism of cyclic fatty acids carrying a 14C atom at the vicinity of the ring. For this purpose, rats were force-fed from 1.1 to 1.3 MBq of a representative fraction of dietary cyclohexenyl cyclic fatty acid monomers of [9-14C] 9-(6-propyl-cyclohex-3-enyl)-non-8-enoic acids and 14CO2 production was monitored for 24h. The animals were then necropsied and the radioactivity was determined in different tissues. No consistent radioactivity was recovered as 14CO2 24h after administration of the molecules. Sixty percent of the radioactivity was recovered in the urine and 30% in the gastrointestinal tract. By combining our previous data on the oxidation of [1-14C] cyclic fatty acids and the present results, we suggest that cyclohexenyl fatty acids are first beta oxidized in a similar way as linolenic acid and that the remaining molecule carrying the ring is detoxified and eliminated in the urine and feces. 相似文献
207.
Interaction between Polo and BicD proteins links oocyte determination and meiosis control in Drosophila 总被引:1,自引:0,他引:1
Meiosis is a specialized cell cycle limited to the gametes in Metazoa. In Drosophila, oocyte determination and meiosis control are interdependent processes, and BicD appears to play a key role in both. However, the exact mechanism of how BicD-dependent polarized transport could influence meiosis and vice versa remains an open question. In this article, we report that the cell cycle regulatory kinase Polo binds to BicD protein during oogenesis. Polo is expressed in all cells during cyst formation before specifically localizing to the oocyte. This is the earliest known example of asymmetric localization of a cell-cycle regulator in this process. This localization is dependent on BicD and the Dynein complex. Loss- and gain-of-function experiments showed that Polo has two independent functions. On the one hand, it acts as a trigger for meiosis. On the other hand, it is independently required, in a cell-autonomous manner, for the activation of BicD-dependent transport. Moreover, we show that Polo overexpression can rescue a hypomorphic mutation of BicD by restoring its localization and its function, suggesting that the requirement for Polo in polarized transport acts through regulation of BicD. Taken together, our data indicate the existence of a positive feedback loop between BicD and Polo, and we propose that this loop represents a functional link between oocyte specification and the control of meiosis. 相似文献
208.
Labreuche Y Lambert C Soudant P Boulo V Huvet A Nicolas JL 《Microbes and infection / Institut Pasteur》2006,8(12-13):2715-2724
The strategies used by bacterial pathogens to circumvent host defense mechanisms remain largely undefined in bivalve molluscs. In this study, we investigated experimentally the interactions between the Pacific oyster (Crassostrea gigas) immune system and Vibrio aestuarianus strain 01/32, a pathogenic bacterium originally isolated from moribund oysters. First, an antibiotic-resistant V. aestuarianus strain was used to demonstrate that only a limited number of bacterial cells was detected in the host circulatory system, suggesting that the bacteria may localize in some organs. Second, we examined the host defense responses to V. aestuarianus at the cellular and molecular levels, using flow-cytometry and real-time PCR techniques. We showed that hemocyte phagocytosis and adhesive capabilities were affected during the course of infection. Our results also uncovered a previously-undescribed mechanism used by a Vibrio in the initial stages of host interaction: deregulation of the hemocyte oxidative metabolism by enhancing the production of reactive oxygen species and down-regulating superoxide dismutase (Cg-EcSOD) gene expression. This deregulation may provide an opportunity to the pathogen by impairing hemocyte functions and survival. These findings provide new insights into the cellular and molecular bases of the host-pathogen interactions in C. gigas oyster. 相似文献
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Over the last decades, cholinesterase (ChE) biosensors have emerged as an ultra sensitive and rapid technique for toxicity analysis in environmental monitoring, food and quality control. These systems have the potential to complement or replace the classical analytical methods by simplifying or eliminating sample preparation protocols and making field testing easier and faster with significant decrease in costs per analysis. Over the years, engineering of more sensitive ChE enzymes, development of more reliable immobilization protocols and progress in the area of microelectronics could allow ChE biosensors to be competitive for field analysis and extend their applications to multianalyte screening, development of small, portable instrumentations for rapid toxicity testing, and detectors in chromatographic systems. In this paper, we will review the research efforts over the last 20 years in fabricating AChE biosensors and the recent trends and challenges encounter once the sensor is used outside research laboratory for in situ real sample applications. The review will discuss the generations of cholinesterase sensors with their advantages and limitations, the existing electrode configurations and fabrication techniques and their applications for toxicity monitoring. We will focus on low-cost electrochemical sensors and the approaches used for enzyme immobilization. Recent works for achieving high sensitivity and selectivity are also discussed. 相似文献