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Frédéric Coutant Raul Yusef Sanchez David Tristan Félix Aude Boulay Laxmee Caleechurn Philippe Souque Catherine Thouvenot Catherine Bourgouin Anne-Sophie Beignon Pierre Charneau 《PloS one》2012,7(11)
Trials testing the RTS,S candidate malaria vaccine and radiation-attenuated sporozoites (RAS) have shown that protective immunity against malaria can be induced and that an effective vaccine is not out of reach. However, longer-term protection and higher protection rates are required to eradicate malaria from the endemic regions. It implies that there is still a need to explore new vaccine strategies. Lentiviral vectors are very potent at inducing strong immunological memory. However their integrative status challenges their safety profile. Eliminating the integration step obviates the risk of insertional oncogenesis. Providing they confer sterile immunity, nonintegrative lentiviral vectors (NILV) hold promise as mass pediatric vaccine by meeting high safety standards. In this study, we have assessed the protective efficacy of NILV against malaria in a robust pre-clinical model. Mice were immunized with NILV encoding Plasmodium yoelii Circumsporozoite Protein (Py CSP) and challenged with sporozoites one month later. In two independent protective efficacy studies, 50% (37.5–62.5) of the animals were fully protected (p = 0.0072 and p = 0.0008 respectively when compared to naive mice). The remaining mice with detectable parasitized red blood cells exhibited a prolonged patency and reduced parasitemia. Moreover, protection was long-lasting with 42.8% sterile protection six months after the last immunization (p = 0.0042). Post-challenge CD8+ T cells to CSP, in contrast to anti-CSP antibodies, were associated with protection (r = −0.6615 and p = 0.0004 between the frequency of IFN-g secreting specific T cells in spleen and parasitemia). However, while NILV and RAS immunizations elicited comparable immunity to CSP, only RAS conferred 100% of sterile protection. Given that a better protection can be anticipated from a multi-antigen vaccine and an optimized vector design, NILV appear as a promising malaria vaccine. 相似文献
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Isabel Cornejo María Isabel Niemeyer Leandro Zúñiga Yamil R. Yusef Francisco V. Sepúlveda L. Pablo Cid 《Journal of cellular physiology》2009,221(3):650-657
ClC‐2 chloride channel is present in the brain and some transporting epithelia where its function is poorly understood. We have now demonstrated that the surface channels are rapidly internalised and approximately the 70% of the surface membrane protein recycles after 4‐ to 8‐min internalisation. Endocytosis of ClC‐2 was dependent upon tyrosine 179 located within an endocytic motif. Rapid recycling accompanied by an even faster internalisation could account for the abundant presence of ClC‐2 in intracellular membranous structures. At least a proportion of ClC‐2 resides in lipid rafts. Use of β‐cyclodextrin led to an increase in cell surface channel, but, surprisingly, a decrease in functionally active channels. We suggest that ClC‐2 requires residing in β‐cyclodextrin sensitive clusters with other molecules in order to remain active. Regulation of ClC‐2 trafficking to and within the membrane could be a means of modulating its activity. J. Cell. Physiol. 221: 650–657, 2009. © 2009 Wiley‐Liss, Inc. 相似文献
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Reef coral survival and mortality at low temperatures in the Arabian Gulf: new species-specific lower temperature limits 总被引:8,自引:0,他引:8
A series of cold fronts passing over the western Arabian Gulf from December 1988 to March 1989 produced the longest period of sustained low water temperatures ever recorded in a coral reef area. Sea water temperatures recorded on two reefs during this period provide new estimates of lower thermal limits for reef coral survival. Severe mortality of the corals Acropora pharaonis and Platygyra daedalea occurred at the northern site where minimum temperatures fell below 11.5°C on four consecutive days and mean daily temperatures were 13°C or less for more than 30 days. However, Porites compressa, the principal reef-former in this area, and various faviid corals initially showed only sub-lethal effects and appeared normal after six months. Corals were not damaged at the southern site, where minimum water temperature fell below 12.5°C for two consecutive days, but mean temperatures were 14°C or less for only 5 non-consecutive days. 相似文献
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Diversity and cold-active hydrolytic enzymes of culturable bacteria associated with Arctic sea ice,Spitzbergen 总被引:8,自引:0,他引:8
Groudieva T Kambourova M Yusef H Royter M Grote R Trinks H Antranikian G 《Extremophiles : life under extreme conditions》2004,8(6):475-488
The diversity of culturable bacteria associated with sea ice from four permanently cold fjords of Spitzbergen, Arctic Ocean, was investigated. A total of 116 psychrophilic and psychrotolerant strains were isolated under aerobic conditions at 4°C. The isolates were grouped using amplified rDNA restriction analysis fingerprinting and identified by partial sequencing of 16S rRNA gene. The bacterial isolates fell in five phylogenetic groups: subclasses and of Proteobacteria, the Bacillus–Clostridium group, the order Actinomycetales, and the Cytophaga–Flexibacter–Bacteroides (CFB) phylum. Over 70% of the isolates were affiliated with the Proteobacteria subclass. Based on phylogenetic analysis (<98% sequence similarity), over 40% of Arctic isolates represent potentially novel species or genera. Most of the isolates were psychrotolerant and grew optimally between 20 and 25°C. Only a few strains were psychrophilic, with an optimal growth at 10–15°C. The majority of the bacterial strains were able to secrete a broad range of cold-active hydrolytic enzymes into the medium at a cultivation temperature of 4°C. The isolates that are able to degrade proteins (skim milk, casein), lipids (olive oil), and polysaccharides (starch, pectin) account for, respectively, 56, 31, and 21% of sea-ice and seawater strains. The temperature dependences for enzyme production during growth and enzymatic activity were determined for two selected enzymes, -amylase and -galactosidase. Interestingly, high levels of enzyme productions were measured at growth temperatures between 4 and 10°C, and almost no production was detected at higher temperatures (20–30°C). Catalytic activity was detected even below the freezing point of water (at –5°C), demonstrating the unique properties of these enzymes. 相似文献
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Yusef H. Fadlallah 《Coral reefs (Online)》1983,2(3):129-150
This paper brings together widely scattered information on sexual reproduction in scleractinian corals. It includes a review of information and ideas on sex determination, gametogenesis, gametogenic cycles, fertilization and embryonic development, spawning and planula release, larval behavior, settlement and metamorphosis. The review deals with corals from different habitats and organismic assemblages, including tropical reef corals, temperate water corals, solitary and colonial forms. A summary table of coral species and their known reproductive characteristics is presented. 相似文献
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Dadkhah A Fatemi F Kazemnejad S Rasmi Y Ashrafi-Helan J Allameh A 《Molecular and cellular biochemistry》2006,281(1-2):145-152
Recently we reported that ferric reducing ability of plasma (FRAP) assay, as an index of total antioxidant activity, increases
in growing rats in response to high dose of vitamin K. In this study, it was found that acetaminophen (APAP) can cause elevation
in FRAP in suckling and adult rats. This study was initiated to assess the contribution of individual antioxidant factors
on elevation in FRAP. A surge in FRAP, 1 h after high dose APAP (250 or 450 mg/kg BW) administration was recorded in both
young as well as adults. Whereas, low dose drug (25 mg/kg) failed to alter FRAP in both the age groups. Time-course studies
show that drug-dependent elevation in FRAP begin rapidly, reaching a maximum at 1 h (> 500%). Increased FRAP was associated
with a marked increase (∼14-fold) in plasma bilirubin, 6 h after drug administration at 450 mg/kg only in suckling rats. Similarly,
APAP-related increase in superoxide dismutase activity in erythrocytes was limited to young rats of both the age groups. Other
factors measured during this period viz., plasma uric acid, bilirubin and total protein together with catalase activity of
erythrocytes remained unchanged in treated rats. Under these circumstances, APAP-related depletion in liver glutathione was
almost similar in both the age groups. During a 12 h study, the concentration of lipid peroxidation products, in liver of
treated groups remained within the levels of respective controls. The endpoint hepatotoxic effects of APAP was almost similar
in both the age groups, suggesting that like adults, immature rats can cope with toxic effects of APAP owing to their drug-dependent
induction in certain antioxidant factors. 相似文献