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111.
Cheng C Wang L Wang L Gall JG Nason M Schwartz RM McElrath MJ DeRosa SC Hural J Corey L Buchbinder SP Nabel GJ 《PloS one》2012,7(4):e33969
Background
The Step trial raised the possibility that uncircumcised men with pre-existing Ad5 neutralizing antibodies carried an increased risk of HIV infection after vaccination. Thus, understanding Ad seropositivity in humans is important to the development of an AIDS vaccine. Here, we analyze the impact of different Ad5-specific neutralizing antibodies on immune function and clinical outcome.Methods and Findings
Ad seropositivity in the Step trial volunteers was analyzed using chimeric rAd5/35 vectors to characterize their specificity for Ad5 fiber and non-fiber external (capsid) proteins. Immune responses and HIV seropositivity were correlated with the specificity of Ad5-neutralizing antibodies. Neutralizing antibodies induced by the vaccine in Ad5 seronegative subjects were directed preferentially to Ad5 capsid proteins, although some fiber-neutralizing antibodies could be detected. Pre-vaccination Ad5 serostatus did not affect the capsid-directed response after three vaccinations. In contrast, anti-fiber antibody titers were significantly higher in volunteers who were Ad5 seropositive prior to vaccination. Those Ad5 seropositive subjects who generated anti-capsid responses showed a marked reduction in vaccine-induced CD8 responses. Unexpectedly, anti-vector immunity differed qualitatively in Ad5 seropositive participants who became HIV-1 infected compared to uninfected case controls; Ad5 seropositive participants who later acquired HIV had lower neutralizing antibodies to capsid. Moreover, Ad35 seropositivity was decreased in HIV-infected subjects compared with uninfected case controls, while seroprevalence for other serotypes including Ad14, Ad28 and Ad41 was similar in both groups.Conclusions
Together, these findings suggest that the case subjects were less immunologically responsive prior to infection. Subjects infected during the Step trial had qualitative differences in immunity that increased their risk of HIV-1 infection independent of vaccination. 相似文献112.
The Revised Classification of Eukaryotes 总被引:1,自引:0,他引:1
Sina M. Adl Alastair G. B. Simpson Christopher E. Lane Julius Lukeš David Bass Samuel S. Bowser Matthew W. Brown Fabien Burki Micah Dunthorn Vladimir Hampl Aaron Heiss Mona Hoppenrath Enrique Lara Line le Gall Denis H. Lynn Hilary McManus Edward A. D. Mitchell Sharon E. Mozley‐Stanridge Laura W. Parfrey Jan Pawlowski Sonja Rueckert Laura Shadwick Conrad L. Schoch Alexey Smirnov Frederick W. Spiegel 《The Journal of eukaryotic microbiology》2012,59(5):429-514
This revision of the classification of eukaryotes, which updates that of Adl et al. [J. Eukaryot. Microbiol. 52 (2005) 399], retains an emphasis on the protists and incorporates changes since 2005 that have resolved nodes and branches in phylogenetic trees. Whereas the previous revision was successful in re‐introducing name stability to the classification, this revision provides a classification for lineages that were then still unresolved. The supergroups have withstood phylogenetic hypothesis testing with some modifications, but despite some progress, problematic nodes at the base of the eukaryotic tree still remain to be statistically resolved. Looking forward, subsequent transformations to our understanding of the diversity of life will be from the discovery of novel lineages in previously under‐sampled areas and from environmental genomic information. 相似文献
113.
The suprachiasmatic nucleus (SCN) is part of a wake-promoting circuit comprising the dorsomedial hypothalamus (DMH) and locus coeruleus (LC). Although widely considered a “master clock,” the SCN of adult rats is also sensitive to feedback regarding an animal''s behavioral state. Interestingly, in rats at postnatal day (P)2, repeated arousing stimulation does not increase neural activation in the SCN, despite doing so in the LC and DMH. Here we show that, by P8, the SCN is activated by arousing stimulation and that selective destruction of LC terminals with DSP-4 blocks this activational effect. We next show that bidirectional projections among the SCN, DMH, and LC are nearly absent at P2 but present at P8. Despite the relative lack of SCN connectivity with downstream structures at P2, day-night differences in sleep-wake activity are observed, suggesting that the SCN modulates behavior at this age via humoral factors. To test this hypothesis, we lesioned the SCN at P1 and recorded sleep-wake behavior at P2: Day-night differences in sleep and wake were eliminated. We next performed precollicular transections at P2 and P8 that isolate the SCN and DMH from the brainstem and found that day-night differences in sleep-wake behavior were retained at P2 but eliminated at P8. Finally, the SCN or DMH was lesioned at P8: When recorded at P21, rats with either lesion exhibited similarly fragmented wake bouts and no evidence of circadian modulation of wakefulness. These results suggest an age-related decline in the SCN''s humoral influence on sleep-wake behavior that coincides with the emergence of bidirectional connectivity among the SCN, DMH, and LC. 相似文献
114.
Evaluating the Ribosomal Internal Transcribed Spacer (ITS) as a Candidate Dinoflagellate Barcode Marker 总被引:4,自引:0,他引:4
RF Stern RA Andersen I Jameson FC Küpper MA Coffroth D Vaulot F Le Gall B Véron JJ Brand H Skelton F Kasai EL Lilly PJ Keeling 《PloS one》2012,7(8):e42780
Background
DNA barcoding offers an efficient way to determine species identification and to measure biodiversity. For dinoflagellates, an ancient alveolate group of about 2000 described extant species, DNA barcoding studies have revealed large amounts of unrecognized species diversity, most of which is not represented in culture collections. To date, two mitochondrial gene markers, Cytochrome Oxidase I (COI) and Cytochrome b oxidase (COB), have been used to assess DNA barcoding in dinoflagellates, and both failed to amplify all taxa and suffered from low resolution. Nevertheless, both genes yielded many examples of morphospecies showing cryptic speciation and morphologically distinct named species being genetically similar, highlighting the need for a common marker. For example, a large number of cultured Symbiodinium strains have neither taxonomic identification, nor a common measure of diversity that can be used to compare this genus to other dinoflagellates.Methodology/Principal Findings
The purpose of this study was to evaluate the Internal Transcribed Spacer units 1 and 2 (ITS) of the rDNA operon, as a high resolution marker for distinguishing species dinoflagellates in culture. In our study, from 78 different species, the ITS barcode clearly differentiated species from genera and could identify 96% of strains to a known species or sub-genus grouping. 8.3% showed evidence of being cryptic species. A quarter of strains identified had no previous species identification. The greatest levels of hidden biodiversity came from Scrippsiella and the Pfiesteriaceae family, whilst Heterocapsa strains showed a high level of mismatch to their given species name.Conclusions/Significance
The ITS marker was successful in confirming species, revealing hidden diversity in culture collections. This marker, however, may have limited use for environmental barcoding due to paralogues, the potential for unidentifiable chimaeras and priming across taxa. In these cases ITS would serve well in combination with other markers or for specific taxon studies. 相似文献115.
116.
Ralph Theo Schermuly Christiane Inholte Hossein Ardeschir Ghofrani Henning Gall Norbert Weissmann Andreas Weidenbach Werner Seeger Friedrich Grimminger 《Respiratory research》2005,6(1):76
Inhaled prostanoids and phosphodiesterase (PDE) inhibitors have been suggested for treatment of severe pulmonary hypertension. In catheterized rabbits with acute pulmonary hypertension induced by continuous infusion of the stable thromboxane analogue U46619, we asked whether sildenafil (PDE1/5/6 inhibitor), motapizone (PDE3 inhibitor) or 8-Methoxymethyl-IBMX (PDE1 inhibitor) synergize with inhaled iloprost. Inhalation of iloprost caused a transient pulmonary artery pressure decline, levelling off within <20 min, without significant changes in blood gases or systemic hemodynamics. Infusion of 8-Methoxymethyl-IBMX, motapizone and sildenafil caused each a dose-dependent decrease in pulmonary artery pressure, with sildenafil possessing the highest efficacy and at the same time selectivity for the pulmonary circulation. When combining a per se ineffective dose of each PDE inhibitor (200 μg/kg × min 8-Methoxymethyl-IBMX, 1 μg/kg × min sildenafil, 5 μg/kg × min motapizone) with subsequent iloprost nebulization, marked amplification of the prostanoid induced pulmonary vasodilatory response was noted and the area under the curve of PPA reduction was nearly threefold increased with all approaches, as compared to sole iloprost administration. Further amplification was achieved with the combination of inhaled iloprost with sildenafil plus motapizone, but not with sildenafil plus 8MM-IBMX. Systemic hemodynamics and gas exchange were not altered for all combinations. We conclude that co-administration of minute systemic doses of selective PDE inhibitors with inhaled iloprost markedly enhances and prolongs the pulmonary vasodilatory response to inhaled iloprost, with maintenance of pulmonary selectivity and ventilation perfusion matching. The prominent effect of sildenafil may be operative via both PDE1 and PDE5, and is further enhanced by co-application of a PDE3 inhibitor. 相似文献
117.
France Bellisle Karine Clment Michelle Le Barzic Annie Le Gall Bernard Guy‐Grand Arnaud Basdevant 《Obesity (Silver Spring, Md.)》2004,12(12):2023-2030
Objective: To examine how chronic dietary restraint, disinhibition, and hunger, as assessed by the Eating Inventory, vary over a broad range of BMI values from leanness to massive obesity, in subjects with family obesity. Eating Inventory factors were also studied as a function of personal weight history. Research Methods and Procedures: Subjects were 2509 participants in a genetic study of obesity. BMIs ranged from 15 to 87 kg/m2. Six BMI groups were formed (<27, 27 to 30, 30 to 35, 35 to 40, 40 to 45, and >45). Results: Multivariate analyses showed that restraint and disinhibition were significantly associated with BMI in men, whereas only disinhibition was in women. Disinhibition scores correlated strongly with hunger scores in both genders in all BMI categories; dietary restraint tended to correlate with the other two factors positively in leaner subjects and negatively in the highest BMI categories. Highly restrained normal‐weight subjects were likely to exhibit disinhibition and hunger, whereas massively obese persons with very high disinhibition scores showed high hunger but little restraint. The highest restraint scores were observed in nonobese adult women with previous obesity in childhood and/or adolescence. Discussion: The factor most strongly associated with BMI in this large population was disinhibition, suggesting that obesity treatment should target behaviors associated with disinhibition, especially in individuals showing a low level of dietary restraint. High restraint scores in formerly obese normal‐weight women suggest that dietary restraint may exert a beneficial influence on body weight control under conditions that deserve further investigation. 相似文献
118.
J G Gall 《FEBS letters》2001,498(2-3):164-167
119.
Pedro M. Matias Cláudio M. Soares Lígia M. Saraiva Ricardo Coelho José Morais Jean Le Gall Maria Arménia Carrondo 《Journal of biological inorganic chemistry》2001,6(1):63-81
The primary and three-dimensional structures of a [NiFe] hydrogenase isolated from D. desulfitricans ATCC 27774 were determined, by nucleotide analysis and single-crystal X-ray crystallography. The three-dimensional structural model was refined to R=0.167 and Rfree=0.223 using data to 1.8 A resolution. Two unique structural features are observed: the [4Fe-4S] cluster nearest the [NiFe] centre has been modified [4Fe-3S-3O] by loss of one sulfur atom and inclusion of three oxygen atoms; a three-fold disorder was observed for Cys536 which binds to the nickel atom in the [NiFe] centre. Also, the bridging sulfur atom that caps the active site was found to have partial occupancy, thus corresponding to a partly activated enzyme. These structural features may have biological relevance. In particular, the two less-populated rotamers of Cys536 may be involved in the activation process of the enzyme, as well as in the catalytic cycle. Molecular modelling studies were carried out on the interaction between this [NiFe] hydrogenase and its physiological partner, the tetrahaem cytochrome c3 from the same organism. The lowest energy docking solutions were found to correspond to an interaction between the haem IV region in tetrahaem cytochrome c3 with the distal [4Fe-4S] cluster in [NiFe] hydrogenase. This interaction should correspond to efficient electron transfer and be physiologically relevant, given the proximity of the two redox centres and the fact that electron transfer decay coupling calculations show high coupling values and a short electron transfer pathway. On the other hand, other docking solutions have been found that, despite showing low electron transfer efficiency, may give clues on possible proton transfer mechanisms between the two molecules. 相似文献
120.
Attila Torma Miklós Bozsó Csaba Tölgyesi Róbert Gallé 《Journal of Insect Conservation》2017,21(4):645-656
Eastern European grasslands are still inhabited by a rich arthropod fauna, but the drivers and mechanisms influencing their communities have to be understood to ensure their future survival. Heteroptera communities were studied in 20 plot-pairs in Pannonic salt steppe–salt marsh mosaics in Hungary. The effects of vegetation characteristics, landscape diversity and the proportion of surrounding grasslands on the composition, species richness and abundance of different feeding groups of true bugs (carnivores, specialist and generalist herbivores) were examined using ordinations and mixed-effect models. We found distinct herbivorous assemblages corresponding to microtopography-driven differences in water regime and vegetation between steppe and marsh plots, but this pattern was less pronounced in carnivorous assemblages. A higher species richness of true bugs was found in the more diverse steppe vegetation than in the salt marsh vegetation, while the abundance pattern of true bugs was opposite. Landscape diversity had a positive effect on the species richness and abundance of generalist herbivores and carnivores. Our results suggested that generalist herbivores and carnivores appear to drive diversity patterns in the local landscape due to their high dispersal abilities and the broader range of resources they can utilize. Specialist herbivores strongly influence the local insect biomass in relation to the distribution and density of their host plants. The present study highlights the importance of both habitat and landscape diversity for local insect diversity in Pannonic salt grasslands and suggests that the main threats for arthropod diversity are those processes and activities that homogenize these areas. 相似文献