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51.
Banks AS Kon N Knight C Matsumoto M Gutiérrez-Juárez R Rossetti L Gu W Accili D 《Cell metabolism》2008,8(4):333-341
In yeast, worms, and flies, an extra copy of the gene encoding the Sirtuin Sir2 increases metabolic efficiency, as does administration of polyphenols like resveratrol, thought to act through Sirtuins. But evidence that Sirtuin gain of function results in increased metabolic efficiency in mammals is limited. We generated transgenic mice with moderate overexpression of SirT1, designed to mimic the Sirtuin gain of function that improves metabolism in C. elegans. These mice exhibit normal insulin sensitivity but decreased food intake and locomotor activity, resulting in decreased energy expenditure. However, in various models of insulin resistance and diabetes, SirT1 transgenics display improved glucose tolerance due to decreased hepatic glucose production and increased adiponectin levels, without changes in body weight or composition. We conclude that SirT1 gain of function primes the organism for metabolic adaptation to insulin resistance, increasing hepatic insulin sensitivity and decreasing whole-body energy requirements. These findings have important implications for Sirtuin-based therapies in humans. 相似文献
52.
Maria João Fernandes Martins Francesc Mezquita Olivier Schmit Juan Rueda Giampaolo Rossetti Tadeusz Namiotko 《Hydrobiologia》2009,636(1):219-232
Eucypris virens is a freshwater ostracod in which both sexual reproduction and parthenogenesis occur. Sympatric coexistence of both reproductive
modes is known in zones of overlap. This renders the species a potentially valuable model organism to study the ‘queen of
evolutionary problems’, i.e. why sex is so successful despite its costs (paradox of sex). In order to maximally exploit this
potential, a broad knowledge of the species’ ecology is essential, including an understanding of its life history and population
dynamics. Here, the phenology of the species was followed in three temporary ponds through monthly (Spain) or fortnightly
(Poland) samplings, throughout an inundation period. This study confirms the wide ecological tolerances of E. virens. Although the species is generally assumed to be univoltine, two hatching periods were observed in the Spanish sites. Biotic
interactions, especially predation, appear to be the important determinants of population dynamics in long-hydroperiod sites.
Abiotic conditions may influence population dynamics through their impact on egg hatching. In the site with male presence,
the initially female-biased sex ratio evolved towards a balanced sex ratio through the season. No consistent differences in
limb morphology were observed between females originating from the three study sites. On the other hand, valve size of adult
females varied among sites, possibly influenced by local environmental conditions (mainly salinity and pH) as well as the
expected genetic diversity. 相似文献
53.
54.
The influence of local (i.e. physico-chemical constraints) and regional (i.e. dispersal) processes in determining the structure of zooplankton communities in lentic waters was analysed in a mountain district of 4500 km2 (northern Apennines, Italy). In the 47 lakes and ponds considered in this study, a total of 139 taxa were found. Surface area (SA) and maximum depth (Zmax) significantly influenced species richness and nestedness, stressing the importance of habitat availability for zooplankton diversity and composition. Species richness and nestedness did not correlate with site isolation, indicating low influence of dispersal for these community properties. A negative relationship between the similarity in species composition among sites and their mutual geographic distance was also found. The relative importance of different sources of compositional variation was quantified by direct ordination. Local environmental conditions (i.e. Zmax, altitude, pH and conductivity) accounted for 65.9 % of the variation in rotifer assemblages. The importance of environmental constraints in structuring zooplankton communities was best documented by the microcrustacean distribution in the study area, which was mainly correlated (73.4 % of the variation in the species data) with water ionic content, surface area and hydroperiod of the habitats.Although previous studies on processes shaping zooplankton assemblages that operate at different scales have yielded contrasting results, our data provide clear evidence for a major role of local constraints. 相似文献
55.
Sergio Luiz Montego Ferreira Junior Elis Regina Dalla Costa Paula Gon?alves dos Santos Harrison Magdinier Gomes Marcia Susana Nunes Silva Leonardo Souza Esteves Martha Maria Oliveira Raquel de Abreu Maschmann Afranio Lineu Kritski Philip Noel Suffys Maria Lucia Rosa Rossetti 《Memórias do Instituto Oswaldo Cruz》2014,109(3):307-314
Drug-resistant tuberculosis (TB) threatens global TB control and is a major public
health concern in several countries. We therefore developed a multiplex assay
(LINE-TB/MDR) that is able to identify the most frequent mutations related to
rifampicin (RMP) and isoniazid (INH) resistance. The assay is based on multiplex
polymerase chain reaction, membrane hybridisation and colorimetric detection
targeting of rpoB and katG genes, as well as the
inhA promoter, which are all known to carry specific mutations
associated with multidrug-resistant TB (MDR-TB). The assay was validated on a
reference panel of 108 M. tuberculosis isolates that were characterised by the
proportion method and by DNA sequencing of the targets. When comparing the
performance of LINE-TB/MDR with DNA sequencing, the sensitivity, specificity and
agreement were 100%, 100% and 100%, respectively, for RMP and 77.6%, 90.6% and 88.9%,
respectively, for INH. Using drug sensibility testing as a reference standard, the
performance of LINE-TB/MDR regarding sensitivity, specificity and agreement was 100%,
100% and 100% (95%), respectively, for RMP and 77%, 100% and 88.7% (82.2-95.1),
respectively, for INH. LINE-TB/MDR was compared with GenoType MTBDRplus for 65
isolates, resulting in an agreement of 93.6% (86.7-97.5) for RIF and 87.4%
(84.3-96.2) for INH. LINE-TB/MDR warrants further clinical validation and may be an
affordable alternative for MDR-TB diagnosis. 相似文献
56.
The first 17 amino acids of Huntingtin protein (N17) play a crucial role in the protein's aggregation. Here we predict its free energy landscape in aqueous solution by using bias exchange metadynamics. All our findings are consistent with experimental data. N17 populates four main kinetic basins, which interconvert on the microsecond time-scale. The most populated basin (about 75%) is a random coil, with an extended flat exposed hydrophobic surface. This might create a hydrophobic seed promoting Huntingtin aggregation. The other main populated basins contain helical conformations, which could facilitate N17 binding on its cellular targets. 相似文献
57.
Carvalho WA Ianella P Arnoldi FG Caetano AR Maruyama SR Ferreira BR Conti LH da Silva MR Paula JO Maia AA Santos IK 《Immunogenetics》2011,63(5):319-324
Bovines present contrasting, heritable phenotypes of infestations with the cattle tick, Rhipicephalus (Boophilus) microplus. Tick salivary glands produce IgG-binding proteins (IGBPs) as a mechanism for escaping from host antibodies that these ectoparasites ingest during blood meals. Allotypes that occur in the constant region of IgG may differ in their capacity to bind with tick IGBPs; this may be reflected by the distribution of distinct allotypes according to phenotypes of tick infestations. In order to test this hypothesis, we investigated the frequency of haplotypes of bovine IgG2 among tick-resistant and tick-susceptible breeds of bovines. Sequencing of the gene coding for the heavy chain of IgG2 from 114 tick-resistant (Bos taurus indicus, Nelore breed) and tick-susceptible (B. t. taurus, Holstein breed) bovines revealed SNPs that generated 13 different haplotypes, of which 11 were novel and 5 were exclusive of Holstein and 3 of Nelore breeds. Alignment and modeling of coded haplotypes for hinge regions of the bovine IgG2 showed that they differ in the distribution of polar and hydrophobic amino acids and in shape according to the distribution of these amino acids. We also found that there was an association between genotypes of the constant region of the IgG2 heavy chain with phenotypes of tick infestations. These findings open the possibility of investigating if certain IgG allotypes hinder the function of tick IGBPs. If so, they may be markers for breeding for resistance against tick infestations. 相似文献
58.
Rossetti G Cong X Caliandro R Legname G Carloni P 《Journal of molecular biology》2011,411(3):700-1431
Human (Hu) familial prion diseases are associated with about 40 point mutations of the gene coding for the prion protein (PrP). Most of the variants associated with these mutations are located in the globular domain of the protein. We performed 50 ns of molecular dynamics for each of these mutants to investigate their structure in aqueous solution. Overall, 1.6 μs of molecular dynamics data is presented. The calculations are based on the AMBER(parm99) force field, which has been shown to reproduce very accurately the structural features of the HuPrP wild type and a few variants for which experimental structural information is available. The variants present structural determinants different from those of wild-type HuPrP and the protective mutation HuPrP(E219K-129M). These include the loss of salt bridges in α2-α3 regions and the loss of π-stacking interactions in the β2-α2 loop. In addition, in the majority of the mutants, the α3 helix is more flexible and Y169 is more solvent exposed. The presence of similar traits in this large spectrum of mutations hints to a role of these fingerprints in their known disease-causing properties. Overall, the regions most affected by disease-linked mutations in terms of structure and/or flexibility are those involved in the pathogenic conversion to the scrapie form of the protein and in the interaction with cellular partners. These regions thus emerge as optimal targets for antibody- and ligand-binding studies. 相似文献
59.
Caroline Tanski Bueno Cláudia Maria Dornelles da Silva Regina Bones Barcellos Juliana da Silva Carla Rossana dos Santos Jo?o Evangelista Sampaio Menezes Honório Sampaio Menezes Maria Lucia Rosa Rossetti 《Genetics and molecular biology》2014,37(3):496-499
The aim of this study was to evaluate the association between the frequency of micronuclei (MN) and the cellular changes detected in the conventional Papanicolaou test. One hundred and seventy-four Papanicolaou test smears with cellular changes were examined. MN screening was done in cytopathological smears by counting 1,000 cervical cells in a light microscope. MN frequencies were significantly higher in the group with cellular changes compared to the control group (p < 0.001). The mean MN frequencies were 0.95 ± 1.12 (mean ± SD) in the control group (n = 223), 2.98 ± 1.20 in individuals with atypical squamous cells of undetermined significance (ASC-US) (n = 50), 4.04 ± 1.45 in cervical intraepithelial neoplasia (CIN) I (n = 52), 5.97 ± 1.83 in CIN II (n = 30), 7.29 ± 1.55 in CIN III (n = 17) and 8.64 ± 1.55 in invasive cancer (n = 25). These findings suggest that MN monitoring should be included as an additional criterion for the early detection of cytogenetic damage in routine examinations. This monitoring should be done in the same smear as used for cytopathological examination. More specific and systematic studies are necessary to confirm this proposal. 相似文献
60.