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991.
John D. Harling Angela M. Deakin Sébastien Campos Rachel Grimley Laiq Chaudry Catherine Nye Oxana Polyakova Christina M. Bessant Nick Barton Don Somers John Barrett Rebecca H. Graves Laura Hanns William J. Kerr Roberto Solari 《The Journal of biological chemistry》2013,288(39):28195-28206
IL-2-inducible tyrosine kinase (Itk) plays a key role in antigen receptor signaling in T cells and is considered an important target for anti-inflammatory drug discovery. In order to generate inhibitors with the necessary potency and selectivity, a compound that targeted cysteine 442 in the ATP binding pocket and with an envisaged irreversible mode of action was designed. We incorporated a high degree of molecular recognition and specific design features making the compound suitable for inhaled delivery. This study confirms the irreversible covalent binding of the inhibitor to the kinase by x-ray crystallography and enzymology while demonstrating potency, selectivity, and prolonged duration of action in in vitro biological assays. The biosynthetic turnover of the kinase was also examined as a critical factor when designing irreversible inhibitors for extended duration of action. The exemplified Itk inhibitor demonstrated inhibition of both TH1 and TH2 cytokines, was additive with fluticasone propionate, and inhibited cytokine release from human lung fragments. Finally, we describe an in vivo pharmacodynamic assay that allows rapid preclinical development without animal efficacy models. 相似文献
992.
Artur Campos Dália Maia Marc Gibernau Airton Torres Carvalho Eduardo Gomes Gonçalves Clemens Schlindwein 《Biological journal of the Linnean Society. Linnean Society of London》2013,108(1):22-34
Taccarum ulei (Araceae, Spathicarpeae) is a seasonal geophytic aroid, native to north‐eastern Brazil, that flowers during two months of the rainy season. Patterns of floral thermogenesis, pollination biology, and floral traits associated with pollination syndromes were studied and compared with those of other Araceae. Two species of cyclocephaline scarabs (Scarabaeidae, Cyclocephalini) were recognized as effective pollinators: Cyclocephala celata and Cyclocephala cearae. Larvae of an unidentified species of fruit fly (Melanoloma spp., Richardiidae, Diptera) were also frequently observed in inflorescences at various maturation stages, feeding on the connectives of male florets and fruits, and thus lowering the reproductive success of individual plants. Beetles were attracted by odoriferous inflorescences in the early evening of the first day of anthesis, during the female phase. The emission of attractive volatiles was coupled with intense thermogenic activity in the entire spadix, unlike other aroids in which only certain zones of the spadix heat up. Pollen release, which marks the beginning of the male phase on the subsequent evening, was not related to floral thermogenesis. Comparative multivariate analysis of the floral traits of T. ulei points to a beetle‐pollinated aroid, although some of the observed traits of the species are not common to other taxa sharing this pollination strategy. Such incongruence might be explained by the evolutionary history of the tribe Spathicarpeae and potential pollinator shifts. © 2012 The Linnean Society of London, Biological Journal of the Linnean Society, 2012, ??, ??–??. 相似文献
993.
Sasha Larsen Jun Weaver Katherine de Sa Campos Rhobe Bulahan Jackson Nguyen Heather Grove Amy Huang Lauren Low Namphuong Tran Seth Gomez Jennifer Yau Thomas Ilustrisimo Jessica Kawilarang Jonathan Lau Maivi Tranphung Irene Chen Christina Tran Marcia Fox Joan Lin-Cereghino Geoff P. Lin-Cereghino 《Biotechnology letters》2013,35(11):1925-1935
Although Pichia pastoris is a popular protein expression system, it exhibits limitations in its ability to secrete heterologous proteins. Therefore, a REMI (restriction enzyme mediated insertion) strategy was utilized to select mutant beta-g alactosidase s upersecretion (bgs) strains that secreted increased levels of a β-galactosidase reporter. Many of the twelve BGS genes may have functions in intracellular signaling or vesicle transport. Several of these strains also appeared to contain a more permeable cell wall. Preliminary characterization of four bgs mutants showed that they differed in the ability to enhance the export of other reporter proteins. bgs13, which has a disruption in a gene homologous to Saccharomyces cerevisiae protein kinase C (PKC1), gave enhanced secretion of most recombinant proteins that were tested, raising the possibility that it has the universal super-secreter phenotype needed in an industrial production strain of P. pastoris. 相似文献
994.
Luísa Antônia Campos Barros Hilton Jeferson Alves Cardoso de Aguiar Cléa dos Santos Ferreira Mariano Silvia das Graças Pompolo 《法国昆虫学会纪事》2013,49(4):367-373
The genus Trachymyrmex is a key group in the tribe Attini because of its close phylogenetic relationship to leaf-cutter ants, Acromyrmex and Atta. Cytogenetic data are only available for five taxa of Trachymyrmex, with chromosome numbers of 2n = 12, 18, 20 and 22, and morphology with predominantly metacentric chromosomes. The aim of the present study was to characterize the karyotype of the ant Trachymyrmex fuscus Emery, 1934, by means of the number and morphology of its chromosomes, heterochromatin pattern, CMA3 and DAPI fluorochromes in the population of two nests collected at Paraopeba, state of Minas Gerais, Brazil. Nineteen females presented 2n = 18 chromosomes (16m + 2sm) and a single male presented n = 9 (8m + 1sm). A size chromosomal polymorphism involving the short arm of the submetacentric pair was confirmed by statistical analysis, with three character conditions: heterozygous SB (with a difference in size between the short arms), standard SS (smaller short arms) and homozygote BB (bigger short arms). In the first nest, both SB and SS workers were observed. The other nest contained heterozygous (SB), homozygous (BB), and a male carrying the B chromosome (larger size). The presence of heterochromatin on all centromeric and pericentromeric chromosomes of T. fuscus suggests that the size difference observed in the submetacentric pair in the SB and BB workers is not related to the heterochromatin but to a duplication of euchromatic regions through intra- or inter- chromosomal rearrangements. The fluorochrome CMA3 matched the C-banding markings, indicating that the heterochromatin is rich in GC base pairs. As far as we know, this is the first chromosomal polymorphism reported in the tribe Attini. 相似文献
995.
Luciana Bonome Zeminian Juliana Lara Padovani Sílvia Maria Corvino Giovanni Faria Silva Maria Inês de Moura Campos Pardini Rejane Maria Tommasini Grotto 《Memórias do Instituto Oswaldo Cruz》2013,108(1):13-17
The goal of treatment of chronic hepatitis C is to achieve a sustained virological response, which is defined as exhibiting undetectable hepatitis C virus (HCV) RNA levels in serum following therapy for at least six months. However, the current treatment is only effective in 50% of patients infected with HCV genotype 1, the most prevalent genotype in Brazil. Inhibitors of the serine protease non-structural protein 3 (NS3) have therefore been developed to improve the responses of HCV-infected patients. However, the emergence of drug-resistant variants has been the major obstacle to therapeutic success. The goal of this study was to evaluate the presence of resistance mutations and genetic polymorphisms in the NS3 genomic region of HCV from 37 patients infected with HCV genotype 1 had not been treated with protease inhibitors. Plasma viral RNA was used to amplify and sequence the HCV NS3 gene. The results indicate that the catalytic triad is conserved. A large number of substitutions were observed in codons 153, 40 and 91; the resistant variants T54A, T54S, V55A, R155K and A156T were also detected. This study shows that resistance mutations and genetic polymorphisms are present in the NS3 region of HCV in patients who have not been treated with protease inhibitors, data that are important in determining the efficiency of this new class of drugs in Brazil. 相似文献
996.
Javier Díaz-Castro Yenela García Inmaculada López-Aliaga María J. M. Alférez Silvia Hijano Aurora Ramos Margarita S. Campos 《Biological trace element research》2013,152(3):403-410
Nanoparticles (NPs) in agricultural systems can potentially be used as appropriate candidate for change in growth, development, productivity, and quality of plants. In the present study, we assessed the effect of TiO2 NP concentrations (0, 2, 5, and 10 ppm) on changes of membrane damage indexes like electrolyte leakage index (ELI) and malondialdehyde (MDA) during cold stress (CS) 4 °C in sensitive (ILC 533) and tolerant (Sel 11439) chickpea (Cicer arietinum L.) genotypes. Aggregation of NPs within the vacuole and chloroplast indicated absorbed NPs in seedlings. Bioaccumulation of NPs showed that, under thermal treatments, the sensitive genotype had more permeability to NPs compared to the tolerant one, and TiO2 content was higher during CS compared to optimum temperature. Physiological indexes were positively affected by NP treatments during thermal treatments. TiO2 NP treatments (especially 5 ppm) caused a decrease in ELI during thermal treatments, whereas ELI content under CS treatment increased at 0 ppm TiO2 in both genotypes. Under thermal treatments, although the genotype 11439 showed lower accumulation of MDA than ILC 533 genotype, a significant decrease was observed in MDA content at 5 ppm TiO2. Results showed that TiO2 treatments not only did not induce oxidative damage in sensitive and tolerant chickpea genotypes but also alleviated membrane damage indexes under CS treatment. It was suggested for the first time that TiO2 NPs improved redox status of the genotypes under thermal treatments. New findings possibly would reveal the use of NPs generally or TiO2 NPs especially for increase of cold tolerance in crops. 相似文献
997.
Ana Paula Oliveira Ferreira Fernanda Silva Rodrigues Iuri Domingues Della-Pace Bibiana Castagna Mota Sara Marchesan Oliveira Camila de Campos Velho Gewehr Franciane Bobinski Clarissa Vasconcelos de Oliveira Juliana Sperotto Brum Mauro Schneider Oliveira Ana Flavia Furian Claudio Severo Lombardo de Barros Juliano Ferreira Adair Roberto Soares dos Santos Michele Rechia Fighera Luiz Fernando Freire Royes 《Neurochemistry international》2013
998.
Marcia Gilceane Cardozo Niara Medeiros Denise dos Santos Lacerda Daniela Campos de Almeida João Antônio Pegas Henriques Caroline Dani Cláudia Funchal 《Cellular and molecular neurobiology》2013,33(8):1123-1133
Serra Gaucha is described as the most important wine region of Brazil. Regarding cultivars widespread in the Serra Gaucha, about 90 % of the area is occupied by vines of Vitis labrusca that is the most important specie used in grape juice production. The objective of this study was to investigate the antioxidant and neuroprotective effect of chronic intake of purple grape juice (organic and conventional) from Bordo variety (V. labrusca) on oxidative stress in different brain regions of rats supplemented with high-fat diet (HFD) for 3 months. A total of 40 male rats were randomly divided into 4 groups. Group 1 received a standard diet and water, group 2 HFD and water, group 3 HFD and conventional grape juice (CGJ), and group 4 HFD and organic grape juice (OGJ). All groups had free access to food and drink and after 3 months of treatment the rats were euthanized by decapitation and the cerebral cortex, hippocampus and cerebellum isolated and homogenized on ice for oxidative stress analysis. We observed that the consumption of calories in HFD and control groups, were higher than the groups supplemented with HFD and grape juices and that HFD diet group gain more weight than the other animals. Our results also demonstrated that HDF enhanced lipid peroxidation (TBARS) and protein damage (carbonyl) in cerebral cortex and hippocampus, reduced the non-enzymatic antioxidants defenses (sulfhydryl) in cerebral cortex and cerebellum, reduced catalase and superoxide dismutase activities in all brain tissues and enhanced nitric oxide production in all cerebral tissues. CGJ and OGJ were able to ameliorate these oxidative alterations, being OGJ more effective in this protection. Therefore, grape juices could be useful in the treatment of some neurodegenerative diseases associated with oxidative damage. 相似文献
999.
Mariana C. R. de Campos Stuart J. Pearse Rafael S. Oliveira Hans Lambers 《Annals of botany》2013,111(3):445-454
Background and Aims
Previous research has suggested a trade-off between the capacity of plants to downregulate their phosphorus (P) uptake capacity and their efficiency of P resorption from senescent leaves in species from P-impoverished environments.Methods
To investigate this further, four Australian native species (Banksia attenuata, B. menziesii, Acacia truncata and A. xanthina) were grown in a greenhouse in nutrient solutions at a range of P concentrations [P]. Acacia plants received between 0 and 500 µm P; Banksia plants received between 0 and 10 µm P, to avoid major P-toxicity symptoms in these highly P-sensitive species.Key Results
For both Acacia species, the net P-uptake rates measured at 10 µm P decreased steadily with increasing P supply during growth. In contrast, in B. attenuata, the net rate of P uptake from a solution with 10 µm P increased linearly with increasing P supply during growth. The P-uptake rate of B. menziesii showed no significant response to P supply in the growing medium. Leaf [P] of the four species supported this finding, with A. truncata and A. xanthina showing an increase up to a saturation value of 19 and 21 mg P g−1 leaf dry mass, respectively (at 500 µm P), whereas B. attenuata and B. menziesii both exhibited a linear increase in leaf [P], reaching 10 and 13 mg P g−1 leaf dry mass, respectively, without approaching a saturation point. The Banksia plants grown at 10 µm P showed mild symptoms of P toxicity, i.e. yellow spots on some leaves and drying and curling of the tips of the leaves. Leaf P-resorption efficiency was 69 % (B. attenuata), 73 % (B. menziesii), 34 % (A. truncata) and 36 % (A. xanthina). The P-resorption proficiency values were 0·08 mg P g−1 leaf dry mass (B. attenuata and B. menziesii), 0·32 mg P g−1 leaf dry mass (A. truncata) and 0·36 mg P g−1 leaf dry mass (A. xanthina). Combining the present results with additional information on P-remobilization efficiency and the capacity to downregulate P-uptake capacity for two other Australian woody species, we found a strong negative correlation between these traits.Conclusions
It is concluded that species that are adapted to extremely P-impoverished soils, such as many south-western Australian Proteaceae species, have developed extremely high P-resorption efficiencies, but lost their capacity to downregulate their P-uptake mechanisms. The results support the hypothesis that the ability to resorb P from senescing leaves is inversely related to the capacity to downregulate net P uptake, possibly because constitutive synthesis of P transporters is a prerequisite for proficient P remobilization from senescing tissues. 相似文献1000.
Arelí López-Uriarte Fabiola Quintero-Rivera Beatriz de la Fuente Cortez Viviana Gómez Puente María del Roble Velazco Campos Laura E. Martínez de Villarreal 《Gene》2013
We report here a child with a ring chromosome 2 [r(2)] associated with failure to thrive, microcephaly and dysmorphic features. The chromosomal aberration was defined by chromosome microarray analysis, revealing two small deletions of 2p25.3 (139 kb) and 2q37.3 (147 kb). 相似文献