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131.
Adam J. Davenport Christopher C. Stimson Massimo Corsi Darshan Vaidya Edward Glenn Timothy D. Jones Sarah Bailey Mark J. Gemkow Ulrike Fritz David J. Hallett 《Bioorganic & medicinal chemistry letters》2010,20(17):5165-5169
A series of potent and subtype selective H3 receptor antagonists containing a novel tetrazole core and diamine motif is reported. A one-pot multi-component Ugi reaction was utilised to rapidly develop the structure–activity relationships (SAR) of these compounds. Optimisation for liver microsome stability (t1/2 >60 min), minimal CYP inhibition (IC50 >50 μM) and high cell permeability (Caco-2 Papp >20 × 10?6 cm/s) identified several compounds with drug-like properties. 相似文献
132.
Background
Worse health outcomes including higher morbidity and mortality are most often observed among the poorest fractions of a population. In this paper we present and validate national, regional and state-level distributions of national wealth index scores, for urban and rural populations, derived from household asset data collected in six survey rounds in India between 1992–3 and 2007–8. These new indices and their sub-national distributions allow for comparative analyses of a standardized measure of wealth across time and at various levels of population aggregation in India.Methods
Indices were derived through principal components analysis (PCA) performed using standardized variables from a correlation matrix to minimize differences in variance. Valid and simple indices were constructed with the minimum number of assets needed to produce scores with enough variability to allow definition of unique decile cut-off points in each urban and rural area of all states.Results
For all indices, the first PCA components explained between 36% and 43% of the variance in household assets. Using sub-national distributions of national wealth index scores, mean height-for-age z-scores increased from the poorest to the richest wealth quintiles for all surveys, and stunting prevalence was higher among the poorest and lower among the wealthiest. Urban and rural decile cut-off values for India, for the six regions and for the 24 major states revealed large variability in wealth by geographical area and level, and rural wealth score gaps exceeded those observed in urban areas.Conclusions
The large variability in sub-national distributions of national wealth index scores indicates the importance of accounting for such variation when constructing wealth indices and deriving score distribution cut-off points. Such an approach allows for proper within-sample economic classification, resulting in scores that are valid indicators of wealth and correlate well with health outcomes, and enables wealth-related analyses at whichever geographical area and level may be most informative for policy-making processes. 相似文献133.
Sérgio A Batista Gifone A Rocha Andreia MC Rocha Ivan EB Saraiva Mônica MDA Cabral Rodrigo C Oliveira Dulciene MM Queiroz 《BMC microbiology》2011,11(1):61
Background
Helicobacter pylori infection is one of the most common infections worldwide and is associated with gastric cancer and peptic ulcer. Bacterial virulence factors such as CagA have been shown to increase the risk of both diseases. Studies have suggested a causal role for CagA EPIYA polymorphisms in gastric carcinogenesis, and it has been shown to be geographically diverse. We studied associations between H. pylori CagA EPIYA patterns and gastric cancer and duodenal ulcer, in an ethnically admixed Western population from Brazil. CagA EPIYA was determined by PCR and confirmed by sequencing. A total of 436 patients were included, being 188 with gastric cancer, 112 with duodenal ulcer and 136 with gastritis. 相似文献134.
C. Cazzin L. Piccoli M. Massagrande N. Garbati F. Michielin H.‐G. Knaus C. J. A. Ring A. D. Morrison E. Merlo‐Pich Z. Rovo S. Astori A. Lüthi C. Corti M. Corsi 《Genes, Brain & Behavior》2011,10(8):817-827
The voltage‐gated potassium channel Kv1.2 belongs to the shaker‐related family and has recently been implicated in the control of sleep profile on the basis of clinical and experimental evidence in rodents. To further investigate whether increasing Kv1.2 activity would promote sleep occurrence in rats, we developed an adeno‐associated viral vector that induces overexpression of rat Kv1.2 protein. The viral vector was first evaluated in vitro for its ability to overexpress rat Kv1.2 protein and to produce functional currents in infected U2OS cells. Next, the adeno‐associated Kv1.2 vector was injected stereotaxically into the central medial thalamic area of rats and overexpression of Kv1.2 was showed by in situ hybridization, ex vivo electrophysiology and immunohistochemistry. Finally, the functional effect of Kv1.2 overexpression on sleep facilitation was investigated using telemetry system under normal conditions and following administration of the arousing agent caffeine, during the light phase. While no differences in sleep profile were observed between the control and the treated animals under normal conditions, a decrease in the pro‐arousal effect of caffeine was seen only in the animals injected with the adeno‐associated virus‐Kv1.2 vector. Overall, our data further support a role of the Kv1.2 channel in the control of sleep profile, particularly under conditions of sleep disturbance. 相似文献
135.
Li Liu Nidia MM Oliveira Kelly M Cheney Corinna Pade Hanna Dreja Ann-Marie H Bergin Viola Borgdorff David H Beach Cleo L Bishop Matthias T Dittmar Áine McKnight 《Retrovirology》2011,8(1):1-15
Background
Human T-cell leukemia virus type 1 (HTLV-1) causes adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in a small percentage of infected individuals. ATL is often associated with general immune suppression and an impaired HTLV-1-specific T-cell response, an important host defense system. We previously found that a small fraction of asymptomatic HTLV-1-carriers (AC) already showed impaired T-cell responses against the major target antigen, Tax. However, it is unclear whether the impaired HTLV-1 Tax-specific T-cell response in these individuals is an HTLV-1-specific phenomenon, or merely reflects general immune suppression. In this study, in order to characterize the impaired HTLV-1-specific T-cell response, we investigated the function of Tax-specific CD8+ T-cells in various clinical status of HTLV-1 infection.Results
By using tetramers consisting of HLA-A*0201, -A*2402, or -A*1101, and corresponding Tax epitope peptides, we detected Tax-specific CD8+ T-cells in the peripheral blood from 87.0% of ACs (n = 20/23) and 100% of HAM/TSP patients (n = 18/18) tested. We also detected Tax-specific CD8+ T-cells in 38.1% of chronic type ATL (cATL) patients (n = 8/21), although its frequencies in peripheral blood CD8+ T cells were significantly lower than those of ACs or HAM/TSP patients. Tax-specific CD8+ T-cells detected in HAM/TSP patients proliferated well in culture and produced IFN-γ when stimulated with Tax peptides. However, such functions were severely impaired in the Tax-specific CD8+ T-cells detected in cATL patients. In ACs, the responses of Tax-specific CD8+ T-cells were retained in most cases. However, we found one AC sample whose Tax-specific CD8+ T-cells hardly produced IFN-γ, and failed to proliferate and express activation (CD69) and degranulation (CD107a) markers in response to Tax peptide. Importantly, the same AC sample contained cytomegalovirus (CMV) pp65-specific CD8+ T-cells that possessed functions upon CMV pp65 peptide stimulation. We further examined additional samples of two smoldering type ATL patients and found that they also showed dysfunctions of Tax-specific but not CMV-specific CD8+ T-cells.Conclusions
These findings indicated that Tax-specific CD8+ T-cells were scarce and dysfunctional not only in ATL patients but also in a limited AC population, and that the dysfunction was selective for HTLV-1-specifc CD8+ T-cells in early stages. 相似文献136.
Mazzucchelli S Verderio P Sommaruga S Colombo M Salvadè A Corsi F Galeffi P Tortora P Prosperi D 《Bioconjugate chemistry》2011,22(11):2296-2303
Spherical silica nanoparticles (SNP) have been synthesized and functionalized with anti-HER-2 scFv800E6 antibody by both localized histidine-tag recognition, leading to an oriented protein ligation, and glutaraldehyde cross-linking, exploiting a statistical reactivity of lysine amine groups in the primary sequence of the molecule. The targeting efficiency of nanocomplexes in comparison with free scFv was evaluated by flow cytometry using a HER-2 antigen-positive MCF-7 breast cancer cell line, exhibiting a 4-fold increase in scFv binding efficacy, close to the affinity of intact anti-HER-2 monoclonal antibody, which suggests the effectiveness of presenting multiple scFv molecules on nanoparticles in improving antigen recognition. Unexpectedly, the conjugation method did not affect the binding efficacy of scFv, suggesting a structural role of lysines in the scFv molecule. Confocal laser scanning microscopy confirmed the binding of nanocomplexes to HER-2 and also provided evidence of their localization at the cell surface. 相似文献
137.
DJ Corsi SV Subramanian M McKee W Li S Swaminathan P Lopez-Jaramillo A Avezum SA Lear G Dagenais S Rangarajan K Teo S Yusuf CK Chow 《PloS one》2012,7(9):e44410
BACKGROUND: Public health research has turned towards examining upstream, community-level determinants of cardiovascular disease risk factors. Objective measures of the environment, such as those derived from direct observation, and perception-based measures by residents have both been associated with health behaviours. However, current methods are generally limited to objective measures, often derived from administrative data, and few instruments have been evaluated for use in rural areas or in low-income countries. We evaluate the reliability of a quantitative tool designed to capture perceptions of community tobacco, nutrition, and social environments obtained from interviews with residents in communities in 5 countries. METHODOLOGY/ PRINCIPAL FINDINGS: Thirteen measures of the community environment were developed from responses to questionnaire items from 2,360 individuals residing in 84 urban and rural communities in 5 countries (China, India, Brazil, Colombia, and Canada) in the Environmental Profile of a Community's Health (EPOCH) study. Reliability and other properties of the community-level measures were assessed using multilevel models. High reliability (>0.80) was demonstrated for all community-level measures at the mean number of survey respondents per community (n?=?28 respondents). Questionnaire items included in each scale were found to represent a common latent factor at the community level in multilevel factor analysis models. CONCLUSIONS/ SIGNIFICANCE: Reliable measures which represent aspects of communities potentially related to cardiovascular disease (CVD)/risk factors can be obtained using feasible sample sizes. The EPOCH instrument is suitable for use in different settings to explore upstream determinants of CVD/risk factors. 相似文献
138.
139.
MM Fierro L Cruz-López D Sánchez R Villanueva-Gutiérrez R Vandame 《Neotropical Entomology》2012,41(2):95-104
We recorded stingless bee colony abundance and nesting habits in three sites with different anthropogenic activities in the Soconusco region of Chiapas, Mexico: (1) agroforestry (7 hacacao crop), (2) grassland (12?ha), and (3) urban area (3?ha). A total of 67 nests were found, representing five stingless bee species, Tetragonisca angustula angustula (Lepeletier), Trigona fulviventris (Guérin), Scaptotrigona mexicana (Guérin), Scaptotrigona pectoralis (Dalla Torre), and Oxytrigona mediorufa (Cockerell). The most abundant stingless bee in each site was T. angustula angustula (>50%). The primary tree species used by the bees were Ficus spp. (Moraceae, 37.8%) and Cordia alliodora (Boraginaceae, 13.5%). The nest entrance height of T. angustula angustula (96?±?19?cm) was different than the other species, and this bee was the only one that used all different nesting sites. Volatiles analyzed by gas chromatography from pollen collected by the stingless bees differed between bee species, but were highly similar in respect to the fragrances of the pollen collected by the same species at any site. Our data indicate that T. angustula angustula experienced low heterospecific and high intraspecific foraging overlap especially in the urban site. We observed cluster spatial distribution in grassland and in agroforestry sites. In the urban site, T. angustula angustula presented random distribution tended to disperse. Trigona fulviventris was the only overdispersed and solitary species. 相似文献
140.
Lucia Viegi Anna Maria Pagni Gabriella Corsi Giovanna Cela Renzoni 《Plant biosystems》2013,147(4-5):347-357
Abstract Embryo suspensor in Cruciferae. I. Morphology and structure. — Embryo suspensors in seven species of Cruciferae (Alyssum argenteum All., Brassica nigra (L.) Koch, Capsella bursa-pastoris (L.) Medicus, Diplotaxis erucoides (L.) DC., Eruca sativa Miller, Lepidium graminifolium L., Matthiola tricuspidata (L.) R. Br.) were morphologically investigated. These species have significant differences in their seeds, so that probable differences could be found in the structure of their ovules and therefore of their suspensors. Results indicate that it is impossible to generalize on the suspensor morphology and structure even in the same family. In Eruca sativa and Brassica nigra polyploidy and polyteny were found, suggesting a probably important metabolic function of their suspensors. In the other species polyteny was not present; a various degree of polyploidy could probably be assumed, suggesting a less active function of suspensors, maybe absorption and transport of nutritive material from the integuments to the developing embryo. The development of the endosperm is almost the same in all species, so that seems to be improbable a negative correlation with the suspensor and endosperm function in the early embryogenesis. 相似文献