965 resultados para Rudolf Schwarz
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Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ∼ 2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10⁻⁸), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.
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The spatial resolution visualized with hydrological models and the conceptualized images of subsurface hydrological processes often exceed resolution of the data collected with classical instrumentation at the field scale. In recent years it was possible to increasingly diminish the inherent gap to information from point like field data through the application of hydrogeophysical methods at field-scale. With regards to all common geophysical exploration techniques, electric and electromagnetic methods have arguably to greatest sensitivity to hydrologically relevant parameters. Of particular interest in this context are induced polarisation (IP) measurements, which essentially constrain the capacity of a probed subsurface region to store an electrical charge. In the absence of metallic conductors the IP- response is largely driven by current conduction along the grain surfaces. This offers the perspective to link such measurements to the characteristics of the solid-fluid-interface and thus, at least in unconsolidated sediments, should allow for first-order estimates of the permeability structure.¦While the IP-effect is well explored through laboratory experiments and in part verified through field data for clay-rich environments, the applicability of IP-based characterizations to clay-poor aquifers is not clear. For example, polarization mechanisms like membrane polarization are not applicable in the rather wide pore-systems of clay free sands, and the direct transposition of Schwarz' theory relating polarization of spheres to the relaxation mechanism of polarized cells to complex natural sediments yields ambiguous results.¦In order to improve our understanding of the structural origins of IP-signals in such environments as well as their correlation with pertinent hydrological parameters, various laboratory measurements have been conducted. We consider saturated quartz samples with a grain size spectrum varying from fine sand to fine gravel, that is grain diameters between 0,09 and 5,6 mm, as well as corresponding pertinent mixtures which can be regarded as proxies for widespread alluvial deposits. The pore space characteristics are altered by changing (i) the grain size spectra, (ii) the degree of compaction, and (iii) the level of sorting. We then examined how these changes affect the SIP response, the hydraulic conductivity, and the specific surface area of the considered samples, while keeping any electrochemical variability during the measurements as small as possible. The results do not follow simple assumptions on relationships to single parameters such as grain size. It was found that the complexity of natural occurring media is not yet sufficiently represented when modelling IP. At the same time simple correlation to permeability was found to be strong and consistent. Hence, adaptations with the aim of better representing the geo-structure of natural porous media were applied to the simplified model space used in Schwarz' IP-effect-theory. The resulting semi- empiric relationship was found to more accurately predict the IP-effect and its relation to the parameters grain size and permeability. If combined with recent findings about the effect of pore fluid electrochemistry together with advanced complex resistivity tomography, these results will allow us to picture diverse aspects of the subsurface with relative certainty. Within the framework of single measurement campaigns, hydrologiste can than collect data with information about the geo-structure and geo-chemistry of the subsurface. However, additional research efforts will be necessary to further improve the understanding of the physical origins of IP-effect and minimize the potential for false interpretations.¦-¦Dans l'étude des processus et caractéristiques hydrologiques des subsurfaces, la résolution spatiale donnée par les modèles hydrologiques dépasse souvent la résolution des données du terrain récoltées avec des méthodes classiques d'hydrologie. Récemment il est possible de réduire de plus en plus cet divergence spatiale entre modèles numériques et données du terrain par l'utilisation de méthodes géophysiques, notamment celles géoélectriques. Parmi les méthodes électriques, la polarisation provoquée (PP) permet de représenter la capacité des roches poreuses et des sols à stocker une charge électrique. En l'absence des métaux dans le sous-sol, cet effet est largement influencé par des caractéristiques de surface des matériaux. En conséquence les mesures PP offrent une information des interfaces entre solides et fluides dans les matériaux poreux que nous pouvons lier à la perméabilité également dirigée par ces mêmes paramètres. L'effet de la polarisation provoquée à été étudié dans différentes études de laboratoire, ainsi que sur le terrain. A cause d'une faible capacité de polarisation des matériaux sableux, comparé aux argiles, leur caractérisation par l'effet-PP reste difficile a interpréter d'une manière cohérente pour les environnements hétérogènes.¦Pour améliorer les connaissances sur l'importance de la structure du sous-sol sableux envers l'effet PP et des paramètres hydrologiques, nous avons fait des mesures de laboratoire variées. En détail, nous avons considéré des échantillons sableux de quartz avec des distributions de taille de grain entre sables fins et graviers fins, en diamètre cela fait entre 0,09 et 5,6 mm. Les caractéristiques de l'espace poreux sont changées en modifiant (i) la distribution de taille des grains, (ii) le degré de compaction, et (iii) le niveau d'hétérogénéité dans la distribution de taille de grains. En suite nous étudions comment ces changements influencent l'effet-PP, la perméabilité et la surface spécifique des échantillons. Les paramètres électrochimiques sont gardés à un minimum pendant les mesures. Les résultats ne montrent pas de relation simple entre les paramètres pétro-physiques comme par exemples la taille des grains. La complexité des media naturels n'est pas encore suffisamment représenté par les modèles des processus PP. Néanmoins, la simple corrélation entre effet PP et perméabilité est fort et consistant. En conséquence la théorie de Schwarz sur l'effet-PP a été adapté de manière semi-empirique pour mieux pouvoir estimer la relation entre les résultats de l'effet-PP et les paramètres taille de graines et perméabilité. Nos résultats concernant l'influence de la texture des matériaux et celles de l'effet de l'électrochimie des fluides dans les pores, permettront de visualiser des divers aspects du sous-sol. Avec des telles mesures géo-électriques, les hydrologues peuvent collectionner des données contenant des informations sur la structure et la chimie des fluides des sous-sols. Néanmoins, plus de recherches sur les origines physiques de l'effet-PP sont nécessaires afin de minimiser le risque potentiel d'une mauvaise interprétation des données.
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The objective of this work was to confirm the hybrids obtained in plants originated from the crossing between the mandarins Citrus deliciosa 'Montenegrina' and C. nobilis 'King', and to estimate the genetic similarity among hybrids, and between each hybrid and its parents. Twenty‑three pairs of microsatellite primers were tested. Fourteen of these pairs showed polymorphic bands between parents. Primers CCSM 129 and CCSME 52 were sufficient to identify the 12 nucellar clones observed in the studied population. Genetic similarity analysis of the population (hybrids and parents) showed 0.56 average similarity. Besides the 12 clones of 'Montenegrina' identified, 25 hybrids were found of which D18, C32, D06, C05 and D09 are the more similar to 'Montenegrina'.
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O objetivo deste trabalho foi determinar o efeito do método de exposição ao macho e da idade da leitoa, por ocasião da exposição, sobre o percentual de manifestação do primeiro estro, idade de início da puberdade e intervalo entre estímulo e puberdade. Leitoas Danbred F1 Landrace x Large White foram induzidas à puberdade com dois sistemas de exposição ao macho - Baia, estímulo feito pela introdução de macho na baia das fêmeas; Bear, estímulo feito pela colocação de fêmeas na área de permanência de machos - , em três idades de início do estímulo - 150, 170 e 200 dias. Não houve diferença entre os sistemas de estimulação quanto à percentagem de leitoas em estro, idade à puberdade e intervalo entre estimulação e puberdade. Esse intervalo foi menor, quando a exposição das fêmeas foi feita aos 200 dias de idade, e a proporção de fêmeas que atingiram a puberdade aos 10, 20, 30 e 42 dias após o início da exposição foi maior. A indução da puberdade tem maior sucesso quando a exposição da fêmea ao macho é feita aos 200 dias de idade, independentemente do sistema de estimulação.
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O objetivo deste trabalho foi avaliar modelos de regressão aleatória com diferentes ordens de polinômios de Legendre, quanto ao melhor ajuste para a produção de ovos de codornas de corte. Foram avaliados os grupos genéticos UFV1 e UFV2 de codornas de corte, de origens distintas, do programa de melhoramento genético da Universidade Federal de Viçosa. Determinou-se a produção semanal de ovos de 1.294 matrizes, da 6ª até a 57ª semana de idade, das quais 644 do grupo genético UFV1 e 650 do UFV2. Utilizou-se o modelo animal em regressão aleatória pelo programa Wombat e, para modelar as trajetórias das características com o tempo, aplicaram-se as funções polinomiais de Legendre. Foram feitas comparações pelo critério de informação de Akaike, critério de informação bayesiano de Schwarz, logaritmo da função de verossimilhança e teste da razão de verossimilhança. O modelo com K = 3, para efeitos fixos, Ka = 4, para efeitos genéticos, e Kc = 4, para efeito de ambiente, propicia melhor ajuste para ambas as linhagens, não provoca grandes alterações nos componentes de variância e fornece melhores estimativas de herdabilidade.
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Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
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Neuropeptide- and hormone-containing secretory granules (SGs) are synthesized at the trans-Golgi network (TGN) as immature secretory granules (ISGs) and complete their maturation in the F-actin-rich cell cortex. This maturation process is characterized by acidification-dependent processing of cargo proteins, condensation of the SG matrix and removal of membrane and proteins not destined to mature secretory granules (MSGs). Here we addressed a potential role of Rab3 isoforms in these maturation steps by expressing their nucleotide-binding deficient mutants in PC12 cells. Our data show that the presence of Rab3D(N135I) decreases the restriction of maturing SGs to the F-actin-rich cell cortex, blocks the removal of the endoprotease furin from SGs and impedes the processing of the luminal SG protein secretogranin II. This strongly suggests that Rab3D is implicated in the subcellular localization and maturation of ISGs.
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ABSTRACT: INTRODUCTION: Prospective epidemiologic studies have consistently shown that levels of circulating androgens in postmenopausal women are positively associated with breast cancer risk. However, data in premenopausal women are limited. METHODS: A case-control study nested within the New York University Women's Health Study was conducted. A total of 356 cases (276 invasive and 80 in situ) and 683 individually-matched controls were included. Matching variables included age and date, phase, and day of menstrual cycle at blood donation. Testosterone, androstenedione, dehydroandrosterone sulfate (DHEAS) and sex hormone-binding globulin (SHBG) were measured using direct immunoassays. Free testosterone was calculated. RESULTS: Premenopausal serum testosterone and free testosterone concentrations were positively associated with breast cancer risk. In models adjusted for known risk factors of breast cancer, the odds ratios for increasing quintiles of testosterone were 1.0 (reference), 1.5 (95% confidence interval (CI), 0.9 to 2.3), 1.2 (95% CI, 0.7 to 1.9), 1.4 (95% CI, 0.9 to 2.3) and 1.8 (95% CI, 1.1 to 2.9; Ptrend = 0.04), and for free testosterone were 1.0 (reference), 1.2 (95% CI, 0.7 to 1.8), 1.5 (95% CI, 0.9 to 2.3), 1.5 (95% CI, 0.9 to 2.3), and 1.8 (95% CI, 1.1 to 2.8, Ptrend = 0.01). A marginally significant positive association was observed with androstenedione (P = 0.07), but no association with DHEAS or SHBG. Results were consistent in analyses stratified by tumor type (invasive, in situ), estrogen receptor status, age at blood donation, and menopausal status at diagnosis. Intra-class correlation coefficients for samples collected from 0.8 to 5.3 years apart (median 2 years) in 138 cases and 268 controls were greater than 0.7 for all biomarkers except for androstenedione (0.57 in controls). CONCLUSIONS: Premenopausal concentrations of testosterone and free testosterone are associated with breast cancer risk. Testosterone and free testosterone measurements are also highly reliable (that is, a single measurement is reflective of a woman's average level over time). Results from other prospective studies are consistent with our results. The impact of including testosterone or free testosterone in breast cancer risk prediction models for women between the ages of 40 and 50 years should be assessed. Improving risk prediction models for this age group could help decision making regarding both screening and chemoprevention of breast cancer.
Resumo:
Resumo: O objetivo deste trabalho foi avaliar o efeito da interação entre sistemas produtivos e estações do ano sobre a qualidade química e microbiológica do leite bovino, além de propor um índice de potencial nutracêutico do perfil de ácidos graxos do leite. Três propriedades foram avaliadas mensalmente, durante as diferentes estações do ano, em quatro graus de especialização dos sistemas de produção: altamente especializado, especializado, semiespecializado e não especializado. Os sistemas de produção e as estações do ano interferem de forma conjunta no perfil de ácidos graxos e, de forma isolada, na qualidade química e microbiológica do leite. As maiores contagens de células somáticas e os menores conteúdos de proteína foram observados no verão, e o grau de especialização das unidades produtivas esteve indiretamente relacionado à contagem bacteriana total no leite. No inverno, sistemas não especializados produziram leite com o melhor índice nutracêutico, que apresentaram os maiores teores de ácidos graxos poli-insaturados, ácido rumênico (CLA, 18:2n7-c9,t11) e ácido t10,c12-octadecadienoico (CLA, 18:2n6-t10,c12).
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Optimal vaccine strategies must be identified for improving T-cell vaccination against infectious and malignant diseases. MelQbG10 is a virus-like nano-particle loaded with A-type CpG-oligonucleotides (CpG-ODN) and coupled to peptide(16-35) derived from Melan-A/MART-1. In this phase IIa clinical study, four groups of stage III-IV melanoma patients were vaccinated with MelQbG10, given (i) with IFA (Montanide) s.c.; (ii) with IFA s.c. and topical Imiquimod; (iii) i.d. with topical Imiquimod; or (iv) as intralymph node injection. In total, 16/21 (76%) patients generated ex vivo detectable Melan-A/MART-1-specific T-cell responses. T-cell frequencies were significantly higher when IFA was used as adjuvant, resulting in detectable T-cell responses in all (11/11) patients, with predominant generation of effector-memory-phenotype cells. In turn, Imiquimod induced higher proportions of central-memory-phenotype cells and increased percentages of CD127(+) (IL-7R) T cells. Direct injection of MelQbG10 into lymph nodes resulted in lower T-cell frequencies, associated with lower proportions of memory and effector-phenotype T cells. Swelling of vaccine site draining lymph nodes, and increased glucose uptake at PET/CT was observed in 13/15 (87%) of evaluable patients, reflecting vaccine triggered immune reactions in lymph nodes. We conclude that the simultaneous use of both Imiquimod and CpG-ODN induced combined memory and effector CD8(+) T-cell responses.
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To assess the effect of a fructose meal on resting energy expenditure (EE), indirect calorimetry was used in 23 women (10 lean and 13 obese) for 30 min before and 6 h after the ingestion of a mixed meal containing 20% protein, 33% fat, and either 75 g glucose or 75 g fructose as carbohydrate source (47%). Expressed as a percentage of the energy content of the meal, the thermogenic response to the fructose meal was significantly greater (10.2 +/- 0.5%) than that of the glucose meal (8.4 +/- 0.4%, P less than 0.01). This difference was still apparent when the lean and obese women were considered separately. The mean respiratory quotient during the 6-h postprandial period was significantly greater (P less than 0.01) for the fructose (0.85 +/- 0.01) than for the glucose meal (0.83 +/- 0.01) in the combined subjects. In addition, cumulative carbohydrate oxidation was significantly greater after the fructose than after the glucose meal (51.1 +/- 2.3 vs. 40.9 +/- 2.0 g/6 h, respectively, P less than 0.01). Only small changes were observed in postprandial plasma levels of glucose and insulin after the fructose meal, but the plasma levels of lactate increased more with fructose than with the glucose meal. These results suggest that there might be some advantages (higher thermogenesis and carbohydrate oxidations) in using fructose as part of the carbohydrate source in diet of people with obesity and/or insulin resistance.
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A tangerineira-'Montenegrina' (Citrus deliciosa Ten.), devido às boas características de sabor, conservação e colheita tardia dos frutos, é muito apreciada e cultivada no Rio Grande do Sul. Os pomares comerciais são praticamente formados por mudas enxertadas sobre Poncirus trifoliata (L.) Raf. Devido à escassez de informações relativas à combinação desta cultivar com outros porta-enxertos, bem como sua propagação por estaquia, esta pesquisa objetivou estudar o comportamento inicial de plantas enxertadas sobre citrange 'Troyer' (Citrus sinensis (L.) Osb. x P. trifoliata), citrumelo 'Swingle' (C. paradisi Macf. x P. trifoliata) e P. trifoliata e de plantas propagadas por estaquia. O experimento foi instalado na Estação Experimental Agronômica da Universidade Federal do Rio Grande do Sul - UFRGS, em junho de 1989, delineado em blocos casualisados, com cinco plantas úteis por parcela e quatro repetições. Os resultados compreenderam as primeiras safras ocorridas de 1993 a 1998. O citrumeleiro 'Swingle' foi o porta-enxerto que melhores resultados apresentou, aumentando a eficiência produtiva da tangerineira-'Montenegrina', cultivada na Depressão Central do Rio Grande do Sul, sendo que o Poncirus trifoliata diminuiu o desenvolvimento vegetativo das copas e induziu baixa eficiência produtiva. A propagação por estaquia não ofereceu vantagens em relação à enxertia sobre citrumeleiro 'Swingle' e citrangeiro 'Troyer'.
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Objetivando a determinação do período de produção de laranjas no município de Eldorado do Sul, Depressão Central do Rio Grande do Sul, foram avaliados parâmetros de maturação de seis cultivares de laranjeiras-doces. O estudo foi realizado durante 6 anos, de 1992 a 1997, com as cultivares, Rubi, Hamlin, Tobias e Pêra-Rio, durante 4 anos com 'Valência' e 3 anos com 'Folha-Murcha', na coleção de citros da Estação Experimental Agronômica da Universidade Federal do Rio Grande do Sul (UFRGS), situada em Eldorado do Sul-RS, à latitude 30°39'S e longitude 51°06'W, em solo Podzólico Vermelho Amarelo. Quinzenalmente, com início em abril e término em março, foram colhidas amostras de 20 frutos de 5 plantas de cada cultivar; a coleta de amostras começou no início da mudança de coloração da casca do fruto de verde para amarelo. Após a amostragem, os frutos foram acondicionados em sacos de polietileno e armazenados durante 1 a 5 dias a temperaturas entre 4 e 7ºC, até serem analisados, para determinação dos teores percentuais da relação suco/bagaço, sólidos solúveis totais (SST), acidez total titulável (ATT) e relação SST/ATT. A colheita pode ser iniciada na 2ª quinzena de abril, com laranjas-'Hamlin' e prolongar-se até a 2ª quinzena de fevereiro, com laranjas-'Folha-Murcha'. As laranjas-'Hamlin' podem ser colhidas desde a 2ª quinzena de abril até a 1ª quinzena de outubro; as laranjas-'Rubi' desde a 1ª quinzena de maio até a 2ª quinzena de setembro; as laranjas-'Tobias', desde a 1ª quinzena de julho até a 1ª quinzena de novembro; as laranjas-'Pêra-Rio' desde a 2ª quinzena de agosto até a 1ª quinzena de fevereiro; as laranjas-'Valência' desde a 2ª quinzena de agosto até a 1ª quinzena de janeiro e as laranjas-'Folha-Murcha' desde a 1ª quinzena de setembro até a 2ª quinzena de fevereiro.