910 resultados para Wilt, Joshua


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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

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Pós-graduação em Agronomia (Proteção de Plantas) - FCA

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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

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The purpose of this study was to determine the effect of PEGylation on the interaction of poly(amidoamine) (PAMAM) dendrimer nanocarriers (DNCs) with in vitro and in vivo models of the pulmonary epithelium. Generation-3 PAMAM dendrimers with varying surface densities of PEG 1000 Da were synthesized and characterized. The results revealed that the apical to basolateral transport of DNCs across polarized Calu-3 monolayers increases with an increase in PEG surface density. DNC having the greatest number of PEG groups (n = 25) on their surface traversed at a rate 10-fold greater than its non-PEGylated counterpart, in spite of their larger size. This behavior was attributed to a significant reduction in charge density upon PEGylation. We also observed that PEGylation can be used to modulate cellular internalization. The total uptake of PEG-free DNC into polarized Calu-3 monolayers was 12% (w/w) vs 2% (w/w) for that with 25 PEGs. Polarization is also shown to be of great relevance in studying this in vitro model of the lung epithelium. The rate of absorption of DNCs administered to mice lungs increased dramatically when conjugated with 25 PEG groups, thus supporting the in vitro results. The exposure obtained for the DNC with 25PEG was determined to be very high, with peak plasma concentrations reaching 5 mu gmL(-1) within 3 h. The combined in vitro and in vivo results shown here demonstrate that PEGylation can be potentially used to modulate the internalization and transport of DNCs across the pulmonary epithelium. Modified dendrimers thereby may serve as a valuable platform that can be tailored to target the lung tissue for treating local diseases, or the circulation, using the lung as pathway to the bloodstream, for systemic delivery.

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Perioperative fluid therapy remains a highly debated topic. Its purpose is to maintain or restore effective circulating blood volume during the immediate perioperative period. Maintaining effective circulating blood volume and pressure are key components of assuring adequate organ perfusion while avoiding the risks associated with either organ hypo- or hyperperfusion. Relative to perioperative fluid therapy, three inescapable conclusions exist: overhydration is bad, underhydration is bad, and what we assume about the fluid status of our patients may be incorrect. There is wide variability of practice, both between individuals and institutions. The aims of this paper are to clearly define the risks and benefits of fluid choices within the perioperative space, to describe current evidence-based methodologies for their administration, and ultimately to reduce the variability with which perioperative fluids are administered. Based on the abovementioned acknowledgements, a group of 72 researchers, well known within the field of fluid resuscitation, were invited, via email, to attend a meeting that was held in Chicago in 2011 to discuss perioperative fluid therapy. From the 72 invitees, 14 researchers representing 7 countries attended, and thus, the international Fluid Optimization Group (FOG) came into existence. These researches, working collaboratively, have reviewed the data from 162 different fluid resuscitation papers including both operative and intensive care unit populations. This manuscript is the result of 3 years of evidence-based, discussions, analysis, and synthesis of the currently known risks and benefits of individual fluids and the best methods for administering them. The results of this review paper provide an overview of the components of an effective perioperative fluid administration plan and address both the physiologic principles and outcomes of fluid administration. We recommend that both perioperative fluid choice and therapy be individualized. Patients should receive fluid therapy guided by predefined physiologic targets. Specifically, fluids should be administered when patients require augmentation of their perfusion and are also volume responsive. This paper provides a general approach to fluid therapy and practical recommendations.

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Pós-graduação em Agronomia (Proteção de Plantas) - FCA

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Iron, copper, and zinc are essential for all living organisms. Moreover, the homeostasis of these metals is vital to microorganisms during pathogenic interactions with a host. Most pathogens have developed specific mechanisms for the uptake of micronutrients from their hosts in order to counteract the low availability of essential ions in infected tissues. We report here an analysis of genes potentially involved in iron, copper, and zinc uptake and homeostasis in the fungal pathogens Paracoccidioides brasiliensis, Cryptococcus neoformans var. grubii, and Cryptococcus gattii. Although prior studies have identified certain aspects of metal regulation in Cryptococcus species, little is known regarding the regulation of these elements in P. brasiliensis. We also present amino acid sequences analyses of deduced proteins in order to examine possible conserved domains. The genomic data reveals, for the first time, genes associated to iron, copper, and zinc assimilation and homeostasis in P. brasiliensis. Furthermore, analyses of the three fungal species identified homologs to genes associated with high-affinity uptake systems, vacuolar and mitochondrial iron storage, copper uptake and reduction, and zinc assimilation. However, homologs to genes involved in siderophore production were only found in P. brasiliensis. Interestingly, in silico analysis of the genomes of P. brasiliensis Pb01, Pb03, and Pb18 revealed significant differences in the presence and/or number of genes involved in metal homeostasis, such as in genes related to iron reduction and oxidation. The broad analyses of the genomes of P. brasiliensis, C. neoformans var. grubii, and C. gattii for genes involved in metal homeostasis provide important groundwork for numerous interesting future areas of investigation that are required in order to validate and explore the function of the identified genes and gene pathways.

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

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Pós-graduação em Agronomia (Horticultura) - FCA

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In cooperation with the Lower Platte South Natural Resources District for a collaborative study of the cumulative effects of water and channel management practices on stream and riparian ecology, the U.S. Geological Survey (USGS) compiled, analyzed, and summarized hydrologic information from long-term gaging stations on the lower Platte River to determine any significant temporal differences among six discrete periods during 1895-2006 and to interpret any significant changes in relation to changes in climatic conditions or other factors. A subset of 171 examined hydrologic indices (HIs) were selected for use as indices that (1) included most of the variance in the larger set of indices, (2) retained utility as indicators of the streamflow regime, and (3) provided information at spatial and temporal scale(s) that were most indicative of streamflow regime(s). The study included the most downstream station within the central Platte River segment that flowed to the confluence with the Loup River and all four active streamflow-gaging stations (2006) on the lower Platte River main stem extending from the confluence of the Loup River and Platte River to the confluence of the Platte River and Missouri River south of Omaha. The drainage areas of the five streamflow-gaging stations covered four (of eight) climate divisions in Nebraska—division 2 (north central), 3 (northeast), 5 (central), and 6 (east central).

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During ethanol production, starch is the primary nutrient fermented and the remaining byproducts are excellent sources of fiber and protein. In addition, inclusion of byproducts in finishing diets may reduce the incidence of acidosis. As a result, roughage level and quality could potentially be reduced in finishing diets containing byproducts. Three experiments were conducted to examine the effects of roughage and wet corn gluten feed (WCGF) in finishing cattle diets containing corn distillers grains plus solubles. Cattle fed finishing diets containing wet distillers grains plus solubles (WDGS) with no roughage had decreased DMI and ADG compared to cattle fed roughage. Within roughage level, ADG was similar for cattle fed alfalfa hay, corn silage or corn stalks when included on an equal NDF basis. Apparent total tract digestibility of OM, NDF, and CP linearly decreased and ruminal pH variables increased linearly due to increasing roughage levels. Roughage sources can be exchanged on an equal NDF basis in beef finishing diets containing 30% WDGS (DM basis). In finishing diets containing modified distillers grains plus solubles (MDGS), DMI linearly increased due to increasing roughage levels but ADG responded quadratically and was lowest for cattle fed diets without roughage. There was also a quadratic response for DMI and ADG due to WCGF inclusion level. Gain:feed decreased linearly with increasing roughage and WCGF inclusion levels. Feeding 15% WCGF resulted in similar cattle performance and carcass traits to cattle fed no WCGF in diets containing 30% MDGS, but cattle fed diets with 60% total byproduct inclusion made up of 30% WCGF and 30% MDGS had reduced performance (DM basis). Additionally, reducing corn silage inclusion level to 7.5% resulted in similar finishing cattle performance and carcass traits to cattle fed 15% corn silage in diets containing 30% MDGS with or without inclusion of WCGF. Elimination of roughage in diets containing either WDGS or MDGS resulted in negative impacts on finishing cattle performance, ruminal metabolism, and carcass traits.

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Medulloblastoma, the most common malignant paediatric brain tumour, is currently treated with nonspecific cytotoxic therapies including surgery, whole-brain radiation, and aggressive chemotherapy. As medulloblastoma exhibits marked intertumoural heterogeneity, with at least four distinct molecular variants, previous attempts to identify targets for therapy have been underpowered because of small samples sizes. Here we report somatic copy number aberrations (SCNAs) in 1,087 unique medulloblastomas. SCNAs are common in medulloblastoma, and are predominantly subgroup-enriched. The most common region of focal copy number gain is a tandem duplication of SNCAIP, a gene associated with Parkinson's disease, which is exquisitely restricted to Group 4 alpha. Recurrent translocations of PVT1, including PVT1-MYC and PVT1-NDRG1, that arise through chromothripsis are restricted to Group 3. Numerous targetable SCNAs, including recurrent events targeting TGF-beta signalling in Group 3, and NF-kappa B signalling in Group 4, suggest future avenues for rational, targeted therapy.