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941.
Manuela T. Raimondi Elisa Bonacina Gabriele Candiani Matteo Laganà Elena Rolando Giuseppe Talò Daniele Pezzoli Roberto D’Anchise Riccardo Pietrabissa Matteo Moretti 《Biomechanics and modeling in mechanobiology》2011,10(2):259-268
We present an integrated experimental–computational mechanobiology model of chondrogenesis. The response of human articular
chondrocytes to culture medium perfusion, versus perfusion associated with cyclic pressurisation, versus non-perfused culture,
was compared in a pellet culture model, and multiphysic computation was used to quantify oxygen transport and flow dynamics
in the various culture conditions. At 2 weeks of culture, the measured cell metabolic activity and the matrix content in collagen
type II and aggrecan were greatest in the perfused+pressurised pellets. The main effects of perfusion alone, relative to static
controls, were to suppress collagen type I and GAG contents, which were greatest in the non-perfused pellets. All pellets
showed a peripheral layer of proliferating cells, which was thickest in the perfused pellets, and most pellets showed internal
gradients in cell density and matrix composition. In perfused pellets, the computed lowest oxygen concentration was 0.075 mM
(7.5% tension), the maximal oxygen flux was 477.5 nmol/m2/s and the maximal fluid shear stress, acting on the pellet surface, was 1.8 mPa (0.018 dyn/cm2). In the non-perfused pellets, the lowest oxygen concentration was 0.003 mM (0.3% tension) and the maximal oxygen flux was
102.4 nmol/m2/s. A local correlation was observed, between the gradients in pellet properties obtained from histology, and the oxygen fields
calculated with multiphysic simulation. Our results show up-regulation of hyaline matrix protein production by human chondrocytes
in response to perfusion associated with cyclic pressurisation. These results could be favourably exploited in tissue engineering
applications. 相似文献
942.
Isabel Rubio-Aliaga Baukje de Roos Susan J. Duthie L. Katie Crosley Claus Mayer Graham Horgan Ian J. Colquhoun Gw��na?lle Le Gall Fritz Huber Werner Kremer Michael Rychlik Suzan Wopereis Ben van Ommen Gabriele Schmidt Carolin Heim Freek G. Bouwman Edwin C. Mariman Francis Mulholland Ian T. Johnson Abigael C. Polley Ruan M. Elliott Hannelore Daniel 《Metabolomics : Official journal of the Metabolomic Society》2011,7(3):375-387
Fasting is one of the simplest metabolic challenges that can be performed in humans. We here report for the first time a comprehensive analysis of the human ??fasting metabolome?? obtained from analysis of plasma and urine samples in a small cohort of healthy volunteers, using nuclear magnetic resonance (NMR), gas chromatography- and liquid chromatography-mass spectrometry (GC-MS and LC-MS). Intra- and inter-individual variation of metabolites was on measurement of four overnight fasting samples collected from each volunteer over a four week period. One additional sample per volunteer was collected following a prolonged fasting period of 36?h. Amongst a total of 377 quantified entities in plasma around 44% were shown to change significantly in concentration when volunteers extended fasting from 12 to 36?h. In addition to known markers (plasma free fatty acids, glycerol, ketone bodies) that reflect changes in the body??s fuel management under fasting conditions a wide range of ??new?? entities such as ??-aminobutyrate as well as other amino and keto acids were identified as fasting markers. Based on multiple correlations amongst the metabolites and selected hormones in plasma such as leptin or insulin-like-growth-factor-1 (IGF-1), a robust metabolic network with coherent regulation of a wide range of metabolites could be identified. The metabolomics approach described here demonstrates the plasticity of human metabolism and identifies new and robust markers of the fasting state. 相似文献
943.
Francesco Ferretti Gabriele Bertoldi Andrea Sforzi Lorenzo Fattorini 《European Journal of Wildlife Research》2011,57(4):775-783
The analysis of the relationships between population density and habitat features is important to evaluate the ecological
needs of a species, its potential impact on ecosystems and its interspecific interactions. We analysed the spatial variation
of roe deer Capreolus capreolus and fallow deer Dama dama densities in a Mediterranean area in summer 2007 and winter 2007/2008. Previous research has shown that fallow deer can actively
displace and exclude roe deer from natural feeding sites. Here we show that both species have the greatest densities in ecotone
habitats between wood and open fields (abandoned olive groves and pastures), but with contrasting geographic patterns. The
fallow deer showed the greatest densities in the central northern part of the study area near to local historical release
sites. The densities of roe deer were great where fallow deer were rare and low where fallow deer were abundant. Spatial overlap
was great at the habitat scale, indicating a high potential for competition, but was low at the plot scale, suggesting that
partitioning of space occurred at a fine scale. Supporting great numbers of deer, the ecotone areas are crucial for the management
of ecosystems. We suggest that roe deer avoid areas with great densities of fallow deer and that interspecific interference
from the latter affects the density and distribution of the former both at a fine and at a large scale. 相似文献
944.
945.
Zinc is indispensable to all forms of life as it is an essential component of many different proteins involved in a wide range of biological processes. Not differently from other metals, zinc in proteins can play different roles that depend on the features of the metal-binding site. In this work, we describe zinc sites in proteins with known structure by means of three-dimensional templates that can be automatically extracted from PDB files and consist of the protein structure around the metal, including the zinc ligands and the residues in close spatial proximity to the ligands. This definition is devised to intrinsically capture the features of the local protein environment that can affect metal function, and corresponds to what we call a minimal functional site (MFS). We used MFSs to classify all zinc sites whose structures are available in the PDB and combined this classification with functional annotation as available in the literature. We classified 77% of zinc sites into ten clusters, each grouping zinc sites with structures that are highly similar, and an additional 16% into seven pseudo-clusters, each grouping zinc sites with structures that are only broadly similar. Sites where zinc plays a structural role are predominant in eight clusters and in two pseudo-clusters, while sites where zinc plays a catalytic role are predominant in two clusters and in five pseudo-clusters. We also analyzed the amino acid composition of the coordination sphere of zinc as a function of its role in the protein, highlighting trends and exceptions. In a period when the number of known zinc proteins is expected to grow further with the increasing awareness of the cellular mechanisms of zinc homeostasis, this classification represents a valuable basis for structure-function studies of zinc proteins, with broad applications in biochemistry, molecular pharmacology and de novo protein design. 相似文献
946.
947.
Ranta F Leveringhaus J Theilig D Schulz-Raffelt G Hennige AM Hildebrand DG Handrick R Jendrossek V Bosch F Schulze-Osthoff K Häring HU Ullrich S 《PloS one》2011,6(12):e28828
Background
High fat diet-induced hyperglycemia and palmitate-stimulated apoptosis was prevented by specific inhibition of protein kinase C delta (PKCδ) in β-cells. To understand the role of PKCδ in more detail the impact of changes in PKCδ activity on proliferation and survival of insulin-secreting cells was analyzed under stress-free conditions.Methodology and Principal Findings
Using genetic and pharmacological approaches, the effect of reduced and increased PKCδ activity on proliferation, apoptosis and cell cycle regulation of insulin secreting cells was examined. Proteins were analyzed by Western blotting and by confocal laser scanning microscopy. Increased expression of wild type PKCδ (PKCδWT) significantly stimulated proliferation of INS-1E cells with concomitant reduced expression and cytosolic retraction of the cell cycle inhibitor p21Cip1/WAF1. This nuclear extrusion was mediated by PKCδ-dependent phosphorylation of p21Cip1/WAF1 at Ser146. In kinase dead PKCδ (PKCδKN) overexpressing cells and after inhibition of endogenous PKCδ activity by rottlerin or RNA interference phosphorylation of p21Cip1/WAF1 was reduced, which favored its nuclear accumulation and apoptotic cell death of INS-1E cells. Human and mouse islet cells express p21Cip1/WAF1 with strong nuclear accumulation, while in islet cells of PKCδWT transgenic mice the inhibitor resides cytosolic.Conclusions and Significance
These observations disclose PKCδ as negative regulator of p21Cip1/WAF1, which facilitates proliferation of insulin secreting cells under stress-free conditions and suggest that additional stress-induced changes push PKCδ into its known pro-apoptotic role. 相似文献948.
Serviddio G Giudetti AM Bellanti F Priore P Rollo T Tamborra R Siculella L Vendemiale G Altomare E Gnoni GV 《PloS one》2011,6(9):e24084
There is growing evidence that mitochondrial dysfunction, and more specifically fatty acid β-oxidation impairment, is involved in the pathophysiology of non-alcoholic steatohepatitis (NASH). The goal of the present study was to achieve more understanding on the modification/s of carnitinepalmitoyltransferase-I (CPT-I), the rate-limiting enzyme of the mitochondrial fatty acid β-oxidation, during steatohepatitis. A high fat/methionine-choline deficient (MCD) diet, administered for 4 weeks, was used to induce NASH in rats.We demonstrated that CPT-I activity decreased, to the same extent, both in isolated liver mitochondria and in digitonin-permeabilized hepatocytes from MCD-diet fed rats.At the same time, the rate of total fatty acid oxidation to CO(2) and ketone bodies, measured in isolated hepatocytes, was significantly lowered in treated animals when compared to controls. Finally, an increase in CPT-I mRNA abundance and protein content, together with a high level of CPT-I protein oxidation was observed in treated rats. A posttranslational modification of rat CPT-I during steatohepatitis has been here discussed. 相似文献
949.
Czibere L Baur LA Wittmann A Gemmeke K Steiner A Weber P Pütz B Ahmad N Bunck M Graf C Widner R Kühne C Panhuysen M Hambsch B Rieder G Reinheckel T Peters C Holsboer F Landgraf R Deussing JM 《PloS one》2011,6(8):e23604
Behavioral endophenotypes are determined by a multitude of counteracting but precisely balanced molecular and physiological mechanisms. In this study, we aim to identify potential novel molecular targets that contribute to the multigenic trait "anxiety". We used microarrays to investigate the gene expression profiles of different brain regions within the limbic system of mice which were selectively bred for either high (HAB) or low (LAB) anxiety-related behavior, and also show signs of comorbid depression-like behavior. We identified and confirmed sex-independent differences in the basal expression of 13 candidate genes, using tissue from the entire brain, including coronin 7 (Coro7), cathepsin B (Ctsb), muscleblind-like 1 (Mbnl1), metallothionein 1 (Mt1), solute carrier family 25 member 17 (Slc25a17), tribbles homolog 2 (Trib2), zinc finger protein 672 (Zfp672), syntaxin 3 (Stx3), ATP-binding cassette, sub-family A member 2 (Abca2), ectonucleotide pyrophosphatase/phosphodiesterase 5 (Enpp5), high mobility group nucleosomal binding domain 3 (Hmgn3) and pyruvate dehydrogenase beta (Pdhb). Additionally, we confirmed brain region-specific differences in the expression of synaptotagmin 4 (Syt4).Our identification of about 90 polymorphisms in Ctsb suggested that this gene might play a critical role in shaping our mouse model's behavioral endophenotypes. Indeed, the assessment of anxiety-related and depression-like behaviors of Ctsb knock-out mice revealed an increase in depression-like behavior in females. Altogether, our results suggest that Ctsb has significant effects on emotionality, irrespective of the tested mouse strain, making it a promising target for future pharmacotherapy. 相似文献
950.
Protein-protein interactions take place at defined binding interfaces. One protein may bind two or more proteins at different interfaces at the same time. So far it has been commonly accepted that non-overlapping interfaces allow a given protein to bind other proteins simultaneously while no collisions occur between the binding protein structures. To test this assumption, we performed a comprehensive analysis of structural protein interactions to detect potential collisions. Our results did not indicate cases of biologically relevant collisions in the Protein Data Bank of protein structures. However, we discovered a number of collisions that originate from alternative protein conformations or quaternary structures due to different experimental conditions. 相似文献