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221.
Dragosits M Frascotti G Bernard-Granger L Vázquez F Giuliani M Baumann K Rodríguez-Carmona E Tokkanen J Parrilli E Wiebe MG Kunert R Maurer M Gasser B Sauer M Branduardi P Pakula T Saloheimo M Penttilä M Ferrer P Luisa Tutino M Villaverde A Porro D Mattanovich D 《Biotechnology progress》2011,27(1):38-46
Microorganisms encounter diverse stress conditions in their native habitats but also during fermentation processes, which have an impact on industrial process performance. These environmental stresses and the physiological reactions they trigger, including changes in the protein folding/secretion machinery, are highly interrelated. Thus, the investigation of environmental factors, which influence protein expression and secretion is still of great importance. Among all the possible stresses, temperature appears particularly important for bioreactor cultivation of recombinant hosts, as reductions of growth temperature have been reported to increase recombinant protein production in various host organisms. Therefore, the impact of temperature on the secretion of proteins with therapeutic interest, exemplified by a model antibody Fab fragment, was analyzed in five different microbial protein production hosts growing under steady-state conditions in carbon-limited chemostat cultivations. Secretory expression of the heterodimeric antibody Fab fragment was successful in all five microbial host systems, namely Saccharomyces cerevisiae, Pichia pastoris, Trichoderma reesei, Escherichia coli and Pseudoalteromonas haloplanktis. In this comparative analysis we show that a reduction of cultivation temperature during growth at constant growth rate had a positive effect on Fab 3H6 production in three of four analyzed microorganisms, indicating common physiological responses, which favor recombinant protein production in prokaryotic as well as eukaryotic microbes. 相似文献
222.
Kristin Tøndel Ulf G Indahl Arne B Gjuvsland Jon Olav Vik Peter Hunter Stig W Omholt Harald Martens 《BMC systems biology》2011,5(1):1-17
Background
Network inference methods reconstruct mathematical models of molecular or genetic networks directly from experimental data sets. We have previously reported a mathematical method which is exclusively data-driven, does not involve any heuristic decisions within the reconstruction process, and deliveres all possible alternative minimal networks in terms of simple place/transition Petri nets that are consistent with a given discrete time series data set.Results
We fundamentally extended the previously published algorithm to consider catalysis and inhibition of the reactions that occur in the underlying network. The results of the reconstruction algorithm are encoded in the form of an extended Petri net involving control arcs. This allows the consideration of processes involving mass flow and/or regulatory interactions. As a non-trivial test case, the phosphate regulatory network of enterobacteria was reconstructed using in silico-generated time-series data sets on wild-type and in silico mutants.Conclusions
The new exact algorithm reconstructs extended Petri nets from time series data sets by finding all alternative minimal networks that are consistent with the data. It suggested alternative molecular mechanisms for certain reactions in the network. The algorithm is useful to combine data from wild-type and mutant cells and may potentially integrate physiological, biochemical, pharmacological, and genetic data in the form of a single model. 相似文献223.
224.
Engel KM Schröck K Teupser D Holdt LM Tönjes A Kern M Dietrich K Kovacs P Krügel U Scheidt HA Schiller J Huster D Brockmann GA Augustin M Thiery J Blüher M Stumvoll M Schöneberg T Schulz A 《PloS one》2011,6(12):e29400
G protein-coupled receptors (GPCR) are involved in the regulation of numerous physiological functions. Therefore, GPCR variants may have conferred important selective advantages during periods of human evolution. Indeed, several genomic loci with signatures of recent selection in humans contain GPCR genes among them the X-chromosomally located gene for GPR82. This gene encodes a so-called orphan GPCR with unknown function. To address the functional relevance of GPR82 gene-deficient mice were characterized. GPR82-deficient mice were viable, reproduced normally, and showed no gross anatomical abnormalities. However, GPR82-deficient mice have a reduced body weight and body fat content associated with a lower food intake. Moreover, GPR82-deficient mice showed decreased serum triacylglyceride levels, increased insulin sensitivity and glucose tolerance, most pronounced under Western diet. Because there were no differences in respiratory and metabolic rates between wild-type and GPR82-deficient mice our data suggest that GPR82 function influences food intake and, therefore, energy and body weight balance. GPR82 may represent a thrifty gene most probably representing an advantage during human expansion into new environments. 相似文献
225.
Humans remove large amounts of biomass from natural ecosystems, and large bodied high trophic level animals are especially sensitive and vulnerable to exploitation. The effects of removing top-predators on food webs are often difficult to predict because of limited information on species interaction strengths. Here we used a three species predator-prey model to explore relationships between energetic properties of trophodynamic linkages and interaction strengths to provide heuristic rules that indicate observable energetic conditions that are most likely to lead to stable and strong top-down control of prey by predator species. We found that strong top-down interaction strengths resulted from low levels of energy flow from prey to predators. Strong interactions are more stable when they are a consequence of low per capita predation and when predators are subsidized by recruitment. Diet composition also affects stability, but the relationship depends on the form of the functional response. Our results imply that for generalist satiating predators, strong top-down control on prey is most likely for prey items that occupy a small portion of the diet and when density dependent recruitment is moderately high. 相似文献
226.
Taube C Tertilt C Gyülveszi G Dehzad N Kreymborg K Schneeweiss K Michel E Reuter S Renauld JC Arnold-Schild D Schild H Buhl R Becher B 《PloS one》2011,6(7):e21799
Interleukin (IL)-22 is an effector cytokine, which acts primarily on epithelial cells in the skin, gut, liver and lung. Both pro- and anti-inflammatory properties have been reported for IL-22 depending on the tissue and disease model. In a murine model of allergic airway inflammation, we found that IL-22 is predominantly produced by innate lymphoid cells in the inflamed lungs, rather than TH cells. To determine the impact of IL-22 on airway inflammation, we used allergen-sensitized IL-22-deficient mice and found that they suffer from significantly higher airway hyperreactivity upon airway challenge. IL-22-deficiency led to increased eosinophil infiltration lymphocyte invasion and production of CCL17 (TARC), IL-5 and IL-13 in the lung. Mice treated with IL-22 before antigen challenge displayed reduced expression of CCL17 and IL-13 and significant amelioration of airway constriction and inflammation. We conclude that innate IL-22 limits airway inflammation, tissue damage and clinical decline in allergic lung disease. 相似文献
227.
Lin AY Chua MS Choi YL Yeh W Kim YH Azzi R Adams GA Sainani K van de Rijn M So SK Pollack JR 《PloS one》2011,6(2):e16636
Purpose
We sought to identify genes of clinical significance to predict survival and the risk for colorectal liver metastasis (CLM), the most common site of metastasis from colorectal cancer (CRC).Patients and Methods
We profiled gene expression in 31 specimens from primary CRC and 32 unmatched specimens of CLM, and performed Significance Analysis of Microarrays (SAM) to identify genes differentially expressed between these two groups. To characterize the clinical relevance of two highly-ranked differentially-expressed genes, we analyzed the expression of secreted phosphoprotein 1 (SPP1 or osteopontin) and lymphoid enhancer factor-1 (LEF1) by immunohistochemistry using a tissue microarray (TMA) representing an independent set of 154 patients with primary CRC.Results
Supervised analysis using SAM identified 963 genes with significantly higher expression in CLM compared to primary CRC, with a false discovery rate of <0.5%. TMA analysis showed SPP1 and LEF1 protein overexpression in 60% and 44% of CRC cases, respectively. Subsequent occurrence of CLM was significantly correlated with the overexpression of LEF1 (chi-square p = 0.042), but not SPP1 (p = 0.14). Kaplan Meier analysis revealed significantly worse survival in patients with overexpression of LEF1 (p<0.01), but not SPP1 (p = 0.11). Both univariate and multivariate analyses identified stage (p<0.0001) and LEF1 overexpression (p<0.05) as important prognostic markers, but not tumor grade or SPP1.Conclusion
Among genes differentially expressed between CLM and primary CRC, we demonstrate overexpression of LEF1 in primary CRC to be a prognostic factor for poor survival and increased risk for liver metastasis. 相似文献228.
Geboes KP De Preter V Luypaerts A Bammens B Evenepoel P Ghoos Y Rutgeerts P Verbeke K 《American journal of physiology. Gastrointestinal and liver physiology》2005,288(5):G994-G999
In vitro experiments have shown that fermentation of carbohydrates prevents accumulation of nitrogen in the colon. Variable results have been obtained on modulation of dietary intakes in vivo. Lactose[15N,15N]-labeled ureide has been proposed as a tool to study colonic nitrogen metabolism. However, on oral administration of the marker, different urinary excretion patterns of the 15N label have been found. In this study, 50 mg lactose[15N,15N]ureide was directly instilled in the colon through an orocecal tube to investigate the colonic handling of this molecule in a direct way. In basal conditions, 42% (range, 37-48%) of labeled nitrogen administered as lactose[15N,15N]ureide was retrieved in urine after 72 h. A substantial variability in total urinary excretion of the label was found, but the urinary excretion pattern of the label was similar in all volunteers. When inulin, a fermentable carbohydrate, was administered together with the labeled marker, a significant decrease in urinary excretion of 15N after 72 h was found, to 29% (range, 23-34%). The effect of a smaller dose of inulin (250 mg) on colonic handling of lactose[15N,15N]ureide (50 mg), was investigated in another group of volunteers, and this time, fecal excretion of the marker was also evaluated. The results seem to indicate that fermentation of inulin causes an increased fecal excretion of the marker, thereby reducing urinary excretion but not retention in the human nitrogen pool. This instillation study shows that lactose[15N,15N]ureide is a tool with good properties to investigate the effect of different types of carbohydrates on nitrogen metabolism in the proximal colon in vivo. 相似文献
229.
We have characterized two mutations in the MC1R gene of the blue variant of the arctic fox (Alopex lagopus) that both incorporate a novel cysteine residue into the receptor. A family study in farmed arctic foxes verified that the dominant expression of the blue color phenotype cosegregates completely with the allele harboring these two mutations. Additionally to the altered pigment synthesis, the blue fox allele suppresses the seasonal change in coat color found in the native arctic fox. Consequently, these findings suggest that the MC1R/agouti regulatory system is involved in the seasonal changes of coat color found in arctic fox. 相似文献