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 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A kinetic-metabolic model approach describing and simulating Chinese hamster ovary (CHO) cell behavior is presented. The model includes glycolysis, pentose phosphate pathway, TCA cycle, respiratory chain, redox state and energetic metabolism. Growth kinetic is defined as a function of the major precursors for the synthesis of cell building blocks. Michaelis-Menten type kinetic is used for metabolic intermediates as well as for regulatory functions from energy shuttles (ATP/ADP) and cofactors (NAD/H and NADP/H). Model structure and parameters were first calibrated using results from bioreactor cultures of CHO cells expressing recombinant t-PA. It is shown that the model can simulate experimental data for all available experimental data, such as extracellular glucose, glutamine, lactate and ammonium concentration time profiles, as well as cell energetic state. A sensitivity analysis allowed identifying the most sensitive parameters. The model was then shown to be readily adaptable for studying the effect of sodium butyrate on CHO cells metabolism, where it was applied to the cases with sodium butyrate addition either at mid-exponential growth phase (48 h) or at the early plateau phase (74 h). In both cases, a global optimization routine was used for the simultaneous estimation of the most sensitive parameters, while the insensitive parameters were considered as constants. Finally, confidence intervals for the estimated parameters were calculated. Results presented here further substantiate our previous findings that butyrate treatment at mid-exponential phase may cause a shift in cellular metabolism toward a sustained and increased efficiency of glucose utilization channeled through the TCA cycle.
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PMID:A kinetic-metabolic model based on cell energetic state: study of CHO cell behavior under Na-butyrate stimulation. 2297 19

This chapter outlines the physiology of Yersinia pestis with emphasis on identifying unique functions required for tissue invasion and acute disease. These activities are opposed to often incompatible processes expressed by very closely related Yersinia pseudotuberculosis, which causes localized gastrointestinal infection. Gain of new information in Y. pestis entailed lateral transfer of plasminogen activator and anti-phagocytic capsular antigen via the plasmids pPCP and pMT, respectively, and derepression of the pigmentation locus facilitating colonization of the flea vector. The ability to survive in austere natural environments became unnecessary following mastery of the closed flea-rodent-flea life cycle permitting concomitant chromosomal degeneration (large and small deletions, additions, inversions, translocations, transposon inserts, and single base substitutions causing nonsense and missense mutations). Consequently, modern Y. pestis lacks a functional pentose-phosphate pathway, glyoxylate bypass, and is unable to directly catabolize L-aspartate and close metabolic derivatives directly via the tricarboxylic acid cycle. The missing gene products accounting for these and numerous other metabolic lesions are now well-established. This group includes formyltetrahydrofolate deformylase (PurU) required for synthesis of glycine. This deficiency is associated with a dramatic ability of Y. pestis to catabolize L-serine, required by the host to initiate methylation of DNA (necessary in turn to initiate successful innate immune processes leading to delayed-type hypersensitivity).
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PMID:Physiology of Yersinia pestis. 2772 61

Purpose: Type 2 Diabetes mellitus (DM) is a major health problem and its ocular complications like orbital infections, cataract and diabetic retinopathy cause blindness. Meibomian gland (MG) dysfunction and dry eye disease are also important ocular complications of type 2 DM but not enough research has been conducted on these complications. Our hypothesis suggests type 2 DM can alter significant gene expressions of MG. In our study, MGs of leptin-deficient spontaneous diabetic and non-diabetic mice were extracted, and gene expression profiles were analyzed with microarray technology.Methods: Mice were divided into two groups; nine Lep b/ob spontaneous diabetic mice as type 2 DM group and nine non-diabetic Balb/c mice as controls. Blood glucose levels, tearfilm break-up time and fluorescein scores were measured in both two groups for 12 weeks. MGs were dissected and RNAs were isolated for microarray gene expression analysis. We filtered probes with standard deviation of more than 0.1 and we used 40452 of 45281 probes for processing. We performed fold change analysis and identified which genes are affected, and we analyzed the impact of genes on proteins, pathways and gene ontologies by using various databases.Results: We observed 172 up-regulated and 118 down-regulated genes in type 2 diabetic mice when compared to non-diabetic mice. Interestingly, expression of collagen type I, integrin beta-I binding protein-I, pyruvate dehydrogenase kinase, TNF receptor genes up-regulated with DM; on the other hand, IL-33, cholecystokinin, plasminogen activator, IL-1 and serine peptidase inhibitor genes down-regulated significantly. Also, we have seen a significant decrease in WNT signaling and pentose phosphate pathways-related genes.Conclusion: Our data show these changes in gene expression caused by endocrine and immune mechanisms of type 2 DM which result disrupted homeostasis of epithelial cells of MG. Increased expressions of apoptosis and inflammation-related genes and their effects on related pathways have proven that MGs were negatively affected by type-2 DM.
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PMID:Effects of Type 2 Diabetes Mellitus on Gene Expressions of Mouse Meibomian Glands. 3142 65