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991.
We investigate how stochastic reaction processes are affected by external perturbations. We describe an extension of the deterministic metabolic control analysis (MCA) to the stochastic regime. We introduce stochastic sensitivities for mean and covariance values of reactant concentrations and reaction fluxes and show that there exist MCA-like summation theorems among these sensitivities. The summation theorems for flux variances is shown to depend on the size of the measurement time window (?) within which reaction events are counted for measuring a single flux. It is found that the degree of the ?-dependency can become significant for processes involving multi-time-scale dynamics and is estimated by introducing a new measure of time-scale separation. This ?-dependency is shown to be closely related to the power-law scaling observed in flux fluctuations in various complex networks. 相似文献
992.
Wouter Everaerts Bernd Nilius Grzegorz Owsianik 《Progress in biophysics and molecular biology》2010,103(1):2-17
The Transient Receptor Potential Vanilloid 4 channel, TRPV4, is a Ca2+ and Mg2+ permeable non-selective cation channel involved in many different cellular functions. It is activated by a variety of physical and chemical stimuli, including heat, mechano-stimuli, endogenous substances such as arachidonic acid and its cytochrome P450-derived metabolites (epoxyeicosatrienoic acids), endocannabinoids (anandamide and 2-arachidonoylglycerol), as well as synthetic α-phorbol derivatives. Recently, TRPV4 has been characterized as an important player modulating osteoclast differentiation in bone remodelling and as a urothelial mechanosensor that controls normal voiding. Several TRPV4 gain-of-function mutations are shown to cause autosomal-dominant bone dysplasias such as brachyolmia and Koszlowski disease. In this review we comprehensively describe the structural, biophysical and (patho)physiological properties of the TRPV4 channel and we summarize the current knowledge about the role of TRPV4 in the pathogenesis of several diseases. 相似文献
993.
Takashi Suzuki Koko Moriya Kei Nagatoshi Yoshinobu Ota Toru Ezure Eiji Ando Susumu Tsunasawa Toshihiko Utsumi 《Proteomics》2010,10(9):1780-1793
To establish a strategy for the comprehensive identification of human N‐myristoylated proteins, the susceptibility of human cDNA clones to protein N‐myristoylation was evaluated by metabolic labeling and MS analyses of proteins expressed in an insect cell‐free protein synthesis system. One‐hundred‐and‐forty‐one cDNA clones with N‐terminal Met‐Gly motifs were selected as potential candidates from ~2000 Kazusa ORFeome project human cDNA clones, and their susceptibility to protein N‐myristoylation was evaluated using fusion proteins, in which the N‐terminal ten amino acid residues were fused to an epitope‐tagged model protein. As a result, the products of 29 out of 141 cDNA clones were found to be effectively N‐myristoylated. The metabolic labeling experiments both in an insect cell‐free protein synthesis system and in the transfected COS‐1 cells using full‐length cDNA revealed that 27 out of 29 proteins were in fact N‐myristoylated. Database searches with these 27 cDNA clones revealed that 18 out of 27 proteins are novel N‐myristoylated proteins that have not been reported previously to be N‐myristoylated, indicating that this strategy is useful for the comprehensive identification of human N‐myristoylated proteins from human cDNA resources. 相似文献
994.
995.
Rongjun Chen Najeem Folarin Vincent H.B. Ho David McNally David Darling Farzin Farzaneh Nigel K.H. Slater 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2010,878(22):1939-1945
Desthiobiotin-tagged lentiviral vectors have been metabolically produced by DBL producer cells in a 7,8-diaminopelargonic acid (7-DAPA) dependent manner for envelope independent, single-step affinity purification. 7-DAPA, which has little or no affinity for avidin/streptavidin, was synthesised and verified by NMR spectroscopy and mass spectrometry. By expressing the biotin acceptor, biotin ligase and desthiobiotin synthase bioD, DBL cells converted exogenous 7-DAPA into membrane-bound desthiobiotin. Desthiobiotin on the DBL cell surface was visualised by confocal microscopy and the desthiobiotin density was quantified by HABA-avidin assay. Desthiobiotin was then spontaneously incorporated onto the surface of lentiviral vectors produced by the DBL cells. It has been demonstrated by flow cytometry that the desthiobiotinylated lentiviruses were captured from the crude 7-DAPA-containing viral supernatant by Streptavidin Magnespheres® and eluted by biotin solution efficiently whilst retaining infectivity. The practical, high yielding virus purification using Pierce monomeric avidin coated columns indicates a highly efficient biotin-dependent recovery of infectious lentiviruses at 68%. The recovered lentiviral vectors had a high purity and the majority were eluted within 45 min. This 7-DAPA mediated desthiobiotinylation technology can be applied in scalable production of viral vectors for clinical gene therapy. 相似文献
996.
噻托溴铵及噻托溴铵联合布地奈德福莫特罗治疗COPD疗效分析 总被引:2,自引:0,他引:2
目的:观察噻托溴铵与布地奈德/福莫特罗联合吸入和噻托溴铵单独吸入对慢性阻塞性肺疾病(COPD)患者的疗效及安全性。方法:58例COPD患者随机分为2组:治疗组30例,给予噻托溴铵(18μg,1次/d)联合布地奈德/福莫特罗(160/4.5μg,2次/d)吸入治疗;对照组28例,给予噻托溴铵(18μg,1次/d)吸入治疗。观察患者治疗前、治疗8周和16周后肺功能及临床症状的变化。结果:治疗8周和16周后,2组FEV1和SGRQ症状评分均较治疗前明显改善(P<0.05),治疗组FEV1和SGRQ症状评分的改善显著高于对照组(P<0.05);治疗组白天使用沙丁胺醇次数更少(P<0.05)。各组均未出现明显不良反应。结论:噻托溴铵与布地奈德/福莫特罗联合吸入治疗COPD,疗效优于噻托溴铵单药治疗。 相似文献
997.
Plasmacytoid dendritic cells (pDCs) represent a unique and crucial immune cell population capable of producing large amounts
of type I interferons (IFNs) in response to viral infection. The function of pDCs as the professional type I IFN-producing
cells is linked to their selective expression of Toll-like receptor 7 (TLR7) and TLR9, which sense viral nucleic acids within
the endosomal compartments. Type I IFNs produced by pDCs not only directly inhibit viral replication but also play an essential
role in linking the innate and adaptive immune system. The aberrant activation of pDCs by self nucleic acids through TLR signaling
and the ongoing production of type I IFNs do occur in some autoimmune diseases. Therefore, pDC may serve as an attractive
target for therapeutic manipulations of the immune system to treat viral infectious diseases and autoimmune diseases. 相似文献
998.
Clark J. Nelson Jessica P. Otis Hannah V. Carey 《Comparative biochemistry and physiology. Part D, Genomics & proteomics》2010,5(4):265-273
Hibernation in mammals involves major alterations in nutrition and metabolism that would be expected to affect levels of circulating molecules. To gain insight into these changes we conducted a non-targeted LC–MS based metabolomic analysis of plasma using hibernating ground squirrels in late torpor (LT, Tb ~ 5 °C) or during an interbout arousal period (IBA, Tb ~ 5 °C) and non-hibernating squirrels in spring (Tb ~ 37 °C). Several metabolites varied and allowed differentiation between hibernators and spring squirrels, and between torpid and euthermic squirrels. Methionine and the short-chain carnitine esters of propionate and butyryate/isobutyrate were reduced in LT compared with the euthermic groups. Pantothenic acid and several lysophosphatidylcholines were elevated in LT relative to the euthermic groups, whereas lysophosphatidylethanolamines were elevated during IBA compared to LT and spring animals. Two regulatory lipids varied among the groups: sphingosine 1-phosphate was lower in LT vs. euthermic groups, whereas cholesterol sulfate was elevated in IBA compared to spring squirrels. Levels of long-chain fatty acids (LCFA) and total NEFA tended to be elevated in hibernators relative to spring squirrels. Three long-chain acylcarnitines were reduced in LT relative to IBA; free carnitine was also lower in LT vs. IBA. Our results identified several biochemical changes not previously observed in the seasonal hibernation cycle, including some that may provide insight into the metabolic limitations of mammalian torpor. 相似文献
999.
Nathaniel D. Maynard Miriam V. Gutschow Elsa W. Birch Markus W. Covert Professor 《Biotechnology journal》2010,5(7):686-694
Recent genome-wide screens of host genetic requirements for viral infection have reemphasized the critical role of host metabolism in enabling the production of viral particles. In this review, we highlight the metabolic aspects of viral infection found in these studies, and focus on the opportunities these requirements present for metabolic engineers. In particular, the objectives and approaches that metabolic engineers use are readily comparable to the behaviors exhibited by viruses during infection. As a result, metabolic engineers have a unique perspective that could lead to novel and effective methods to combat viral infection. 相似文献
1000.
Seung Bum Sohn Tae Yong Kim Jong Myoung Park Sang Yup Lee Professor 《Biotechnology journal》2010,5(7):739-750
Genome-scale metabolic models have been appearing with increasing frequency and have been employed in a wide range of biotechnological applications as well as in biological studies. With the metabolic model as a platform, engineering strategies have become more systematic and focused, unlike the random shotgun approach used in the past. Here we present the genome-scale metabolic model of the versatile Gram-negative bacterium Pseudomonas putida, which has gained widespread interest for various biotechnological applications. With the construction of the genome-scale metabolic model of P. putida KT2440, PpuMBEL1071, we investigated various characteristics of P. putida, such as its capacity for synthesizing polyhydroxyalkanoates (PHA) and degrading aromatics. Although P. putida has been characterized as a strict aerobic bacterium, the physiological characteristics required to achieve anaerobic survival were investigated. Through analysis of PpuMBEL1071, extended survival of P. putida under anaerobic stress was achieved by introducing the ackA gene from Pseudomonas aeruginosa and Escherichia coli. 相似文献