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151.
152.
Prashant Sonawane Krunal Patel Rishi Kishore Vishwakarma Somesh Singh Bashir Mohammad Khan 《Bioinformation》2013,9(5):224-232
Cinnamoyl CoA reductase (CCR) carries out the first committed step in monolignol biosynthesis and acts as a first regulatory point
in lignin formation. CCR shows multiple substrate specificity towards various cinnamoyl CoA esters. Here, in Silico mutagenesis
studies of active site residues of Ll-CCRH1 were carried out. Homology modeling based modeled 3D structure of Ll-CCRH1 was
used as template for in Silico mutant preparations. Docking simulations of Ll-CCRH1 mutants with CoA esters by AutoDock Vina
tools showed altered substrate specificity as compared to wild type. The study evidences that conformational changes, and change
in geometry or architecture of active site pocket occurred following mutations. The altered substrate specificity for active site
mutants suggests the possible physiological role of CCR either in lignin formation or in defense system in plants.
Abbreviations
Ll-CCRH1 - Leucaena leucocephala cinnamoyl CoA reductase 1, OPLS - Optimized Potentials for Liquid Simulations, RMSD - Root Mean Square Deviation. 相似文献153.
Sainath R. Kotha Melissa G. Piper Rishi B. Patel Sean Sliman Smitha Malireddy Lingying Zhao Christopher P. Baran Patrick S. Nana-Sinkam Mark D. Wewers Debra Romberger Clay B. Marsh Narasimham L. Parinandi 《Cell biochemistry and biophysics》2013,67(2):415-429
The mechanisms of poultry particulate matter (PM)-induced agricultural respiratory disorders are not thoroughly understood. Hence, it is hypothesized in this article that poultry PM induces the release of interleukin-8 (IL-8) by lung epithelial cells that is regulated upstream by the concerted action of cytosolic phospholipase A2 (cPLA2) and extracellular signal-regulated kinase (ERK). To test this hypothesis, the widely used cultured human lung epithelial cells (A549) were chosen as the model system. Poultry PM caused a significant activation of PLA2 in A549 cells, which was attenuated by AACOCF3 (cPLA2 inhibitor) and PD98059 (ERK-1/2 upstream inhibitor). Poultry PM induced upstream ERK-1/2 phosphorylation and downstream cPLA2 serine phosphorylation, in a concerted fashion, in cells with enhanced association of ERK-1/2 and cPLA2. The poultry PM-induced cPLA2 serine phosphorylation and IL-8 release were attenuated by AACOCF3, PD98059, and by transfection with dominant-negative ERK-1/2 DNA in cells. The poultry PM-induced IL-8 release by the bone marrow-derived macrophages of cPLA2 knockout mice was significantly lower. For the first time, this study demonstrated that the poultry PM-induced IL-8 secretion by human lung epithelial cells was regulated by cPLA2 activation through ERK-mediated serine phosphorylation, suggesting a mechanism of airway inflammation among poultry farm workers. 相似文献
154.
Mihailescu M Vaswani RG Jardón-Valadez E Castro-Román F Freites JA Worcester DL Chamberlin AR Tobias DJ White SH 《Biophysical journal》2011,100(6):1455-1462
A central feature of the lipid raft concept is the formation of cholesterol-rich lipid domains. The introduction of relatively rigid cholesterol molecules into fluid liquid-disordered (Ld) phospholipid bilayers can produce liquid-ordered (Lo) mixtures in which the rigidity of cholesterol causes partial ordering of the flexible hydrocarbon acyl chains of the phospholipids. Several lines of evidence support this concept, but direct structural information about Lo membranes is lacking. Here we present the structure of Lo membranes formed from cholesterol and dioleoylphosphatidylcholine (DOPC). Specific deuteration of the DOPC acyl-chain methyl groups and neutron diffraction measurements reveal an extraordinary disorder of the acyl chains of neat Ld DOPC bilayers. The disorder is so great that >20% of the methyl groups are in intimate contact with water in the bilayer interface. The ordering of the DOPC acyl chains by cholesterol leads to retraction of the methyl groups away from the interface. Molecular dynamics simulations based on experimental systems reveal asymmetric transbilayer distributions of the methyl groups associated with each bilayer leaflet. 相似文献
155.
Both hypertension and depression are common disorders which may both involve components of the hypothalamic-pituitary-adrenal
axis system and the Renin-Angiotensin-Aldosterone System (RAAS). These observations, coupled with growing evidence that RAAS-active
drugs may have anti-depressant properties prompted us to study the frequency of anti-depressant medication usage in the patients
receiving RAAS-active agents. A chart review was performed on 378 patients who were seen during a 3-month period in a primary
care clinic and who were diagnosed with hypertension. Demographic information and data on the rates of co-administration of
antihypertensive and anti-depressant medications was collected. Overall, 23.7% of the sample was on an antidepressant. 20%
of the patients taking a RAAS-modifying medication were on an antidepressant, compared to 34% of those not taking a RAAS-modifying
medication (Χ
2 = 8.88, P = 0.003). The patients taking a beta-blocker alone had the highest rate of antidepressant usage (40%). The use of RAAS-modifying
medications was associated with an even lower rate of anti-depressant usage in males compared with females. It was also observed
that the patients taking an additional diuretic had a significantly lower rate of antidepressant use (17.6%, Χ
2 = 5.81, P = 0.016) compared with the patients not taking a diuretic. The patients being treated with an ACE inhibitor or ARB showed
significantly lower rates of antidepressant usage. The data is supportive of the hypothesis that these agents may possess
anti-depressant effects. 相似文献
156.
In the present study we describe heterodimerization, trafficking, coupling to adenylyl cyclase and signaling in HEK-293 cells cotransfected with human-somatostatin receptor 5 (hSSTR5) and β1-adrenergic receptor (β1AR). hSSTR5/β1AR exists as heterodimers in basal conditions which was further enhanced upon synergistic activation of both receptors. Activation of either β1AR or hSSTR5 displayed dissociation of heterodimerization. In cotransfectants, β1AR effect on cAMP was predominant; however, blocking β1AR with antagonist resulted in 60% inhibition of forskolin-stimulated cAMP in the presence of hSSTR5 agonists. cAMP/PKA pathway in cotransfected cells was regulated in receptor-specific manner, in contrast, the status of pERK1/2 and pPI3K/AKT was predominantly regulated by hSSTR5. The expression levels of phosphorylated NFAT remained unchanged indicating blockade of calcineurin-mediated dephosphorylation and nuclear translocation of NFAT, the process predominantly regulated by pJNK in SSTR5 dependent manner. Taken together, the functional consequences of results described here might have relevance in the cardiovascular system where SSTR and AR subtypes play important roles. 相似文献
157.
Sharma Sampriya Mandhan Rishi Pal Sharma Jitender 《World journal of microbiology & biotechnology》2011,27(11):2697-2701
A cellulase free, alkaline, thermo-tolerant pectinase was produced by a novel yeast strain Pseudozyma sp. SPJ using citrus peel as inexpensive carbon source. The crude enzyme showed good prospects in degumming of flax fibers
for textile industry. An optimum pectinase dose of 80 U g−1 resulted in reduction of 15 ± 1.92% dry weight of the fibers, releasing maximum galacturonic acid (10825.5 ± 34.2 μg g−1 dry fiber) after the incubation of 6 h. The yeast culture could grow on the flax fibers (as sole carbon source) without addition
of any other nutrient and produce good enzyme yield (9235.5 ± 21.51 U g−1 dry fiber). After 12 h incubation of the fibers with the isolated yeast strain, 4471 ± 19.5 μg g−1 dry fiber galacturonic acid was achieved with maximum weight loss of 11 ± 1.2%. This process reduced the amount of chemicals
and energy used in conventional methods. It also contributed to enhance fineness and overall quality of the fiber strands.
This study is relevant to the textile industry as it provided a fast, economical and eco-friendly method for degumming of
flax fibers. 相似文献
158.
Zhigang Yuan Marissa Frazer Anupam Rishi Kujtim Latifi Michal R. Tomaszewski Eduardo G. Moros Vladimir Feygelman Seth Felder Julian Sanchez Sophie Dessureault Iman Imanirad Richard D. Kim Louis B. Harrison Sarah E. Hoffe Geoffrey G. Zhang Jessica M. Frakes 《Reports of Practical Oncology and Radiotherapy》2021,26(1):29
BackgroundThe purpose of this study was to characterize pre-treatment non-contrast computed tomography (CT) and 18F-fluorodeoxyglucose positron emission tomography (PET) based radiomics signatures predictive of pathological response and clinical outcomes in rectal cancer patients treated with neoadjuvant chemoradiotherapy (NACR T).Materials and methodsAn exploratory analysis was performed using pre-treatment non-contrast CT and PET imaging dataset. The association of tumor regression grade (TRG) and neoadjuvant rectal (NAR) score with pre-treatment CT and PET features was assessed using machine learning algorithms. Three separate predictive models were built for composite features from CT + PET.ResultsThe patterns of pathological response were TRG 0 (n = 13; 19.7%), 1 (n = 34; 51.5%), 2 (n = 16; 24.2%), and 3 (n = 3; 4.5%). There were 20 (30.3%) patients with low, 22 (33.3%) with intermediate and 24 (36.4%) with high NAR scores. Three separate predictive models were built for composite features from CT + PET and analyzed separately for clinical endpoints. Composite features with α = 0.2 resulted in the best predictive power using logistic regression. For pathological response prediction, the signature resulted in 88.1% accuracy in predicting TRG 0 vs. TRG 1–3; 91% accuracy in predicting TRG 0–1 vs. TRG 2–3. For the surrogate of DFS and OS, it resulted in 67.7% accuracy in predicting low vs. intermediate vs. high NAR scores.ConclusionThe pre-treatment composite radiomics signatures were highly predictive of pathological response in rectal cancer treated with NACR T. A larger cohort is warranted for further validation. 相似文献
159.
Vino T. Cheriyan Ying Wang Magesh Muthu Shazia Jamal Di Chen Huanjie Yang Lisa A. Polin Adi L. Tarca Harvey I. Pass Q. Ping Dou Sunita Sharma Anil Wali Arun K. Rishi 《PloS one》2014,9(4)
Dithiocarbamate compound Disulfiram (DSF) that binds with copper and functions as an inhibitor of aldehyde dehydrogenase is a Food and Drug Administration approved agent for treatment of alcoholism. Copper complexed DSF (DSF-Cu) also possesses anti-tumor and chemosensitizing properties; however, its molecular mechanisms of action remain unclear. Here we investigated malignant pleural mesothelioma (MPM) suppressive effects of DSF-Cu and the molecular mechanisms involved. DSF-Cu inhibited growth of the murine as well as human MPM cells in part by increasing levels of ubiquitinated proteins. DSF-Cu exposure stimulated apoptosis in MPM cells that involved activation of stress-activated protein kinases (SAPKs) p38 and JNK1/2, caspase-3, and cleavage of poly-(ADP-ribose)-polymerase, as well as increased expression of sulfatase 1 and apoptosis transducing CARP-1/CCAR1 protein. Gene-array based analyses revealed that DSF-Cu suppressed cell growth and metastasis-promoting genes including matrix metallopeptidase 3 and 10. DSF inhibited MPM cell growth and survival by upregulating cell cycle inhibitor p27Kip1, IGFBP7, and inhibitors of NF-κB such as ABIN 1 and 2 and Inhibitory κB (IκB)α and β proteins. DSF-Cu promoted cleavage of vimentin, as well as serine-phosphorylation and lysine-63 linked ubiquitination of podoplanin. Administration of 50 mg/kg DSF-Cu by daily i.p injections inhibited growth of murine MPM cell-derived tumors in vivo. Although podoplanin expression often correlates with metastatic disease and poor prognosis, phosphorylation of serines in cytoplasmic domain of podoplanin has recently been shown to interfere with cellular motility and migration signaling. Post-translational modification of podoplanin and cleavage of vimentin by DSF-Cu underscore a metastasis inhibitory property of this agent and together with our in vivo studies underscore its potential as an anti-MPM agent. 相似文献
160.