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31.
Cheng A Schweissinger D Dawood F Kumar N Yeager M 《Cell communication & adhesion》2003,10(4-6):187-191
We previously used electron cryo-crystallography to determine the three-dimensional structure of recombinant gap junction channels formed by a C-terminal truncation mutant of Cx43 (11). The dodecameric channel is formed by the end-to-end docking of two hexameric connexons, each comprised of 24 transmembrane alpha-helices. We have now generated two-dimensional crystals of the recombinant, full-length channel, as well as crystals in which the C-tail has been completely removed by trypsin digestion. Projection density maps at 7.5 A resolution closely resemble our previous analysis of the C-terminal truncation mutant (9). A difference map between the full length and trypsin-treated channels suggests that there are small but significant shifts in protein density upon removal of the C-tail. 相似文献
32.
Oliveira DM Nakaie CR Sousa AD Farah CS Reinach FC 《The Journal of biological chemistry》2000,275(36):27513-27519
The in vitro Ca(2+) regulation of the actomyosin Mg(2+)-ATPase at physiological ratios of actin, tropomyosin, and troponin occurs only in the presence of troponin T. We have previously demonstrated that a polypeptide corresponding to the first 191 amino acids of troponin T (TnT-(1-191)) activates the actomyosin Mg(2+)-ATPase in the presence of tropomyosin. In order to further characterize this activation domain, we constructed troponin T fragments corresponding to residues 1-157 (TnT-(1-157)), 1-76 (TnT-(1-76)), 77-157 (TnT-(77-157)), 77-191 (TnT-(77-191)), and 158-191 (TnT-(158-191)). Assays using these fragments demonstrated the following: (a) residues 1-76 do not bind to tropomyosin or actin; (b) residues 158-191 bind to actin cooperatively but not to tropomyosin; (c) the sequence 77-157 is necessary for troponin interaction with residue 263 of tropomyosin; (d) TnT-(77-191) on its own activates the actomyosin ATPase activity as described previously for TnT-(1-191). TnT-(1-157), TnT-(1-76), TnT-(77-157), TnT-(158-191), and combinations of TnT-(158-191) with TnT-(1-157) or TnT-(77-157) showed no effect on the ATPase activity. We conclude that the activation of actomyosin ATPase activity is mediated by a direct interaction between amino acids 77 and 191 of troponin T, tropomyosin, and actin. 相似文献
33.
Fusarium spp. are ubiquitous fungi infecting cereals and grains, and therefore constitute a major problem for agriculture. Their trichothecene metabolites, and in particular deoxynivalenol and its 3-acetylated derivative, are the mycotoxins involved. The major metabolite produced by Fusarium culmorum is 3-acetyldeoxynivalenol. Studies in vivo with Fusarium culmorum have established that its tricyclic intermediate, isotrichodermin, is a major biosynthetic precursor, which is hydroxylated at position 15 to give 15-deacetylcalonectrin, prior to being converted to the product. In a preliminary in vitro investigation of the cell-free system involved in this transformation, we suggested that cytochrome P450 enzymes are not involved. In this paper, the isotrichodermin-15-hydroxylase from the microsomal fraction of Fusarium culmorum was solubilized and partially purified (60 fold). Our studies with cofactors indicate that this enzyme is a flavoprotein, and the inducers tested highly indicate that indeed the hydroxylase is not attached to cytochrome P450. This is particularly interesting, since the only other enzyme catalyzing the same reaction isolated from Fusarium sporotrichiodes is attached to cytochrome P450. 相似文献
34.
The objective of this study was to look for early pathological changes in stress target organs, adrenal glands, and stomachs in captured wild African green monkeys (AGMs). Three wild-caught male AGMs and seven singly housed wild AGMs were euthanized on day 1 and day 45 post-capture, respectively, and compared with four wild males euthanized with a rifle as controls. Morphometric analyses of the adrenal cortices and the cortical zones were done using an image analyzer. By day 45, the confined animals were clinically healthy, but had lost 47% mean body weight despite ad libitum feeding. The width of zona fasciculata in the controls was significantly smaller compared with that of 45-day monkeys (P < 0.05). Numerous acidophilic, hyperplastic and hypertrophic cells were present in the zona fasciculata of the 1-day confined AGMs. In the 45-day monkeys, there was glandular hyperplasia in the zona glomerulosa and the acini were distended and vacuous; yellow, granular pigmentation was distributed in the zona fasciculata. Acute stomach lesions represented by petechiation were seen in one monkey on day 1. Deep, circular, mucosal erosions, one to five in number and measuring from 0.5 to 1 mm in diameter, were present in three monkeys on day 45 post-capture. There were no adrenal cortex or stomach lesions in the rifle-shot monkeys. In conclusion, pathological lesions in the adrenal glands, and stomachs of the wild AGMs and weight loss occurred within the initial 45-day period following capture and confinement. 相似文献
35.
D.L. Langoi P.G. Mwethera K.S.P. Abelson I.O. Farah & H.E. Carlsson 《Journal of medical primatology》2009,38(6):404-410
Background The potential of Atipamezole (ATI) to reverse Ketamine/Xylazine (KET/XYL) anesthesia in the Olive baboon ( Papio anubis ) was studied.
Methods Anesthesia was induced with 10 mg/kg KET and 0.5 mg/kg XYL intramuscularly. Mean arousal time (MAT), heart rate (HR), systolic arterial blood pressure (SAP), rectal temperature, respiratory rate (RR), and hemoglobin oxygen saturation (SpO2 ) were monitored. Baboons were treated with: KET/XYL only, KET/XYL followed by 100 μg/kg ATI or by 200 μg/kg ATI administered 25 minutes after KET/XYL.
Results Atipamezole rapidly reversed depressed HR and SAP (10 ± 5.2 minutes), RR (5 ± 2 minutes) and SpO2 (3 ± 6 minutes) and significantly decreased MAT (13 ± 2.2 minutes) vs. KET/XYL alone (35 ± 5 minutes). Emesis was absent and salivation was observed after administration of 200 μg/kg ATI only.
Conclusions Atipamezole at 100 μg/kg is sufficient for rapid and smooth reversal of KET/XYL anesthesia in the Olive baboon with minimal side effects. 相似文献
Methods Anesthesia was induced with 10 mg/kg KET and 0.5 mg/kg XYL intramuscularly. Mean arousal time (MAT), heart rate (HR), systolic arterial blood pressure (SAP), rectal temperature, respiratory rate (RR), and hemoglobin oxygen saturation (SpO
Results Atipamezole rapidly reversed depressed HR and SAP (10 ± 5.2 minutes), RR (5 ± 2 minutes) and SpO
Conclusions Atipamezole at 100 μg/kg is sufficient for rapid and smooth reversal of KET/XYL anesthesia in the Olive baboon with minimal side effects. 相似文献
36.
Shubha Priyamvada Sara A. Khan Md.Wasim Khan Sheeba Khan Neelam Farooq Farah Khan A.N.K. Yusufi 《Prostaglandins, leukotrienes, and essential fatty acids》2010,82(1):35-44
Human and animal exposure demonstrates that uranium is nephrotoxic. However, attempts to reduce it were not found suitable for clinical use. Dietary fish oil (FO) enriched in ω-3 fatty acids reduces the severity of cardiovascular and renal diseases. Present study investigates the protective effect of FO on uranyl nitrate (UN)-induced renal damage. Rats prefed with experimental diets for 15 days, given single nephrotoxic dose of UN (0.5 mg/kg body weight) intraperitoneally. After 5 d of UN treatment, serum/urine parameters, enzymes of carbohydrate metabolism, brush border membrane (BBM), oxidative stress and phosphate transport were analyzed in rat kidney. UN nephrotoxicity was characterized by increased serum creatinine and blood urea nitrogen. UN increased the activity of lactate dehydrogenase and NADP-malic enzyme whereas decreased malate, isocitrate and glucose-6-phophate dehydrogenases; glucose-6-phophatase, fructose-1, 6-bisphosphatase and BBM enzyme activities. UN caused oxidant/antioxidant imbalances as reflected by increased lipid peroxidation, activities of superoxide dismutase, glutathione peroxidase and decreased catalase activity. Feeding FO alone increased activities of enzymes of glucose metabolism, BBM, oxidative stress and Pi transport. UN-elicited alterations were prevented by FO feeding. However, corn oil had no such effects and was not similarly effective. In conclusion, FO appears to protect against UN-induced nephrotoxicity by improving energy metabolism and antioxidant defense mechanism. 相似文献
37.
Purpose
Evidence is inconsistent regarding alcohol and pancreatic cancer risk, although heavy drinking may increase risk.Methods
A population-based case-control study was conducted using 345 pancreas cancer cases diagnosed 2011–2012 and 1,285 frequency-matched controls from Ontario, Canada. Logistic regression was used to evaluate alcohol consumption and pancreatic cancer risk; data was also stratified by sex and smoking status to assess interaction.Results
Alcohol consumption was not associated with pancreatic cancer risk (age-adjusted odds ratio=0.78, 95% CI: 0.58, 1.05 for 1 - 3 drinks/week; age-adjusted odds ratio=0.86, 95% CI: 0.63, 1.17 for 4 - 20 drinks/week), however there was a non-significant increased risk for heavy drinkers consuming ≥21 drinks/week (age-adjusted odds ratio=1.35, 95% CI: 0.81, 2.27). Cigarette smoking modified the alcohol-cancer relationship; among current smokers, heavy alcohol consumption was associated with a significantly increased pancreatic cancer risk (age-adjusted odds ratio=4.04, 95% CI: 1.58, 10.37), whereas this significant association with heavy drinking was not observed among non-smokers (age-adjusted odds ratio=2.01, 95% CI: 0.50, 8.18). Furthermore, light – moderate alcohol intake was associated with increased pancreas cancer risk among current smokers.Conclusions
While alcohol was not significantly associated with pancreatic cancer risk, smoking status modified this relationship such that among current smokers, alcohol intake was associated with a greater than two-fold increased risk of pancreatic cancer. The results should be interpreted with caution due to small sample sizes within subgroups and correction for multiple comparisons should be considered. These findings should be replicated in larger studies where more precise estimates of risk can be obtained. 相似文献38.
39.
Nina Klee Pui Ee Wong Beatriz Baragaña Farah El Mazouni Margaret A. Phillips Michael P. Barrett Ian H. Gilbert 《Bioorganic & medicinal chemistry letters》2010,20(15):4364-4366
Trypanosoma brucei, the parasite that causes human African trypanosomiasis, is auxotrophic for purines and has specialist nucleoside transporters to import these metabolites. In particular, the P2 aminopurine transporter can also selectively accumulate melamine derivatives. In this Letter, we report the coupling of the melamine moiety to 2-hydroxy APA, a potent ornithine decarboxylase inhibitor, with the aim of selectively delivering this compound to the parasite. The best compound described here shows an increased in vitro trypanocidal activity compared with the parent. 相似文献
40.