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21.
Thornton TM Pedraza-Alva G Deng B Wood CD Aronshtam A Clements JL Sabio G Davis RJ Matthews DE Doble B Rincon M 《Science (New York, N.Y.)》2008,320(5876):667-670
Glycogen synthase kinase 3beta (GSK3beta) is involved in metabolism, neurodegeneration, and cancer. Inhibition of GSK3beta activity is the primary mechanism that regulates this widely expressed active kinase. Although the protein kinase Akt inhibits GSK3beta by phosphorylation at the N terminus, preventing Akt-mediated phosphorylation does not affect the cell-survival pathway activated through the GSK3beta substrate beta-catenin. Here, we show that p38 mitogen-activated protein kinase (MAPK) also inactivates GSK3beta by direct phosphorylation at its C terminus, and this inactivation can lead to an accumulation of beta-catenin. p38 MAPK-mediated phosphorylation of GSK3beta occurs primarily in the brain and thymocytes. Activation of beta-catenin-mediated signaling through GSK3beta inhibition provides a potential mechanism for p38 MAPK-mediated survival in specific tissues. 相似文献
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Use of Porcine Meal in Plant‐based Practical Diets for Pacific White Shrimp,Litopenaeus vannamei 下载免费PDF全文
Two growth trials were conducted to evaluate and confirm the efficacy of a porcine meal (PM) with high protein content (>90%) as an alternative feed ingredient in commercial‐type feed formulation for Pacific white shrimp, Litopenaeus vannamei. Six experimental diets were formulated for the two growth trials. The first five diets contained increasing levels (0, 1, 2, 4, and 6%) of PM as a replacement for soybean meal in a plant‐based diet with low inclusion level (6%) of fish meal (FM). The last experimental diet was produced utilizing 4.2% PM to completely replace FM. In Trial 1, shrimp (1.5 g initial mean weight, 20 shrimp/tank, n = 4) were offered test diets for 6 wk in a semirecirculation system. At the end of Trial 1, shrimp fed with the diet containing 6% PM exhibited significantly enhanced weight gain (WG), feed conversion ratio (FCR), and survival compared to those fed with the diet devoid of FM. As survival was poor across all treatments and different densities could mask growth results the trial was repeated. In Trial 2, shrimp (0.85 g, 15 shrimp/tank, n = 4) were offered diets for 6 wk. Dietary supplementation of PM at 6% significantly improved WG, FCR, and apparent net protein retention in contrast with the treatment devoid of FM, confirming the same trends in Trial 1. No significant difference was detected in protein, lipid, moisture, and mineral profiles of whole‐body shrimp as well as survival across all the treatments. Results of this study indicate that PM is a good high protein source in shrimp feeds, which can be included up to 6% in the low FM‐based diet without compromising the growth of shrimp. 相似文献
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Kip E. Panter Bryan L. Stegelmeier Dale R. Gardner Clinton A. Stonecipher Stephen T. Lee Don Kitchen Adeline Brackett Charlie Davis 《Journal of veterinary diagnostic investigation》2021,33(3):538
Salvia reflexa (lance-leaf sage)-contaminated alfalfa hay was fed to ~500 mixed-breed beef cattle. Within hours of exposure, nearly half of the cattle developed lethargy, anorexia, depression, and recumbency, followed by bellowing, colic, and death. Even though the uneaten contaminated hay was removed the first day, nearly 100 animals died within the first 48 h. Three of these cattle were examined postmortem, and tissues and hay samples were collected for microscopic and chemical analysis. Several days later, a smaller number of the clinically poisoned cattle developed neurologic disease with aberrant behavior, aggression, icterus, blindness, exhaustion, and death. A total of 165 cattle were fatally poisoned. Poisoned cattle had swollen, dark, mottled livers that had a prominent nutmeg-like lobular pattern on cut section. Histologically, there was severe centrilobular-to-panlobular hepatic necrosis with marked hepatocellular swelling, degeneration, and necrosis. The surviving cattle developed liver disease characterized by altered serum biochemical analyses and microscopic hepatocellular degeneration and necrosis. In subsequent biopsies and analysis, these lesions resolved within 6–7 mo. After confirming toxicity of the hay in cattle, goats, and mice, followed by a mouse bioassay–guided chemical fractionation process, Salvia reflexa was identified as the contaminant in the hay responsible for the hepatotoxicity. S. reflexa has not been reported previously to cause fatal hepatotoxicity in livestock in North America, to our knowledge. 相似文献
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Little D Brown SA Campbell NB Moeser AJ Davis JL Blikslager AT 《American journal of veterinary research》2007,68(6):614-624
OBJECTIVE: To determine the effect of meloxicam and flunixin meglumine on recovery of ischemia-injured equine jejunum. ANIMALS: 18 horses. PROCEDURES: Horses received butorphanol tartrate; were treated IV with saline (0.9% NaCl) solution (SS; 12 mL; n = 6), flunixin meglumine (1.1 mg/kg; 6), or meloxicam (0.6 mg/kg; 6) 1 hour before ischemia was induced for 2 hours in a portion of jejunum; and were allowed to recover for 18 hours. Flunixin and SS treatments were repeated after 12 hours; all 3 treatments were administered immediately prior to euthanasia. Selected clinical variables, postoperative pain scores, and meloxicam pharmacokinetic data were evaluated. After euthanasia, assessment of epithelial barrier function, histologic evaluation, and western blot analysis of ischemia-injured and control jejunal mucosa samples from the 3 groups were performed. RESULTS: Meloxicam- or flunixin-treated horses had improved postoperative pain scores and clinical variables, compared with SS-treated horses. Recovery of transepithelial barrier function in ischemia-injured jejunum was inhibited by flunixin but permitted similarly by meloxicam and SS treatments. Eighteen hours after cessation of ischemia, numbers of neutrophils in ischemia-injured tissue were higher in horses treated with meloxicam or flunixin than SS. Plasma meloxicam concentrations were similar to those reported previously, but clearance was slower. Changes in expression of proteins associated with inflammatory responses to ischemic injury and with different drug treatments occurred, suggesting cyclooxygenase-independent effects. CONCLUSIONS AND CLINICAL RELEVANCE: Although further assessment is needed, these data have suggested that IV administration of meloxicam may be a useful alternative to flunixin meglumine for postoperative treatment of horses with colic. 相似文献
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Williamson KK Willard MD McKenzie EC Royer CM Payton ME Davis MS 《Journal of veterinary internal medicine / American College of Veterinary Internal Medicine》2007,21(5):924-927
BACKGROUND: Omeprazole reduces the severity of exercise-induced gastritis but not the prevalence of gastric lesions in sled dogs. The frequent feeding of sled dogs during competition likely results in decreased absorption of omeprazole and, thereby, decreased efficacy. HYPOTHESIS: Famotidine, a histamine-2 blocker with good bioavailability in the presence of food, would reduce the incidence and severity of exercise-induced gastric disease in sled dogs. ANIMALS: Sixteen fit Alaskan sled dogs (4 female, 12 male, all intact, age 2-6 years). METHODS: Dogs were randomly assigned to treatment (22 mg famotidine PO q24h) or control groups (n = 8 per group). Famotidine was administered with a meal to the treatment group once daily for 7 days before a challenge and once during exercise. Control dogs were fed an identical diet as the principal group. The 16 dog team completed a 100-mile exercise challenge in 18 hours. A gastroscopy was performed 24 hours after the challenge. The appearance of the mucosa was scored by an individual by using a scoring system. RESULTS: Treatment with famotidine significantly reduced the severity score compared with control (P = .0004). No adverse effects of treatment were reported. CONCLUSIONS AND CLINICAL RELEVANCE: Famotidine is effective in reducing the severity of exercise-induced gastric disease in racing Alaskan sled dogs, with minimal to no adverse effects, and may be recommended for prophylactic use in short distance races. 相似文献