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31.
Ihara E Edwards E Borman MA Wilson DP Walsh MP MacDonald JA 《American journal of physiology. Cell physiology》2007,292(5):C1951-C1959
As a regulator of smooth muscle contractility, zipper-interacting protein kinase (ZIPK) appears to phosphorylate the regulatory myosin light chain (RLC20), directly or indirectly, at Ser19 and Thr18 in a Ca2+-independent manner. The calmodulin-binding and autoinhibitory domain of myosin light chain kinase (MLCK) shares similarity to a sequence found in ZIPK. This similarity in sequence prompted an investigation of the SM1 peptide, which is derived from the autoinhibitory region of MLCK, as a potential inhibitor of ZIPK. In vitro studies showed that SM1 is a competitive inhibitor of a constitutively active 32-kDa form of ZIPK with an apparent Ki value of 3.4 µM. Experiments confirmed that the SM1 peptide is also active against full-length ZIPK. In addition, ZIPK autophosphorylation was reduced by SM1. ZIPK activity is independent of calmodulin; however, calmodulin suppressed the in vitro inhibitory potential of SM1, likely as a result of nonspecific binding of the peptide to calmodulin. Treatment of ileal smooth muscle with exogenous ZIPK was accompanied by an increase in RLC20 diphosphorylation, distinguishing between ZIPK [and integrin-linked kinase (ILK)] and MLCK actions. Administration of SM1 suppressed steady-state muscle tension developed by the addition of exogenous ZIPK to Triton-skinned rat ileal muscle strips with or without calmodulin depletion by trifluoperazine. The decrease in contractile force was associated with decreases in both RLC20 mono- and diphosphorylation. In summary, we present the SM1 peptide as a novel inhibitor of ZIPK. We also conclude that the SM1 peptide, which has no effect on ILK, can be used to distinguish between ZIPK and ILK effects in smooth muscle tissues. inhibitory peptide; calcium sensitization 相似文献
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Celina B. Baines Justin M. J. Travis Shannon J. McCauley Greta Bocedi 《Evolution; international journal of organic evolution》2020,74(10):2238-2249
Empirical studies have documented both positive and negative density-dependent dispersal, yet most theoretical models predict positive density dependence as a mechanism to avoid competition. Several hypotheses have been proposed to explain the occurrence of negative density-dependent dispersal, but few of these have been formally modeled. Here, we developed an individual-based model of the evolution of density-dependent dispersal. This model is novel in that it considers the effects of density on dispersal directly, and indirectly through effects on individual condition. Body condition is determined mechanistically, by having juveniles compete for resources in their natal patch. We found that the evolved dispersal strategy was a steep, increasing function of both density and condition. Interestingly, although populations evolved a positive density-dependent dispersal strategy, the simulated metapopulations exhibited negative density-dependent dispersal. This occurred because of the negative relationship between density and body condition: high density sites produced low-condition individuals that lacked the resources required for dispersal. Our model, therefore, generates the novel hypothesis that observed negative density-dependent dispersal can occur when high density limits the ability of organisms to disperse. We suggest that future studies consider how phenotype is linked to the environment when investigating the evolution of dispersal. 相似文献
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DiDonato M Krishna SS Schwarzenbacher R McMullan D Jaroszewski L Miller MD Abdubek P Agarwalla S Ambing E Axelrod H Biorac T Chiu HJ Deacon AM Elsliger MA Feuerhelm J Godzik A Grittini C Grzechnik SK Hale J Hampton E Haugen J Hornsby M Klock HE Knuth MW Koesema E Kreusch A Kuhn P Lesley SA Moy K Nigoghossian E Okach L Paulsen J Quijano K Reyes R Rife C Spraggon G Stevens RC van den Bedem H Velasquez J White A Wolf G Xu Q Hodgson KO Wooley J Wilson IA 《Proteins》2006,63(1):256-260
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Genevieve G. A. Fouda Joshua D. Amos Andrew B. Wilks Justin Pollara Caroline A. Ray Anjali Chand Erika L. Kunz Brooke E. Liebl Kaylan Whitaker Angela Carville Shannon Smith Lisa Colvin David J. Pickup Herman F. Staats Glenn Overman Krissey Eutsey-Lloyd Robert Parks Haiyan Chen Celia LaBranche Susan Barnett Georgia D. Tomaras Guido Ferrari David C. Montefiori Hua-Xin Liao Norman L. Letvin Barton F. Haynes Sallie R. Permar 《Journal of virology》2013,87(12):6986-6999
We previously demonstrated that vaccination of lactating rhesus monkeys with a DNA prime/vector boost strategy induces strong T-cell responses but limited envelope (Env)-specific humoral responses in breast milk. To improve vaccine-elicited antibody responses in milk, hormone-induced lactating rhesus monkeys were vaccinated with a transmitted/founder (T/F) HIV Env immunogen in a prime-boost strategy modeled after the moderately protective RV144 HIV vaccine. Lactating rhesus monkeys were intramuscularly primed with either recombinant DNA (n = 4) or modified vaccinia virus Ankara (MVA) poxvirus vector (n = 4) expressing the T/F HIV Env C.1086 and then boosted twice intramuscularly with C.1086 gp120 and the adjuvant MF59. The vaccines induced Env-binding IgG and IgA as well as neutralizing and antibody-dependent cellular cytotoxicity (ADCC) responses in plasma and milk of most vaccinated animals. Importantly, plasma neutralization titers against clade C HIV variants MW965 (P = 0.03) and CAP45 (P = 0.04) were significantly higher in MVA-primed than in DNA-primed animals. The superior systemic prime-boost regimen was then compared to a mucosal-boost regimen, in which animals were boosted twice intranasally with C.1086 gp120 and the TLR 7/8 agonist R848 following the same systemic prime. While the systemic and mucosal vaccine regimens elicited comparable levels of Env-binding IgG antibodies, mucosal immunization induced significantly stronger Env-binding IgA responses in milk (P = 0.03). However, the mucosal regimen was not as potent at inducing functional IgG responses. This study shows that systemic MVA prime followed by either intranasal or systemic protein boosts can elicit strong humoral responses in breast milk and may be a useful strategy to interrupt postnatal HIV-1 transmission. 相似文献
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Gisela Granados-González Maricela Villagrán-SantaCruz Eric Peña-Herrera Justin L. Rheubert Kevin M. Gribbins Oswaldo Hernández-Gallegos 《Acta zoologica》2019,100(1):43-52
Gaining a deeper understanding of spermatogenic cycles within squamates has aided in our knowledge of the controls of reproduction and has bettered our understanding of reproductive phenology. One of the most studied genera of squamates, Sceloporus, is widely distributed along a latitudinal and elevational gradient in temperate, tropical, low-elevation and high-elevation habitats. Due to this wide distribution and varying habitats, Sceloporus exhibit differences in their spermatogenic activity (including both cyclical and acyclical patterns) and may be one of the most useful genera for understanding the abiotic correlations with spermatogenesis. The spermatogenic activity in Sceloporus variabilis was studied histologically (in a population that inhabits a tropical region at Los Tuxtlas, Veracruz, Mexico) and found to exhibit a unique cyclical pattern with an extended period of maximum activity (from November to July) and the absence of regression and quiescence. Furthermore, these data corroborate previous works on the spermatogenic cycles of S. variabilis despite different populations utilised. These data suggest that although abiotic factors may play a role in the timing of spermatogenesis, phylogenetic signal may be equally as important. More data concerning spermatogenic cycles in phylogenetically related taxa from differing habitats will elucidate the patterns of spermatogenic diversity. 相似文献
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