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81.
82.
Ferreira AJ Jacoby BA Araújo CA Macedo FA Silva GA Almeida AP Caliari MV Santos RA 《American journal of physiology. Heart and circulatory physiology》2007,292(2):H1113-H1119
The nonpeptide AVE-0991, which has been reported as a selective ligand for the angiotensin-(1-7) [ANG-(1-7)] receptor Mas, has actions similar to those attributed to the cardioprotective product of the renin-angiotensin system, ANG-(1-7). In this study, we evaluated the cardiac effects of AVE-0991 in normal and infarcted male Wistar rats. Myocardial infarction was induced by left coronary artery ligation. At the end of the treatment, the Langendorff technique was used to analyze cardiac function. Left ventricle serial sections were dyed with Gomori trichrome stain to quantify the infarcted area. In normal hearts, AVE-0991 produced a significant decrease in perfusion pressure and an increase in systolic tension, rate of tension rise and fall (+/-dT/dt), and heart rate. These effects were completely blocked by the perfusion of the hearts with a solution containing the selective ANG-(1-7) antagonist A-779. N(G)-nitro-l-arginine methyl ester treatment abolished the AVE-0991-induced vasodilation in isolated hearts. AVE-0991 significantly attenuated the decrease in systolic tension (sham operated, 13.00 +/- 1.02 g; infarction, 7.18 +/- 0.66 g; AVE treated, 9.23 +/- 1.05 g, n = 5), +dT/dt, -dT/dt, and heart rate induced by myocardial infarction. Infarction-induced vasoconstriction was completely prevented by AVE-0991 treatment. Furthermore, AVE-0991 significantly decreased the infarcted area (6.98 +/- 1.01 vs. 3.94 +/- 1.04 mm(2) in AVE-treated rats). These data indicate that the compound AVE-0991 produces beneficial effects in isolated perfused rat hearts involving the ANG-(1-7) receptor Mas and the release of nitric oxide. In addition, our results indicate that AVE-0991 attenuates postischemic heart failure. 相似文献
83.
Duarte FS Codeço Martins PR Romeiro GA Monteiro De Lima TC 《Bioorganic & medicinal chemistry》2007,15(4):1645-1650
This study investigated the antidepressant-like effect of 4-amine derivatives of 10,11-dihydro-5H-dibenzo-alkylamine-cycloheptane, 4-amine (3-N,N-dimethylpropylamine)-10,11-dihydro-5H-dibenzo[a,d]cycloheptane-5-one (ADDCH1) and 1,2,3,4,8,9-hexahydro-dibenzocyclohepta[4,4a,5-ef]1,4-diazepin (ADDCH2), in a validated experimental model of depression, the forced swimming test (FST) in mice. Female adult mice were sub-chronically (three doses in 24 h) or repeatedly (once a day for 10 days) treated with either of the compounds and evaluated in the FST. The sub-chronic treatment promoted a dose-dependent reduction in the immobility time in the FST with the doses of 50 mg/kg (ADDCH1) and 30 mg/kg (ADDCH2) ip being the most effective (33% and 37% of reduction, respectively). A similar profile of action was observed in the animals repeatedly treated with ADDCH1 50 mg/kg or ADDCH2 30 mg/kg ip (for 10 days) and there was no sign of motor impairment or locomotor activation as evaluated in the rota-rod and open-field tests, respectively. These findings suggest that these amine derivatives of the system dibenzocycloheptane have an antidepressant-like action which could be of clinical interest and, therefore, deserves further investigation. In addition, putative underlying mechanisms of action are discussed. 相似文献
84.
Zinc is one of the biologically most abundant and important metal elements, present in a plethora of enzymes from a broad array of species of all phyla. In this study we report a thorough analysis of the geometrical properties of Zinc coordination spheres performed on a dataset of 994 high quality protein crystal structures from the Protein Data Bank, and complemented with Quantum mechanical calculations at the DFT level of theory (B3LYP/SDD) on mononuclear model systems. The results allowed us to draw interesting conclusions on the structural characteristics of Zn centres and to evaluate the importance of such effects as the resolution of X-ray crystallographic structures, the enzyme class in which the Zn centre is included, and the identity of the ligands at the Zn coordination sphere. Altogether, the set of results obtained provides useful data for the enhancement of the atomic models normally applied to the theoretical and computational study of zinc enzymes at the quantum mechanical level (in particular enzymatic mechanisms), and for the development of molecular mechanical parameters for the treatment of zinc coordination spheres with molecular mechanics or molecular dynamics in studies with the full enzyme. 相似文献
85.
Carel P. van Schaik Redouan Bshary Gretchen Wagner Filipe Cunha 《Ethology : formerly Zeitschrift fur Tierpsychologie》2022,128(1):1-14
In species in which adults of the two sexes show long-term association, males often engage in acts of assistance (“services”) aimed at females and/or their young in various behavioural contexts that are not reciprocated. We conducted a quantitative review of the primate literature on sex differences in involvement in protection against predation. We found that males were more likely to be at the front of group progressions, especially in contexts of increased risk, were more vigilant, sometimes to the point of becoming sentinels, were more active in mobbing, and were far more likely to counter-attack felids and monkey-eating raptors than females did. Our evaluation showed that these services may be an expression of male parental care or aimed at bonded partners, but we also encountered many cases in which non-sires, unrelated to either females or immatures, provide them. We hence investigate explanations invoking group augmentation or costly signalling. Currently, available data on male anti-predation services in nonhuman primates do not allow us to distinguish among them, although costly signalling better explains data on birds and humans. We develop predictions that will allow more detailed tests of the various hypotheses for this understudied phenomenon. 相似文献
86.
Louisy Sanches dos Santos Camila Azevedo Antunes Cintia Silva dos Santos José Augusto Adler Pereira Priscila Soares Sabbadini Maria das Gra?as de Luna Vasco Azevedo Raphael Hirata Júnior Andreas Burkovski Lídia Maria Buarque de Oliveira Asad Ana Luíza Mattos-Guaraldi 《Memórias do Instituto Oswaldo Cruz》2015,110(5):662-668
Corynebacterium diphtheriae, the aetiologic agent of diphtheria,
also represents a global medical challenge because of the existence of invasive
strains as causative agents of systemic infections. Although tellurite
(TeO32-) is toxic to most microorganisms, TeO32--resistant
bacteria, including C. diphtheriae, exist in
nature. The presence of TeO32--resistance (TeR)
determinants in pathogenic bacteria might provide selective advantages in the natural
environment. In the present study, we investigated the role of the putative
TeR determinant (CDCE8392_813gene) in the virulence
attributes of diphtheria bacilli. The disruption of CDCE8392_0813 gene expression in
the LDCIC-L1 mutant increased susceptibility to TeO32- and reactive oxygen
species (hydrogen peroxide), but not to other antimicrobial agents. The LDCIC-L1
mutant also showed a decrease in both the lethality of Caenorhabditis elegans
and the survival inside of human epithelial cells compared to wild-type
strain. Conversely, the haemagglutinating activity and adherence to and formation of
biofilms on different abiotic surfaces were not regulated through the CDCE8392_0813
gene. In conclusion, the CDCE8392_813 gene contributes to the TeR and
pathogenic potential of C. diphtheriae. 相似文献
87.
The effects of deer exclusion on the development of a Mediterranean plant community affected by a wildfire
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Joaquim S. Silva Filipe X. Catry Francisco Moreira Miguel N. Bugalho 《Restoration Ecology》2015,23(6):760-767
Despite the resilience of Mediterranean ecosystems to fire, the ecological restoration of burned plant communities can be hindered by ungulate herbivores, particularly in areas with high population densities. This study compares the postfire development of a shrub community with and without deer, after a wildfire occurred in 2003 in a protected area in Central Portugal. We monitored 12 fenced and 12 unfenced plots 2, 3, 4, and 8 years after fire. Within each plot, we established a linear transect and measured the monospecific canopy projections (plant patches). Five plant community indicators (patch number, average patch length, average patch height, patch cover, and patch phytovolume per square meter) were obtained. The diameter and height of individuals of the most abundant shrub species (Cistus salvifolius, Erica scoparia, Myrtus communis, Pistacia lentiscus, Rubus ulmifolius, and Ulex jussiaei) were also measured. These measurements were used as response variables in generalized linear mixed models in order to assess the effects of time‐after‐fire and fencing, on the development of the plant community. Patch height and phytovolume had a significantly higher growth in fenced plots. At the species level, C. salvifolius, M. communis, R. ulmifolius, and U. jussiaei showed a higher growth across time both in height and in diameter, in the absence of herbivory. This work shows that deer exclusion needs to be considered when aiming at the postfire restoration of Mediterranean shrub communities. 相似文献
88.
Croft DR Crighton D Samuel MS Lourenco FC Munro J Wood J Bensaad K Vousden KH Sansom OJ Ryan KM Olson MF 《Cell research》2011,21(4):666-682
The central arbiter of cell fate in response to DNA damage is p53, which regulates the expression of genes involved in cell cycle arrest, survival and apoptosis. Although many responses initiated by DNA damage have been characterized, the role of actin cytoskeleton regulators is largely unknown. We now show that RhoC and LIM kinase 2 (LIMK2) are direct p53 target genes induced by genotoxic agents. Although RhoC and LIMK2 have well-established roles in actin cytoskeleton regulation, our results indicate that activation of LIMK2 also has a pro-survival function following DNA damage. LIMK inhibition by siRNA-mediated knockdown or selective pharmacological blockade sensitized cells to radio- or chemotherapy, such that treatments that were sub-lethal when administered singly resulted in cell death when combined with LIMK inhibition. Our findings suggest that combining LIMK inhibitors with genotoxic therapies could be more efficacious than single-agent administration, and highlight a novel connection between actin cytoskeleton regulators and DNA damage-induced cell survival mechanisms. 相似文献
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90.