RESUMO
In Saccharomyces cerevisiae cAMP regulates different cellular processes through PKA. The specificity of the response of the cAMP-PKA pathway is highly regulated. Here we address the mechanism through which the cAMP-PKA pathway mediates its response to heat shock and thermal adaptation in yeast. PKA holoenzyme is composed of a regulatory subunit dimer (Bcy1) and two catalytic subunits (Tpk1, Tpk2, or Tpk3). PKA subunits are differentially expressed under certain growth conditions. Here we demonstrate the increased abundance and half-life of TPK1 mRNA and the assembly of this mRNA in cytoplasmic foci during heat shock at 37 °C. The resistance of the foci to cycloheximide-induced disassembly along with the polysome profiling analysis suggest that TPK1 mRNA is impaired for entry into translation. TPK1 expression was also evaluated during a recurrent heat shock and thermal adaptation. Tpk1 protein level is significantly increased during the recovery periods. The crosstalk of cAMP-PKA pathway and CWI signalling was also studied. Wsc3 sensor and some components of the CWI pathway are necessary for the TPK1 expression upon heat shock. The assembly in foci upon thermal stress depends on Wsc3. Tpk1 expression is lower in a wsc3∆ mutant than in WT strain during thermal adaptation and thus the PKA levels are also lower. An increase in Tpk1 abundance in the PKA holoenzyme in response to heat shock is presented, suggesting that a recurrent stress enhanced the fitness for the coming favourable conditions. Therefore, the regulation of TPK1 expression by thermal stress contributes to the specificity of cAMP-PKA signalling.
Assuntos
Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/genética , Meia-Vida , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas de Membrana/metabolismo , Polirribossomos/metabolismo , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Subunidades Proteicas/genética , Subunidades Proteicas/metabolismo , RNA Mensageiro/metabolismo , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/genética , TemperaturaRESUMO
The spatial and temporal distribution of the number of benthic species located in an important area under ecological stress (Puerto CALICA, Quintana Roo, Mexico) is analyzed by means of Gaussian Spatial Linear Mixed Models. Following a model-based approach we derive spatial predictions taking into account temporal variations between May 1996 and June 1999. The proposed models were evaluated in terms of their ability to detect the underlying spatial structure for further interpolation. Uncertainty in the prediction could be evaluated by using the Bayesian paradigm. The results can be used as a guide for further environmental management policies in the region.
Assuntos
Invertebrados , Modelos Teóricos , Animais , Meio Ambiente , Poluentes Ambientais/efeitos adversos , Cadeia Alimentar , Previsões , Sedimentos Geológicos , Dinâmica Populacional , Fatores de TempoRESUMO
OBJECTIVE: To evaluate the response rate of Hispanics with chronic hepatitis C to combination therapy of interferon alfa-2b plus ribavirin and to assess its adverse events. BACKGROUND: Hepatitis C virus may lead to chronic infection and multiple complications. Response to combination therapy of interferon plus ribavirin has been studied in many populations. African Americans have been found to have a lower response rate than Caucasians. However, little data exist for Hispanics. METHODS: Hispanic patients from Puerto Rico with chronic hepatitis C were eligible for the study between November 1997 and February 2000. The Institutional Review Boards of the participating institutions approved the study. Written informed consents were obtained. Combination therapy was given for 48 weeks and patients were followed for 24 weeks after treatment. Analysis of response to therapy was performed in an intention-to-treat basis. RESULTS: The most frequent adverse event was anemia (89%), associated to ribavirin. Sustained response was 23% for naive patients, 45% for relapsers, and 8% for non-responders to previous interferon monotherapy (p < 0.001). Data to analyze response was not available in 27% of patients. Hispanic patients had a low response rate to combination therapy. CONCLUSIONS: Response rates to combination therapy for Hispanic naive and previously non-responder patients are lower than in other reported populations. This may be due to a high prevalence of genotype 1 in Puerto Rico, which is associated to poor response. The higher response rate of relapsers, similar to those reported previously, was expected since these patients showed a previous response to interferon monotherapy. Ethnic factors may play a role in the response to therapy and should be further studied to determine proper treatment strategies for this population.
Assuntos
Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Hispânico ou Latino , Interferon-alfa/uso terapêutico , Ribavirina/uso terapêutico , Quimioterapia Combinada , Feminino , Humanos , Interferon alfa-2 , Masculino , Pessoa de Meia-Idade , Proteínas RecombinantesRESUMO
Treatment of chronic hepatitis C consists of inteferon plus ribavirin. The major adverse effect of ribavirin is hemolytic anemia, a complication that limits therapy. Folic acid supplementation is used to improve erythropoiesis in chronic hemolytic anemia. The aim of this study was to evaluate the effectiveness of folic acid supplementation in the prevention of ribavirin-induced anemia in patients being treated for hepatitis C. Twenty one patients enrolled in treatment protocols for hepatitis C received folic acid 1 mg daily and 22 did not. Groups were similar in age, gender, ribavirin dose and baseline hemoglobin. Folic acid supplementation had no effect in the decrease in hemoglobin or the measured parameters of hemolysis. No difference between males and females was noted for hemoglobin decrease or lowest hemoglobin levels. In our study, folic acid showed no beneficial effect in the prevention of ribavirin-induced anemia.