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1.
PLoS Pathog ; 14(5): e1007052, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29750817

RESUMO

To survive diverse host environments, the human pathogen Streptococcus pneumoniae must prevent its self-produced, extremely high levels of peroxide from reacting with intracellular iron. However, the regulatory mechanism(s) by which the pneumococcus accomplishes this balance remains largely enigmatic, as this pathogen and other related streptococci lack all known redox-sensing transcription factors. Here we describe a two-component-derived response regulator, RitR, as the archetype for a novel family of redox sensors in a subset of streptococcal species. We show that RitR works to both repress iron transport and enable nasopharyngeal colonization through a mechanism that exploits a single cysteine (Cys128) redox switch located within its linker domain. Biochemical experiments and phylogenetics reveal that RitR has diverged from the canonical two-component virulence regulator CovR to instead dimerize and bind DNA only upon Cys128 oxidation in air-rich environments. Atomic structures show that Cys128 oxidation initiates a "helical unravelling" of the RitR linker region, suggesting a mechanism by which the DNA-binding domain is then released to interact with its cognate regulatory DNA. Expanded computational studies indicate this mechanism could be shared by many microbial species outside the streptococcus genus.


Assuntos
Proteínas Repressoras/metabolismo , Streptococcus pneumoniae/metabolismo , Proteínas de Bactérias/metabolismo , Cisteína/metabolismo , Regulação Bacteriana da Expressão Gênica/genética , Peróxido de Hidrogênio/metabolismo , Transporte de Íons/fisiologia , Ferro/metabolismo , Oxirredução , Elementos de Resposta/fisiologia , Transdução de Sinais , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/patogenicidade , Streptococcus pyogenes/genética , Streptococcus pyogenes/metabolismo , Fatores de Transcrição/metabolismo , Fatores de Transcrição/fisiologia , Virulência/genética
2.
Heart Fail Rev ; 22(6): 731-741, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28733911

RESUMO

This systematic review and meta-analysis aimed to evaluate the effects of cognitive behavioural therapy (CBT) on depression, quality of life, hospitalisations and mortality in heart failure patients. The search strategy was developed for Ovid MEDLINE and modified accordingly to search the following bibliographic databases: PubMed, EMBASE, PsycINFO, CENTRAL and CINAHL. Databases were searched from inception to 6 March 2016 for randomised controlled trials (RCTs) or observational studies that used CBT in heart failure patients with depression or depressive symptoms. Six studies were identified: 5 RCTs and 1 observational study, comprising 320 participants with predominantly NYHA classes II-III, who were mostly male, with mean age ranging from 55 to 66 years. Compared to usual care, CBT was associated with a greater improvement in depression scores both initially after CBT sessions (standardised mean difference -0.34, 95% CI -0.60 to -0.08, p = 0.01) and at 3 months follow-up (standardised mean difference -0.32, 95% CI -0.59 to -0.04, p = 0.03). Greater improvement in quality of life scores was evident for the CBT group initially after CBT sessions, but with no difference at 3 months. Hospital admissions and mortality were similar, regardless of treatment group. CBT may be more effective than usual care at improving depression scores and quality of life for heart failure patients initially following CBT and for depression at 3 months. Larger and more robust RCTs are needed to evaluate the long-term clinical effects of CBT in heart failure patients.


Assuntos
Terapia Cognitivo-Comportamental/métodos , Depressão , Insuficiência Cardíaca , Qualidade de Vida , Depressão/etiologia , Depressão/psicologia , Depressão/terapia , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/psicologia , Insuficiência Cardíaca/reabilitação , Humanos
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