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1.
J Biol Chem ; 299(6): 104752, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37100288

RESUMO

Homologs of the protein Get3 have been identified in all domains yet remain to be fully characterized. In the eukaryotic cytoplasm, Get3 delivers tail-anchored (TA) integral membrane proteins, defined by a single transmembrane helix at their C terminus, to the endoplasmic reticulum. While most eukaryotes have a single Get3 gene, plants are notable for having multiple Get3 paralogs. Get3d is conserved across land plants and photosynthetic bacteria and includes a distinctive C-terminal α-crystallin domain. After tracing the evolutionary origin of Get3d, we solve the Arabidopsis thaliana Get3d crystal structure, identify its localization to the chloroplast, and provide evidence for a role in TA protein binding. The structure is identical to that of a cyanobacterial Get3 homolog, which is further refined here. Distinct features of Get3d include an incomplete active site, a "closed" conformation in the apo-state, and a hydrophobic chamber. Both homologs have ATPase activity and are capable of binding TA proteins, supporting a potential role in TA protein targeting. Get3d is first found with the development of photosynthesis and conserved across 1.2 billion years into the chloroplasts of higher plants across the evolution of photosynthesis suggesting a role in the homeostasis of photosynthetic machinery.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Fotossíntese , Adenosina Trifosfatases/metabolismo , Embriófitas , Retículo Endoplasmático/metabolismo , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo
2.
Indian J Community Med ; 45(3): 367-370, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33354021

RESUMO

BACKGROUND: A robust disaggregated understanding of the determinants of tuberculosis (TB) in each local setting is essential for effective health system and policy action to control TB. OBJECTIVES: The objective of the study was to identify population attributable risk (PAR) for TB disease based on the locally available evidences for Kerala, India. METHODS: Systematic review was done for risk factors of TB in the state. The second set of searches was done to understand the prevalence of the identified risk factors in general population in Kerala. With all available studies and reports, an expert group consensus was made to finalize state-specific prevalence of risk factors. Population attributable fractions were calculated for identified risk factors. RESULTS: PAR for TB disease in Kerala obtained was 24% for undernutrition, 15% for diabetes, 15% for tobacco use, and 1% for HIV. CONCLUSION: Kerala state's PAR for TB was comparatively lower for HIV but higher for diabetes mellitus. Similar exercises for summarizing population risk factors need to happen at all states for making plans to effectively combat TB.

3.
Indian J Tuberc ; 67(2): 202-207, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32553312

RESUMO

INTRODUCTION: Kerala, the southern Indian state piloted Lung Health Care Project (LHCP) which is a locally adopted version of WHO recommended Practical Approach to Lung health (PAL). The current study assessed the impact of the project on the prescribing practices of doctors and consumption of antibiotics and other drugs. METHODS: This study compared performance of primary health care institutions with regard to drug prescriptions and consumptions before and after the implementation of the project. Chronic respiratory disease (CRD) patients in institutions implemented the project were interviewed in the OPD at exit and their prescriptions were documented at baseline and after six months. Focus group discussions were conducted with doctors to explore the reasons behind changes in drug consumption pattern. RESULTS: In the project implementing institutions, mean number of drugs prescribed for CRDs was 3.88 (SD 1.50) and 2.73 (SD 1.18) at baseline and after six months respectively (p < 0.001). Adjusted odds ratio for prescribing an antibiotic and injection to a CRD patient during impact assessment at institutions implementing project was 0.34 (95% CI 0.15-0.75 p 0.008) and 0.39 (95% CI 0.20-0.74 p 0.004) respectively, as compared to baseline. The factors which helped in reducing antibiotic and injection use as felt by the doctors were presence of a protocol, good quality trainings, supportive supervision and monitoring, availability of alternate drugs and good participation of staff nurses especially in-patient education. CONCLUSION: Strict adherence to diagnostic and management algorithms of Lung health care project in a primary health care setting in India helped in reducing pill burden to patients and prescription of antibiotics and injections.


Assuntos
Antibacterianos/uso terapêutico , Asma/tratamento farmacológico , Broncodilatadores/administração & dosagem , Glucocorticoides/administração & dosagem , Padrões de Prática Médica , Atenção Primária à Saúde , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Teofilina/administração & dosagem , Adulto , Idoso , Broncodilatadores/uso terapêutico , Dexametasona/administração & dosagem , Dexametasona/uso terapêutico , Feminino , Grupos Focais , Glucocorticoides/uso terapêutico , Humanos , Hidrocortisona/administração & dosagem , Hidrocortisona/uso terapêutico , Índia , Masculino , Pessoa de Meia-Idade , Médicos , Projetos Piloto , Polimedicação , Guias de Prática Clínica como Assunto , Teofilina/uso terapêutico
4.
Artigo em Inglês | MEDLINE | ID: mdl-18590983

RESUMO

Severe hypoxia exposure and exhaustive exercise in goldfish both elicit a strong activation of substrate-level phosphorylation with the majority of the metabolic perturbations occurring in the white muscle. Approximately half of the muscle glycogen breakdown observed during severe hypoxia exposure was accounted for by ethanol production and loss to the environment, which limited the extent of muscle glycogen recovery when animals were returned to normoxic conditions. Ethanol production in goldfish is not solely a response to anoxia/hypoxia exposure however, as a transient increase in ethanol production was observed during the early stages of recovery from exhaustive exercise. These data suggest that ethanol production is a ubiquitous "anaerobic" end product, which accumulates whenever metabolic demands exceed mitochondrial oxidative potential. Exhaustive exercise and hypoxia exposure both caused a 7 to 8 micromol g(-1) wet mass increase in muscle [lactate] and the rates of recovery following these perturbations were similar. The rates of muscle PCr and pHi recovery after hypoxia exposure and exhaustive exercise were similar with levels returning to controls values within 0.5 h. Surprisingly, liver [glycogen] was not depleted during exposure to severe hypoxia, however, during recovery from both hypoxia and exercise dramatically different responses in liver [glycogen] were noted. During the early stages of recovery, liver [glycogen] transiently increased to high levels after exhaustive exercise, while during recovery from hypoxia there was a transient decrease in liver glycogen over the same time frame. Overall, this points to the liver playing a dramatically different role in facilitating recovery from exercise compared with hypoxia exposure.


Assuntos
Metabolismo Energético , Carpa Dourada/metabolismo , Hipóxia/metabolismo , Fígado/metabolismo , Músculo Esquelético/metabolismo , Esforço Físico , Trifosfato de Adenosina/metabolismo , Animais , Etanol/metabolismo , Glicogênio/metabolismo , Concentração de Íons de Hidrogênio , Hipóxia/fisiopatologia , Fígado/fisiopatologia , Fibras Musculares de Contração Rápida/metabolismo , Músculo Esquelético/fisiopatologia , Fosfocreatina/metabolismo , Recuperação de Função Fisiológica , Índice de Gravidade de Doença , Fatores de Tempo
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