Mycobacterial polyketide-associated proteins are acyltransferases: proof of principle with Mycobacterium tuberculosis PapA5

Mycobacterium tuberculosis (Mt) produces complex virulence-enhancing lipids with scaffolds consisting of phthiocerol and phthiodiolone dimycocerosate esters (PDIMs). Sequence analysis suggested that PapA5, a so-called polyketide-associated protein (Pap) encoded in the PDIM synthesis gene cluster, as well as PapA5 homologs found in Mt and other species, are a subfamily of acyltransferases. Studies with recombinant protein confirmed that PapA5 is an acyltransferase [corrected]. Deletion analysis in Mt demonstrated that papA5 is required for PDIM synthesis. We propose that PapA5 catalyzes diesterification of phthiocerol and phthiodiolone with mycocerosate. These studies present the functional characterization of a Pap and permit inferences regarding roles of other Paps in the synthesis of complex lipids, including the antibiotic rifamycin.     

Aumento de Óbitos Domiciliares devido a Parada Cardiorrespiratória em Tempos de Pandemia de COVID-19

BackgroundCardiovascular diseases constitute an important group of causes of death in the country. Ischemic heart diseases that are the main causes of cardiopulmonary arrest, leading to an impact on the mortality of the cardiovascular diseases in the health system.ObjectiveAssess the number of home deaths by cardiopulmonary arrest notified by the Mobile Emergency Medical Service (SAMU) in March 2018, 2019 and 2020.MethodsObservational study carried out from the analysis of cardiopulmonary arrest mortality data of citizens assisted by SAMU in Belo Horizonte, Minas Gerais, Brazil. Social and clinical characteristics and occurrence information of the patients were analyzed. The mortality rate due to cardiopulmonary arrest in relation to the total number of attendances was assessed. A significance level of 95% was considered.ResultsThere was increase of home deaths due to cardiopulmonary arrest in March 2020 compared to March 2018 (p<0.001) and March 2019 (p=0.050). Of the deaths reported in 2020, 63.8% of the patients were aged 60 years or older, 63.7% of the occurrences were performed in the afternoon and approximately 87% of the cardiopulmonary arrest notified had associated clinical comorbidities, with systemic arterial hypertension and heart failure represented by 22.87% and 13.03% of the reported cases, respectively. The majority of the evaluated sample of this study did not have any medical care follow-up (88.7%).ConclusionConsidering the increase in the number of the deaths, we suggest reflections and readjustments regarding the monitoring of chronic non-transmissible diseases during a pandemic, as well as improvements in death surveillance. (Arq Bras Cardiol. 2021; 116(2):266-271)     

A single injection of pregabalin induces short- and long-term beneficial effects on fear memory and anxiety-like behavior in rats with experimental type-1 diabetes mellitus

Metabolic Brain Disease - Anxiety Disorders and Posttraumatic Stress Disorders (PTSD) associated with type-1 diabetes mellitus (T1DM) are increasingly common comorbidities and the treatment is...     

Comparative susceptibility of anopheline mosquitoes in Rondonia, Brazil to infection by Plasmodium vivax

Seven anopheline species from Costa Marques, Rondonia, Brazil were compared with Anopheles darlingi for susceptibility to infection by Plasmodium vivax. Laboratory-reared F1 progeny of field-collected An. darlingi and the test anopheline species were fed at the same time on the same patients, all of whom had gametocytes in peripheral blood before treatment. Mosquitoes were dissected on day 8 after infection for oocysts and on days 14-16 after infection for sporozoites. The mean numbers of P. vivax oocysts and the percent of salivary gland infections for An. darlingi and An. deaneorum were similar and far exceeded those found in the other anopheline species tested. Anopheles albitarsis and An. mediopunctatus were less susceptible to infection by oocyst measurements than An. darlingi. However, for oocyst-infected An. albitarsis and An. mediopunctatus, the percent of mosquitoes with salivary gland infections and the numbers of sporozoites in the salivary glands were similar to An. darlingi. Anopheles triannulatus and An. oswaldoi were both susceptible to P. vivax infection, but the sporozoite infection rates and the numbers of sporozoites observed in the salivary glands were very low. Anopheles braziliensis and An. benarrochi both developed oocysts, but were never observed to have sporozoites in the salivary glands. These studies implicate some anopheline species as potential malaria vectors, but also show that species previously incriminated by ELISA techniques are not vectors of malaria parasites in Costa Marques, Rondonia, Brazil.