Acetohydroxyacid synthase (AHAS) is the first enzyme in the branched-chain amino acid biosynthesis pathway in bacteria. Bioinformatics analysis revealed that the Mycobacterium tuberculosis genome contains four genes (ilvB1, ilvB2, ilvG and ilvX) coding for the large catalytic subunit of AHAS, whereas only one gene (ilvN or ilvH) coding for the smaller regulatory subunit of this enzyme was found. In order to understand the physiological role of AHAS in survival of the organism in vitro and in vivo, we inactivated the ilvB1 gene of M. tuberculosis. The mutant strain was found to be auxotrophic for all of the three branched-chain amino acids (isoleucine, leucine and valine), when grown with either C 6 or C 2 carbon sources, suggesting that the ilvB1 gene product is the major AHAS in M. tuberculosis. Depletion of these branched chain amino acids in the medium led to loss of viability of the DilvB1 strain in vitro, resulting in a 4-log reduction in colony-forming units after 10 days. Survival kinetics of the mutant strain cultured in macrophages maintained with sub-optimal concentrations of the branched-chain amino acids did not show any loss of viability, indicating either that the intracellular environment was rich in these amino acids or that the other AHAS catalytic subunits were functional under these conditions. Furthermore, the growth kinetics of the DilvB1 strain in mice indicated that although this mutant strain showed defective growth in vivo, it could persist in the infected mice for a long time, and therefore could be a potential vaccine candidate.
Plants synthesize secondary metabolites, including flavonoids, which play important role during various stresses for their survival. These metabolites are also considered as health-protective components in functional foods. Flavonols, one of the important groups of flavonoids, apart from performing several roles in plants have been recognized as potent phytoceuticals for human health. Tomato fruits are deficient in this group of flavonoids and have been an important target for enhancing the accumulation of flavonols through genetic manipulations. In the present study, AtMYB12 transcription factor of the Arabidopsis has been expressed under constitutive promoter in tomato. Transgenic tomato lines exhibited enhanced accumulation of flavonols and chlorogenic acid (CGA) in leaf and fruit accompanied with elevated expression of phenylpropanoid pathway genes involved in flavonol biosynthesis. In addition, global gene expression analysis in leaf and fruit suggested that AtMYB12 modulates number of molecular processes including aromatic amino acid biosynthesis, phytohormone signaling and stress responses. Besides this, a differential modulation of the genes in fruits and leaves is reported in this study. Taken together, results demonstrate that modulation of primary carbon metabolism and other pathways by AtMYB12 in tomato may lead to sufficient substrate supply for enhanced content of phenolics in general and flavonols in particular.
Background: The pandemic of the severe acute respiratory distress syndrome-associated Coronavirus-2 (SARS-CoV-2) has affected millions around the world. In pregnancy the dangers to the mother and fetus are still being explored. SARS-CoV2 can potentially compromise maternal and neonatal outcomes and this may be dependent on the pregnancy stage during which the infection occurs. Objective: The present study was done to find the histopathological alterations in the placenta of SARS-CoV-2 positive pregnancies with either no symptoms or mild coronavirus disease (COVID)-19 related symptoms and its association with neonatal outcomes. Study design: This was a prospective analytical study. Twenty seven asymptomatic or mildly symptomatic SARS-CoV-2 positive pregnant women with a singleton pregnancy delivered between 1 st July 2020 and 15 th September 2020, were included as cases. An equal number of SARS-CoV-2 negative singleton pregnancies matched for maternal and gestational age during the same period were included as controls. After delivery the histopathological examination of the placenta of these women was done and the findings recorded on a predesigned proforma based on the Amsterdam consensus criteria for evidence of maternal and fetal vascular malperfusion changes. Results: The baseline characteristics were comparable between the cases and controls. The following features of maternal vascular malperfusion (MVM) were significantly higher in the placentae of COVID-19 positive pregnancies: retroplacental hematomas (RPH), accelerated villous maturation (AVM), distal villous hyperplasia (DVH), atherosis, fibrinoid necrosis, mural hypertrophy of membrane arterioles (MHMA), vessel ectasia and persistence of intramural endovascular trophoblast (PIEVT). Fetal vascular malperfusion (FVM) significantly associated with the positive pregnancies were chorioangiosis, thrombosis of the fetal chorionic plate (TFCP), intramural fibrin deposition (IMFD) and vascular ectasia. Additionally, perivillous fibrin deposition was also significantly higher in the placentae of cases. The percentage of spontaneously delivered women was comparable in the two groups. The sex and weight of the newborn and the number of live births were comparable between the two groups. Conclusions: Asymptomatic or mildly symptomatic SARS-CoV-2 positive pregnant women, with otherwise uncomplicated pregnancies, show evidence of placental injury at a microscopic level. Similar findings have been demonstrated in other studies too. This placental injury apparently does not lead to poor pregnancy outcomes. The extent of this injury in symptomatic cases of COVID-19 pregnancies and its consequences on the outcomes need to be analysed.
Background. Lower segment caesarean section (LSCS) is a common mode of delivery now and surgical site infection is the second most common infectious complication in these patients. This study was planned with this background to have a comprehensive approach to SSI following LSCS. Methods. 500 consecutive patients undergoing LSCS, irrespective of indication, were studied. A questionnaire was developed to assess the risk factors associated with development of SSI. All patients were followed up from day one of surgery till discharge and then up till the postoperative day 30 after discharge. Results. SSI was identified in 121 (24.2%) out of 500 patients. In all age groups, Gram-negative bacilli were the commonest finding. The commonest isolate was Acinetobacter species (32.03%) followed by Staphylococcus aureus and coagulase negative Staphylococcus (21.09%). 23.8% of Staphylococcus aureus strains were MRSA. By multivariate logistic regression premature rupture of membrane (PROM), antibiotics given earlier than 2 hours and increased duration of stay in the hospital were found to be significant. Conclusions. A proper assessment of risk factors that predispose to SSI and their modification may help in reduction of SSI rates. Also, frequent antimicrobial audit and qualitative research could give an insight into the current antibiotic prescription practices and the factors affecting these practices.
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