Mycobacterium tuberculosis-Driven Targeted Recalibration of Macrophage Lipid Homeostasis Promotes the Foamy Phenotype

SummaryUpon infection, Mycobacterium tuberculosis (Mtb) metabolically alters the macrophage to create a niche that is ideally suited to its persistent lifestyle. Infected macrophages acquire a “foamy” phenotype characterized by the accumulation of lipid bodies (LBs), which serve as both a source of nutrients and a secure niche for the bacterium. While the functional significance of the foamy phenotype is appreciated, the biochemical pathways mediating this process are understudied. We found that Mtb induces the foamy phenotype via targeted manipulation of host cellular metabolism to divert the glycolytic pathway toward ketone body synthesis. This dysregulation enabled feedback activation of the anti-lipolytic G protein-coupled receptor GPR109A, leading to perturbations in lipid homeostasis and consequent accumulation of LBs in the macrophage. ESAT-6, a secreted Mtb virulence factor, mediates the enforcement of this feedback loop. Finally, we demonstrate that pharmacological targeting of pathways mediating this host-pathogen metabolic crosstalk provides a potential strategy for developing tuberculosis chemotherapy

Effect of trikatu pretreatment on the pharmacokinetics of pefloxacin administered orally in mountain Gaddi goats

The pharmacokinetics of orally administered pefloxacin were studied to evaluate the bio-enhancing effect of the herbal bio-enhancer, trikatu, in mountain Gaddi goats (n = 6). The findings of the study revealed a decreased plasma concentration (p > 0.05) of pefloxacin following trikatu administration during the absorption phase (10, 15, 20 min post pefloxacin administration). In contrast, the plasma concentrations of pefloxacin were significantly higher at 4, 6, 8 and 12 h (during the elimination phase) of the pefloxacin administration. The findings of the investigation revealed higher values for the area under the curve, the area under the first moment of the plasma drug concentration time curve, the mean residential time, the total duration of pharmacological action and bioavailability. Trikatu treatment, however, significantly reduced the elimination half life (t1/2β) and zero time intercept of the elimination phase. The apparent volume of distribution based on the total area under the plasma drug concentration curve [(Vd(area)] and the apparent volume of distribution based on the zero time plasma concentration intercept of the elimination phase [Vd(B)] were significantly higher in trikatu treated animals indicating a better penetration of the drug. Based on the MIC of 0.8 µg/ml of pefloxacin, a priming dose of 6.0 mg/kg and a maintenance dose of 2.21 mg/kg is required to be administered at 8 h intervals. For practical purposes in goats this would mean a priming dose of 6 mg/kg and a maintenance dose of 2 mg/kg given by the oral route, to be repeated at 8 h intervals

Effect of electric load and dual atmosphere on the properties of an alkali containing diopside-based glass sealant for solid oxide cells

© 2019 Elsevier B.V. All rights reserved.A new alkali-containing diopside based glass-ceramic sealant for solid oxide cells was synthesized, characterized and tested. The composition was designed to match the coefficient of thermal expansion (CTE) of Crofer22APU interconnect. The sealant has a glass transition temperature of 600°C, a crystallization peak temperature of 850°C and a maximum shrinkage temperature of 700°C, thus suggesting effective densification prior to crystallization. The CTE of the glass-ceramic is 11.5 10-6 K-1, a value which is compatible with the CTE for Crofer22APU stainless steel. Crofer22APU/glass-ceramic/Crofer22APU joined samples were tested in simulated real-life operating conditions at 800°C in dual atmosphere under an applied voltage, monitoring the electrical resistivity. The effect of two different applied voltages (0.7V and 1.3V) was evaluated. A voltage of 1.3V led to a rapid decrease in the electrical resistivity during the test;such a drop was due to the formation of Cr2O3 “bridges” that connected the two Crofer22APU plates separated by the sealant. There was no decrease in the resistivity when a voltage of 0.7V was applied. Instead,resistivity value remained stable at around 105 Ω cm for the 100h test duration. The degradation mechanisms, due to both the alkali content and the applied voltage, are investigated and discussed.Peer reviewe

Induction of oxidative stress and lipid peroxidation in rats chronically exposed to cypermethrin through dermal application

Present study was undertaken to study the effect of cypermethrin on oxidative stress after chronic dermal application. The insecticide was applied dermally at 50 mg/kg body weight in different groups of Wistar rats of either sex weighing 150~200 g. Significant (p < 0.05) increase in catalase activity was observed after 30 days of exposure. However, the superoxide dismutase activity declined significantly after 60 days of exposure. The activity of glutathione peroxidase and blood glutathione levels declined significantly (p < 0.05) after 30 days of cypermethrin dermal application. However, the activity of glutathione S-transferase increased significantly (p < 0.05) in all groups after 60 days of dermal exposure. Significant increase in lipid peroxidation was observed from 30 days onwards and reached a peak after 120 days of application

A cross cultural study of gender differences in omnichannel retailing contexts

This research examines gender difference in omnichannel experience in modern shopping malls, combining personal, physical and virtual encounters. It proposes a new theoretical model: the gender-based shopping mall omnichannel experience model. Data was collected using 1139 questionnaires completed by millennial shoppers in the United Kingdom and United Arab Emirates. Data was analysed using partial least squares. The results showed a shift in males shopping behaviour as they pay more attention to peer interaction on social platforms, service excellence, convenience, diversity and personalisation in shopping malls than female shoppers, while aesthetics and privacy are more important for female shoppers

On the enhancement of probability of ion induced nucleation on partially wettable, water insoluble planer substrate

138-146The nucleating behaviour of partially wettable, water insoluble planar substrate has been studied. The rate and probability of nucleation were found to be enhanced in ion induced nucleation. It is found that there exits a threshold for angle of contact above which the effect of ions is dominant. The effect of ions is more pronounced at low supersaturation rations and low temperatures for the material of large angle of contact w.r.t. water

Effect of Corona on Ground Electric Field Beneath a Thundercloud

126-130The effect of corona space charge on growth rate of ground electric field beneath a thundercloud has been studied. The maximum electric fields have been calculated at the ground surface and aloft. It has been found that the corona limits the magnitude of the electrostatic field and also influences the time behaviour of the electric field at the ground surface. The computed results are found to be in good agreement with the available experimental observations

Variation in Ground Electric Field due to Various Forms of Intracloud Lightning Discharges

104-109The calculations for instantaneous and total changes in ground electric field due to various forms of intracloud lightning discharges are presented. To place in perspective the significance of the individual form of intra cloud discharge, three possible cases, namely, propagation of positive, negative and complex streamers have been studied separately. The important aspects of thunderclouds such as spatially inhomogeneous charge distribution, redistribution of charge due to propagation of streamers, and concept of finite dimensions of streamers and thunderclouds have been taken into account. The present study points out the incapability of the electric field variation dependent hypothesis to distinguish between a negative and a complex streamer because both these streamers produce negative changes in ground electric field. Our theoretical findings suggest that a more convincing hypothesis to classify the nature of intracloud discharges should incorporate magnitudes of electric field variations along with the nature of electric field changes. Plots of total electric field change against distance of observing point show a reasonable agreement with the observed magnitude variations and electric field sign reversal distances at ground