IMPACT OF OBESITY ON PULMONARY FUNCTIONS AMONG YOUNG NON-SMOKER HEALTHY FEMALE OF SHAH ALAM, MALAYSIA

Objectives: The sedentary lifestyle, physical inactivity, and unhealthy diet of Malaysian female have become important contributing factors to the rise of obesity. Studies on pulmonary function in relation to obesity are very few in Malaysia. Therefore, the study was aimed to evaluate the effect of obesity on pulmonary functions among young adult healthy female students of Shah Alam, Malaysia.Methods: A cross-sectional comparative study was conducted in a total of 100 (50 obese and 50 non-obese) adult non-smoker healthy female students aged 18–25 years. Forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV1), FEV1 as a percentage of FVC (FEV1/FVC%), maximum midexpiratory flow rate (FEF 25–75%), and peak expiratory flow rate (PEFR) were measured using a computerized spirometer. Body weight, height, waist circumference (WC), and hip circumference (HC) were measured.Results: The mean FVC (L), FEV1 (L), FEV1/FVC ratio, FEF 25–75% (L/s), and PEFR (L/s) of obese group were marginally lower than non-obese control group, but the differences were not statistically significant. WC and waist–hip ratio exhibited significant (p<0.05) inverse correlation with all pulmonary function measurements except FEV1/FVC%. However, body mass index had no significant correlation with any spirometric variables in studied obese females.Conclusion: There was no significant effect of obesity on pulmonary functions in the studied Malaysian females. However, abdominal obesity had more impact on the impairment of pulmonary functions than overall relative obesity

CarD stabilizes mycobacterial open complexes via a two-tiered kinetic mechanism

CarD is an essential and global transcriptional regulator in mycobacteria. While its biological role is unclear, CarD functions by interacting directly with RNA polymerase (RNAP) holoenzyme promoter complexes. Here, using a fluorescent reporter of open complex, we quantitate RP(o) formation in real time and show that Mycobacterium tuberculosis CarD has a dramatic effect on the energetics of RNAP bound complexes on the M. tuberculosis rrnAP3 ribosomal RNA promoter. The data reveal that Mycobacterium bovis RNAP exhibits an unstable RP(o) that is stabilized by CarD and suggest that CarD uses a two-tiered, concentration-dependent mechanism by associating with open and closed complexes with different affinities. Specifically, the kinetics of open-complex formation can be explained by a model where, at saturating concentrations of CarD, the rate of bubble collapse is slowed and the rate of opening is accelerated. The kinetics and open-complex stabilities of CarD mutants further clarify the roles played by the key residues W85, K90 and R25 previously shown to affect CarD-dependent gene regulation in vivo. In contrast to M. bovis RNAP, Escherichia coli RNAP efficiently forms RP(o) on rrnAP3, suggesting an important difference between the polymerases themselves and highlighting how transcriptional machinery can vary across bacterial genera

Effects of increasing the affinity of CarD for RNA polymerase on Mycobacterium tuberculosis growth, rRNA transcription, and virulence

CarD is an essential RNA polymerase (RNAP) interacting protein in Mycobacterium tuberculosis that stimulates formation of RNAP-promoter open complexes. CarD plays a complex role in M. tuberculosis growth and virulence that is not fully understood. Therefore, to gain further insight into the role of CarD in M. tuberculosis growth and virulence, we determined the effect of increasing the affinity of CarD for RNAP. Using site-directed mutagenesis guided by crystal structures of CarD bound to RNAP, we identified amino acid substitutions that increase the affinity of CarD for RNAP. Using these substitutions, we show that increasing the affinity of CarD for RNAP increases the stability of the CarD protein in M. tuberculosis. In addition, we show that increasing the affinity of CarD for RNAP increases the growth rate in M. tuberculosis without affecting 16S rRNA levels. We further show that increasing the affinity of CarD for RNAP reduces M. tuberculosis virulence in a mouse model of infection despite the improved growth rate in vitro. Our findings suggest that the CarD-RNAP interaction protects CarD from proteolytic degradation in M. tuberculosis, establish that growth rate and rRNA levels can be uncoupled in M. tuberculosis and demonstrate that the strength of the CarD-RNAP interaction has been finely tuned to optimize virulence. IMPORTANCE Mycobacterium tuberculosis, the causative agent of tuberculosis, remains a major global health problem. In order to develop new strategies to battle this pathogen, we must gain a better understanding of the molecular processes involved in its survival and pathogenesis. We have previously identified CarD as an essential transcriptional regulator in mycobacteria. In this study, we detail the effects of increasing the affinity of CarD for RNAP on transcriptional regulation, CarD protein stability, and virulence. These studies expand our understanding of the global transcription regulator CarD, provide insight into how CarD activity is regulated, and broaden our understanding of prokaryotic transcription

Systematic Definition of Protein Constituents along the Major Polarization Axis Reveals an Adaptive Reuse of the Polarization Machinery in Pheromone-Treated Budding Yeast

Polarizing cells extensively restructure cellular components in a spatially and temporally coupledmanner along the major axis of cellular extension. Budding yeast are a useful model of polarized growth, helping to define many molecular components of this conserved process. Besides budding, yeast cells also differentiate upon treatment with pheromone from the opposite mating type, forming a mating projection (the ‘shmoo’) by directional restructuring of the cytoskeleton, localized vesicular transport and overall reorganization of the cytosol. To characterize the proteomic localization changes ac-companying polarized growth, we developed and implemented a novel cell microarray-based imaging assay for measuring the spatial redistribution of a large fraction of the yeast proteome, and applied this assay to identify proteins localized along the mating projection following pheromone treatment. We further trained a machine learning algorithm to refine the cell imaging screen, identifying additional shmoo-localized proteins. In all, we identified 74 proteins that specifically localize to the mating projection, including previously uncharacterized proteins (Ycr043c, Ydr348c, Yer071c, Ymr295c, and Yor304c-a) and known polarization complexes such as the exocyst. Functional analysis of these proteins, coupled with quantitative analysis of individual organelle movements during shmoo formation, suggests a model in which the basic machinery for cell polarization is generally conserved between processe

Cooperative stabilization of Mycobacterium tuberculosis rrnAP3 promoter open complexes by RbpA and CarD

The essential mycobacterial transcriptional regulators RbpA and CarD act to modulate transcription by associating to the initiation complex and increasing the flux of transcript production. Each of these factors interacts directly with the promoter DNA template and with RNA polymerase (RNAP) holoenzyme. We recently reported on the energetics of CarD-mediated open complex stabilization on the Mycobacterium tuberculosis rrnAP3 ribosomal promoter using a stopped-flow fluorescence assay. Here, we apply this approach to RbpA and show that RbpA stabilizes RNAP-promoter open complexes (RP(o)) via a distinct mechanism from that of CarD. Furthermore, concentration-dependent stopped-flow experiments with both factors reveal positive linkage (cooperativity) between RbpA and CarD with regard to their ability to stabilize RP(o). The observation of positive linkage between RbpA and CarD demonstrates that the two factors can act on the same transcription initiation complex simultaneously. Lastly, with both factors present, the kinetics of open complex formation is significantly faster than in the presence of either factor alone and approaches that of E. coli RNAP on the same promoter. This work provides a quantitative framework for the molecular mechanisms of these two essential transcription factors and the critical roles they play in the biology and pathology of mycobacteria

Study protocol for the safety and efficacy of probiotic therapy on days alive and out of hospital in adult ICU patients: The multicentre, randomised, placebo-controlled Restoration Of gut microflora in Critical Illness Trial (ROCIT)

Introduction The effect of early and sustained administration of daily probiotic therapy on patients admitted to the intensive care unit (ICU) remains uncertain. Methods and analysis The Restoration Of gut microflora in Critical Illness Trial (ROCIT) study is a multicentre, randomised, placebo-controlled, parallel-group, two-sided superiority trial that will enrol 220 patients in five ICUs. Adult patients who are within 48 hours of admission to an ICU and are expected to require intensive care beyond the next calendar day will be randomised in a 1:1 ratio to receive early and sustained Lactobacillus plantarum 299v probiotic therapy in addition to usual care or placebo in addition to usual care. The primary endpoint is days alive and out of hospital to day 60. Ethics and dissemination ROCIT has been approved by the South Metropolitan Health Service Human Research Ethics Committee (ref: RGS00000004) and the St John of God Health Care Human Research Ethics Committee (ref: 1183). The trial results will be submitted for publication in a peer-reviewed journal. Trial registration number Australian and New Zealand Clinical Trials Registry (ANZCTR12617000783325); Pre-results

A convenient synthetic approach to 5-(het)arylhydrazine substituted 1,2,4‑triazines

Received: 09.09.2020. Accepted: 20.12.2020. Published:30.12.2020.A convenient synthesis of 1,2,4‑triazines bearing the moieties of (hetero) arylhydrazines at the position of C5 of the 1,2,4‑triazine core is reported

Assertion, Negotiation and Subjugation of Identity: Understanding the Tamil-Malayali Conflict in Munnar

Social identities play a critical role in the various phases of conflict. Existing literature often examines the role of social identity of groups in inducing conflict in heterogeneous societies. This article puts forward the view that the role of identity is not limited in terms of inducing conflict, but it also plays a vital role in influencing the dynamics of conflict. Based on this conceptual framework, the article outlines the conflict dynamics observable in the Kannan Devan Hills village in Kerala, where several factors, over the course of time in the last century, have led to the perception of conflict between the Tamils and the Malayalis. As a major objective, the article identifies the issues and processes of social interaction between the two groups that necessarily influence the nature of the conflict. The article identifies that the conflict between the two communities, though mostly latent, can be seen through three important aspects: assertion, negotiation and subjugation of identities. Through assertion of identity, the conflict is perceived over ethnic lines, whereas the process of negotiation and subjugation of identity constantly undermines the ethnic nature of conflict to specific grievances, thus giving insight into the dynamic nature of the conflict

Demographic predictors of wellbeing in Carers of people with psychosis: secondary analysis of trial data

Background: Carers of people with psychosis are at a greater risk of physical and mental health problems compared to the general population. Yet, not all carers will experience a decline in health. This predicament has provided the rationale for research studies exploring what factors predict poor wellbeing in carers of people with psychosis. Our study builds on previous research by testing the predictive value of demographic variables on carer wellbeing within a single regression model. Methods: To achieve this aim, we conducted secondary analysis on two trial data sets that were merged and recoded for the purposes of this study. Results: Contrary to our hypotheses, only carer gender and age predicted carer wellbeing; with lower levels of carer wellbeing being associated with being female or younger (aged under 50). However, the final regression model explained only 11% of the total variance. Conclusions: Suggestions for future research are discussed in light of the limitations inherent in secondary analysis studies. Further research is needed where sample sizes are sufficient to explore the interactive and additive impact of other predictor variables

The Entrapment of Unfree Labor: Theory and Examples from India

In this article we explore some aspects of contemporary unfree labor in rural south India. We draw on 130 case studies and (informally) extensive field research. We do so in order to make the central point that the conditions of unfreedom are variable and subject to change but that the basic vulnerabilities are significant. Being unfree in a labor relationship is a contingent effect of a set of factors. We stress the role of (a) entrapment of laborers, (b) immiseration within bondage, and (c) barriers to exit from the labor contract. In explanations, structural factors are also important. The article forms a basis for further empirical research in a variety of global settings even beyond India