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        The Mycobacterium tuberculosis relBE toxin:antitoxin genes are stress-responsive modules that regulate growth through translation inhibition

        Shaleen B. Korch,Vandana Malhotra,Heidi Contreras,Josephine E. Clark-Curtiss 한국미생물학회 2015 The journal of microbiology Vol.53 No.11

        Toxin-antitoxin (TA) genes are ubiquitous among bacteria and are associated with persistence and dormancy. Following exposure to unfavorable environmental stimuli, several species (Escherichia coli, Staphylococcus aureus, Myxococcus xanthus) employ toxin proteins such as RelE and MazF to downregulate growth or initiate cell death. Mycobacterium tuberculosis possesses three Rel TA modules (RelMtb): RelBEMtb, RelFGMtb and RelJKMtb (Rv1246c-Rv1247c, Rv2865-Rv2866, and Rv3357-Rv3358, respectively), which inhibit mycobacterial growth when the toxin gene (relE, relG, relK) is expressed independently of the antitoxin gene (relB, relF, relJ). In the present study, we examined the in vivo mechanism of the RelEMtb toxin protein, the impact of RelEMtb on M. tuberculosis physiology and the environmental conditions that regulate all three relMtb modules. RelEMtb negatively impacts growth and the structural integrity of the mycobacterial envelope, generating cells with aberrant forms that are prone to extensive aggregation. At a time coincident with growth defects, RelEMtb mediates mRNA degradation in vivo resulting in significant changes to the proteome. We establish that relMtb modules are stress responsive, as all three operons are transcriptionally activated following mycobacterial exposure to oxidative stress or nitrogen-limiting growth environments. Here we present evidence that the relMtb toxin:antitoxin family is stress-responsive and, through the degradation of mRNA, the RelEMtb toxin influences the growth, proteome and morphology of mycobacterial cells.

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        Bone microarchitecture and bone mineral density in Graves’ disease

        Hiya Boro,Rakhi Malhotra,Suraj Kubihal,Saurav Khatiwada,Vinay Dogra,Velmurugan Mannar,Ashok Kumar Ahirwar,Vandana Rastogi 대한골다공증학회 2023 Osteoporosis and Sarcopenia Vol.9 No.2

        Objectives: Graves' disease (GD) is the most common cause of thyrotoxicosis. There are many studies that have evaluated bone mineral density (BMD) in Graves’ disease. However, the strength of a bone also depends on its microarchitecture which can be assessed by various techniques. Trabecular bone score (TBS) is a new method for assessing bone microarchitecture that is non-invasive and easily performed. Methods: The present study was a cross-sectional study that involved 50 patients with active GD and 50 healthy controls. Both groups were subjected to an assessment of biochemical parameters followed by measurement of BMD and TBS on the same dual energy X-ray absorptiometry (DXA) machine. Results: The mean age of patients with active GD (N ¼ 50) was 31.9 ± 10.9 years while that of controls was 31.2 ± 4.9 years (P ¼ 0.640). The female: male ratio was the same for both groups (F ¼ 31, M ¼ 19). The mean lumbar spine BMD, femoral neck BMD, total hip BMD, and distal radius BMD were significantly reduced in GD when compared to that in controls. The mean absolute lumbar spine TBS in GD was 1.263 ± 0.101 while that in controls was 1.368 ± 0.073 (P < 0.001). On multivariate regression analysis, the factors that predicted TBS were serum thyroxine (T4) and L1-L4 BMD. Conclusions: Patients with Graves’ disease had reduced bone density at all sites and degraded microarchitecture. Long-term studies are required to understand the pattern of recovery of bone microarchitecture after the restoration of euthyroidism.

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