Regulation of homocysteine metabolism by Mycobacterium tuberculosis S-adenosylhomocysteine hydrolase

Mycobacterium tuberculosis modulates expression of various metabolism-related genes to adapt in the adverse host environment. The gene coding for M. tuberculosis S-adenosylhomocysteine hydrolase (Mtb-SahH) is essential for optimal growth and the protein product is involved in intermediary metabolism. However, the relevance of SahH in mycobacterial physiology is unknown. In this study, we analyze the role of Mtb-SahH in regulating homocysteine concentration in surrogate host Mycobacterium smegmatis. Mtb-SahH catalyzes reversible hydrolysis of S-adenosylhomocysteine to homocysteine and adenosine and we demonstrate that the conserved His363 residue is critical for bi-directional catalysis. Mtb-SahH is regulated by serine/threonine phosphorylation of multiple residues by M. tuberculosis PknB. Major phosphorylation events occur at contiguous residues Thr219, Thr220 and Thr221, which make pivotal contacts with cofactor NAD+. Consequently, phosphorylation negatively modulates affinity of enzyme towards NAD+ as well as SAH-synthesis. Thr219, Thr220 and Thr221 are essential for enzyme activity, and therefore, responsible for SahH-mediated regulation of homocysteine

Customized implant full-mouth rehabilitation: A biomechanical depiction

The rationale for implant full-mouth rehabilitation is believed to present the better quality of life to the older population. This type of modalities preserves the soft and hard tissue of oral cavity. It is also helpful to check the temporomandibular joint disease. Literature exposes that implant full-mouth fixed rehabilitation is one of the taxing procedures in the field of prosthodontics. The current clinical report discusses a customized biomechanical approach for the fabrication of implant complete-mouth rehabilitation. A systematic approach in managing this patient can lead to a predictable and favorable prognosis. This article also presents the stages of prosthodontic rehabilitation from diagnosis to final treatment planning as a customized radiographical Gutta Percha template, precise implant surgery of 12 implants (ADIN, Dental Implant System, Israel) over the both the arches and provisional restorations with group function occlusion. Lastly, full-mouth restorations were fabricated as cement-retained (open hole) metal-ceramic restoration. Advocated patient is absolutely happy with customized implant full-mouth rehabilitation

Nitric Oxide Disrupts Zinc Homeostasis in Salmonella enterica Serovar Typhimurium

Nitric oxide (NO·) produced by mammalian cells exerts antimicrobial actions that result primarily from the modification of protein thiols (S-nitrosylation) and metal centers. A comprehensive approach was used to identify novel targets of NO· in Salmonella enterica serovar Typhimurium (S. Typhimurium). Newly identified targets include zinc metalloproteins required for DNA replication and repair (DnaG, PriA, and TopA), protein synthesis (AlaS and RpmE), and various metabolic activities (ClpX, GloB, MetE, PepA, and QueC). The cytotoxic actions of free zinc are mitigated by the ZntA and ZitB zinc efflux transporters, which are required for S. Typhimurium resistance to zinc overload and nitrosative stress in vitro. Zinc efflux also ameliorates NO·-dependent zinc mobilization following internalization by activated macrophages and is required for virulence in NO·-producing mice, demonstrating that host-derived NO· causes zinc stress in intracellular bacteria.Nitric oxide (NO·) is produced by macrophages in response to inflammatory stimuli and restricts the growth of intracellular bacteria. Mechanisms of NO·-dependent antimicrobial actions are incompletely understood. Here, we show that zinc metalloproteins are important targets of NO· in Salmonella, including the DNA replication proteins DnaG and PriA, which were hypothesized to be NO· targets in earlier studies. Like iron, zinc is a cofactor for several essential proteins but is toxic at elevated concentrations. This study demonstrates that NO· mobilizes free zinc in Salmonella and that specific efflux transporters ameliorate the cytotoxic effects of free zinc during infection

Unveiling the novel dual specificity protein kinases in Bacillus anthracis: identification of the first prokaryotic dual specificity tyrosine phosphorylation-regulated kinase (DYRK)-like kinase

Dual specificity protein kinases (DSPKs) are unique enzymes that can execute multiple functions in the cell, which are otherwise performed exclusively by serine/threonine and tyrosine protein kinases. In this study, we have characterized the protein kinases Bas2152 (PrkD) and Bas2037 (PrkG) from Bacillus anthracis. Transcriptional analyses of these kinases showed that they are expressed in all phases of growth. In a serendipitous discovery, both kinases were found to be DSPKs. PrkD was found to be similar to the eukaryotic dual specificity Tyr phosphorylation-regulated kinase class of dual specificity kinases, which autophosphorylates on Ser, Thr, and Tyr residues and phosphorylates Ser and Thr residues on substrates. PrkG was found to be a bona fide dual specificity protein kinase that mediates autophosphorylation and substrate phosphorylation on Ser, Thr, and Tyr residues. The sites of phosphorylation in both of the kinases were identified through mass spectrometry. Phosphorylation on Tyr residues regulates the kinase activity of PrkD and PrkG. PrpC, the only known Ser/Thr protein phosphatase, was also found to possess dual specificity. Genistein, a known Tyr kinase inhibitor, was found to inhibit the activities of PrkD and PrkG and affect the growth of B. anthracis cells, indicating a possible role of these kinases in cell growth and development. In addition, the glycolytic enzyme pyruvate kinase was found to be phosphorylated by PrkD on Ser and Thr residues but not by PrkG. Thus, this study provides the first evidence of DSPKs in B. anthracis that belong to different classes and have different modes of regulation

Ser/Thr protein kinase PrkC-mediated regulation of GroEL is critical for biofilm formation in Bacillus anthracis

International audienc

Factors Affecting the Usage of Wearable Device Technology for Healthcare among Indian Adults: A Cross-Sectional Study

Background: Wearable device technology has recently been involved in the healthcare industry substantially. India is the world’s third largest market for wearable devices and is projected to expand at a compound annual growth rate of ~26.33%. However, there is a paucity of literature analyzing the factors determining the acceptance of wearable healthcare device technology among low-middle-income countries. Methods: This cross-sectional, web-based survey aims to analyze the perceptions affecting the adoption and usage of wearable devices among the Indian population aged 16 years and above. Results: A total of 495 responses were obtained. In all, 50.3% were aged between 25–50 years and 51.3% belonged to the lower-income group. While 62.2% of the participants reported using wearable devices for managing their health, 29.3% were using them daily. technology and task fitness (TTF) showed a significant positive correlation with connectivity (r = 0.716), health care (r = 0.780), communication (r = 0.637), infotainment (r = 0.598), perceived usefulness (PU) (r = 0.792), and perceived ease of use (PEOU) (r = 0.800). Behavioral intention (BI) to use wearable devices positively correlated with PEOU (r = 0.644) and PU (r = 0.711). All factors affecting the use of wearable devices studied had higher mean scores among participants who were already using wearable devices. Male respondents had significantly higher mean scores for BI (p = 0.034) and PEOU (p = 0.009). Respondents older than 25 years of age had higher mean scores for BI (p = 0.027) and Infotainment (p = 0.032). Conclusions: This study found a significant correlation with the adoption and acceptance of wearable devices for healthcare management in the Indian context

Methylation of two-component response regulator MtrA in mycobacteria negatively modulates 1 its DNA binding and transcriptional activation. 2

International audienc

The Ser/Thr protein kinase PrkC imprints phenotypic memory in Bacillus anthracis spores by phosphorylating the glycolytic enzyme enolase

International audienc