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

Nitric Oxide: Perspectives and Emerging Studies of a Well Known Cytotoxin

The free radical nitric oxide (NO•) is known to play a dual role in human physiology and pathophysiology. At low levels, NO• can protect cells; however, at higher levels, NO• is a known cytotoxin, having been implicated in tumor angiogenesis and progression. While the majority of research devoted to understanding the role of NO• in cancer has to date been tissue-specific, we herein review underlying commonalities of NO• which may well exist among tumors arising from a variety of different sites. We also discuss the role of NO• in human physiology and pathophysiology, including the very important relationship between NO• and the glutathione-transferases, a class of protective enzymes involved in cellular protection. The emerging role of NO• in three main areas of epigenetics—DNA methylation, microRNAs, and histone modifications—is then discussed. Finally, we describe the recent development of a model cell line system in which human tumor cell lines were adapted to high NO• (HNO) levels. We anticipate that these HNO cell lines will serve as a useful tool in the ongoing efforts to better understand the role of NO• in cancer

Development and Commercialization of CMS Pigeonpea Hybrids

The role of heterosis in enhancing productivity in food crops is well known. Legume breeders have not been able, however, to take advantage of this genetic phenomenon for a long time, due to biological restrictions, such as the requirement of high seeding rate and the inability to produce large quantities of F1 hybrid seed. Recently, in pigeonpea (Cajanus cajan (L.) Millsp.), a breakthrough has been realized with the development and marketing of the world’s first legume hybrid, ICPH 2671. The key for this achievement was breeding and using a stable cytoplasmic nuclear male sterility (CMS) system obtained from the cross between C. cajanifolius, a wild relative of pigeonpea, and the cultivated type. The inherent partial natural out‐crossing of pigeonpea was knitted with this CMS system to facilitate economically‐viable large‐scale hybrid seed production. These developments provided opportunities to overcome the historic stagnant low yield (0.6–0.8 t ha–1) through heterosis breeding. Among hundreds of hybrid combinations tested, a cross between ICPA 2043 and ICPL 87119 (=ICPR 2671), designated as ICPH 2671, was the most promising, with >40% yield superiority (reaching yields above 3 t ha–1) over the prevalent cultivar ‘Maruti’, in multi‐location, multi‐year, on‐station trials, as well as on‐farm evaluations. The outstanding performance of ICPH 2671 led to its release in 2010 as the first medium duration commercial pigeonpea hybrid in India. Subsequently, two additional pigeonpea hybrids, ICPH 3762 and ICPH 2740 were also released for commercial cultivation in India in 2014 and 2015, respectively. According to recent estimates, in 2015 the CMS‐based pigeonpea hybrids were grown over 150,000 hectares in central and southern India. In this review, we summarize the research efforts that led to the milestone of developing the first commercial hybrid in food legumes

Tanshinone-I for the treatment of uterine fibroids: Molecular docking, simulation, and density functional theory investigations

Uterine fibroids (UF), most prevalent gynecological disorder, require surgery when symptomatic. It is estimated that between 25 and 35 percent of women wait until the symptoms have worsened like extended heavy menstrual bleeding and severe pelvic pain. These UF may be reduced in size through various methods such as medical or surgical intervention. Progesterone (prog) is a crucial hormone that restores the endometrium and controls uterine function. In the current study, 28 plant-based molecules are identified from previous literature and docked onto the prog receptors with 1E3K and 2OVH. Tanshinone-I has shown the best docking score against both proteins. The synthetic prog inhibitor Norethindrone Acetate is used as a standard to evaluate the docking outcomes. The best compound, tanshinone-I, was analyzed using molecular modeling and DFT. The RMSD for the 1E3K protein–ligand complex ranged from 0.10 to 0.42 Å, with an average of 0.21 Å and a standard deviation (SD) of 0.06, while the RMSD for the 2OVH protein–ligand complex ranged from 0.08 to 0.42 Å, with an average of 0.20 Å and a SD of 0.06 showing stable interaction. In principal component analysis, the observed eigen values of HPR-Tanshinone-I fluctuate between −1.11 to 1.48 and −1.07 to 1.25 for PC1 and PC2, respectively (1E3K), and the prog-tanshinone-I complex shows eigen values of −38.88 to −31.32 and −31.32 to 35.87 for PC1 and PC2, respectively (2OVH), which shows Tanshinone-I forms a stable protein–ligand complex with 1E3K in comparison to 2OVH. The Free Energy Landscape (FEL) analysis shows the Gibbs free energy in the range of 0 to 8 kJ/mol for Tanshinone-I with 1E3K and 0 to 14 kJ/mol for Tanshinone-I with the 2OVH complex. The DFT calculation reveals ΔE value of 2.8070 eV shows tanshinone-I as a stable compound. 1E3K modulates the prog pathway, it may have either an agonistic or antagonistic effect on hPRs. Tanshinone-I can cause ROS, apoptosis, autophagy (p62 accumulation), up-regulation of inositol requiring protein-1, enhancer-binding protein homologous protein, p-c-Jun N-terminal kinase (p-JNK), and suppression of MMPs. Bcl-2 expression can change LC3I to LC3II and cause apoptosis through Beclin-1 expression

Chemical shift magnetic resonance imaging is helpful in detecting hepatic steatosis but not fibrosis in patients with nonalcoholic fatty liver disease (NAFLD)

Background &amp; Aim: Imaging modalities have a role in the diagnosis of patients with nonalcoholic fatty liver disease. Aim of the present study was to evaluate the role of chemical shift magnetic resonance imaging in assessing hepatic steatosis and fibrosis in patients with nonalcoholic fatty liver disease.Methods: Chemical shift magnetic resonance imaging was done in 10 biopsy proven patients (7 females, mean age 41 ± 9.2 years) with nonalcoholic fatty liver disease. Objective measurements of signal intensity (SI) were done and a ratio was calculated (SI out-of-phase liver/ SI out-of-phase kidney)/ (SI in-phase liver/ SI in-phase kidney). A lower ratio indicated a higher signal drop and hence higher fat content. The ratio was correlated with hepatic steatosis on histology ( 33%). Patients were classified as having histological NASH or no NASH and MRI was assessed in diagnosing hepatic fi-brosis as seen on liver histology.Results: Six patients had > 33% hepatic steatosis on histology. Five patients (50%) had evidence of histological NASH. MRI was not helpful in differentiating patients with and without his-tological NASH. One patient amongst NASH patients did not have fibrosis, one had stage 1, 2 had stage 2 and one had stage 4 fibrosis. SI ratio ranged between 0.350.69 in 6 patients with steatosis > 33% and was in the range of 0.69-1.20 in four patients with steatosis < 33% on histology. Fibrotic changes seen in 4 patients on biopsy were not detected on MRI.Conclusion: Chemical shift MRI provides objective data on fat infiltration in patients with NAFLD without giving information about hepatic fibrosis

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

International audienc

Emergence and re-emergence of glanders in India: a description of outbreaks from 2006 to 2011

Glanders, a bacterial disease of equines caused by Burkholderia mallei, is a fatal infectious disease of equines and has zoonotic significance. The disease has been eradicated from many countries by statutory testing, elimination of infected animals and import restrictions. However, it is still endemic in parts of Africa, Asia, the Middle East and Central and South America. In India, major glanders outbreaks were reported from different parts of the country between 1976 and 1982. Later, sporadic cases of the disease were reported in 1988, 1990 and 1998. The country remained free of glanders for about eight years until the recent outbreaks occurred in eight States from 2006 to 2007. Recurrent episodes have occurred in Himachal Pradesh and Uttar Pradesh, whereas fresh outbreaks occurred in Chhattisgarh from 2009 to 2010. A total of 164 equines were declared positive; a majority of the positive cases (n = 77) were from Uttar Pradesh, followed by Maharashtra (n = 23), Uttarakhand (n = 21) and Andhra Pradesh (n = 16). Under the provision of Prevention and Control of Infectious and Contagious Disease in Animals Act, 2009, all the infected animals were euthanised and bio-security measures were implemented to curb the further spread of the disease