HUMHOT: a database of human meiotic recombination hot spots

Meiotic recombination occurs preferentially at certain regions in the genome referred to as hot spots. The number of hot spots known in humans has increased manifold in recent years. The identification of these hot spots in humans is of great interest to population and medical geneticists since they influence the structure of Linkage Disequilibrium and Haplotype blocks in human populations, whose patterns have applications in mapping disease genes. HUMHOT is a web-based database of Human Meiotic Recombination Hot Spots. The database comprises DNA sequences corresponding to the hot spot regions from the literature that have been mapped to a high resolution (<4 kb) in humans. It also provides flanking sequence information for the hot spot region along with references describing the hot spot. The database can be queried based on hot spot identity, chromosome position or by homology to user-defined sequences. It is also updated with new hot spot sequences as they are discovered and provides hyperlinks to commonly used tools for estimating recombination rates, performing genetic analysis and new advances in our understanding of meiotic hot spots. Public access to the HUMHOT database is available at

Flavour Enhanced Food Recommendation

We propose a mechanism to use the features of flavour to enhance the quality of food recommendations. An empirical method to determine the flavour of food is incorporated into a recommendation engine based on major gustatory nerves. Such a system has advantages of suggesting food items that the user is more likely to enjoy based upon matching with their flavour profile through use of the taste biological domain knowledge. This preliminary intends to spark more robust mechanisms by which flavour of food is taken into consideration as a major feature set into food recommendation systems. Our long term vision is to integrate this with health factors to recommend healthy and tasty food to users to enhance quality of life.Comment: In Proceedings of 5th International Workshop on Multimedia Assisted Dietary Management, Nice, France, October 21, 2019, MADiMa 2019, 6 page

EVALUATION OF HEPATOPROTECTIVE ACTIVITY OF STEM EXTRACTS OF CUSCUTA REFLEXA (ROXB) IN RATS

Objective: Cuscuta Reflexa (Convolvulaceae) is a plant with a variety of ethnic medicinal uses along with antioxidant activity. Hence it was planned to evaluate the hepatoprotective activity with alcoholic extracts of stem of Cuscuta reflexa (AESCR) and aqueous extracts of stem of Cuscuta reflexa (AQESCR).Methods: Hepatoprotective activity of both the extracts was studied against paracetamol induced hepatotoxicity in rats. Functional (thiopentone induced sleeping time), physical (wet liver weight and volume), biochemical parameters Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Serum alkaline phosphatase (ALP), Serum direct bilirubin (BILD), Serum total bilirubin (BILT), Serum albumin (ALB), Serum total proteins (PRO), Serum cholesterol (CHO), and histopathological changes of livers were assessed in control/toxicant/standard/and extract treated animals with paracetamol induced hepatotoxic models in rats.Results: In LD50 studies for AESCR and AQESCR up to the maximum dose level of 2000 mg/kg dose no mortality was observed in any of the animals, indicating the practically nontoxic. When compared to toxicant control groups both the extracts have significantly reduced the paracetamol induced elevated levels of serum ALT, AST, ALP, BILT, BILD, CHO, and elevated the levels of ALB and PRO. The histopathological changes (steatosis), necrosis etc. Were partly or fully prevented in animals treated with the two extracts.Conclusion: AESCR and AQESCR showed a significant hepatoprotective effect against paracetamol induced hepatic damage. The medium and high doses of AESCR and AQESCR (200 and 400 mg/kg) treated groups showd better hepatoprotective activity when compared to standard drug silymarin (25 mg/kg).Â

OPTIC NEUROPATHY INDUCED BY LOW DOSE OF ETHAMBUTOL: A RARE PRESENTATION

Ethambutol is a bacteriostatic antimicrobial agent used in the treatment of tuberculosis. Optic neuropathy is a potentially severe side effect of ethambutol, which is dose related. Ethambutol-induced optic neuropathy (EON) incidence is 15%, 5% &amp; 1% when taken at 50 mg/kg/day , 25 mg/kg/day &amp; 15 mg/kg/day respectively for 3 months. We report a case of bilateral EON in 20-year-old female after 1 month of exposure to 15 mg/kg/day of ethambutol for tubercular meningitis. Ophthalmologic examination revealed bilateral ill sustained pupillary reactions and optic disc pallor. Deranged color vision test and scotomas on Goldmann perimetry in both eyes, aided in diagnosis.Keywords: Low dose ethambutol, Optic neuropathy, Tuberculosis

The C-Terminal Domain of the MutL Homolog from Neisseria gonorrhoeae Forms an Inverted Homodimer

The mismatch repair (MMR) pathway serves to maintain the integrity of the genome by removing mispaired bases from the newly synthesized strand. In E. coli, MutS, MutL and MutH coordinate to discriminate the daughter strand through a mechanism involving lack of methylation on the new strand. This facilitates the creation of a nick by MutH in the daughter strand to initiate mismatch repair. Many bacteria and eukaryotes, including humans, do not possess a homolog of MutH. Although the exact strategy for strand discrimination in these organisms is yet to be ascertained, the required nicking endonuclease activity is resident in the C-terminal domain of MutL. This activity is dependent on the integrity of a conserved metal binding motif. Unlike their eukaryotic counterparts, MutL in bacteria like Neisseria exist in the form of a homodimer. Even though this homodimer would possess two active sites, it still acts a nicking endonuclease. Here, we present the crystal structure of the C-terminal domain (CTD) of the MutL homolog of Neisseria gonorrhoeae (NgoL) determined to a resolution of 2.4 Å. The structure shows that the metal binding motif exists in a helical configuration and that four of the six conserved motifs in the MutL family, including the metal binding site, localize together to form a composite active site. NgoL-CTD exists in the form of an elongated inverted homodimer stabilized by a hydrophobic interface rich in leucines. The inverted arrangement places the two composite active sites in each subunit on opposite lateral sides of the homodimer. Such an arrangement raises the possibility that one of the active sites is occluded due to interaction of NgoL with other protein factors involved in MMR. The presentation of only one active site to substrate DNA will ensure that nicking of only one strand occurs to prevent inadvertent and deleterious double stranded cleavage

Prevalence and factors associated with tuberculosis infection in India

Background: The risk of tuberculosis (TB) disease is higher in individuals with TB infection. In a TB endemic country like India, it is essential to understand the current burden of TB infection at the population level. The objective of the present analysis is to estimate the prevalence of TB infection in India and to explore the factors associated with TB infection. Methods: Individuals aged > 15 years in the recently completed National TB prevalence survey in India who were tested for TB infection by QuantiFERON-TB Gold Plus (QFT-Plus) assay were considered for this sub- analysis. TB infection was defined as positive by QFT-Plus (value > 0.35 IU/ml). The estimates for prevalence, prevalence ratio (PR) and adjusted risk ratio (aRR) estimates with 95% confidence intervals (CIs) were calculated. Results: Of the 16864 individuals analysed, the prevalence of TB infection was 22.6% (95% CI:19.4 −25.8). Factors more likely to be associated with TB infection include age > 30 years (aRR:1.49;95% CI:1.29–1.73), being male (aRR:1.26; 95%CI: 1.18–1.34), residing in urban location (aRR:1.58; 95%CI: 1.03–2.43) and past history of TB (aRR:1.49; 95%CI: 1.26–1.76). Conclusion: About one fourth (22.6%) of the individuals were infected with TB in India. Individuals aged > 30 years, males, residing in urban location, and those with past history of TB were more likely to have TB infection. Targeted interventions for prevention of TB and close monitoring are essential to reduce the burden of TB in India

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure &lt; 100 mmHg (n = 1127), estimated glomerular filtration rate &lt; 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation