A novel genetic association of IL32 with tuberculosis.

AIM: IL32 is a pleiotropic intracellular cytokine with an emergent role in tuberculosis. The different isoforms of IL32: α, ß, γ and δ have varying pro and anti-inflammatory potentials. We studied the role of genetic variants of IL32 and its isoforms in susceptibility to tuberculosis using a case-household contact association study. METHODOLOGY: Using a targeted sequencing approach, IL32 (+1kb) gene was sequenced in 64 pairs of culture positive TB cases and their culture negative household contacts. Subsequently the identified variants were validated in an independent cohort of cases and household contacts using TaqMan genotyping assay. Regulatory role of the associated variants was assessed using GTExPortal, RegulomeDB score, HaploReg and ENCODE histone ChIP-seq data. Expression of IL32 and its isoforms was evaluated by RT-PCR in PBMC from unexposed healthy controls (N = 25) with different genotype background and stimulated with TB antigens ESAT6 and CFP10. âˆ¼ 200 bp around the associated variant was cloned into pGL3 promoter vector to assess enhancer activity by dual luciferase assay in cell lines. RESULTS: Intronic variant rs9927163(G/T) was found associated with pulmonary TB, T being the risk allele (OR = 2.3(1.40-3.83, p = 0.03)), while G is the protective allele. This finding was validated in independent set of TB cases and household contacts (p = 0.0435). rs9927163 is an eQTL for the genes IL32 (p = 4.1e-10) and BICDL2 (p = 2.1e-7) in whole blood and interrupts an AP-1 binding site. ENCODE histone ChIP-seq data shows rs9927163 residing within T cell specific H3K4me3 peak. The G allele is associated with greater enhancer activity in a T cell line (2.12 fold, p = 0.0059). The TT genotype showed greater normalized expression of IL32δ, a less proinflammatory isoform compared to the GT and GG genotypes together following ESAT6 (p = 0.02288) and CFP10 (p = 0.04595) treatment. This indicates that greater expression of a potentially less protective IL32 isoform within individuals with the TT genotype might be a risk factor for developing TB.

Barriers, Facilitators of Iron and Folic Acid Supplementation, and Deworming Program among School-Going Adolescents of Deoghar, Jharkhand, India: A Mixed-Methods Study.

BACKGROUND: This study aimed to identify barriers and facilitators of iron and folic acid supplementation and deworming programs among school-going adolescents. METHODS: A mixed-method observational study was conducted among adolescents in the 8th to 10th standards and their teachers across four schools in Deoghar, Jharkhand, India, using simple random sampling. The study included a questionnaire on socio-demographics, knowledge (34 items) (α=0.894), attitudes (2 items) (α=0.711) toward iron deficiency anemia, awareness of the Weekly Iron and Folic Acid Supplementation (WIFS) program and deworming (20 items) (α=0.783), and practices related to iron folic acid supplementation (IFS) and deworming, along with qualitative components. Data were analyzed using jamovi. RESULTS: Compliance rates for IFS and deworming were 27.5% and 67.9%, respectively. The multivariable logistic regression analysis showed that sex, religion, caste, father's educational status, per capita monthly family income (PCMI), diet type, adequate knowledge, and positive attitude toward anemia influenced IFS compliance. Religion, PCMI, and prior information on the importance of deworming facilitate compliance. Implementation barriers included irregular medication supply and a lack of student awareness. CONCLUSION: Periodic evaluation, regular sensitization, and a consistent drug supply are necessary to effectively implement WIFS and deworming programs in the study area.

Anti Mtb Medicinal Plants Database (AMMPDB): A curated database of Indian anti-tubercular medicinal plants.

The utilization of medicinal plants for their therapeutic properties has long been a key component of Indian culture. Unique medicinal characteristics can be found in the phytochemicals that are extracted from these plants. Globally, tuberculosis (TB) burden and management are challenged due to the emergence of new resistant strains of Mycobacterium tuberculosis (Mtb). This highlights the importance of new drug molecules from diverse sources as well as their innovative management options. In this context, the present study formulated an Anti Mtb medicinal plant database (AMMPDB Ver. 1.1), a manually curated database of native Indian medicinal plants that reported anti-tubercular (anti-TB) activities and their potential therapeutic phytochemicals. This is the first-ever freely accessible digital repository. The current version of the database provides users, with information regarding 118 native Indian anti-tubercular medicinal plants and their 3374 phytochemicals. The database provides the following information: Taxonomical ID, botanical description, vernacular names, conservation status, geographical distribution maps, IC-50 value, phytochemical details which include - name, Compound ID, Synonyms, location in plant part, 2D, 3D structures (as per the availability), and their medicinal uses reported in the literature. The tools section of the database is equipped with sequentially catalogued and hyperlinked open-access tools utilized for computational drug designing. A case study has been incorporated under the contributors section to validate the tools section and the phytochemicals of the database. AMMPDB Ver 1.1 will be serviceable to research in computational drug designing and discovery with effectiveness and ease. Database URL: https://www.ammpdb.com/.

Cloning and comparative modeling identifies a highly stress tolerant Cu/Zn cytosolic super oxide dismutase 2 from a drought tolerant maize inbred line.

Plants have a complex system of stress response that deals with different types of stresses. Maize (Zea mays L.), one of the most important crops grown throughout the world, across a range of agro-ecological environments, employs complex mechanisms of gene regulation in response to drought stress. HKI 335 is a tropical maize inbred line showing remarkable adaptation to drought stress. Abiotic stresses, like drought, trigger the production of reactive oxygen species (ROS) due to the incomplete reduction or excitation of molecular oxygen, eventually leading to cell damage. Superoxide dismutase (SOD, EC 1.15.1.1) is a metalloenzyme that acts as the first line of defense against ROS. We cloned the Sod2 gene from HKI 335 inbred line and analyzed its protein through detailed in silico characterization. Our comparative modeling revealed that at the level of tertiary structure, the HKI 335 SOD2 protein is highly similar to Potentilla atrosanguinea SOD2, which had been previously identified as highly thermostable SOD that can tolerate autoclaving as well as sub-zero temperatures. We performed phylogenetic analysis, estimated physicochemical properties, post-translational modifications, protein-protein interactions, and domain composition of this SOD2. The phylogenetic analysis showed that orthologous sequences of SOD from different species were clustered into two clusters. Secondary structure prediction indicates that SOD2 is a soluble protein and no transmembrane domains have been found. Most of the beta sheets have RSA value greater than 2. The Ramachandran plot from PDBsum revealed that most of the residues fall in the highly favored region. It was estimated that the value of the instability index was less than 40, the value of the aliphatic index was extremely high and the GRAVY value lies between -2 and +2. We could identify only one phosphorylation site, located at position 20 with a score of 0.692. Overall, the unique stress-tolerant properties of the HKI 335 SOD2, may be one of the reasons contributing to the high drought tolerance trait exhibited by HKI 335 maize inbred line. Further research may reveal more insights into the drought adaptation mechanism in maize and the eventual deployment of the trait in maize hybrids.

National Programme for Prevention and Control of Cancer, Diabetes, Cardiovascular Diseases, and Stroke: A Scoping Review in the Context of Hypertension Prevention and Control in India.

SUMMARY: A scoping review was carried out to identify gaps in the performance of the National Programme for Prevention and Control of Cancer, Diabetes, Cardiovascular Diseases and Stroke (NPCDCS) towards the preparedness of the public health system especially at primary level in dealing with hypertension (HTN). The World Health Organization Innovative Care for Chronic Conditions (WHO ICCC) framework was adapted for the current review under three levels namely micro, meso, and macro. PubMed Central was accessed to retrieve eligible articles published since 2010. Preferred reporting items for systematic reviews and meta-analyses extension for scoping reviews checklist was followed for reporting. A final selection of 27 articles that fulfilled the eligibility criteria of the current review was drawn from a long list of 542 articles. Cross-sectional studies contributed to 51.8% of the included studies. We observed that NPCDCS had gaps across all levels of health care, especially at the primary level. At the micro-level noncommunicable diseases (NCDs), awareness among patients was suboptimal and treatment adherence was poor. At the meso-level, there was a vacancy in all cadres of workers and lack of regular training of workforce, laboratory services, and inconsistent availability of essential drugs, equipment, and related supplies to be ensured. At the macro-level, public spending on NCD care needs to be increased along with strategies to reduce out-of-pocket expenditure and improve universal health coverage. In conclusion, there is a need to improve components related to all three levels of the WHO ICCC framework to amplify the impact of HTN care through NPCDCS, particularly at the primary level.

IL32: The multifaceted and unconventional cytokine.

Interleukin 32 is a unique intracellular cytokine which affects many cellular and physiological functions like cell death and survival, inflammation and response to pathogens. With numerous transcripts, more than one biologically active isoforms, IL32 drives its effect in diverse cellular functions. A cytokine restricted to higher mammals, it is known to fine tune multiple pathways involved in metabolic processes or infection. It modulates the immune response against diverse pathogens like Leishmania, Mycobacterium and HIV. IL32 has been associated with cancers of inflammatory nature too. It also plays an important role in chronic inflammatory diseases like RA, lung and airway disease like COPD. In this review we have discussed about identification and characterization of this non classical cytokine IL32, its structure and function at gene as well as at protein level, isoforms and their diverse functions. Role of IL32 in multiple diseases and particularly mycobacterial disease has been highlighted here. We have also summarised the genetic variants present in the IL32 gene and it's promoter region. Association of these variants, with cellular phenotype, patho-physiological conditions in different disease have also been discussed here.

Residual immune activation in HIV-Infected individuals expands monocytic-myeloid derived suppressor cells.

HIV-infected individuals on combined antiretroviral therapy (ART) with virologic suppression exhibit sustained immune dysfunction. Our recent work has highlighted that monocytic myeloid derived suppressor cells (M-MDSC) are elevated in these individuals and suppress immune responses. Factors responsible for M-MDSC expansion in vivo are unknown. Here we compared circulating frequency of M-MDSC in HIV-infected persons from the US and India where HIV subtype-B or -C predominate, respectively. We further investigated soluble mediators of residual immune activation in two cohorts and determined their correlation with M-MDSC expansion. Our findings show that M-MDSC are elevated and correlate with plasma levels of IL-6 in both cohorts. Chemokines CXCL10, CCL4 and CXCL8 were also elevated in HIV-infected individuals, but did not correlate with M-MDSC. These findings support that IL-6 is important in M-MDSC expansion which is independent of HIV subtype.

Characterization of contrasting genotypes reveals general physiological and molecular mechanisms of heat-stress adaptation in maize (Zea mays L.).

In order to dissect the adaptation response of maize to heat-stress, we characterized and juxtaposed different physio-biochemical parameters for two contrasting genotypes, namely DTPYC9F119 (heat-stress tolerant) and K64R (heat-stress susceptible) under 6 days heat treatment (38/28 °C). Chlorophyll a and b content was found to be reduced under high temperature in both the genotypes, but, it was reduced more prominently in the susceptible genotype (K64R). Net photosynthetic rate was significantly reduced under high temperature in K64R but this reduction was relatively lower in case of DTPYC9F119. Stomatal conductance was increased under stress treatment in both the genotypes but the rate of increase was lower in tolerant one (DTPYC9F119). Activity of anti-oxidant enzymes (viz. catalase, peroxidase and superoxide dismutase) and their gene expression was increased in both the genotypes under heat-stress condition. Thus, the heat-stress tolerant genotype has evolved some strategies like modulation of anti-oxidant gene expression, lower transpiration rate, lower increase of internal CO2 concentration which could make sustain a basic level of photosynthesis even under high temperature stress, etc. that may contribute to its tolerance trait.