Genetic diversity of Mycobacterium leprae: Need to move towards genome-wide approaches.

ABSTRACT: Leprosy, an ancient disease, continues to be a public health concern as it remains endemic in several countries. After reaching the elimination target (1/10,000) as a public health problem in 2005 in India, around 1.2 lakh cases have been detected every year over the last decade indicating active transmission of leprosy bacillus (Mycobacterium leprae). Single-nucleotide polymorphisms (SNPs), genomic insertions/deletions and variable-number tandem repeats (VNTRs) have been identified as genetic markers for tracking M. leprae transmission. As the leprosy bacilli cannot be cultured in vitro, molecular testing of M. leprae genotypes is done by polymerase chain reaction-based sequencing which provides a practical alternative for the identification of strains as well as drug resistance-associated mutations. Whole-genome sequencing (WGS) of M. leprae directly from clinical samples has also proven to be an effective tool for identifying genetic variations which can further help refine the molecular epidemiological schemes based on SNPs and VNTRs. However, the WGS data of M. leprae strains from India are scarce, being responsible for a gross under-representation of the genetic diversity of M. leprae strains present in India and need to be addressed suitably. Molecular studies of leprosy can provide better insight into phylogeographic markers to monitor the transmission dynamics and emergence of antimicrobial resistance. An improved understanding of M. leprae transmission is essential to guide efficient leprosy control strategies. Therefore, this review compiles and discusses the current status of molecular epidemiology, genotyping and the potential of genome-wide analysis of M. leprae strains in the Indian context.

First report on genome wide association study in western Indian population reveals host genetic factors for COVID-19 severity and outcome.

Different human races across the globe responded in a different way to the SARS-CoV-2 infection leading to different disease severity. Therefore, it is anticipated that host genetic factors have a straight association with the COVID-19. We identified a total 6, 7, and 6 genomic loci for deceased-recovered, asymptomatic-recovered, and deceased-asymptomatic group comparison, respectively. Unfavourable alleles of the markers nearby the genes which are associated with lung and heart diseases such as Tumor necrosis factor superfamily (TNFSF4&18), showed noteworthy association with the disease severity and outcome for the COVID-19 patients in the western Indian population. The markers found with significant association with disease prognosis or recovery are of value in determining the individual's response to SARS-CoV-2 infection and can be used for the risk prediction in COVID-19. Besides, GWAS study in other populations from India may help to strengthen the outcome of this study.

Indoor air pollution and its association with poor lung function, microalbuminuria and variations in blood pressure among kitchen workers in India: a cross-sectional study.

BACKGROUND: The present study is an attempt to explore the association between kitchen indoor air pollutants and physiological profiles in kitchen workers with microalbuminuria (MAU) in north India (Lucknow) and south India (Coimbatore). METHODS: The subjects comprised 145 control subjects, 233 kitchen workers from north India and 186 kitchen workers from south India. Information related to the personal and occupational history and health of the subjects at both locations were collected using a custom-made questionnaire. Worker lung function was measured using a spirometer. Blood pressure was monitored using a sphygmomanometer. Urinary MAU was measured using a urine analyzer. Indoor air monitoring in kitchens for particulate matter (PM), total volatile organic compounds (TVOC), carbon dioxide (CO2) and carbon monoxide (CO) was conducted using indoor air quality monitors. The size and shape of PM in indoor air was assessed using a scanning electron microscope (SEM). Fourier transform infrared (FTIR) spectroscopy was used to detect organic or inorganic compounds in the air samples. RESULTS: Particulate matter concentrations (PM2.5 and PM1) were significantly higher in both north and south Indian kitchens than in non-kitchen areas. The concentrations of TVOC, CO and CO2 were higher in the kitchens of north and south India than in the control locations (non-kitchen areas). Coarse, fine and ultrafine particles and several elements were also detected in kitchens in both locations by SEM and elemental analysis. The FTIR spectra of kitchen indoor air at both locations show the presence of organic chemicals. Significant declines in systolic blood pressure and lung function were observed in the kitchen workers with MAU at both locations compared to those of the control subjects. A higher prevalence of obstruction cases with MAU was observed among the workers in the southern region than in the controls (p < 0.01). CONCLUSIONS: Kitchen workers in south India have lower lung capacities and a greater risk of obstructive and restrictive abnormalities than their north Indian counterparts. The study showed that occupational exposure to multiple kitchen indoor air pollutants (ultrafine particles, PM2.5, PM1, TVOC, CO, CO2) and FTIR-derived compounds can be associated with a decline in lung function (restrictive and obstructive patterns) in kitchen workers with microalbuminuria. Further studies in different geographical locations in India among kitchen workers on a wider scale are required to validate the present findings.

Cross-Kingdom Regulation of Putative miRNAs Derived from Happy Tree in Cancer Pathway: A Systems Biology Approach.

MicroRNAs (miRNAs) are well-known key regulators of gene expression primarily at the post-transcriptional level. Plant-derived miRNAs may pass through the gastrointestinal tract, entering into the body fluid and regulate the expression of endogenous mRNAs. Camptotheca acuminata, a highly important medicinal plant known for its anti-cancer potential was selected to investigate cross-kingdom regulatory mechanism and involvement of miRNAs derived from this plant in cancer-associated pathways through in silico systems biology approach. In this study, total 33 highly stable putative novel miRNAs were predicted from the publically available 53,294 ESTs of C. acuminata, out of which 14 miRNAs were found to be regulating 152 target genes in human. Functional enrichment, gene-disease associations and network analysis of these target genes were carried out and the results revealed their association with prominent types of cancers like breast cancer, leukemia and lung cancer. Pathways like focal adhesion, regulation of lipolysis in adipocytes and mTOR signaling pathways were found significantly associated with the target genes. The regulatory network analysis showed the association of some important hub proteins like GSK3B, NUMB, PEG3, ITGA2 and DLG2 with cancer-associated pathways. Based on the analysis results, it can be suggested that the ingestion of the C. acuminata miRNAs may have a functional impact on tumorigenesis in a cross-kingdom way and may affect the physiological condition at genetic level. Thus, the predicted miRNAs seem to hold potentially significant role in cancer pathway regulation and therefore, may be further validated using in vivo experiments for a better insight into their mechanism of epigenetic action of miRNA.

Comparative host transcriptomics as a tool to identify candidate biomarkers for immune reactions in leprosy using meta-analysis.

Background Leprosy is no longer considered an imprecation, as an effective multidrug therapy regimen is available worldwide for its cure. However, its diverse clinical manifestations sometimes involve acute inflammatory reactions. These complications result in irreversible nerve damage, neuritis and anatomical deformities that emerge before, during the treatment or after the completion of treatment. Reversal reaction (Type-I) and erythema nodosum leprosum (Type-II) are the leprosy reactions generally seen in patients with lepromatous and borderline forms of leprosy. At present, there is no accurate diagnostic test available to detect these leprosy reactions. Objectives To identify potential biomarkers indicative of Type-I and Type-II leprosy reactions that could help in their early diagnosis. Methods and Results Host-transcriptomics investigations have been utilised in this study to decipher a correlation between host-gene expression-based biomarkers and exacerbation of leprosy reactions. We present a comparative analysis of publicly available host transcriptomics datasets (from Gene Expression Omnibus) related to leprosy reactions. Individual datasets were analysed and integration of results was carried out using meta-analysis. Common differentially expressed genes (DEGs) were identified using the frequentist and Bayesian ratio association test methods. We have identified several genes - ADAMTS5, ADAMTS9, IFITM2, IFITM3, KIRREL, ANK3, CD1E, CTSF, DOCK9 and KRT73 to name a few - which can serve as potential biomarkers for Type-II reaction. Similarly, ACP5, APOC1, CCL17, S100B, SLC11A1 among others may likely serve as biomarkers for Type-I reaction. Limitations The number of datasets related to leprosy reactions found after the systematic search is less (n = 4) and may limit the accuracy of identified biomarker genes. This could be resolved by including more studies in the data analysis. Conclusion We provide a comprehensive list of gene candidates which could be prioritised further in research focusing on immune reactions in leprosy, as they are likely important in understanding its complexities and could be useful in its early diagnosis.

Tumor Mutational Burden as a Biomarker of Immunotherapy Response: An Immunogram Approach in Onco-immunology.

Immune checkpoint inhibitors have revolutionized cancer treatment by allowing T cells to reactivate. Tumor mutational burden (TMB) is a biomarker that has emerged as a viable diagnostic for locating patients who would benefit from immunotherapy in particular cancer types. Greater neo-antigens mean more opportunities for T cell identification, and TMB is clinically linked to better immune checkpoint inhibitors. Tumor foreignness is a cancer immunogram, and TMB can be used as a substitute for foreignness. The role of TMB analysis as an independent predictor of immunotherapy response in the context of immune checkpoint inhibitor medications is the subject of this mini-review.

Molecular Characterization and Genomic Surveillance of SARS-CoV-2 Lineages in Central India.

Since the first reported case of COVID-19 in December 2019, several SARS-CoV-2 variants have evolved, and some of them have shown higher transmissibility, becoming the prevalent strains. Genomic epidemiological investigations into strains from different time points, including the early stages of the pandemic, are very crucial for understanding the evolution and transmission patterns. Using whole-genome sequences, our study describes the early landscape of SARS-CoV-2 variants in central India retrospectively (including the first known occurrence of SARS-CoV-2 in Madhya Pradesh). We performed amplicon-based whole-genome sequencing of randomly selected SARS-CoV-2 isolates (n = 38) collected between 2020 and 2022 at state level VRDL, ICMR-NIRTH, Jabalpur, from 11899 RT-qPCR-positive samples. We observed the presence of five lineages, namely B.1, B.1.1, B.1.36.8, B.1.195, and B.6, in 19 genomes from the first wave cases and variants of concern (VOCs) lineages, i.e., B.1.617.2 (Delta) and BA.2.10 (Omicron) in the second wave cases. There was a shift in mutational pattern in the spike protein coding region of SRAS-CoV-2 strains from the second wave in contrast to the first wave. In the first wave of infections, we observed variations in the ORF1Ab region, and with the emergence of Delta lineages, the D614G mutation associated with an increase in infectivity became a prominent change. We have identified five immune escape variants in the S gene, P681R, P681H, L452R, Q57H, and N501Y, in the isolates collected during the second wave. Furthermore, these genomes were compared with 2160 complete genome sequences reported from central India that encompass 109 different SARS-CoV-2 lineages. Among them, VOC lineages Delta (28.93%) and Omicron (56.11%) were circulating predominantly in this region. This study provides useful insights into the genetic diversity of SARS-CoV-2 strains over the initial course of the COVID-19 pandemic in central India.

Experimental method for temperature measurement on lateral planes along a Rijke tube to assess efficacy of control method.

The thermo-acoustic instabilities developed inside the combustor causes serious structural damage and reduces the life of power producing devices. The present work involves experimental investigation to assess effect of radial micro-jets air injection on thermo-acoustic instabilities and temperature in lateral planes. A co-axial pre-mixed gas burner used as the heat source inside the Rijke tube with variable location. Two types of Rijke tubes were used for experimental study, one is of steel with 75 mm internal diameter and 750 mm in length for the measurement of wall pressure, temperature and acoustics. •In the first part of the study, acoustic instability zone for different inlet mass flow rates was identified.•In the second part of study, the entire cross-sectional of Rijke tube was divided into 193 subzones and temperatures were measured at 193 locations when instability was present.•In third part, again temperatures were measured at 193 locations with implementation of control method with complete suppression of thermo-acoustic instabilities.

Development of closed-loop active control method for suppression of thermoacoustic instability using radial air micro-jets.

Thermoacoustic instabilities present in the combustor of power producing devices are having adverse effects on the performance. To avoid thermoacoustic instabilities, design of control method is very much essential. Design and development of a closed loop control method is a real challenge for combustor. Active control methods are advantageous than passive methods. The characterization of thermoacoustic instability is essential for effective design of control method. The selection of appropriate controller and it's design depends on characterization of thermoacoustic instabilities. In this method the feedback signal acquired from microphone is used to control the flow rate of radial micro-jets. The developed method is implemented effectively to suppress thermoacoustic instabilities in a one dimensional combustor (Rijke tube). The airflow to the radial micro-jets injector was controlled using a control unit which consist of a stepper motor coupled with a needle valve, and an airflow sensor. Radial micro-jets are used to break a coupling and act as an active closed-loop method. The control method used radial jets effectively to control the thermoacoustic instability and reduces sound pressure level to background level (100 dB to 44 dB) in short span of time (10 Second).•LabVIEW Interface for Arduino (LIFA), LabVIEW, and DAQ are very useful in developed closedloop active control method.•Developed closed loop active control method is very effective for suppression of thermoacoustic instability.•Developed closed loop active control method used air in the form micro jets to control thermoacoustic instabilities.

Suppression of thermo-acoustic instabilities in horizontal Rijke tube using pulsating radial jets.

Thermo-acoustic instability has been observed in gas turbines, rocket engines, and aero-engines. Acoustic perturbations grow and change the characteristics of the flow due to instability. The present work describes the use of pulsating air jets to suppress the thermo-acoustic instabilities. In present study pulsatile micro-jets are placed downstream of the burner radially which breaks the coupling between acoustic waves and unsteady heat release. A microphone connected to LIFA (LabVIEW Interface for Arduino) was used to detect the sound pressure levels. By controlling the airflow rate of the pulsatile jets, the sound pressure levels were suppressed down to the background noise level using minimum energy and time. A closed-loop control system is developed for this purpose, which works on the feedback signal acquired from microphone. To simulate the one dimensional combustion phenomenon, an experimental setup called Rijke tube was used. The suppression was most effective for the pulsatile jets of 27-33 Hz pulsation frequency range and at a flow rate of 6.8 LPM. This control strategy effectively controlled the combustion instability of around 35-42 dB.•The closed loop control method is built on DAQ and Arduino using the LabVIEW interface for Arduino (LIFA).•Developed closed loop active control method was observed to be effective for suppression of thermo-acoustic instability.•Optimum position of the radial planes of micro-jets with respect to the burner was decided to improve the efficacy of the pulsatile jets towards suppression of thermo-acoustic instability.

Interaction of surface glycoprotein of SARS-CoV-2 variants of concern with potential drug candidates: A molecular docking study.

Background: COVID-19 has become a global threat. Since its first outbreak from Wuhan, China in December 2019, the SARS-CoV-2 virus has gone through structural changes arising due to mutations in its surface glycoprotein. These mutations have led to the emergence of different genetic variants threatening public health due to increased transmission and virulence. As new drug development is a long process, repurposing existing antiviral drugs with potential activity against SARS-CoV-2 might be a possible solution to mitigate the current situation. Methods: This study focused on utilizing molecular docking to determine the effect of potential drugs on several variants of concern (VOCs). The effect of various drugs such as baricitinib, favipiravir, lopinavir, remdesivir and dexamethasone, which might have the potential to treat SARS-CoV-2 infections as evident from previous studies, was investigated for different VOCs. Results: Remdesivir showed promising results for B.1.351 variant (binding energy: -7.3 kcal/mol) with residues Gln319 and Val503 facilitating strong binding. Favipiravir showed favorable results against B.1.1.7 (binding energy: -5.6 kcal/mol), B.1.351 (binding energy: -5.1 kcal/mol) and B.1.617.2 (binding energy: -5 kcal/mol). Molecular dynamics simulation for favipiravir/B.1.1.7 was conducted and showed significant results in agreement with our findings. Conclusions: From structural modeling and molecular docking experiments, it is evident that mutations outside the receptor binding domain of surface glycoprotein do not have a sharp impact on drug binding affinity. Thus, the potential use of these drugs should be explored further for their antiviral effect against SARS-CoV-2 VOCs.

Fabrication of a zinc oxide/alginate (ZnO/Alg) bionanocomposite for enhanced dye degradation and its optimization study.

This paper studies a new response surface methodology (RSM) based on the central composite design (CCD) modeling method to optimize the photocatalytic degradation of methylene blue (MB) and methyl orange (MO) by using a synthesized ZnO/Alg bionanocomposite under UV irradiation. ZnO with different content of sodium alginate (Alg) (10, 20, and 30% by weight) has been synthesized by a one-step sol-gel method. Zinc oxide (ZnO) nanoparticles were impregnated on the alginate polymer. Various characterization techniques were used to describe the physical and chemical properties of each catalyst such as XRD, FTIR, UV-vis, PL, FESEM, Raman, and BET. The optimal catalyst for MB and MO photocatalytic degradation process was discussed mathematically as a function of catalyst dose, irradiation time, and MB and MO concentration, which was modeled by CCD-RSM based on a statistical model (quadratic regression) and an optimization process (ANOVA analysis). The photocatalytic degradation efficiency of 98% was achieved for the optimal conditions of a dye concentration of 20 mg L-1, the catalyst dose of 0.34 g L-1, and an irradiation time of 90 min at pH 6. The measurement result (R 2 = 0.9901) showed that the considered model is very suitable, and the selected CCD-RSM successfully optimized the photodegradation conditions of MB and MO.

Genetic Diversity of Mycobacterium tuberculosis Isolates From an Amerindian Population in Chiapas, México.

This is the first report of the genetic diversity of the Mycobacterium tuberculosis complex isolates found in a Mexican-Amerindian setting. In this study, we analyzed isolates collected from the Highlands region of Chiapas, Mexico, by using spoligotyping and whole-genome sequencing analyses. Seventy-three M. tuberculosis isolates were analyzed initially by spoligotyping; no new spoligotypes were identified. Nineteen percent of the isolates were identified as SIT53 (T1) (n = 14), followed by SIT42 (14%, n = 10, LAM9) and SIT119 (11%; n = 8, X1). SIT53, SIT42, and orphan isolates (16.4%, n = 12) constituted about 50% of the isolates studied and were subjected to whole-genome sequencing (WGS) analysis. Most SIT53 (10/12) isolates belonged to the Euro-American sub-lineage 4.8. Most SIT42 isolates (4/7) as .well as most orphan isolates (5/8) belonged to the lineage 4.3.3 LAM group. By comparing the single-nucleotide polymorphism (SNP) patterns of the SIT53 isolates, we found one clone (<7 SNPs) and four clustered isolates (<15 SNPs). In isolates from the SIT42 and orphan groups, we did not find any clones or clusters. This work demonstrates the success of sub-lineage 4.8 to predominate in Mexico and confirms the dominion of sub-lineage 4.3.3 in Central and South America.

Genomic Variations in SARS-CoV-2 Genomes From Gujarat: Underlying Role of Variants in Disease Epidemiology.

Humanity has seen numerous pandemics during its course of evolution. The list includes several incidents from the past, such as measles, Ebola, severe acute respiratory syndrome (SARS), and Middle East respiratory syndrome (MERS), etc. The latest edition to this is coronavirus disease 2019 (COVID-19), caused by the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As of August 18, 2020, COVID-19 has affected over 21 million people from 180 + countries with 0.7 million deaths across the globe. Genomic technologies have enabled us to understand the genomic constitution of pathogens, their virulence, evolution, and rate of mutation, etc. To date, more than 83,000 viral genomes have been deposited in public repositories, such as GISAID and NCBI. While we are writing this, India is the third most affected country by COVID-19, with 2.7 million cases and > 53,000 deaths. Gujarat is the 11th highest affected state with a 3.48% death rate compared to the national average of 1.91%. In this study, a total of 502 SARS-CoV-2 genomes from Gujarat were sequenced and analyzed to understand its phylogenetic distribution and variants against global and national sequences. Further variants were analyzed from diseased and recovered patients from Gujarat and the world to understand its role in pathogenesis. Among the missense mutations present in the Gujarat SARS-CoV-2 genomes, C28854T (Ser194Leu) had an allele frequency of 47.62 and 7.25% in deceased patients from the Gujarat and global datasets, respectively. In contrast, the allele frequency of 35.16 and 3.20% was observed in recovered patients from the Gujarat and global datasets, respectively. It is a deleterious mutation present in the nucleocapsid (N) gene and is significantly associated with mortality in Gujarat patients with a p-value of 0.067 and in the global dataset with a p-value of 0.000924. The other deleterious variant identified in deceased patients from Gujarat (p-value of 0.355) and the world (p-value of 2.43E-06) is G25563T, which is located in Orf3a and plays a potential role in viral pathogenesis. SARS-CoV-2 genomes from Gujarat are forming distinct clusters under the GH clade of GISAID. This study will shed light on the viral haplotype in SARS-CoV-2 samples from Gujarat, India.

Analysis of Nipah Virus Codon Usage and Adaptation to Hosts.

A recent outbreak of Nipah virus (NiV) in India has caused 17 deaths in people living in districts of Kerala state. Its zoonotic nature, as well as high rate of human-to-human transmission, has led researchers worldwide to work toward understanding the different aspects of the NiV. We performed a codon usage analysis, based on publicly available nucleotide sequences of NiV and its host adaptation, along with other members of the Henipavirus genus in ten hosts. NiV genome encodes nine open reading frames; and overall, no significant bias in codon usage was observed. Aromaticity of proteins had no impact on codon usage. An analysis of preferred codons used by NiV and the tRNA pool in human cells indicated that NiV prefers codons from a suboptimal anticodon tRNA pool. We observed that codon usage by NiV is mainly constrained by compositional and selection pressures, not by mutational forces. Parameters that define NiV and host relatedness in terms of codon usage were analyzed, with a codon adaptation index (CAI), relative codon deoptimization index (RCDI), and similarity index calculations; which indicated that, of all hosts analyzed, NiV was best adapted to African green monkeys. A comparative analysis based on the relative codon deoptimization index (RCDI) for host adaptation of NiV, Hendra virus (HeV), Cedar virus (CedV), and Hendra like Mojiang virus (MojV) revealed that except for dogs and ferrets, all evaluated hosts were more susceptible to HeV than NiV.

Differential gene expression analysis of HNSCC tumors deciphered tobacco dependent and independent molecular signatures.

Head and neck cancer is the sixth most common cancer worldwide, with tobacco as the leading cause. However, it is increasing in non-tobacco users also, hence limiting our understanding of its underlying molecular mechanisms. RNA-seq analysis of cancers has proven as effective tool in understanding disease etiology. In the present study, RNA-Seq of 86 matched Tumor/Normal pairs, of tobacco smoking (TOB) and non-smokers (N-TOB) HNSCC samples analyzed, followed by validation on 375 similar datasets. Total 2194 and 2073 differentially expressed genes were identified in TOB and N-TOB tumors, respectively. GO analysis found muscle contraction as the most enriched biological process in both TOB and N-TOB tumors. Pathway analysis identified muscle contraction and salivary secretion pathways enriched in both categories, whereas calcium signaling and neuroactive ligand-receptor pathway was more enriched in TOB and N-TOB tumors respectively. Network analysis identified muscle development related genes as hub node i. e. ACTN2, MYL2 and TTN in both TOB and N-TOB tumors, whereas EGFR and MYH6, depicts specific role in TOB and N-TOB tumors. Additionally, we found enriched gene networks possibly be regulated by tumor suppressor miRNAs such as hsa-miR-29/a/b/c, hsa-miR-26b-5p etc., suggestive to be key riboswitches in regulatory cascade of HNSCC. Interestingly, three genes PKLR, CST1 and C17orf77 found to show opposite regulation in each category, hence suggested to be key genes in separating TOB from N-TOB tumors. Our investigation identified key genes involved in important pathways implicated in tobacco dependent and independent carcinogenesis hence may help in designing precise HNSCC diagnostics and therapeutics strategies.

Significant Role of Segmental Duplications and SIDD Sites in Chromosomal Translocations of Hematological Malignancies: A Multi-parametric Bioinformatic Analysis.

Recurrent non-random chromosomal translocations are hallmark characteristics of leukemogenesis, and however, molecular mechanisms underlying these rearrangements are less explored. The fundamental question is, why and how chromosomes break and reunite so precisely in the genome. Meticulous understanding of mechanism leading to chromosomal rearrangement can be achieved by characterizing breakpoints. To address this hypothesis, a novel multi-parametric computational approach for characterization of major leukemic translocations within and around breakpoint region was performed. To best of our knowledge, this bioinformatic analysis is unique in finding the presence of segmental duplications (SDs) flanking breakpoints of all major leukemic translocation. Breakpoint islands (BpIs) were analyzed for stress-induced duplex destabilization (SIDD) sites along with other complex genomic architecture and physicochemical properties. Our study distinctly emphasizes on the probable correlative role of SDs, SIDD sites and various genomic features in the occurrence of breakpoints. Further, it also highlights potential features which may be playing a crucial role in causing double-strand breaks, leading to translocation.

LeptoDB: an integrated database of genomics and proteomics resource of Leptospira.

Leptospirosis is a potentially fatal zoo-anthroponosis caused by pathogenic species of Leptospira belonging to the family of Leptospiraceae, with a worldwide distribution and effect, in terms of its burden and risk to human health. The 'LeptoDB' is a single window dedicated architecture (5 948 311 entries), modeled using heterogeneous data as a core resource for global Leptospira species. LeptoDB facilitates well-structured knowledge of genomics, proteomics and therapeutic aspects with more than 500 assemblies including 17 complete and 496 draft genomes encoding 1.7 million proteins for 23 Leptospira species with more than 250 serovars comprising pathogenic, intermediate and saprophytic strains. Also, it seeks to be a dynamic compendium for therapeutically essential components such as epitope, primers, CRISPR/Cas9 and putative drug targets. Integration of JBrowse provides elaborated locus centric description of sequence or contig. Jmol for structural visualization of protein structures, MUSCLE for interactive multiple sequence alignment annotation and analysis. The data on genomic islands will definitely provide an understanding of virulence and pathogenicity. Phylogenetics analysis integrated suggests the evolutionary division of strains. Easily accessible on a public web server, we anticipate wide use of this metadata on Leptospira for the development of potential therapeutics.Database URL: http://leptonet.org.in.

Association between PAHs biomarkers and kidney injury biomarkers among kitchen workers with microalbuminuria: A cross-sectional pilot study.

BACKGROUND: To study the association between kidney injury biomarkers and urinary OH-PAH metabolites in kitchen workers, with microalbuminuria. METHODS: A cross-sectional pilot study was conducted among 120 male kitchen workers in a mega kitchen located at Coimbatore, India. Personal and sub-clinical details of study subjects were collected using a questionnaire. Albumin, creatinine, and albumin-creatinine ratio (ACR) were measured using urine dipstick test for the determination of microalbuminuria. Urinary hydroxylated PAHs metabolites (1-NAP, 9-HF, 3-HF, 2-HF, 9-PHN, and 1-OHP) were measured using GC-MS/MS and urinary kidney biomarkers (uNGAL, uCyst-C, uKIM-1, uOPN, and uTIMP-1) were measured using Multiplex Reader. RESULTS: Concentrations of urinary PAHs metabolites (1-NAP, 3-HF, 2-HF, 9-PHN, and 1-OHP) and kidney biomarkers (uKIM-1, uTIMP-1, uCyst-C and uNGAL) were significantly higher among kitchen workers with MAU compared to non-kitchen workers with MAU. Urinary kidney biomarkers viz., uKIM-1, uTIMP-1, uCyst-C, uNGAL, and uOPN showed higher median concentration among the kitchen workers with MAU compared to kitchen workers without MAU. Significant positive correlation was observed for 9-HF with uKIM-1 and uTIMP-1 and 1-OHP with uKIM-1. ACR was also well correlated with urinary kidney biomarkers. ROC analysis showed higher sensitivity and specificity for uKIM-1, uCyst-C, and uNGAL as biomarkers for early prediction of acute kidney injury among kitchen workers. CONCLUSIONS: The PAHs exposure among kitchen workers can lead to kidney injury. This was evident from the association of OH-PAHs and kidney injury biomarkers in kitchen workers with microalbuminuria.

Characterization of chromosomal translocation breakpoint sequences in solid tumours: "an in silico analysis".

Chromosomal translocations that results in formation and activation of fusion oncogenes are observed in numerous solid malignancies since years back. Expression of fusion kinases in these cancers drives the initiation & progression that ultimately leads to tumour development and thus comes out to be clinically imperative in terms of diagnosis and treatment of cancer. Nonetheless, molecular mechanisms beneath these translocations remained unexplored consequently limiting our knowledge of carcinogenesis and hence is the current field where further research is required. The issue of prime focus is the precision with which the chromosomes breaks and reunites within genome. Characterization of Genomic sequences located at Breakpoint region may direct us towards the thorough understanding of mechanism leading to chromosomal rearrangement. A unique computational multi-parametric analysis was performed for characterization of genomic sequence within and around breakpoint region. This study turns out to be novel as it reveals the occurrence of Segmental Duplications flanking the breakpoints of all translocation. Breakpoint Islands were also investigated for the presence of other intricate genomic architecture and various physico-chemical parameters. Our study particularly highlights the probable role of SDs and specific genomic features in precise chromosomal breakage. Additionally, it pinpoints the potential features that may be significant for double-strand breaks leading to chromosomal rearrangements.