Search

Migration and admixture history of populations have always been curious and an interesting theme. The West Coast of India harbours a rich diversity, bestowing various ethno-linguistic groups, with many of them having well-documented history of migrations. The Roman Catholic is one such distinct group, whose origin was much debated. While some historians and anthropologists relating them to ancient group of Gaud Saraswat Brahmins, others relating them for being members of the Jews Lost Tribes in the first Century migration to India. Historical records suggests that this community was later forcibly converted to Christianity by the Portuguese in Goa during the Sixteenth Century. Till date, no genetic study was done on this group to infer their origin and genetic affinity. Hence, we analysed 110 Roman Catholics from three different locations of West Coast of India including Goa, Kumta and Mangalore using both uniparental and autosomal markers to understand their genetic history. We found that the Roman Catholics have close affinity with the Indo-European linguistic groups, particularly Brahmins. Additionally, we detected genetic signal of Jews in the linkage disequilibrium-based admixture analysis, which was absent in other Indo-European populations, who are inhabited in the same geographical regions. Haplotype-based analysis suggests that the Roman Catholics consist of South Asian-specific ancestry and showed high drift. Ancestry-specific historical population size estimation points to a possible bottleneck around the time of Goan inquisition (fifteenth century). Analysis of the Roman Catholics data along with ancient DNA data of Neolithic and bronze age revealed that the Roman Catholics fits well in a basic model of ancient ancestral composition, typical of most of the Indo-European caste groups of India. Mitochondrial DNA (mtDNA) analysis suggests that most of the Roman Catholics have aboriginal Indian maternal genetic ancestry; while the Y chromosomal DNA analysis indicates high frequency of R1a lineage, which is predominant in groups with higher ancestral North Indian (ANI) component. Therefore, we conclude that the Roman Catholics of Goa, Kumta and Mangalore regions are the remnants of very early lineages of Brahmin community of India, having Indo-Europeans genetic affinity along with cryptic Jewish admixture, which needs to be explored further.

The worldwide pandemic situation of COVID-19 generates a situation in which healthcare resources such as diagnostic kits, drugs and basic healthcare infrastructure were on shortage throughout the period, along with negative impact on socio-economic system. Standardized public healthcare models were missing in pandemic situation, covering from hospitalized patient care to local resident’s healthcare managements in terms of monitoring, assess to diagnosis and medicines. This exploratory and intervention-based study with the objective of proposing COVID-19 Care Management Model representing comprehensive care of society including patients (COVID-19 and other diseases) and healthy subjects under integrated framework of healthier management model. Shifting policy towards technology-oriented models with well-aligned infrastructure can achieve better outcomes in COVID-19 prevention and care. The planned development of technical healthcare models for prognosis and improved treatment outcomes that take into account not only genomics, proteomics, nanotechnology, materials science perspectives but also the possible contribution of advanced digital technologies is best strategies for early diagnosis and infections control. In view of current pandemic, a Healthier Healthcare Management Model is proposed here as a source of standardized care having technology support, medical consultation, along with public health model of sanitization, distancing and contact less behaviours practices. Effective healthcare managements have been the main driver of healthier society where, positive action at identified research, technology and management segment more specifically public health, patient health, technology selection and political influence has great potential to enhanced the global response to COVID-19. The implementation of such practices will deliver effective diagnosis and control mechanism and make healthier society.

Sesbania cannabina (Retz.) Pers. (Dhaincha) is a member of family Fabaceae spread over several countries in tropical and subtropical regions of the world. Sesbania aculeata, Sesbania drummondii, Sesbania grandiflora, Sesbania rostrata, Sesbania sesban, and Sesbania speciosa are other members of this family. The agricultural, nutritional and pharmaceutical applications of Sesbania species are known to farmers, villagers, and the tribes since ages and are well studied by researchers. However, the significance of Sesbania as an industrial crop has not been recognized till now. The objective of this study was extraction and characterization of Sesbania cannabina seed oil (SCSO) for potential engineering applications. The seed oil was extracted with hexane in a Soxhlet extractor. Yield was only 2.32% w/w due to long storage at high temperature in seed house. Sesbania cannabina seed oil methyl ester (SCSOME) was prepared via esterification and transesterification for analysis of fatty acid composition of extracted oil. SCSO has high iodine value (118 g I2/100 g) and high saponification value (185.79 mg KOH/g) making the oil suitable for use as candle stocks or in soap making. However, these applications were ruled out on account of being insignificant for oil available in limited quantity. The oil has high viscosity index (174.19), high onset (382°C) and offset (450°C) decomposition temperatures, endothermic nature, and shear rate thickening behaviour. These properties make SCSO a good candidate for application as specialty lubricant required under severe operating conditions of high temperature and high shear rate or as insulating and cooling transformer oil.

The pandemic respiratory disease COVID-19 has spread over the globe within a small span of time. Generally, there are two important points are being highlighted and considered towards the successful diagnosis and treatment process. The first point includes the reduction of the rate of infections and the next one is the decrease of the death rate. The major threat to public health globally progresses due to the absence of effective medication and widely accepted immunization for the COVID-19. Whereas, understanding of host susceptibility, clinical features, adaptation of COVID-19 to new environments, asymptomatic infection is difficult and challenging. Therefore, a rapid and an exact determination of pathogenic viruses play an important role in deciding treatments and preventing pandemic to save the people's lives. It is urgent to fix a standardized diagnostic approach for detecting the COVID-19. Here, this systematic review describes all the current approaches using for screening and diagnosing the COVID-19 infectious patient. The renaissance in pathogen due to host adaptability and new region, facing creates several obstacles in diagnosis, drug, and vaccine development process. The study shows that adaptation of accurate and affordable diagnostic tools based on candidate biomarkers using sensor and digital medicine technology can deliver effective diagnosis services at the mass level. Better prospects of public health management rely on diagnosis with high specificity and cost-effective manner along with multidisciplinary research, specific policy, and technology adaptation. The proposed healthcare model with defined road map represents effective prognosis system.

Migration and admixture history of populations have always been curious and an interesting theme. The West Coast of India harbours a rich diversity, bestowing various ethno-linguistic groups, with many of them having well-documented history of migrations. The Roman Catholic is one such distinct group, whose origin was much debated. While some historians and anthropologists relating them to ancient group of Gaud Saraswat Brahmins, others relating them for being members of the Jews Lost Tribes in the first Century migration to India. Historical records suggests that this community was later forcibly converted to Christianity by the Portuguese in Goa during the Sixteenth Century. Till date, no genetic study was done on this group to infer their origin and genetic affinity. Hence, we analysed 110 Roman Catholics from three different locations of West Coast of India including Goa, Kumta and Mangalore using both uniparental and autosomal markers to understand their genetic history. We found that the Roman Catholics have close affinity with the Indo-European linguistic groups, particularly Brahmins. Additionally, we detected genetic signal of Jews in the linkage disequilibrium-based admixture analysis, which was absent in other Indo-European populations, who are inhabited in the same geographical regions. Haplotype-based analysis suggests that the Roman Catholics consist of South Asian-specific ancestry and showed high drift. Ancestry-specific historical population size estimation points to a possible bottleneck around the time of Goan inquisition (fifteenth century). Analysis of the Roman Catholics data along with ancient DNA data of Neolithic and bronze age revealed that the Roman Catholics fits well in a basic model of ancient ancestral composition, typical of most of the Indo-European caste groups of India. Mitochondrial DNA (mtDNA) analysis suggests that most of the Roman Catholics have aboriginal Indian maternal genetic ancestry; while the Y chromosomal DNA analysis indicates high frequency of R1a lineage, which is predominant in groups with higher ancestral North Indian (ANI) component. Therefore, we conclude that the Roman Catholics of Goa, Kumta and Mangalore regions are the remnants of very early lineages of Brahmin community of India, having Indo-Europeans genetic affinity along with cryptic Jewish admixture, which needs to be explored further.

Background Genetic diathesis of suicide is supported by family and twin studies. Few candidate gene pathways are known, but does not explain fully the complexity of suicide genetic risk. Recent investigations opting for Genome-Wide Association Studies (GWAS) resulted in finding additional targets, but replication remained a challenge. In this respect small isolated population approach in several complex disease phenotypes is found encouraging. The present study is an attempt to re-test some of the reported significant SNPs for suicide among a small historical high- risk isolated population from Northeast India. Methods Two hundred ten cases (inclusive of depressed, suicide attempter and depressed + suicide attempter) and 249 controls were considered in the present study which were evaluated for the psychiatric parameters. Sixteen reported significant SNPs for suicide behaviour were re-tested using association approach under various genetic models. Networking by GeneMANIA tool was used for function prediction of the associated genes. Results Seven SNPs (of 6 genes) remained significant in different genetic models. On networking genes with significant SNPs IL7, RHEB, CTNN3, KCNIP4, ARFGEF3 are found in interaction with already known candidate gene pathways while SNP rs1109089 (RHEB) gained further support from earlier expression studies. NUGGC gene is in complete isolation. Conclusions Small population approach in replicating significant SNPs is useful in complex phenotypes like suicide. This study explored the region-specific demographics of India by identifying vulnerable population for suicide via genetic association analysis in bringing into academic and administrative forum, the importance of suicide as a disease and its biological basis.

Additional file 1: Table S1. Primer sequences used for genotyping along with melting temperature and amplicon base pairs. Table S2. List of suggestive significant SNPs chosen from a review of 10 year study for re-testing in the present study. Table S3. Distribution of genotypes, allele frequencies and HW test of significance among cases and controls of the 16 selected SNPs in the present study. Table S4. Network pathway percentage contribution of different default parameters of the figure S1. Figure S1. Pathway network analysis of 6 significant genes of the present study along with candidate genes of different known pathways of suicide behaviour. Default settings used for creation of network are as described in Table S4.

Context: Diaphyseal fractures of the radius and ulna are common in the pediatric population. The standard management for pediatric forearm fractures remains conservative management with closed reduction and immobilization with above-elbow plaster cast. Although the fracture unites readily, malunion is very common. Stiffness of joints and compartment syndrome are other complications of conservative management with plaster cast. The introduction of titanium elastic nailing system (TENS) has changed the treatment scenario of fracture of both-bone forearm. Aims: The aim of this study is to evaluate the functional and cosmetic outcome of the management of fracture both-bone forearm by closed reduction and internal fixation with titanium elastic nail system. Subjects and Methods: A total of 40 patients aged 5–15 years with fracture of both radius and ulna were managed by internal fixation with titanium elastic nail. Closed reduction under image intensifier control was achieved in most of the patients. Prospective follow-up was done for 6 months. Results: Results were analyzed in reference to union, symptoms, and range of motion of adjacent joints using Price et al. criteria for outcome evaluation. In our study, 87.5% of patients showed excellent, 10% showed good, and 2.5% showed fair outcome. Conclusion: Better functional and cosmetic outcome with minimal complications is achieved with internal fixation with titanium elastic nail system. TENS may be considered as an alternative to conservative treatment.

COVID-19 is considered as a major public health problem caused by the SARS CoV-2. This Viral infection is known to induce worldwide pandemic in short period of time. Emerging evidence suggested that the transmission control and drug therapy may influence the preventive measures extensively as the host surrounding environment and pathogenic mechanism may contribute to the pandemic condition earlier in COVID-19 disease. Although, several animals identified as reservoir to date, however human-to-human transmission is well documented. Human beings are sustaining the virus in the communities and act as an amplifier of the virus. Human activities i.e., living with the patient, touching patient waste etc. in the surrounding of active patients or asymptomatic persons cause significant risk factors for transmission. On the other hand, drug target and mechanism to destroy the virus or virus inhibition depends on diversified approaches of drugs and different target for virus life cycle. This article describes the sustainable chemical preventive models understanding, requirements, technology adaptation and the implementation strategies in these pandemic-like situations. As the outbreak progresses, healthcare models focused on transmission control through disinfections and sanitization based on risk calculations. Identification of the most suitable target of drugs and regional control model of transmission are of high priority. In the early stages of an outbreak, availability of epidemiological information is important to encourage preventive measures efforts by public health authorities and provide robust evidence to guide interventions. Here, we have discussed the level of adaptations in technology that research professionals display toward their public health preventive models. We should compile a representative data set of adaptations that humans can consider for transmission control and adopt for viruses and their hosts. Overall, there are many aspects of the chemical science and technology in virus preventive measures. Herein, the most recent advances in this context are discussed, and the possible reasons behind the sustainable preventive model are presented. This kind of sustainable preventive model having adaptation and implementation with green chemistry system will reduce the shedding of the virus into the community by eco-friendly methods, and thus the risk of transmission and infection progression can be mitigated., Graphical abstract Image 1

A new compact Ultra-Wideband (UWB) antenna is designed for wearable applications using jeans fabric as the substrate. The proposed antenna has an impedance bandwidth from 3.1 to 11.1 GHz. The antenna footprint is of size 18mm x 26 mm, and the thickness of the substrate is 0.8mm. It is based on a simple patch antenna configuration where the radiator consists of a simple rectangular structure and an ellipse added on top. Circular and elliptical notches are removed from the radiator, and rectangular notches are removed from the feed line for bandwidth enhancement. A partial ground plane of size 18mm x 9mm with a square notch is present on the other side of the antenna. Two such antennas are placed side by side as unit cells, one horizontal and the other vertical, to obtain a 2-port diversity set. The unit cells are placed at a distance such that minimal mutual coupling is present between the cells, and the size is also not compromised. The final diversity set so obtained is of size 44mm x 26 mm. The simulation results for reflection coefficients, SAR, and radiation pattern for both unit cell and diversity port are presented. Diversity parameters like ECC and diversity gain are also simulated for diversity antenna. The results obtained by testing the fabricated prototype are found to be matching reasonably with the simulated results. The antenna is also subjected to bending analysis.

The host genetic factors play important role in determining the outcome of visceral leishmaniasis (VL). Macrophage migration inhibitory factor (MIF) is an important host cytokine, which is a key regulator of innate immune system. Genetic variants in MIF gene have been found to be associated with several inflammatory and infectious diseases. Role of MIF is well documented in leishmaniasis diseases, including Indian visceral leishmaniasis, where elevated level of serum MIF has been associated with VL phenotypes. However, there was no genetic study to correlate MIF variants in VL, therefore, we aimed to study the possible association of three reported MIF gene variants −794 CATT, −173G > C and non-coding RNA gene LOC284889 in Indian VL phenotype. Methods: Study subjects comprised of 214 VL patients along with ethnically and demographically matched 220 controls from VL endemic regions of Bihar state in India. Results: We found no significant difference between cases and controls in allelic, genotypic and haplotype frequency of the markers analysed [-794 CATT repeats (χ2 = 0.86; p = 0.35; OR = 0.85; 95% CI = 0.61?1.19); −173 G > C polymorphism (χ2 = 1.11; p = 0.29; OR = 0.83; 95% CI = 0.59?1.16); and LOC284889 (χ2 = 0.78; p = 0.37; OR = 0.86; 95% CI = 0.61?1.20)]. Conclusion: Since we did not find any significant differences between case and control groups, we conclude that sequencing of complete MIF gene and extensive study on innate and adaptive immunity genes may help in identifying genetic variations that are associated with VL susceptibility/resistance among Indians. Fil: Mishra, Anshuman. Vinoba Bhave Research Institute; India. Centre For Cellular And Molecular Biology India; India Fil: Sundaravadivel, Pandarisamy. Centre For Cellular And Molecular Biology India; India Fil: Tripathi, Sunil Kumar. Centre For Cellular And Molecular Biology India; India Fil: Jha, Rajan Kumar. Centre For Cellular And Molecular Biology India; India Fil: Badrukhiya, Jaydeep. Centre For Cellular And Molecular Biology India; India Fil: Basak, Nipa. Academy Of Scientific And Innovative Research; India. Centre For Cellular And Molecular Biology India; India Fil: Anerao, Isha. Centre For Cellular And Molecular Biology India; India Fil: Sharma, A. Surja. Centre For Cellular And Molecular Biology India; India Fil: Ajayi, Ebenezer Idowu O. Centre For Cellular And Molecular Biology India; India. Osun State University; Nigeria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina Fil: Mishra, Abhishek. Institute Of Basic Sciences Agra; India Fil: Pandey, Sonika. Banaras Hindu University; India Fil: Kumar, Umesh. Centre For Cellular And Molecular Biology India; India Fil: Singh, Sakshi. Centre For Cellular And Molecular Biology India; India Fil: Nizamuddin, Sheikh. Centre For Cellular And Molecular Biology India; India Fil: Tupperwar, Nitin C.. Centre For Cellular And Molecular Biology India; India Fil: Jha, Aditya Nath. Sickle Cell Institute Chhattisgarh; India. Centre For Cellular And Molecular Biology India; India Fil: Thangaraj, Kumarasamy. Centre For Cellular And Molecular Biology India; India

Olive flounder (Paralichthys olivaceus) is one of economically valuable fish species in the East Asia. In comparison with its economic importance, available genomic information of the olive flounder is very limited. The mass mortality caused by variety of pathogens (virus, bacteria and parasites) is main problem in aquaculture industry, including in olive flounder culture. In this study, we carried out transcriptome analysis using the olive flounder gill tissues after infection of three types of pathogens (Virus; Viral hemorrhagic septicemia virus, Bacteria; Streptococcus parauberis, and Parasite; Miamiensis avidus), respectively. As a result, we identified total 12,415 differentially expressed genes (DEG) from viral infection, 1,754 from bacterial infection, and 795 from parasite infection, respectively. To investigate the effects of pathogenic infection on immune response, we analyzed Gene ontology (GO) enrichment analysis with DEGs and sorted immune-related GO terms per three pathogen groups. Especially, we verified various GO terms, and genes in these terms showed down-regulated expression pattern. In addition, we identified 67 common genes (10 up-regulated and 57 down-regulated) present in three pathogen infection groups. Our goals are to provide plenty of genomic knowledge about olive flounder transcripts for further research and report genes, which were changed in their expression after specific pathogen infection.

In our country many college and school run by government agencies. There are two categories of employment, one is regular and the other one is contractual. The idea of this paper is conceived looking at violation of human rights in these places. Regular employees enjoy all the facilities such as library, job security air condition chambers in contrast contractual employees deprived from all these facilities. Our intention to find the parameter for why the above said happened by the use of rough set theory ..

Urogenital schistosomiasis caused by Schistosoma haematobium induces a Th2 immune response, including expression of Interleukin-6. IL-6 confers protection from experimental Schistosoma-induced pulmonary hypertension and modulates production of mannose-binding lectin (MBL) and other lectins. We studied IL-6 levels in schistosomiasis and its effect on lectins production. Elevated IL-6 levels occurred in cases, compared to controls. IL-6 correlated with the lectins MBL, ficolin-2 and Collectin Kidney-1 (CL-K1) in cases, but correlated inversely in controls. The study shows that IL-6 levels are elevated in individuals infected with urogenital schistosomiasis. IL-6 was also found to be correlated with the production of lectins in S. haematobium infection. A similar correlation between IL-6 and MBL was observed during visceral leishmaniasis.

Skin color is a highly visible and variable trait across human populations. It is not yet clear how evolutionary forces interact to generate phenotypic diversity. Here we sought to unravel through an integrative framework the role played by three factors – demography and migration, sexual selection, and natural selection – in driving skin color diversity in India. Methods: Skin reflectance data were collected from 10 diverse socio-cultural populations along the latitudinal expanse of India, including both sexes. We first looked at how skin color varies within and between these populations. Secondly, we compared patterns of sexual dimorphism in skin color. Thirdly, we studied the influence of ultraviolet radiation on skin color throughout India. Finally, we attempted to disentangle the interactions between these factors in the context of available genetic data. Results: We found that the relative importance of these forces varied between populations. Social factors and population structure have played a stronger role than natural selection in shaping skin color diversity across India. Phenotypic overprinting resulted from additional genetic mutations overriding the skin lightening effect of variants such as the SLC24A5 rs1426654-A allele in some populations, in the context of the variable influence of sexual selection. Furthermore, specific genotypes are not associated reliably with specific skin color phenotypes. This result has relevance for DNA forensics and ancient DNA research. Conclusion: India is a crucible of macro- and micro-evolutionary forces, and the complex interactions of physical and social forces are visible in the patterns of skin color seen today in the country.

Body mass index (BMI) is a non-invasive measurement of obesity. It is commonly used for assessing adiposity and obesity-related risk prediction. Genetic differences between ethnic groups are important factors, which contribute to the variation in phenotypic effects. India inhabited by the first out-of-Africa human population and the contemporary Indian populations are admixture of two ancestral populations; ancestral north Indians (ANI) and ancestral south Indians (ASI). Although ANI are related to Europeans, ASI are not related to any group outside Indian-subcontinent. Hence, we expect novel genetic loci associated with BMI. In association analysis, we found eight genic SNPs in extreme of distribution (P⩽3.75 × 10(-5)), of which WWOX has already been reported to be associated with obesity-related traits hence excluded from further study. Interestingly, we observed rs1526538, an intronic SNP of THSD7A; a novel gene significantly associated with obesity (P=2.88 × 10(-5), 8.922 × 10(-6) and 2.504 × 10(-9) in discovery, replication and combined stages, respectively). THSD7A is neural N-glycoprotein, which promotes angiogenesis and it is well known that angiogenesis modulates obesity, adipose metabolism and insulin sensitivity, hence our result find a correlation. This information can be used for drug target, early diagnosis of obesity and treatment.

This paper considers the optimal decentralized control of linear systems with stochastically switched cost and system matrices depending on local parameters. Two types of dynamic switched problems are considered, with partially nested and one-step delayed sharing information structures. For the former case, parameters and measurements follow a partially nested structure with the parameters possibly being correlated across all stages. For the latter case, parameters are assumed to be Markov processes, with their values along with measurements available instantaneously to local controllers, but with a one time step delay to others. The solution to both these problems rely on the optimal solution to a static (one-stage) stochastic-parameter problem with local type dependent Gaussian measurements, and for this purpose the static quadratic team problem is examined in some generality. Using an operator theoretic framework, it is shown that the sequential update scheme always converges to the team optimal strategy for general static quadratic team setups. This, when applied to the static stochastic-parameter problem, yields the team optimal strategy. The corresponding strategy is affine in the measurements with the parameter dependent coefficients obtained by solving a set of linear equations. These equations are immediately solvable when the total number of parameter values is finite. However, for the case of infinite parameter values, the update scheme also provides a mechanism to determine an approximation to the team optimal strategy.

Several bacterial etiological agents of streptococcal disease have been associated with fish mortality and serious global economic loss. Bacterial identification based on biochemical, molecular, and phenotypic methods has been routinely used, along with assessment of morphological analyses. Among these, the molecular method of 16S rRNA sequencing is reliable, but presently, advanced genomics are preferred over other traditional identification methodologies. This review highlights the geographical variation in strains, their relatedness, as well as the complexity of diagnosis, pathogenesis, and various control methods of streptococcal infections. Several limitations, from diagnosis to control, have been reported, which make prevention and containment of streptococcal disease difficult. In this review, we discuss the challenges in diagnosis, pathogenesis, and control methods and suggest appropriate molecular (comparative genomics), cellular, and environmental solutions from among the best available possibilities.

MicroRNAs (miRNAs) are small non-coding RNAs (ncRNAs) that mainly bind to the seed sequences located within the 3′ untranslated region (3′ UTR) of target genes. They perform an important biological function as regulators of gene expression. Different genes can be regulated by the same miRNA, whilst different miRNAs can be regulated by the same genes. Here, the evolutionary conservation and expression pattern of miR-10a-3p in olive flounder and rock bream was examined. Binding sites (AAAUUC) to seed region of the 3′ UTR of target genes were highly conserved in various species. The expression pattern of miR-10a-3p was ubiquitous in the examined tissues, whilst its expression level was decreased in gill tissues infected by viral hemorrhagic septicemia virus (VHSV) compared to the normal control. In the case of rock bream, the spleen, kidney, and liver tissues showed dominant expression levels of miR-10a-3p. Only the liver tissues in the rock bream samples infected by the iridovirus indicated a dominant miR-10a-3p expression. The gene ontology (GO) analysis of predicted target genes for miR-10a-3p revealed that multiple genes are related to binding activity, catalytic activity, cell components as well as cellular and metabolic process. Overall the results imply that the miR-10a-3p could be used as a biomarker to detect VHSV infection in olive flounder and iridovirus infection in rock bream. In addition, the data provides fundamental information for further study of the complex interaction between miR-10a-3p and gene expression.

Cytochrome-P450-2C9 (CYP2C9) metabolizes wide range of drugs and highly express in human liver. Various mutations of CYP2C9 (R144C, I359L etc.), associated with drug-response, are highly diverse. We aimed to investigate the genetic diversity of CYP2C9 in Indian-subcontinent, using 1278 subjects from 36 populations. High frequency of CYP2C9*3 (0-0.179) was observed, comparative to other populations, including Europeans. Subjects having CYP2C9*3/*3 requires lower dose of warfarin, comparative to CYP2C9*1/*3 or CYP2C9*1/*1. Since, Indians are practicing marriage among their caste system, we predicted and observed high frequency (0-0.05) of CYP2C9*3/*3. Out of 21 populations, living outside of Indian subcontinent, only Toscani and Southern Han-Chinese have 0.009 and 0.01 CYP2C9*3/*3, respectively, lower than Indians,. We found a non-synonymous mutation (L362V), observed only in Indian-subcontinent, and have 0-0.056 allelic, 0-0.037 L/V and 00.037 V/V genotype frequency. We observed unfavorable interatomic interactions between hydroxylation sites of warfarin and reactive oxyferryl heme in mutant, comparative to wild-type CYP2C9, in molecular dynamic simulations; and predict lower kinetic activity.

To identify susceptibility loci for visceral leishmaniasis, we undertook genome-wide association studies in two populations: 989 cases and 1,089 controls from India and 357 cases in 308 Brazilian families (1,970 individuals). The HLA-DRB1-HLA-DQA1 locus was the only region to show strong evidence of association in both populations. Replication at this region was undertaken in a second Indian population comprising 941 cases and 990 controls, and combined analysis across the three cohorts for rs9271858 at this locus showed P(combined) = 2.76 × 10(-17) and odds ratio (OR) = 1.41, 95% confidence interval (CI) = 1.30-1.52. A conditional analysis provided evidence for multiple associations within the HLA-DRB1-HLA-DQA1 region, and a model in which risk differed between three groups of haplotypes better explained the signal and was significant in the Indian discovery and replication cohorts. In conclusion, the HLA-DRB1-HLA-DQA1 HLA class II region contributes to visceral leishmaniasis susceptibility in India and Brazil, suggesting shared genetic risk factors for visceral leishmaniasis that cross the epidemiological divides of geography and parasite species.

Ninety percent of the 500,000 annual new cases of visceral leishmaniasis occur in India/Bangladesh/Nepal, Sudan and Brazil. Importantly, 80-90% of human infections are sub-clinical or asymptomatic, usually associated with strong cell-mediated immunity. Understanding the environmental and genetic risk factors that determine why two people with the same exposure to infection differ in susceptibility could provide important leads for improved therapies. Recent research using candidate gene association analysis and genome-wide linkage studies (GWLS) in collections of families from Sudan, Brazil and India have identified a number of genes/regions related both to environmental risk factors (e.g. iron), as well as genes that determine type 1 versus type 2 cellular immune responses. However, until now all of the allelic association studies carried out have been underpowered to find genes of small effect sizes (odds ratios or OR

Background Visceral leishmaniasis (VL) is a multifactorial disease, where the host genetics play a significant role in determining the disease outcome. The immunological role of anti-inflammatory cytokine, Interleukin 10 (IL10), has been well-documented in parasite infections and considered as a key regulatory cytokine for VL. Although VL patients in India display high level of IL10 in blood serum, no genetic study has been conducted to assess the VL susceptibility / resistance. Therefore, the aim of this study is to investigate the role of IL10 variations in Indian VL; and to estimate the distribution of disease associated allele in diverse Indian populations. Methodology All the exons and exon-intron boundaries of IL10 were sequenced in 184 VL patients along with 172 ethnically matched controls from VL endemic region of India. Result and Discussion Our analysis revealed four variations; rs1518111 (2195 A>G, intron), rs1554286 (2607 C>T, intron), rs3024496 (4976 T>C, 3’ UTR) and rs3024498 (5311 A>G, 3’ UTR). Of these, a variant g.5311A is significantly associated with VL (χ2=18.87; p =0.00001). In silico approaches have shown that a putative micro RNA binding site (miR-4321) is lost in rs3024498 mRNA. Further, analysis of the above four variations in 1138 individuals from 34 ethnic populations, representing different social and linguistic groups who are inhabited in different geographical regions of India, showed variable frequency. Interestingly, we have found, majority of the tribal populations have low frequency of VL (‘A’ of rs3024498); and high frequency of leprosy (‘T’ of rs1554286), and Behcet’s (‘A’ of rs1518111) associated alleles, whereas these were vice versa in castes. Our findings suggest that majority of tribal populations of India carry the protected / less severe allele against VL, while risk / more severe allele for leprosy and Behcet’s disease. This study has potential implications in counseling and management of VL and other infectious diseases.

Chromosome 6q26–27 is linked to susceptibility to visceral leishmaniasis (VL) in Brazil and Sudan. DLL1 encoding the Delta-like 1 ligand for Notch 3 was implicated as the etiological gene. DLL1 belongs to the family of Notch ligands known to selectively drive antigen-specific CD4 T helper 1 cell responses, which are important in protective immune response in leishmaniasis. Here we provide further genetic and functional evidence that supports a role for DLL1 in a well-powered population-based study centred in the largest global focus of VL in India. Twenty-one single nucleotide polymorphisms (SNPs) at PHF10/C6orf70/DLL1/FAM120B/PSMB1/TBP were genotyped in 941 cases and 992 controls. Logistic regression analysis under an additive model showed association between VL and variants at DLL1 and FAM120B, with top associations (rs9460106, OR=1.17, 95%CI 1.01–1.35, P=0.033; rs2103816, OR=1.16, 95%CI 1.01–1.34, P=0.039) robust to analysis using caste as a covariate to take account of population substructure. Haplotype analysis taking population substructure into account identified a common 2-SNP risk haplotype (frequency 0.43; P=0.028) at FAM120B, while the most significant protective haplotype (frequency 0.18; P=0.007) was a 5-SNP haplotype across the interval 5’ of both DLL1 (negative strand) and FAM120B (positive strand) and extending to intron 4 of DLL1. Quantitative RT/PCR was used to compare expression of 6q27 genes in paired pre- and post-treatment splenic aspirates from VL patients (N=19). DLL1 was the only gene to show differential expression that was higher (P

In this paper we consider spatially distributed heterogeneous discrete-time systems which are interconnected over an infinite lattice. An operator-pencil approach is employed to develop analysis conditions, which are less conservative than those previously available. Synthesis conditions are also obtained and are in the form of operator inequalities. In general these are infinite dimensional but in the case of eventually invariant systems these reduce to a semidefinite program.