Prospect of Protected Agricultural Structure and its Constraints for Utilizing in Nepal

Protected agricultural structures have been adopted by commercial farmers throughout the world including Nepal to cope with climate change and its adverse effects on agriculture. Technology based production system is important for sustainable agricultural development. It could be the tool for low-income countries like Nepal where agriculture is the priority of income generation for the rural people. A field study was conducted in 2021 and 2022 to understand the prospects of protected agriculture structures adaptation by farmers and agricultural entrepreneur in Nepal. The study was traversed with both physical observation and the user’s interviews. The opportunities and the constraints have been critically analysed based on these field study along with the review of different policy documents and success stories published. This study found that the protected cultivation practice has been rapidly increased with increasing number of protected structures like plastic house or tunnel framed with bamboo or GI pipe, Agri-net house, naturally ventilated poly house and semi or hi-tech green house. In contrary, the import of horticulture products has also been increased more than 200% in last 10 years. This study finds the gap mismatching between technology enhancement, production and import of horticulture crops

Sequence and expression variations in 23 genes involved in mitochondrial and non-mitochondrial apoptotic pathways and risk of oral leukoplakia and cancer

Oral cancer is usually preceded by pre-cancerous lesion and related to tobacco abuse. Tobacco carcinogens damage DNA and cells harboring such damaged DNA normally undergo apoptotic death, but cancer cells are exceptionally resistant to apoptosis. Here we studied association between sequence and expression variations in apoptotic pathway genes and risk of oral cancer and precancer. Ninety nine tag SNPs in 23 genes, involved in mitochondrial and non-mitochondrial apoptotic pathways,were genotyped in 525 cancer and 253 leukoplakia patients and 538 healthy controls using Illumina Golden Gate assay. Six SNPs (rs1473418 at BCL2; rs1950252 at BCL2L2; rs8190315 at BID; rs511044 at CASP1; rs2227310 at CASP7 and rs13010627 at CASP10) significantlymodified risk of oral cancer but SNPs only at BCL2, CASP1and CASP10 modulated risk of leukoplakia. Combination of SNPs showed a steep increase in risk of cancerwith increase in “effective” number of risk alleles. In silico analysis of published data set and our unpublished RNAseq data suggest that change in expression of BID and CASP7 may have affected risk of cancer. In conclusion, three SNPs, rs1473418 in BCL2, rs1950252 in BCL2L2 and rs511044 in CASP1, are being implicated for the first time in oral cancer. Since SNPs at BCL2, CASP1 and CASP10modulated risk of both leukoplakia and cancer, so, they should be studied inmore details for possible biomarkers in transition of leukoplakia to cancer. This study also implies importance of mitochondrial apoptotic pathway gene (such as BCL2) in progression of leukoplakia to oral cancer

Basic characteristics of case and control data in discovery phase.

<p>Abbreviation: Con: Control, Can: Oral cancer, Leu: Leukoplakia.</p>a<p>P-values from Mann-Whitney test,</p>b<p>p-values from chi-square test.</p

Allelic association results among different comparison groups.

a<p>MAF: Minor Allele Frequency of reference population is listed;</p>b<p>Association tests abbreviations, CC: case (jointly oral cancer and leukoplakia) vs. control, CAC: cancer vs. control, CAL: cancer vs. leukoplakia and LC: leukoplakia vs. control;</p>c<p>P-values without any adjustment for age, sex and tobacco habits by logistic regression and without any multiple tests correction applied,</p>d<p>P-values without any adjustment for age, sex and tobacco habits by logistic regression but corrected for multiple testing by Benjamini-Hochberg False Discovery Rate method,</p>e<p>P-values after adjustment for age, sex and tobacco habits by logistic regression but no correction multiple testing was applied,</p>f<p>P-values after adjustment for age, sex and tobacco habits by logistic regression and corrected for multiple testing by Benjamini-Hochberg False Discovery Rate method.</p

Allelic associations in with respect to tobacco exposure.

a<p>MAF: Minor allele frequency of the reference population is listed;</p>b<p>Association tests abbreviations, CC: case (jointly oral cancer and leukoplakia) vs. Control, CAC: cancer vs. Control, CAL: cancer vs. Leukoplakia, LC: leukoplakia vs. control, HD: High-dose and LD: Low-dose tobacco exposed group;</p>c<p>Benjamini-Hochberg False Discovery Rate corrected P-values for multiple tests.</p

Basic characteristics of cancer and control in replication phase.

<p>Abbreviation:</p>a<p>p-values from Mann-Whitney test,</p>b<p>P-values from chi-square test.</p

Overall strategy of the association study.

<p>Overall strategy of the association study.</p

Allelic association results of replication study and comparison with discovery data.

a<p>MAF: Minor allele frequency of the reference population is listed;</p>*<p>Benjamini-Hochberg False Discovery Rate corrected P-values for multiple tests;</p>#<p>Unadjusted P-values.</p

Genetic epidemiology of autoinflammatory disease variants in Indian population from 1029 whole genomes

Abstract Background Autoinflammatory disorders are the group of inherited inflammatory disorders caused due to the genetic defect in the genes that regulates innate immune systems. These have been clinically characterized based on the duration and occurrence of unprovoked fever, skin rash, and patient’s ancestry. There are several autoinflammatory disorders that are found to be prevalent in a specific population and whose disease genetic epidemiology within the population has been well understood. However, India has a limited number of genetic studies reported for autoinflammatory disorders till date. The whole genome sequencing and analysis of 1029 Indian individuals performed under the IndiGen project persuaded us to perform the genetic epidemiology of the autoinflammatory disorders in India. Results We have systematically annotated the genetic variants of 56 genes implicated in autoinflammatory disorder. These genetic variants were reclassified into five categories (i.e., pathogenic, likely pathogenic, benign, likely benign, and variant of uncertain significance (VUS)) according to the American College of Medical Genetics and Association of Molecular pathology (ACMG-AMP) guidelines. Our analysis revealed 20 pathogenic and likely pathogenic variants with significant differences in the allele frequency compared with the global population. We also found six causal founder variants in the IndiGen dataset belonging to different ancestry. We have performed haplotype prediction analysis for founder mutations haplotype that reveals the admixture of the South Asian population with other populations. The cumulative carrier frequency of the autoinflammatory disorder in India was found to be 3.5% which is much higher than reported. Conclusion With such frequency in the Indian population, there is a great need for awareness among clinicians as well as the general public regarding the autoinflammatory disorder. To the best of our knowledge, this is the first and most comprehensive population scale genetic epidemiological study being reported from India

Comprehensive SNP Scan of DNA Repair and DNA Damage Response Genes Reveal Multiple Susceptibility Loci Conferring Risk to Tobacco Associated Leukoplakia and Oral Cancer

Polymorphic variants of DNA repair and damage response genes play major role in carcinogenesis. These variants are suspected as predisposition factors to Oral Squamous Cell Carcinoma (OSCC). For identification of susceptible variants affecting OSCC development in Indian population, the ‘‘maximally informative’’ method of SNP selection from HapMap data to non-HapMap populations was applied. Three hundred twenty-five SNPs from 11 key genes involved in double strand break repair, mismatch repair and DNA damage response pathways were genotyped on a total of 373 OSCC, 253 leukoplakia and 535 unrelated control individuals. The significantly associated SNPs were validated in an additional cohort of 144 OSCC patients and 160 controls. The rs12515548 of MSH3 showed significant association with OSCC both in the discovery and validation phases (discovery P-value: 1.43E-05, replication P-value: 4.84E-03). Two SNPs (rs12360870 of MRE11A, P-value: 2.37E-07 and rs7003908 of PRKDC, P-value: 7.99E-05) were found to be significantly associated only with leukoplakia. Stratification of subjects based on amount of tobacco consumption identified SNPs that were associated with either high or low tobacco exposed group. The study reveals a synergism between associated SNPs and lifestyle factors in predisposition to OSCC and leukoplakia