Safety of 3 different reintroduction regimens of antituberculosis drugs after development of antituberculosis treatment-induced hepatotoxicity

Background: Drug-induced hepatotoxicity (DIH) is the most common adverse drug reaction leading to interruption of antituberculosis treatment. Worldwide, different reintroduction regimens have been advocated, but no consensus guidelines are available. Reintroduction of antituberculosis drugs in patients with DIH has never been studied systematically. We aimed to compare the safety of 3 different reintroduction regimens of antituberculosis drugs in patients with antituberculosis DIH. Methods: A total of 175 patients with a diagnosis of antituberculosis DIH were randomized to receive 1 of 3 different predefined reintroduction regimens of antituberculosis drugs and were evaluated prospectively. Patients in arm I were given isoniazid, rifampicin, and pyrazinamide simultaneously at full dosage from day 1. In arm II, drugs were administered in a manner similar to that recommended in the American Thoracic Society guidelines for reintroduction. In arm III, drugs were administered in accordance with British Thoracic Society guidelines. Results: Nineteen patients (10.9%) had recurrence of DIH during follow-up. Eight, 6, and 5 patients had recurrence of hepatitis in arms I, II, and III, respectively (P=.69). Of all the clinical and laboratory parameters, pretreatment serum albumin level was the only statistically significant predictor of future recurrence of DIH on reintroduction of antituberculosis drugs (P<.01). Conclusions: The recurrence rate of hepatotoxicity was not significantly different between the 3 groups. According to the findings of the present study, all 3 of the potentially hepatotoxic drugs (isoniazid, rifampicin, and pyrazinamide) can be reintroduced simultaneously at full dosage safely from day 1, especially for patients with bilateral extensive pulmonary tuberculosis, to halt disease transmission or to treat patients with life-threatening tuberculosis

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Not AvailableErratic rainfall leading to flash flooding causes huge yield losses in lowland rice. The traditional varieties and landraces of rice possess variable levels of tolerance to submergence stress, but gene discovery and utilization of these resources has been limited to the Sub1A-1 allele from variety FR13A. Therefore, we analysed the allelic sequence variation in three Sub1 genes in a panel of 179 rice genotypes and its association with submergence tolerance. Population structure and diversity analysis based on a 36-plex genome wide genic-SNP assay grouped these genotypes into two major categories representing Indica and Japonica cultivar groups with further sub-groupings into Indica, Aus, Deepwater and Aromatic- Japonica cultivars. Targetted re-sequencing of the Sub1A, Sub1B and Sub1C genes identfied 7, 7 and 38 SNPs making 8, 9 and 67 SNP haplotypes, respectively. Haplotype networks and phylogenic analysis revealed evolution of Sub1B and Sub1A genes by tandem duplication and divergence of the ancestral Sub1C gene in that order. The alleles of Sub1 genes in tolerant reference variety FR13A seem to have evolved most recently. However, no consistent association could be found between the Sub1 allelic variation and submergence tolerance probably due to low minor allele frequencies and presence of exceptions to the known Sub1A-1 association in the genotype panel. We identified 18 cultivars with non-Sub1A-1 source of submergence tolerance which after further mapping and validation in biparental populations will be useful for development of superior flood tolerant rice cultivars.Not Availabl

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Not AvailableMango is one of the most important fruits of tropical ecological region of the world, well known for its nutritive value, aroma and taste. Its world production is >45MT worth >200 billion US dollars. Genomic resources are required for improvement in productivity and management of mango germplasm. There is no web-based genomic resources available for mango. Hence rapid and cost-effective high throughput putative marker discovery is required to develop such resources. RAD-based marker discovery can cater this urgent need till whole genome sequence of mango becomes available. Using a panel of 84 mango varieties, a total of 28.6 Gb data was generated by ddRAD-Seq approach on Illumina HiSeq 2000 platform. A total of 1.25 million SNPs were discovered. Phylogenetic tree using 749 common SNPs across these varieties revealed three major lineages which was compared with geographical locations. A web genomic resources MiSNPDb, available at http://webtom.cabgrid.res.in/mangosnps/ is based on 3-tier architecture, developed using PHP, MySQL and Javascript. This web genomic resources can be of immense use in the development of high density linkage map, QTL discovery, varietal differentiation, traceability, genome finishing and SNP chip development for future GWAS in genomic selection program. We report here world’s first web-based genomic resources for genetic improvement and germplasm management of mango.Not Availabl

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Not AvailableMango is one of the most important fruits of tropical ecological region of the world, well known for its nutritive value, aroma and taste. Its world production is >45MT worth >200 billion US dollars. Genomic resources are required for improvement in productivity and management of mango germplasm. There is no web-based genomic resources available for mango. Hence rapid and cost-efective high throughput putative marker discovery is required to develop such resources. RAD-based marker discovery can cater this urgent need till whole genome sequence of mango becomes available. Using a panel of 84 mango varieties, a total of 28.6 Gb data was generated by ddRAD-Seq approach on Illumina HiSeq 2000 platform. A total of 1.25 million SNPs were discovered. Phylogenetic tree using 749 common SNPs across these varieties revealed three major lineages which was compared with geographical locations. A web genomic resources MiSNPDb, available at http://webtom.cabgrid.res.in/mangosnps/ is based on 3-tier architecture, developed using PHP, MySQL and Javascript. This web genomic resources can be of immense use in the development of high density linkage map, QTL discovery, varietal diferentiation, traceability, genome fnishing and SNP chip development for future GWAS in genomic selection program. We report here world’s frst web-based genomic resources for genetic improvement and germplasm management of mango.Not Availabl

Development and Genetic Characterization of A Novel Herbicide (Imazethapyr) Tolerant Mutant in Rice (Oryza sativa L.)

Abstract Background Increased water and labour scarcity in major rice growing areas warrants a shift towards direct seeded rice cultivation under which management of weeds is a major issue. Use of broad spectrum non-selective herbicides is an efficient means to manage weeds. Availability of rice genotypes with complete tolerance against broad-spectrum non-selective herbicides is a pre-requisite for advocating use of such herbicides. In the present study, we developed an EMS induced rice mutant, ‘HTM-N22‘, exhibiting tolerance to a broad spectrum herbicide, ‘Imazethapyr‘, and identified the mutations imparting tolerance to the herbicide. Results We identified a stable and true breeding rice mutant, HTM-N22 (HTM), tolerant to herbicide, Imazethapyr, from an EMS-mutagenized population of approximately 100,000 M2 plants of an upland rice variety, Nagina 22 (N22). Analysis of inheritance of herbicide tolerance in a cross between Pusa 1656-10-61/HTM showed that this trait is governed by a single dominant gene. To identify the causal gene for Imazethapyr tolerance, bulked segregant analysis (BSA) was followed using microsatellite markers flanking the three putative candidate genes viz., an Acetolactate Synthase (ALS) on chromosome 6 and two Acetohydroxy Acid Synthase (AHAS) genes, one on chromosomes 2 and another on chromosome 4. RM 6844 on chromosome 2 located 0.16 Mbp upstream of AHAS (LOC_Os02g30630) was found to co-segregate with herbicide tolerance. Cloning and sequencing of AHAS (LOC_Os02g30630) from the wild type, N22 and the mutant HTM and their comparison with reference Nipponbare sequence revealed several Single Nucleotide Polymorphisms (SNPs) in the mutant, of which eight resulted in non-synonymous mutations. Three of the eight amino acid substitutions were identical to Nipponbare and hence were not considered as causal changes. Of the five putative candidate SNPs, four were novel (at positions 30, 50, 81 and 152) while the remaining one, S627D was a previously reported mutant, known to result in Imidazolinone tolerance in rice. Of the novel ones, G152E was found to alter the hydrophobicty and abolish an N myristoylation site in the HTM compared to the WT, from reference based modeling and motif prediction studies. Conclusions A novel mutant tolerant to the herbicide “Imazethapyr” was developed and characterized for genetic, sequence and protein level variations. This is a HTM in rice without any IPR (Intellectual Property Rights) infringements and hence can be used in rice breeding as a novel genetic stock by the public funded organizations in the country and elsewhere

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Not AvailableMango (Mangifera indica L.) is known as the ‘king of fruits’ for its rich taste, flavor, color, production volume and diverse end usage. It belongs to plant family Anacardiaceae and has a small genome size of 439 Mb (2n = 40). Ancient literature indicates origin of cultivated mango in India. Although wild species of genus Mangifera are distributed throughout South and South-East Asia, recovery of Paleocene mango leaf fossils near Damalgiri, West Garo Hills, Meghalaya point to the origin of genus in peninsular India before joining of the Indian and Asian continental plates. India produces more than fifty percent of the world’s mango and grows more than thousand varieties. Despite its huge economic significance genomic resources for mango are limited and genetics of useful horticultural traits are poorly understood. Here we present a brief account of our recent efforts to generate genomic resources for mango and its use in the analysis of genetic diversity and population structure of mango cultivars. Sequencing of leaf RNA from mango cultivars ‘Neelam’, ‘Dashehari’ and their hybrid ‘Amrapali’ revealed substantially higher level of heterozygosity in ‘Amrapali’ over its parents and helped develop genic simple sequence repeat (SSR) and single nucleotide polymorphism (SNP) markers. Sequencing of double digested restriction-site-associated genomic DNA (ddRAD) of 84 diverse mango cultivars identified 1.67 million high quality SNPs and two major sub-populations. We have assembled 323 Mb of the highly heterozygous ‘Amrapali’ genome using long sequence reads of PacBio single molecule real time (SMRT) sequencing chemistry and predicted 43,247 protein coding genes. We identified in the mango genome 122,332 SSR loci and developed 8,451 Type1 SSR and 835 HSSR markers for high level of polymorphism. Among the published genomes, mango showed highest similarity with sweet orange (Citrus sinensis). These genomic resources will fast track the mango varietal improvement for high productivity, disease resistance and superior end use qualityNot Availabl

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Not AvailableRice is the most important food crop both in value and volume for the Asian population. Frequent drought, flood and salinity stresses exacerbated by global climate change adversely affect rice production in more than fifty percent of the rice growing areas. Green revolution high yielding varieties carrying sd1 dwarfing gene have almost fully replaced the traditional climate resilient landraces and varieties of rice. However, these were bred primarily for yield under high input conditions and therefore are sensitive to adverse climatic conditions. Hence, there is urgent need to combine the high productivity with climate resilience. Knowledge of rice genome and genes for tolerance to different abiotic stresses provided us an opportunity to transfer favorable alleles of these genes into high yielding varieties through genomics-assisted backcross breeding through multi-institutional networks. Six consistent genomic regions (QTLs) for grain yield under drought; namely qDTY1.1, qDTY2.1, qDTY2.2, qDTY3.1, qDTY3.2 and qDTY12.1 have been transferred to flood tolerant versions of mega varieties of rice, Swarna, Samba Mahsuri and IR 64. To address the problem of flash flooding qSUB1 QTL has been transferred to nine popular rice varieties, namely ADT 46, Bahadur, Ranjit, HUR 105, Sarjoo 52, Pooja, Pratikshya MTU 1075 and Rajendra Mahsuri. Further, qSALTOL1 QTL for seedling stage salt tolerance and qSSISFH8.1 for reproductive stage salt tolerance have been transferred to six popular rice varieties, ADT 45, Gayatri, MTU 1010, PR 114, Pusa 44 and Sarjoo 52. We used foreground selection markers for the presence of desired gene/QTL and recombinant selection markers for reduction of linkage drag around these genes. Genotypic background selection was done after BC3F3 stage using a 50K SNP chip on a set of 20 advance lines obtained by phenotypic selection for closeness to the recipient parents. Near-isogenic lines (NILs) with more than 95% similarity to the recipient parent genome have been released and notified for commercial cultivation and are gaining fast popularity. These climate smart rice varieties will provide production stability in the adverse ecologies and support farmer’s income and livelihood.Not Availabl