Mango (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 quality.
The liver is the primary site of metabolism for most drugs. Its major roles include detoxification of the systemic and portal blood, and production and secretion of critical blood and biliary components. A number of liver-derived in vitro systems, such as slices, primary and immortalized hepatocytes, microsomes and S9 fractions are used to assess the metabolism and potential toxicity of new chemical entities. Over the past decade, primary hepatocytes have become a standard in vitro tool to evaluate hepatic drug metabolism, cytochrome P450 (P450) induction, and drug interactions affecting hepatic metabolism. While earlier, hepatocytes were used in suspension for metabolic stability evaluations, more recent studies have demonstrated the added value of using these over longer terms in primary culture. Primary hepatocyte cultures are particularly useful in the evaluation of low turn-over compounds. Hepatic transporter studies are recommended for drug candidates that are predominantly eliminated through the bile. An appropriate strategy is to use primary hepatocytes to assess uptake, followed by singly transfected cell lines to identify the specific transporter(s) involved. Primary hepatocytes can also be used to assess biliary clearance to enable improved hepatic clearance predictions. Newer technologies such as siRNA can be used to knock out specific transporters for more predictive evaluations of potential clinically-based drug-drug interactions. In vitro safety (toxicology) studies have historically been conducted using cell lines. There is increasing evidence that co-cultures of primary hepatocytes and Kupffer cells would be more predictive of the in vivo outcome, as this system provides the complete complement of drug metabolizing enzymes, transcription factors and cytokines necessary to get a more in vivo-like toxicological response. In this review, we will discuss standard and novel in vitro approaches for using primary hepatocytes to extrapolate clinical hepatic metabolism, transport and toxicity.
Thrips palmi (Thysanoptera: Thripidae) is the predominant tospovirus vector in Asia-Pacific region. It transmits economically damaging groundnut bud necrosis virus (GBNV, family Tospoviridae) in a persistent propagative manner. Thrips serve as the alternate host, and virus reservoirs making tospovirus management very challenging. Insecticides and host plant resistance remain ineffective in managing thrips–tospoviruses. Recent genomic approaches have led to understanding the molecular interactions of thrips–tospoviruses and identifying novel genetic targets. However, most of the studies are limited to Frankliniella species and tomato spotted wilt virus (TSWV). Amidst the limited information available on T. palmi–tospovirus relationships, the present study is the first report of the transcriptome-wide response of T. palmi associated with GBNV infection. The differential expression analyses of the triplicate transcriptome of viruliferous vs. nonviruliferous adult T. palmi identified a total of 2,363 (1,383 upregulated and 980 downregulated) significant transcripts. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses showed the abundance of differentially expressed genes (DEGs) involved in innate immune response, endocytosis, cuticle development, and receptor binding and signaling that mediate the virus invasion and multiplication in the vector system. Also, the gene regulatory network (GRN) of most significant DEGs showed the genes like ABC transporter, cytochrome P450, endocuticle structural glycoprotein, gamma-aminobutyric acid (GABA) receptor, heat shock protein 70, larval and pupal cuticle proteins, nephrin, proline-rich protein, sperm-associated antigen, UHRF1-binding protein, serpin, tyrosine–protein kinase receptor, etc., were enriched with higher degrees of interactions. Further, the expression of the candidate genes in response to GBNV infection was validated in reverse transcriptase-quantitative real-time PCR (RT-qPCR). This study leads to an understanding of molecular interactions between T. palmi and GBNV and suggests potential genetic targets for generic pest control.
Objective Prevalence of hyperuricemia (HU) is increasing and it is associated with hypertension, metabolic syndrome, diabetes mellitus (DM), obesity, chronic kidney disease, gout and cardiovascular disease. Elevated level of serum uric acid (SUA) has been shown to be associated with hypertension and diabetes in many countries but there is lack of evidence from India. The aim of this study is to know the prevalence of HU and to know the relationship between SUA and hypertension in newly onset DM. Methods This is a cross-sectional study from a tertiary center. A total of 305 (males: 212; females: 93) newly diagnosed diabetic patients were enrolled. All patients were categorized as normotensive (<140/90) and hypertensive (≥140/90) based on ADA criteria. Based on SUA level participants were grouped into 3 tertile (T1: <4.52; T2: 4.52–5.64; T3: >5.64 mg/dl). Results The mean age, systolic blood pressure (SBP) and diastolic blood pressure (DBP) of the patients were 46.76 ±0.61 years, 130.6±1.06 mmHg and 84.11±0.63 mmHg, respectively. The mean level of SUA was 5.14±0.073 mg/dl and level was significantly higher in males compared with females (P <0.000). Overall prevalence of HU and hypertension was 12.13% and 44.59%, respectively. There was an increase in the prevalence of hypertension across the SUA tertile. SBP and DBP significantly increased across the SUA tertile (P <0.014 and <0.001, respectively). A multiple logistic regression analysis revealed that SUA tertile was independently associated with presence of hypertension (P <0.01). Conclusion This first report on the population of the eastern part of India indicates a significant positive relationship between SUA and hypertension among the newly onset Indian diabetic patients. Therefore, routine measurement of SUA is recommended in newly onset hypertensive diabetic patients to prevent HU and its related complications.
Heat stress is one of the significant constraints affecting wheat production worldwide. To ensure food security for ever-increasing world population, improving wheat for heat stress tolerance is needed in the presently drifting climatic conditions. At the molecular level, heat stress tolerance in wheat is governed by a complex interplay of various heat stress-associated genes. We used a comparative transcriptome sequencing approach to study the effect of heat stress (5°C above ambient threshold temperature of 20°C) during grain filling stages in wheat genotype K7903 (Halna). At 7 DPA (days post-anthesis), heat stress treatment was given at four stages: 0, 24, 48, and 120 h. In total, 115,656 wheat genes were identified, including 309 differentially expressed genes (DEGs) involved in many critical processes, such as signal transduction, starch synthetic pathway, antioxidant pathway, and heat stress-responsive conserved and uncharacterized putative genes that play an essential role in maintaining the grain filling rate at the high temperature. A total of 98,412 Simple Sequences Repeats (SSR) were identified from de novo transcriptome assembly of wheat and validated. The miRNA target prediction from differential expressed genes was performed by psRNATarget server against 119 mature miRNA. Further, 107,107 variants including 80,936 Single nucleotide polymorphism (SNPs) and 26,171 insertion/deletion (Indels) were also identified in de novo transcriptome assembly of wheat and wheat genome Ensembl version 31. The present study enriches our understanding of known heat response mechanisms during the grain filling stage supported by discovery of novel transcripts, microsatellite markers, putative miRNA targets, and genetic variant. This enhances gene functions and regulators, paving the way for improved heat tolerance in wheat varieties, making them more suitable for production in the current climate change scenario.
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