Responsible Use of Oral Corticosteroids in People with Comorbid Diabetes: An Expert Consensus.

Globally, diabetes mellitus (DM) is a substantial contributor to morbidity and mortality. Comorbidities and intercurrent illnesses in people with diabetes may necessitate the use of steroids. Acute as well as chronic use of steroids contributes substantially to the development of various complications. Despite this, there are no standard guidelines or consensus to provide a unified approach for the rational use of steroids in people with diabetes. Also, there is scant harmonization among clinicians with the use of different steroids in routine practice. To address the inconsistencies in this clinical arena, the consensus working group (CWG) formulated a unified consensus for steroid use in people with diabetes. In people with diabetes, the use of steroids causes hyperglycemia and may precipitate diabetic ketoacidosis (DKA). An increase in weight is directly related to the dose and duration of the steroid therapy. Steroid-related alterations in hyperglycemia, dyslipidemia, and hypertension (HTN) add to the increased risk of cardiovascular (CV) disease. The risk of complications such as infections, osteoporosis, myopathy, acne, cataracts, and glaucoma may increase with the use of steroids. Appropriate and timely monitoring of these complications is necessary for early detection and treatment of such complications. Given the systemic effects of various antihyperglycemic drugs, there is a possibility of aggravating or diminishing the specific complications. Preference to a safer steroid is required matching the steroid dose equivalence and individualizing patient management. In conclusion, short-, intermediate-, or long-term use of steroids in people with diabetes demands their rational use and holistic approach to identify, monitor, and treat the complications induced or aggravated by the steroids.

Discovering New QTNs and Candidate Genes Associated with Rice-Grain-Related Traits within a Collection of Northeast Core Set and Rice Landraces.

Grain-related traits are pivotal in rice cultivation, influencing yield and consumer preference. The complex inheritance of these traits, involving multiple alleles contributing to their expression, poses challenges in breeding. To address these challenges, a multi-locus genome-wide association study (ML-GWAS) utilizing 35,286 high-quality single-nucleotide polymorphisms (SNPs) was conducted. Our study utilized an association panel comprising 483 rice genotypes sourced from a northeast core set and a landraces set collected from various regions in India. Forty quantitative trait nucleotides (QTNs) were identified, associated with four grain-related traits: grain length (GL), grain width (GW), grain aroma (Aro), and length-width ratio (LWR). Notably, 16 QTNs were simultaneously identified using two ML-GWAS methods, distributed across multiple chromosomes. Nearly 258 genes were found near the 16 significant QTNs. Gene annotation study revealed that sixty of these genes exhibited elevated expression levels in specific tissues and were implicated in pathways influencing grain quality. Gene ontology (GO), trait ontology (TO), and enrichment analysis pinpointed 60 candidate genes (CGs) enriched in relevant GO terms. Among them, LOC_Os05g06470, LOC_Os06g06080, LOC_Os08g43470, and LOC_Os03g53110 were confirmed as key contributors to GL, GW, Aro, and LWR. Insights from QTNs and CGs illuminate rice trait regulation and genetic connections, offering potential targets for future studies.

Revolutionizing biomedicine: Aptamer-based nanomaterials and nanodevices for therapeutic applications.

With the progress in two distinct areas of nanotechnology and aptamer identification technologies, the two fields have merged to what is known as aptamer nanotechnology. Aptamers have varying properties in the biomedical field include their small size, non-toxicity, ease of manufacturing, negligible immunogenicity, ability to identify a wide range of targets, and high immobilizing capacity. Nevertheless, aptamers can utilize the distinct characteristics offered by nanomaterials like optical, magnetic, thermal, electronic properties to become more versatile and function as a novel device in diagnostics and therapeutics. This engineered aptamer conjugated nanomaterials, in turn provides a potentially new and unique properties apart from the pre-existing characteristics of aptamer and nanomaterials, where they act to offer wide array of applications in the biomedical field ranging from drug targeting, delivery of drugs, biosensing, bioimaging. This review gives comprehensive insight of the different aptamer conjugated nanomaterials and their utilization in biomedical field. Firstly, it introduces on the aptamer selection methods and roles of nanomaterials offered. Further, different conjugation strategies are explored in addition, the class of aptamer conjugated nanodevices being discussed. Typical biomedical examples and studies specifically, related to drug delivery, biosensing, bioimaging have been presented.

Transcriptome-wide association mapping provides insights into the genetic basis and candidate genes governing flowering, maturity and seed weight in rice bean (Vigna umbellata).

BACKGROUND: Rice bean (Vigna umbellata), an underrated legume, adapts to diverse climatic conditions with the potential to support food and nutritional security worldwide. It is used as a vegetable, minor food crop and a fodder crop, being a rich source of proteins, minerals, and essential fatty acids. However, little effort has been made to decipher the genetic and molecular basis of various useful traits in this crop. Therefore, we considered three economically important traits i.e., flowering, maturity and seed weight of rice bean and identified the associated candidate genes employing an associative transcriptomics approach on 100 diverse genotypes out of 1800 evaluated rice bean accessions from the Indian National Genebank. RESULTS: The transcriptomics-based genotyping of one-hundred diverse rice bean cultivars followed by pre-processing of genotypic data resulted in 49,271 filtered markers. The STRUCTURE, PCA and Neighbor-Joining clustering of 100 genotypes revealed three putative sub-populations. The marker-trait association analysis involving various genome-wide association study (GWAS) models revealed significant association of 82 markers on 48 transcripts for flowering, 26 markers on 22 transcripts for maturity and 22 markers on 21 transcripts for seed weight. The transcript annotation provided information on the putative candidate genes for the considered traits. The candidate genes identified for flowering include HSC80, P-II PsbX, phospholipid-transporting-ATPase-9, pectin-acetylesterase-8 and E3-ubiquitin-protein-ligase-RHG1A. Further, the WRKY1 and DEAD-box-RH27 were found to be associated with seed weight. Furthermore, the associations of PIF3 and pentatricopeptide-repeat-containing-gene with maturity and seed weight, and aldo-keto-reductase with flowering and maturity were revealed. CONCLUSION: This study offers insights into the genetic basis of key agronomic traits in rice bean, including flowering, maturity, and seed weight. The identified markers and associated candidate genes provide valuable resources for future exploration and targeted breeding, aiming to enhance the agronomic performance of rice bean cultivars. Notably, this research represents the first transcriptome-wide association study in pulse crop, uncovering the candidate genes for agronomically useful traits.

Uncovering DNA methylation landscapes to decipher evolutionary footprints of phenotypic diversity in chickpea.

Genetic diversity and environmental factors are long believed to be the dominant contributors to phenotypic diversity in crop plants. However, it has been recently established that, besides genetic variation, epigenetic variation, especially variation in DNA methylation, plays a significant role in determining phenotypic diversity in crop plants. Therefore, assessing DNA methylation diversity in crop plants becomes vital, especially in the case of crops like chickpea, which has a narrow genetic base. Thus, in the present study, we employed whole-genome bisulfite sequencing to assess DNA methylation diversity in wild and cultivated (desi and kabuli) chickpea. This revealed extensive DNA methylation diversity in both wild and cultivated chickpea. Interestingly, the methylation diversity was found to be significantly higher than genetic diversity, suggesting its potential role in providing vital phenotypic diversity for the evolution and domestication of the Cicer gene pool. The phylogeny based on DNA methylation variation also indicates a potential complementary role of DNA methylation variation in addition to DNA sequence variation in shaping chickpea evolution. Besides, the study also identified diverse epi-alleles of many previously known genes of agronomic importance. The Cicer MethVarMap database developed in this study enables researchers to readily visualize methylation variation within the genes and genomic regions of their interest (http://223.31.159.7/cicer/public/). Therefore, epigenetic variation like DNA methylation variation can potentially explain the paradox of high phenotypic diversity despite the narrow genetic base in chickpea and can potentially be employed for crop improvement.

Identification of superior haplotypes for flowering time in pigeonpea through candidate gene-based association study of a diverse minicore collection.

KEY MESSAGE: In current study candidate gene (261 genes) based association mapping on 144 pigeonpea accessions for flowering time and related traits and 29 MTAs producing eight superior haplotypes were identified. In the current study, we have conducted an association analysis for flowering-associated traits in a diverse pigeonpea mini-core collection comprising 144 accessions using the SNP data of 261 flowering-related genes. In total, 13,449 SNPs were detected in the current study, which ranged from 743 (ICP10228) to 1469 (ICP6668) among the individuals. The nucleotide diversity (0.28) and Watterson estimates (0.34) reflected substantial diversity, while Tajima's D (-0.70) indicated the abundance of rare alleles in the collection. A total of 29 marker trait associations (MTAs) were identified, among which 19 were unique to days to first flowering (DOF) and/or days to fifty percent flowering (DFF), 9 to plant height (PH), and 1 to determinate (Det) growth habit using 3 years of phenotypic data. Among these MTAs, six were common to DOF and/or DFF, and four were common to DOF/DFF along with the PH, reflecting their pleiotropic action. These 29 MTAs spanned 25 genes, among which 10 genes clustered in the protein-protein network analysis, indicating their concerted involvement in floral induction. Furthermore, we identified eight haplotypes, four of which regulate late flowering, while the remaining four regulate early flowering using the MTAs. Interestingly, haplotypes conferring late flowering (H001, H002, and H008) were found to be taller, while those involved in early flowering (H003) were shorter in height. The expression pattern of these genes, as inferred from the transcriptome data, also underpinned their involvement in floral induction. The haplotypes identified will be highly useful to the pigeonpea breeding community for haplotype-based breeding.

Exploring the potential of 2-arylbenzimidazole scaffolds as novel α-amylase inhibitors: QSAR, molecular docking, simulation and pharmacokinetic studies.

Previous studies have shown that 2-arylbenzimidazole derivatives have a strong anti-diabetic effect. To further explore this potential, we develop new analogues of the compound using ligand-based drug design and tested their inhibitory and binding properties through QSAR analyses, molecular docking, dynamic simulations and pharmacokinetic studies. By using quantitative structure activity relationship and ligand-based modification, a highly precise predictive model and design of potent compounds was developed from the derivatives of 2-arylbenzimidazoles. Molecular docking and simulation studies were then conducted to identify the optimal binding poses and pharmacokinetic profiles of the newly generated therapeutic drugs. DFT was employed to optimize the chemical structures of 2-arylbenzimidazole derivatives using B3LYP/6-31G* as the basis set. The model with the highest R2trng set, R2adj, Q2cv, and R2test sets (0.926, 0.912, 0.903, and 0.709 respectively) was chosen to predict the inhibitory activities of the derivatives. Five analogues designed using ligand-based strategy had higher activity than the hit molecule. Additionally, the designed molecules had more favorable MolDock scores than the hit molecule and acarbose and simulation studies confirm on their stability and binding affinities towards the protein. The ADME and druglikeness properties of the analogues indicated that they are safe to consume orally and have a high potential for total clearance. The results of this study showed that the suggested analogues could act as α-amylase inhibitors, which could be used as a basis for the creation of new drugs to treat type 2 diabetes mellitus.

QTLs and Genes for Salt Stress Tolerance: A Journey from Seed to Seed Continued.

Rice (Oryza sativa L.) is a crucial crop contributing to global food security; however, its production is susceptible to salinity, a significant abiotic stressor that negatively impacts plant germination, vigour, and yield, degrading crop production. Due to the presence of exchangeable sodium ions (Na+), the affected plants sustain two-way damage resulting in initial osmotic stress and subsequent ion toxicity in the plants, which alters the cell's ionic homeostasis and physiological status. To adapt to salt stress, plants sense and transfer osmotic and ionic signals into their respective cells, which results in alterations of their cellular properties. No specific Na+ sensor or receptor has been identified in plants for salt stress other than the SOS pathway. Increasing productivity under salt-affected soils necessitates conventional breeding supplemented with biotechnological interventions. However, knowledge of the genetic basis of salinity stress tolerance in the breeding pool is somewhat limited because of the complicated architecture of salinity stress tolerance, which needs to be expanded to create salt-tolerant variants with better adaptability. A comprehensive study that emphasizes the QTLs, genes and governing mechanisms for salt stress tolerance is discussed in the present study for future research in crop improvement.

Simple virus-free mouse models of COVID-19 pathologies and oral therapeutic intervention.

The paucity of preclinical models that recapitulate COVID-19 pathology without requiring SARS-COV-2 adaptation and humanized/transgenic mice limits research into new therapeutics against the frequently emerging variants-of-concern. We developed virus-free models by C57BL/6 mice receiving oropharyngeal instillations of a SARS-COV-2 ribo-oligonucleotide common in all variants or specific to Delta/Omicron variants, concurrently with low-dose bleomycin. Mice developed COVID-19-like lung pathologies including ground-glass opacities, interstitial fibrosis, congested alveoli, and became moribund. Lung tissues from these mice and bronchoalveolar lavage and lung tissues from patients with COVID-19 showed elevated levels of hyaluronic acid (HA), HA-family members, an inflammatory signature, and immune cell infiltration. 4-methylumbelliferone (4-MU), an oral drug for biliary-spasm treatment, inhibits HA-synthesis. At the human equivalent dose, 4-MU prevented/inhibited COVID-19-like pathologies and long-term morbidity; 4-MU and metabolites accumulated in mice lungs. Therefore, these versatile SARS-COV-2 ribo-oligonucleotide oropharyngeal models recapitulate COVID-19 pathology, with HA as its critical mediator and 4-MU as a potential therapeutic for COVID-19.

Genomic insight into variations associated with flowering-time and early-maturity in pigeonpea mutant TAT-10 and its wild type parent T21.

Pigeonpea [Cajanus cajan (L.) Millspaugh] is an important grain legume crop with a broad range of 90 to 300 days for maturity. To identify the genomic variations associated with the early maturity, we conducted whole-genome resequencing of an early-maturing pigeonpea mutant TAT-10 and its wild type parent T21. A total of 135.67 and 146.34 million sequencing reads were generated for T21 and TAT-10, respectively. From this resequencing data, 1,397,178 and 1,419,904 SNPs, 276,741 and 292,347 InDels, and 87,583 and 92,903 SVs were identified in T21 and TAT-10, respectively. We identified 203 genes in the pigeonpea genome that are homologs of flowering-related genes in Arabidopsis and found 791 genomic variations unique to TAT-10 linked to 94 flowering-related genes. We identified three candidate genes for early maturity in TAT-10; Suppressor of FRI 4 (SUF4), Early Flowering In Short Days (EFS), and Probable Lysine-Specific Demethylase ELF6. The variations in ELF6 were predicted to be possibly damaging and the expression profiles of EFS and ELF6 also supported their probable role during early flowering in TAT-10. The present study has generated information on genomic variations associated with candidate genes for early maturity, which can be further studied and exploited for developing the early-maturing pigeonpea cultivars.

Comparative transcriptome analysis of two contrasting genotypes provides new insights into the drought response mechanism in pigeon pea (Cajanus cajan L. Millsp.).

BACKGROUND: Despite plant's ability to adapt and withstand challenging environments, drought poses a severe threat to their growth and development. Although pigeon pea is already quite resistant to drought, the prolonged dehydration induced by the aberrant climate poses a serious threat to their survival and productivity. OBJECTIVE: Comparative physiological and transcriptome analyses of drought-tolerant (CO5) and drought-sensitive (CO1) pigeon pea genotypes subjected to drought stress were carried out in order to understand the molecular basis of drought tolerance in pigeon pea. METHODS: The transcriptomic analysis allowed us to examine how drought affects the gene expression of C. cajan. Using bioinformatics tools, the unigenes were de novo assembled, annotated, and functionally evaluated. Additionally, a homology-based sequence search against the droughtDB database was performed to identify the orthologs of the DEGs. RESULTS: 1102 potential drought-responsive genes were found to be differentially expressed genes (DEGs) between drought-tolerant and drought-sensitive genotypes. These included Abscisic acid insensitive 5 (ABI5), Nuclear transcription factor Y subunit A-7 (NF-YA7), WD40 repeat-containing protein 55 (WDR55), Anthocyanidin reductase (ANR) and Zinc-finger homeodomain protein 6 (ZF-HD6) and were highly expressed in the tolerant genotype. Further, GO analysis revealed that the most enriched classes belonged to biosynthetic and metabolic processes in the biological process category, binding and catalytic activity in the molecular function category and nucleus and protein-containing complex in the cellular component category. Results of KEGG pathway analysis revealed that the DEGs were significantly abundant in signalling pathways such as plant hormone signal transduction and MAPK signalling pathways. Consequently, in our investigation, we have identified and validated by qPCR a group of genes involved in signal reception and propagation, stress-specific TFs, and basal regulatory genes associated with drought response. CONCLUSION: In conclusion, our comprehensive transcriptome dataset enabled the discovery of candidate genes connected to pathways involved in pigeon pea drought response. Our research uncovered a number of unidentified genes and transcription factors that could be used to understand and improve susceptibility to drought.

The chickpea WIP2 gene underlying a major QTL contributes to lateral root development.

Lateral roots are a major component of root system architecture, and lateral root count (LRC) positively contributes to yield under drought in chickpea. To understand the genetic regulation of LRC, a biparental mapping population derived from two chickpea accessions having contrasting LRCs was genotyped by sequencing, and phenotyped to map four major quantitative trait loci (QTLs) contributing to 13-32% of the LRC trait variation. A single- nucleotide polymorphism tightly linked to the locus contributing to highest trait variation was located on the coding region of a gene (CaWIP2), orthologous to NO TRANSMITTING TRACT/WIP domain protein 2 (NTT/WIP2) gene of Arabidopsis thaliana. A polymorphic simple sequence repeat (SSR) in the CaWIP2 promoter showed differentiation between low versus high LRC parents and mapping individuals, suggesting its utility for marker-assisted selection. CaWIP2 promoter showed strong expression in chickpea apical root meristem and lateral root primordia. Expression of CaWIP2 under its native promoter in the Arabidopsis wip2wip4wip5 mutant rescued its rootless phenotype to produce more lateral roots than the wild-type plants, and led to formation of amyloplasts in the columella. CaWIP2 expression also induced the expression of genes that regulate lateral root emergence. Our study identified a gene-based marker for LRC which will be useful for developing drought-tolerant, high-yielding chickpea varieties.

Immunoinformatics and reverse vaccinology approach in designing a novel highly immunogenic multivalent peptide-based vaccine against the human monkeypox virus.

Background: Monkeypox is a highly infectious zoonotic disease, often resulting in complications ranging from respiratory illnesses to vision loss. The escalating global incidence of its cases demands prompt attention, as the absence of a proven post-exposure treatment underscores the criticality of developing an effective vaccine. Methods: Interactions of the viral proteins with TLR2 and TLR4 were investigated to assess their immunogenic potentials. Highly immunogenic proteins were selected and subjected to epitope mapping for identifying B-cell and MHC class I and II epitopes. Epitopes with high antigenicity were chosen, considering global population coverage. A multi-target, multi-epitope vaccine peptide was designed, incorporating a beta-defensin 2 adjuvant, B-cell epitopes, and MHC class I and II epitopes. Results: The coordinate structure of the engineered vaccine was modeled and validated. In addition, its physicochemical properties, antigenicity, allergenicity, and virulence traits were evaluated. Molecular docking studies indicated strong interactions between the vaccine peptide and the TLR2 receptor. Furthermore, molecular dynamics simulations and immune simulation studies reflected its potent cytosolic stability and robust immune response dynamics induced by the vaccine. Conclusion: This study explored an innovative structure-guided approach in the use of immunoinformatics and reverse vaccinology in pursuit of a novel multi-epitope vaccine against the highly immunogenic monkeypox viral proteins. The simulation studies indicated the engineered vaccine candidate to be promising in providing prophylaxis to the monkeypox virus; nevertheless, further in vitro and in vivo investigations are required to prove its efficacy.

Fine mapping of qBK1.2, a major QTL governing resistance to bakanae disease in rice.

Bakanae disease caused by Fusarium fujikuroi is an emerging disease of rice causing losses in all rice-growing regions around the world. A BC2F2 population was developed by backcrossing the recurrent parent Pusa Basmati 1121 (PB1121) with the recombinant inbred line RIL28, which harbors a major quantitative trait locus (QTL) governing resistance to bakanae, qBK1.2. MassARRAY-based single-nucleotide polymorphism (SNP) assays targeting the genomic region of qBK1.2 helped in fine mapping the QTL to a region of 130 kb between the SNP markers rs3164311 and rs3295562 using 24 recombinants. In-silico mining of the fine-mapped region identified 11 putative candidate genes with functions related to defense. The expression analysis identified two significantly differentially expressed genes, that is, LOC_Os01g06750 and LOC_Os01g06870, between the susceptible genotype PB1121 and the resistant genotypes Pusa1342 and R-NIL4. Furthermore, the SNPs identified in LOC_Os01g06750 produced minor substitutions of amino acids with no major effect on the resistance-related functional motifs. However, LOC_Os01g06870 had 21 amino acid substitutions, which led to the creation of the leucine-rich repeat (LRR) domain in the resistant genotype Pusa1342, thereby making it a potential candidate underlying the major bakanae-resistant QTL qBK1.2. The markers used in the fine mapping program are of immense utility in marker-assisted breeding for bakanae resistance in rice.

Identification of high-affinity pyridoxal kinase inhibitors targeting cancer therapy: an integrated docking and molecular dynamics simulation approach.

Pyridoxal kinase (PDXK) is a vitamin B6-dependent transferase enzyme encoded by the PDXK gene, crucial for leukemic cell proliferation. Disruption of its activity causes altered metabolism and reduced levels of nucleotides and polyamines. PDXK and pyridoxal 5'-phosphate (PLP) are overexpressed in various carcinomas, making them promising targets for drug design against cancer. Targeting PDXK may hold promise as a therapeutic approach for cancer treatment. This study focused on discovering potential inhibitors that could selectively interrupt the binding of pyridoxal phosphate (PLP) to pyridoxal kinase (PDXK). A commercially available library of 7,28,747 natural and druglike compounds was virtually screened using a molecular docking approach to target the substrate binding pocket of PDXK. Six promising inhibitors were identified, and all-atom molecular dynamics simulations were conducted on the PDXK-ligand complexes for 100 ns to assess their binding conformational stability. The simulation results indicated that the binding of ZINC095099376, ZINC01612996, ZINC049841390, ZINC095098959, ZINC01482077, and ZINC03830976 induced a slight structural change and stabilized the PDXK structure. This analysis provided valuable information about the critical residues involved in the PDXK-PLP complex formation and can be utilized in designing specific and effective PDXK inhibitors. According to this study, these compounds could be developed as anticancer agents targeting PDXK as a potential candidate for further study.Communicated by Ramaswamy H. Sarma.

Ufmylation of UFBP1 Is Dispensable for Endoplasmic Reticulum Stress Response, Embryonic Development, and Cardiac and Intestinal Homeostasis.

Protein modification by ubiquitin fold modifier 1 (UFM1), termed ufmylation, regulates various physiological and pathological processes. Among emerging UFM1 targets, UFM1 binding protein 1 (UFBP1) is the first identified ufmylation substrate. Recent clinical and animal studies have demonstrated the pivotal roles of UFBP1 in development, hematopoiesis, intestinal homeostasis, chondrogenesis, and neuronal development, which has been linked to its function in maintaining endoplasmic reticulum (ER) homeostasis. However, the importance of UFBP1 ufmylation in these cellular and physiological processes has yet to be determined. It has been proposed that ufmylation of lysine 268 (267 in humans) in UFBP1 plays a critical role in mediating the effects of the ufmylation pathway. In this study, we for the first time probe the pathophysiological significance of UFBP1 ufmylation in vivo by creating and characterizing a mouse UFBP1 knockin (KI) model in which the lysine 268 of UFBP1, the amino acid accepting UFM1, was mutated to arginine. Our results showed that the K268R mutation reduced the total ufmylated proteins without altering the expression levels of individual ufmylation enzymes in mouse embryonic fibroblasts. The K268R mutation did not alter ER stress-stimuli-induced ER stress signaling or cell death in mouse embryonic fibroblasts. The homozygous KI mice were viable and morphologically indistinguishable from their littermate wild-type controls up to one year of age. Serial echocardiography revealed no cardiac functional impairment of the homozygous KI mice. Furthermore, the homozygous KI mice exhibited the same susceptibility to dextran sulfate sodium (DSS) -induced colitis as wild-type mice. Taken together, these results suggest that UFBP1 K268 is dispensable for ER stress response, embryonic development, cardiac homeostasis under physiological conditions, and intestinal homeostasis under pathological conditions. Our studies call for future investigations to understand the biological function of UFBP1 ufmylation and offer a new mouse model to determine the roles of UFBP1 ufmylation in different tissues under stress conditions.

Phylogenomic Analysis of micro-RNA Involved in Juvenile to Flowering-Stage Transition in Photophilic Rice and Its Sister Species.

Vegetative to reproductive phase transition in phototropic plants is an important developmental process and is sequentially mediated by the expression of micro-RNA MIR172. To obtain insight into the evolution, adaptation, and function of MIR172 in photophilic rice and its wild relatives, we analyzed the genescape of a 100 kb segment harboring MIR172 homologs from 11 genomes. The expression analysis of MIR172 revealed its incremental accumulation from the 2-leaf to 10-leaf stage, with maximum expression coinciding with the flag-leaf stage in rice. Nonetheless, the microsynteny analysis of MIR172s revealed collinearity within the genus Oryza, but a loss of synteny was observed in (i) MIR172A in O. barthii (AA) and O. glaberima (AA); (ii) MIR172B in O. brachyantha (FF); and (iii) MIR172C in O. punctata (BB). Phylogenetic analysis of precursor sequences/region of MIR172 revealed a distinct tri-modal clade of evolution. The genomic information generated in this investigation through comparative analysis of MIRNA, suggests mature MIR172s to have evolved in a disruptive and conservative mode amongst all Oryza species with a common origin of descent. Further, the phylogenomic delineation provided an insight into the adaptation and molecular evolution of MIR172 to changing environmental conditions (biotic and abiotic) of phototropic rice through natural selection and the opportunity to harness untapped genomic regions from rice wild relatives (RWR).

High resolution mapping of QTLs for fruit color and firmness in Amrapali/Sensation mango hybrids.

Introduction: Mango (Mangifera indica L.), acclaimed as the 'king of fruits' in the tropical world, has historical, religious, and economic values. It is grown commercially in more than 100 countries, and fresh mango world trade accounts for ~3,200 million US dollars for the year 2020. Mango is widely cultivated in sub-tropical and tropical regions of the world, with India, China, and Thailand being the top three producers. Mango fruit is adored for its taste, color, flavor, and aroma. Fruit color and firmness are important fruit quality traits for consumer acceptance, but their genetics is poorly understood. Methods: For mapping of fruit color and firmness, mango varieties Amrapali and Sensation, having contrasting fruit quality traits, were crossed for the development of a mapping population. Ninety-two bi-parental progenies obtained from this cross were used for the construction of a high-density linkage map and identification of QTLs. Genotyping was carried out using an 80K SNP chip array. Results and discussion: Initially, we constructed two high-density linkage maps based on the segregation of female and male parents. A female map with 3,213 SNPs and male map with 1,781 SNPs were distributed on 20 linkages groups covering map lengths of 2,844.39 and 2,684.22cM, respectively. Finally, the integrated map was constructed comprised of 4,361 SNP markers distributed on 20 linkage groups, which consisted of the chromosome haploid number in Mangifera indica (n =20). The integrated genetic map covered the entire genome of Mangifera indica cv. Dashehari, with a total genetic distance of 2,982.75 cM and an average distance between markers of 0.68 cM. The length of LGs varied from 85.78 to 218.28 cM, with a mean size of 149.14 cM. Phenotyping for fruit color and firmness traits was done for two consecutive seasons. We identified important consistent QTLs for 12 out of 20 traits, with integrated genetic linkages having significant LOD scores in at least one season. Important consistent QTLs for fruit peel color are located at Chr 3 and 18, and firmness on Chr 11 and 20. The QTLs mapped in this study would be useful in the marker-assisted breeding of mango for improved efficiency.

Repurposing of drugs against methyltransferase as potential Zika virus therapies.

In recent years, the outbreak of infectious disease caused by Zika Virus (ZIKV) has posed a major threat to global public health, calling for the development of therapeutics to treat ZIKV disease. Several possible druggable targets involved in virus replication have been identified. In search of additional potential inhibitors, we screened 2895 FDA-approved compounds using Non-Structural Protein 5 (NS5) as a target utilizing virtual screening of in-silco methods. The top 28 compounds with the threshold of binding energy -7.2 kcal/mol value were selected and were cross-docked on the three-dimensional structure of NS5 using AutoDock Tools. Of the 2895 compounds screened, five compounds (Ceforanide, Squanavir, Amcinonide, Cefpiramide, and Olmesartan_Medoxomil) ranked highest based on filtering of having the least negative interactions with the NS5 and were selected for Molecular Dynamic Simulations (MDS) studies. Various parameters such as RMSD, RMSF, Rg, SASA, PCA and binding free energy were calculated to validate the binding of compounds to the target, ZIKV-NS5. The binding free energy was found to be -114.53, -182.01, -168.19, -91.16, -122.56, and -150.65 kJ mol-1 for NS5-SFG, NS5-Ceforanide, NS5-Squanavir, NS5-Amcinonide, NS5-Cefpiramide, and NS5-Ol_Me complexes respectively. The binding energy calculations suggested Cefpiramide and Olmesartan_Medoxomil (Ol_Me) as the most stable compounds for binding to NS5, indicating a strong rationale for their use as lead compounds for development of ZIKV inhibitors. As these drugs have been evaluated on pharmacokinetics and pharmacodynamics parameters only, in vitro and in vivo testing and their impact on Zika viral cell culture may suggest their clinical trials on ZIKV patients.