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.

Unlocking the Immunomodulatory Potential of Rosmarinic Acid Isolated from Punica granatum L. using Bioactivity-Guided Approach: In Silico, In Vitro, and In Vivo Approaches.

BACKGROUND: Punica granatum L. is well-known for its multifaceted therapeutic potential, including anti-inflammatory and immunomodulatory activities. AIM: This study aimed to characterize an immunomodulatory compound isolated from Punica granatum L. using a bioactivity-guided approach. METHODS: Chromatographic techniques were adopted for isolation and purification of secondary metabolites. In silico, in vitro, and in vivo methods were performed to characterize the therapeutic potential of the isolated compound. RESULTS: Using preparative thin-layer chromatography, rosmarinic acid was isolated from F4 (column chromatography product obtained from a butanolic fraction of the extract). The impact of rosmarinic acid was assessed in rats using the neutrophil adhesion test, DTH response, and phagocytic index. In immunized rats, rosmarinic acid demonstrated significant immunomodulatory potential. Computational experiments, like molecular docking and molecular dynamics, were also conducted against two targeted receptors, Cereblon (PDB ID: 8AOQ) and human CD22 (PDB ID: 5VKM). Computational studies suggested that an increase in phagocytic index by rosmarinic acid could be attributed to inhibiting Cereblon and CD22. Pharmacokinetics and toxicity prediction also suggested the drug-likeness of rosmarinic acid. CONCLUSION: Rosmarinic acid is a potential candidate, but extensive research needs to be done to translate this molecule from bench to bedside.

Functional allele of a MATE gene selected during domestication modulates seed color in chickpea.

Seed color is one of the key target traits of domestication and artificial selection in chickpeas due to its implications on consumer preference and market value. The complex seed color trait has been well dissected in several crop species; however, the genetic mechanism underlying seed color variation in chickpea remains poorly understood. Here, we employed an integrated genomics strategy involving QTL mapping, high-density mapping, map-based cloning, association analysis, and molecular haplotyping in an inter-specific RIL mapping population, association panel, wild accessions, and introgression lines (ILs) of Cicer gene pool. This delineated a MATE gene, CaMATE23, encoding a Transparent Testa (TT) and its natural allele (8-bp insertion) and haplotype underlying a major QTL governing seed color on chickpea chromosome 4. Signatures of selective sweep and a strong purifying selection reflected that CaMATE23, especially its 8-bp insertion natural allelic variant, underwent selection during chickpea domestication. Functional investigations revealed that the 8-bp insertion containing the third cis-regulatory RY-motif element in the CaMATE23 promoter is critical for enhanced binding of CaFUSCA3 transcription factor, a key regulator of seed development and flavonoid biosynthesis, thereby affecting CaMATE23 expression and proanthocyanidin (PA) accumulation in the seed coat to impart varied seed color in chickpea. Consequently, overexpression of CaMATE23 in Arabidopsis tt12 mutant partially restored the seed color phenotype to brown pigmentation, ascertaining its functional role in PA accumulation in the seed coat. These findings shed new light on the seed color regulation and evolutionary history, and highlight the transcriptional regulation of CaMATE23 by CaFUSCA3 in modulating seed color in chickpea. The functionally relevant InDel variation, natural allele, and haplotype from CaMATE23 are vital for translational genomic research, including marker-assisted breeding, for developing chickpea cultivars with desirable seed color that appeal to consumers and meet global market demand.

Identification of synthetically tractable MERS-CoV main protease inhibitors using structure-based virtual screening and molecular dynamics potential of mean force (PMF) calculations.

The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is a potentially lethal infection that presents a substantial threat to health, especially in Middle East nations. Given that no FDA-approved specific therapy for MERS infection exists, designing and discovering a potent antiviral therapy for MERS-CoV is crucial. One pivotal strategy for inhibiting MERS replication is to focus on the viral main protease (Mpro). In this study, we identify potential novel Mpro inhibitors employing structure-based virtual screening of our recently reported Ugi reaction-derived library (URDL) consisting of cherry-picked molecules from the literature. The key features of the URDL library include synthetic tractability (1-2 pot synthesis) of the molecules scaffold and unexplored chemical space. The hits were ranked based on the docking score, MM-GBSA free energy of binding, and the interaction pattern with the active site residues. A molecular dynamics (MD) simulation study was performed for the first two top-ranked compounds to analyze the stability and free binding energy based on the molecular mechanics Poisson-Boltzmann surface area. The potential mean force calculated from the steered molecular dynamics (SMD) simulations of the hits indicates improved H-bond potential, enhanced conformational stability, and binding affinity toward the target, compared to the cocrystallized ligand. The discovered hits represent novel synthetically tractable scaffolds as potential MERS-CoV Mpro inhibitors.Communicated by Ramaswamy H. Sarma.

A Multi-Model Based Stability Analysis Employing Multi-Environmental Trials (METs) Data for Discerning Heat Tolerance in Chickpea (Cicer arietinum L.) Landraces.

Identifying a congenially targeted production environment and understanding the effects of genotype by environmental interactions on the adaption of chickpea genotypes is essential for achieving an optimal yield stability. Different models like additive main effect and multiplicative interactions (AMMI 1, AMM2), weighted average absolute scores of BLUPs (WAASB), and genotype plus genotype-environment (GGE) interactions were used to understand their suitability in the precise estimation of variance and their interaction. Our experiment used genotypes that represent the West Asia-North Africa (WANA) region. This trial involved two different sowing dates, two distinct seasons, and three different locations, resulting in a total of 12 environments. Genotype IG 5871(G1) showed a lower heat susceptibility index (HSI) across environments under study. The first four interactions principal component axis (IPCA) explain 93.2% of variations with significant genotype-environment interactions. Considering the AMMI stability value (ASV), the genotypes IG5862(G7), IG5861(G6), ILC239(G40), IG6002(G26), and ILC1932(G39), showing ASV scores of 1.66, 1.80, 2.20, 2.60, and 2.84, respectively, were ranked as the most stable and are comparable to the weighted average absolute scores of BLUPs (WAASB) ranking of genotypes. The which-won-where pattern of genotype plus genotype-environment (GGE) interactions suggested that the target environment consists of one mega environment. IG5866(G10), IG5865(G9), IG5884(G14), and IG5862(G7) displayed higher stability, as they were nearer to the origin. The genotypes that exhibited a superior performance in the tested environments can serve as ideal parental lines for heat-stress tolerance breeding programs. The weighted average absolute scores of BLUPs (WAASB) serve as an ideal tool to discern the variations and identify the stable genotype among all methods.

Patients' perception about polycystic ovarian syndrome (PCOS) in Sub-Himalayan region of India-A facility-based cross-sectional study.

Background: In modern times, metabolic disorders are most common and one of them is polycystic ovarian syndrome (PCOS) in women, which causes high morbidity and complications. PCOS has largely been a neglected and less researched area; however, it is gaining importance in recent times as PCOS is increasing as well as it can be prevented to a considerable extent. Methods: A cross-sectional study was conducted to assess knowledge among females in government hospitals in Northern India. Data were collected using a pretested structured questionnaire on 300 women (completed 270), selected by proportionate sampling technique, and admitted in government hospitals. Data were analyzed by SPSS version 23. Results: The results showed that the mean age of respondents was 33.02 ± 9.039 years, the mean age at menarche was 12.33 ± 2.13 years, and the mean of gravida status was 1.82 ± 0.78 years. Only half of the respondents had good knowledge about PCOS. Conclusion: This study suggests that efforts are needed to reinforce women's knowledge through setting-based awareness campaigns and health education in this context to enable them to identify and seek timely treatment and improve their quality of life.

"Never Judge a Book by its Cover"-The socio-cultural aspects of non-epileptic seizures in India-A case study.

"Health for All" will never be attained if sociocultural bias and pervasive hypocrisy are not eliminated. The patient mentioned in this case study had difficulty gaining access to health care for more than two decades. The seizure history was modified due to social pressure. The primary healthcare workers' ability to provide timely access to healthcare regardless of caste, religion, or gender, even in the most remote regions of the country, is of paramount importance. The patient was diagnosed with hypoparathyroidism and treated with calcium and vitamin D in high oral doses. The case also illustrates the significance of medical examination in preventing future difficulties in patients with presenile cataract.

A superior gene allele involved in abscisic acid signaling enhances drought tolerance and yield in chickpea.

Identifying potential molecular tags for drought tolerance is essential for achieving higher crop productivity under drought stress. We employed an integrated genomics-assisted breeding and functional genomics strategy involving association mapping, fine mapping, map-based cloning, molecular haplotyping and transcript profiling in the introgression lines (ILs)- and near isogenic lines (NILs)-based association panel and mapping population of chickpea (Cicer arietinum). This combinatorial approach delineated a bHLH (basic helix-loop-helix) transcription factor, CabHLH10 (Cicer arietinum bHLH10) underlying a major QTL, along with its derived natural alleles/haplotypes governing yield traits under drought stress in chickpea. CabHLH10 binds to a cis-regulatory G-box promoter element to modulate the expression of RD22 (responsive to desiccation 22), a drought/abscisic acid (ABA)-responsive gene (via a trans-expression QTL), and two strong yield-enhancement photosynthetic efficiency (PE) genes. This, in turn, upregulates other downstream drought-responsive and ABA signaling genes, as well as yield-enhancing PE genes, thus increasing plant adaptation to drought with reduced yield penalty. We showed that a superior allele of CabHLH10 introgressed into the NILs improved root and shoot biomass and PE, thereby enhancing yield and productivity during drought without compromising agronomic performance. Furthermore, overexpression of CabHLH10 in chickpea and Arabidopsis (Arabidopsis thaliana) conferred enhanced drought tolerance by improving root and shoot agro-morphological traits. These findings facilitate translational genomics for crop improvement and the development of genetically tailored, climate-resilient, high-yielding chickpea cultivars.