The growing challenges of antibiotic resistance and cancer highlight the need for new bioactive compounds from unexplored ecological niches. This study investigates the gut microbiome of the earthworm Eisenia fetida as a source of fungal metabolites with potential therapeutic value. Four fungal species were isolated from the earthworm gut, and their extracts were screened for antimicrobial and anticancer activities. A key bioactive molecule, comenic acid (HE-1), was isolated from Mycothermus thermophilus extract (HF-3) and demonstrated moderate cytotoxicity against prostate cancer cells (IC50 9.92 mu g/mL). In addition, a triglyceride-based compound (DC-2) was isolated from the same fungal extract; however, its functional roles and bioactivities remain to be explored. These findings support E. fetida as a promising source of bioactive fungal metabolites and emphasize the potential of earthworm-associated microbiomes in natural product discovery. Further investigations are required to characterize additional metabolites and evaluate their biological and ecological relevance.

Abstract Cytochrome P450 monooxygenases (CYP450s) are key oxidative enzymes that diversify plant specialized metabolites and play a central role in the biosynthesis of bioactive withanolides in Withania somnifera (L.) Dunal. Despite their importance, genome-wide information on CYP450s in W. somnifera has remained elusive. Herein, the first high-quality genome assembly (2.2 Gb, scaffold N50: 47.4 kb) of an Indian W. somnifera cultivar was generated using a hybrid Oxford Nanopore-Illumina sequencing strategy. Comparative analysis with the NCBI reference genome revealed moderate SNP and indel variations, reflecting intraspecific genetic diversity. A comprehensive CYP450 catalog was established and analyzed phylogenomically across nine plant genomes, encompassing both withanolide-producing and non-producing Solanaceae and non-Solanaceae species. Unique CYP families (CYP450A, CYP1194, and CYP705A) were detected exclusively in W. somnifera, suggesting lineage-specific metabolic innovations, while Solanaceae-restricted (CYP82E/M) and absent (CYP81B, CYP6) lineages highlight taxonomic divergence. Across all analyzed genomes, 36 conserved CYP450 subfamilies, including triterpenoid-associated members, were identified, suggesting a shared oxidative framework adaptable to specialized metabolism. Moreover, potential candidate genes in the triterpenoid pathway, including CYP72A692_1, CYP72A560_4, CYP716A48, CYP724B2, and CYP51G1, were identified through phylogenetic integration with functionally validated triterpenoid-modifying enzymes from other plant species. Gene family evolution analysis further revealed contraction of monoterpenoid-related subfamilies (CYP76A), implying a metabolic shift toward triterpenoid specialization. The comprehensive genome assembly and CYPome of W. somnifera offer a valuable resource for functional characterization, evolutionary analysis, and the identification of genes underlying its specialized metabolism. Furthermore, the study advances our understanding of CYP450 diversity and evolution, revealing lineage-specific innovations, conserved subfamilies, and key candidate genes involved in triterpenoid biosynthesis. Together, these findings lay a foundation for future functional studies and pathway engineering aimed at optimizing the metabolic potential of this important medicinal plant.

Freshwater unionid mussels are ecologically important yet genomically underrepresented relative to marine bivalves. Field surveys conducted across two freshwater streams indicated that Lamellidens corrianus was consistently abundant and widely distributed, motivating its selection for genome-level characterization. We present a draft genome assembly of the freshwater mussel Lamellidens corrianus and characterize its sequence-level genomic features. The 1.41 Gb draft genome assembly, while fragmented (N50 = 1816 bp), captures an overall AT content of 64.82%, while predicted coding sequences showed approximately 57% AT content. Functional annotation of high-confidence gene models revealed representation of conserved pathways related to translation, metabolism, cytoskeletal organization, stress response, and DNA repair, confirming representation of core molecular systems. Codon usage bias (CUB) was evaluated using ENC, CAI, CBI, correspondence analysis, neutrality plots, PR2, ENC-GC3 analysis, and correlation tests. A mean ENC value of 48.9 suggests relatively weak synonymous codon usage bias accompanied by preference for A/U ending codons. Neutrality and ENC-GC3 analyses (slope = 0.1023) indicate that codon usage patterns reflect a mutation-selection balance in which nucleotide composition exerts primary influence with secondary mutational contributions. Comparative RSCU analysis across marine and freshwater bivalves revealed broadly conserved synonymous patterns, with lineage-associated differences in selected codons. Amino acid frequencies were highly conserved, characterized by enrichment of six-fold degenerate residues and consistent prevalence of leucine and scarcity of tryptophan. Orthogroup analysis of predicted proteins identified 959 clusters, with interpretation constrained by assembly fragmentation. These results demonstrate that draft genome assemblies can provide informative insights into compositional bias, codon architecture, and comparative gene content, establishing L. corrianus as a compositional and translational baseline for freshwater unionid research.

Gut-associated fungal endofauna confronted with stressful conditions have the potential to secrete diverse bioactive metabolites. In this context, the present study aims to uncover the hidden metabolite profiling of less explored fungal gut parasites associated with rhizosphere nematodes of Withania somnifera. The nematode Xiphinema nuragicum, predominantly found in W. somnifera rhizosphere, was explored for its gut endofauna. This study represents the first report on the isolation of X. nuragicum from the rhizosphere of W. somnifera and the exploration of endofauna inhabiting the gut of X. nuragicum. Among different fungal isolates inhabiting the gut of X. nuragicum, Fusarium fujikuroi (R3) was found to be the most potent isolate and was therefore selected for the isolation and identification of its active metabolites. Three compounds were characterized from F. fujikuroi, namely di (2-ethylhexyl) phthalate (DEHP), 2,5-bis(1,1-dimethylethyl) phenol, and 1,4-di-tert-butyl-2-chlorobenzene. The compounds exhibited strong cytotoxic and anti-inflammatory activities with potential therapeutic applications. The present study also revealed the bioremediation potential of X. nuragicum, hosting F. fujikuroi already known for its ability to eliminate environmental pollutants such as DEHP and polycyclic aromatic hydrocarbons (PAHs). Despite these promising findings, in-depth mechanistic studies would be the future perspective of the current study.

This study investigates the complex host-parasite interactions between Unionicola mites and freshwater mussels, focusing on infestation patterns across four mussel species from two river streams. Furthermore, this study explores the metabolic adaptations of a parasitic mite infesting Himalayan freshwater mussels, focusing on producing the macromolecule 13-cis-docosenamide.Lamellidens corrianus emerged as the primary host, with environmental and morphometric factors influencing infestation dynamics. Using combined morphological and molecular taxonomy, the mites were identified as Unionicola (Myanmaratax) savadiensis, and their biochemical adaptations were explored. Metabolomics profiling highlighted the presence of 13-cis-docosenamide in gill-associated mites, indicating a potential host-specific adaptation. This compound is novel to mites and suggests a unique interaction with the host's chemical environment. GC-MS profiling of mussels stated the presence of the precursor docosenoic acid but not the final compound, supporting the hypothesis that mites synthesize 13-cis-docosenamide from host-derived precursors. The absence of this compound in mites from accidental hosts further highlights the specificity of this metabolic adaptation. Additionally, other isolated compounds were identified as polymer additives, which are known for their toxic and endocrine-disrupting properties, exacerbating ecological threats to mussel populations. This study highlights the dual ecological pressures of parasitism and the dynamics of these organisms, advancing our understanding of freshwater ecosystems and their threats.

Over the past decade, accumulating evidence has shed light on the pivotal roles played by diverse classes of noncoding RNAs, including miRNAs, siRNAs, piRNAs, lncRNAs, and circRNAs, in regulating the plant growth and development. In-depth studies have revealed the regulatory functions of miRNAs and siRNAs in post-transcriptional gene regulation, highlighting their involvement in various developmental processes, stress responses, and hormone signaling pathways. Additionally, the emerging field of piRNAs has unveiled their crucial contributions to transposon silencing, genome stability maintenance, and reproductive development. The versatility of lncRNAs as regulators in chromatin remodeling, splicing regulation, and epigenetic modifications has been elucidated, alongside the functional significance of circular RNAs in alternative splicing regulation and gene expression control. Overall, this review article presents a significant advancement in our understanding of the intricate regulatory networks governing plant biology, with the potential to drive innovations in plant biotechnology, sustainable agriculture, and global food security.

Tuberculosis (TB) is an international public health problem that results in preventable deaths each year. About 10

Genus Plantago of Plantaginaceae family is bestowed with a repertoire of structurally diverse secondary metabolites that have not only been used as therapeutics but also effect the plant physiology by conferring adaptive advantages under stress. Assuming that domestication process in plants has influenced their secondary metabolites, we performed a comparative transcriptome of wild and cultivated species of Plantago to analyze the variation in the expression of genes related to secondary metabolite pathways. GO and KEGG analysis of DEGs in wild species showed their enrichment in abiotic stresses, oxidation–reduction and secondary metabolite related pathways. Overall, we found upregulation of genes of carotenoid, flavonoid and phenylpropanoid, isoprenoid, terpenoid and alkaloid pathways in wild species of Plantago in particular, P. lanceolata while mucilage pathway-related genes showed higher expression in P. ovata. Moreover, transcriptome data presented putative transcription factors associated with terpenoids, carotenoid and phenylpropanoid biosynthetic pathways which were also identified using co-expression analysis of cluster 9 (secondary metabolite enriched gene cluster). Taken together, the genomic resource obtained from the present study form a valuable repository of genetic information for elucidating and exploring the secondary metabolic circuitry of Plantagos. Further, information on the regulatory aspects of genes related to secondary metabolites, shall aid in the enhanced production of valuable metabolites in these plants.

Wild pomegranate is a potent medicinal plant known for its medicinal and nutritional attributes. Despite its healing and curative properties, the genome of this wild species remains elusive, thus limiting our understanding on the genetic processes involved in the biosynthesis of functional molecules. This study presents the annotation of a de novo genome assembly of wild pomegranate, with a genome size of 279.0 Mb. From the assembly, 34.8 GB of the data was retained, encompassing 72,055 scaffolds. A total of 49,178 genes were predicted, with an average of 5.36 exons per gene and a GC content of 49

Fungal endophytes are valued for biosynthesizing chemically diverse metabolic cascade with interesting biological activities. In the current investigation, two compounds were isolated from Penicillium polonicum, an endophyte of Zingiber officinale. The active moieties, glaucanic acid (1) and dihydrocompactin acid (2) were isolated from the ethyl acetate extract of P. polonicum and characterized by NMR and mass spectroscopy. Further, bioactive potential of the isolated compounds was evaluated by antimicrobial, antioxidant and cytotoxicity assays. Compounds 1 and 2 displayed antifungal activity against phytopathogen Colletotrichum gloeosporioides with more than 50% reduction in its growth. Both the compounds exhibited antioxidant activity against free radicals (DPPH and ABTS) and cytotoxicity activity against cancer cell lines respectively. The compounds, glaucanic acid and dihydrocompactin acid are being reported for the first time from an endophytic fungus. This is the first report on the biological activities of Dihydrocompactin acid produced by endophytic fungal strain.

This study explores the prevalence, distribution, and codon usage bias of nematode species, primarily Heterodera glycines and Heterodera avenae, within saffron corms. Nematode analysis identified H. glycines and H. avenae as the predominant species. Geographical locations exhibited distinct cyst infestation levels, with H. avenae showing higher prevalence. The study reveals the preference of these nematodes for saffron corms, raising concerns for saffron production and suggesting the implementation of monitoring and management strategies. Additionally, the study analyzes the codon usage bias (CUB) of saffron and its associated nematode pathogens. Codon usage bias analysis revealed an AT bias in Crocus sativus and its pathogens. Codon Adaptation Index (CAI) values suggested pathogen adaptation to the host. Correlation analysis highlighted the interplay of nucleotide composition, mutational pressure, and natural selection in codon usage patterns. Amino acid frequency and codon context analyses provided insights into evolution and physiological functions. Furthermore, the study observed a mutual codon preference between the host and pathogens for certain amino acids, highlighting specific interactions at the molecular level. This study provides valuable information for understanding the molecular biology of plant-nematode interactions, and its findings can be useful for developing effective management strategies against these pests in saffron production and other crops such as crop rotation, use of resistant cultivars, and application of nematode-suppressive amendments.

BACKGROUND AND OBJECTIVES:Cadherin13 (CDH13) is an uncommon cadherin family member, lacking a transmembrane domain, and attaches via a glycosylphosphatidylinositol anchor to the peripheral surface of the cell membrane. CDH13 plays an important role in the development and maintenance of axonal growth cones, synapse morphogenesis, and the embryonic neural tube. Cadherin superfamily genes have been associated with many neuropsychiatric diseases. Studies have shown the Cadherin13 gene as a risk locus for Schizophrenia (SCZ). In this study, we investigated CDH13 gene variants rs7204454 in the promotor region and rs9940180 in the intronic region of the gene with susceptibility to SCZ risk in the population of Jammu region of J&K, India.METHODS:The genotyping was performed using TaqMan assay, where 560 individuals, comprising 164 patients and 396 healthy controls, were genotyped.RESULTS:The result of the study suggested rs9940180 was significantly found to be associated with Schizophrenia and the "C" allele of rs9940180 was associated with increased risk for SCZ (P = 0.03817; OR = 1.527; 95% CI, 1.022-2.28) whereas the other variant rs7204454 of CDH13 gene did not show significant association with schizophrenia risk with P = 0.8827, OR = 0.582-1.33 at 95% CI.CONCLUSION:This is the first report suggesting a significant association of polymorphism at CDH13 rs9940180 with Schizophrenia in the Dogra population group of the Jammu region. The current study offers a piece of important information on the genetic reason for CDH13 in the Jammu population of J&K. Also, it supports the GWAS findings on the correlation of CDH13 in schizophrenia.

The present study investigates the phenomenon of codon usage bias (CUB) in Meloidogyne incognita, a parasitic nematode that infests plants. It explores the patterns of CUB, the factors that influence it, and its correlation with gene expression. Understanding codon usage bias in M. incognita is important for developing effective strategies for controlling nematode infections in plants. The results indicated a weak CUB in M. incognita, with an overall AT bias in the genome. The analysis of relative synonymous codon usage (RSCU) revealed that preferred and high-frequency codons mostly ended with G/C, indicating the influence of compositional constraints on codon usage. Further analysis using ENC plot, PR2 plot, Neutrality plot, and correspondence analysis suggested that natural selection and mutation pressure both played a role in observed CUB, with mutation pressure being the decisive factor. Amino acid composition analysis showed that glycine was the most frequently used amino acid, while histidine was the least utilized. Interestingly, the study found a negative correlation between codon usage and gene expression in M. incognita. Overall, this study provides a comprehensive understanding of codon usage bias in M. incognita and highlights its potential implications for gene expression and pathogenesis in plants by understanding preferred, avoided, and unique codons, which could further aid in the development of effective strategies for controlling nematode infections.

Codon usage bias (CUB) is a ubiquitous phenomenon perseveres in genome of all the organisms. It impinges the gene expression and other genetic intricacies within a genome. The present study explains the pattern of codon usage in the protein coding sequence of Crocus sativus and its relation with gene expression. Gene expression analysis in C. sativus showed genes with high expression had a preference of G base at third position. CUB had an inverse relation with gene expression. Coding sequences with effective number of codons (ENC) < 50 had low Fragments Per Kilobase Million (FPKM) value while low codon bias group ENC >50 possessed high FPKM value. The low tAI values showed the low translation efficiency of genes in C. sativus. The non-significant MILC-based expression level predictor (MELP) and ENC correlation analysis suggested that expression of genes might not be associated with codon usage bias. ENC and PR-2 plot revealed mutation pressure and natural selection played role in shaping Codon usage patterns. However, neutrality plot conclusively depicted the dominance of natural selection in regulating the configuration of codons in all the selected species. In addition, the role of Codon usage bias regarding the predilection of fungal pathogens Aspergillus fumigatus, Fusarium oxysporum, Aspergillus niger and Aspergillus flavus towards host plant C. sativus has also been expounded. We found a similar trend of codon usage operative in plant and fungal pathogens as all the fungal pathogens and host plant showed similar GC rich genomic content as well as preference for GC ending codons at third codon position. This concurrence might be attributed for the colonization of fungal pathogens in C. sativus. Overall, different indices reflected a weak codon bias in the C. sativus, and its associated pathogens.

Background and objective: Schizophrenia (SCZ) is a severe mental biological disorder with a multifactorial manner of transmission and inheritance associated with environmental, developmental, and genetic set-off. It is a heritable disorder that involves genes and metabolic mechanisms in a combined effect, each conferring a small increase in the overall disease burden. Its etiology is not fully understood, although recent studies showed a relationship between SCZ and inflammation. Evidence from various studies indicates that dysregulation of TLR genes may have a role in the physiopathology of schizophrenia. In the present study, 4 polymorphisms, each in TLR1, TLR2, TLR4, and TLR6, were studied to explore their role in susceptibility to SCZ in the Dogra population of the Jammu region. Methods: Five hundred (500) individuals including 200 SCZ and 300 healthy controls were included in the study. DNA was isolated and Sanger's sequencing was performed after PCR amplification. Results: Statistically significant association of TLR2 (rs3804099) was observed in the study population, the C allele of rs3804099 is associated with the increased risk for SCZ (OR=2.667; [1.4196 -5.0093 at 95%CI] P = 0.0023). No statistically significant associations with SCZ were observed in the target population at TLR1, TLR4, and TLR6. Conclusion: Study concludes that TLR2 (rs3804099) may be associated with schizophrenia in the targeted population. Advance studies can be carried out focusing on finding potential SNPs for establishing a candidate gene approach. (c) 2022 Asociacion Universitaria de Zaragoza para el Progreso de la Psiquiatria y la Salud Mental. Published by Elsevier Espana, S.L.U. All rights reserved.

With the increasing accumulation of genomic sequence information of echinoderms, the study of codon usage bias has gained renewed attention. The purpose of this study was to examine codon selection pattern among three echinoderm species Heliocidaris erythrogramma (Sea urchin), Apostichopus japonicus (Sea cucumber) and Asterias rubens (Star fish) belonging to similar habitats. We performed detailed comparative analysis of echinodermal genomes with respect to codon bias. Our analysis reflects that the genome of H. erythrogramma and A. rubens was found to be GC rich, whereas the genome of A. japonicus was found to be AT rich. The RSCU (Relative usage of synonymous codons) analysis revealed dominance of A- and/or C-ending codons in H. erythrogramma and A. rubens while A- and/or U-ending codons were preferred in A. japonicus. Overall, a weak codon bias was prevailed in all the three genomes of selected echinoderm species. The main influencing elements in developing codon usage bias (CUB) appeared to be mutational pressure and natural selection. Despite sharing the same ecological habitat and functional features, CUB analysis revealed a close relationship between H. erythrogramma and A. rubens among the three Echinoderm species chosen for this study. The present study will be helpful in understanding the genetic features prevalent in Echinoderms and would lay a foundation for future research on other Echinoderm species.

Abstract Codon usage bias (CUB) is a ubiquitous phenomenon perseveres in genome of all the organisms. It impinges the gene expression and other genetic intricacies within a genome. The present study explicates the pattern of codon usage in the protein coding sequence of Crocus sativus and its relation with gene expression. Gene expression analysis in C. sativus showed genes with high expression had a preference of G base at third position. CUB had an inverse relation with gene expression. Coding sequences with ENC < 50 had low FPKM value while low codon bias group (ENC > 50) possessed high FPKM value. The low tAI values showed the low translation efficiency of genes in C. sativus. The non-significant MELP and ENC correlation analysis suggested that expression of genes might not be associated with CUB. ENC and PR-2 plot revealed mutation pressure and natural selection played role in shaping CUB. However, neutrality plot conclusively depicted the dominance of natural selection in regulating the configuration of codons in all three species. In addition, the role of CUB regarding the predilection of fungal pathogens Aspergillus fumigatus and Fusarium oxysporum towards host plant C. sativus has also been expounded. We found a similar trend of codon usage pattern operative in plant and fungal pathogens as both the fungal pathogens and host plant showed similar GC rich genomic content as well as preference for GC ending codons at third codon position. This concurrence might be attributed for the colonization of fungal pathogens in C. sativus. Overall, different CUB indices reflected a weak codon bias in the C. sativus, F. oxysporum and A. fumigatus genome.

Abstract Bioinformatic approaches were utilized to investigate the pattern of codon usage in 109 epilepsy-related genes. The genes were found to be rich in G and C nucleotides, with GC usage 7% higher than AT. Preferred codon analysis confirmed the dominance of G and C at the wobble position of codons. CAG is the most frequently used codon. The ENc analysis, on the other hand, did not reveal any exceptional codon usage bias. Correlation of GC content at the first and second codon positions with the third codon position (neutrality plot) suggested the impact of selection pressure in shaping the GC enriched compositional pattern observed in epilepsy-related genes. It was further confirmed by correspondence analysis. Altogether, our findings imply that the pattern of evolutionary processes (especially selection pressure) operating on epilepsy-related genes. This might aid in identifying disease genes compositional signatures and deciphering the genetic mechanisms underlying epilepsy. Further this information would be useful in facilitating the existing epilepsy related therapies like gene therapy, cell therapy etc.

Aim: The aim of the present study was to understand the molecular relationship between nematode (parasite) and fish (host) through codon usage bias (CUB) analysis. Methodology: The Codon usage bias analysis has been performed in fish Carassius gibelio (Prussian carp) and nematode fish parasite Anisakis simplex. The complete coding sequences (CDS) of C. gibelio (Prussian carp) and A. simplex (Nematode) were retrieved from National Center for Biotechnology Information and followed to that we have performed bioinformatics analysis to understand the codon usage pattern between host and parasite. Results: Different CUB indices like Relative synonymous codon usage (RSCU), Effective number of codons (ENC), Codon adaptation index (CAI) and Codon bias index (CBI) revealed a similar pattern in the codon usage in C. gibelio and A. simplex. In addition, inclusive analysis using different plots (ENC, parity, neutrality) had shown the influence of both the evolutionary forces i.e mutational and translational selection on codon usage pattern. This describes the role of evolutionary forces in determining the conserved genome to establish species-specific function-level differences for efficient survival. Interpretation: The present study elucidated the association between Carassiusgibelio (host) and Anisakis simplex (parasite) based on the similar pattern of codon usage bias between both the species.

Circular RNAs (circRNAs) are endogenous RNA formed by the back splicing process. They are ubiquitous, stable, evolutionally conserved, and are tissue-specific. The biochemical and molecular features of circRNAs hold the potential to be used as biomarkers in various diseases to achieve pharmacological goals. CircRNAs have numerous latent modes of action, from acting as sponges for microRNAs and RNA binding proteins to serve as transcriptional regulators, epigenetic alterations, etc. Dysregulated functioning of several circular RNAs lead to the progression of a plethora of diseases. Due to their extremely stable nature and amazing tissue specificity, circRNAs have paved the way for advanced clinical studies as a novel method of early disease detection and treatment efficacy. Therefore, they have been recognized as a latent diagnostic biomarker for neurodegenerative diseases, diabetes, osteoarthritis, and cardiovascular diseases.