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Roychowdhury, T.

Publications and source records attributed to Roychowdhury, T..

7 recordsLinked to original sources

Temperature-dependent biofilm and sublancin production immobilise arsenic and antibiotic resistance gene mobility in soil system

Climate change-induced warming and arsenic soil contamination synergistically threaten agricultural sustainability by restructuring microbial communities and accelerating antibiotic resistance evolution. Here, we demonstrate that Bacillus subtilis 168-derived sublancin, a temperature-optimised glycosylated antimicrobial peptide, simultaneously maximises microbial arsenic sequestration and suppresses antibiotic resistance gene (ARG) horizontal transfer. Temperature-dependent biofilm formation increased progressively from 25-35{degrees}C (absorbance: 0.37-1.2), correlating with enhanced arsenic accumulation within the extracellular polymeric substance matrix (74% increase in weight percentage). Time-of-flight secondary ion mass spectrometry confirmed maximum arsenic sequestration at 35{degrees}C (total counts: 4.725x10). Sublancin production peaked at 30.8{degrees}C (129.72 mg/L) and significantly reduced soil microbial biomass carbon by 33% (p < 0.001), with selective suppression of Gram-positive bacteria (42%-28% survival reduction). Conjugation assays revealed sublancin bio-amendment dramatically suppressed horizontal ARG transfer, reducing HGT frequency by 74.7% (6.64 x 10-3 to 1.68 x 10-3, p < 0.001) through dual mechanisms: decreased donor viability and reduced conjugation efficiency. Gene ontology enrichment identified coordinated upregulation of exopolysaccharide synthesis (FDR ~1.0x10-{superscript 2}), phosphotransferase systems, and arsenic resistance pathways, alongside downregulation of conventional antibiotic resistance genes. These findings establish sublancin as a dual-function soil amendment simultaneously addressing two critical agricultural threats: heavy metal bioaccumulation and antibiotic resistance dissemination under climate warming.

microbiology↗

Molecular Insights Into PGPR-Biochar-Mediated Arsenic Detoxification and Nutritional Enhancement in Rice Rhizospheres

Arsenic (As) contamination in paddy soils threatens rice productivity and food safety through enhanced As(III) mobility under anaerobic conditions. This study evaluated the synergistic effects of rice biochar (RBC) and plant growth-promoting rhizobacteria (PGPR) on arsenic bioavailability and rice physiological responses under controlled and field conditions. Rice straw biochar pyrolyzed at 400 {degrees}C exhibited high porosity and surface functionality, while Metabacillus indicus AMB4 demonstrated arsenic tolerance ([&le;]3500 mg kg-1) and multiple PGPR traits (IAA: 45.2 g mL-1, phosphate solubilization index: 2.8, ACC deaminase: 18.7 nmol -ketobutyrate mg-1 h-1). Combined RBC+PGPR treatment reduced soil arsenic bioavailability by 85% (p<0.001) and plant arsenic accumulation by 78% compared to controls, while significantly enhancing antioxidant enzyme activities (CAT: 4.2-fold, SOD: 3.7-fold, APX: 3.1-fold increase). Metagenomics revealed restructured microbial communities with increased Proteobacteria abundance and upregulated arsenic detoxification genes (arsC, arsB, aioA) coupled with enhanced nutrient cycling pathways (nifH, phoD, soxA). Network analysis demonstrated functional integration between As-transformation and nutrient metabolism, with coordinated expression of 47 arsenic-responsive and 126 nutrient-cycling genes. Field trials confirmed superior plant performance with RBC+PGPR treatment yielding 56% more tillers and 73% more panicles than controls, while maintaining enhanced soil nutrient status. This integrated biochar-PGPR system provides a mechanistically robust approach for simultaneous arsenic remediation and crop productivity enhancement in contaminated rice ecosystems, demonstrating practical applicability for sustainable paddy agriculture.

microbiology↗

Furrow tillage reduces soil carbon loss and enhances microbial metabolism

With increasing global carbon loss from agricultural fields, agricultural practices should be monitored with proper regulatory measures. To address three problems of minimising carbon loss, optimising soil fertility and enhancing soil microbiota together, this study has developed a new innovative "Furrow tillage" approach that affords a balance between conventional and conservative tillage. Based on two years of trials in rice fields at multiple sites, this practice has justifications from agronomy, geochemistry, crop physiology, and molecular microbiology. Furrow tillage illustrated low carbon loss, similar to no-tillage, while retaining high nutrient bioavailability, similar to deep tillage. Microbial diversity, molecular responses and metabolic activities showed that furrow tillage induced microbial interactions while allowing a better entrapment of carbon dioxide in the soil. The study used CO2 flux, spatial distribution, total and available elemental analysis, plant ultra-structural observations, microbial metagenomics, high-throughput sequencing and molecular modelling to establish an optimal soil-crop quality, microbial maintenance and reduce carbon loss through furrow tillage practice.

ecology↗

In Silico designed cell-penetrating anti-cancer peptide specifically inhibits VEGF-A expression

Vascular Endothelial Growth Factor-A (VEGF-A), a pluripotent cytokine and angiogenic growth factor mediates the switch to an angiogenic phenotype in cancer cells. The interaction of VEGF-A protein with the VEGF receptors (VEGFR-1and VEGFR-2) starts downstream effect that promotes angiogenesis by mediating migration and increasing the permeability of endothelial cells. A cis-regulatory elements consisting of a polypurine/polypyrimidine (pPu/pPy) tract in the proximal 36-bp region (-85 to -50), can participate in the formation of a stable higher order G-quadruplex structure (G4) which is essential for VEGF promoter activity. During cancer progression the VEGF-A G4 succumbs to cellular pressure and fails to maintain the stable structure. This shifts the balance to form duplex structure thereby increasing the rate of transcription. Earlier research has tried to develop small-molecule ligands to target and stabilize G4, however they either lack specificity or non-toxicity. Peptide on the other hand are very less studied. Here we used bioinformatics in-silico tool to develop peptides which can successfully bind and stabilize the VEGF-A G4 while reducing its gene expression. This further alters the expression fate of the VEGF-A signalling cascade and prevents angiogenesis in cancer cells. We used high resolution Nuclear magnetic resonance and molecular dynamics simulation to map the chemistry of the interaction while the qPCR and western blot allowed us to check the expression pattern of the molecules of VEGF-A signalling cascade. In this investigation, we navigate the complex interplay between peptides and quadruplex structures, unravelling valuable insights that can enhance the crafting of pharmacophores directed at the dynamic quadruplex structure. The outcomes of our study are promising, paving the way for progress in the realms of research, characterization, and optimization of peptides binding to G-quadruplexes, with potential implications for therapeutic applications.

biophysics↗

ALTering cancer by triggering telomere replication stress through the stabilization of promoter G-quadruplex in SMARCAL1

Most of the human cancers are dependent on telomerase to extend the telomeres. But [~]10% of all cancers use a telomerase-independent, homologous recombination mediated pathway called alternative lengthening of telomeres (ALT). Due to poor prognosis, the ALT status is not being considered yet in the diagnosis of cancer. No such specific treatment is available till date for ALT cancers. ALT positive cancers are dependent on replication stress to deploy DNA repair pathways to the telomeres to execute homology recombination mediated telomere extension. SMARCAL1 (SWI/SNF related, matrix-associated, actin-dependent regulator of chromatin, subfamily A-like 1) is associated with the ALT telomeres to resolve replication stress thus providing telomere stability. Thus, the dependency on replication stress regulatory factors like SMARCAL1 made it a suitable therapeutic target for the treatment of ALT positive cancers. In this study, we found a significant downregulation of SMARCAL1 expression by stabilizing the G-quadruplex (G4) motif found in the promoter of SMARCAL1 by potent G4 stabilizers, like TMPyP4 and BRACO-19. SMARCAL1 downregulation led towards the increased localization of PML (promyelocytic leukaemia) bodies in ALT telomeres and triggered the formation of APBs (ALT-associated promyelocytic leukaemia bodies) in ALT positive cell lines, thus increasing telomere replication stress and DNA damage at genomic level. Induction of replication stress and hyper recombinogenic phenotype in ALT cells mediated by G4 stabilizing molecules already highlighted their possible application as a new therapeutic window to target ALT-positive tumors. In accordance with this, our study will also provide a valuable insight towards the development of G4 based ALT-therapeutics targeting SMARCAL1.

biochemistry↗

Loss-of-function genomic variants with impact on liver-related blood traits highlight potential therapeutic targets for cardiovascular disease

Cardiovascular diseases (CVD), and in particular cerebrovascular and ischemic heart diseases, are leading causes of death globally.1 Lowering circulating lipids is an important treatment strategy to reduce risk.2,3 However, some pharmaceutical mechanisms of reducing CVD may increase risk of fatty liver disease or other metabolic disorders.4,5,6 To identify potential novel therapeutic targets, which may reduce risk of CVD without increasing risk of metabolic disease, we focused on the simultaneous evaluation of quantitative traits related to liver function and CVD. Using a combination of low-coverage (5x) whole-genome sequencing and targeted genotyping, deep genotype imputation based on the TOPMed reference panel7, and genome-wide association study (GWAS) meta-analysis, we analyzed 12 liver-related blood traits (including liver enzymes, blood lipids, and markers of iron metabolism) in up to 203,476 people from three population-based cohorts of different ancestries. We identified 88 likely causal protein-altering variants that were associated with one or more liver-related blood traits. We identified several loss-of-function (LoF) variants reducing low-density lipoprotein cholesterol (LDL-C) or risk of CVD without increased risk of liver disease or diabetes, including variants in known lipid genes (e.g. APOB, LPL). A novel LoF variant, ZNF529:p.K405X, was associated with decreased levels of LDL-C (P=1.3x10-8) but demonstrated no association with liver enzymes or non-fasting blood glucose levels. Silencing of ZNF529 in human hepatocytes resulted in upregulation of LDL receptor (LDLR) and increased LDL-C uptake in the cells, suggesting that inhibition of ZNF529 or its gene product could be used for treating hypercholesterolemia and hence reduce the risk of CVD. Taken together, we demonstrate that simultaneous consideration of multiple phenotypes and a focus on rare protein-altering variants may identify promising therapeutic targets.

genomics↗

De novo genome and transcriptome analyses provide insights into the biology of the trematode human parasite Fasciolopsis buski

Many trematode parasites cause infection in humans and are thought to be a major public health problem. Their ecological diversity in different regions provides challenging questions on evolution of these organisms. In this report, we perform transcriptome analysis of the giant intestinal fluke, Fasciolopsis buski, using next generation sequencing technology. Short read sequences derived from polyA containing RNA of this organism were assembled into 30677 unigenes that led to the annotation of 12380 genes. Annotation of the assembled transcripts enabled insight into processes and pathways in the intestinal fluke, such as RNAi pathway and energy metabolism. The expressed kinome of the organism was characterized by identifying all protein kinases. We have also carried out whole genome sequencing and used the sequences to confirm absence of some of the genes, not observed in transcriptome data, such as genes involved in fatty acid biosynthetic pathway. Transcriptome data also helped us to identify some of the expressed transposable elements. Though many Long Interspersed elements (LINEs) were identified, only two Short Interspersed Elements (SINEs) were visible. Overall transcriptome and draft genome analysis of F. buski helped us to characterize some its important biological characteristics and provided enormous resources for development of a suitable diagnostic system and anti-parasitic therapeutic molecules.

evolutionary biology↗