Biology subjects

K, A.

Publications and source records attributed to K, A..

9 recordsLinked to original sources

bioRxiv2026

Anti-diabetic drug Repaglinide induces Apoptosis, Cell Cycle Arrest, and Inhibits Cell Migration in Human Breast and Lung Cancer Cells.

IntroductionDrug repurposing offers a cost-effective and time-efficient strategy for cancer therapy by leveraging existing drugs with established safety profiles, thus functioning as an alternative therapeutic strategy in demanding diseases such as cancer. Antidiabetic agents, in particular, have demonstrated encouraging anticancer potential. Among them, the non-sulfonylurea insulin secretagogue repaglinide (RPG) has shown emerging anticancer potential, yet its effects on breast and lung cancers remain largely unexplored. Thus, this study investigates the anticancer activity of repaglinide in human breast (MCF-7) and lung (A549) cancer cell lines, focusing on its cytotoxic, pro-apoptotic, anti-proliferative, and anti-migratory effects and the underlying possible molecular mechanisms. Methodology and ResultsMTT cytotoxic assay revealed that RPG reduced cell viability in a dose-/time-dependent manner, with an IC (48h) of 100.8 {+/-} 3.98 {micro}M for MCF-7 and 104 {+/-} 3 {micro}M for A549. Further, the apoptotic effect of RPG on both cell lines was evidenced by double staining assays, comet assay, and western blotting analysis, suggesting that RPG explicitly caused DNA damage and activated intrinsic and extrinsic apoptosis pathways. Additionally, RPG suppressed clonogenicity and enforced G1 arrest in MCF7 and A549 cells by modulating cell cycle regulations as well as cell proliferation pathways. Moreover, RPG markedly suppressed cell motility, as demonstrated by scratch and Transwell migration/invasion assays, which is correlated with reduced MMP-2 and MMP-9 expression, confirmed by gelatin zymography and western blotting. ConclusionConclusively, Repaglinide exerts potent anticancer effects in breast and lung cancer cells by modulating key oncogenic signaling pathways, and thus can be considered a promising candidate for repurposing in cancer therapy.

cancer biology↗

bioRxiv2026

Characterization of a novel soluble melanin secreted by Gliomastix polychroma

Melanin is a heterogeneous, amorphous biopolymer widely distributed in biological systems, yet most canonical forms are intrinsically insoluble. Soluble melanins are rare and remain poorly characterized, with pyomelanin and peptidomelanin representing the best-described fungal examples. Here, we report the isolation and characterization of a distinct, polyphyletic class of soluble melanin that we term `colloidal melanin'. This class of polymers was isolated from four different species of Ascomycetous fungi occupying varied environmental niches. Colloidal melanin was found to be phenolic and nitrogenous, with a low amino acid content. The polymers form particles with median diameters ranging from 79 to 127 nm, suggesting that small particle size may contribute to aqueous solubility via colloidal dispersion. Using chemical inhibition of melanin biosynthesis together with whole-genome sequencing, we show that colloidal melanin can be produced through multiple distinct biochemical pathways. Further, genes identified as involved in melanin biosynthesis across species do not share any detectable common ancestry, consistent with convergent evolution. Together, these findings identify a distinct class of soluble melanin that does not conform to existing soluble melanin classifications.

biochemistry↗

bioRxiv2025

The Duality of Insect Macroevolution: Pulsed Genomes and Gradual Morphology Shape Lineage Diversification

Insects, comprising over half of all known species, are pivotal to ecosystems and ideal for studying trait evolution due to their morphological and genomic diversity. Yet, the macroevolutionary interplay between their phenotypic traits and genomic architecture is poorly resolved. Using a Tree of Life framework and phylogenetic comparative methods, we investigated the evolutionary dynamics of morphological and genomic traits across multiple insect orders with trait-specific taxonomic sampling optimized for data availability. Critically, while traditional metrics showed no correlation between species richness and evolutionary mode, the pattern of pulsed evolution revealed a clear macroevolutionary signal. Morphological diversification tended towards gradualism, whereas genomic evolution was predominantly pulsed. Notably, this pulsed signal manifested differently: large morphological pulses were associated with species-poor clades like Odonata, while species-rich clades exhibited major pulses in genome size. These results demonstrate that interpreting pulsed evolutions contribution to diversification requires careful consideration of both trait identity and phylogenetic context. Further, for both morphological and genomic traits, the degree of phylogenetic conservatism was independent of the evolutionary distance between orders.

evolutionary biology↗

bioRxiv2025

Deciphering the Population Ecology of Blossom Midge, Contarinia maculipennis Felt: An Emerging Threat to Tuberose Cultivation in India

The blossom midge Contarinia maculipennis is a devastating pest of ornamental and vegetable crops, yet its population ecology remains poorly understood. This study employs an age-stage two-sex life table model to analyze its life history with additional focus on below-ground soil environment. Tuberose (Agave amica), a newly identified host, was selected for study. The average fecundity of C. maculipennis was 39.13 eggs, with an intrinsic rate of increase (r) of 0.137, and a mean generation time (T) of 19.73 days. The population doubling time was 5.05 days, with the highest survival rate observed in the first instar larvae (0.95), and the lowest in the adult stage (< 0.38). The population doubling time was 5.05 days. Survival was highest in first-instar larvae (0.95) and lowest in adults (< 0.38). Life expectancy peaked at age zero (e0 =15.57 days) and decreased with pivotal age. The reproductive value (Vx) peaked between 13 and 19 days post-field appearance. Pupal development was fastest, with a significantly higher adult-emergence recorded in sandy clay loam soil (9.67 days); however pupal development and adult-emergence were severely impacted in black cotton and marshy soils. Moderate soil moisture (20%) favored pupation and eclosion rate, while dry (10%) and saturated (30%) soils hindered pupation and emergence. Population projections over 90 days, starting with 133 eggs, estimated an adult population of 3,80738. These findings highlight pupal and adult stages as critical targets for management. Soil type and moisture strongly influence population dynamics, with strategies such as maintaining dry conditions between rows, deep ploughing to bury pupae, and mass trapping recommended for effective control. These insights offer practical strategies for the sustainable management of C. maculipennis.

ecology↗

bioRxiv2022

UBA52 attunes VDAC1-mediated mitochondrial dysfunction and dopaminergic neuronal death

Mitochondrial homeostasis regulates energy metabolism, calcium buffering, cell function and apoptosis. The present study has been conducted to investigate the implications of ubiquitin-encoding gene UBA52 in mitochondrial physiology. Transient expression of Myc-UBA52 in neurons significantly inhibited the rotenone-induced increase in reactive oxygen species generation, nitrite level and depleted glutathione level. Mass spectrometric and co-immunoprecipitation data suggested the profound interaction of UBA52 with mitochondrial outer membrane channel protein, VDAC1 in both the wild-type and Myc--synuclein overexpressed neuronal cells and in the Parkinsons disease (PD)-specific substantia nigra and striatal region of the rat brain. In vitro ubiquitylation assay revealed that UBA52 participates in the ubiquitylation of VDAC1 through E3 ligase CHIP. Myc-UBA52 overexpression in neurons further improved the mitochondrial functionality and cell viability by preventing the alteration in mitochondrial membrane potential, mitochondrial complex-I activity, translocation of cytochrome-c and p-Nrf2 along with effect on intracellular calcium uptake, thus collectively inhibiting the opening of mitochondrial permeability transition pore. Additionally, Myc-UBA52 expression in neuronal cells offered protection against apoptotic and autophagic cell death. Altogether, our findings delineate functional association between UBA52 and mitochondrial homeostasis, providing new insights into the deterrence of dopaminergic cell death during acute PD pathogenesis.

neuroscience↗

bioRxiv2021

Altered expression of Api5 affects breast carcinogenesis by modulating FGF2 signalling

Apoptosis or programmed cell death plays a vital role in maintaining homeostasis and, therefore, is a tightly regulated process. Deregulation of apoptosis signalling can favour carcinogenesis. Apoptosis inhibitor 5 (Api5), an inhibitor of apoptosis, is upregulated in cancers. Interestingly, Api5 is shown to regulate both apoptosis and cell proliferation. To address the precise functional significance of Api5 in carcinogenesis here we investigate the role of Api5 in breast carcinogenesis. Consistently, in-silico analysis revealed elevated levels of Api5 transcript in breast cancer patients which correlated with poor prognosis. Overexpression of Api5 in non-tumorigenic breast acinar cultures resulted in increased proliferation and cells exhibited a partial EMT-like phenotype with higher migratory potential and disruption in cell polarity. Furthermore, during acini development, the influence of Api5 is mediated via the combined action of FGF2 activated PDK1-Akt/cMYC signalling and Ras-ERK pathways. Conversely, Api5 knock-down downregulated FGF2 signalling leading to reduced proliferation and diminished in vivo tumorigenic potential of the breast cancer cells. Thus, taken together, our study identifies Api5 as a central player involved in regulating multiple events during breast carcinogenesis.

cancer biology↗

bioRxiv2021

Anti-SARS-CoV-2 potential of Cissampelos pareira L. identified by Connectivity map-based analysis and in vitro studies

BackgroundViral infections have a history of abrupt and severe eruptions through the years in the form of pandemics. And yet, definitive therapies or preventive measures are not present. PurposeHerbal medicines have been a source of various antiviral compounds. An accelerated repurposing potential of antiviral herbs can provide usable drugs and identify druggable targets. In this study, we dissect the anti-coronavirus activity of Cissampelos pareira L (Cipa). using an integrative approach. MethodsWe analysed the signature similarities between predicted antiviral agents and Cipa using the connectivity map (https://clue.io/). Next, we tested the anti-SARS-COV-2 activity of Cipa in vitro. A three-way comparative analysis of Cipa transcriptome, COVID-19 BALF transcriptome and CMAP signatures of small compounds was also performed. ResultsSeveral predicted antivirals showed a high positive connectivity score with Cipa such as apcidin, emetine, homoharringtonine etc. We also observed 98% inhibition of SARS-COV-2 replication in infected Vero cell cultures with the whole extract. Some of its prominent pure constituents e.g pareirarine, cissamine, magnoflorine exhibited 40-80% inhibition. Comparison of genes between BALF and Cipa showed an enrichment of biological processes like transcription regulation and response to lipids, to be downregulated in Cipa while being upregulated in COVID-19. CMAP also showed that Triciribine, torin-1 and VU-0365114-2 had positive connectivity with BALF 1 and 2, and negative connectivity with Cipa.

systems biology↗

bioRxiv2019

Biodiversity clock and conservation triangle: Integrative platform for biodiversity monitoring, evaluation, and preemptive conservation intervention

Business-as-usual is no more an option on the table for biodiversity conservation. Disruptive transformation at both policy and polity levels are pressing needs. The possibilities presented by the current wave of information and communication technology can act as travelators to meet the conservation targets. Here, we introduce twin concepts of biodiversity clock and conservation triangle that posit as convergence plane to seamlessly consolidate ongoing discrete efforts and convey real-time biodiversity information in a lucid schematic form. In its present form, the biodiversity clock depicts 12 ecological and 6 biophysical components. The universal consistency in clock-reading facilitates the biodiversity clock to be read and interpreted identically across the world. A ternary plot of the International Union of Conservation of Nature (IUCN) species conservation status is presented as the conservation triangle. Together, the biodiversity clock and the conservation triangle are invaluable in strategizing biodiversity conservation, post-2020. Leveraged smartly, they make possible pre-emptive intervention for biodiversity conservation.

ecology↗

bioRxiv2019

Non-coding RNAs control metabolic state in mycobacteria

Non-coding RNAs play pivotal roles in bacterial signaling. However, RNAs from certain phyla (specially high-GC actinobacteria) remain elusive. Here, by revamping existing approaches we discover a family of structurally conserved RNAs in actinobacteria. These RNAs function by the recruiting ANTAR proteins to select transcripts; regulating them via translational repression. By overlapping with ORF start sites, these RNAs provide mechanisms by which even leader-less transcripts are regulated. In mycobacteria, transcripts marked by ANTAR-target RNAs are few but encode important redox enzymes especially involved in lipid metabolism. Notably, the cellular response to ANTAR-regulation is hierarchical, wherein immediate metabolic changes induced by ANTAR-RNA binding are amplified through a global transcriptomic response. This includes several genes from oxidative/reductive pathways; ultimately switching cells towards reductive metabolism. This discovery of ANTAR-target RNAs and associated regulation places RNAs as crucial players in controlling metabolic flexibility of mycobacteria, proposing a prominent role for ANTAR regulation across actinobacteria.

biochemistry↗