Biology subjects

Augustine, A.

Publications and source records attributed to Augustine, A..

5 recordsLinked to original sources

bioRxiv2026

Patient CACNA1A variant uncouples calcium channel conductance from synaptic output

Channelopathies are a class of neurodevelopmental disorders with often devastating consequences, and effective therapies depend on understanding how patient variants alter channel function. These effects are typically assessed by biophysical characterization in heterologous expression systems. Mutations in CACNA1A, which encodes the P/Q-type calcium channel CaV2.1, underlie a spectrum of neurological disorders in which symptoms are generally classified as loss-of-function (LoF) or gain-of-function (GoF). However, some patients present with overlapping phenotypes that defy this binary framework. Here we describe a CACNA1A variant for which heterologous assays fail to capture a key in vivo functional effect. We characterize a de novo variant of a highly conserved residue, D1634N, identified in a patient with a mixed clinical presentation that includes both LoF- and GoF-associated symptoms. Biophysical characterization in HEK293T cells supports a classic and severe LoF effect, including reduced current density and a right-shifted current-voltage relationship. In contrast, in vivo analysis of the corresponding endogenous variant in the C. elegans homolog reveals a paradoxical increase in spontaneous synaptic vesicle release, despite reduced channel expression. Molecular dynamics simulations predict that the mutation prolongs dwell time in a partially open state, potentially increasing calcium influx at rest. This model is supported by biophysical recordings of the human channel showing increased current at hyperpolarized potentials and by rescue of the C. elegans phenotype through genetic elevation of resting membrane potential. Together, these findings reconcile the patients clinical presentation by describing a complex, mixed-function variant, highlight the importance of cellular context in variant interpretation and therapeutic development, and establish C. elegans as a powerful in vivo platform for evaluating the functional consequences of pathogenic ion channel variants.

neuroscience↗

bioRxiv2025

Punarnavayolepa Choornam in Iron Deficiency Anaemia management: Pharmaceutic insights and biological activity.

Background and AimIndigenous medical systems employ unique pharmaceutical techniques to meet the therapeutic needs. In the Indian System of Medicine, Ayurveda, a unique method called "Ayolepam" is described that facilitates efficient iron absorption from its source to the formulation. Punarnavayolepa Choornam (PC), prepared from Boerhavia diffusa L., is one such novel Ayolepam formulation developed by a traditional Ayurveda school of South India, widely used in the clinical management of iron deficiency anaemia. This study aims at scientifically evaluating the Ayolepam technique by assessing the iron binding and bioavailability properties of PC, prepared from the leaves, root and whole plant of B. diffusa, using in-vitro model systems.. Experimental ProcedureThe iron content in both raw and processed samples of PC was quantified using Inductively Coupled Plasma Mass Spectrometry (ICP-MS). A simulated in-vitro digestion model employed to assess the release of bioavailable iron from the formulation. Subsequently, iron bioavailability was evaluated using the Caco-2 cell model of human intestinal epithelium following the ferrozine method. Results and ConclusionPC preparation from leaves, whole plant and roots of B. diffusa, showed significant increase in iron content compared to the raw material. In-vitro digestion studies confirmed the efficient release of bioavailable iron from these formulations, and subsequent Caco-2 cell assays confirmed their iron bioavailability properties. In conclusion, these findings provide a preliminary scientific basis for this novel and unique pharmaceutical design from a traditional school of Ayurveda, supporting its clinical application.

pharmacology and toxicology↗

bioRxiv2023

The RAD51 paralogue HvXRCC2 regulates meiosis and recombination in barley

Using a positional candidate-gene approach we show that semi-sterile desynaptic8 mutants are associated with deletions in or complete knockout of the barley homolog of XRCC2 (X-Ray Repair Cross Complementing 2). In barley XRCC2 mutants, the initial meiotic progression is normal, albeit with a small delay in initiation, with completion of synapsis. However, the absence of HvXRCC2 subsequently leads to a dramatic reduction in the number of crossovers, chromosome mis-segregation, and infertility, suggesting that HvXRCC2 plays a major role in recombination. This mutant phenotype is congruent with that reported in mammalian studies but contrasts with the XRCC2 mutant in Arabidopsis which is fertile, exhibits normal chromosome pairing and correct chromosome segregation, and is associated with an increased rate of crossovers. This indicates that the XRCC2 mutant phenotype in Arabidopsis is not representative of all plants and that XRCC2 is not a good candidate for the modulation of recombination in barley. HighlightThe mutants of the barley homolog of XRCC2 exhibit delays in replication leading to defective meiosis, altered RAD51 orthologue behaviour, and significant reduction in the number of crossovers as in canonical mammalian XRCC2 mutants but unlike those in Arabidopsis.

plant biology↗

bioRxiv2020

Antioxidant, Anti-inflammatory and Anticancer activities of Methanolic Extract of Thottea siliquosa: An In Vitro study

Background and AimOxidative stress and inflammation are the predominant cause of chronic diseases including cancers, thereby making it as an essential target for preventing these disorders. Various natural products and plants have been shown to prevent the process of free radical induced damages. The present study evaluated the biological properties of Thottea siliquosa, belonging to the family Aristolochiaceae, which is a traditionally used Ayurvedic plant. Experimental ProcedureAntioxidant assays carried out were DPPH, FRAP, hydrogen peroxide scavenging and hemolysis inhibition assay; nitric oxide and lipoxygenase inhibition assays were used for anti-inflammatory studies. Anticancer activity was done using human endometrial and breast cancer cells by MTT assay. Results and ConclusionThe results of the present study showed antioxidant properties for the methanolic crude extract of T. siliquosa as DPPH radical scavenging (110.40{+/-} 4.5g/mL), FRAP capacity (41.1{+/-} 6.2), peroxide scavenging (233.4{+/-} 14.2 g/mL) etc. In addition, anti-inflammatory properties are also evident in terms of nitric oxide radical scavenging (28.76{+/-} 3.9 g/mL) and lipoxygenase inhibition (39.2{+/-} 3.2 g/mL) assays. Further, the anticancer activity of these extract has been identified against human endometrial and breast cancer cells. Further studies together with a bioassay guided fractionation may identify possible bioactive compounds. HighlightsO_LIThottea siliquosa is a traditional Ayurvedic medicine C_LIO_LIT. siliquosa exhibits significant anti-inflammatory and anticancer properties C_LIO_LIPolyphenolic compounds may be responsible for the bioactivities of T. siliquosa C_LIO_LIT. siliquosa may be a source for novel bioactive components C_LI

pharmacology and toxicology↗

bioRxiv2019

Identification of blaGIM-1 in Acinetobacter variabilis isolated from the hospital environment in Tamil Nadu, India

BackgroundEmergence of carbapenem resistance mechanisms among Gram-negative bacteria is a worrisome health problem. Here, we focused on to identify the presence of carbapenem-resistant bacteria among the samples collected from hospital environments in Tamil Nadu.\n\nMethodsA total of 30 hospital environmental samples were collected between August 2017 and January 2018 from hospitals located in Chennai and Vellore such as lift switches, stair rails, switchboards, nursing desks, used nursing gloves, door handles, wheelchairs, touch screens, chairs and from pillars inside the hospitals.\n\nResults and discussionA total of 22 carbapenem-resistant Gram-negative bacteria were isolated that included Escherichia coli, Klebsiella sp., Enterobacter sp., Salmonella sp., Pseudomonas aeruginosa and Acinetobacter sp. Interestingly, blaGIM-1 was detected in Acinetobacter variabilis strain isolated in samples collected from hospitals. Unlike other studies, the identified GIM-1 was not plasmid encoded, and this is the first report for the presence of GIM-1 (German imipenemase) in India.\n\nConclusionExtensive surveillance programs are necessary to trace the uncontrolled spread of carbapenem-resistance genes in order to reduce the rapid spread of resistance.

microbiology↗