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SARKAR, R.

Publications and source records attributed to SARKAR, R..

2 recordsLinked to original sources

Polyisobutylene Micro/Nanoplastics Induce Multi-System Toxicity, Intestinal Barrier Dysfunction, and Neurodegeneration in Drosophila melanogaster

Micro/nanoplastics (MNPs) are increasingly recognized as a persistent environmental contaminant of concern, yet polyisobutylene (PIB), an industrially significant polymer used as industrial sealants, adhesives, cable insulation, lubricant additives, and chewing gum bases, remains poorly studied relative to more commonly studied plastics such as polyethylene terephthalate (PET), polystyrene (PS), and polyethylene (PE). This study investigated the multisystem toxicological effects of chronic dietary exposure to PIB-MNPs in Drosophila melanogaster. PIB-MNPs (> 5 micron) were synthesized via the solvent evaporation method and characterized using scanning electron microscopy (SEM) and Fourier Transform Infrared spectroscopy (FTIR), confirming successful synthesis. Flies were chronically exposed to PIB-MNPs (1, 2, or 3 mg) alongside an SDS control and a water control to 50 mg of yeast over 21 days, with toxicological outcomes assessed via survival analysis, climbing assays, fluorescence brain imaging, fertility/fecundity assays, the Smurf gut-permeability assay, Ellman's AChE activity assay, and RT-qPCR analysis of Stat92E expression, a marker of inflammation. Chronic exposure to PIB-MNPs reduced survival, with females exhibiting markedly greater susceptibility than males. Exposure progressively impaired locomotor performance and induced brain vacuolization suggestive of neurodegeneration, peaking at day 15. AChE activity declined in a concentration-dependent manner by day 21. Female fecundity, egg-hatching rate, and ovarian egg-chamber maturation were significantly reduced, while male gonadal cyst cell numbers remained largely unaffected. PIB-MNPs exposure also induced a positive Smurf phenotype, indicating compromised intestinal barrier integrity and upregulated Stat92E expression, consistent with activation of a systemic stress response. Notably, several endpoints showed non-monotonic, concentration-independent trends, suggesting particle aggregation may influence effective bioavailability. Collectively, these findings establish PIB-MNPs as a multi-system toxicant in Drosophila.

cell biology↗

Free Energy Landscape of Magnesium Chelation Reveals Dynamic Pre-Chelate Complexes Stabilized by Meta-Sphere RNA-Ion Coordination

Magnesium ions (Mg{superscript 2}) play a critical role in RNA structure stabilization by forming various coordinated complexes, preferentially interacting with the backbone phosphate groups. Using extensive atomistic and free energy simulations across simple models and RNA structures of varying complexity, we characterized critical components of the RNA-ion-atmosphere. Radial distribution function analysis reveals distinct peak positions for direct (inner) and solvent-separated (outer-sphere) Mg2+-phosphate coordination layers, aligning with solution X-ray diffraction data. Addressing forcefield limitations, the free energy calculations quantify the kinetic barriers for Mg{superscript 2}-phosphate binding, benchmarking parameters against {superscript 2}Mg NMR measurement. Free energy calculations further explore Mg{superscript 2} chelation with bi-phosphate coordinated Mg2+ systems, identifying a dynamic ensemble of pre-chelate complexes, in addition to a chelated and outer-sphere hexa-hydrated state of Mg2+. In the pre-chelated states, Mg{superscript 2} maintains one inner-sphere interaction while simultaneously coordinating with multiple other phosphates in a solvent-separated manner, referred to as meta-sphere coordination. The pre-chelated complexes from different solvents-separated layers undergo a frequent transition and mediate a unique oxygen exchange mechanism between phosphate and water ligands. Insights into the free energy landscape of SAM-I RNA aptamer further emphasize the significance of pre-chelate complexes for complex RNA structure stabilization, where a number of such solvent-separated dynamic phosphate groups are found to influence Mg2+-RNA coordination. The comprehensive thermodynamic analysis of Mg{superscript 2} chelation and quantitative characterizations of various RNA-ion coordination modes, including this new meta-sphere coordination, provides vital insights for advancing RNA modelling and experimental exploration of complex phosphate networks in the RNA structures.

biophysics↗