Biology subjects

Ranjan, N.

Publications and source records attributed to Ranjan, N..

3 recordsLinked to original sources

bioRxiv2024

Complement Biosensors Identify a Classical Pathway Stimulus in Complement-Mediated Hemolytic Uremic Syndrome

Complement-mediated hemolytic uremic syndrome (CM-HUS) is a thrombotic microangiopathy characterized by germline variants or acquired antibodies to complement proteins and regulators. Building upon our prior experience with the modified Ham (mHam) assay for ex vivo diagnosis of complementopathies, we have developed an array of cell-based complement "biosensors by selective removal of complement regulatory proteins (CD55 and CD59, CD46, or a combination thereof) in an autonomously bioluminescent HEK293 cell line. These biosensors can be used as a sensitive method for diagnosing CM-HUS and monitoring therapeutic complement blockade. Using specific complement pathway inhibitors, this model identifies IgM-driven classical pathway stimulus during both acute disease and in many patients during clinical remission. This provides a potential explanation for ~50% of CM-HUS patients who lack an alternative pathway "driving" variant and suggests at least a subset of CM-HUS is characterized by a breakdown of IgM immunologic tolerance. Key PointsO_LICM-HUS has a CP stimulus driven by polyreactive IgM, addressing the mystery of why 40% of CM-HUS lack complement specific variants C_LIO_LIComplement biosensors and the bioluminescent mHam can be used to aid in diagnosis of CM-HUS and monitor complement inhibitor therapy C_LI

immunology↗

bioRxiv2023

Converging paths: Harnessing ensemble modelling to predict human wild pig conflict risk zones in Tamil Nadu, India

Growing human populations and human activity intensify human-wildlife conflicts, particularly with wild pigs (Sus scrofa), necessitating consideration of both human and wildlife requirements. This complexity demands a comprehensive assessment of causes, impacts, and mitigation strategies for such conflicts. In order to address these issues, we conducted studies across the forest divisions of Tamil Nadu by collecting secondary data on conflicts from 2016 to 2021. Out of the 3301 incidents we collected, 94.4% were specifically related to crop damage and occurred mostly during the month of December, followed by November. Dharmapuri Forest Division was found to be the highest contributor to overall conflicts. Temporal analysis revealed conflict peaks in December, followed by November and September. Using ensemble modelling we predicted a conflict risk zone of approximately 49,223 km2, which represents 37.8% of the total area of Tamil Nadu. Variables like human modification index and mean annual temperature had the highest contribution to model performance. Our models projections indicate that areas with cultivated lands in close proximity to the fringes of forests, especially in regions where there is a greater degree of human modification, are associated with heightened levels of conflict risk. This study provides a concise overview of a comprehensive study on human-wild pig conflict, encompassing an exploration of conflict triggers and ecological impacts in the state of Tamil Nadu. The study offers a comprehensive roadmap for managing human-wild pig conflicts in Tamil Nadu, highlighting key triggers, ecological impacts, and conflict risk factors.

ecology↗

bioRxiv2020

eEF3 promotes late stages of tRNA translocation on the ribosome

SummaryIn addition to the conserved translation elongation factors eEF1A and eEF2, fungi require a third essential elongation factor, eEF3. While eEF3 has been implicated in tRNA binding and release at the A and E sites, its exact mechanism of action is unclear. Here we show that eEF3 acts at the mRNA–tRNA translocation step by promoting the dissociation of the tRNA from the E site, but independent of aminoacyl-tRNA recruitment to the A site. Depletion of eEF3 in vivo leads to a general slow-down in translation elongation due to accumulation of ribosomes with an occupied A site. Cryo-EM analysis of ex vivo eEF3-ribosome complexes shows that eEF3 facilitates late steps of translocation by favoring non-rotated ribosomal states as well as by opening the L1 stalk to release the E-site tRNA. Additionally, our analysis provides structural insights into novel translation elongation states, enabling presentation of a revised yeast translation elongation cycle.Competing Interest StatementThe authors have declared no competing interest.View Full Text

molecular biology↗