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Panigrahi, M.

Publications and source records attributed to Panigrahi, M..

7 recordsLinked to original sources

Protein Biomarker in Focal Cortical Dysplasia: Molecular Clues to Pathogenesis

Focal Cortical Dysplasia (FCD) is a major cause of drug-resistant epilepsy (DRE), particularly in pediatric and young adult populations characterized by structural abnormalities in cortical development. This study investigated 60 patients with histologically confirmed FCD, combining clinical, histopathological, and molecular data to identify subtype-specific molecular signatures. we investigated a panel of candidate protein biomarkers (AKT, PTEN, mTOR, HTR6, RHEB, KCNT1, RALA, DEPDC5) across FCD subtypes using patient-derived tissue samples. Our results reveal subtype-specific alterations in biomarker expression, particularly within the mTOR signaling pathway, supporting its central role in cortical malformations. Key dysregulated genes AKT, mTOR, PTEN, RHEB, DEPDC5, KCNT1, RALA, and HTR6 involved in mTOR signaling, neuronal excitability, and cortical development. Western blotting and IHC revealed marked upregulation of AKT and mTOR in FCD III, consistent with mTOR pathway hyperactivation. In contrast, KCNT1, RALA, and DEPDC5 were significantly downregulated across all subtypes, suggesting disrupted inhibitory signaling and GATOR1 complex dysfunction. ELISA assays validated increased expression of AKT, mTOR, and HTR6, particularly in higher-grade lesions. This study bridges clinical, histopathological, and protein-level data, providing novel insight into the molecular basis of FCD and highlighting candidate biomarkers for future diagnostic and therapeutic applications

neuroscience↗

What's next for Indian Ornithology? 101 key research questions

India has a rich history of ornithology, and bird research in this field has expanded considerably in recent decades, spurred by a growing number of birdwatchers and ornithologists. Despite this progress, critical gaps remain. This paper highlights key areas where further research is needed and identifies pressing questions that will shape Indian ornithology in the coming years. Drawing from diverse inputs, we present a curated list of 101 research questions spanning across the various disciplines in ornithology - Natural History, Physiology and Disease Ecology, Behaviour, Population and Community Ecology, Habitat Ecology, Macroecology and Biogeography, Population Genetics and Evolution, Applied/Economic Ornithology and Conservation. The list was compiled through a multi-stage process, starting with a public open call for questions, followed by review and curation by a smaller panel of subject specialists. Each question was independently scored by a panel of experts based on three criteria: generality, novelty, and relevance. To account for variation in scoring styles, scores were normalised using Z-scores. The top 101 research questions were then selected based on these standardised scores. Each question is accompanied by an annotation that describes the significance of the question, and highlights opportunities to address it. While our list of research questions highlights significant research priorities, it is not intended to be exhaustive. Rather, it reflects the perspectives of those involved in its curation, who deemed these questions particularly relevant and impactful towards advancing Indian ornithology. We expect these questions to spark new project ideas among students, researchers, and citizen scientists, while guiding funders, managers, and policymakers toward priority research areas.

ecology↗

miR-122 affects both the initiation and maintenance of Hepatitis C Virus infections

A liver-specific microRNA, miR-122, anneals to the HCV genomic 5 terminus and is essential for virus replication in cell culture. However, bicistronic HCV replicons and full length RNAs with specific mutations in the 5 UTR can replicate, albeit to low levels, without miR-122. In this study, we have identified that HCV RNAs lacking the structural gene region or having EMCV IRES-regulated translation had reduced requirements for miR-122. In addition, we found that a smaller proportion of cells supported miR-122-independent replication when compared a population of cells supporting miR-122-dependent replication, while viral protein levels per positive cell were similar. Further, the proportion of cells supporting miR-122-independent replication increased with the amount of viral RNA delivered, suggesting that establishment of miR-122-independent replication in a cell is affected by amount of viral RNA delivered. HCV RNAs replicating independent of miR-122 were not affected by supplementation with miR-122, suggesting that miR-122 is not essential for maintenance of a miR-122-independent HCV infection. However, miR-122 supplementation had a small positive impact on miR-122-dependent replication suggesting a minor role in enhancing ongoing virus RNA accumulation. We suggest that miR-122 functions primarily to initiate an HCV infection but has a minor influence on its maintenance, and we present a model in which miR-122 is required for replication complex formation at the beginning of an infection, and also supports new replication complex formation during ongoing infection and after infected cell division. IMPORTANCEThe mechanism by which miR-122 promotes the HCV life cycle is not well understood, and a role in directly promoting genome amplification is still debated. In this study, we have shown that miR-122 increases the rate of viral RNA accumulation and promotes the establishment of an HCV infection in a greater number of cells than in the absence of miR-122. However, we also confirm a minor role in promoting ongoing virus replication and propose a role in the initiation of new replication complexes throughout a virus infection. This study has implications for the use of anti-miR-122 as potential HCV therapy.

microbiology↗

Enhanced virus translation enables miR-122-independent Hepatitis C Virus propagation

The 5UTR of the Hepatitis C Virus genome forms RNA structures that regulate virus replication and translation. The region contains a viral internal ribosomal entry site and a 5 terminal region. Binding of the liver specific miRNA, miR-122, to two conserved binding sites in the 5 terminal region regulates viral replication, translation, and genome stability, and is essential for efficient virus replication, but its precise mechanism of its action is still under debate. A current hypothesis is that miR-122 binding stimulates viral translation by facilitating the viral 5 UTR to form the translationally active HCV IRES RNA structure. While miR-122 is essential for detectable virus replication in cell culture, several viral variants with 5 UTR mutations exhibit low level replication in the absence of miR-122. We show that HCV mutants capable of replicating independently of miR-122 also replicate independently of other microRNAs generated by the canonical miRNA synthesis pathway. Further, we also show that the mutant genomes display an enhanced translation phenotype that correlates with their ability to replicate independently of miR-122. Finally, we provide evidence that translation regulation is the major role for miR-122, and show that miR-122-independent HCV replication can be rescued to miR-122-dependent levels by the combined impacts of 5 UTR mutations that stimulate translation, and by stabilizing the viral genome by knockdown of host exonucleases and phosphatases that degrade the genome. Thus, we provide a model suggesting that translation stimulation and genome stabilization are the primary roles for miR-122 in the virus life cycle. IMPORTANCEThe unusual role of miR-122 in promoting HCV propagation is incompletely understood but is essential for an HCV infection. To better understand its role, we have analyzed HCV mutants capable of replicating independently of miR-122. Our data show that the ability of viruses to replicate independently of miR-122 correlates with enhanced virus translation, but that genome stabilization is required to restore efficient HCV replication. This suggests that viruses must gain both abilities to escape the need for miR-122 and impacts the possibility that HCV can evolve to replicate outside of the liver.

microbiology↗

Genome-wide SNP data unravel the ancestry and signatures of divergent selection in Ghurrah pigs of India

The evolution and domestication of pigs is a complex and ongoing process. Despite its rich biodiversity and proximity to the geographical origins of Sus scrofa domesticus, the place of Indian pigs in the global phylogeny is unclear. Using microarray-derived (porcine 60K SNP chip) genotypes of 11 Ghurrah pigs from North-Western India and a public dataset comprising 2113 pigs of 146 breeds, we determined the genomic ancestry of Ghurrah pigs and compared their genetic constitution to European and Asian breeds to ascertain signatures of divergent selection. Results showed that Ghurrah pigs contain genes of Asian and European ancestry with signs of inter-species introgression. Using Admixture LD - decay statistics, the European admixture event was dated to the recent past, coinciding with the start of cross-breeding efforts in India. The complex Asian ancestry pattern of the breed resembled that of wild boars of South - Central China and Thailand, possibly suggesting introgression from an Indian wild boar relative. FST and XP - EHH comparisons with Asian breeds highlighted divergent selection in genomic regions associated with odontogenesis and skeletal muscle development. Comparisons with European commercial breeds revealed that genomic regions governing olfaction and response to sensory stimulation were under selection in Ghurrah pigs. QTL for meat and carcass traits also showed divergent selection between European breeds and Ghurrah pigs. Our results present the first genomic characterization of an Indian pig breed using dense microarray-derived genotypes and highlight the importance of further genomic characterization of Indian domestic and wild pigs.

genomics↗

In Vitro Patients Derived Glioma Culture Model: Identification of Aggressive, Drug Resistant Phenotype Among Low-Grade Gliomas

BackgroundClinical management of glioma is crucial irrespective of tumor grade. Despite newer treatment modalities, the prognosis of glioma is abysmal and, survival statistics are not remarkable. In vitro glioma culture is emerging as a standard model to get insight into phenotypic transformation, drug response, and tumor relapse. In this viewpoint, this study established comprehensive patient-specific short-term cultures comprising low-grade, and high-grade glioma, and evaluated their pertinence in the potential disease management. Methods50 patients with MRI diagnosed glioma were recruited for this study. Primary glioma cultures established from fresh surgical tumor tissues, which were then evaluated for their intrinsic growth kinetics, response to temozolomide, and expression profile of Glial-Mesenchymal Transition (GMT) markers along with an oncogenic marker, cMyc. ResultsShort-term glioma culture was successfully established in 40 clinical samples. Glioma culture, irrespective of tumor grade, displayed two distinct patterns of growth kinetics - one with shorter doubling time (high-proliferating) and another group with longer doubling time (low-proliferating). Significant distinctive features were noticed between these two groups in terms of response to temozolomide, the expression pattern of GMT markers and their association with 1p/19q co-deletion and p53 expression. ConclusionOur findings effectively demonstrated the practicality of the development of short-term glioma culture toward a functional approach for personalized medicine. Our study revealed the presence of a highly proliferative, drug-resistant phenotype irrespective of tumor grade. Hence, short-term culture could be an important prognostic tool for predicting patient clinical responses and cue about imminent tumor relapse.

cancer biology↗

Prediction analysis of SARS-COV-2 entry in Livestock and Wild animals

BackgroundSARS-CoV-2 is a viral pathogen causing life-threatening disease in human. Interaction between spike protein of SARS-CoV-2 and ACE2 receptor on the cells is a potential factor in the infectivity of a host. The interaction of SARS-CoV-2 spike receptor-binding domain with its receptor - ACE2, in different hosts was evaluated to understand and predict viral entry. The protein and nucleotide sequences of ACE2 were initially compared across different species to identify key differences among them. The ACE2 receptor of various species was homology modeled (6LZG, 6M0J, and 6VW1 as a reference), and its binding ability to the spike ACE2 binding domain of SARS-CoV-2 was assessed. Initially, the spike binding parameters of ACE2 of known infected and uninfected species were compared with each Order (of animals) as a group. Finally, a logistic regression model vis-a-vis the spike binding parameters of ACE2 (considering data against 6LZG and 6M0J) was constructed to predict the probability of viral entry in different hosts. ResultsPhylogeny and alignment comparison did not lead to any meaningful conclusion on viral entry in different hosts. Out of several spike binding parameters of ACE2, a significant difference between the known infected and uninfected species was observed for six parameters. However, these parameters did not specifically categorize the Orders (of animals) into infected or uninfected. The logistic regression model constructed revealed that in the mammalian class, most of the species of Carnivores, Artiodactyls, Perissodactyls, Pholidota, and Primates had high probability of viral entry. However, among the primates, African Elephant had low probability of viral entry. Among rodents, hamsters were highly probable for viral entry with rats and mice having a medium to low probability. Rabbits have a high probability of viral entry. In Birds, ducks have a very low probability, while chickens seemed to have medium probability and turkey showed the highest probability of viral entry. ConclusionsMost of the species considered in this study showed high probability of viral entry. This study would prompt us to closely follow certain species of animals for determining pathogenic insult by SARS-CoV-2 and for determining their ability to act as a carrier and/or disseminator.

microbiology↗