Biology subjects

Panchal, K.

Publications and source records attributed to Panchal, K..

5 recordsLinked to original sources

bioRxiv2026

Non-canonical proteoforms of the human fusiform gyrus in Alzheimers disease

For a long time, the protein coding potential of our genome was underestimated. Only 2% of the genome was thought to be coding for the protein while the rest was called non-coding and junk. The two main sources of biasness which resulted in underestimation were prioritising conservation and length of the open reading frames (ORFs). But recent Ribo-seq studies and high throughput quantitative proteomics studies have shown that many ORFs previously annotated as non-coding are actually getting translated into proteins and these non-canonical proteins do have certain biological functions. These findings have added more parameter perspectives to look from about different diseases. This study aims to understand translation dynamics of these proteins encoded from non-canonical ORFs in neurological disorders affecting cognitive functions specifically targeting fusiform gyrus which is linked with face recognition and anime associations which are crucial symptoms in neurological disorders. This study uses transcriptomics and proteomics analysis to understand transcriptional and translational dynamics of ncORFs. A patient cohort from the Banner Sun Health Research Institute cohort is used, corresponding RNA-seq data and Quantitative MS/MS proteomics data published in different studies are used. A custom-made protein search database was created using transcriptomics tools like STAR, StringTie and Salmon to filter out expressed ncORFs within the non-coding region and not annotated as protein coding in either GENCODE or UniProt annotations. The custom ncORF-database was then later used in proteomics analysis as search space along with the canonical proteins. The entire comprehensive analysis has resulted in identification of 22,135 ncORF-encode proteins (ncPs) and out of which 67 are differentially expressed across different neurological conditions based on the | log2FC | >1 & p.adj < 0.05 criteria. The study highlights new molecular players which might be the missing links of known mechanisms.

bioinformatics↗

bioRxiv2026

FABP8/PMP2 is a positive regulator of PNS myelination

Myelin formation in peripheral nerves is orchestrated by axon-derived signals and the ability of Schwann cells to expand lipid-rich membrane. Axonal Neuregulin-1 type III (NRG1t3) is known to promote thicker myelin and is associated with increased lipid abundance in peripheral nerves. NRG1t3 also strongly upregulates peripheral myelin protein 2 (FABP8/PMP2), a fatty acid binding protein in myelinating Schwann cells. Here, we directly tested whether elevating PMP2 in Schwann cells is sufficient to enhance myelin growth in nerves. We generated transgenic mice with Schwann cell-specific PMP2 overexpression and showed that PMP2 overexpression drove significant myelin thickening in peripheral nerves, without altering myelin ultrastructure, impairing nerve conduction, or causing detectable adverse effects despite sustained expression. Strikingly, this hypermyelination occurred without activating canonical promyelinating signaling pathways. Instead, elevated PMP2 selectively enhanced fatty acid uptake in Schwann cells, identifying PMP2 as a dosage sensitive enhancer of myelin growth. These findings suggest that in the absence of axonal signaling-driven upregulation, enhanced PMP2 expression itself promotes myelin membrane expansion and enhanced fatty acid availability that could favor complex lipid synthesis. These findings reveal new role for PMP2 as a regulator for myelin expansion in vivo, highlighting a key link between lipid trafficking and myelin growth.

neuroscience↗

bioRxiv2025

Age-dependent tumor-immune interactions underlie immunotherapy response in pediatric cancer

Pediatric cancers originate in rapidly growing tissues within the context of a developing host. However, the interactions between cancer cells and the developing immune system are incompletely understood. Here, we established a suite of pediatric syngeneic mouse cancer models across diverse anatomical sites and compared their tumor immune microenvironment with that in adult mice. Tumors in pediatric mice exhibited significantly accelerated growth and diminished leukocyte infiltration, dominated by naive-like PD-1low/CD8+ T cells, and proliferative MHCIIlow/PD-L1hi/CD86low macrophages. Tumor-infiltrating leukocytes in pediatric mice were enriched for MYC targets, which was also observed in pediatric patient samples. Furthermore, pediatric mice displayed poor responses to anti-PD-1/PD-L1 or bispecific T cell engager antibodies, which could be reversed by inducing a proinflammatory microenvironment via MYC inhibition or inducing macrophage polarization to an MHCIIhi phenotype. These findings underscore the significant influence of young age on cancer immune responses and reveal potential new therapeutic opportunities for pediatric cancers. HIGHLIGHTSO_LIAllograft tumors exhibit markedly accelerated growth in pediatric hosts compared to adults. C_LIO_LITumors growing in pediatric mice have reduced leukocyte infiltration, dominated by naive-like PD-1low/CD8+ T cells, and MHCIIlow/M2-like macrophages. C_LIO_LIEnrichment of MYC target genes is observed in pediatric mouse tumors and confirmed in primary patient tumor samples. C_LIO_LIPediatric mice display reduced response to anti-PD-1/PD-L1 and BiTE immunotherapy, which can be reversed by remodeling the TIME, using either MYC inhibition or macrophage polarization. C_LI

cancer biology↗

bioRxiv2023

Identification of methylation markers for age and Bovine Respiratory Disease in dairy cattle

Methylation profiles of animals is known to differ by age and disease status. Bovine respiratory disease (BRD), a complex infectious disease, primarily affects calves and has significant impact on animal welfare and the cattle industry, predominantly from production losses. BRD susceptibility is multifactorial, influenced by both environmental and genetic factors. We investigated the epigenetic profile of BRD susceptibility in calves and age-related methylation differences between healthy calves and adult dairy cows using Reduced Representation Bisulfite Sequencing (RRBS). We identified 3,452 genes within differentially methylated regions between calves and adults. Functional analysis revealed enrichment of developmental pathways including cell fate commitment and tissue morphogenesis. Between healthy and BRD affected calves, 964 genes were identified within differentially methylated regions. Immune and vasculature regulatory pathways were enriched and key candidates in BRD susceptibility involved in complement cascade regulation, vasoconstriction and respiratory cilia structure and function were identified.

genetics↗

bioRxiv2021

Metabolic dysfunction induced by high-fat diet modulates hematopoietic stem and myeloid progenitor cells in brown adipose tissue of mice

Brown adipose tissue (BAT) may be an important metabolic regulator of whole-body glucose. While important roles have been ascribed to macrophages in regulating metabolic functions in BAT, little known is known of the roles of other immune cells subsets, particularly dendritic cells (DCs). Eating a high fat diet may compromise the development of hematopoietic stem and progenitor cells (HSPC) - which give rise to DCs - in bone marrow, with less known of its effects in BAT. We have previously demonstrated that ongoing exposure to low-dose ultraviolet radiation (UVR) significantly reduced the whitening effect of eating a high-fat diet upon interscapular (i)BAT of mice. Here, we examined whether this observation may be linked to changes in the phenotype of HSPC and myeloid-derived immune cells in iBAT and bone marrow of mice using 12-colour flow cytometry. Many HSPC subsets declined in both iBAT and bone marrow with increasing metabolic dysfunction. Conversely, with rising adiposity and metabolic dysfunction, conventional (c)DCs increased in both of these tissues. When compared to low-fat diet, consumption of high-fat diet significantly reduced proportions of myeloid, common myeloid and megakaryocyte-erythrocyte progenitors in iBAT, and short-term hematopoietic stem cells in bone marrow. In mice fed a high-fat diet, exposure to low-dose UVR significantly reduced proportions of cDCs in iBAT, independently of nitric oxide release from irradiated skin (blocked using the scavenger, cPTIO), but did not significantly modify HSPC subsets in either tissue. Further studies are needed to determine whether changes in these cell populations contribute towards metabolic dysfunction.

cell biology↗