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Shinde, R.

Publications and source records attributed to Shinde, R..

4 recordsLinked to original sources

Curvature-guided chiral collective organization of myoblast tissues

Surface curvature is a fundamental geometric cue in tissue morphogenesis, yet its role in guiding collective cell organization has remained elusive. Here, we show that curvature acts as a geometric control parameter that shapes supracellular alignment and chirality while modulating myogenic differentiation in myoblast tissues. Cells cultured on curved substrates self-organize into robust helical assemblies whose handedness is set, and can be reversed, by the sign of curvature: convex fibers produce right-handed helices, whereas concave channels invert the chirality. We identify a previously hidden clockwise bias in single-cell motion associated with the helical actin cytoskeleton. A minimal continuum theory coupling an effective chiral drive to curvature quantitatively captures the emergence and reversal of tissue-scale chiral alignment. On substrates with spatially varying curvature, local curvature gradients organize patterned multicellular architectures while preserving a global handedness. Curvature is also associated with myogenic state, with higher curvature linked to reduced or delayed differentiation. Together, these findings reveal how complex geometries shape the alignment, symmetry, and cellular state of living tissues.

biophysics↗

Age Stratified Meta Transcriptomic Analysis Reveals Early and Core Dysregulated Pathways in Parkinson's Disease

Parkinsons disease (PD) is strongly age-associated, yet how aging reshapes PD-related transcriptional changes remains unclear. We performed an age-stratified meta-analysis of 16 bulk RNA-seq datasets (646 samples: 314 PD, 332 controls) to distinguish early-onset (<60 years) from late-onset ([&ge;]60 years) signatures. In the full dataset, 131 significantly (padj<0.05, |log2FC|>1) differentially expressed genes (DEGs) were observed, spanning neuronal activity-dependent genes (NPAS4, PVALB, ARC, FOSB) and immune/stress-related transcripts (IL3RA, SLC25A6, HSPA1A/B). Age-specific analyses revealed 31 DEGs in <60, dominated by large-effect changes in uncharacterized lncRNA LINC02188, pseudogene loci (MUC20P1, RPS28P7), calcium-modulating gene CALML6, lipid{square}associated gene TLCD3B, and cytoskeletal regulators (TIAM2, KCTD8). In contrast, the [&ge;]60 group showed 181 DEGs enriched for neuronal markers (NPAS4, PVALB) and immune-metabolic genes (FGA, NPC1L1, UPK1A, HSPA1A/B). GO/KEGG analyses indicated that the <60 signature centers on actin remodeling, filopodia, axonogenesis, and Rap1-mediated adhesion/signaling, consistent with early neurite and structural reorganization. The [&ge;]60 signature was enriched for blood microparticles, chemokine activity, infection-related pathways, ER protein processing, and arachidonic/ether lipid and cytokine signaling, pointing to broad immune-metabolic and proteostasis dysregulation. Cross-age comparison showed that classical PD neuronal immediate-early gene changes are largely [&ge;]60-driven, whereas early-onset PD involves novel lncRNA-calcium-lipid and cytoskeletal modules. These findings highlight LINC02188, TLCD3B and related cytoskeletal/lncRNA genes as novel early-onset PD-associated candidates, and NPC1L1, IL3RA and PVALB as age-amplified markers within the broader PD transcriptomic signature.

bioinformatics↗

Targeting Siglec-10/α3β1 Integrin Interactions Enhances Macrophage-Mediated Phagocytosis of Pancreatic Cancer

Tumor-associated macrophages (TAMs) in the pancreatic ductal adenocarcinoma (PDAC) tumor microenvironment (TME) exhibit immunosuppressive phenotypes and impaired phagocytic activity, facilitating tumor progression and immune evasion. Here, we identify integrin 3{beta}1, composed of ITGA3 and ITGB1 subunits, as a sialylated glycoprotein ligand for Siglec-10, an inhibitory glyco-immune checkpoint receptor highly expressed on TAMs in PDAC. The interaction between Siglec-10 on TAMs and 3{beta}1 on PDAC cells suppresses macrophage-mediated phagocytosis, thereby promoting immune evasion. Consistently, disrupting Siglec-10 interactions with monoclonal antibodies significantly enhances macrophage phagocytosis of PDAC cells and alleviates myeloid cell-mediated inhibition of T cell proliferation and activation in vitro. In both a PDAC xenograft mouse model engrafted with human macrophages and a human Siglec-10 transgenic mouse model, targeting Siglec-10 with monoclonal antibodies reduces PDAC tumor growth. These findings suggest that Siglec-10 interactions are key mediators of TAM-driven immune evasion in PDAC and highlight the therapeutic potential of targeting these interactions to restore anti-tumor immunity. SIGNIFICANCEPancreatic tumor cells exploit integrin 3{beta}1 to engage the immunosuppressive checkpoint receptor Siglec-10 on myeloid cells, driving immune evasion, and antibody-mediated blockade of Siglec-10 restores myeloid cell-mediated anti-PDAC immunity.

immunology↗

Intraperitoneal activation of myeloid cells clears ascites and reveals IL27-dependent regression of metastatic ovarian cancer

Patients with metastatic ovarian cancer (OvCa) have a 5-year survival rate of less than 30% due to persisting dissemination of chemoresistant cells in the peritoneal fluid and the immunosuppressive microenvironment in the peritoneal cavity. Here, we report that intraperitoneal administration of {beta}-glucan and IFN{gamma} (BI) induced robust tumor regression in clinically relevant models of metastatic OvCa. BI induced tumor regression by controlling fluid tumor burden and activating localized antitumor immunity. {beta}-glucan alone cleared ascites and eliminated fluid tumor cells by inducing intraperitoneal clotting in the fluid and Dectin-1-Syk-dependent NETosis in the omentum. In omentum tumors, BI expanded a novel subset of immunostimulatory IL27+ macrophages and neutralizing IL27 impaired BI efficacy in vivo. Moreover, BI directly induced IL27 secretion in macrophages where single agent treatment did not. Finally, BI extended mouse survival in a chemoresistant model and significantly improved chemotherapy response in a chemo-sensitive model. In summary, we propose a new therapeutic strategy for the treatment of metastatic OvCa.

immunology↗