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Das, P.

Publications and source records attributed to Das, P..

5 recordsLinked to original sources

A gradient in inner pressure of germline cells controls overlaying epithelial cell morphogenesis

It is unknown how growth in one tissue impacts morphogenesis in a neighboring tissue. To address this, we used the Drosophila ovarian follicle, where a cluster of 15 nurse cells and a posteriorly located oocyte are surrounded by a layer of epithelial cells. It is known that as the nurse cells grow, the overlying epithelial cells flatten in a wave that begins in the anterior. Here, we demonstrate that an anterior to posterior gradient of decreasing cytoplasmic pressure is present across the nurse cells and that this gradient acts through TGF{beta} to control both the triggering and the progression of the wave of epithelial cell flattening. Our data indicate that intrinsic nurse cell growth is important to control proper nurse cell pressure. Finally, we reveal that nurse cell pressure and subsequent TGF{beta} activity in the StC combine to increase follicle elongation in the anterior, which is crucial for allowing nurse cell growth and pressure control. More generally, our results reveal that during development, inner cytoplasmic pressure in individual cells has an important role in shaping their neighbors. Impact StatementCell shape change depends on extrinsic forces exerted by cytoplasmic pressure in neighbouring cells.

developmental biology

MiR-146a-dependent regulation of CD24/AKT/β-catenin axis drives stem cell phenotype in oral cancer

Cancer stem cells (CSCs) are known to potentiate tumor initiation and maintenance in Oral Squamous Cell Carcinoma (OSCC). Increasing evidences suggest that CD44highCD24low population in OSCC are potential CSCs. MicroRNAs (miRNAs) have emerged as crucial players in tumor development. However, their role in maintenance of OSCC stem cells remains unclear. Here we report that CD44highCD24low population within OSCC cells and primary HNSCC tumors have an elevated expression of miR-146a. Moreover, over-expression of miR-146a results in enhanced stemness phenotype by augmenting CD44highCD24low population. We demonstrate that miR-146a induces stemness by stabilizing {beta}-catenin with concomitant loss of E-cadherin and CD24. Interestingly, CD24 is identified as a novel functional target of miR-146a and ectopic expression of CD24 abrogates miR-146a driven potential CSC phenotype. Mechanistic analysis reveals that higher CD24 levels inhibit AKT phosphorylation leading to {beta}-catenin degradation. Using stably expressing miR-146a/CD24 OSCC cell lines, we also validate that the miR-146a/ CD24/AKT loop significantly alters tumorigenic ability in vivo. Furthermore, we confirmed that {beta}-catenin trans-activates miR-146a, thereby forming a positive feedback loop contributing to stem cell maintenance. Collectively, our study demonstrates that miR-146a regulate CSCs in OSCC through CD24-AKT-{beta}-catenin axis.\n\nHighlightsO_LIMiR-146a induces cancer stem cell characteristics in OSCC by targeting CD24\nC_LIO_LICD24 abrogates miR-146a mediated stemness via {beta}-catenin degradation in non-CSCs\nC_LIO_LIAkt/Wnt pathway is critical for sustenance of miR-146a driven potential CSCs\nC_LIO_LIThe miR-146a/CD24/AKT loop significantly alters tumorigenic ability in vivo\nC_LI

cancer biology

Dose Escalation for Locally Advanced Pancreatic Cancer: How High Can We Go?

Introduction Introduction Methods Results Discussion References Locally advanced pancreatic cancer (LAPC) is particularly difficult to treat given that it exhibits a poor response to chemotherapy and is by definition unresectable. A large proportion of patients experience significant morbidity and mortality due to local progression. As systemic therapy improves with the advent of gemcitabine/ abraxane1 and FOLFIRINOX2, the burden of local disease will only increase. Standard radiation therapy doses have failed to improve survival, which is not unexpected given anatomical and technical limitations. Although the LAP-07 trial3 failed to show an overall survival benefit to radiation at standard doses, it did show benefits in terms of local control and t ...

clinical trials

Early warning signals regarding environmental suitability in the Drosophila antenna

HighlightsO_LIA novel geotaxis assay showed high intensity odorant exposures are harmful to flies\nC_LIO_LIRepulsion at high odor intensities can be a protective mechanism\nC_LIO_LIOlfactory receptor neuron (ORN) excitability abruptly changes with odor intensity\nC_LIO_LIA linear combination of ORN activities can robustly predict intensity-dependent behavioral repulsion\nC_LI\n\nSummaryThe olfactory system is uniquely positioned to warn an organism of environmental threats. Whether and how it encodes such information is not understood. Here, we examined this issue in the fruit fly Drosophila melanogaster. We found that intensity-dependent repulsion to chemicals safeguarded flies from harmful, high-intensity vapor exposures. To understand how sensory input changed as the odor valence switched from innocuous to threatening, we recorded from olfactory receptor neurons (ORNs) in the fly antenna. Primarily, we observed two response non-linearities: recruitment of non-active ORNs at higher intensities, and abrupt transitions in neural excitability from regular spiking to high-firing oscillatory regime. Although non-linearities observed in any single ORN was not a good indicator, a simple linear combination of firing events from multiple neurons provided robust recognition of threating/repulsive olfactory stimuli. In sum, our results reveal how information necessary to avoid environmental threats may also be encoded in the insect antenna.

neuroscience

SUPERMAN prevents stamen formation and promotes stem cell termination in the fourth whorl of the Arabidopsis flower

The molecular and genetic networks underlying the determination of floral organ identity are well studied, but much less is known about how the flower is partitioned into four developmentally distinct whorls. The SUPERMAN gene is required for proper specification of the boundary between stamens in whorl 3 and carpels in whorl 4, as superman mutants exhibit supernumerary stamens but usually lack carpels. However, it has remained unclear whether extra stamens in superman mutants originate from an organ identity change in whorl 4 or the overproliferation of whorl 3. Using live confocal imaging, we show that the extra stamens in superman mutants arise from cells in whorl 4, which change their fate from female to male, while floral stem cells proliferate longer, allowing for the production of additional stamens.

developmental biology