9 research outputs found

    Cortical contraction drives the 3D patterning of epithelial cell surfaces

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    Cellular protrusions create complex cell surface topographies, but biomechanical mechanisms regulating their formation and arrangement are largely unknown. To study how protrusions form, we focused on the morphogenesis of microridges, elongated actin-based structures that are arranged in maze-like patterns on the apical surfaces of zebrafish skin cells. Microridges form by accreting simple finger-like precursors. Live imaging demonstrated that microridge morphogenesis is linked to apical constriction. A nonmuscle myosin II (NMII) reporter revealed pulsatile contractions of the actomyosin cortex, and inhibiting NMII blocked apical constriction and microridge formation. A biomechanical model suggested that contraction reduces surface tension to permit the fusion of precursors into microridges. Indeed, reducing surface tension with hyperosmolar media promoted microridge formation. In anisotropically stretched cells, microridges formed by precursor fusion along the stretch axis, which computational modeling explained as a consequence of stretch-induced cortical flow. Collectively, our results demonstrate how contraction within the 2D plane of the cortex can pattern 3D cell surfaces

    Genomic Profiling Identifies GATA6 as a Candidate Oncogene Amplified in Pancreatobiliary Cancer

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    Pancreatobiliary cancers have among the highest mortality rates of any cancer type. Discovering the full spectrum of molecular genetic alterations may suggest new avenues for therapy. To catalogue genomic alterations, we carried out array-based genomic profiling of 31 exocrine pancreatic cancers and 6 distal bile duct cancers, expanded as xenografts to enrich the tumor cell fraction. We identified numerous focal DNA amplifications and deletions, including in 19% of pancreatobiliary cases gain at cytoband 18q11.2, a locus uncommonly amplified in other tumor types. The smallest shared amplification at 18q11.2 included GATA6, a transcriptional regulator previously linked to normal pancreas development. When amplified, GATA6 was overexpressed at both the mRNA and protein levels, and strong immunostaining was observed in 25 of 54 (46%) primary pancreatic cancers compared to 0 of 33 normal pancreas specimens surveyed. GATA6 expression in xenografts was associated with specific microarray gene-expression patterns, enriched for GATA binding sites and mitochondrial oxidative phosphorylation activity. siRNA mediated knockdown of GATA6 in pancreatic cancer cell lines with amplification led to reduced cell proliferation, cell cycle progression, and colony formation. Our findings indicate that GATA6 amplification and overexpression contribute to the oncogenic phenotypes of pancreatic cancer cells, and identify GATA6 as a candidate lineage-specific oncogene in pancreatobiliary cancer, with implications for novel treatment strategies

    SAtellite-based Marine Process Understanding, Development, Research and Applications for Blue Economy (SAMUDRA): A Technology Demonstration Program in the Bay of Bengal

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    SAtellite-based Marine Process Understanding, Development, Research and Applications (SAMUDRA) for blue economy, a technology development program of the Space Applications Centre, is an umbrella program covering research and applications geared toward physical and biological oceanography making use of current and future satellite observations for developing the nation’s blue economy. The main motivation behind this project was to develop satellite and numerical model-based information and value-added products and to demonstrate the implementation of developed applications for operational requirements. The program also aimed at improving existing methodologies for various applications by utilizing space-based inputs. Several field campaigns with the use of NavIC-enabled instruments and NABHMITRA were conducted for measuring biophysical parameters and validation of developed applications in the coastal regions. One of the key aspects of this project was development of web-based customized tools/dissemination system for providing the information to the end users. Some of the key/notable achievements of SAMUDRA were development of a portal OceanEye (tailor-made web-portal for Shipping Corporation of India), storm-surge/inundation system, oil-spill trajectory modeling, level-next potential fishing zone algorithm and rip current alert system
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