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Benjamin P. Towler Amy L. Pashler Hope J. Haime Katarzyna M. Przybyl Sandra C. Viegas Rute G. Matos Simon J. Morley Cecilia M. Arraiano Sarah F. Newbury 《PLoS genetics》2020,16(12)
Dis3L2 is a highly conserved 3’-5’ exoribonuclease which is mutated in the human overgrowth disorders Perlman syndrome and Wilms’ tumour of the kidney. Using Drosophila melanogaster as a model system, we have generated a new dis3L2 null mutant together with wild-type and nuclease-dead genetic lines in Drosophila to demonstrate that the catalytic activity of Dis3L2 is required to control cell proliferation. To understand the cellular pathways regulated by Dis3L2 to control proliferation, we used RNA-seq on dis3L2 mutant wing discs to show that the imaginal disc growth factor Idgf2 is responsible for driving the wing overgrowth. IDGFs are conserved proteins homologous to human chitinase-like proteins such as CHI3L1/YKL-40 which are implicated in tissue regeneration as well as cancers including colon cancer and non-small cell lung cancer. We also demonstrate that loss of DIS3L2 in human kidney HEK-293T cells results in cell proliferation, illustrating the conservation of this important cell proliferation pathway. Using these human cells, we show that loss of DIS3L2 results in an increase in the PI3-Kinase/AKT signalling pathway, which we subsequently show to contribute towards the proliferation phenotype in Drosophila. Our work therefore provides the first mechanistic explanation for DIS3L2-induced overgrowth in humans and flies and identifies an ancient proliferation pathway controlled by Dis3L2 to regulate cell proliferation and tissue growth. 相似文献
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Gleb P. Tolstykh Gary L. Thompson Hope T. Beier Zachary A. Steelman Bennett L. Ibey 《Biochemistry and Biophysics Reports》2017
Cell swelling and blebbing has been commonly observed following nanosecond pulsed electric field (nsPEF) exposure. The hypothesized origin of these effects is nanoporation of the plasma membrane (PM) followed by transmembrane diffusion of extracellular fluid and disassembly of cortical actin structures. This investigation will provide evidence that shows passive movement of fluid into the cell through nanopores and increase of intracellular osmotic pressure are not solely responsible for this observed phenomena. We demonstrate that phosphatidylinositol-4,5-bisphosphate (PIP2) depletion and hydrolysis are critical steps in the chain reaction leading to cellular blebbing and swelling. PIP2 is heavily involved in osmoregulation by modulation of ion channels and also serves as an intracellular membrane anchor to cortical actin and phospholipase C (PLC). Given the rather critical role that PIP2 depletion appears to play in the response of cells to nsPEF exposure, it remains unclear how its downstream effects and, specifically, ion channel regulation may contribute to cellular swelling, blebbing, and unknown mechanisms of the lasting “permeabilization” of the PM. 相似文献
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Thomas P. Wiegand Braley Gentry Zachary McCoy Craig Tanis Hope Klug Michael B. Bonsall Jennifer Nagel Boyd 《Ecology and evolution》2020,10(17):9037-9047
Understanding the ecological and evolutionary factors that influence species rarity has important theoretical and applied implications, yet the reasons why some species are rare while others are common remain unresolved. As a novel exploration of scientific knowledge, we used network analysis conceptually to visualize the foci of a comprehensive base of >800 studies on plant species rarity within the context of ecology and evolution. In doing so, we highlight existing research strengths that could substantiate novel syntheses and gaps that could inspire new research. Our results reveal strong integrated foci on population dynamics with other ecological concepts. In contrast, despite the potential for ecological and evolutionary processes to interact, few studies explored the interplay of environmental factors and microevolutionary patterns. The cellular and molecular biology, physiology, and plasticity of rare plant species within both ecological and evolutionary contexts similarly provide avenues for impactful future investigations. 相似文献
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Hayat Hage Shingo Miyauchi Máté Virágh Elodie Drula Byoungnam Min Delphine Chaduli David Navarro Anne Favel Manon Norest Laurence Lesage-Meessen Balázs Bálint Zsolt Merényi Laura de Eugenio Emmanuelle Morin Angel T. Martínez Petr Baldrian Martina Štursová María Jesús Martínez Cenek Novotny Jon K. Magnuson Joey W. Spatafora Sundy Maurice Jasmyn Pangilinan Willian Andreopoulos Kurt LaButti Hope Hundley Hyunsoo Na Alan Kuo Kerrie Barry Anna Lipzen Bernard Henrissat Robert Riley Steven Ahrendt László G. Nagy Igor V. Grigoriev Francis Martin Marie-Noëlle Rosso 《Environmental microbiology》2021,23(10):5716-5732
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