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Yoana Rabanal-Ruiz Adam Byron Alexander Wirth Ralitsa Madsen Lucia Sedlackova Graeme Hewitt Glyn Nelson Julian Stingele Jimi C. Wills Tong Zhang Andr Zeug Reinhard Fssler Bart Vanhaesebroeck Oliver D.K. Maddocks Evgeni Ponimaskin Bernadette Carroll Viktor I. Korolchuk 《The Journal of cell biology》2021,220(5)
The mammalian target of rapamycin complex 1 (mTORC1) integrates mitogenic and stress signals to control growth and metabolism. Activation of mTORC1 by amino acids and growth factors involves recruitment of the complex to the lysosomal membrane and is further supported by lysosome distribution to the cell periphery. Here, we show that translocation of lysosomes toward the cell periphery brings mTORC1 into proximity with focal adhesions (FAs). We demonstrate that FAs constitute discrete plasma membrane hubs mediating growth factor signaling and amino acid input into the cell. FAs, as well as the translocation of lysosome-bound mTORC1 to their vicinity, contribute to both peripheral and intracellular mTORC1 activity. Conversely, lysosomal distribution to the cell periphery is dispensable for the activation of mTORC1 constitutively targeted to FAs. This study advances our understanding of spatial mTORC1 regulation by demonstrating that the localization of mTORC1 to FAs is both necessary and sufficient for its activation by growth-promoting stimuli. 相似文献
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草本植物的进化:解决难题的关键在于忍耐而非逃避
木本植物延续了其祖先被子植物的生长形态,而草本植物则不断地从中进化演变。虽然关于驱动草本植物习性进化的因素已有许多假设,但是通过舍弃地上生物质从而避免冬季冻害的能力常常被认为是促使其进化的主要力量。然而,鉴于草本植物在反复干扰中依旧能够轻松存活,我们提出了不可预测的干扰可能比季节性霜冻更为重要的假设。我们通过比较草本植物和木本植物应对3种模拟干扰(容易预测的冬季冰冻、不易预测的春季冰冻和食草作用)的能力来验证这一假设。通过比较20种不同植物在同质园实验中的表现,我们评估了这些干扰对植物死亡和再生方面的影响。研究结果表明,在冬季冰冻条件下,比起木本植物,草本植物在存活率上并没有优势。在不易预测的春季冰冻条件下,草本植物比木本植物的存活率更高。而在模拟食草作用的条件下,草本植物的这种生存优势更大。在不可预测的条件下,草本植物相较于木本植物的生存优势表明,草本植物的生长形式可能是对不可预测的干扰的适应,这种逆境忍耐通过其损失地上生物质也能够生存的能力得以实现。因此,哺乳动物的食草行为或火灾等原因或许最有可能是木本植物向草本植物过渡的因素。 相似文献
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Nicholas Murgolo Alex G. Therien Bonnie Howell Daniel Klein Kenneth Koeplinger Linda A. Lieberman Gregory C. Adam Jessica Flynn Philip McKenna Gokul Swaminathan Daria J. Hazuda David B. Olsen 《PLoS pathogens》2021,17(2)
Since the initial report of the novel Coronavirus Disease 2019 (COVID-19) emanating from Wuhan, China, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has spread globally. While the effects of SARS-CoV-2 infection are not completely understood, there appears to be a wide spectrum of disease ranging from mild symptoms to severe respiratory distress, hospitalization, and mortality. There are no Food and Drug Administration (FDA)-approved treatments for COVID-19 aside from remdesivir; early efforts to identify efficacious therapeutics for COVID-19 have mainly focused on drug repurposing screens to identify compounds with antiviral activity against SARS-CoV-2 in cellular infection systems. These screens have yielded intriguing hits, but the use of nonhuman immortalized cell lines derived from non-pulmonary or gastrointestinal origins poses any number of questions in predicting the physiological and pathological relevance of these potential interventions. While our knowledge of this novel virus continues to evolve, our current understanding of the key molecular and cellular interactions involved in SARS-CoV-2 infection is discussed in order to provide a framework for developing the most appropriate in vitro toolbox to support current and future drug discovery efforts. 相似文献
159.
Adam J. Golman Kerry A. Danelson James P. Gaewsky 《Computer methods in biomechanics and biomedical engineering》2013,16(10):1044-1055
This study's purpose was to implement injury metrics into the Total Human Model for Safety (THUMS) mirroring the spinal accelerometers, rib accelerometers and chest band instrumentation from two lateral post-mortem human subject sled test configurations. In both sled configurations, THUMS contacted a flat rigid surface (either a wall or beam) at 6.7 m/s. Sled A maximum simulated wall forces for the thorax, abdomen and pelvis were 7.1, 5.0 and 10.0 kN versus 5.7 ± 0.8, 3.4 ± 1.2 and 6.2 ± 2.7 kN experimentally. Sled B maximum simulated beam forces for the torso and pelvis were 8.0 and 7.6 kN versus 8.5 ± 0.2 and 7.9 ± 2.5 kN experimentally. Quantitatively, force magnitude contributed more to variation between simulated and experimental forces than phase shift. Acceleration-based injury metrics were within one standard deviation of experimental means except for the lower spine in the rigid wall sled test. These validated metrics will be useful for quantifying occupant loading conditions and calculating injury risks in various loading configurations. 相似文献
160.
Ferdinand C. O. Los Tara M. Randis Raffi V. Aroian Adam J. Ratner 《Microbiology and molecular biology reviews》2013,77(2):173-207