Evaluating the effects of temperature variations on animals plays an important role in understanding the threat of climate warming.The effects of developmental temperature on offspring performance are critical in eval...Evaluating the effects of temperature variations on animals plays an important role in understanding the threat of climate warming.The effects of developmental temperature on offspring performance are critical in evaluating the effects of warming temperatures on the fitness of ovipa-rous species,but the physiological and biochemical basis of this developmental plasticity is largely unknown.In this study,we incubated eggs of the turtle Pelodiscus sinensis at low(24℃),medium(28℃),and high(32℃)temperatures,and evaluated the effects of developmental temperature on offspring fitness,and metabolic enzymes in the neck and limb muscles of hatchlings.The hatchlings from eggs incubated at the medium temperature showed better fitness-related performance(righting response and swimming capacity)and higher activities of metabolic enzymes(hexokinase,HK;lactate dehydrogenase,LDH)than hatchlings from the eggs incubated at high or low temperatures.In addition,the swimming speed and righting response were significantly correlated with the HK activities in limb(swimming speed)and neck(righting response)muscles,suggesting that the developmental plasticity of energy metabolic pathway might play a role in determining the way incubation temperature affects offspring phenotypes.Integrating the fitness-related performance and the activities of metabolic enzymes,we predict that the P sinensis from high latitude would not face the detrimental effects of climate warming until the average nest temperatures reach 32℃.展开更多
Mammalian target of rapamycin (mTOR) is aberrantly activated in many cancer types, and two rapamycin derivatives are currently approved by the Food and Drug Administration (FDA) of the United States for treating renal...Mammalian target of rapamycin (mTOR) is aberrantly activated in many cancer types, and two rapamycin derivatives are currently approved by the Food and Drug Administration (FDA) of the United States for treating renal cell carcinoma. Mechanistically, mTOR is hyperactivated in human cancers either due to the genetic activation of its upstream activating signaling pathways or the genetic inactivation of its negative regulators. The tumor suppressor liver kinase B1 (LKB1), also known as serine/threonine kinase 11 (STK11), is involved in cell polarity, cell detachment and adhesion, tumor metastasis, and energetic stress response. A key role of LKB1 is to negatively regulate the activity of mTOR complex 1 (mTORC1). This review summarizes the molecular basis of this negative interaction and recent research progress in this area.展开更多
基金supported by the National Natural Science Foundation of China(31870391,32271572)supported by Youth Innovation Promotion Association Chinese Academy of Sciences(No.2019085).
文摘Evaluating the effects of temperature variations on animals plays an important role in understanding the threat of climate warming.The effects of developmental temperature on offspring performance are critical in evaluating the effects of warming temperatures on the fitness of ovipa-rous species,but the physiological and biochemical basis of this developmental plasticity is largely unknown.In this study,we incubated eggs of the turtle Pelodiscus sinensis at low(24℃),medium(28℃),and high(32℃)temperatures,and evaluated the effects of developmental temperature on offspring fitness,and metabolic enzymes in the neck and limb muscles of hatchlings.The hatchlings from eggs incubated at the medium temperature showed better fitness-related performance(righting response and swimming capacity)and higher activities of metabolic enzymes(hexokinase,HK;lactate dehydrogenase,LDH)than hatchlings from the eggs incubated at high or low temperatures.In addition,the swimming speed and righting response were significantly correlated with the HK activities in limb(swimming speed)and neck(righting response)muscles,suggesting that the developmental plasticity of energy metabolic pathway might play a role in determining the way incubation temperature affects offspring phenotypes.Integrating the fitness-related performance and the activities of metabolic enzymes,we predict that the P sinensis from high latitude would not face the detrimental effects of climate warming until the average nest temperatures reach 32℃.
基金supported by NIH Grant R01-CA140571 (to W.Z.)P01-CA116676 (to W.Z. and P.V.). W.Z. is an Anise McDaniel BrockScholar, Georgia Cancer Coalition Scholar, and American Cancer Research Scholar
文摘Mammalian target of rapamycin (mTOR) is aberrantly activated in many cancer types, and two rapamycin derivatives are currently approved by the Food and Drug Administration (FDA) of the United States for treating renal cell carcinoma. Mechanistically, mTOR is hyperactivated in human cancers either due to the genetic activation of its upstream activating signaling pathways or the genetic inactivation of its negative regulators. The tumor suppressor liver kinase B1 (LKB1), also known as serine/threonine kinase 11 (STK11), is involved in cell polarity, cell detachment and adhesion, tumor metastasis, and energetic stress response. A key role of LKB1 is to negatively regulate the activity of mTOR complex 1 (mTORC1). This review summarizes the molecular basis of this negative interaction and recent research progress in this area.
