CTP synthase is compartmentalized within a subcellular structure,termed the cytoophidium,in a range of organisms including bacteria, yeast,fruit fly and rat.Here we show that CTP synthase is also compartmentalized int...CTP synthase is compartmentalized within a subcellular structure,termed the cytoophidium,in a range of organisms including bacteria, yeast,fruit fly and rat.Here we show that CTP synthase is also compartmentalized into cytoophidia in human cells.Surprisingly,the occurrence of cytoophidia in human cells increases upon treatment with a glutamine analog 6-diazo-5-oxo-L-norleucine（DON）,an inhibitor of glutamine-dependent enzymes including CTP synthase.Experiments in flies confirmed that DON globally promotes cytoophidium assembly.Clonal analysis via CTP synthase RNA interference in somatic cells indicates that CTP synthase expression level is critical for the formation of cytoophidia.Moreover,DON facilitates cytoophidium assembly even when CTP synthase level is low.A second glutamine analog azaserine also promotes cytoophidum formation.Our data demonstrate that glutamine analogs serve as useful tools in the study of cytoophidia.展开更多
BACKGROUND： Some research exists on the effect of non-pharmacological approaches for labor pain relief However, there is limited information about effectiveness of breathing exercises in pregnant women to reduce mate...BACKGROUND： Some research exists on the effect of non-pharmacological approaches for labor pain relief However, there is limited information about effectiveness of breathing exercises in pregnant women to reduce maternal pain during labor. OBJECTIVE： To determine whether breathing exercises for pregnant women during the second stage of labor have beneficial effects on maternal pain, duration of labor, and the first-minute Appearance, Pulse, Grimace, Activity and Respiration （APGAR） scores. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS： This randomized clinical trial involved 250 pregnant women, who were randomly divided into two groups： intervention group （IG; n = 125） and control group （CG; n = 125）. IG received one session breathing exercise training and performed breathing exercises during the second stage of labor versus the CG that did not receive any breathing exercise training. MAIN OUTCOME MEASURES： The effects of breathing exercises on maternal pain were determined by Visual Analogue Scale （VAS）, duration of the second stage of labor, and the first-minute APGAR scores. RESULTS： The mean age of the participants was （23.2 _＋ 4.2） （range： 18 to 42） years. Both IG and CG had similar baseline characteristics in terms of age, education level, occupation, and smoking （P 〉 0.05）. The mean VAS scores of IG and CG were （88.2 ＋_ 6.3） and （90.5 ＋_ 7.0）, respectively （P 〈 0.001）. The duration of the second stage of labor was （369.6 ＋ 92.0） s for IG and （440.7 ＋ 142.5） s for CG （P 〈 0.001 ）. The mean first-minute APGAR scores were （8.84 ＋ 0.50） for IG and （8.73 ＋ 0.89） for CG （P 〉 0.05）. CONCLUSION： Based on this study, breathing exercises with deep inhalation and exhalation in pregnant women are effective in reducing the perception of labor pain and shortening the duration of the second stage of delivery. Therefore, we recommend breathing exercises as an effective modality for labor pain management and shortening t展开更多
AIM:To investigate the effect of lacidipine,thiamine pyrophosphate(TPP)and the combination of lacidipine and TPP against oxidative and inflammatory eye damage induced by bilateral common carotid artery ligation in rat...AIM:To investigate the effect of lacidipine,thiamine pyrophosphate(TPP)and the combination of lacidipine and TPP against oxidative and inflammatory eye damage induced by bilateral common carotid artery ligation in rats.METHODS:Male albino Wistar rats were categorized as those who underwent sham surgery(SG),right and left common carotid cross-clamping and unclamping procedure(CCU),lacidipine+CCU(LCCU),TPP+CCU(TCCU),and combination of lacidipine and TPP(LTC)+CCU(LTCCU).One hour before anesthesia,the LCCU(n=6)received lacidipine(4 mg/kg,orally)and the TCCU(n=6)received TPP(20 mg/kg,intraperitoneally).The SG(n=6)and CCU(n=6)received the same volume of distilled water from the same route.After anesthesia(60 mg/kg ketamine,intraperitoneally),the necks of the rats were opened in the midline.Ischemia was created for 10min by placing clips on the right and left common carotid arteries.Rats in the SG only underwent subcutaneous incision.After 10min,the clips were removed and reperfusion was achieved for six days.Then,the animals were euthanized(120 mg/kg ketamine,intraperitoneally)and the levels of oxidant,antioxidant and proinflammatory cytokines in the eye tissues were determined.The retinal tissue of the eye was also examined histopathologically.RESULTS:Lacidipine,TPP,and LTC significantly prevent the increase in malondialdehyde,tumor necrosis factoralpha,interleukin-1β(IL-1β),and IL-6 levels,decrease in total glutathione levels,superoxide dismutase and catalase activities and histopathological retinal damage in eye tissue induced by bilateral common carotid artery ligation in rats.The impact of these drugs on protection is determined to be LTC>lacidipine>TPP.CONCLUSION:As a result of the study,it is concluded that LTC may be more effective than lacidipine and TPP alone in treating ocular ischemic syndrome.展开更多
CTP synthase （CTPsyn） is a metabolic enzyme responsible for the de novo synthesis of the nucleotide CTE Several recent studies have shown that CTPsyn forms filamentous subcellular structures known as cytoophidia in ...CTP synthase （CTPsyn） is a metabolic enzyme responsible for the de novo synthesis of the nucleotide CTE Several recent studies have shown that CTPsyn forms filamentous subcellular structures known as cytoophidia in bacteria, yeast, fruit flies and humans. However, it remains elusive whether and how CTPsyn and cytoophidia play a role during development. Here, we show that cytoophidia are abundant in the neuroepithelial stem cells in Drosophila optic lobes. Optic lobes are underdeveloped in CTPsyn mutants as well as in CTPsyn RNAi. Moreover, overexpressing CTPsyn impairs the development of optic lobes, specifically by blocking the transition from neuro- epithelium to neuroblast. Taken together, our results indicate that CTPsyn is critical for optic lobe homeostasis in Drosophila.展开更多
Compartmentation of enzymes via filamentation has arisen as a mechanism for the regulation of metabolism.In 2010,three groups independently reported that CTP synthase(CTPS)can assemble into a filamentous structure ter...Compartmentation of enzymes via filamentation has arisen as a mechanism for the regulation of metabolism.In 2010,three groups independently reported that CTP synthase(CTPS)can assemble into a filamentous structure termed the cytoophidium.In searching for CTPS-interacting proteins,here we perform a yeast two-hybrid screening of Drosophila proteins and identify a putative CTPS-interacting protein,△~1-pyrroline-5-carboxylate synthase(P5CS).Using the Drosophila follicle cell as the in vivo model,we confirm that P5CS forms cytoophidia,which are associated with CTPS cytoophidia.Overexpression of P5CS increases the length of CTPS cytoophidia.Conversely,filamentation of CTPS affects the morphology of P5CS cytoophid ia.Finally,in vitro analyses confirm the filament-fo rming property of P5CS.Our work links CTPS with P5CS,two enzymes involved in the rate-limiting steps in pyrimidine and proline biosynthesis,respectively.展开更多
The International Conference on Arginine and Pyrimidines （ICAP） had its origin as an arginine workshop organised by a group of microbiologists led by Werner Maas in 1972 （Rubio, 2003）. The shared requirement of ca...The International Conference on Arginine and Pyrimidines （ICAP） had its origin as an arginine workshop organised by a group of microbiologists led by Werner Maas in 1972 （Rubio, 2003）. The shared requirement of carbamoyl phosphate in both arginine and pyrimidine metabolism led to a natural association of researchers working in both fields.展开更多
基金the TRiP at Harvard Medical School(NIH/ NIGMS R01-GM084947)
文摘CTP synthase is compartmentalized within a subcellular structure,termed the cytoophidium,in a range of organisms including bacteria, yeast,fruit fly and rat.Here we show that CTP synthase is also compartmentalized into cytoophidia in human cells.Surprisingly,the occurrence of cytoophidia in human cells increases upon treatment with a glutamine analog 6-diazo-5-oxo-L-norleucine（DON）,an inhibitor of glutamine-dependent enzymes including CTP synthase.Experiments in flies confirmed that DON globally promotes cytoophidium assembly.Clonal analysis via CTP synthase RNA interference in somatic cells indicates that CTP synthase expression level is critical for the formation of cytoophidia.Moreover,DON facilitates cytoophidium assembly even when CTP synthase level is low.A second glutamine analog azaserine also promotes cytoophidum formation.Our data demonstrate that glutamine analogs serve as useful tools in the study of cytoophidia.
文摘BACKGROUND： Some research exists on the effect of non-pharmacological approaches for labor pain relief However, there is limited information about effectiveness of breathing exercises in pregnant women to reduce maternal pain during labor. OBJECTIVE： To determine whether breathing exercises for pregnant women during the second stage of labor have beneficial effects on maternal pain, duration of labor, and the first-minute Appearance, Pulse, Grimace, Activity and Respiration （APGAR） scores. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS： This randomized clinical trial involved 250 pregnant women, who were randomly divided into two groups： intervention group （IG; n = 125） and control group （CG; n = 125）. IG received one session breathing exercise training and performed breathing exercises during the second stage of labor versus the CG that did not receive any breathing exercise training. MAIN OUTCOME MEASURES： The effects of breathing exercises on maternal pain were determined by Visual Analogue Scale （VAS）, duration of the second stage of labor, and the first-minute APGAR scores. RESULTS： The mean age of the participants was （23.2 _＋ 4.2） （range： 18 to 42） years. Both IG and CG had similar baseline characteristics in terms of age, education level, occupation, and smoking （P 〉 0.05）. The mean VAS scores of IG and CG were （88.2 ＋_ 6.3） and （90.5 ＋_ 7.0）, respectively （P 〈 0.001）. The duration of the second stage of labor was （369.6 ＋ 92.0） s for IG and （440.7 ＋ 142.5） s for CG （P 〈 0.001 ）. The mean first-minute APGAR scores were （8.84 ＋ 0.50） for IG and （8.73 ＋ 0.89） for CG （P 〉 0.05）. CONCLUSION： Based on this study, breathing exercises with deep inhalation and exhalation in pregnant women are effective in reducing the perception of labor pain and shortening the duration of the second stage of delivery. Therefore, we recommend breathing exercises as an effective modality for labor pain management and shortening t
文摘AIM:To investigate the effect of lacidipine,thiamine pyrophosphate(TPP)and the combination of lacidipine and TPP against oxidative and inflammatory eye damage induced by bilateral common carotid artery ligation in rats.METHODS:Male albino Wistar rats were categorized as those who underwent sham surgery(SG),right and left common carotid cross-clamping and unclamping procedure(CCU),lacidipine+CCU(LCCU),TPP+CCU(TCCU),and combination of lacidipine and TPP(LTC)+CCU(LTCCU).One hour before anesthesia,the LCCU(n=6)received lacidipine(4 mg/kg,orally)and the TCCU(n=6)received TPP(20 mg/kg,intraperitoneally).The SG(n=6)and CCU(n=6)received the same volume of distilled water from the same route.After anesthesia(60 mg/kg ketamine,intraperitoneally),the necks of the rats were opened in the midline.Ischemia was created for 10min by placing clips on the right and left common carotid arteries.Rats in the SG only underwent subcutaneous incision.After 10min,the clips were removed and reperfusion was achieved for six days.Then,the animals were euthanized(120 mg/kg ketamine,intraperitoneally)and the levels of oxidant,antioxidant and proinflammatory cytokines in the eye tissues were determined.The retinal tissue of the eye was also examined histopathologically.RESULTS:Lacidipine,TPP,and LTC significantly prevent the increase in malondialdehyde,tumor necrosis factoralpha,interleukin-1β(IL-1β),and IL-6 levels,decrease in total glutathione levels,superoxide dismutase and catalase activities and histopathological retinal damage in eye tissue induced by bilateral common carotid artery ligation in rats.The impact of these drugs on protection is determined to be LTC>lacidipine>TPP.CONCLUSION:As a result of the study,it is concluded that LTC may be more effective than lacidipine and TPP alone in treating ocular ischemic syndrome.
文摘CTP synthase （CTPsyn） is a metabolic enzyme responsible for the de novo synthesis of the nucleotide CTE Several recent studies have shown that CTPsyn forms filamentous subcellular structures known as cytoophidia in bacteria, yeast, fruit flies and humans. However, it remains elusive whether and how CTPsyn and cytoophidia play a role during development. Here, we show that cytoophidia are abundant in the neuroepithelial stem cells in Drosophila optic lobes. Optic lobes are underdeveloped in CTPsyn mutants as well as in CTPsyn RNAi. Moreover, overexpressing CTPsyn impairs the development of optic lobes, specifically by blocking the transition from neuro- epithelium to neuroblast. Taken together, our results indicate that CTPsyn is critical for optic lobe homeostasis in Drosophila.
基金supported by ShanghaiTech University,the UK Medical Research Council(Grant No.MC_UU_12021/3 and MC_U137788471)National Natural Science Foundation of China(Grant No.31771490)。
文摘Compartmentation of enzymes via filamentation has arisen as a mechanism for the regulation of metabolism.In 2010,three groups independently reported that CTP synthase(CTPS)can assemble into a filamentous structure termed the cytoophidium.In searching for CTPS-interacting proteins,here we perform a yeast two-hybrid screening of Drosophila proteins and identify a putative CTPS-interacting protein,△~1-pyrroline-5-carboxylate synthase(P5CS).Using the Drosophila follicle cell as the in vivo model,we confirm that P5CS forms cytoophidia,which are associated with CTPS cytoophidia.Overexpression of P5CS increases the length of CTPS cytoophidia.Conversely,filamentation of CTPS affects the morphology of P5CS cytoophid ia.Finally,in vitro analyses confirm the filament-fo rming property of P5CS.Our work links CTPS with P5CS,two enzymes involved in the rate-limiting steps in pyrimidine and proline biosynthesis,respectively.
基金sponsored by MRC Functional Genomics Unit at the University of Oxford, the Journal of Genetics and Genomics, and Dutscher Scientific
文摘The International Conference on Arginine and Pyrimidines （ICAP） had its origin as an arginine workshop organised by a group of microbiologists led by Werner Maas in 1972 （Rubio, 2003）. The shared requirement of carbamoyl phosphate in both arginine and pyrimidine metabolism led to a natural association of researchers working in both fields.
