Salicylic acid(SA)is an important phytohormone mediating both local and systemic defense responses in plants.Despite over half a century of research,how plants biosynthesize SA remains unresolved.In Arabidop-sis,a maj...Salicylic acid(SA)is an important phytohormone mediating both local and systemic defense responses in plants.Despite over half a century of research,how plants biosynthesize SA remains unresolved.In Arabidop-sis,a major part of SA is derived from isochorismate,a key intermediate produced by the isochorismate syn-thase,which is reminiscent of SA biosynthesis in bacteria.Whereas bacteria employ an isochorismate pyru-vate lyase(IPL)that catalyzes the turnover of isochorismate to pyruvate and SA,plants do not contain an IPL ortholog and generate SA from isochorismate through an unknown mechanism.Combining genetic and biochemical approaches,we delineated the SA biosynthetic pathway downstream of isochorismate in Ara-bidopsis.We found that PBS3,a GH3 acyl adenylase-family enzyme important for SA accumulation,catalyzes ATP-and Mg2+-dependent conjugation of L-glutamate primarily to the 8-carboxyl of isochorismate and yields the key SA biosynthetic intermediate,isochorismoyl-glutamate A.Moreover,we discovered that EPS1,a BAHD acyltransferase-family protein with a previously implicated role in SA accumulation upon pathogen attack,harbors a noncanonical active site and an unprecedented isochorismoyl-glutamate A pyruvoyl-glutamate lyase activity that produces SA from the isochorismoyl-glutamate A substrate.Together,PBS3 and EPS1 form a two-step metabolic pathway to produce SA from isochorismate in Arabidopsis,which is distinct from how SA is biosynthesized in bacteria.This study closes a major knowledge gap in plant SA meta-bolism and would help develop new strategies for engineering disease resistance in crop plants.展开更多
Introduction: The frequency, severity, cost of treatment, morbidity and mortality of stroke make it a real public health problem. In industrialized countries, strokes are the leading cause of physical disability in ad...Introduction: The frequency, severity, cost of treatment, morbidity and mortality of stroke make it a real public health problem. In industrialized countries, strokes are the leading cause of physical disability in adults, the second leading cause of dementia (after Alzheimer’s disease), and the third leading cause of death (after cancer and cardiovascular disease). It’s also a major cause of depression. The objective of our study was to describe the epidemiological, clinical and evolutionary aspects of stroke in the internal medicine department of Tivaouane Hospital. Material and Method: This is a retrospective study carried out from January 1, 2015 to December 31, 2018 on the files of patients hospitalized for stroke in the medical department of the EPS1 in Tivaouane. We took into account all the patients who had a brain CT (computed tomography) scan. We collected data related to socio-demographic characteristics, history, risk factors, reasons for admission, clinical signs, paraclinical examinations, as well as evolution. Results: Out of 1999 patients, 206 files of patients with stroke were collected, i.e. a proportion of 10.3%. Our study population had a mean age of 65.53 years [16 - 97 years]. We noted a clear predominance of women (50.5%). The majority of the population came from the outskirts of Tivaouane (56.7%). Risk factors for stroke were dominated by hypertension (90.3%), dyslipidemia (19.4%), previous stroke (18.9%), and diabetes (16%). The clinical signs were dominated by a motor deficit (94.1%), speech disorders (67.4%) and consciousness disorders (47%). Ischemic strokes were predominant (65%) over hemorrhagic strokes (34.5%). The outcome was generally unfavorable with 14.6% total recovery, 58.7% recovery with sequelae and a case fatality of 26.7%. Conclusion: It emerges from this study that strokes still remain a real public health problem. Knowledge of populations of risk factors as well as their proper management is fundamental in primary prevention strategies, the only guarantee for a reduc展开更多
Background and Aims:This study was designed to uncov-er the mechanism for extracellular polysaccharide(EPS1-1)-mediated effects on hepatocellular carcinoma(HCC)devel-opment.Methods:HCC cells were treated with EPS1-1,m...Background and Aims:This study was designed to uncov-er the mechanism for extracellular polysaccharide(EPS1-1)-mediated effects on hepatocellular carcinoma(HCC)devel-opment.Methods:HCC cells were treated with EPS1-1,miR-494-3p mimic,sh-TRIM36,and pcDNA3.1-TRIM36.The levels of miR-494-3p and TRIM36 were measured in nor-mal hepatocytes,THLE-2,and HepG2 and HuH7HCC cell lines,along with the protein expression of cyclin D/E and p21.The proliferation,cell cycle,and apoptosis of HCC cells were assayed.The interactions between miR-494-3p and TRIM36,and between TRIM36 and cyclin E were assessed.Finally,the expression and localization of TRIM36 and cyclin E were monitored,and tumor apoptosis was detected,in tumor xenograft model.Results:EPS1-1 suppressed HCC cell proliferation and cyclin D/E expression and promoted apoptosis and p21 expression.miR-494-3p was upregulated and TRIM36 was downregulated in HCC cells.Transfection with miR-494-3p mimic or sh-TRIM36 facilitated HCC cell proliferation and the expression of cyclin D/E protein but they inhibited apoptosis and p21 expression in the pres-ence of EPS1-1.Overexpression of TRIM36 further con-solidated EPS1-1-mediated inhibition of HCC proliferation,cyclin D/E,and the promotion of apoptosis and p21 expres-sion.Those effects were reversed by miR-494-3p overex-pression.TRIM36 was a target gene of miR-494-3p,and TRIM36 induced cyclin E ubiquitination.EPS1-1 suppressed cyclin E expression,promoted TRIM36 expression and tu-mor apoptosis,all of which were abrogated by increasing the expression of miR-494-3p in vivo.Conclusions:EPS1-1 protected against HCC by limiting its proliferation and sur-vival through the miR-494-3p/TRIM36 axis and by inducing cyclin E ubiquitination.展开更多
基金This work was supported by the Pew Scholar Program in the Biomedical Sciences,the Searle Scholars Program,and the National Science Foundation(CHE-1709616).
文摘Salicylic acid(SA)is an important phytohormone mediating both local and systemic defense responses in plants.Despite over half a century of research,how plants biosynthesize SA remains unresolved.In Arabidop-sis,a major part of SA is derived from isochorismate,a key intermediate produced by the isochorismate syn-thase,which is reminiscent of SA biosynthesis in bacteria.Whereas bacteria employ an isochorismate pyru-vate lyase(IPL)that catalyzes the turnover of isochorismate to pyruvate and SA,plants do not contain an IPL ortholog and generate SA from isochorismate through an unknown mechanism.Combining genetic and biochemical approaches,we delineated the SA biosynthetic pathway downstream of isochorismate in Ara-bidopsis.We found that PBS3,a GH3 acyl adenylase-family enzyme important for SA accumulation,catalyzes ATP-and Mg2+-dependent conjugation of L-glutamate primarily to the 8-carboxyl of isochorismate and yields the key SA biosynthetic intermediate,isochorismoyl-glutamate A.Moreover,we discovered that EPS1,a BAHD acyltransferase-family protein with a previously implicated role in SA accumulation upon pathogen attack,harbors a noncanonical active site and an unprecedented isochorismoyl-glutamate A pyruvoyl-glutamate lyase activity that produces SA from the isochorismoyl-glutamate A substrate.Together,PBS3 and EPS1 form a two-step metabolic pathway to produce SA from isochorismate in Arabidopsis,which is distinct from how SA is biosynthesized in bacteria.This study closes a major knowledge gap in plant SA meta-bolism and would help develop new strategies for engineering disease resistance in crop plants.
文摘Introduction: The frequency, severity, cost of treatment, morbidity and mortality of stroke make it a real public health problem. In industrialized countries, strokes are the leading cause of physical disability in adults, the second leading cause of dementia (after Alzheimer’s disease), and the third leading cause of death (after cancer and cardiovascular disease). It’s also a major cause of depression. The objective of our study was to describe the epidemiological, clinical and evolutionary aspects of stroke in the internal medicine department of Tivaouane Hospital. Material and Method: This is a retrospective study carried out from January 1, 2015 to December 31, 2018 on the files of patients hospitalized for stroke in the medical department of the EPS1 in Tivaouane. We took into account all the patients who had a brain CT (computed tomography) scan. We collected data related to socio-demographic characteristics, history, risk factors, reasons for admission, clinical signs, paraclinical examinations, as well as evolution. Results: Out of 1999 patients, 206 files of patients with stroke were collected, i.e. a proportion of 10.3%. Our study population had a mean age of 65.53 years [16 - 97 years]. We noted a clear predominance of women (50.5%). The majority of the population came from the outskirts of Tivaouane (56.7%). Risk factors for stroke were dominated by hypertension (90.3%), dyslipidemia (19.4%), previous stroke (18.9%), and diabetes (16%). The clinical signs were dominated by a motor deficit (94.1%), speech disorders (67.4%) and consciousness disorders (47%). Ischemic strokes were predominant (65%) over hemorrhagic strokes (34.5%). The outcome was generally unfavorable with 14.6% total recovery, 58.7% recovery with sequelae and a case fatality of 26.7%. Conclusion: It emerges from this study that strokes still remain a real public health problem. Knowledge of populations of risk factors as well as their proper management is fundamental in primary prevention strategies, the only guarantee for a reduc
文摘Background and Aims:This study was designed to uncov-er the mechanism for extracellular polysaccharide(EPS1-1)-mediated effects on hepatocellular carcinoma(HCC)devel-opment.Methods:HCC cells were treated with EPS1-1,miR-494-3p mimic,sh-TRIM36,and pcDNA3.1-TRIM36.The levels of miR-494-3p and TRIM36 were measured in nor-mal hepatocytes,THLE-2,and HepG2 and HuH7HCC cell lines,along with the protein expression of cyclin D/E and p21.The proliferation,cell cycle,and apoptosis of HCC cells were assayed.The interactions between miR-494-3p and TRIM36,and between TRIM36 and cyclin E were assessed.Finally,the expression and localization of TRIM36 and cyclin E were monitored,and tumor apoptosis was detected,in tumor xenograft model.Results:EPS1-1 suppressed HCC cell proliferation and cyclin D/E expression and promoted apoptosis and p21 expression.miR-494-3p was upregulated and TRIM36 was downregulated in HCC cells.Transfection with miR-494-3p mimic or sh-TRIM36 facilitated HCC cell proliferation and the expression of cyclin D/E protein but they inhibited apoptosis and p21 expression in the pres-ence of EPS1-1.Overexpression of TRIM36 further con-solidated EPS1-1-mediated inhibition of HCC proliferation,cyclin D/E,and the promotion of apoptosis and p21 expres-sion.Those effects were reversed by miR-494-3p overex-pression.TRIM36 was a target gene of miR-494-3p,and TRIM36 induced cyclin E ubiquitination.EPS1-1 suppressed cyclin E expression,promoted TRIM36 expression and tu-mor apoptosis,all of which were abrogated by increasing the expression of miR-494-3p in vivo.Conclusions:EPS1-1 protected against HCC by limiting its proliferation and sur-vival through the miR-494-3p/TRIM36 axis and by inducing cyclin E ubiquitination.
