CRISPR/Cas9 is a versatile genome editing tool that has the potential to be used to cure many genetic diseases.The system works via a guide RNA(gRNA)interacting with the Cas9 protein to form a complex that binds to a ...CRISPR/Cas9 is a versatile genome editing tool that has the potential to be used to cure many genetic diseases.The system works via a guide RNA(gRNA)interacting with the Cas9 protein to form a complex that binds to a specific DNA sequence.1 The site-specific DNA binding feature of the Cas9 system can be utilized in a variety of ways to correct gene mutations or to regulate gene expression.First,the Cas9 protein can make a site-specific double-stranded break that is mainly repaired by homology-directed repair or non-homologous end-joining.展开更多
Background:There is significant need for accurate diagnostic tools for Cryptosporidium spp.and Qiordia duodenalis infections in resource limited countries where diarrhoeal disease caused by these parasites is often pr...Background:There is significant need for accurate diagnostic tools for Cryptosporidium spp.and Qiordia duodenalis infections in resource limited countries where diarrhoeal disease caused by these parasites is often prevalent.The present study assessed the diagnostic performance of three commercially available rapid diagnostic tests(RDTs)based on faecal-antigen detection for Cryptosporidium spp.and/or G.duodenalis infections in stool samples of children admitted with severe acute malnutrition(SAM)and diarrhoea.An established multiplex PCR was used as reference test.Methods:Stool samples from children with SAM and diarrhoea enrolled in a randomized controlled trial(registered at clinicaltrials.gov/ct2/show/NCT02246296)in Malawi(n=175)and Kenya(n=120)between December 2014 and December 2015 were analysed by a multiplex PCR for the presence of Cryptosporidium sppv G.duodenalis or Entomoebo histolytica parasite DNA.Cryptosporidium-positive samples were species typed using restriction fragment length polymorphism analysis.A sub-sample of the stool specimens(n=236)was used for testing with three different RDTs.Diagnostic accuracy of the tests under evaluation was assessed using the results of PCR as reference standard using MedCalc software.Pearson Chi-square test and Fisher's exact test were used to determine(significant)difference between the number of cryptosporidiosis or giardiasis cases found by PCR in Malawi and Kenya.The overall diagnostic accuracy of each RDT was calculated by plotting a receiver operating characteristic(ROC)curve for each test and to determine the area under the curve(AUC)using SPSS8 software.Results:Prevalence of Cryptosporidium spp.by PCR was 20.0 and 21.7%in Malawi and Kenya respectively,mostly C.hominis.G.duodenalis prevalence was 23.4 and 5.8%in Malawi and Kenya respectively.E histolytica was not detected by PCR.RDT testing followed the same pattern of prevalence.RDT sensitivities ranged for cryptosporidiosis from 42.9 to 76.9%and for G.duodenalis from 48.2 to 85.7%.RDT specificities ranged from 88.4 to 100%for Cryptosporidium spp.and from 91.2 to 99.2%for G.duodenalis infections.Based on the estimated area under the curve(AUC)values,all tests under evaluation had an acceptable overall diagnostic accuracy(>0.7),with the exception of one RDT for Cryptosporidium spp.in Malawi.Conclusions:All three RDTs for Cryptosporidium spp.and Giardia duodenalis evaluated in this study have a moderate sensitivity,but sufficient specificity.The main value of the RDTs is within their rapidness and their usefulness as screening assays in surveys for diarrhoea.展开更多
The impact of alternate-day fasting(ADF)on atherosclerosis remains poorly understood,particularly in high-risk populations.In a recent paper published in Life Metabolism,Deng et al.revealed that ADF exacerbated both e...The impact of alternate-day fasting(ADF)on atherosclerosis remains poorly understood,particularly in high-risk populations.In a recent paper published in Life Metabolism,Deng et al.revealed that ADF exacerbated both early and advanced atherosclerotic lesion development in Apoe^(-/-)mice through suppression of hepatic activating transcription factor 3(ATF3)and consequent dysregulation of cholesterol metabolism.展开更多
基金supported by the New Frontiers in Research Fund(NFRF),administered by the Social Sciences and Humanities Research Council(SSHRC)on behalf of CIHR,NSERC,and SSHRC(Grant#NFRFE-2021-00713).
文摘CRISPR/Cas9 is a versatile genome editing tool that has the potential to be used to cure many genetic diseases.The system works via a guide RNA(gRNA)interacting with the Cas9 protein to form a complex that binds to a specific DNA sequence.1 The site-specific DNA binding feature of the Cas9 system can be utilized in a variety of ways to correct gene mutations or to regulate gene expression.First,the Cas9 protein can make a site-specific double-stranded break that is mainly repaired by homology-directed repair or non-homologous end-joining.
基金This research project was financially supported Stichting Dioraphte(The Netherlands).
文摘Background:There is significant need for accurate diagnostic tools for Cryptosporidium spp.and Qiordia duodenalis infections in resource limited countries where diarrhoeal disease caused by these parasites is often prevalent.The present study assessed the diagnostic performance of three commercially available rapid diagnostic tests(RDTs)based on faecal-antigen detection for Cryptosporidium spp.and/or G.duodenalis infections in stool samples of children admitted with severe acute malnutrition(SAM)and diarrhoea.An established multiplex PCR was used as reference test.Methods:Stool samples from children with SAM and diarrhoea enrolled in a randomized controlled trial(registered at clinicaltrials.gov/ct2/show/NCT02246296)in Malawi(n=175)and Kenya(n=120)between December 2014 and December 2015 were analysed by a multiplex PCR for the presence of Cryptosporidium sppv G.duodenalis or Entomoebo histolytica parasite DNA.Cryptosporidium-positive samples were species typed using restriction fragment length polymorphism analysis.A sub-sample of the stool specimens(n=236)was used for testing with three different RDTs.Diagnostic accuracy of the tests under evaluation was assessed using the results of PCR as reference standard using MedCalc software.Pearson Chi-square test and Fisher's exact test were used to determine(significant)difference between the number of cryptosporidiosis or giardiasis cases found by PCR in Malawi and Kenya.The overall diagnostic accuracy of each RDT was calculated by plotting a receiver operating characteristic(ROC)curve for each test and to determine the area under the curve(AUC)using SPSS8 software.Results:Prevalence of Cryptosporidium spp.by PCR was 20.0 and 21.7%in Malawi and Kenya respectively,mostly C.hominis.G.duodenalis prevalence was 23.4 and 5.8%in Malawi and Kenya respectively.E histolytica was not detected by PCR.RDT testing followed the same pattern of prevalence.RDT sensitivities ranged for cryptosporidiosis from 42.9 to 76.9%and for G.duodenalis from 48.2 to 85.7%.RDT specificities ranged from 88.4 to 100%for Cryptosporidium spp.and from 91.2 to 99.2%for G.duodenalis infections.Based on the estimated area under the curve(AUC)values,all tests under evaluation had an acceptable overall diagnostic accuracy(>0.7),with the exception of one RDT for Cryptosporidium spp.in Malawi.Conclusions:All three RDTs for Cryptosporidium spp.and Giardia duodenalis evaluated in this study have a moderate sensitivity,but sufficient specificity.The main value of the RDTs is within their rapidness and their usefulness as screening assays in surveys for diarrhoea.
基金supported by the Canadian Institute of Health Research(CIHR)Fellowship.H.K.S.was supported by the Canadian Institute of Health Research(CIHR,PJT-190016)the Natural Sciences and Engineering Research Council(NSERC,RGPIN-2016-06610)of Canadathe Sun Life Financial New Investigator Award of Banting&Best Diabetes Centre(BBDC)of University of Toronto.
文摘The impact of alternate-day fasting(ADF)on atherosclerosis remains poorly understood,particularly in high-risk populations.In a recent paper published in Life Metabolism,Deng et al.revealed that ADF exacerbated both early and advanced atherosclerotic lesion development in Apoe^(-/-)mice through suppression of hepatic activating transcription factor 3(ATF3)and consequent dysregulation of cholesterol metabolism.
