This study investigated whether four cumulus-specific genes: follicular stimulating hormone receptor (FSHr), hyaluronan synthase 2 (Has2), prostaglandin synthase 2 (Ptgs2) and steroidogenic acute regulator protein (St...This study investigated whether four cumulus-specific genes: follicular stimulating hormone receptor (FSHr), hyaluronan synthase 2 (Has2), prostaglandin synthase 2 (Ptgs2) and steroidogenic acute regulator protein (Star), were correctly reprogrammed to be transcriptionally silent following somatic cell nuclear transfer (SCNT) in a murine model. Cumulus cells of C57×CBA F1 female mouse were injected into enucleated oocytes, followed by activation in 10 μmol/L strontium chloride for 5 h and subsequent in vitro culture up to the blastocyst stage. Expression of cumulus-specific genes in SCNT-derived embryos at 2-cell, 4-cell and day 4.5 blastocyst stages was compared with corresponding in vivo fertilized embryos by real-time PCR. It was demonstrated that immediately after the first cell cycle, SCNT-derived 2-cell stage embryos did not express all four cumulus-specific genes, which continually remained silent at the 4-cell and blastocyst stages. It is therefore concluded that all four cumulus-specific genes were correctly reprogrammed to be silent following nuclear transfer with cumulus donor cells in the mouse model. This would imply that the poor preimplantation developmental competence of SCNT embryos derived from cumulus cells is due to incomplete reprogramming of other embryonic genes, rather than cumulus-specific genes.展开更多
OBJECTIVE： To observe the influence of Sijunzi decoction and Yupingfeng powder on the expression of the relevant DNAs of janus kinase （JAK）-signal transducer and activator of transcription （STAT） sig- nal pathway...OBJECTIVE： To observe the influence of Sijunzi decoction and Yupingfeng powder on the expression of the relevant DNAs of janus kinase （JAK）-signal transducer and activator of transcription （STAT） sig- nal pathway of the brain in spleen-deficiency mod- el rats. METHODS： Eighty male Wistar rats of sanitary degree were divided randomly into four groups： nor- mal group, model group, treatment group 1, treatment group 2. Besides the rats in the normal group, all the rats in other 3 groups were prepared as spleen deficiency model. The treatment group 1 were treated with Sijunzi decoction and the treat- ment group 2 were treated with Yupingfeng powder. After treatment for 6 weeks, perfusion was given and the brain was taken for detection of the ex- pression of the relevant DNAs of JAK-STAT signal pathwayofthe brain in SD rats bygene chip method. RESULTS： Spleen deficiency could lead to increase expression of JAKI, STATI and Interleukin 4 （IL-4） in the brain, but the decrease expression of Suppres- sor of cytokine signaling I （SOCSI）, prolactin recep- tor （PRLR） and binding protein 3 （GATA 3）. Sijunzi decoction could increase expression of STAT3, Pro- lactin （PRL） and GATA3, but decrease expression of JAKI, STAT, STAT4, Interleukin 10 receptor, alpha （ILIORA）, Coagulation factor II （F2）, PRLR, MAD homolog 3 （SMAD3） and IL-4. Yupingfeng powder could decrease expression of JAKI, STATI, STAT4, SOCS4_ predicted, Epidermal growth factor receptor （EGFR）, PRLR, High mobility group AT-hook I （HMGAI 0）, IL-4. CONCLUSION： Sijunzi decoction and Yupingfeng powder can improve immune function of the rat through influencing the genetic expression of JAK-STAT signal pathway.展开更多
The laboratory rat is a valuable mammalian model organism for basic research and drug discovery. Here we demonstrate an efficient methodology by applying transcription activator-like effector nucleases(TALENs) technol...The laboratory rat is a valuable mammalian model organism for basic research and drug discovery. Here we demonstrate an efficient methodology by applying transcription activator-like effector nucleases(TALENs) technology to generate Leptin receptor(Lepr) knockout rats on the Sprague Dawley(SD) genetic background. Through direct injection of in vitro transcribed m RNA of TALEN pairs into SD rat zygotes, somatic mutations were induced in two of three resulting pups. One of the founders carrying bi-allelic mutation exhibited early onset of obesity and infertility. The other founder carried a chimeric mutation which was efficiently transmitted to the progenies. Through phenotyping of the resulting three lines of rats bearing distinct mutations in the Lepr locus, we found that the strains with a frame-shifted or premature stop codon mutation led to obesity and metabolic disorders. However, no obvious defect was observed in a strain with an in-frame 57 bp deletion in the extracellular domain of Lepr. This suggests the deleted amino acids do not significantly affect Lepr structure and function. This is the first report of generating the Lepr mutant obese rat model in SD strain through a reverse genetic approach. This suggests that TALEN is an efficient and powerful gene editing technology for the generation of disease models.展开更多
OBJECTIVE:To observe the effects of Bushen Huoxue Yin(补肾活血饮,BSHXY) on nuclear transcription factor kappa B(NF-κB) and nitric oxide(NO) in the brain of the Parkinson's disease(PD) model mouse.METHODS:Forty-fi...OBJECTIVE:To observe the effects of Bushen Huoxue Yin(补肾活血饮,BSHXY) on nuclear transcription factor kappa B(NF-κB) and nitric oxide(NO) in the brain of the Parkinson's disease(PD) model mouse.METHODS:Forty-five C57BL/6 mice were randomly divided into three groups;normal,model and BSHXY treatment groups.Concentrations of NF-κB and NO in mouse brain tissue were determined by ELISA and spectrophotometry,respectively.RESULTS:NF-κB concentration in brain tissue in the model group was 14.04±4.38 μg· L-1,which was higher than that in normal(P<0.01) and BSHXY(P< 0.05) groups.NO content in brain tissue in the model group was 5.93±0.79 μmol · gprot-1,which was also higher than that in model(P<0.01) and BSHXY(P<0.01) groups.However,there were no significant differences in the content of NF-κB and NO between BSHXY and normal groups(P>0.05).CONCLUSION:The mechanism of BSHXY for treatment of PD is possibly related to inhibition ofNF-κB activation and decreased NO content in the brain.展开更多
The availability of a large number of sequenced bacterial genomes facilitates in-depth studies about why genes(operons)in a bacterial genome are globally organized the way they are.We have previously discovered that(t...The availability of a large number of sequenced bacterial genomes facilitates in-depth studies about why genes(operons)in a bacterial genome are globally organized the way they are.We have previously discovered that(the relative)transcription-activation frequencies among different biological pathways encoded in a genome have a dominating role in the global arrangement of operons.One complicating factor in such a study is that some operons may be involved in multiple pathways with different activation frequencies.A quantitative model has been developed that captures this information,which tends to be minimized by the current global arrangement of operons in a bacterial(and archaeal)genome compared to possible alternative arrangements.A study is carried out here using this model on a collection of 52 closely related Escherichia coli genomes,which revealed interesting new insights about how bacterial genomes evolve to optimally adapt to their environments through adjusting the(relative)genomic locations of the encoding operons of biological pathways once their utilization and hence transcription activation frequencies change,to maintain the above energy-efficiency property.More specifically we observed that it is the frequencies of the transcription activation of pathways relative to those of the other encoded pathways in an organism as well as the variation in the activation frequencies of a specific pathway across the related genomes that play a key role in the observed commonalities and differences in the genomic organizations of genes(and operons)encoding specific pathways across different genomes.展开更多
OBJECTIVE:To investigate the molecular effect of Socheongryong Tang(SCRT,Xiaoqinglong Tang in Chinese) on whole genome level in asthma mouse model by microarray technology.METHODS:Asthma was induced by intranasal inst...OBJECTIVE:To investigate the molecular effect of Socheongryong Tang(SCRT,Xiaoqinglong Tang in Chinese) on whole genome level in asthma mouse model by microarray technology.METHODS:Asthma was induced by intranasal instillation of ovalbumin in mouse.After administration of SCRT on asthma-induced mouse,the expression of genes in lung tissue was measured using whole genome microarray.The functional implication of differentially expressed genes was performed using ontological analysis and the similarity of promoter structure of genes was also analyzed.RESULTS:Treatment of SCRT restored expression level of many up- or down-regulated genes in asthma model,and this recovery rate means SCRT could regulate a set of genes having specific TFBS binding sites.CONCLUSION:In this study,we identified a set of genes subjected to similar regulation by SCRT in asthma model in mice.展开更多
To study the transition dynamics of resistant-type human immunodeficiency virus 1 （HIV-1） in highly active antiretroviral therapy （HAART） and the affect of neutral mutation in the evolution of HIV-1, a mathematica...To study the transition dynamics of resistant-type human immunodeficiency virus 1 （HIV-1） in highly active antiretroviral therapy （HAART） and the affect of neutral mutation in the evolution of HIV-1, a mathematical model is proposed when mutation occurs mainly during reproduction. The derived results show that the resistant-type will certainly colonize in patients once mutation occurs. Furthermore, a neutral mutation is closely related to the colonized pattern of resistant-type HIV-1 quasispecies and there are some changes in the pattern of transmission dynamics when mutation occurs mainly during reproduction or in the absence of reproduction, which may lead to significant strategies for predicting or checking HIV-1 drug resistance in HAART.展开更多
基金Project (No. R-174-000-065-112/303) supported by the NationalUniversity of Singapore
文摘This study investigated whether four cumulus-specific genes: follicular stimulating hormone receptor (FSHr), hyaluronan synthase 2 (Has2), prostaglandin synthase 2 (Ptgs2) and steroidogenic acute regulator protein (Star), were correctly reprogrammed to be transcriptionally silent following somatic cell nuclear transfer (SCNT) in a murine model. Cumulus cells of C57×CBA F1 female mouse were injected into enucleated oocytes, followed by activation in 10 μmol/L strontium chloride for 5 h and subsequent in vitro culture up to the blastocyst stage. Expression of cumulus-specific genes in SCNT-derived embryos at 2-cell, 4-cell and day 4.5 blastocyst stages was compared with corresponding in vivo fertilized embryos by real-time PCR. It was demonstrated that immediately after the first cell cycle, SCNT-derived 2-cell stage embryos did not express all four cumulus-specific genes, which continually remained silent at the 4-cell and blastocyst stages. It is therefore concluded that all four cumulus-specific genes were correctly reprogrammed to be silent following nuclear transfer with cumulus donor cells in the mouse model. This would imply that the poor preimplantation developmental competence of SCNT embryos derived from cumulus cells is due to incomplete reprogramming of other embryonic genes, rather than cumulus-specific genes.
基金Supported by State Natural Science Fund (No. 30772685)
文摘OBJECTIVE： To observe the influence of Sijunzi decoction and Yupingfeng powder on the expression of the relevant DNAs of janus kinase （JAK）-signal transducer and activator of transcription （STAT） sig- nal pathway of the brain in spleen-deficiency mod- el rats. METHODS： Eighty male Wistar rats of sanitary degree were divided randomly into four groups： nor- mal group, model group, treatment group 1, treatment group 2. Besides the rats in the normal group, all the rats in other 3 groups were prepared as spleen deficiency model. The treatment group 1 were treated with Sijunzi decoction and the treat- ment group 2 were treated with Yupingfeng powder. After treatment for 6 weeks, perfusion was given and the brain was taken for detection of the ex- pression of the relevant DNAs of JAK-STAT signal pathwayofthe brain in SD rats bygene chip method. RESULTS： Spleen deficiency could lead to increase expression of JAKI, STATI and Interleukin 4 （IL-4） in the brain, but the decrease expression of Suppres- sor of cytokine signaling I （SOCSI）, prolactin recep- tor （PRLR） and binding protein 3 （GATA 3）. Sijunzi decoction could increase expression of STAT3, Pro- lactin （PRL） and GATA3, but decrease expression of JAKI, STAT, STAT4, Interleukin 10 receptor, alpha （ILIORA）, Coagulation factor II （F2）, PRLR, MAD homolog 3 （SMAD3） and IL-4. Yupingfeng powder could decrease expression of JAKI, STATI, STAT4, SOCS4_ predicted, Epidermal growth factor receptor （EGFR）, PRLR, High mobility group AT-hook I （HMGAI 0）, IL-4. CONCLUSION： Sijunzi decoction and Yupingfeng powder can improve immune function of the rat through influencing the genetic expression of JAK-STAT signal pathway.
基金supported by the State Key Development Programs of China (2012CB910400 to Mingyao Liu)the National Natural Science Foundation of China (31371455, 31171318 and 81330049)the Science and Technology Commission of Shanghai Municipality (14140900300)
文摘The laboratory rat is a valuable mammalian model organism for basic research and drug discovery. Here we demonstrate an efficient methodology by applying transcription activator-like effector nucleases(TALENs) technology to generate Leptin receptor(Lepr) knockout rats on the Sprague Dawley(SD) genetic background. Through direct injection of in vitro transcribed m RNA of TALEN pairs into SD rat zygotes, somatic mutations were induced in two of three resulting pups. One of the founders carrying bi-allelic mutation exhibited early onset of obesity and infertility. The other founder carried a chimeric mutation which was efficiently transmitted to the progenies. Through phenotyping of the resulting three lines of rats bearing distinct mutations in the Lepr locus, we found that the strains with a frame-shifted or premature stop codon mutation led to obesity and metabolic disorders. However, no obvious defect was observed in a strain with an in-frame 57 bp deletion in the extracellular domain of Lepr. This suggests the deleted amino acids do not significantly affect Lepr structure and function. This is the first report of generating the Lepr mutant obese rat model in SD strain through a reverse genetic approach. This suggests that TALEN is an efficient and powerful gene editing technology for the generation of disease models.
基金Supported by National Natural Science Foundation (No.30672762)
文摘OBJECTIVE:To observe the effects of Bushen Huoxue Yin(补肾活血饮,BSHXY) on nuclear transcription factor kappa B(NF-κB) and nitric oxide(NO) in the brain of the Parkinson's disease(PD) model mouse.METHODS:Forty-five C57BL/6 mice were randomly divided into three groups;normal,model and BSHXY treatment groups.Concentrations of NF-κB and NO in mouse brain tissue were determined by ELISA and spectrophotometry,respectively.RESULTS:NF-κB concentration in brain tissue in the model group was 14.04±4.38 μg· L-1,which was higher than that in normal(P<0.01) and BSHXY(P< 0.05) groups.NO content in brain tissue in the model group was 5.93±0.79 μmol · gprot-1,which was also higher than that in model(P<0.01) and BSHXY(P<0.01) groups.However,there were no significant differences in the content of NF-κB and NO between BSHXY and normal groups(P>0.05).CONCLUSION:The mechanism of BSHXY for treatment of PD is possibly related to inhibition ofNF-κB activation and decreased NO content in the brain.
基金supported in part by National Science Foundation (#NSF DEB-0830024 and NSF MCB-0958172)the US Department of Energy’s BioEnergy Science Center grant through the Office of Biological and Environmental Research+1 种基金The BioEnergy Science Center is a US Department of Energy Bioenergy Research Center supported by the Office of Biological and Environmental Research in the DOE Office of ScienceFunding for open access charge: US Department of Energy’s BioEnergy Science Center
文摘The availability of a large number of sequenced bacterial genomes facilitates in-depth studies about why genes(operons)in a bacterial genome are globally organized the way they are.We have previously discovered that(the relative)transcription-activation frequencies among different biological pathways encoded in a genome have a dominating role in the global arrangement of operons.One complicating factor in such a study is that some operons may be involved in multiple pathways with different activation frequencies.A quantitative model has been developed that captures this information,which tends to be minimized by the current global arrangement of operons in a bacterial(and archaeal)genome compared to possible alternative arrangements.A study is carried out here using this model on a collection of 52 closely related Escherichia coli genomes,which revealed interesting new insights about how bacterial genomes evolve to optimally adapt to their environments through adjusting the(relative)genomic locations of the encoding operons of biological pathways once their utilization and hence transcription activation frequencies change,to maintain the above energy-efficiency property.More specifically we observed that it is the frequencies of the transcription activation of pathways relative to those of the other encoded pathways in an organism as well as the variation in the activation frequencies of a specific pathway across the related genomes that play a key role in the observed commonalities and differences in the genomic organizations of genes(and operons)encoding specific pathways across different genomes.
文摘OBJECTIVE:To investigate the molecular effect of Socheongryong Tang(SCRT,Xiaoqinglong Tang in Chinese) on whole genome level in asthma mouse model by microarray technology.METHODS:Asthma was induced by intranasal instillation of ovalbumin in mouse.After administration of SCRT on asthma-induced mouse,the expression of genes in lung tissue was measured using whole genome microarray.The functional implication of differentially expressed genes was performed using ontological analysis and the similarity of promoter structure of genes was also analyzed.RESULTS:Treatment of SCRT restored expression level of many up- or down-regulated genes in asthma model,and this recovery rate means SCRT could regulate a set of genes having specific TFBS binding sites.CONCLUSION:In this study,we identified a set of genes subjected to similar regulation by SCRT in asthma model in mice.
基金Acknowledgments This work is supported by the National Natural Science Fund of P. R. China （No. 11271369） and the Natural Science Foundation Project of CQ CSTC （2010BB5020）.
文摘To study the transition dynamics of resistant-type human immunodeficiency virus 1 （HIV-1） in highly active antiretroviral therapy （HAART） and the affect of neutral mutation in the evolution of HIV-1, a mathematical model is proposed when mutation occurs mainly during reproduction. The derived results show that the resistant-type will certainly colonize in patients once mutation occurs. Furthermore, a neutral mutation is closely related to the colonized pattern of resistant-type HIV-1 quasispecies and there are some changes in the pattern of transmission dynamics when mutation occurs mainly during reproduction or in the absence of reproduction, which may lead to significant strategies for predicting or checking HIV-1 drug resistance in HAART.
