Isolated protoplasts from thalli of Porphyra haitanensis and Porphyra yezoensis were treated with colchicine or irradiated by ultraviolet (UV ). Several types of color variants were observed among the protoplast offsp...Isolated protoplasts from thalli of Porphyra haitanensis and Porphyra yezoensis were treated with colchicine or irradiated by ultraviolet (UV ). Several types of color variants were observed among the protoplast offspring. After treatment with colchicine: (1) 0.04-0.09% of red type variants in P. haitanensis were obtained; (2) The rate of red type variants and the variegated chimeral thalli composed of red type and wild type of sectors were 6.31- 1.11% in P. yezoensis. After irradiation with UV: (1) 3.5- 10.5% of red type variants in P. yezoensis were obtained: (2) 0.5-2-0% of red type variants and the variegated chimeral thalli composed of red type and wild type of sectors were obtained in P. haitanensis. Colchicine and UV’s mutangenic effects on P. yezoensis protoplasts were stronger than those on P. haitanensis protoplasts. The most efficient concentration of colchicine was 0.05%. The optimal length of UV-radiation was 1/2 min (radiation distance 5 cm). The red type variants induced, by colchicine展开更多
What is pursued by multi-product type and variant volume(MPTVV)production is rapid response and quick switching,so that structure of transferring line in manufacturing system is no longer unalterable.Cell formation(CF...What is pursued by multi-product type and variant volume(MPTVV)production is rapid response and quick switching,so that structure of transferring line in manufacturing system is no longer unalterable.Cell formation(CF)algorithm is the key technology of cellular manufacturing system(CMS).Currently,CF methods are mainly extended on the idea of group technology(GT)that covers a lot on analysis of resource capability matching and its algorithm.Various constraints are considered,but seldom utilized comprehensively.Aimed to the problem of manufacturing cell(MC)formation under MPTVV production mode,integrated formation technologies for typical MC as group type of cell(GC),flow type of cell(FC)and inherited cell(IC)are presented based on technical analysis of CF.Oriented to practical production constraints like delivery time,product batch,equipment ability,key machine,key part and machine sharing,etc,an integrated formation model is constructed and internal interrelations of these constraints are analyzed synthetically.Ulteriorly,formation goals of types of MCs and their formation procedures under joint effect of formation constraints and rules are spread.In case study,three highly balanced GC are formed first;then FC formation are implemented based on the same data which indicate good balancing effect of cell load and flow-style production for key tasks;When task is adjusted,a new scheme is constructed on the result of FC configuration by using IC formation method,and more optimal performance of flow-style production is manifested.The proposed comparative study of different type of cells strongly explains the validation of integrated MC formation in support of rapid manufacturing resource transformation under MPTVV production mode.展开更多
AIM:To investigate the association of 10 known common gene variants with susceptibility to type 2diabetes mellitus(T2D)among Omanis.METHODS:Using case-control design,a total of992 diabetic patients and 294 normoglycem...AIM:To investigate the association of 10 known common gene variants with susceptibility to type 2diabetes mellitus(T2D)among Omanis.METHODS:Using case-control design,a total of992 diabetic patients and 294 normoglycemic Omani Arabs were genotyped,by an allelic discrimination assay-by-design TaqMan method on fast real time polymerase chain reaction system,for the following gene variants:KCNJ11(rs5219),TCF7L2(rs7903146),CDKAL1(rs10946398),CDKN2A/B(rs10811661),FTO(rs9939609 and rs8050136),IGF2BP2(rs4402960),SLC30A8(rs13266634)CAPN10(rs3792267)and HHEX(rs1111875).T2D patients were recruited from the Diabetes Clinic(n=243)and inpatients(n=749)at Sultan Qaboos Univesity Hospital(SQUH),Muscat,Oman.Adult control participants(n=294)were volunteers from the community and from those visiting Family Medicine Clinic at SQU,for regular medical checkup.The difficulty in recruiting Omani participants with no family history of diabetes was the main reason behind the small number of control participants in this study.Almost all volunteers questioned had a relativewith diabetes mellitus.Inspite of the small number of normoglycemic controls in this study,this sample was sufficient for detection of genes and loci for common alleles influencing T2D with an odds ratio of≥1.3reaching at least 80%power.Data was collected from June 2010 to February 2012.RESULTS:Using binary logistic regression analysis,four gene variants showed significant association with T2D risk:KCNJ11(rs5219,P=5.8×10^(-6),OR=1.74),TCF7L2(rs7903146,P=0.001,OR=1.46),CDKAL1(rs10946398,P=0.002,OR=1.44)and CDKN2A/B(rs10811661,P=0.020,OR=1.40).The fixation index analysis of these four gene variants indicated significant genetic differentiation between diabetics and controls{[KCNJ11(rs5219),P<0.001],[TCF7L2(rs7903146),P<0.001],[CDKAL1(rs10946398),P<0.05],[CDKN2A/B(rs10811661),P<0.05]}.The highest genotype variation%between diabetics and controls was found at KCNJ11(2.07%)and TCF7L2(1.62%).This study was not able to detect an association of T2D risk with gene variants of IGF2BP2(rs4402960),SLC30A8(rs13266634),CAPN10(rs3792267)and HHEX(rs1111875).Moreover,no association was found between FTO gene variants(rs9939609 and rs8050136)and T2D risk.However,T2D risk was found to be significantly associated with obesity(P=0.002,OR=2.22);and with the Waist-to-Hip ratio(n=532,P=1.9×10^(-7),OR=2.4),[among males(n=234,P=1.2×10^(-4),OR=2.0)and females(n=298,P=0.001,OR=6.3)].CONCLUSION:Results confirmed the association of KCNJ11(rs5219),TCF7L2(rs7903146),CDKAL1(rs10946398)and CDKN2A/B(rs10811661)gene variants with susceptibility to T2D among Omani Arabs.展开更多
Type 2 diabetes mellitus(T2DM) is a silent progressive polygenic metabolic disorder resulting from ineffective insulin cascading in the body. World-wide, about 415 million people are suffering from T2DM with a project...Type 2 diabetes mellitus(T2DM) is a silent progressive polygenic metabolic disorder resulting from ineffective insulin cascading in the body. World-wide, about 415 million people are suffering from T2DM with a projected rise to 642 million in 2040. T2DM is treated with several classes of oral antidiabetic drugs(OADs) viz. biguanides, sulfonylureas, thiazolidinediones, meglitinides, etc. Treatment strategies for T2DM are to minimize long-term micro and macro vascular complications by achieving an optimized glycemic control. Genetic variations in the human genome not only disclose the risk of T2DM development but also predict the personalized response to drug therapy. Inter-individual variability in response to OADs is due to polymorphisms in genes encoding drug receptors, transporters, and metabolizing enzymes for example, genetic variants in solute carrier transporters(SLC22A1, SLC22A2, SLC22A3, SLC47A1 and SLC47A2) are actively involved in glycemic/HbA1c management of metformin. In addition, CYP gene encoding Cytochrome P450 enzymes also play a crucial role with respect to metabolism of drugs. Pharmacogenetic studies provide insights on the relationship between individual genetic variants and variable therapeutic outcomes of various OADs. Clinical utility of pharmacogenetic study is to predict the therapeutic dose of various OADs on individual basis. Pharmacogenetics therefore, is a step towards personalized medicine which will greatly improve the efficacy of diabetes treatment.展开更多
Introduction: Diffuse variant of GC is composed of gastric-type mucous cells, which generally do not form glands, but rather permit the mucosa and wall as scattered individual cells or small clusters in an “infiltrat...Introduction: Diffuse variant of GC is composed of gastric-type mucous cells, which generally do not form glands, but rather permit the mucosa and wall as scattered individual cells or small clusters in an “infiltrative” growth pattern. These cells appear to arise from the middle layer of the mucosa, and the presence of intestinal metaplasia is not a prerequisite. In this version, mucin formation expands the malignant cells and pushes the nucleus to the periphery, creating a “signet ring” conformation. If the signetring cells are more than 50% of the tumor, the tumor is classified as signetring cell carcinoma [1]. This case is important for reporting because we encountered for the first time such a carcinoma type, due to the new age and its atypical presentation. Case Presentation: We report a case of a 20 years Albanian old patient with Signet Ring Cell Type of Gastric CA. The patient was brought at the urgency with severe abdominal pain, nausea and peritoneal irritation. Clinical examination has been made in emergency, where we conclude the signs of peritoneal irritation, from native Ro no signs of pneumoperitoneum, while laboratory tests found a slight anemia (erythrocytes 3.36, HCT 25, HGB 8.6). Two hours later we repeated the native RTG and there were present the signs of pneumoperitoneum. It was indicated urgent surgical in-tervention. Intraoperatively, we found Ulcer duodenal perforation and?undertook the operation procedures by Roscoe Graham technique. Conclusions: At this age, it is rare, and it is difficult to detect in its early stages, because the signs and symptoms are often non-existent, non-specific, or mimic as an ulcer. The most common symptoms are early heartburn indigestion, abdominal pain or discomfort, vomiting, constipation, diarrhea or to feel of filling after a small meal, loss of appetite, weakness and fatigue. Less common symptoms are anemia and weight loss.展开更多
Glial cell line-derived neurotrophic factor(GDNF) plays a critical role in neuronal survival and function. GDNF has two major splice variants in the brain,α-pro-GDNF and β-pro-GDNF, and both isoforms have strong neu...Glial cell line-derived neurotrophic factor(GDNF) plays a critical role in neuronal survival and function. GDNF has two major splice variants in the brain,α-pro-GDNF and β-pro-GDNF, and both isoforms have strong neuroprotective effects on dopamine neurons. However, the expression of the GDNF splice variants in dopaminergic neurons in the brain remains unclear. Therefore, in this study, we investigated the mRNA and protein expression of α-and β-pro-GDNF in the mouse brain by real-time quantitative polymerase chain reaction, using splice variant-specific primers, and western blot analysis. At the mRNA level,β-pro-GDNF expression was significantly greater than that of α-pro-GDNF in the mouse brain. In contrast, at the protein level,α-pro-GDNF expression was markedly greater than that of β-pro-GDNF. To clarify the mechanism underlying this inverse relationship in mRNA and protein expression levels of the GDNF splice variants, we analyzed the expression of sorting protein-related receptor with A-type repeats(SorLA) by real-time quantitative polymerase chain reaction. At the mRNA level, SorLA was positively associated with β-pro-GDNF expression, but not with α-pro-GDNF expression. This suggests that the differential expression of α-and β-pro-GDNF in the mouse brain is related to SorLA expression. As a sorting protein, SorLA could contribute to the inverse relationship among the mRNA and protein levels of the GDNF isoforms. This study was approved by the Animal Ethics Committee of Xuzhou Medical University, China on July 14, 2016.展开更多
The pharmacological interventions currently available to control type 2 diabetes mellitus(T2DM) show a wide interindividual variability in drug response, emphasizing the importance of a personalized, more effective me...The pharmacological interventions currently available to control type 2 diabetes mellitus(T2DM) show a wide interindividual variability in drug response, emphasizing the importance of a personalized, more effective medical treatment for each individual patient. In this context, a growing interest has emerged in recent years and has focused on pharmacogenetics, a discipline aimed at understanding the variability in patients' drug response, making it possible to predict which drug is best for each patient and at what doses. Recent pharmacological and clinical evidences indicate that genetic polymorphisms(or genetic variations) of certain genes can adversely affect drug response and therapeutic efficacy of oral hypoglycemic agents in patients with T2 DM, through pharmacokinetic- and/or pharmacodynamic-based mechanisms that may reduce the therapeutic effects or increase toxicity. For example, genetic variants in genes encoding enzymes of the cytochrome P-450 superfamily, or proteins of the ATP-sensitive potassium channel on the beta-cell of the pancreas, are responsible for the interindividual variability of drug response to sulfonylureas in patients with T2 DM. Instead, genetic variants in the genes that encode for the organic cation transporters of metformin have been related to changes in both pharmacodynamic and pharmacokinetic responses to metformin in metformin-treated patients. Thus, based on the individual's genotype, the possibility, in these subjects, of a personalized therapy constitutes the main goal of pharmacogenetics, directly leading to the development of the right medicine for the right patient. Undoubtedly, this represents an integral part of the translational medicine network.展开更多
旨在研究中国本土槐猪和引入瘦肉型猪(杜洛克猪、大约克夏猪、长白猪)在生长育肥相关基因MC4R和MSTN、脊椎数量相关基因NR6A1和VRTN、肉质性状相关基因PHKG1和PRKAG3以及病原感染相关基因SYNGR2和FUT1这8个基因9个SNP位点的遗传变异特...旨在研究中国本土槐猪和引入瘦肉型猪(杜洛克猪、大约克夏猪、长白猪)在生长育肥相关基因MC4R和MSTN、脊椎数量相关基因NR6A1和VRTN、肉质性状相关基因PHKG1和PRKAG3以及病原感染相关基因SYNGR2和FUT1这8个基因9个SNP位点的遗传变异特征。利用竞争性等位基因特异性PCR(KASP)和聚合酶链反应-限制性片段长度多态性(PCR-restriction fragment length polymorphism,PCR-RFLP)方法对突变位点进行基因分型,根据原始文献对各位点进行有利等位基因判定,并制作各猪种在各位点有利等位基因和不利等位基因的百分比示意图。结果:槐猪在NR6A1基因突变位点存在一定多态性,有利等位基因频率为0.24,其他位点表现为单一基因型,其中,PHKG1、PRKAG3突变位点为有利等位基因,而在MC4R、MSTN、VRTN、SYNGR2和FUT1突变位点为不利等位基因;杜洛克猪在MC4R、NR6A1、VRTN、SYNGR2和FUT1突变位点有利等位基因占优,然而,PHKG1基因不利等位基因仍有一定的比例;大约克夏猪在MC4R、SYNGR2、NR6A1和VRTN基因突变位点有利等位基因占优,而其他位点为不利等位基因;长白猪在MC4R、MSTN、PRKAG3(p.Val249Ile)和SYNGR2这4个基因突变位点不利基因占优;杜洛克猪在VRTN基因、长白猪在MC4R基因突变位点处于遗传不平衡状态(P<0.05)。以上结果为槐猪品种保护与利用以及瘦肉型猪种分子遗传标记选育提供了有益的信息。展开更多
A variant of Fermat’s last Diophantine equation is proposed by adjusting the number of terms in accord with the power of terms and a theorem describing the solubility conditions is stated. Numerically obtained primit...A variant of Fermat’s last Diophantine equation is proposed by adjusting the number of terms in accord with the power of terms and a theorem describing the solubility conditions is stated. Numerically obtained primitive solutions are presented for several cases with number of terms equal to or greater than powers. Further, geometric representations of solutions for the second and third power equations are devised by recasting the general equation in a form with rational solutions less than unity. Finally, it is suggested to consider negative and complex integers in seeking solutions to Diophantine forms in general.展开更多
文摘Isolated protoplasts from thalli of Porphyra haitanensis and Porphyra yezoensis were treated with colchicine or irradiated by ultraviolet (UV ). Several types of color variants were observed among the protoplast offspring. After treatment with colchicine: (1) 0.04-0.09% of red type variants in P. haitanensis were obtained; (2) The rate of red type variants and the variegated chimeral thalli composed of red type and wild type of sectors were 6.31- 1.11% in P. yezoensis. After irradiation with UV: (1) 3.5- 10.5% of red type variants in P. yezoensis were obtained: (2) 0.5-2-0% of red type variants and the variegated chimeral thalli composed of red type and wild type of sectors were obtained in P. haitanensis. Colchicine and UV’s mutangenic effects on P. yezoensis protoplasts were stronger than those on P. haitanensis protoplasts. The most efficient concentration of colchicine was 0.05%. The optimal length of UV-radiation was 1/2 min (radiation distance 5 cm). The red type variants induced, by colchicine
基金supported by National Defence Science&Technology Foundation of China(Grant No.K1301020706)
文摘What is pursued by multi-product type and variant volume(MPTVV)production is rapid response and quick switching,so that structure of transferring line in manufacturing system is no longer unalterable.Cell formation(CF)algorithm is the key technology of cellular manufacturing system(CMS).Currently,CF methods are mainly extended on the idea of group technology(GT)that covers a lot on analysis of resource capability matching and its algorithm.Various constraints are considered,but seldom utilized comprehensively.Aimed to the problem of manufacturing cell(MC)formation under MPTVV production mode,integrated formation technologies for typical MC as group type of cell(GC),flow type of cell(FC)and inherited cell(IC)are presented based on technical analysis of CF.Oriented to practical production constraints like delivery time,product batch,equipment ability,key machine,key part and machine sharing,etc,an integrated formation model is constructed and internal interrelations of these constraints are analyzed synthetically.Ulteriorly,formation goals of types of MCs and their formation procedures under joint effect of formation constraints and rules are spread.In case study,three highly balanced GC are formed first;then FC formation are implemented based on the same data which indicate good balancing effect of cell load and flow-style production for key tasks;When task is adjusted,a new scheme is constructed on the result of FC configuration by using IC formation method,and more optimal performance of flow-style production is manifested.The proposed comparative study of different type of cells strongly explains the validation of integrated MC formation in support of rapid manufacturing resource transformation under MPTVV production mode.
基金Supported by The Research Council(TRC),Muscat,Oman,No.RC/MED/BIOC/10/01
文摘AIM:To investigate the association of 10 known common gene variants with susceptibility to type 2diabetes mellitus(T2D)among Omanis.METHODS:Using case-control design,a total of992 diabetic patients and 294 normoglycemic Omani Arabs were genotyped,by an allelic discrimination assay-by-design TaqMan method on fast real time polymerase chain reaction system,for the following gene variants:KCNJ11(rs5219),TCF7L2(rs7903146),CDKAL1(rs10946398),CDKN2A/B(rs10811661),FTO(rs9939609 and rs8050136),IGF2BP2(rs4402960),SLC30A8(rs13266634)CAPN10(rs3792267)and HHEX(rs1111875).T2D patients were recruited from the Diabetes Clinic(n=243)and inpatients(n=749)at Sultan Qaboos Univesity Hospital(SQUH),Muscat,Oman.Adult control participants(n=294)were volunteers from the community and from those visiting Family Medicine Clinic at SQU,for regular medical checkup.The difficulty in recruiting Omani participants with no family history of diabetes was the main reason behind the small number of control participants in this study.Almost all volunteers questioned had a relativewith diabetes mellitus.Inspite of the small number of normoglycemic controls in this study,this sample was sufficient for detection of genes and loci for common alleles influencing T2D with an odds ratio of≥1.3reaching at least 80%power.Data was collected from June 2010 to February 2012.RESULTS:Using binary logistic regression analysis,four gene variants showed significant association with T2D risk:KCNJ11(rs5219,P=5.8×10^(-6),OR=1.74),TCF7L2(rs7903146,P=0.001,OR=1.46),CDKAL1(rs10946398,P=0.002,OR=1.44)and CDKN2A/B(rs10811661,P=0.020,OR=1.40).The fixation index analysis of these four gene variants indicated significant genetic differentiation between diabetics and controls{[KCNJ11(rs5219),P<0.001],[TCF7L2(rs7903146),P<0.001],[CDKAL1(rs10946398),P<0.05],[CDKN2A/B(rs10811661),P<0.05]}.The highest genotype variation%between diabetics and controls was found at KCNJ11(2.07%)and TCF7L2(1.62%).This study was not able to detect an association of T2D risk with gene variants of IGF2BP2(rs4402960),SLC30A8(rs13266634),CAPN10(rs3792267)and HHEX(rs1111875).Moreover,no association was found between FTO gene variants(rs9939609 and rs8050136)and T2D risk.However,T2D risk was found to be significantly associated with obesity(P=0.002,OR=2.22);and with the Waist-to-Hip ratio(n=532,P=1.9×10^(-7),OR=2.4),[among males(n=234,P=1.2×10^(-4),OR=2.0)and females(n=298,P=0.001,OR=6.3)].CONCLUSION:Results confirmed the association of KCNJ11(rs5219),TCF7L2(rs7903146),CDKAL1(rs10946398)and CDKN2A/B(rs10811661)gene variants with susceptibility to T2D among Omani Arabs.
文摘Type 2 diabetes mellitus(T2DM) is a silent progressive polygenic metabolic disorder resulting from ineffective insulin cascading in the body. World-wide, about 415 million people are suffering from T2DM with a projected rise to 642 million in 2040. T2DM is treated with several classes of oral antidiabetic drugs(OADs) viz. biguanides, sulfonylureas, thiazolidinediones, meglitinides, etc. Treatment strategies for T2DM are to minimize long-term micro and macro vascular complications by achieving an optimized glycemic control. Genetic variations in the human genome not only disclose the risk of T2DM development but also predict the personalized response to drug therapy. Inter-individual variability in response to OADs is due to polymorphisms in genes encoding drug receptors, transporters, and metabolizing enzymes for example, genetic variants in solute carrier transporters(SLC22A1, SLC22A2, SLC22A3, SLC47A1 and SLC47A2) are actively involved in glycemic/HbA1c management of metformin. In addition, CYP gene encoding Cytochrome P450 enzymes also play a crucial role with respect to metabolism of drugs. Pharmacogenetic studies provide insights on the relationship between individual genetic variants and variable therapeutic outcomes of various OADs. Clinical utility of pharmacogenetic study is to predict the therapeutic dose of various OADs on individual basis. Pharmacogenetics therefore, is a step towards personalized medicine which will greatly improve the efficacy of diabetes treatment.
文摘Introduction: Diffuse variant of GC is composed of gastric-type mucous cells, which generally do not form glands, but rather permit the mucosa and wall as scattered individual cells or small clusters in an “infiltrative” growth pattern. These cells appear to arise from the middle layer of the mucosa, and the presence of intestinal metaplasia is not a prerequisite. In this version, mucin formation expands the malignant cells and pushes the nucleus to the periphery, creating a “signet ring” conformation. If the signetring cells are more than 50% of the tumor, the tumor is classified as signetring cell carcinoma [1]. This case is important for reporting because we encountered for the first time such a carcinoma type, due to the new age and its atypical presentation. Case Presentation: We report a case of a 20 years Albanian old patient with Signet Ring Cell Type of Gastric CA. The patient was brought at the urgency with severe abdominal pain, nausea and peritoneal irritation. Clinical examination has been made in emergency, where we conclude the signs of peritoneal irritation, from native Ro no signs of pneumoperitoneum, while laboratory tests found a slight anemia (erythrocytes 3.36, HCT 25, HGB 8.6). Two hours later we repeated the native RTG and there were present the signs of pneumoperitoneum. It was indicated urgent surgical in-tervention. Intraoperatively, we found Ulcer duodenal perforation and?undertook the operation procedures by Roscoe Graham technique. Conclusions: At this age, it is rare, and it is difficult to detect in its early stages, because the signs and symptoms are often non-existent, non-specific, or mimic as an ulcer. The most common symptoms are early heartburn indigestion, abdominal pain or discomfort, vomiting, constipation, diarrhea or to feel of filling after a small meal, loss of appetite, weakness and fatigue. Less common symptoms are anemia and weight loss.
基金supported by the National Natural Science Foundation of China,No.81772688(to DSG)the Postdoctoral Science Foundation of Jiangsu Province of China,No.1202119C(to HL)
文摘Glial cell line-derived neurotrophic factor(GDNF) plays a critical role in neuronal survival and function. GDNF has two major splice variants in the brain,α-pro-GDNF and β-pro-GDNF, and both isoforms have strong neuroprotective effects on dopamine neurons. However, the expression of the GDNF splice variants in dopaminergic neurons in the brain remains unclear. Therefore, in this study, we investigated the mRNA and protein expression of α-and β-pro-GDNF in the mouse brain by real-time quantitative polymerase chain reaction, using splice variant-specific primers, and western blot analysis. At the mRNA level,β-pro-GDNF expression was significantly greater than that of α-pro-GDNF in the mouse brain. In contrast, at the protein level,α-pro-GDNF expression was markedly greater than that of β-pro-GDNF. To clarify the mechanism underlying this inverse relationship in mRNA and protein expression levels of the GDNF splice variants, we analyzed the expression of sorting protein-related receptor with A-type repeats(SorLA) by real-time quantitative polymerase chain reaction. At the mRNA level, SorLA was positively associated with β-pro-GDNF expression, but not with α-pro-GDNF expression. This suggests that the differential expression of α-and β-pro-GDNF in the mouse brain is related to SorLA expression. As a sorting protein, SorLA could contribute to the inverse relationship among the mRNA and protein levels of the GDNF isoforms. This study was approved by the Animal Ethics Committee of Xuzhou Medical University, China on July 14, 2016.
文摘The pharmacological interventions currently available to control type 2 diabetes mellitus(T2DM) show a wide interindividual variability in drug response, emphasizing the importance of a personalized, more effective medical treatment for each individual patient. In this context, a growing interest has emerged in recent years and has focused on pharmacogenetics, a discipline aimed at understanding the variability in patients' drug response, making it possible to predict which drug is best for each patient and at what doses. Recent pharmacological and clinical evidences indicate that genetic polymorphisms(or genetic variations) of certain genes can adversely affect drug response and therapeutic efficacy of oral hypoglycemic agents in patients with T2 DM, through pharmacokinetic- and/or pharmacodynamic-based mechanisms that may reduce the therapeutic effects or increase toxicity. For example, genetic variants in genes encoding enzymes of the cytochrome P-450 superfamily, or proteins of the ATP-sensitive potassium channel on the beta-cell of the pancreas, are responsible for the interindividual variability of drug response to sulfonylureas in patients with T2 DM. Instead, genetic variants in the genes that encode for the organic cation transporters of metformin have been related to changes in both pharmacodynamic and pharmacokinetic responses to metformin in metformin-treated patients. Thus, based on the individual's genotype, the possibility, in these subjects, of a personalized therapy constitutes the main goal of pharmacogenetics, directly leading to the development of the right medicine for the right patient. Undoubtedly, this represents an integral part of the translational medicine network.
文摘旨在研究中国本土槐猪和引入瘦肉型猪(杜洛克猪、大约克夏猪、长白猪)在生长育肥相关基因MC4R和MSTN、脊椎数量相关基因NR6A1和VRTN、肉质性状相关基因PHKG1和PRKAG3以及病原感染相关基因SYNGR2和FUT1这8个基因9个SNP位点的遗传变异特征。利用竞争性等位基因特异性PCR(KASP)和聚合酶链反应-限制性片段长度多态性(PCR-restriction fragment length polymorphism,PCR-RFLP)方法对突变位点进行基因分型,根据原始文献对各位点进行有利等位基因判定,并制作各猪种在各位点有利等位基因和不利等位基因的百分比示意图。结果:槐猪在NR6A1基因突变位点存在一定多态性,有利等位基因频率为0.24,其他位点表现为单一基因型,其中,PHKG1、PRKAG3突变位点为有利等位基因,而在MC4R、MSTN、VRTN、SYNGR2和FUT1突变位点为不利等位基因;杜洛克猪在MC4R、NR6A1、VRTN、SYNGR2和FUT1突变位点有利等位基因占优,然而,PHKG1基因不利等位基因仍有一定的比例;大约克夏猪在MC4R、SYNGR2、NR6A1和VRTN基因突变位点有利等位基因占优,而其他位点为不利等位基因;长白猪在MC4R、MSTN、PRKAG3(p.Val249Ile)和SYNGR2这4个基因突变位点不利基因占优;杜洛克猪在VRTN基因、长白猪在MC4R基因突变位点处于遗传不平衡状态(P<0.05)。以上结果为槐猪品种保护与利用以及瘦肉型猪种分子遗传标记选育提供了有益的信息。
文摘A variant of Fermat’s last Diophantine equation is proposed by adjusting the number of terms in accord with the power of terms and a theorem describing the solubility conditions is stated. Numerically obtained primitive solutions are presented for several cases with number of terms equal to or greater than powers. Further, geometric representations of solutions for the second and third power equations are devised by recasting the general equation in a form with rational solutions less than unity. Finally, it is suggested to consider negative and complex integers in seeking solutions to Diophantine forms in general.
