在白血病细胞中普遍存在着Janus激酶(Janus kinase,JAK)-信号传导和转录激活因子(signal transduction and activator of transcription,STAT)信号通路的持续激活,该通路在急性白血病(acute leukemia,AL)中占据了重要地位。JAK2/JAK1基...在白血病细胞中普遍存在着Janus激酶(Janus kinase,JAK)-信号传导和转录激活因子(signal transduction and activator of transcription,STAT)信号通路的持续激活,该通路在急性白血病(acute leukemia,AL)中占据了重要地位。JAK2/JAK1基因突变在急性髓系白血病和急性淋巴细胞白血病中均有发现,并可能对疾病治疗和总体预后存在影响。在STAT家族成员中,STAT3和STAT5被证明是AL的关键影响因素。这些基因突变都可能为AL的治疗提供新靶点与新思路。该文就有关JAK-STAT信号通路及相关基因突变与AL的研究进展作一综述。展开更多
Genetic linkage analyses, genome-wide association studies of single nucleotide polymorphisms, copy number variation surveys, and mutation screenings found the human chromosomal 12q24 locus, with the genes SH2B3 and AT...Genetic linkage analyses, genome-wide association studies of single nucleotide polymorphisms, copy number variation surveys, and mutation screenings found the human chromosomal 12q24 locus, with the genes SH2B3 and ATXN2 in its core, to be associated with an exceptionally wide spectrum of disease susceptibilities. Hematopoietic traits of red and white blood cells(like erythrocytosis and myeloproliferative disease), autoimmune disorders(like type 1 diabetes, coeliac disease, juvenile idiopathic arthritis, rheumatoid arthritis, thrombotic antiphospholipid syndrome, lupus erythematosus, multiple sclerosis, hypothyroidism and vitiligo), also vascular pathology(like kidney glomerular filtration rate deficits, serum urate levels, plasma beta-2-microglobulin levels, retinal microcirculation problems, diastolic and systolic blood pressure and hypertension, cardiovascular infarction), furthermore obesity, neurodegenerative conditions(like the polyglutamine-expansion disorder spinocerebellar ataxia type 2, Parkinson's disease, the motor-neuron disease amyotrophic lateral sclerosis, and progressive supranuclear palsy), andfinally longevity were reported. Now it is important to clarify, in which ways the loss or gain of function of the locally encoded proteins SH2B3/LNK and ataxin-2, respectively, contribute to these polygenic health problems. SH2B3/LNK is known to repress the JAK2/ABL1 dependent proliferation of white blood cells. Its null mutations in human and mouse are triggers of autoimmune traits and leukemia(acute lymphoblastic leukemia or chronic myeloid leukemia-like), while missense mutations were found in erythrocytosis-1 patients. Ataxin-2 is known to act on RNA-processing and trophic receptor internalization. While its polyglutamine-expansion mediated gain-of-function causes neuronal atrophy in human and mouse, its deletion leads to obesity and insulin resistance in mice. Thus, it is conceivable that the polygenic pathogenesis of type 1 diabetes is enhanced by an SH2B3-dysregulation-mediated predisposition to au展开更多
The potential energy profile of the reaction between the atomic oxygen radical anion and acetonitrile has been mapped at the G3MP2B3 level of theory. Geometries of the reactants, products, intermediate complexes, and ...The potential energy profile of the reaction between the atomic oxygen radical anion and acetonitrile has been mapped at the G3MP2B3 level of theory. Geometries of the reactants, products, intermediate complexes, and transition states involved in this reaction have been optimized at the （U）B3LYP/6-31＋G（d,p） level, and then their accurate relative energies have been improved using the G3MP2B3 method. The potential energy profile is confirmed via intrinsic reaction coordinate calculations of transition states. Four possible production channels are examined respectively, as H＋ transfer, H-atom transfer, H2＋ transfer, and bi- molecular nucleophilic substitution （SN2） reaction pathways. Based on present calculations, the H2＋ transfer reaction is major among these four channels, which agrees with previous experimental conclusions.展开更多
Theoretical calculations of the [2,3]-sila-wittig rearrangement of isomers of [（allyloxy）silyl]lithium （C3H5O）HzSiLi have been performed in the gas phase and THF solvent using the G3MP2B3 method. Seven isomers of ...Theoretical calculations of the [2,3]-sila-wittig rearrangement of isomers of [（allyloxy）silyl]lithium （C3H5O）HzSiLi have been performed in the gas phase and THF solvent using the G3MP2B3 method. Seven isomers of silylenoid （C3H5O）H2SiLi, 1-7, are found. The [2,3]-silawittig rearrangement paths are followed using two isomers, 2 and 4, to yield the transition states as well as the products. In the transition state, the silicon center functions as a nucleophile and the aUyl as an electrophile. The interaction between the silicon and allylic sites leads to the formation of SiC（3） bond and the break of O-C（1） bond. Finally, the （allylsilyl）oxylithium （C3H5）H2SiOLi is obtained. The rearrangement paths are confirmed by the intrinsic reaction coordinate （IRC） calculations. The rearrangement mechanisms of reactions of 2 and 4 are similar, and the latter reaction is more favored in the gas phase and THF solvent. Also, the solvent effects are analyzed in this work.展开更多
文摘在白血病细胞中普遍存在着Janus激酶(Janus kinase,JAK)-信号传导和转录激活因子(signal transduction and activator of transcription,STAT)信号通路的持续激活,该通路在急性白血病(acute leukemia,AL)中占据了重要地位。JAK2/JAK1基因突变在急性髓系白血病和急性淋巴细胞白血病中均有发现,并可能对疾病治疗和总体预后存在影响。在STAT家族成员中,STAT3和STAT5被证明是AL的关键影响因素。这些基因突变都可能为AL的治疗提供新靶点与新思路。该文就有关JAK-STAT信号通路及相关基因突变与AL的研究进展作一综述。
文摘Genetic linkage analyses, genome-wide association studies of single nucleotide polymorphisms, copy number variation surveys, and mutation screenings found the human chromosomal 12q24 locus, with the genes SH2B3 and ATXN2 in its core, to be associated with an exceptionally wide spectrum of disease susceptibilities. Hematopoietic traits of red and white blood cells(like erythrocytosis and myeloproliferative disease), autoimmune disorders(like type 1 diabetes, coeliac disease, juvenile idiopathic arthritis, rheumatoid arthritis, thrombotic antiphospholipid syndrome, lupus erythematosus, multiple sclerosis, hypothyroidism and vitiligo), also vascular pathology(like kidney glomerular filtration rate deficits, serum urate levels, plasma beta-2-microglobulin levels, retinal microcirculation problems, diastolic and systolic blood pressure and hypertension, cardiovascular infarction), furthermore obesity, neurodegenerative conditions(like the polyglutamine-expansion disorder spinocerebellar ataxia type 2, Parkinson's disease, the motor-neuron disease amyotrophic lateral sclerosis, and progressive supranuclear palsy), andfinally longevity were reported. Now it is important to clarify, in which ways the loss or gain of function of the locally encoded proteins SH2B3/LNK and ataxin-2, respectively, contribute to these polygenic health problems. SH2B3/LNK is known to repress the JAK2/ABL1 dependent proliferation of white blood cells. Its null mutations in human and mouse are triggers of autoimmune traits and leukemia(acute lymphoblastic leukemia or chronic myeloid leukemia-like), while missense mutations were found in erythrocytosis-1 patients. Ataxin-2 is known to act on RNA-processing and trophic receptor internalization. While its polyglutamine-expansion mediated gain-of-function causes neuronal atrophy in human and mouse, its deletion leads to obesity and insulin resistance in mice. Thus, it is conceivable that the polygenic pathogenesis of type 1 diabetes is enhanced by an SH2B3-dysregulation-mediated predisposition to au
文摘The potential energy profile of the reaction between the atomic oxygen radical anion and acetonitrile has been mapped at the G3MP2B3 level of theory. Geometries of the reactants, products, intermediate complexes, and transition states involved in this reaction have been optimized at the （U）B3LYP/6-31＋G（d,p） level, and then their accurate relative energies have been improved using the G3MP2B3 method. The potential energy profile is confirmed via intrinsic reaction coordinate calculations of transition states. Four possible production channels are examined respectively, as H＋ transfer, H-atom transfer, H2＋ transfer, and bi- molecular nucleophilic substitution （SN2） reaction pathways. Based on present calculations, the H2＋ transfer reaction is major among these four channels, which agrees with previous experimental conclusions.
基金PhD Special Research Foundation of Chinese Education Department (No. 20040422010)the Scientific Research Foundation of Yangzhou University
文摘Theoretical calculations of the [2,3]-sila-wittig rearrangement of isomers of [（allyloxy）silyl]lithium （C3H5O）HzSiLi have been performed in the gas phase and THF solvent using the G3MP2B3 method. Seven isomers of silylenoid （C3H5O）H2SiLi, 1-7, are found. The [2,3]-silawittig rearrangement paths are followed using two isomers, 2 and 4, to yield the transition states as well as the products. In the transition state, the silicon center functions as a nucleophile and the aUyl as an electrophile. The interaction between the silicon and allylic sites leads to the formation of SiC（3） bond and the break of O-C（1） bond. Finally, the （allylsilyl）oxylithium （C3H5）H2SiOLi is obtained. The rearrangement paths are confirmed by the intrinsic reaction coordinate （IRC） calculations. The rearrangement mechanisms of reactions of 2 and 4 are similar, and the latter reaction is more favored in the gas phase and THF solvent. Also, the solvent effects are analyzed in this work.
