Gene Function & Disease最新文献_第4页

Genes, deafness, and balance disorders 基因，耳聋和平衡障碍

Gene Function & Disease Pub Date : 2001-10-02 DOI: 10.1002/1438-826X(200110)2:2/3<76::AID-GNFD76>3.0.CO;2-G

Jan Siemens, Amanda Littlewood-Evans, Mathias Senften, Ulrich Müller

{"title":"Genes, deafness, and balance disorders","authors":"Jan Siemens, Amanda Littlewood-Evans, Mathias Senften, Ulrich Müller","doi":"10.1002/1438-826X(200110)2:2/3<76::AID-GNFD76>3.0.CO;2-G","DOIUrl":"10.1002/1438-826X(200110)2:2/3<76::AID-GNFD76>3.0.CO;2-G","url":null,"abstract":"The mammalian auditory sense organ is subdivided into three principle compartments, the outer-, middle- and inner ear. The main task of the outer- and middle ear is to channel sound waves towards the cochlea within the inner ear. The inner ear also contains the vestibule, the end organ for the perception of gravity and acceleration. Hair cells within the sensory epithelia of the cochlea and the vestibule contain stereocilia that harbor mechanically gated ion channels. These ion channels open or close upon deflection of the stereocilia leading to changes in cell polarization and the rate of neurotransmitter release from hair cells onto sensory neurons. In this way, mechanical signals evoked by sound waves or head movement are transformed into electrochemical signals. The positional cloning of human disease genes and the analysis of mouse mutants has led to the identification of numerous genes that cause deafness and balance disorders. These findings provide insights into the molecular and cellular requirements for mechanosensory transduction and establish an entry point to understand deafness at the molecular level. We will summarize results that have shed light on the function of extracellular matrix glycoproteins, cell adhesion molecules, and components of the actin cytoskeleton in the inner ear.","PeriodicalId":100573,"journal":{"name":"Gene Function & Disease","volume":"2 2-3","pages":"76-82"},"PeriodicalIF":0.0,"publicationDate":"2001-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/1438-826X(200110)2:2/3<76::AID-GNFD76>3.0.CO;2-G","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72887721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Effects of farnesyltransferase inhibitors on cell cycle progression of human cancer cells 法尼基转移酶抑制剂对人癌细胞细胞周期进展的影响

Gene Function & Disease Pub Date : 2001-10-02 DOI: 10.1002/1438-826X(200110)2:2/3<99::AID-GNFD99>3.0.CO;2-V

Chen Jiang, Juan Kato-Stankiewicz, Chia-Ling Gau, Fuyuhiko Tamanoi

{"title":"Effects of farnesyltransferase inhibitors on cell cycle progression of human cancer cells","authors":"Chen Jiang, Juan Kato-Stankiewicz, Chia-Ling Gau, Fuyuhiko Tamanoi","doi":"10.1002/1438-826X(200110)2:2/3<99::AID-GNFD99>3.0.CO;2-V","DOIUrl":"10.1002/1438-826X(200110)2:2/3<99::AID-GNFD99>3.0.CO;2-V","url":null,"abstract":"Farnesyltransferase inhibitors (FTIs) represent a novel class of anti-cancer drugs with preferential effects on transformed cells. FTIs are currently evaluated in clinical trials. They are developed with the idea to inhibit farnesylation and membrane association of proteins such as Ras. In support of this idea, FTIs are effective in interfering with phenotypes due to H-ras activation, although K-ras activated events are resistant to FTIs. Recent studies on farnesylated proteins also raised the possibility that FTIs affect farnesylated proteins other than H-ras. To gain insight into this possibility, we have examined cellular effects of FTIs on human cancer cells. We, as well as others, have observed that FTIs cause enrichment of G0/G1-phase cells with a number of cancer cells. In addition, FTIs affect proteins involved in cell cycle regulation, such as retinoblastoma protein, p21Waf1/Cip1 and cyclins. With some cancer cell lines, FTI causes G2/M enrichment. Proteins, such as farnesylated Rho proteins and centromere binding proteins CENP-E/F may play roles in these cell cycle effects.","PeriodicalId":100573,"journal":{"name":"Gene Function & Disease","volume":"2 2-3","pages":"99-107"},"PeriodicalIF":0.0,"publicationDate":"2001-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/1438-826X(200110)2:2/3<99::AID-GNFD99>3.0.CO;2-V","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86631563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

RNA binding proteins in epilepsy 癫痫中的RNA结合蛋白

Gene Function & Disease Pub Date : 2001-10-02 DOI: 10.1002/1438-826X(200110)2:2/3<95::AID-GNFD95>3.0.CO;2-I

Miklos Toth

{"title":"RNA binding proteins in epilepsy","authors":"Miklos Toth","doi":"10.1002/1438-826X(200110)2:2/3<95::AID-GNFD95>3.0.CO;2-I","DOIUrl":"10.1002/1438-826X(200110)2:2/3<95::AID-GNFD95>3.0.CO;2-I","url":null,"abstract":"RNA binding proteins are involved in a diverse array of biological functions including mRNA transport, splicing, localization, stability and translation. Jerky is an RNA binding protein, complexed with mRNAs in neurons, that regulates mRNA utilization and consequently translation. The mouse line defective in the jerky gene shows recurrent seizures; a hallmark of epilepsy. Lack of FMRP (Fragile X Mental Retardation Protein), another RNA binding protein involved in mRNA processing and translation, also results in seizures in mice. This finding is consistent with the high incidence of epilepsy in fragile X syndrome. These two mutant mice are examples of a seizure condition elicited by a deficiency in RNA binding proteins. It is hypothesized that lack of Jerky and FMRP results in the abnormal translation of target-RNAs compromising the development and/or function of neurons. It is known that perturbation of neuronal development/function can result in recurrent seizures. The seizure phenotype of Jerky and FMRP deficient mice raises the possibility that a dysfunction in RNA binding proteins may be a more general disease mechanism in epilepsy.","PeriodicalId":100573,"journal":{"name":"Gene Function & Disease","volume":"2 2-3","pages":"95-98"},"PeriodicalIF":0.0,"publicationDate":"2001-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/1438-826X(200110)2:2/3<95::AID-GNFD95>3.0.CO;2-I","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79386354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Gene transfer with high-capacity „gutless”︁ adenoviral vectors 基因转移与高容量“无胆”︁腺病毒载体

Gene Function & Disease Pub Date : 2001-10-02 DOI: 10.1002/1438-826X(200110)2:2/3<122::AID-GNFD122>3.0.CO;2-7

Stefan Kochanek

引用次数: 0

Identification of two amino acid residues which determine the substrate specificity of human β-D-N-acetylhexosaminidase A 测定人β- d - n -乙酰己糖苷酶A底物特异性的两个氨基酸残基的鉴定

Gene Function & Disease Pub Date : 2001-08-21 DOI: 10.1002/1438-826X(20018)2:1<38::AID-GNFD38>3.0.CO;2-#

F. Kaplan, B. Boulay, P. Cordeiro, P. Hechtman

{"title":"Identification of two amino acid residues which determine the substrate specificity of human β-D-N-acetylhexosaminidase A","authors":"F. Kaplan, B. Boulay, P. Cordeiro, P. Hechtman","doi":"10.1002/1438-826X(20018)2:1<38::AID-GNFD38>3.0.CO;2-#","DOIUrl":"https://doi.org/10.1002/1438-826X(20018)2:1<38::AID-GNFD38>3.0.CO;2-#","url":null,"abstract":"β-D-N-acetylhexosaminidases A (Hex A, αβ) and B (Hex B, ββ) cleave N-acetylglucosamine and N-acetylgalactosamine termini of glycoconjugates. Hex B hydrolyzes neutral substrates whereas Hex A also hydrolyzes electronegative substrates, including GM2 ganglioside, which accumulates in the neurons of patients with Tay-Sachs disease (TSD). We hypothesized that enzyme-substrate electrostatic interactions influence substrate specificities of the two isozymes. Among seven positively charged candidate residues in Hex A, at which substitution for the homolgous β residue was performed, only the α424RL mutation resulted in loss of activity toward the electronegative substrate 4-methylumbellifery-N-acetylglucosamine-6-sulfate (4MUGS). The substitution LR at the homolgous β position 453 increased Hex B activity to 4MUGS 5-fold. αR453 projects into the α-subunit substrate cavity opposite three active site amino acids. The adjacent residue, βD452, may repel negatively charged substrates. Double substitution, βL453R and βD452N (the α-subunit homologue), increases 4MUGS hydrolysis by 22-fold relative to wild type Hex B. These results indicate that the homology model for hexosaminidase gives an accurate picture of the active site region and may furnish other candidate residues to test as determinants of the unique substrate specificity of Hex A.","PeriodicalId":100573,"journal":{"name":"Gene Function & Disease","volume":"27 1","pages":"38-45"},"PeriodicalIF":0.0,"publicationDate":"2001-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89452753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Mechanisms and brain specific consequences of genomic imprinting in Prader-Willi and Angelman syndromes Prader-Willi综合征和Angelman综合征中基因组印记的机制和脑特异性后果

Gene Function & Disease Pub Date : 2001-08-21 DOI: 10.1002/1438-826X(20018)2:1<7::AID-GNFD7>3.0.CO;2-N

Axel Schumacher

{"title":"Mechanisms and brain specific consequences of genomic imprinting in Prader-Willi and Angelman syndromes","authors":"Axel Schumacher","doi":"10.1002/1438-826X(20018)2:1<7::AID-GNFD7>3.0.CO;2-N","DOIUrl":"10.1002/1438-826X(20018)2:1<7::AID-GNFD7>3.0.CO;2-N","url":null,"abstract":"Genomic imprinting is a curious manifestation of epigenetic inheritance that defies normal Mendelian genetics. Most vertebrate genes are expressed from both, the paternal and maternal alleles. However, a subset of mammalian genes is monoallelically expressed in a parent-of-origin manner due to imprinting mechanisms that confer a parent-specific memory to individual cells. Epigenetically correct inheritance of imprinted genes requires appropriate germ-line specific chromosomal modifications like histone acetylation or DNA methylation. Some of these modified, imprinted genes are organized in clusters as exemplified by the 2 Mb domain on human chromosome 15q11-q13. Deletion, uniparental disomy (UPD), or inappropriate imprinting of this chromosomal region results in the neurogenetic disorders Prader-Willi syndrome (PWS) and Angelman syndrome (AS), respectively. Recently, new genes and regulatory mechanisms that contribute to imprint regulation within the affected regions have been characterized. This review focuses on the role of these imprinted genes on human chromosome 15q11-13, imprinting center elements, and epigenetic mechanisms in the development of specific regions of the mammalian brain.","PeriodicalId":100573,"journal":{"name":"Gene Function & Disease","volume":"2 1","pages":"7-25"},"PeriodicalIF":0.0,"publicationDate":"2001-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/1438-826X(20018)2:1<7::AID-GNFD7>3.0.CO;2-N","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77021320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 11

Human monoamine oxidase: from genetic variation to complex human phenotypes 人类单胺氧化酶:从遗传变异到复杂的人类表型

Gene Function & Disease Pub Date : 2001-08-21 DOI: 10.1002/1438-826X(20018)2:1<26::AID-GNFD26>3.0.CO;2-D

Jorune Balciuniene, Elena E. Jazin

引用次数: 8

Identification of two amino acid residues which determine the substrate specificity of human β-D-N-acetylhexosaminidase A 测定人β- d - n -乙酰己糖苷酶A底物特异性的两个氨基酸残基的鉴定

Gene Function & Disease Pub Date : 2001-08-21 DOI: 10.1002/1438-826X(20018)2:1<38::AID-GNFD38>3.0.CO;2-%23

Feige Kaplan, Bernard Boulay, Paulo Cordeiro, Peter Hechtman

{"title":"Identification of two amino acid residues which determine the substrate specificity of human β-D-N-acetylhexosaminidase A","authors":"Feige Kaplan, Bernard Boulay, Paulo Cordeiro, Peter Hechtman","doi":"10.1002/1438-826X(20018)2:1<38::AID-GNFD38>3.0.CO;2-%23","DOIUrl":"https://doi.org/10.1002/1438-826X(20018)2:1<38::AID-GNFD38>3.0.CO;2-%23","url":null,"abstract":"β-D-N-acetylhexosaminidases A (Hex A, αβ) and B (Hex B, ββ) cleave N-acetylglucosamine and N-acetylgalactosamine termini of glycoconjugates. Hex B hydrolyzes neutral substrates whereas Hex A also hydrolyzes electronegative substrates, including GM2 ganglioside, which accumulates in the neurons of patients with Tay-Sachs disease (TSD). We hypothesized that enzyme-substrate electrostatic interactions influence substrate specificities of the two isozymes. Among seven positively charged candidate residues in Hex A, at which substitution for the homolgous β residue was performed, only the α424R→L mutation resulted in loss of activity toward the electronegative substrate 4-methylumbellifery-N-acetylglucosamine-6-sulfate (4MUGS). The substitution L→R at the homolgous β position 453 increased Hex B activity to 4MUGS 5-fold. αR453 projects into the α-subunit substrate cavity opposite three active site amino acids. The adjacent residue, βD452, may repel negatively charged substrates. Double substitution, βL453R and βD452→N (the α-subunit homologue), increases 4MUGS hydrolysis by 22-fold relative to wild type Hex B. These results indicate that the homology model for hexosaminidase gives an accurate picture of the active site region and may furnish other candidate residues to test as determinants of the unique substrate specificity of Hex A.","PeriodicalId":100573,"journal":{"name":"Gene Function & Disease","volume":"2 1","pages":"38-45"},"PeriodicalIF":0.0,"publicationDate":"2001-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"109172433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Prokaryotic expression analysis of I269L and R270K mutations of the phenylalanine hydroxylase gene 苯丙氨酸羟化酶基因I269L和R270K突变的原核表达分析

Gene Function & Disease Pub Date : 2001-08-21 DOI: 10.1002/1438-826X(20018)2:1<46::AID-GNFD46>3.0.CO;2-9

Paula Leandro, Isabel Rivera, Maria Celeste Lechner, David Konecki, Isabel Tavares de Almeida

引用次数: 2

A comparison of methods to extract pure DNA from mammalian intestinal contents and from feces 从哺乳动物肠道内容物和粪便中提取纯DNA方法的比较

Gene Function & Disease Pub Date : 2001-08-21 DOI: 10.1002/1438-826X(20018)2:1<51::AID-GNFD51>3.0.CO;2-0

Maria Palka Santini, Doris Renz, Walter Doerfler

引用次数: 6