The peripheral myelin protein gene PMP-22 is contained within the Charcot-Marie-Tooth disease type 1A duplication.

Charcot-Marie-Tooth disease (CMT1) is the most common form of inherited peripheral neuropathy. Although the disease is genetically heterogeneous, it has been demonstrated that the gene defect is the most frequent type (CMT1A) is the result of a partial duplication of band 17p11.2. Recent studies suggested that the peripheral hypomyelination syndrome in the trembler (Tr) mouse, a possible animal model for CMT1 disease, is associated with a point mutation in the peripheral myelin protein-22 gene (pmp-22). Expression of pmp-22 is particularly high in Schwann cells, and the protein is found in peripheral myelin. We now report that the human PMP-22 gene is contained within the CMT1A duplication. We therefore, suggest that increased dosage of the PMP-22 gene may be the cause of CMT1A neuropathy.     

Isolation of a candidate gene for Norrie disease by positional cloning.

The gene for Norrie disease, an X-linked disorder characterized by progressive atrophy of the eyes, mental disturbances and deafness, has been mapped to chromosome Xp11.4 close to DXS7 and the monoamine oxidase (MAO) genes. By subcloning a YAC with a 640 kilobases (kb) insert which spans the DXS7-MAOB interval we have generated a cosmid contig which extends 250 kb beyond the MAOB gene. With one of these cosmids, microdeletions were detected in several patients with Norrie disease. Screening of cDNA libraries has enabled us to isolate and sequence a likely candidate gene for Norrie disease which is expressed in retina, choroid and fetal brain. No homologous sequences were found in DNA and protein databases indicating that this cDNA is part of a gene encoding a 'pioneer' protein.     

Telomere-associated chromosome fragmentation: applications in genome manipulation and analysis.

Telomere-associated chromosome fragmentation (TACF) is a new approach for chromosome mapping based on the non-targeted introduction of cloned telomeres into mammalian cells. TACF has been used to generate a panel of somatic cell hybrids with nested terminal deletions of the long arm of the human X chromosome, extending from Xq26 to the centromere. This panel has been characterized using a series of X chromosome loci. Recovery of the end clones by plasmid rescue produces a telomeric marker for each cell line and partial sequencing will allow the generation of sequence tagged sites (STSs). TACF provides a powerful and widely applicable method for genome analysis, a general way of manipulating mammalian chromosomes and a first step towards constructing artificial mammalian chromosomes.     

ZQ—1型自放式防火卷帘门启闭机的研制

介绍2K—H型少齿差行星传动在ZQ—1型自放式防火卷帘门启闭机中的应用,阐述了工作机理、设计计算及强度校核等。传动部分采用了固体润滑。     

推力轴承对单质量转子弯曲振动状态的影响

本文建立了计及推力轴承动特性影响的单质量转子运动方程。系统地分析和计算了推力轴承对转子弯曲振动状态的影响,并且对一些影响转子弯曲振动状态的参数进行了讨论。计算结果表明,在一定的工作状态下,推力轴承的存在可以显著地提高转子系统的临界转速及失稳转速,降低共振振幅。     

Different beta-subunits determine G-protein interaction with transmembrane receptors.

Regulatory GTP-binding proteins (G proteins) are membrane-attached heterotrimers (alpha, beta, gamma) that mediate cellular responses to a wide variety of extracellular stimuli. They undergo a cycle of guanine-nucleotide exchange and GTP hydrolysis, during which they dissociate into alpha-subunit and beta gamma complex. The roles of G-protein alpha-subunits in these processes and for the specificity of signal transduction are largely established; the beta- and gamma-subunits are essential for receptor-induced G-protein activation and seem to be less diverse and less specific. Although the complementary DNAs for several beta-subunits have been cloned, isolated subunits have only been studied as beta gamma complexes. Functional differences have been ascribed to the gamma-subunit on the basis of extensive sequence similarity among beta-subunits and apparent heterogeneity in gamma-subunit sequences. Beta gamma complexes can interact directly or indirectly with different effectors. They seem to be interchangeable in their interaction with pertussis toxin-sensitive alpha-subunits, so we tested this by microinjecting antisense oligonucleotides into nuclei of a rat pituitary cell line to suppress the synthesis of individual beta-subunits selectively. Here we show that two out of four subtypes of beta-subunits tested (beta 1 and beta 3) are selectively involved in the signal transduction cascades from muscarinic M4 (ref. 4) and somatostatin receptors, respectively, to voltage-dependent Ca2+ channels.     

Successive action of DnaK, DnaJ and GroEL along the pathway of chaperone-mediated protein folding.

The main stress proteins of Escherichia coli function in an ordered protein-folding reaction. DnaK (heat-shock protein 70) recognizes the folding polypeptide as an extended chain and cooperates with DnaJ in stabilizing an intermediate conformational state lacking ordered tertiary structure. Dependent on GrpE and ATP hydrolysis, the protein is then transferred to GroEL (heat-shock protein 60) which acts catalytically in the production of the native state. This sequential mechanism of chaperone action may represent an important pathway for the folding of newly synthesized polypeptides.     

Retinoic acid alters hindbrain Hox code and induces transformation of rhombomeres 2/3 into a 4/5 identity.

It has been suggested that Hox genes play an important part in the patterning of limbs, vertebrae and craniofacial structures by providing an ordered molecular system of positional values, termed the Hox code. Little is known about the nature of the signals that govern the establishment and regulation of Hox genes, but retinoic acid can affect the expression of these genes in cell lines and in embryonic tissues. On the basis of experimental and clinical evidence, the hindbrain and branchial region of the head are particularly sensitive to the effects of retinoic acid but the phenotypes are complex and hard to interpret, and how and if they relate to Hox expression has not been clear. Here we follow the changes induced by retinoic acid to hindbrain segmentation and the branchial arches using transgenic mice which contain lacZ reporter genes that reveal the endogenous segment-restricted expression of the Hox-B1 (Hox-2.9), Hox-B2(Hox-2.8) and Krox-20 genes. Our results show that these genes rapidly respond to exposure to retinoic acid at preheadfold stages and undergo a progressive series of changes in segmental expression that are associated with specific phenotypes in hindbrain of first branchial arch. Together the molecular and anatomical alterations indicate that retinoic acid has induced changes in the hindbrain Hox code which result in the homeotic transformation of rhombomeres (r) 2/3 to an r4/5 identity. A main feature of this rhombomeric phenotype is that the trigeminal motor nerve is transformed to a facial identity. Furthermore, in support of this change in rhombomeric identity, neural crest cells derived from r2/3 also express posterior Hox markers suggesting that the retinoic acid-induced transformation extends to multiple components of the first branchial arch.