Microtubule transport defects in neurological and ciliary disease

Microtubules are primarily responsible for facilitating long-distance transport of both proteins and organelles. Given the critical role of this process in cellular function, it is not surprising that perturbation of microtubule-based transport can lead to diverse phenotypes in humans, including cancer and neurodegenerative disorders such as Alzheimer or Huntington disease. Recent investigations have also indicated that defects in specialized microtubule-based transport systems, such as mutations affecting the transport of protein particles along the length of cilia (intraflagellar transport) can cause retinal dystrophy, polycystic kidney disease or more complex syndromic phenotypes, such as Bardet-Biedl syndrome. In this review, we discuss recent findings implicating defects in microtubule-associated transport and motor proteins in a variety of diseases, particularly the role of defective microtubular transport in neurological and ciliary disease. These defects frequently display phenotypic consequences that manifest as human disease yet do not cause organismal lethality.Received 7 Janury 2005; received after revision 23 February 2005; accepted 21 March 2005     

Springtime movements, boost Use, and foraging activity of Townsend's big-eared bat ( Plecotus townsendii ) in central Oregon

Seasonal movements, roost-site fidelity, and foraging activity patterns are largely unknown for western populations of Townsend's big-eared bat ( Plecotus townsendii ). We used miniature radiotelemetry units to track springtime movements of six bats inhabiting forested lava flows in central Oregon, and found that bats moved up to 24 km from hibernacula to foraging areas. Individual bats returned to the same foraging area on successive nights but shifted to different areas in presumed response to changes in insect availability. Both sexes apparently use a series of interim roost sites between emergence from hibernation and the time females enter into maternity colonies, with little individual fidelity to these sites. In regions characterized by extensive lava-flow topography, suitable daytime roosts are numerous and dispersed over a large area, allowing bats to move relatively great distances to locate foraging ranges. Hence, the actual area of concern for effective management of individual populations can be considerably larger than indicated solely by locations of hibernacula and maternity caves of this declining species.     

Multiple self-healing squamous epithelioma is caused by a disease-specific spectrum of mutations in TGFBR1

Multiple self-healing squamous epithelioma (MSSE), also known as Ferguson-Smith disease (FSD), is an autosomal-dominant skin cancer condition characterized by multiple squamous-carcinoma-like locally invasive skin tumors that grow rapidly for a few weeks before spontaneously regressing, leaving scars. High-throughput genomic sequencing of a conservative estimate (24.2 Mb) of the disease locus on chromosome 9 using exon array capture identified independent mutations in TGFBR1 in three unrelated families. Subsequent dideoxy sequencing of TGFBR1 identified 11 distinct monoallelic mutations in 18 affected families, firmly establishing TGFBR1 as the causative gene. The nature of the sequence variants, which include mutations in the extracellular ligand-binding domain and a series of truncating mutations in the kinase domain, indicates a clear genotype-phenotype correlation between loss-of-function TGFBR1 mutations and MSSE. This distinguishes MSSE from the Marfan syndrome-related disorders in which missense mutations in TGFBR1 lead to developmental defects with vascular involvement but no reported predisposition to cancer.     

上市公司经营活动状况对金融资产规模影响探究

越来越多的非金融业上市公司开始参与金融投资.通过实证研究来探索非金融业上市公司经营状况对其金融资产投资规模的影响,发现上市公司的金融资产有显著规模效应,同一行业内经营活动状况较好的上市公司有较少的金融投资,经营活动收入稳定增长的上市公司有较少的金融投资.     

Membrane traffic in the secretory pathway

Vesicular transport is the basic communication mechanism between different compartments in a cell and with the environment. In this review I discuss the principles of vesicle generation and consumption with particular emphasis on the different types of coat proteins and the timing of the shedding of the coat proteins from transport containers. In recent years it has become clear that there are more coat complexes than the classical COPI, COPII and clathrin coats. These additional coats may generate vesicles that transport cargo in a temporally and/or spatially controlled manner. Work over the last years suggests that GTP hydrolysis occurs early during vesicle biogenesis, destabilizing the coat perhaps before fission of the vesicle from the donor membrane occurs. Recent findings imply, however, that tethers at the receiving compartment specifically detect the coat on vesicle. (Part of a Multi-author Review)