Inactivation of the peroxisomal ABCD2 transporter in the mouse leads to late-onset ataxia involving mitochondria, Golgi and endoplasmic reticulum damage

ATP-binding cassette (ABC) transporters facilitate unidirectional translocation of chemically diverse substances, ranging from peptides to lipids, across cell or organelle membranes. In peroxisomes, a subfamily of four ABC transporters (ABCD1 to ABCD4) has been related to fatty acid transport, because patients with mutations in ABCD1 (ALD gene) suffer from X-linked adrenoleukodystrophy (X-ALD), a disease characterized by an accumulation of very-long-chain fatty acids (VLCFAs). Inactivation in the mouse of the abcd1 gene leads to a late-onset neurodegenerative condition, comparable to the late-onset form of X-ALD [Pujol, A., Hindelang, C., Callizot, N., Bartsch, U., Schachner, M. and Mandel, J.L. (2002) Late onset neurological phenotype of the X-ALD gene inactivation in mice: a mouse model for adrenomyeloneuropathy. Hum. Mol. Genet., 11, 499-505.]. In the present work, we have generated and characterized a mouse deficient for abcd2, the closest paralog to abcd1. The main pathological feature in abcd2-/- mice is a late-onset cerebellar and sensory ataxia, with loss of cerebellar Purkinje cells and dorsal root ganglia cell degeneration, correlating with accumulation of VLCFAs in the latter cellular population. Axonal degeneration was present in dorsal and ventral columns in spinal cord. We have identified mitochondrial, Golgi and endoplasmic reticulum damage as the underlying pathological mechanism, thus providing evidence of a disturbed organelle cross-talk, which may be at the origin of the pathological cascade.     

Bacteremia due to a novel Microbacterium species in a patient with leukemia and description of Microbacterium paraoxydans sp. nov

A yellow-pigmented coryneform rod was isolated from the blood of a child with acute lymphoblastic leukemia who was perfused with a central venous catheter. The culture bottles were positive twice, at a 2-month interval. The isolate was identified as a Microbacterium sp. and studied along with five other similar strains. Phenotypic, chemotaxonomic, and genetic characteristics indicated that they are closely related to Microbacterium oxydans but that they belong to a distinct species, for which the name Microbacterium paraoxydans sp. nov. is proposed. The type strain of M. paraoxydans is CF36(T) = DSM 15019(T). The G+C content of its DNA is 69.9 mol%.     

Molecular Analysis of SV-40-CAL,a New Slow Growing SV-40 Strain from the Kidney of a Caged New World Monkey with Fatal Renal Disease

A decline of the Callimico goeldii population in American zoos is presently occurring due to glomerulonephritis of unknown etiology. We hypothesized that this emerging idiopathic fatal renal disease (IFRD) was caused by a virus. We therefore attempted to isolate virus from the kidneys three C. goeldi in Illinois that had IFRD. Along with other viruses, Simian virus 40 (SV-40) strain CAL was isolated. SV-40-CAL is currently the slowest-growing natural isolate of SV-40 in CV-1 cells. Inefficient SV-40-CAL growth in CV-1 cells stems from two features: a suboptimal protoarchetypal regulatory region, and a Large tumor antigen gene sequence like that of SV-40 strain T302, previously considered the slow-growing natural isolate of SV-40. To our knowledge, this is the first documented isolation of SV-40 from a New World monkey outside of a laboratory setting. Though SV-40 is renaltropic, the role of SV-40-CAL in IFRD is uncertain. Transmission of SV-40 to C. goeldii through anthropogenic activity is suspected.     

Assessment of Self-Reward Strategies for Maintenance of Breast Self-Examination

This study examined the relative impact of different self-reward strategies on maintenance of breast self-examination (BSE) practice among 1649 women trained to do BSE. Training groups were randomized into four conditions: (a) self-reward instructions and materials delivered at the end of the BSE training session; (b) self-reward suggestions delivered through the mail each month, contingent upon the BSE performance; (c) external monetary rewards and self-reward suggestions delivered through the mail each month on an intermittent schedule, contingent upon BSE practice; and (d) a no-reward control condition. Follow-up assessments 12 months following training revealed a pattern of evidence in support of the benefits of external monetary rewards and self-reward prompts on BSE frequency and quality; however, it is likely that the value of that condition lies in the external reward component.     

Reevaluation of a genetic model for the development of exostosis in hereditary multiple exostosis

EXT1 and EXT2 are genes that have been shown to cause hereditary multiple exostosis (HME), a syndrome marked by the formation of bony growths juxtaposed to the growth plate. These genes are members of a growing family of proteins with glycosyltransferase activity required for the synthesis of heparan sulfate chains. This protein activity is predicted to play a role in the expression of proteoglycans on the cell surface and in the extracellular matrix. We and others have previously suggested that a two-hit mutational model applies to the development of an exostosis where a germline mutation coupled with a somatic mutation results in the loss of EXT1 or EXT2 function and subsequent tumor formation. We report the direct sequencing and loss of heterozygosity (LOH) analysis of 12 exostoses from 10 HME families, 4 solitary exostoses, and their corresponding constitutional DNA. Of the 16 exostoses screened, we find only one solitary case in which two somatic mutations, a deletion and an LOH, are present. This provides limited support for the two-hit hypothesis involving the EXT1 and EXT2 genes for the development of an exostosis. Alternative models are developed based on the functional significance of EXT proteins in heparan sulfate biosynthesis.     

CD45R gives immunofluorescence and transduces signals on mouse T cells

The expression of CD45R on mouse T cells has been studied. This antigen is expressed on the two higher molecular weight bands of CD45 (or T200) and in mouse it is currently used as a marker of B cells (B220). Here we confirm that CD45R is expressed on some mouse T cell clones. We show that a small but measurable proportion of mouse spleen and peripheral blood lymphocyte T cells gives positive immunofluorescence with B220. Also CD45R-specific antibodies increase the proliferation response to phytohemagglutinin up to 3-fold, thus confirming that CD45R molecules transduce a signal into mouse T cells.     

Activation of mucosal Vβ3+ T cells and tissue damage in human small intestine by the bacterial superantigen,Staphylococcus aureus enterotoxin B

Staphylococcus aureus enterotoxin B (SEB) was added to explants of fetal human intestine in organ culture or administered into the lumen of fetal small intestine prior to culture. Both routes produced a massive increase in lamina propria T cells expressing Vβ33, and to a lesser extent, those expressing Vβ5 and Vβ12. SEB-activated lamina propria T cells produced interleukin-2 and interferon-Y and T cell activation was accompanied by tissue damage, which was inhibited by FK506.     

What impairs subitizing in cerebral palsied children?

The goal of this study was to investigate the factors responsible for the low subitizing limit of cerebral palsied (CP) children. For this purpose, 44 CPs were tested on two tasks involving the rapid recognition of dot configurations. The answer was either a number (subitizing task) or the name of a pattern (pattern recognition task). The CPs were compared to controls of the same age. All children were evaluated for visual and visuospatial short-term memory. The results showed that CPs with a low subitizing limit did not do better with a canonical arrangement than the random one, were impaired to the same extent on the pattern recognition task as on the subitizing task, and had a short visuospatial short-term memory span. These results suggest that the low subitizing limit of CPs stems from a (non-number-dependent) lesser capacity to perceive a dot configuration as a gestalt. A low subitizing limit was almost always associated with a right-hemisphere lesion.     

Tetraspanins: molecular organisers of the leukocyte surface

Tetraspanins are a large superfamily of cell surface membrane proteins characterised by their four transmembrane domains. They are expressed in a wide variety of cell types and have functional roles in processes, such as cellular adhesion, motility, activation and tumour invasion. Leukocytes express 相似文献