Receiving mixed signals: uncoupling oligodendrocyte differentiation and myelination

The development and maturation of an oligodendroglial cell is comprised of three intimately related processes that include proliferation, differentiation, and myelination. Here we review how proliferation and differentiation are controlled by distinct molecular mechanisms and discuss whether differentiation is merely a default of inhibited proliferation. We then address whether differentiation and myelination can be uncoupled in a similar manner. This task is particularly challenging because an oligodendrocyte cannot myelinate without first differentiating, and these processes are therefore not mutually exclusive. Is it solely the presence of the axon that distinguishes a differentiated oligodendrocyte from a myelinating one? Uncoupling these two processes requires identifying specific signals that regulate myelination without affecting the differentiation process. We will review current understanding of the relationship between differentiation and myelination and discuss whether these two processes can truly be uncoupled.     

Alternative exon usage selectively determines both tissue distribution and subcellular localization of the acyl-CoA thioesterase 7 gene products

Acyl-CoA thioesterases (ACOTs) catalyze the hydrolysis of acyl-CoAs to free fatty acids and coenzyme A. Recent studies have demonstrated that one gene named Acot7, reported to be mainly expressed in brain and testis, is transcribed in several different isoforms by alternative usage of first exons. Strongly decreased levels of ACOT7 activity and protein in both mitochondria and cytosol was reported in patients diagnosed with fatty acid oxidation defects, linking ACOT7 function to regulation of fatty acid oxidation in other tissues. In this study, we have identified five possible first exons in mouse Acot7 (Acot7a–e) and show that all five first exons are transcribed in a tissue-specific manner. Taken together, these data show that the Acot7 gene is expressed as multiple isoforms in a tissue-specific manner, and that expression in tissues other than brain and testis is likely to play important roles in fatty acid metabolism. Received 5 February 2007: received after revision 3 April 2007; accepted 19 April 2007     

P pili in uropathogenic E. coli are composite fibres with distinct fibrillar adhesive tips.

Escherichia coli is a frequent cause of several common bacterial infections in humans and animals, including urinary tract infections, bacteraemia and bacteria-related diarrhoea and is also the main cause of neonatal meningitis. Microbial attachment to surfaces is a key event in colonization and infection and results mainly from a stereochemical fit between microbial adhesins and complementary receptors on host cells. Bacterial adhesins required for extracellular colonization by Gram-negative bacteria are often minor components of heteropolymeric fibres called pili which must be oriented in an accessible manner in these structures to be able to bind to specific receptor architectures. P pili mediate the binding of uropathogenic E. coli to a digalactoside receptor determinant present in the urinary tract epithelium. We report here that the adhesin is a component of distinct fibrillar structures present at the tips of the pili. These virulence-associated tip fibrillae are thin, flexible polymers composed mostly of repeating subunits of PapE that frequently terminate with the alpha-D-galactopyranosyl-(1-4)-beta-D-galactopyranose or Gal alpha (1-4)Gal binding PapG adhesin.     

Overcompensation and population cycles in an ungulate.

Although theoretical studies show that overcompensatory density-dependent mechanisms can potentially generate regular or chaotic fluctuations in animal numbers, the majority of realistic single-species models of invertebrate populations are not overcompensatory enough to cause sustained population cycles. The possibility that overcompensation may generate cycles or chaos in vertebrate populations has seldom been considered. Here we show that highly overcompensatng density-dependent mortality can generate recurrent population crashes consistent with those observed in a naturally limited population of Soay sheep. The observed interval of three or more years between crashes points to sharp 'focusing' of mortality over a narrow range of population density.     

The humoral immune response to heat shock proteins.

Humoral immune reactions to heat shock proteins (hsp) from microorganisms are one aspect of microbial infections in humans. The production of antibodies which are specific to epitopes present on procaryotic hsp leads also to the appearance of cross-reactive serum antibodies in the host organism that react with human hsp. This article discusses the consequences of such autoreactive antibodies for the host in context with the development of immune tolerance and autoimmune diseases, especially rheumatoid arthritis (RA), and in experimental animal models for arthritis such as adjuvant arthritis in rats. On the basis of epitope cross-reactivity between hsp and other host proteins, a hypothesis is presented for the development of autoimmune disease following the production of hsp-specific antibodies.     

灰铸铁的应力屈服曲面及其三维热弹塑性应力解析

对原有的灰铸铁件应力屈服曲面进行了合理的简化,使其在理论上合理,工程应用上更为方便。建立了灰铸铁件三维非稳态热弹塑性应力场的有限元方法。以灰铸铁哑铃件为对象,用新屈服曲面对其应力发展过程进行了模拟,且比较了用新旧屈服面计算得到的结果。     

Ca2+ release induced by inositol 1,4,5-trisphosphate is a steady-state phenomenon controlled by luminal Ca2+ in permeabilized cells.

Low concentrations of inositol 1,4,5-trisphosphate (InsP3) evoke a very rapid mobilization of intracellular Ca2+ stores in many cell types, which can be followed by a further, much slower efflux. Two explanations have been suggested for this biphasic release. The first proposes that the Ca2+ stores vary in their sensitivity to InsP3, and each store releases either its entire contents or nothing (all-or-none release); the second proposes instead that the stores are uniformly sensitive to the effects of InsP3, but that they can release only a fraction of their Ca2+ before their sensitivity is somehow attenuated (steady-state release). Experiments using purified InsP3 receptor molecules reconstituted into lipid vesicles have shown heterogeneity of the receptors in their response to InsP3 under conditions in which the total Ca2+ level at both sides of the receptor is held constant. We now report that in permeabilized A7r5 smooth-muscle cells incubated in Ca(2+)-free medium, the amount of 45Ca2+ remaining in the stores after the rapid transient phase of release is independent of their initial Ca2+ levels, indicating that partially depleted stores are less sensitive to InsP3. Moreover, if the stores are reloaded with 40Ca2+ after the first stimulus, reapplication of the same low concentration of InsP3 will release further 45Ca2+. This recovery of InsP3 sensitivity is almost complete. Under these conditions, Ca2+ release must thus occur by a steady-state mechanism, in which the decreasing Ca2+ content of the stores slows down further release.