Somatic misexpression of germline P granules and enhanced RNA interference in retinoblastoma pathway mutants

Caenorhabditis elegans homologues of the retinoblastoma (Rb) tumour suppressor complex specify cell lineage during development. Here we show that mutations in Rb pathway components enhance RNA interference (RNAi) and cause somatic cells to express genes and elaborate perinuclear structures normally limited to germline-specific P granules. Furthermore, particular gene inactivations that disrupt RNAi reverse the cell lineage transformations of Rb pathway mutants. These findings suggest that mutations in Rb pathway components cause cells to revert to patterns of gene expression normally restricted to germ cells. Rb may act by a similar mechanism to transform mammalian cells.     

The afterglow and elliptical host galaxy of the short gamma-ray burst GRB 050724

Despite a rich phenomenology, gamma-ray bursts (GRBs) are divided into two classes based on their duration and spectral hardness--the long-soft and the short-hard bursts. The discovery of afterglow emission from long GRBs was a watershed event, pinpointing their origin to star-forming galaxies, and hence the death of massive stars, and indicating an energy release of about 10(51) erg. While theoretical arguments suggest that short GRBs are produced in the coalescence of binary compact objects (neutron stars or black holes), the progenitors, energetics and environments of these events remain elusive despite recent localizations. Here we report the discovery of the first radio afterglow from the short burst GRB 050724, which unambiguously associates it with an elliptical galaxy at a redshift z = 0.257. We show that the burst is powered by the same relativistic fireball mechanism as long GRBs, with the ejecta possibly collimated in jets, but that the total energy release is 10-1,000 times smaller. More importantly, the nature of the host galaxy demonstrates that short GRBs arise from an old (> 1 Gyr) stellar population, strengthening earlier suggestions and providing support for coalescing compact object binaries as the progenitors.     

Monovalent cation leaks in human red cells caused by single amino-acid substitutions in the transport domain of the band 3 chloride-bicarbonate exchanger, AE1

We identified 11 human pedigrees with dominantly inherited hemolytic anemias in both the hereditary stomatocytosis and spherocytosis classes. Affected individuals in these families had an increase in membrane permeability to Na and K that is particularly marked at 0 degrees C. We found that disease in these pedigrees was associated with a series of single amino-acid substitutions in the intramembrane domain of the erythrocyte band 3 anion exchanger, AE1. Anion movements were reduced in the abnormal red cells. The 'leak' cation fluxes were inhibited by SITS, dipyridamole and NS1652, chemically diverse inhibitors of band 3. Expression of the mutated genes in Xenopus laevis oocytes induced abnormal Na and K fluxes in the oocytes, and the induced Cl transport was low. These data are consistent with the suggestion that the substitutions convert the protein from an anion exchanger into an unregulated cation channel.     

小动物单光子发射计算体层摄影成像技术

本书系统地介绍了单光子发射计算体层摄影这一现代先进的成像技术。单光子发射计算体层摄影有助于新药的研发、药物的研究、分子成像和成像科学的发展。     

Erythroid developmental agglutinin is a protein lectin mediating specific cell-cell adhesion between differentiating rabbit erythroblasts

In many developmental systems beta-galactoside-specific protein lectins have been identified as components which appear at the cell surface in concert with an initial requirement for cell-cell adhesion during tissue formation. Although some of these lectins have been purified, there has been little direct evidence concerning their role in establishing specific cell-cell contact. A mammalian system where selective cell-cell adhesion is evident and which is amenable to study is that of erythroid differentiation in the adult bone marrow. Here, the differentiation of erythroblasts takes place with the participants clustered together in the vicinity of a macrophage 'nurse' cell until the enucleation stage, when the immature reticulocyte is released and passes through the sinusoidal wall into the circulation. We show here that a small, beta-galactoside-specific, protein lectin can be extracted from erythroblast-enriched marrow and purified to homogeneity. This factor, termed erythroid developmental agglutinin (EDA), exhibits properties which strongly suggest that it is responsible for inter-erythroblast recognition and adhesion in vivo.     

Cotranslocational insertion of apolipoprotein B into the inner leaflet of the endoplasmic reticulum

Apolipoprotein (apo) B100 is required for the distribution of hepatic triglyceride to peripheral tissues as very-low-density lipoproteins. The translocation of apo B100 into the endoplasmic reticulum (ER) and its subsequent assembly into lipoprotein particles is of particular interest as the protein is both very large (relative molecular mass 512,000) and insoluble in water. It has been proposed that apo B translocation occurs in discrete stages and is completed post-translationally. Several sites of arrest of translocation were reported to be present in apo B15 (the N-terminal 15% of the protein). We have re-examined this question by in vitro translation coupled with translocation into microsomes, and find no evidence for transmembrane segments in truncated apo B proteins. Translocated apo B17 is strongly associated with the membrane of the ER, being only partially releasable with alkaline carbonate, and remaining bound to the microsomes following disruption with saponin. The efficient binding of short segments of apo B, despite the absence of transmembrane domains, suggests that apo B is cotranslationally inserted into the inner leaflet of the ER. This will obviate problems caused by the size and insolubility of apo B100, because the growing hydrophobic protein chains will never exist in a lipid-free form during translocation. From the inner leaflet, apo B in association with membrane-derived lipid can bud into the lumen of the ER to form nascent lipoprotein particles.     

Corrosion of magnesium and magnesium –calcium alloy in biologically-simulated environment

A study of biocompatibility and corrosion of both metallic magnesium(Mg) and a magnesium alloy containing 1% calcium(Mg–Ca) were investigated in in vitro culture conditions with and without the presence of bone marrow derived human mesenchymal stem cells(h MSCs).Chemical analysis of the degraded samples was performed using XRD and FEGSEM. The results from the XRD analysis strongly suggested that crystalline phase of magnesium carbonate was present on the surface of both the Mg and Mg–Ca samples. Flame absorption spectrometry was used to analyse the release of magnesium and calcium ions into the cell culture medium. Magnesium concentration was kept consistently at a level ranging from 40 to 80 m M for both Mg and Mg–Ca samples. No cell growth was observed when in direct contact with the metals apart from a few cells observed at the bottom of culture plate containing Mg–Ca alloy. In general, in vitro study of corrosion of Mg–Ca in a biologicallysimulated environment using cell culture medium with the presence of h MSCs demonstrated close resemblances to in vivo corrosion. Although in vitro corrosion of Mg–Ca revealed slow corrosion rate and no immediate cytotoxicity effects to h MSCs, its corrosion rate was still too high to achieve normal stem cell growth when cells and alloys were cultured in vitro in direct contact.