Expression of a candidate sex-determining gene during mouse testis differentiation

The development of a eutherian mammal as a male is a consequence of testis formation in the embryo, which is thought to be initiated by a gene on the Y chromosome. In the absence of this gene, ovaries are formed and female characteristics develop. Sex determination therefore hinges on the action of this testis-determining gene, known as Tdy in mice and TDF in humans. In the past, several genes proposed as candidates for Tdy/TDF have subsequently been dismissed on the grounds of inappropriate location or expression. We have recently described a candidate for Tdy, which maps to the minimum sex-determining region of the mouse Y chromosome. To examine further the involvement of this gene, Sry, in testis development, we have studied its expression in detail. Fetal expression of Sry is limited to the period in which testes begin to form. This expression is confined to gonadal tissue and does not require the presence of germ cells. Our observations strongly support a primary role for Sry in mouse sex determination.     

Host-parasitoid associations in patchy environments

Studies of insect host-parasitoid interactions have contributed much to the consensus that spatial patchiness is important in the regulation of natural populations. A variety of theoretical models predict that host and parasitoid populations, although unstable in the absence of environmental heterogeneity, may persist at roughly steady overall densities in a patchy environment owing to variation in levels of parasitism from patch to patch. Observed patterns of parasitism, however, have a variety of forms (with variation in attack rates among patches depending directly or indirectly on host density, or showing variation uncorrelated with host density). There is some confusion about the dynamical consequences of these different forms. Here we first show how the dynamical effects of all these forms of environmental heterogeneity can be assessed by a common criterion. This 'CV2 greater than 1 rule' states that the overall population densities will remain roughly steady from generation to generation if the coefficient of variation squared (CV2) of the density of searching parasitoids in the vicinity of each host exceeds approximately unity. By partitioning CV2 into components, we show that both direct and inverse patterns of dependence on host density, and density-independent patterns, all contribute to population regulation in the same way. Second, we show how a maximum-likelihood method can be applied to the kind of field data that are usually available (that is, percentage parasitism versus local host density) to estimate the components of CV2. This analysis indicates that heterogeneity is large enough to stabilize dynamics in 9 of 34 published studies, and that density-independent heterogeneity is the main factor in most cases.     

Molecular cloning of the microtubule-associated mechanochemical enzyme dynamin reveals homology with a new family of GTP-binding proteins

A complementary DNA encoding the D100 polypeptide of rat brain dynamin--a force-producing, microtubule-activated nucleotide triphosphatase--has been cloned and sequenced. The predicted amino acid sequence includes a guanine nucleotide-binding domain that is homologous with those of a family of antiviral factors, inducible by interferon and known as Mx proteins, and with the product of the essential yeast vacuolar protein sorting gene VPS1. These relationships imply the existence of a new family of GTPases with physiological roles that may include microtubule-based motility and protein sorting.     

氨酯键和脲键对嵌段聚氨酯和嵌段聚脲性质影响的研究

用溶液聚合法合成了四种聚氨酯、聚脲模型化合物.并用凝胶渗透色谱,应力—应变,广角X射线衍射等手段检验了在相界面或在硬段微区,不同键对聚合物分子量、力学性质和聚合物形态的影响.     

GM-CSF induces human neutrophil IgA-mediated phagocytosis by an IgA Fc receptor activation mechanism

Immunoglobulin A is the primary immunoglobulin isotype in tears, saliva, breast milk and other mucosal secretions, constituting between 6% and 15% of the total serum immunoglobulins. Human peripheral blood neutrophils have IgA receptors, but these cells do not normally participate in IgA-mediated phagocytosis. The haematopoietic factors granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) prime neutrophils to be more responsive to a variety of stimuli. We therefore studied their effect on IgA-mediated phagocytosis. GM-CSF and G-CSF both induce a change from low to high-affinity neutrophil IgA Fc crystallizable fragment receptors within 30 min; a change which is associated with the development of IgA-mediated phagocytosis. Human IL-3, which does not affect neutrophil function, is inactive in this system. These results define a new mechanism for CSF-augmented host defence whereby neutrophil function can be modulated by CSF-mediated IgA Fc receptor activation.     

Protease inhibitor domain encoded by an amyloid protein precursor mRNA associated with Alzheimer's disease

Amyloid B-protein/amyloid A4 is a peptide present in the neuritic plaques, neurofibrillary tangles and cerebrovascular deposits in patients with Alzheimer's disease and Down's syndrome (trisomy 21) and may be involved in the pathogenesis of Alzheimer's disease. Recent molecular genetic studies have indicated that amyloid protein is encoded as part of a larger protein by a gene on human chromosome 21 (refs 6-9). The amyloid protein precursor (APP) gene is expressed in brain and in several peripheral tissues, but the specific biochemical events leading to deposition of amyloid are not known. We have now screened complementary DNA libraries constructed from peripheral tissues to determine whether the messenger RNA encoding APP in these tissues is identical to that expressed in brain, and we identify a second APP mRNA that encodes an additional internal domain with a sequence characteristic of a Kunitz-type serine protease inhibitor. The alternative APP mRNA is present in both brain and peripheral tissues of normal individuals and those with Alzheimer's disease, but its pattern of expression differs from that of the previously reported APP mRNA.     

Type I phosphatidylinositol kinase makes a novel inositol phospholipid, phosphatidylinositol-3-phosphate

The generation of second messengers from the hydrolysis of phosphatidylinositol-4,5-bisphosphate (PtdInsP2) by phosphoinositidase C has been implicated in the mediation of cellular responses to a variety of growth factors and oncogene products. The first step in the production of PtdInsP2 from phosphatidylinositol (PtdIns) is catalysed by PtdIns kinase. A PtdIns kinase activity has been found to associate specifically with several oncogene products, as well as with the platelet-derived growth factor (PDGF) receptor. We have previously identified two biochemically distinct PtdIns kinases in fibroblasts, and have found that only one of these, designated type I, specifically associates with activated tyrosine kinases. We have now characterized the site on the inositol ring phosphorylated by type I PtdIns kinase, and find that this kinase specifically phosphorylates the D-3 ring position to generate a novel phospholipid, phosphatidylinositol-3-phosphate (PtdIns(3)P). In contrast, the main PtdIns kinase in fibroblasts, designated type II, specifically phosphorylates the D-4 position to produce phosphatidylinositol-4-phosphate (PtdIns(4)P), previously considered to be the only form of PtdInsP. We have also tentatively identified PtdIns(3)P as a minor component of total PtdInsP in intact fibroblasts. We propose that type I PtdIns kinase is responsible for the generation of PtdIns(3)P in intact cells, and that this novel phosphoinositide could be important in the transduction of mitogenic and oncogenic signals.     

Myeloid leukaemia inhibitory factor maintains the developmental potential of embryonic stem cells

Embryonic stem (ES) cells, the totipotent outgrowths of blastocysts, can be cultured and manipulated in vitro and then returned to the embryonic environment where they develop normally and can contribute to all cell lineages. Maintenance of the stem-cell phenotype in vitro requires the presence of a feeder layer of fibroblasts or of a soluble factor, differentiation inhibitory activity (DIA) produced by a number of sources; in the absence of DIA the ES cells differentiate into a wide variety of cell types. We recently noted several similarities between partially purified DIA and a haemopoietic regulator, myeloid leukaemia inhibitory factor (LIF), a molecule which induces differentiation in M1 myeloid leukaemic cells and which we have recently purified, cloned and characterized. We demonstrate here that purified, recombinant LIF can substitute for DIA in the maintenance of totipotent ES cell lines that retain the potential to form chimaeric mice.