Suppression of in vitro haematopoiesis following human immunodeficiency virus infection

Viral infections are frequently associated with haematological disorders. Abnormalities including leukopenia, anaemia and thrombocytopenia are commonly observed in patients with the acquired immune deficiency syndrome (AIDS) or the AIDS-related complex (ARC). The underlying cause of these haematological abnormalities is poorly understood. We report here that bone marrow progenitors isolated from AIDS or ARC patients are responsive to recombinant human granulocyte-macrophage colony stimulating factor (rGM-CSF) and recombinant erythropoietin. Antibodies present in the serum of patients infected with the human immunodeficiency virus (HIV), however, could suppress the growth of these progenitors, but not the growth of progenitors from HIV seronegative controls. A component of this immune-mediated suppression appears to be antibodies directed towards the envelope glycoprotein (gp120) of HIV.     

Millisecond X-ray diffraction and the first electron density map from Laue photographs of a protein crystal

Attempts to use X-ray crystallography to extract three-dimensional information on transient phenomena in crystals have been hampered primarily by long data collection times. Here we report on the first difference Fourier map obtained from Laue diffraction photographs of a protein crystal, glycogen phosphorylase b. Data collection time was 3 s using the high-intensity white X-radiation generated on the wiggler magnet of the Daresbury Synchrotron Radiation Source (SRS), but data acquisition in the millisecond-submillisecond range is possible. The method presented here uses a simple difference technique and was designed to analyse structural changes relative to a known starting structure. The combination of this approach with cine techniques allows the recording of three-dimensional motion pictures at atomic resolution and opens up new areas in structural biology and chemistry.     

Accelerated carbonation and leaching behavior of the slag from iron and steel making industry

Ground granulated blast furnace slag(GGBFS)and steelmaking slag have been used as a raw material for cement production or as an aggregate to make concrete,which contribute aluminum,calcium,iron,and silicon oxides.The suitability of the slag for a particular application depends on its reactivity,cost,availability,and its influence on the properties of the resulting concrete.For the interest of durability studying of concrete in the presence of slag,the accelerated carbonation products and leaching behavior of the slag and Portland cement(PC)were studied.The experimental results confirmed that the slag was more resistant to carbonation compared to PC.The carbonation degree of GGBFS reduced by 17.74%;and the carbonation degrees of steelmaking slags reduced by 9.51%-11.94%.Carbonation neutralized the alkaline nature of the hydrated pastes and gave rise to the redox potential of the leachate slightly(30-77 mV).The carbonation also increased the release of most of the elements presented,except for calcium,to the aqueous environment.It is concluded that blend cements(PC plus slag)have economical advantages and better durability compared to PC.     

挑战粒子物理学作为通向真理的途径

粒子物理学家倾向于把自然界视为具体化的数学 ;而固体物理学家则认为 ,从超导体和超流体等奇异形态到晶体和金属等常见形态 ,物质的许多形式都不能用基本粒子的相互作用来描述     

Regulation of sodium and body fluid homeostasis during development: Implications for the pathogenesis of hypertension

The spontaneously hypertensive rat (SHR) is an important animal model of human essential hypertension. During the first month of life, increased retention of sodium is present in the SHR which appears to be mediated by the renin-angiotensin system. The present review will discuss the role that increased activity of the renin-angiotensin system plays in sodium/body fluid regulation during early development. It is hypothesized that disordered regulation of sodium/body fluid homeostasis during this stage leads to pathological cardiovascular regulation in adulthood. Through an understanding of the relationship between sodium/body fluid balance in the young and cardiovascular function in the adult insights may be gained into both the pathological state of hypertension and the critical role played by early development in shaping homeostatic mechanisms in adulthood.     

Regulation of sodium and body fluid homeostasis during development: implications for the pathogenesis of hypertension.

The spontaneously hypertensive rat (SHR) is an important animal model of human essential hypertension. During the first month of life, increased retention of sodium is present in the SHR which appears to be mediated by the renin-angiotensin system. The present review will discuss the role that increased activity of the renin-angiotensin system plays in sodium/body fluid regulation during early development. It is hypothesized that disordered regulation of sodium/body fluid homeostasis during this stage leads to pathological cardiovascular regulation in adulthood. Through an understanding of the relationship between sodium/body fluid balance in the young and cardiovascular function in the adult insights may be gained into both the pathological state of hypertension and the critical role played by early development in shaping homeostatic mechanisms in adulthood.     

Mutations in CUBN, encoding the intrinsic factor-vitamin B12 receptor, cubilin, cause hereditary megaloblastic anaemia 1

Megaloblastic anaemia 1 (MGA1, OMIM 261100) is a rare, autosomal recessive disorder characterized by juvenile megaloblastic anaemia, as well as neurological symptoms that may be the only manifestations. At the cellular level, MGA1 is characterized by selective intestinal vitamin B12 (B12, cobalamin) malabsorption. MGA1 occurs worldwide, but its prevalence is higher in several Middle Eastern countries and Norway, and highest in Finland (0.8/100,000). We previously mapped the MGA1 locus by linkage analysis in Finnish and Norwegian families to a 6-cM region on chromosome 10p12.1 (ref. 8). A functional candidate gene encoding the intrinsic factor (IF)-B12 receptor, cubilin, was recently cloned; the human homologue, CUBN, was mapped to the same region. We have now refined the MGA1 region by linkage disequilibrium (LD) mapping, fine-mapped CUBN and identified two independent disease-specific CUBN mutations in 17 Finnish MGA1 families. Our genetic and molecular data indicate that mutations in CUBN cause MGA1.     

CACP, encoding a secreted proteoglycan, is mutated in camptodactyly-arthropathy-coxa vara-pericarditis syndrome.

Altered growth and function of synoviocytes, the intimal cells which line joint cavities and tendon sheaths, occur in a number of skeletal diseases. Hyperplasia of synoviocytes is found in both rheumatoid arthritis and osteoarthritis, despite differences in the underlying aetiologies of the two disorders. We have studied the autosomal recessive disorder camptodactyly-arthropathy-coxa vara-pericarditis syndrome (CACP; MIM 208250) to identify biological pathways that lead to synoviocyte hyperplasia, the principal pathological feature of this syndrome. Using a positional-candidate approach, we identified mutations in a gene (CACP) encoding a secreted proteoglycan as the cause of CACP. The CACP protein, which has previously been identified as both 'megakaryocyte stimulating factor precursor' and 'superficial zone protein', contains domains that have homology to somatomedin B, heparin-binding proteins, mucins and haemopexins. In addition to expression in joint synovium and cartilage, CACP is expressed in non-skeletal tissues including liver and pericardium. The similarity of CACP sequence to that of other protein families and the expression of CACP in non-skeletal tissues suggest it may have diverse biological activities.     

SB-restricted presentation of influenza and herpes simplex virus antigens to human T-lymphocyte clones

The HLA-D region of the human major histocompatibility complex (MHC) has been shown to be homologous to the murine I region in terms of both structure and function. Both regions encode class II MHC molecules which restrict T-lymphocyte interactions with antigen-presenting cells. We have recently described the MHC restriction and antigen specificities of human T-lymphocyte clones directed at strain A influenza virus. The majority of T-lymphocyte clones recognized antigen in the context of cell surface interaction products encoded by HLA-D/DR genes. However, a few clones recognized antigen presented by cells histoincompatible for D/DR antigens. We report here that some of these clones recognized viral antigens in association with antigens encoded by genes identical with or closely linked to the recently described secondary B-cell (SB) locus of the MHC. This is the first report that SB-restricted antigen recognition may form an integral part of normal, human immune responses.     

Evolution and ecological correlates of uniparental reproduction in freshwater snails

We review the spatial and temporal correlates of uniparental reproduction in freshwater snails as they pertain to the ecological hypotheses for the maintenance of biparental sex. The biogeographic evidence from two species (Potamopyrgus antipodarum andBulinus truncatus) presently supports the Red Queen hypothesis that biparental reproduction is selected as a way to reduce the risk to progeny of parasite attack. Uniparental reproduction in these species is associated with low levels of infection by parasites (castrating digenetic trematodes), suggesting that parthenogenesis or self-fertilization can replace cross-fertilization when the risk of infection is low. In addition, inB. truncatus, the opportunity for cross-fertilization coincides with the season in which parasite attack is highest. In a third species (Campeloma decisum), parthenogenetic reproduction is correlated with latitude and the presence of a non-castrating trematode that may prevent cross-fertilization; these patterns suggest that parthenogenesis has been selected as a mechanism to assure reproduction. Finally, we discuss the spotty taxonomic distribution of parthenogenetic species.