Identification of the V factor needed for synthesis of the iron-molybdenum cofactor of nitrogenase as homocitrate

Nitrogenase catalyses the ATP-dependent reduction of N2 to NH3, and is composed of two proteins, dinitrogenase (MoFe protein or component I) and dinitrogenase reductase (Fe protein or component II). Dinitrogenase contains a unique prosthetic group (iron-molybdenum cofactor, FeMoco) comprised of Fe, Mo and S, which has been proposed as the site of N2 reduction. Biochemical and genetic studies of Nif- (nitrogen fixation) mutants of Klebsiella pneumoniae which are defective in nitrogen fixation, have shown that the nifB, nifQ, nifN, nifE and nifV genes are required for the biosynthesis of FeMo-co. Recently, a system for in vitro synthesis of FeMoco was described. The assay requires at least the nifB, nifN and nifE gene products, and a low-molecular-weight factor (V factor) produced in the presence of the nifV gene product. We have used this system to study FeMoco biosynthesis. We report here the isolation of V factor and identify it as homocitric acid ([R]2-hydroxy-1,2,4-butanetricarboxylic acid).     

Transduction of endogenous envelope genes by feline leukaemia virus in vitro

Feline leukaemia viruses (FeLV) are exogenous retroviruses that can be detected in most cats with leukaemia, aplastic anaemia, myeloproliferative diseases and fatal immunosuppression. FeLV isolates have been divided into three subgroups, based on the viral envelope-determined properties of interference and host range in vitro. FeLV-A is present in all natural isolates and is generally minimally pathogenic. FeLV-B is found with FeLV-A in isolates from approximately 40% of natural infections and in a higher percentage of cats with lymphoma. Following the fundamental observations of genetic reassortment of avian retroviruses with endogenous viral genes and the origination of lymphomagenic viruses during the ontogeny of AKR mice, we show here that transfection of feline cells with FeLV-A DNA results in its recombination with endogenous FeLV-related sequences to produce viruses with the structural and host range properties of FeLV-B. Thus in vitro propagation of a retrovirus may result in the generation of variants with very different properties.     

A massive, cooling-flow-induced starburst in the core of a luminous cluster of galaxies

In the cores of some clusters of galaxies the hot intracluster plasma is dense enough that it should cool radiatively in the cluster's lifetime, leading to continuous 'cooling flows' of gas sinking towards the cluster centre, yet no such cooling flow has been observed. The low observed star-formation rates and cool gas masses for these 'cool-core' clusters suggest that much of the cooling must be offset by feedback to prevent the formation of a runaway cooling flow. Here we report X-ray, optical and infrared observations of the galaxy cluster SPT-CLJ2344-4243 (ref. 11) at redshift z = 0.596. These observations reveal an exceptionally luminous (8.2?×?10(45)?erg?s(-1)) galaxy cluster that hosts an extremely strong cooling flow (around 3,820 solar masses a year). Further, the central galaxy in this cluster appears to be experiencing a massive starburst (formation of around 740 solar masses a year), which suggests that the feedback source responsible for preventing runaway cooling in nearby cool-core clusters may not yet be fully established in SPT-CLJ2344-4243. This large star-formation rate implies that a significant fraction of the stars in the central galaxy of this cluster may form through accretion of the intracluster medium, rather than (as is currently thought) assembling entirely via mergers.     

猫免疫缺陷综合症的实验研究

<正> 作者描述了具有强烈免疫抑制作用的一株猫白血病病毒(FeLV)的鉴定、实验性感染及致病特性。该毒株从一只自然感染猫白血病病毒的猫胸腺淋巴瘤组织中分离得到。作者称之为猫白血病—艾滋病病毒(FeLVFAIDS)。25只SPF猫经鼻腔、腹腔接种这种病毒后,都能产生持续性的病毒血症及致死性和获得性免疫缺陷综合症(AIDS)。由于接种时猫年龄的不同,可发生急性免疫缺陷综合症和慢性免疫缺陷综合症。前者的接种后存活时间在3月以下,多发生于8周龄以下的猫,后者的存活时间在一年以上,多发生于15周龄以上的猫。猫白血病—艾滋病病毒诱发的免疫缺陷综合症有如下特征:接种后有一个无症状的病毒血症时期;体重逐渐下降;当淋巴组织的淋巴小结增生时,病毒     

Genome-wide association study of prostate cancer identifies a second risk locus at 8q24

Recently, common variants on human chromosome 8q24 were found to be associated with prostate cancer risk. While conducting a genome-wide association study in the Cancer Genetic Markers of Susceptibility project with 550,000 SNPs in a nested case-control study (1,172 cases and 1,157 controls of European origin), we identified a new association at 8q24 with an independent effect on prostate cancer susceptibility. The most significant signal is 70 kb centromeric to the previously reported SNP, rs1447295, but shows little evidence of linkage disequilibrium with it. A combined analysis with four additional studies (total: 4,296 cases and 4,299 controls) confirms association with prostate cancer for rs6983267 in the centromeric locus (P = 9.42 x 10(-13); heterozygote odds ratio (OR): 1.26, 95% confidence interval (c.i.): 1.13-1.41; homozygote OR: 1.58, 95% c.i.: 1.40-1.78). Each SNP remained significant in a joint analysis after adjusting for the other (rs1447295 P = 1.41 x 10(-11); rs6983267 P = 6.62 x 10(-10)). These observations, combined with compelling evidence for a recombination hotspot between the two markers, indicate the presence of at least two independent loci within 8q24 that contribute to prostate cancer in men of European ancestry. We estimate that the population attributable risk of the new locus, marked by rs6983267, is higher than the locus marked by rs1447295 (21% versus 9%).     

A genome-wide association study identifies alleles in FGFR2 associated with risk of sporadic postmenopausal breast cancer

We conducted a genome-wide association study (GWAS) of breast cancer by genotyping 528,173 SNPs in 1,145 postmenopausal women of European ancestry with invasive breast cancer and 1,142 controls. We identified four SNPs in intron 2 of FGFR2 (which encodes a receptor tyrosine kinase and is amplified or overexpressed in some breast cancers) that were highly associated with breast cancer and confirmed this association in 1,776 affected individuals and 2,072 controls from three additional studies. Across the four studies, the association with all four SNPs was highly statistically significant (P(trend) for the most strongly associated SNP (rs1219648) = 1.1 x 10(-10); population attributable risk = 16%). Four SNPs at other loci most strongly associated with breast cancer in the initial GWAS were not associated in the replication studies. Our summary results from the GWAS are available online in a form that should speed the identification of additional risk loci.     

Disease-specific and tissue-specific production of unintegrated feline leukaemia virus variant DNA in feline AIDS

Feline leukaemia viruses (FeLVs) have long been known to be associated with induction of proliferative and anti-proliferative diseases of domestic cats. Strains of FeLV have been recognized which specifically induce lymphosarcoma, aplastic anaemia, myelodysplastic anaemia, and, recently, feline AIDS (acquired immune deficiency syndrome), a naturally occurring immunosuppressive syndrome strikingly similar to human AIDS which is lethal in 100% of inoculated and viraemic specific-pathogen-free (SPF) cats. Here, we have analysed FeLV DNA in tissues of 22 SPF cats that had been inoculated with the feline AIDS strain (FeLV-FAIDS) and we find two classes of viral DNA--a monotypic common form which is detectable in bone marrow regardless of disease state, and variant forms, recognizable by restriction site differences, whose appearance correlates with onset of disease symptoms and persists throughout the course of the disease. FeLV-FAIDS variant DNA is detected at high concentration (10-50 copies per cell) and principally as unintegrated viral DNA (UVD) in bone marrow of cats with feline AIDS. In marked contrast high levels of UVD were not present in cats in the terminal-stages of T-cell lymphosarcoma, aplastic anaemia, or myelodysplastic anaemia induced by other FeLV strains. These results parallel recent observations in humans, where high levels of UVD were sometimes found in cells derived from AIDS patients infected with human T-lymphotropic virus type III (HTLV-III)/lymph-adenopathy-associated virus (LAV), and suggest that persistence of unintegrated variant viral DNA is a crucial indicator of retrovirus-induced cytopathic disease syndromes such as AIDS.