Vaccinia virus encodes a polypeptide homologous to epidermal growth factor and transforming growth factor

Epidermal growth factor (EGF) and transforming growth factor type I (TGF) are polypeptides of 53 and 50 amino acid residues, respectively. Both bind to EGF receptor, a 1,200-residue transmembranous glycoprotein, leading to phosphorylation of the receptor, enhancement of its tyrosine-specific kinase activity and ultimately to stimulation of cell growth. We report here that a 140-residue polypeptide encoded by one of the early genes of vaccinia virus (VV) is related closely to EGF and TGF. The presence of putative signal and transmembranous sequences further suggests that the viral protein might be an integral membrane protein, but that, as in the case of EGF itself, the membrane-associated form may be the precursor of a soluble growth factor. Production of EGF-like growth factors by virally infected cells could account for the proliferative diseases associated with members of the poxvirus family such as Shope fibroma virus, Yaba tumour virus, and molluscum contagiosum virus (MCV).     

DNA in wheat seeds from European archaeological sites

We have used hybridization analysis to detect ancient DNA in wheat seeds collected from three archaeological sites in Europe and the Middle East. One of these samples, carbonizedT. spelta dated to the first millennium BC, has yielded PCR products after amplification with primers directed at the leader regions of the HMW (high molecular weight) glutenin alleles. Sequences obtained from these products suggest that the DNA present in the Danebury seeds is chemically damaged, as expected for ancient DNA, and also indicate that it should be possible to study the genetic variability of archaeological wheat by ancient DNA analysis. Finally, we describe a PCR-based system that enables tetraploid and hexaploid wheats to be distinguished.     

ANG mutations segregate with familial and 'sporadic' amyotrophic lateral sclerosis

We recently identified angiogenin (ANG) as a candidate susceptibility gene for amyotrophic lateral sclerosis (ALS), a neurodegenerative disorder characterized by adult-onset loss of motor neurons. We now report the finding of seven missense mutations in 15 individuals, of whom four had familial ALS and 11 apparently 'sporadic' ALS. Our findings provide further evidence that variations in hypoxia-inducible genes have an important role in motor neuron degeneration.     

Common variants near MC4R are associated with fat mass, weight and risk of obesity

To identify common variants influencing body mass index (BMI), we analyzed genome-wide association data from 16,876 individuals of European descent. After previously reported variants in FTO, the strongest association signal (rs17782313, P = 2.9 x 10(-6)) mapped 188 kb downstream of MC4R (melanocortin-4 receptor), mutations of which are the leading cause of monogenic severe childhood-onset obesity. We confirmed the BMI association in 60,352 adults (per-allele effect = 0.05 Z-score units; P = 2.8 x 10(-15)) and 5,988 children aged 7-11 (0.13 Z-score units; P = 1.5 x 10(-8)). In case-control analyses (n = 10,583), the odds for severe childhood obesity reached 1.30 (P = 8.0 x 10(-11)). Furthermore, we observed overtransmission of the risk allele to obese offspring in 660 families (P (pedigree disequilibrium test average; PDT-avg) = 2.4 x 10(-4)). The SNP location and patterns of phenotypic associations are consistent with effects mediated through altered MC4R function. Our findings establish that common variants near MC4R influence fat mass, weight and obesity risk at the population level and reinforce the need for large-scale data integration to identify variants influencing continuous biomedical traits.     

Localization of the X inactivation centre on the human X chromosome in Xq13

X-chromosome inactivation results in the strictly cis-limited inactivation of many but not all genes on one of the two X chromosomes during early development in somatic cells of mammalian females. One feature of virtually all models of X inactivation is the existence of an X-inactivation centre (XIC) required in cis for inactivation to occur. This concept predicts that all structurally abnormal X chromosomes capable of being inactivated have in common a defineable region of the X chromosome. Here we report an analysis of several such rearranged human X chromosomes and define a minimal region of overlap. The results are consistent with models invoking a single XIC and provide a molecular foothold for cloning and analysing the XIC region. One of the markers that defines this region is the XIST gene, which is expressed specifically from inactive, but not active, X chromosomes. The localization of the XIST gene to the XIC region on the human X chromosome implicates XIST in some aspect of X inactivation.     

Synaptosomal adenosine triphosphatase (ATPase) inhibition by organophosphates

Summary Chicken spinal cord adenosine triphosphatases (both Na⁺, K⁺ stimulated and ouabain insensitive) were inhibited by tri-o-tolyl phosphate (TOTP, a neurotoxic organophosphate which is not a cholinesterase inhibitor) and mevinphos (a non-neurotoxic compound but inhibitor of cholinesterases). The inhibition was concentration and time dependent, with an initial rapid drop in activity followed by a gradual exponential decline.