Nitric oxide-related pancreatic endocrine responses to hyperglycaemia in the conscious calf

Mean plasma insulin concentration was reduced and mean plasma glucose concentration increased following the administration of N-nitro-L-arginine methyl ester (L-NAME; 100 mol kg^–1 i.a.) in conscious calves given continuous infusions of exogenous glucose (30–60 mol min^–1 kg^–1 i.v.). It is concluded that the rise in plasma insulin concentration which occurs in these animals in response to glucose is mediated, at least in part, by a nitric oxide-related factor (NOx).     

Variability of sterol utilization in stored-products insects

A comparison of sterol utilization by 3 stored-products insects revealed very different capabilities. The fluor beetle,Tribolium castaneum dealkylates and converts dietary sitosterol to about equal amounts of cholesterol (43.7%) and 7-dehydrocholeterol (39.8%), whereas another flour beetle,Tenebrio molitor, produces considerably less 7-dehydrocholesterol (16.8%) and relatively more cholesterol (66.7%) from sitosterol. The lepidopteran,Plodia interpunctella, utilized dietary sterol very similar to plant-feeding lepidoptera, producing primarily cholesterol (86.5%) from sitosterol.     

A novel mechanism for jumping in the indian ant<Emphasis Type="Italic">Harpegnathos saltator</Emphasis> (Jerdon) (Formicidae,Ponerinae)

The Indian antHarpegnathos saltator may be unique among insects in using its jumping capacity not only as an escape mechanism but also as a normal means of locomotion, and for catching its prey in flight. High-speed cinematography used to analyse the various phases of the jump suggests thatHarpegnathos employs a novel jumping mechanism to mediate these behaviours: namely the synchronous activation of its middle and hindlegs. Electrophysiological recordings from muscles or nerves in pairs of middle and hindlegs show remarkably synchronous activity during fictive jumping, supporting the synchronous activation hypothesis.Harpegnathos is not the only ant to jump, and a cladistic analysis suggests that jumping behaviour evolved independently three times during ant evolutionary history.     

The in vivo expression of the globin genes of theβ cistron in γ-,δ-, andδβ-thalassemia heterozygotes

There is considerable evidence suggesting that the switch from to and chain production after birth is due, in part, to silencing of the genes by stage-specific factors which bind to their promoters and to the competition from the adult ( and ) genes for a common enhancer element located in the locus control region. As a consequence one can expect that the increased Hb F production in adults with hereditary persistence of fetal hemoglobin or -thalassemia is directed mainly by -globin genes in cis to the deletion(s) responsible for these conditions. Here we review data on heterozygotes with -, -, or -thalassemia, who also had an^AT mutation, in cis or in trans, which was used as a marker of gene expression. The results show that a deletion affecting adult genes favors the expression of genes in cis, while the deletion of a single gene does not affect the expression of the gene in cis but leads to a faster switch postnatally.     

What everybody should know about the rat genome and its online resources

It has been four years since the original publication of the draft sequence of the rat genome. Five groups are now working together to assemble, annotate and release an updated version of the rat genome. As the prevailing model for physiology, complex disease and pharmacological studies, there is an acute need for the rat's genomic resources to keep pace with the rat's prominence in the laboratory. In this commentary, we describe the current status of the rat genome sequence and the plans for its impending 'upgrade'. We then cover the key online resources providing access to the rat genome, including the new SNP views at Ensembl, the RefSeq and Genes databases at the US National Center for Biotechnology Information, Genome Browser at the University of California Santa Cruz and the disease portals for cardiovascular disease and obesity at the Rat Genome Database.     

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.     

Strong association of de novo copy number mutations with sporadic schizophrenia

Schizophrenia is an etiologically heterogeneous psychiatric disease, which exists in familial and nonfamilial (sporadic) forms. Here, we examine the possibility that rare de novo copy number (CN) mutations with relatively high penetrance contribute to the genetic component of schizophrenia. We carried out a whole-genome scan and implemented a number of steps for finding and confirming CN mutations. Confirmed de novo mutations were significantly associated with schizophrenia (P = 0.00078) and were collectively approximately 8 times more frequent in sporadic (but not familial) cases with schizophrenia than in unaffected controls. In comparison, rare inherited CN mutations were only modestly enriched in sporadic cases. Our results suggest that rare de novo germline mutations contribute to schizophrenia vulnerability in sporadic cases and that rare genetic lesions at many different loci can account, at least in part, for the genetic heterogeneity of this disease.