Reputed rat scotophobin prepared by a solid-phase procedure shown invalid by comparison with a product derived from a classical synthesis on the basis of physical and biological properties

Zusammenfassung Eine Synthese von Scotophobin mit klassischen Methoden ergab ein Produkt, das sich vom natürlichen Peptid hinsichtlich seiner biologischen, chromatographischen und physiologischen Eigenschaften unterschied. Es wird daraus gefolgert, dass die für das natürliche Produkt vorgeschlagene Strukturformel nicht korrekt ist.     

Multiobjective routing in multiservice MPLS networks with traffic splitting — A network flow approach

A multiobjective routing model for Multiprotocol Label Switching networks with multiple service types and traffic splitting is presented in this paper.The routing problem is formulated as a multiobjective mixed-integer program,where the considered objectives are the minimization of the bandwidth routing cost and the minimization of the load cost in the network links with a constraint on the maximal splitting of traffic trunks.Two different exact methods are developed for solving the formulated problem,one based on the classical constraint method and another based on a modified constraint method.Avery extensive experimental study,with results on network performance measures in various reference test networks and in randomly generated networks,is also presented and its results are discussed.     

Genotype, haplotype and copy-number variation in worldwide human populations

Genome-wide patterns of variation across individuals provide a powerful source of data for uncovering the history of migration, range expansion, and adaptation of the human species. However, high-resolution surveys of variation in genotype, haplotype and copy number have generally focused on a small number of population groups. Here we report the analysis of high-quality genotypes at 525,910 single-nucleotide polymorphisms (SNPs) and 396 copy-number-variable loci in a worldwide sample of 29 populations. Analysis of SNP genotypes yields strongly supported fine-scale inferences about population structure. Increasing linkage disequilibrium is observed with increasing geographic distance from Africa, as expected under a serial founder effect for the out-of-Africa spread of human populations. New approaches for haplotype analysis produce inferences about population structure that complement results based on unphased SNPs. Despite a difference from SNPs in the frequency spectrum of the copy-number variants (CNVs) detected--including a comparatively large number of CNVs in previously unexamined populations from Oceania and the Americas--the global distribution of CNVs largely accords with population structure analyses for SNP data sets of similar size. Our results produce new inferences about inter-population variation, support the utility of CNVs in human population-genetic research, and serve as a genomic resource for human-genetic studies in diverse worldwide populations.     

Mutations in the facilitative glucose transporter GLUT10 alter angiogenesis and cause arterial tortuosity syndrome

Arterial tortuosity syndrome (ATS) is an autosomal recessive disorder characterized by tortuosity, elongation, stenosis and aneurysm formation in the major arteries owing to disruption of elastic fibers in the medial layer of the arterial wall. Previously, we used homozygosity mapping to map a candidate locus in a 4.1-Mb region on chromosome 20q13.1 (ref. 2). Here, we narrowed the candidate region to 1.2 Mb containing seven genes. Mutations in one of these genes, SLC2A10, encoding the facilitative glucose transporter GLUT10, were identified in six ATS families. GLUT10 deficiency is associated with upregulation of the TGFbeta pathway in the arterial wall, a finding also observed in Loeys-Dietz syndrome, in which aortic aneurysms associate with arterial tortuosity. The identification of a glucose transporter gene responsible for altered arterial morphogenesis is notable in light of the previously suggested link between GLUT10 and type 2 diabetes. Our data could provide new insight on the mechanisms causing microangiopathic changes associated with diabetes and suggest that therapeutic compounds intervening with TGFbeta signaling represent a new treatment strategy.