University of Düsseldorf

About: University of Düsseldorf is a education organization based out in Düsseldorf, Germany. It is known for research contribution in the topics: Population & Transplantation. The organization has 25225 authors who have published 49155 publications receiving 1946434 citations.

Anatomical left-right asymmetry of language-related temporal cortex is different in left- and right-handers

Abstract: Asymmetry of the planum temporale, a language-related intrasylvian area on the superior temporal gyrus, is the most remarkable anatomical left-right asymmetry of the human brain. The in vivo application of magnetic resonance morphometry in 52 healthy volunteers (26 dextrals and 26 sinistrals) revealed that planum temporale asymmetry is correlated with hand dominance. Left-handers had a significantly lesser degree of leftward planum temporale asymmetry than right-handers. Thus, a structural-functional relation exists in cerebral asymmetry. The correlation is likely to reflect language representation. Because familial sinistrality influenced the anatomical pattern in left-handers and planum temporale asymmetry is already present in the newborn, prenatal factors must play an important role in the development of functional laterality.

An immune origin of type 2 diabetes

Abstract: Subclinical, low-grade systemic inflammation has been observed in patients with type 2 diabetes and in those at increased risk of the disease. This may be more than an epiphenomenon. Alleles of genes encoding immune/inflammatory mediators are associated with the disease, and the two major environmental factors the contribute to the risk of type 2 diabetes-diet and physical activity-have a direct impact on levels of systemic immune mediators. In animal models, targeting of immune genes enhanced or suppressed the development of obesity or diabetes. Obesity is associated with the infiltration and proinflammatory activity of macrophages in adipose tissue, and immune mediators may be important regulators of insulin resistance, mitochondrial function, ectopic lipid storage and beta cell dysfunction or death. Intervention studies targeting these pathways would help to determine the contribution of an activated innate immune system to the development of type 2 diabetes.

Somatic mutations in the PTCH, SMOH, SUFUH and TP53 genes in sporadic basal cell carcinomas

Abstract: Summary Background Basal cell carcinoma (BCC) of the skin is the most common human cancer. The genetic alterations underlying BCC development are only partly understood. Objectives To investigate further the molecular genetics of sporadic BCCs, we performed mutation analyses of 10 skin cancer-associated genes in 42 tumours. Methods Single-strand conformational polymorphism analysis followed by DNA sequencing was used to screen for mutations in the sonic hedgehog pathway genes PTCH, SMOH, SUFUH and GLI1, in the TP53 tumour suppressor gene, and in the proto-oncogenes NRAS, KRAS, HRAS, BRAF and CTNNB1. Microsatellite markers flanking the PTCH, SUFUH and TP53 loci at 9q22, 10q24 and 17p13, respectively, were studied for loss of heterozygosity (LOH). Results PTCH mutations were found in 28 of 42 tumours (67%). Microsatellite analysis revealed LOH on 9q22 in 20 of 38 tumours investigated (53%), including 14 tumours with and six tumours without PTCH mutations. SMOH mutations were identified in four of the 42 BCCs (10%) while two tumours demonstrated mutations in SUFUH, including one missense mutation and one silent mutation. None of the BCCs showed LOH at markers flanking the SUFUH locus. Seventeen BCCs (40%) carried TP53 mutations, with only three tumours showing evidence of biallelic TP53 inactivation. TP53 mutations were present in BCCs with and without mutations in PTCH, SMOH or SUFUH. Interestingly, 72% of the TP53 alterations were presumably ultraviolet (UV)-induced transition mutations. In contrast, only 40% of the PTCH and SMOH alterations corresponded to UV signature mutations. No mutations were identified in GLI1, NRAS, KRAS, HRAS, BRAF or CTNNB1. Conclusions Our data confirm the importance of PTCH, SMOH and TP53 mutations in the pathogenesis of sporadic BCCs. SUFUH alterations are restricted to individual cases while the other investigated genes do not appear to be important targets for mutations in BCCs.

Mutation of the RAD51C gene in a Fanconi anemia-like disorder

Abstract: Fanconi anemia (FA) is a rare chromosomal-instability disorder associated with a variety of developmental abnormalities, bone marrow failure and predisposition to leukemia and other cancers. We have identified a homozygous missense mutation in the RAD51C gene in a consanguineous family with multiple severe congenital abnormalities characteristic of FA. RAD51C is a member of the RAD51-like gene family involved in homologous recombination-mediated DNA repair. The mutation results in loss of RAD51 focus formation in response to DNA damage and in increased cellular sensitivity to the DNA interstrand cross-linking agent mitomycin C and the topoisomerase-1 inhibitor camptothecin. Thus, biallelic germline mutations in a RAD51 paralog are associated with an FA-like syndrome.

Kinetic characterization of individual hexose transporters of Saccharomyces cerevisiae and their relation to the triggering mechanisms of glucose repression.

Abstract: In Saccharomyces cerevisiae, there are a large number of genes (HXT1-HXT17/SNF3/RGT2) encoding putative hexose transporters which, together with a galactose permease gene (GAL2), belong to a superfamily of monosaccharide facilitator genes. We have performed a systematic analysis of the HXT1-7 and GAL2 genes and their function in hexose transport. Glucose uptake was below the detection level in the hxt1-7 null strain growing on maltose. Determination of the kinetic parameters of individual hexose transporter-related proteins (Hxtp) expressed in the hxt null background revealed Hxt1p and Hxt3p as low-affinity transporters (Km(glucose) = 50-100 mM), Hxt2p and Hxt4p as moderately low in affinity (Km(glucose) about 10 mM), and Hxt6p, Hxt7p as well as Gal2p as high-affinity transporters (Km(glucosse) = 1-2 mM). However, Hxt2p kinetics in cells grown on low glucose concentrations showed a high-affinity (Km = 1.5 mM) and a low-affinity component (Km = 60 mM). Furthermore, we investigated the involvement of glucose transport in glucose signalling. Glucose repression of MAL2, SUC2 and GAL1 was not dependent on a specific transporter but, instead, the strength of the repression signal was dependent on the level of expression, the properties of the individual transporters and the kind of sugar transported. The strength of the glucose repression signal correlated with the glucose consumption rates in the different strains, indicating that glucose transport limits the provision of a triggering signal rather then being directly involved in the triggering mechanism.