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 & Diabetes mellitus. The organization has 25225 authors who have published 49155 publications receiving 1946434 citations.

p63 Gene mutations in EEC syndrome, limb-mammary syndrome, and isolated split hand-split foot malformation suggest a genotype-phenotype correlation

Abstract: p63 mutations have been associated with EEC syndrome (ectrodactyly, ectodermal dysplasia, and cleft lip/palate), as well as with nonsyndromic split hand–split foot malformation (SHFM). We performed p63 mutation analysis in a sample of 43 individuals and families affected with EEC syndrome, in 35 individuals affected with SHFM, and in three families with the EEC-like condition limb-mammary syndrome (LMS), which is characterized by ectrodactyly, cleft palate, and mammary-gland abnormalities. The results differed for these three conditions. p63 gene mutations were detected in almost all (40/43) individuals affected with EEC syndrome. Apart from a frameshift mutation in exon 13, all other EEC mutations were missense, predominantly involving codons 204, 227, 279, 280, and 304. In contrast, p63 mutations were detected in only a small proportion (4/35) of patients with isolated SHFM. p63 mutations in SHFM included three novel mutations: a missense mutation (K193E), a nonsense mutation (Q634X), and a mutation in the 3′ splice site for exon 5. The fourth SHFM mutation (R280H) in this series was also found in a patient with classical EEC syndrome, suggesting partial overlap between the EEC and SHFM mutational spectra. The original family with LMS (van Bokhoven et al. 1999) had no detectable p63 mutation, although it clearly localizes to the p63 locus in 3q27. In two other small kindreds affected with LMS, frameshift mutations were detected in exons 13 and 14, respectively. The combined data show that p63 is the major gene for EEC syndrome, and that it makes a modest contribution to SHFM. There appears to be a genotype-phenotype correlation, in that there is a specific pattern of missense mutations in EEC syndrome that are not generally found in SHFM or LMS.

Pathogenetic mechanisms of hepatic encephalopathy

Abstract: Hepatic encephalopathy (HE) in liver cirrhosis is a clinical manifestation of a low-grade cerebral oedema, which is exacerbated in response to ammonia and other precipitating factors. This low-grade cerebral oedema is accompanied by an increased production of reactive oxygen and nitrogen oxide species (ROS/RNOS), which trigger multiple protein and RNA modifications, thereby affecting brain function. The action of ammonia, inflammatory cytokines, benzodiazepines and hyponatraemia integrates at the level of astrocyte swelling and oxidative stress. This explains why heterogenous clinical conditions can precipitate HE episodes. Oxidised RNA species, which are formed in response to oxidative stress, also participate in local postsynaptic protein synthesis in neurons, which is required for memory formation. Although the functional consequences of RNA oxidation in this context remain to be established, these findings bear a potential biochemical explanation for the multiple alterations of neurotransmitter receptor systems and of synaptic plasticity. Such changes may in part also underlie the pathologically altered oscillatory networks in the brain of HE patients in vivo, as detected by magnetencephalography. These disturbances of oscillatory networks, which in part are triggered by hypothalamic structures, can explain the motor and cognitive deficits in patients with HE. Current therapeutic strategies aim at the elimination of precipitating factors. The potential of therapies targeting downstream pathophysiological events in HE has not yet been explored, but offers novel potential sites of therapeutic intervention.

Probabilistic Maps, Morphometry, and Variability of Cytoarchitectonic Areas in the Human Superior Parietal Cortex

Abstract: Recently, 8 areas (5Ci, 5M, 5L, 7PC, 7A, 7P, 7M, hIP3) in the human superior parietal cortex (SPC) were delineated in 10 postmortem brains using observer-independent cytoarchitectonic analysis. Here we present 3D probabilistic maps of these areas, quantifying the interindividual overlap for each voxel in stereotaxic reference space, and a maximum probability map, providing a contiguous parcellation. For all areas, we determined probabilities of mutual borders, calculated stereotaxic centers of gravity, and estimated volumes. A basic pattern of areas and borders was observed, which showed, however, intersubject variations and a significant interhemispheric asymmetry (7P, 7M) that may be functionally relevant. There was a trend toward higher intersubject anatomical variability in lateral compared with medial areas. For several areas (5M, 7PC, 7A, 7P), variability was significantly higher in the left hemisphere and/or in men, whereas for areas 5Ci and 5M there was a hemisphere-by-gender interaction. Differences in anatomical variability could bias group analyses in functional imaging studies by reducing sensitivity for activations of entities with high variability. The probabilistic maps provide an objective anatomical reference and account for the structural variability of the human brain. Integrated into functional imaging experiments, they can improve structure–function investigations of the human SPC.

Anatomical and functional connectivity of cytoarchitectonic areas within the human parietal operculum.

Abstract: In monkeys, the somatosensory cortex on the parietal operculum can be differentiated into several distinct cortical fields. Potential human homologues for these areas have already been defined by cytoarchitectonic mapping and functional imaging experiments. Differences between the two most widely studied areas [operculum parietale (OP) 1 and OP 4] within this region particularly pertain to their connection with either the perceptive parietal network or the frontal motor areas. In the present study, we investigated differences in anatomical connection patterns probed by probabilistic tractography on diffusion tensor imaging data. Functional connectivity was then mapped by coordinate-based meta-analysis of imaging studies. Comparison between these two aspects of connectivity showed a good congruency and hence converging evidence for an involvement of these areas in matching brain networks. There were, however, also several instances in which anatomical and functional connectivity diverged, underlining the independence of these measures and the need for multimodal characterization of brain connectivity. The connectivity analyses performed showed that the two largest areas within the human parietal operculum region display considerable differences in their connectivity to frontoparietal brain regions. In particular, relative to OP 1, area OP 4 is more closely integrated with areas responsible for basic sensorimotor processing and action control, while OP 1 is more closely connected to the parietal networks for higher order somatosensory processing. These results are largely congruent with data on nonhuman primates. Differences between anatomical and functional connectivity as well as between species, however, highlight the need for an integrative view on connectivity, including comparison and cross-validation of results from different approaches.

The protein kinase C‐mediated MAP kinase pathway involved in the maintenance of cellular integrity in Saccharomyces cerevisiae

Abstract: Signal transduction mediated by the single yeast isozyme of protein kinase C (Pkc1p) is essential for the maintenance of cellular integrity in this model eukaryote. The past few years have seen a dramatic increase in our knowledge of the upstream regulatory factors that modulate Pkc1p activity (e.g. Tor2p, Rom1p, Rom2p, Rho1p, Slg1p, Mid2p) and of the downstream targets of the MAP kinase cascade triggered by it (e.g. Rlm1p, SBF complex). The picture that has emerged connects this pathway to a variety of other cellular processes, such as cell cycle progression (Cdc28p, Swi4p), mating (Ste20p), nutrient sensing (Ira1p), calcium homeostasis (calcineurin, Mid2p, Fks2p) and the structural dynamics of the cytoskeleton (Spa1p, Bni1p).