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.

Direct Observation of Hydrogen Bonds in Nucleic Acid Base Pairs by Internucleotide 2JNN Couplings

Abstract: Hydrogen bonds play a key role in the stabilization of protein and nucleic acid secondary structure. Currently, most of the experimental evidence for the interaction of hydrogen bond donor and acceptor atoms is indirect. Here we show that scalar couplings across the hydrogen bond are observable for Watson−Crick base pairs in 15N-labeled RNA. These scalar couplings correlate the imino donor 15N nucleus and the corresponding acceptor 15N nucleus on the complementary base. The two-bond JNN couplings between the N3 of uridine and the N1 of adenosine, and between the N1 of guanosine and the N3 of cytidine, have values of approximately 7 Hz as determined by a novel quantitative J-correlation experiment for the 69-nucleotide T1 domain of the potato spindle tuber viroid. In contrast, for non-Watson−Crick base pairs the hydrogen bond acceptor is usually not a nitrogen, but an oxygen atom, and thus, the two-bond JNN couplings are not observed.

Molecular genetic analysis of oligodendroglial tumors shows preferential allelic deletions on 19q and 1p.

Abstract: The molecular genetic alterations of oligodendroglial tumors and mixed gliomas of the central nervous system were studied in a series of 37 cases (8 oligodendrogliomas, 13 anaplastic oligodendrogliomas, 8 oligoastrocytomas, and 8 anaplastic oligoastrocytomas). A total of 180 polymorphic loci and 5 nonpolymorphic gene loci, distributed over all chromosomes, were examined by restriction fragment length polymorphism analysis. Loss of heterozygosity was most frequently observed for loci on 19q with a commonly deleted region at 19q13.2-q13.4 distal to the CYP2a gene and proximal to the D19S22 locus. The incidence of allelic loss on 19q was particularly high (81%) in oligodendroglial tumors and equal to 31% in mixed gliomas. More than 75% of the tumors with allelic deletions on 19q also showed loss of heterozygosity for loci on 1p with one tumor showing only loss of alleles distal to the NGFB gene (1p13-pter). Seven (19%) tumors had lost alleles from 17p with the deleted region including the TP53 tumor suppressor gene in all cases. Sequencing of the TP53 transcripts from exons 2 to 10, however, did not reveal mutations of the remaining allele in any of these tumors. Anaplastic oligodendrogliomas and anaplastic oligoastrocytomas demonstrated an increased incidence of additional allelic losses involving most frequently chromosomes 9p and 10. Gene amplification was detected in two anaplastic tumors, affecting the epidermal growth factor receptor gene in both cases, with additional amplification of the renin gene at 1q32 in one of these cases. In total our results indicate both differences and similarities between the molecular genetic alterations in tumors with oligodendroglial and astrocytic differentiation. The loss of genetic information from 19q and 1p as well as the rarity of TP53 mutations in oligodendroglial tumors suggests that the early events in their oncogenesis are distinct from those associated with astrocytic tumors. However, similarities are indicated by the allelic losses on 9p and 10 in the anaplastic tumors, suggesting the utilization of common pathways of progression.

Unexpected complexity of the Wnt gene family in a sea anemone

Abstract: The Wnt gene family encodes secreted signalling molecules that control cell fate in animal development and human diseases. Despite its significance, the evolution of this metazoan-specific protein family is unclear. In vertebrates, twelve Wnt subfamilies were defined, of which only six have counterparts in Ecdysozoa (for example, Drosophila and Caenorhabditis). Here, we report the isolation of twelve Wnt genes from the sea anemone Nematostella vectensis, a species representing the basal group within cnidarians. Cnidarians are diploblastic animals and the sister-group to bilaterian metazoans. Phylogenetic analyses of N. vectensis Wnt genes reveal a thus far unpredicted ancestral diversity within the Wnt family. Cnidarians and bilaterians have at least eleven of the twelve known Wnt gene subfamilies in common; five subfamilies appear to be lost in the protostome lineage. Expression patterns of Wnt genes during N. vectensis embryogenesis indicate distinct roles of Wnts in gastrulation, resulting in serial overlapping expression domains along the primary axis of the planula larva. This unexpectedly complex inventory of Wnt family signalling factors evolved in early multi-cellular animals about 650 million years (Myr) ago, predating the Cambrian explosion by at least 100 Myr (refs 5, 8). It emphasizes the crucial function of Wnt genes in the diversification of eumetazoan body plans.

Expert position paper on air pollution and cardiovascular disease

Abstract: Air pollution has wide-ranging and deleterious effects on human health and is a major issue for the global community. The Global Burden of Disease study has described the worldwide impact of air pollution with as many as 3.1 million of 52.8 million all-cause and all-age deaths being attributable to ambient air pollution in the year 2010.1 Moreover, ambient air pollution ranked ninth among the modifiable disease risk factors, being listed above other commonly recognized factors, such as low physical activity, a high-sodium diet, high cholesterol, and drug use. Finally, air pollution accounts for 3.1% of global disability-adjusted life years, an index that measures the time spent in states of reduced health.1 Although it is intuitive that air pollution is an important stimulus for the development and exacerbation of respiratory diseases, such as asthma, chronic obstructive pulmonary disease, and lung cancer, there is generally less public awareness of its substantial impact on cardiovascular disease. Historically, the 1952 Great Smog of London led to an increase in cardiovascular death as well as deaths due to respiratory disease. Subsequent studies in the 1990s, such as the Harvard Six Cities2 and American Cancer Society cohort studies,2,3 established an enduring positive association between long-term exposure to air pollution and total and cardiovascular mortality, mainly due to coronary artery disease.4 In Europe, the first study that supported this association between long-term exposure and mortality was the Netherlands Cohort Study on Diet and Cancer.5 Associations with cardiovascular morbidity and mortality are also seen with short-term (e.g. day-to-day fluctuations) pollutant exposures of residents in large urban areas worldwide, including the United States of America6 …

Neuropsychological and psychiatric changes after deep brain stimulation for Parkinson's disease: a randomised, multicentre study

Abstract: Summary Background Deep brain stimulation (DBS) of the subthalamic nucleus (STN) reduces motor symptoms in patients with Parkinson's disease (PD) and improves their quality of life; however, the effect of DBS on cognitive functions and its psychiatric side-effects are still controversial. To assess the neuropsychiatric consequences of DBS in patients with PD we did an ancillary protocol as part of a randomised study that compared DBS with the best medical treatment. Methods 156 patients with advanced Parkinson's disease and motor fluctuations were randomly assigned to have DBS of the STN or the best medical treatment for PD according to the German Society of Neurology guidelines. 123 patients had neuropsychological and psychiatric examinations to assess the changes between baseline and after 6 months. The primary outcome was the comparison of the effect of DBS with the best medical treatment on overall cognitive functioning (Mattis dementia rating scale). Secondary outcomes were the effects on executive function, depression, anxiety, psychiatric status, manic symptoms, and quality of life. Analysis was per protocol. The study is registered at ClinicalTrials.gov, number NCT00196911. Findings 60 patients were randomly assigned to receive STN-DBS and 63 patients to have best medical treatment. After 6 months, impairments were seen in executive function (difference of changes [DBS–best medical treatment] in verbal fluency [semantic] −4·50 points, 95% CI −8·07 to −0·93, Cohen's d =−;0·4; verbal fluency [phonemic] −3·06 points, −5·50 to −0·62, −0·5; Stroop 2 naming colour error rate −0·37 points, −0·73 to 0·00, −0·4; Stroop 3 word reading time −5·17 s, −8·82 to −1·52, −0·5; Stroop 4 colour naming time −13·00 s, −25·12 to −0·89, −0·4), irrespective of the improvement in quality of life (difference of changes in PDQ-39 10·16 points, 5·45 to 14·87, 0·6; SF-36 physical 16·55 points, 10·89 to 22·21, 0·9; SF-36 psychological 9·74 points, 2·18 to 17·29, 0·5). Anxiety was reduced in the DBS group compared with the medication group (difference of changes in Beck anxiety inventory 10·43 points, 6·08 to 14·78, 0·8). Ten patients in the DBS group and eight patients in the best medical treatment group had severe psychiatric adverse events. Interpretation DBS of the STN does not reduce overall cognition or affectivity, although there is a selective decrease in frontal cognitive functions and an improvement in anxiety in patients after the treatment. These changes do not affect improvements in quality of life. DBS of the STN is safe with respect to neuropsychological and psychiatric effects in carefully selected patients during a 6-month follow-up period. Funding German Federal Ministry of Education and Research (01GI0201).