62 research outputs found

    Subclavian artery rupture in a young man during excessive weight lifting

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    We report a 19-year-old man with rupture of the right subclavian artery after an excessive exercise of weight lifting. Imaging showed a hematothorax and hematomediastinum, a pseudoaneurysm with a maximum diameter of 4 cm, and a dissection of the right vertebral artery. As an emergency procedure an interposition graft was performed for reconstruction of the right subclavian artery. The patient's postoperative course was uneventful, and he was symptom free except for regressive hoarseness due to a paresis of the right recurrent laryngeal nerve

    Erythropoietin and the effect of oxygen during proliferation and differentiation of human neural progenitor cells

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    <p>Abstract</p> <p>Background</p> <p>Hypoxia plays a critical role in various cellular mechanisms, including proliferation and differentiation of neural stem and progenitor cells. In the present study, we explored the impact of lowered oxygen on the differentiation potential of human neural progenitor cells, and the role of erythropoietin in the differentiation process.</p> <p>Results</p> <p>In this study we demonstrate that differentiation of human fetal neural progenitor cells under hypoxic conditions results in an increased neurogenesis. In addition, expansion and proliferation under lowered oxygen conditions also increased neuronal differentiation, although proliferation rates were not altered compared to normoxic conditions. Erythropoietin partially mimicked these hypoxic effects, as shown by an increase of the metabolic activity during differentiation and protection of differentiated cells from apoptosis.</p> <p>Conclusion</p> <p>These results provide evidence that hypoxia promotes the differentiation of human fetal neural progenitor cells, and identifies the involvement of erythropoietin during differentiation as well as different cellular mechanisms underlying the induction of differentiation mediated by lowered oxygen levels.</p

    Ortho2ExpressMatrix—a web server that interprets cross-species gene expression data by gene family information

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    <p>Abstract</p> <p>Background</p> <p>The study of gene families is pivotal for the understanding of gene evolution across different organisms and such phylogenetic background is often used to infer biochemical functions of genes. Modern high-throughput experiments offer the possibility to analyze the entire transcriptome of an organism; however, it is often difficult to deduct functional information from that data.</p> <p>Results</p> <p>To improve functional interpretation of gene expression we introduce Ortho2ExpressMatrix, a novel tool that integrates complex gene family information, computed from sequence similarity, with comparative gene expression profiles of two pre-selected biological objects: gene families are displayed with two-dimensional matrices. Parameters of the tool are object type (two organisms, two individuals, two tissues, etc.), type of computational gene family inference, experimental meta-data, microarray platform, gene annotation level and genome build. Family information in Ortho2ExpressMatrix bases on computationally different protein family approaches such as EnsemblCompara, InParanoid, SYSTERS and Ensembl Family. Currently, respective all-against-all associations are available for five species: human, mouse, worm, fruit fly and yeast. Additionally, microRNA expression can be examined with respect to miRBase or TargetScan families. The visualization, which is typical for Ortho2ExpressMatrix, is performed as matrix view that displays functional traits of genes (differential expression) as well as sequence similarity of protein family members (BLAST e-values) in colour codes. Such translations are intended to facilitate the user's perception of the research object.</p> <p>Conclusions</p> <p>Ortho2ExpressMatrix integrates gene family information with genome-wide expression data in order to enhance functional interpretation of high-throughput analyses on diseases, environmental factors, or genetic modification or compound treatment experiments. The tool explores differential gene expression in the light of orthology, paralogy and structure of gene families up to the point of ambiguity analyses. Results can be used for filtering and prioritization in functional genomic, biomedical and systems biology applications. The web server is freely accessible at <url>http://bioinf-data.charite.de/o2em/cgi-bin/o2em.pl</url>.</p

    The wake vortex prediction and monitoring system WSVBS Part II: Performance and ATC integration at Frankfurt airport

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    The performance and ATC integration of DLR’s wake vortex advisory system “WSVBS” (Wirbelschleppen-Vorhersage- und -Beobachtungssystem) for the dependent parallel runway system 25L and 25R at Frankfurt Airport are described. WSVBS has compo-nents to forecast and monitor the local weather and to predict and monitor wake trans-port and decay along the glide paths. It is integrated in the arrival manager AMAN of DLR. Each 10 minutes it delivers minimum safe aircraft separation times for the next hour to air traffic control. These times are translated into operational modes for runways 25L/R aiming at improving the capacity. From 66 days of a performance test at Frank-furt it was found that the system ran stable and the predicted minimum separation times were safe. The capacity improving concepts of operation could have been used in 75% of the time and continuously applied for at least several tens of minutes. From fast-time simulations the eventual capacity gain for Frankfurt was estimated to be 3% taking into account the real traffic mix and operational constraints in the period of one month

    Abdominal Aortic Aneurysms

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    Abdominal aortic aneurysms represent both an individual risk of mortality and a socioeconomic burden for health care systems worldwide, but screening is not performed in all countries. Here, the authors summarize the pros and cons of screening to reduce abdominal aortic aneurysm–related mortality

    DIALIGN: finding local similarities by multiple sequence alignment

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    Morgenstern B, Frech K, Dress A, Werner T. DIALIGN: finding local similarities by multiple sequence alignment. Bioinformatics. 1998;14(3):290-294.Motivation: DIALIGN is a new method for pairwise as Well as multiple alignment oSlzucleic acid and protein sequences. While standard alignment programs rely on comparing single residues and imposing gap penalties, DIALIGN constructs alignments by comparing whole segments of the sequences. No gap penalty is employed. This point of view is especially adequate if sequences ai-e not globally related, bur share only local similarities, as is the case in genomic DNA sequences and in many protein families. Results: Using four different data sers, we show that DIALICN is able correctly to align conserved motifs in protein sequences. Alignments produced by DIALIGN are compared systematically to the results of five other alignment programs

    Pluripotent Stem Cells for Disease Modeling and Drug Discovery in Niemann-Pick Type C1

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    The lysosomal storage disorders Niemann-Pick disease Type C1 (NPC1) and Type C2 (NPC2) are rare diseases caused by mutations in the NPC1 or NPC2 gene. Both NPC1 and NPC2 are proteins responsible for the exit of cholesterol from late endosomes and lysosomes (LE/LY). Consequently, mutations in one of the two proteins lead to the accumulation of unesterified cholesterol and glycosphingolipids in LE/LY, displaying a disease hallmark. A total of 95% of cases are due to a deficiency of NPC1 and only 5% are caused by NPC2 deficiency. Clinical manifestations include neurological symptoms and systemic symptoms, such as hepatosplenomegaly and pulmonary manifestations, the latter being particularly pronounced in NPC2 patients. NPC1 and NPC2 are rare diseases with the described neurovisceral clinical picture, but studies with human primary patient-derived neurons and hepatocytes are hardly feasible. Obviously, induced pluripotent stem cells (iPSCs) and their derivatives are an excellent alternative for indispensable studies with these affected cell types to study the multisystemic disease NPC1. Here, we present a review focusing on studies that have used iPSCs for disease modeling and drug discovery in NPC1 and draw a comparison to commonly used NPC1 models

    Impact of Organelle Transport Deficits on Mitophagy and Autophagy in Niemann–Pick Disease Type C

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    Defective mitochondria are pathophysiological features of a number of neurodegenerative diseases. Here, we investigated mitochondrial dysfunction in the context of the rare lysosomal storage diseases Niemann–Pick disease type C1 and type C2 (NP-C1 and NP-C2). Mutations in either the NPC1 or NPC2 gene lead to cholesterol accumulation in late endosomes and lysosomes, resulting in impaired cholesterol homeostasis. The extent to which this may lead to mitochondrial dysfunction has been poorly studied so far. Therefore, we investigated the morphology, function, and transport of mitochondria, as well as their degradation via mitophagy, in a disease-associated human neural cell model of NP-C. By performing live cell imaging, we observed markedly reduced mitochondrial transport, although morphology and function were not appreciably altered. However, we observed a defective mitophagy induction shown by a reduced capability to elevate parkin expression and engulf mitochondria in autophagosomes after treatment with carbonyl cyanide 3-chlorophenylhydrazone (CCCP). This was accompanied by defects in autophagy induction, exhibited by a hampered p62 expression and progression, shown by increased LC3BII levels and a defective fusion of autophagosomes and lysosomes. The latter might have been additionally influenced by the observed reduced lysosomal transport. Hence, we hypothesized that a reduced recycling of mitochondria contributes to the pathophysiology of NP-C
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