The angiotensin converting enzyme insertion/deletion polymorphism alters the response of muscle energy supply lines to exercise

The presence of a silencing sequence (the I-allele) in the gene for the upstream regulator of blood flow, angiotensin I-converting enzyme (ACE), is associated with superior endurance performance and its trainability. We tested in a retrospective study with 36 Caucasian men of Swiss descent whether carriers of the ACE I-allele demonstrate a modified adaptive response of energy supply lines in knee extensor muscle, and aerobic fitness, to endurance training based on 6weeks of supervised bicycle exercise or 6months of self-regulated running (p value <Bonferroni-corrected 5%). Body weight related maximal oxygen uptake and capillary density in vastus lateralis muscle before training were 20 and 23% lower, respectively, in carriers of the I-allele. Bicycle (n=16) but not running type endurance training (n=19) increased the volume content of subsarcolemmal mitochondria (2.5-fold) and intramyocellular lipid (2.1-fold). This was specifically amplified in I-allele carriers after 6weeks of bicycle exercise. The enhanced adjustment in myocellular organelles of aerobic metabolism with bicycle training corresponded to ACE I-allele dependent upregulation of 23 muscle transcripts during recovery from the bicycle stimulus and with training. The majority of affected transcripts were associated with glucose (i.e. ALDOC, Glut2, LDHC) and lipid metabolism (i.e. ACADL, CPTI, CPTII, LIPE, LPL, FATP, CD36/FAT); all demonstrating an enhanced magnitude of change in carriers of the ACE I-allele. Our observations suggest that local improvements in mitochondrial metabolism, through a novel expression pathway, contribute to the varying trainability in endurance performance between subjects with genetically modified expression of the regulator of vascular tone, AC

Pneumolysin boosts the neuroinflammatory response to Streptococcus pneumoniae through enhanced endocytosis.

In pneumococcal meningitis, bacterial growth in the cerebrospinal fluid results in lysis, the release of toxic factors, and subsequent neuroinflammation. Exposure of primary murine glia to Streptococcus pneumoniae lysates leads to strong proinflammatory cytokine and chemokine production, blocked by inhibition of the intracellular innate receptor Nod1. Lysates enhance dynamin-dependent endocytosis, and dynamin inhibition reduces neuroinflammation, blocking ligand internalization. Here we identify the cholesterol-dependent cytolysin pneumolysin as a pro-endocytotic factor in lysates, its elimination reduces their proinflammatory effect. Only pore-competent pneumolysin enhances endocytosis in a dynamin-, phosphatidylinositol-3-kinase- and potassium-dependent manner. Endocytic enhancement is limited to toxin-exposed parts of the membrane, the effect is rapid and pneumolysin permanently alters membrane dynamics. In a murine model of pneumococcal meningitis, mice treated with chlorpromazine, a neuroleptic with a complementary endocytosis inhibitory effect show reduced neuroinflammation. Thus, the dynamin-dependent endocytosis emerges as a factor in pneumococcal neuroinflammation, and its enhancement by a cytolysin represents a proinflammatory control mechanism

The virtual reconstruction of the synagogue Atzgersdorf

Abweichender Titel laut Übersetzung der Verfasserin/des VerfassersIm Gedenkjahr 1998 entstand an der TU-Wien unter Prof. Bob Martens die Idee, zerstörte Wiener Synagogen virtuell zu rekonstruieren.Vorbild war das an der TU-Darmstadt entwickelte Projekt "Synagogen in Deutschland - Eine Virtuelle Rekonstruktion". Die computergestützten Rekonstruktionen sollen den kulturellen Verlust aufzeigen, und die zerstörten Gotteshäuser wieder in Erinnerung rufen. Die Synagoge Atzgersdorf, im heutigen 23. Wiener Gemeindebezirk, ist eine dieser, während des Novemberpogroms 1938, zerstörten Synagogen. Die Basis der Diplomarbeit war der historische Hintergrund der Synagoge, und die Quellen, die die Rekonstruktion erst ermöglichten. Der historische Hintergrund umfasst die Geschichte der Juden in Niederösterreich und speziell in Liesing. Weiters wird die Baugeschichte der Synagoge und die Geschichte des Architekten Richard Esriels beschrieben. Vor der Rekonstruktion standen die Diskussion und die Beurteilung der gefundenen Quellen. Die Rekonstruktion erfolgte mit ArchiCAD von Graphisoft, einer CAD-Software. Es wird der Arbeitsprozess der Modellierung und die Strukturierung der Daten des virtuellen Modells im CAD-Programm beschrieben. Das Ergebnis der Rekonstruktion der Synagoge Atzgersdorf war ein virtuelles Gebäudemodell. Dieses bildete den Ausgangspunkt für Visualisierungen des Gebäudes. So entstanden mit Hilfe von ArtLantis, einem Renderprogramm, fotorealistische Abbildungen. Mit Hilfe eines 3D-Druckes wurde aus den Daten ein physisches Schnittmodell der Synagoge erzeugt.9

Impact of observation on disposition of elderly patients presenting to emergency departments with non-specific complaints.

Emergency Departments (EDs) have to cope with an increasing number of elderly patients, often presenting with non-specific complaints (NSC), such as generalized weakness. Acute morbidity requiring early intervention is present in the majority of patients with NSC. Therefore, an early and optimal disposition plan is crucial. The objective of this study was to prospectively study the disposition process of patients presenting to the ED with NSC.For two years, all patients presenting with NSC presenting to an urban ED were screened and consecutively included. The initial disposition plan was compared to the effective transfer after observation. Optimal disposition was defined as a high accuracy regarding disposition of patients with acute morbidity to an internal medicine ward.The final study population consisted of 669 patients with NSC. Admission to internal medicine increased from 297 (44%) planned admissions to 388 (58%) effective admissions after observation. Conversely, transfers to geriatric community hospitals and discharges decreased from the initially planned 372 (56%) patients to 281 (42%) effectively transferred and discharged patients. The accuracy regarding disposition of patients with acute morbidity increased from 53% to 68% after observation.Disposition planning in patients with NSC improves after observation, if defined by the accuracy regarding hospitalization of patients with acute morbidity. Further research should focus on risk stratification tools for timely disposition planning in order to reduce high admission rates for patients without acute morbidity and high readmission rates for discharged patients with non-specific complaints

Lethal toxin of Clostridium sordellii is associated with fatal equine atypical myopathy

The lethal toxin of Clostridium sordellii (TcsL) evokes severe, mostly fatal disease patterns like toxic shock syndrome in humans and animals. Since this large clostridial toxin-induced severe muscle damaging when injected intramuscularly into mice, we hypothesized that TcsL is also associated with equine atypical myopathy (EAM), a fatal myodystrophy of hitherto unknown etiology. Transmission electron microscopy revealed skeletal and heart muscles of EAM-affected horses to undergo degeneration ultrastructurally similar to the damage found in TcsL-treated mice. Performing immunohistochemistry, myofibers of EAM-affected horses specifically reacted with sera derived from horses with EAM as well as an antibody specific for the N-terminal part of TcsL, while both antibodies failed to bind to the myofibers of either healthy horses or those with other myopathies. The presence of TcsL in myofibers of horses with EAM suggests that it plays a role as trigger or even as lethal factor in this disease

Genotype-specific risk factors for Staphylococcus aureus in Swiss dairy herds with an elevated yield-corrected herd somatic cell count

Bovine mastitis is a frequent problem in Swiss dairy herds. One of the main pathogens causing significant economic loss is Staphylococcus aureus. Various Staph. aureus genotypes with different biological properties have been described. Genotype B (GTB) of Staph. aureus was identified as the most contagious and one of the most prevalent strains in Switzerland. The aim of this study was to identify risk factors associated with the herd-level presence of Staph. aureus GTB and Staph. aureus non-GTB in Swiss dairy herds with an elevated yield-corrected herd somatic cell count (YCHSCC). One hundred dairy herds with a mean YCHSCC between 200,000 and 300,000cells/mL in 2010 were recruited and each farm was visited once during milking. A standardized protocol investigating demography, mastitis management, cow husbandry, milking system, and milking routine was completed during the visit. A bulk tank milk (BTM) sample was analyzed by real-time PCR for the presence of Staph. aureus GTB to classify the herds into 2 groups: Staph. aureus GTB-positive and Staph. aureus GTB-negative. Moreover, quarter milk samples were aseptically collected for bacteriological culture from cows with a somatic cell count ≥150,000cells/mL on the last test-day before the visit. The culture results allowed us to allocate the Staph. aureus GTB-negative farms to Staph. aureus non-GTB and Staph. aureus-free groups. Multivariable multinomial logistic regression models were built to identify risk factors associated with the herd-level presence of Staph. aureus GTB and Staph. aureus non-GTB. The prevalence of Staph. aureus GTB herds was 16% (n=16), whereas that of Staph. aureus non-GTB herds was 38% (n=38). Herds that sent lactating cows to seasonal communal pastures had significantly higher odds of being infected with Staph. aureus GTB (odds ratio: 10.2, 95% CI: 1.9-56.6), compared with herds without communal pasturing. Herds that purchased heifers had significantly higher odds of being infected with Staph. aureus GTB (rather than Staph. aureus non-GTB) compared with herds without purchase of heifers. Furthermore, herds that did not use udder ointment as supportive therapy for acute mastitis had significantly higher odds of being infected with Staph. aureus GTB (odds ratio: 8.5, 95% CI: 1.6-58.4) or Staph. aureus non-GTB (odds ratio: 6.1, 95% CI: 1.3-27.8) than herds that used udder ointment occasionally or regularly. Herds in which the milker performed unrelated activities during milking had significantly higher odds of being infected with Staph. aureus GTB (rather than Staph. aureus non-GTB) compared with herds in which the milker did not perform unrelated activities at milking. Awareness of 4 potential risk factors identified in this study guides implementation of intervention strategies to improve udder health in both Staph. aureus GTB and Staph. aureus non-GTB herds

Transcriptional adaptations of lipid metabolism in tibialis anterior muscle of endurance-trained athletes

It was hypothesized that transcriptional reprogramming is involved in the structural and functional adaptations of lipid metabolism in human tibialis anterior muscle (TA) from endurance-trained male subjects. RT-PCR experiments demonstrated a significant upregulation of the mRNA level of key enzymes involved in 1) lipolytic mobilization of fatty acids (FA) from intramyocellular lipid (IMCL) stores via hormone-sensitive lipase (LIPE), 2) intramyocellular FA transport via muscle fatty acid binding protein (FABP3), and 3) oxidative phosphorylation (cytochrome c oxidase I, COI), in TA of endurance-trained vs. untrained subjects. In contrast, mRNAs for factors involved in glycolysis (muscle 6-phosphofructokinase, PFKM), intramyocellular storage of FA (diacylglycerol O-acyltransferase 1, DGAT), and ß-oxidation (long-chain acyl-coenzyme A dehydrogenase, ACADL) were invariant between TA of trained and untrained subjects. Correlation analysis identified an association of LIPE with FABP3 and LPL (lipoprotein lipase) mRNA levels and indicated coregulation of the transcript level for LIPE, FABP3, and COI with the level of mRNA encoding peroxisome proliferator-activated receptor- (PPAR-), the master regulator of lipid metabolism. Moreover, a significant correlation existed between LPL mRNA and the absolute rate of IMCL repletion determined by magnetic resonance spectroscopy after exhaustive exercise. Additionally, the LIPE mRNA level correlated with ultrastructurally determined IMCL content and mitochondrial volume density. The present data point to a training-induced, selective increase in mRNA levels of enzymes which are involved in metabolization of intramuscular FA, and these data confirm the well-established phenomenon of enhanced lipid utilization during exercise at moderate intensity in muscles of endurance-trained subjects

Angiogenesis-related ultrastructural changes to capillaries in human skeletal muscle in response to endurance exercise

The ultrastructure of capillaries in skeletal muscle was morphometrically assessed in vastus lateralis muscle (VL) biopsies taken before and after exercise from 22 participants of two training studies. In study 1 (8 wk of ergometer training), light microscopy revealed capillary-fiber (C/F) ratio (+27%) and capillary density (+16%) to be higher (P ≤ 0.05) in postexercise biopsies than in preexercise biopsies from all 10 participants. In study 2 (6 mo of moderate running), C/F ratio and capillary density were increased (+23% and +20%; respectively, P ≤ 0.05) in VL biopsies from 6 angiogenesis responders (AR) after training, whereas 6 nonangiogenesis responders (NR) showed nonsignificant changes in these structural indicators (-4%/-4%, respectively). Forty capillary profiles per participant were evaluated by point and intersection counting on cross sections after transmission electron microscopy. In study 1, volume density (Vv) and mean arithmetic thickness (T) of endothelial cells (ECs; +19%/+17%, respectively) and pericytes (PCs; +20%/+21%, respectively) were higher (P ≤ 0.05), whereas Vv and T of the pericapillary basement membrane (BM) were -23%/-22% lower (P ≤ 0.05), respectively, in posttraining biopsies. In study 2, exercise-related differences between AR and NR-groups were found for Vv and T of PCs (AR, +26%/+22%, respectively, both P ≤ 0.05; NR, +1%/-3%, respectively, both P > 0.05) and BM (AR, -14%/-13%, respectively, both P ≤ 0.05; NR, -9%/-11%, respectively, P = 0.07/0.10). Vv and T of ECs were higher (AR, +16%/+18%, respectively; NR, +6%/+6%, respectively; all P ≤ 0.05) in both groups. The PC coverage was higher (+13%, P ≤ 0.05) in VL biopsies of individuals in the AR group but nonsignificantly altered (+3%, P > 0.05) in those of the NR group after training. Our study suggests that intensified PC mobilization and BM thinning are related to exercise-induced angiogenesis in human skeletal muscle, whereas training per se induces EC-thickening