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Ein neues Ziel-Inhalts-Konzept des Rahmenlehrplans nimmt in dieser Lehrerhandreiche Gestalt an. Fachwissenschaftliche und didaktische Instruktionen sowie ein ideenreicher Arbeitsteil (Materialien und Aufgaben) helfen bei der Unterrichtsvorbereitung. Aus dem Inhalt: - ein integratives Antike-Projekt untersucht Möglichkeiten und Grenzen gesellschaftlicher Teilhabe in Athen und der römischen Republik; - Augustus und Alexander als Zentralgestalten universaler Monarchie und Reichsbildung werden in der biografischen Rekonstruktion und im historischen Kontext lebendig; - das Thema Erinnerungskultur in der Antike und heute verweist auf Grundprobleme der Geschichtskultur; - Anregungen zur Arbeit mit dem Spielfilm „Alexander“ als historische Quelle führen an rezeptionsgeschichtliche und medienspezifische Aspekte historischen Lernens heran
Major depressive disorder (MDD) is a common and severe disease characterized by mood changes, somatic alterations, and often suicide. MDD is treated with antidepressants, but the molecular mechanism of their action is unknown. We found that widely used antidepressants such as amitriptyline and fluoxetine induce autophagy in hippocampal neurons via the slow accumulation of sphingomyelin in lysosomes and Golgi membranes and of ceramide in the endoplasmic reticulum (ER). ER ceramide stimulates phosphatase 2A and thereby the autophagy proteins Ulk, Beclin, Vps34/Phosphatidylinositol 3-kinase, p62, and Lc3B. Although treatment with amitriptyline or fluoxetine requires at least 12 days to achieve sphingomyelin accumulation and the subsequent biochemical and cellular changes, direct inhibition of sphingomyelin synthases with tricyclodecan-9-yl-xanthogenate (D609) results in rapid (within 3 days) accumulation of ceramide in the ER, activation of autophagy, and reversal of biochemical and behavioral signs of stress-induced MDD. Inhibition of Beclin blocks the antidepressive effects of amitriptyline and D609 and induces cellular and behavioral changes typical of MDD. These findings identify sphingolipid-controlled autophagy as an important target for antidepressive treatment methods and provide a rationale for the development of novel antidepressants that act within a few days.
To explore the genetic determinants of obesity and Type 2 diabetes (T2D), the German Center for Diabetes Research (DZD) conducted crossbreedings of the obese and diabetes-prone New Zealand Obese mouse strain with four different lean strains (B6, DBA, C3H, 129P2) that vary in their susceptibility to develop T2D. Genome-wide linkage analyses localized more than 290 quantitative trait loci (QTL) for obesity, 190 QTL for diabetes-related traits and 100 QTL for plasma metabolites in the out-cross populations. A computational framework was developed that allowed to refine critical regions and to nominate a small number of candidate genes by integrating reciprocal haplotype mapping and transcriptome data. The efficiency of the complex procedure was demonstrated for one obesity QTL. The genomic interval of 35 Mb with 502 annotated candidate genes was narrowed down to six candidates. Accordingly, congenic mice retained the obesity phenotype owing to an interval that contains three of the six candidate genes. Among these the phospholipase PLA2G4A exhibited an elevated expression in adipose tissue of obese human subjects and is therefore a critical regulator of the obesity locus. Together, our broad and complex approach demonstrates that combined- and comparative-cross analysis exhibits improved mapping resolution and represents a valid tool for the identification of disease genes.
Abdominal and general adiposity are independently associated with mortality, but there is no consensus on how best to assess abdominal adiposity. We compared the ability of alternative waist indices to complement body mass index (BMI) when assessing all-cause mortality. We used data from 352,985 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) and Cox proportional hazards models adjusted for other risk factors. During a mean follow-up of 16.1 years, 38,178 participants died. Combining in one model BMI and a strongly correlated waist index altered the association patterns with mortality, to a predominantly negative association for BMI and a stronger positive association for the waist index, while combining BMI with the uncorrelated A Body Shape Index (ABSI) preserved the association patterns. Sex-specific cohort-wide quartiles of waist indices correlated with BMI could not separate high-risk from low-risk individuals within underweight (BMI<18.5 kg/m(2)) or obese (BMI30 kg/m(2)) categories, while the highest quartile of ABSI separated 18-39% of the individuals within each BMI category, which had 22-55% higher risk of death. In conclusion, only a waist index independent of BMI by design, such as ABSI, complements BMI and enables efficient risk stratification, which could facilitate personalisation of screening, treatment and monitoring.
Objective: Fibroblast growth factor (FGF)21 is promptly induced by short fasting in animal models to regulate glucose and fat metabolism. Data on FGF21 in humans are inconsistent and FGF21 has not yet been investigated in old patients with cachexia, a complex syndrome characterized by inflammation and weight loss. The aim of this study was to explore the association of FGF21 with cachexia in old patients compared with their healthy counterparts. Methods: Serum FGF21 and its inactivating enzyme fibroblast activation protein (FAP)-cc were measured with enzyme-linked immunoassays. Cachexia was defined as >= 5% weight loss in the previous 3 mo and concurrent anorexia (Council on Nutrition appetite questionnaire). Results: We included 103 patients with and without cachexia (76.9 +/- 5.2 y of age) and 56 healthy controls (72.9 +/- 5.9 y of age). Cachexia was present in 16.5% of patients. These patients had significantly higher total FGF21 levels than controls (952.1 +/- 821.3 versus 525.2 +/- 560.3 pg/mL; P= 0.012) and the lowest FGF21 levels (293.3 +/- 150.9 pg/mL) were found in the control group (global P < 0.001). Although FAP-alpha did not differ between the three groups (global P = 0.082), bioactive FGF21 was significantly higher in patients with cachexia (global P = 0.002). Risk factor-adjusted regression analyses revealed a significant association between cachexia and total ((beta = 649.745 pg/mL; P < 0.001) and bioactive FGF21 (beta = 393.200 pg/mL; P <0.001), independent of sex, age, and body mass index. Conclusions: Patients with cachexia exhibited the highest FGF21 levels. Clarification is needed to determine whether this is an adaptive response to nutrient deprivation in disease-related cachexia or whether the increased FGF21 values contribute to the catabolic state. (C) 2018 Elsevier Inc. All rights reserved.
Background: Several equipment interventions like optimizing seat position or optimizing shoe/insole/pedal interface are suggested to reduce overuse injury in cycling. Data analyzing clinical or biomechanical effects of those interventions is sparse. Foot orthoses out of carbon fiber are one possibility to alter the interface between foot and pedal. The aim of this study was therefore to analyze plantar pressure distribution in carbon fiber foot orthoses in comparison to standard insoles of commercially available cycling shoes. Materials and Methods: 11 pain-free triathletes (Age: 29 +/- 9, 1.77 +/- 0.04 m, 68 5 kg) were tested on a cycle ergometer at 60 and 90 rotations per minute (rpm) at workloads of 200 and 300 Watts. Subjects wore in randomized order a cycling shoe with its standard insole (control condition CO) or the shoe with carbon fiber foot orthoses (Condition CA). Mean peak pressure out of 30 movement cycles were extracted for the total foot and specific foot regions (rear, mid, fore foot (medial, central, lateral) and toe region). Three-factor ANOVAs (factor foot orthoses, rpm, workload) for repeated measures (alpha = 0.05) were used to analyze the main question of a foot orthoses effect on peak in-shoe plantar pressure. Results: Peak pressures in the total foot were in a range of 70-75 kPa for 200 Watts (W) (300 W: 85-110 kPa). The carbon fiber foot orthoses reduced peak pressures by -4,1% compared to the standard insole (p = 0,10). In the foot regions rear(-16,6%, p<0.001), mid (-20,0%, p<0.001) and fore foot (-5.9%, p < 0.03)CA reduced peak pressure compared to CO. In the toe region, peak pressure was higher in CA (+16,2%) compared to CO (p<0,001). The lateral fore foot showed higher peak pressures in CA (+34%) and CO (+59%) compared to medial and central fore foot. Conclusion: Carbon fiber can serve as a suitable material for foot orthoses manufacturing in cycling. Plantar pressures do not increase due to the stiffness of the carbon. Individual customization may have the potential to reduce peak pressure in certain foot areas.
In Germany, active bat rabies surveillance was conducted between 1993 and 2012. A total of 4546 oropharyngeal swab samples from 18 bat species were screened for the presence of EBLV-1- , EBLV-2- and BBLV-specific RNA. Overall, 0 center dot 15% of oropharyngeal swab samples tested EBLV-1 positive, with the majority originating from Eptesicus serotinus. Interestingly, out of seven RT-PCR-positive oropharyngeal swabs subjected to virus isolation, viable virus was isolated from a single serotine bat (E. serotinus). Additionally, about 1226 blood samples were tested serologically, and varying virus neutralizing antibody titres were found in at least eight different bat species. The detection of viral RNA and seroconversion in repeatedly sampled serotine bats indicates long-term circulation of the virus in a particular bat colony. The limitations of random-based active bat rabies surveillance over passive bat rabies surveillance and its possible application of targeted approaches for future research activities on bat lyssavirus dynamics and maintenance are discussed.
Inhalt:
- Hinweis auf die elektronischen Ressourcen, bereitgestellt von der Alexander von-Humboldt-Forschungsstelle der Berlin-Brandenburgischen Akademie der Wissenschaften
- Anne Jobst: „wie man die Gabe aplicirt“ : der Briefwechsel zwischen Humboldt und Ehrenberg, ein Beispiel
- Ottmar Ette: Hallar e inventar un público. Nuevos proyectos editoriales acerca de la obra de Alexander von Humboldt
- María Rosario Martí Marco: La figura del botánico Valenciano Antonio José Cavanilles en su relación científica con Humboldt y los botánicos alemanes
- Tom Müller: Roger Bacon in der Sicht Alexander von Humboldts
Ulrich Päßler: Alexander von Humboldt und die transnationale Wissenschaftskommunikation im 19. Jahrhundert
- Ursula Thiemer-Sachse: La visión de Alejandro de Humboldt de la situación social y cultural de los indígenas mexicanos contemporáneos, tal como fue reflejada en su diario de iaje y en el “Ensayo Político del Reino de la Nueva España”
- Kurt-R. Biermann/Ingo Schwarz: Warum bezeichnete sich Alexander von Humboldt als DER ALTE VOM BERGE (Vecchio della Montagna)?