Ginkgo Biloba Extract Ameliorates Oxidative Phosphorylation Performance and Rescues Aβ-Induced Failure

Energy deficiency and mitochondrial failure have been recognized as a prominent, early event in Alzheimer's disease (AD). Recently, we demonstrated that chronic exposure to amyloid-beta (Abeta) in human neuroblastoma cells over-expressing human wild-type amyloid precursor protein (APP) resulted in (i) activity changes of complexes III and IV of the oxidative phosphorylation system (OXPHOS) and in (ii) a drop of ATP levels which may finally instigate loss of synapses and neuronal cell death in AD. Therefore, the aim of the present study was to investigate whether standardized Ginkgo biloba extract LI 1370 (GBE) is able to rescue Abeta-induced defects in energy metabolism

Stroke genetics informs drug discovery and risk prediction across ancestries

Previous genome-wide association studies (GWASs) of stroke — the second leading cause of death worldwide — were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis3, and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach4, we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry5. Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries

Wildnis als Thema einer Bildung für nachhaltige Entwicklung – Wildnisbezogene Dimensionen des Leitbildes der nachhaltigen Entwicklung und Analyse von Curricula verschiedener Bildungsbereiche am Beispiel des Landes Sachsen-Anhalt

Das 21. Jahrhundert stellt die Menschheit vor große globale Herausforderungen wie Klimawandel, Bevölkerungswachstum, Bodendegradation und Verlust von Biodiversität. Einen wichtigen Beitrag zur Lösung dieser Herausforderungen kann Bildung für nachhaltige Entwicklung (BNE) leisten. Anne-Kathrin Lindau, Fabian Mohs, Alma Reinboth und Martin Lindner stellen Wildnisbildung als ein mögliches Konzept zur Umsetzung von BNE vor. Hierbei werden Lernende über das Erleben von wilder beziehungsweise verwildernder Natur zum Verstehen komplexer Systemzusammenhänge befähigt - um auf dieser Basis Nachhaltigkeitsfragen kritisch zu reflektieren und zu einem nachhaltigeren Handeln angeregt zu werden. Im ersten Teil des Buches werden theoretische Perspektiven (z. B. Wildnis als sozio-ökologisches System oder die Anknüpfungsfähigkeit von Wildnisbildung an eine BNE) vorgestellt, während der zweite Teil eher bildungsbezogene Forschungsergebnisse in Bezug auf Wildnis in den Blick nimmt. Der dritte Teil ist den Ergebnissen des von der Deutschen Bundesstiftung Umwelt (DBU) geförderten Projektes »Wilde Nachbarschaft - Entwicklung, Erprobung und Evaluierung eines Konzeptes zur Wildnisbildung für Vorschule, Schule und Hochschule« gewidmet, in dessen Rahmen die Publikation entstanden ist. In allen drei Teilbereichen werden die Potenziale der Wildnisbildung außerhalb der bisher stark fokussierten Großschutzgebiete aufgezeigt

Cardiac troponin I: a valuable biomarker indicating the cardiac involvement in fabry disease

Objectives: Assessment of the clinical severity of Fabry disease (FD), an X-linked, rare, progressive disorder based on a genetic defect in alpha-galactosidase is challenging, especially regarding cardiac involvement. The aim of the study was to evaluate the diagnostic value of cardiac troponin I (cTnI) in discriminating FD patients with cardiac involvement in a large FD patient cohort. Methods: cTnI levels were measured with a contemporary sensitive assay in plasma samples taken routinely from FD patients. The assay was calibrated to measure cTnI levels ≥0.01 ng/ml. Elevated cTnI values (cut-off ≥0.04 ng/ml) were correlated with clinical data. Results: cTnI was assessed in 62 FD patients (median age: 47 years, males: 36%). Elevated cTnI levels were detected in 23 (37%) patients. Patients with a cTnI elevation were older (median 55 years versus 36 years, p<0.001). Elevated cTnI levels were associated with the presence of a LVH (16/23 versus 1/39; OR 65.81, CI: 6.747–641.859; p<0.001). In almost all patients with a left ventricular hypertrophy (LVH) elevated cTnI levels were detected (16/17, 94%). Absolute cTnI levels in patients with LVH were higher than in those without (median 0.23 ng/ml versus 0.02 ng/ml; p<0.001). A cTnI level <0.04ng/ml had a high negative predictive value regarding the presence of a LVH (38/39, 97%). In a control group of non-FD patients (n = 17) with LVH (due to hypertension) none showed cTnI levels ≥0.01 ng/ml. Conclusions: Elevated cTnI levels are common in FD patients, reflecting cardiac involvement. FD patients might benefit from a continuous cTnI monitoring

Comparison of cardiac troponin I levels.

<p>Presented are patients with Fabry disease (FD) and left ventricular hypertrophy (LVH) (n = 17) versus FD patients without LVH (n = 18) and non-FD patients with LVH of other cause (n = 17). The cut-off level for cTnI in diagnosing myocardial infarction (≥0.04 ng/ml) is indicated in the figure.</p

Patients with Fabry disease: comparison of patients with cTnI elevation ≥0.04 ng/ml versus without.

<p>Patients with Fabry disease: comparison of patients with cTnI elevation ≥0.04 ng/ml versus without.</p

Multiple logistic regression analysis for elevated cardiac troponin (cut-off ≥0.04 ng/ml) patients with Fabry disease (n = 62).

<p>Multiple logistic regression analysis for elevated cardiac troponin (cut-off ≥0.04 ng/ml) patients with Fabry disease (n = 62).</p