Das Problem der Biopiraterie

Aufgrund der raschen Entwicklung der Biotechnologie haben genetische Res­sourcen in Industrie und Politik an Aufmerksamkeit gewonnen. Im Mittelpunkt einer kontroversen Diskussion stehen Regelungen bezüglich des Zugangs zu ge­netischen Ressourcen und der Beteiligung ihrer Bereitsteller an den Vorteilen, die ihre Nutzung bringt. Die beiden hierfür relevanten internationalen Abkom­men, die Biodiversitätskonvention und das Abkommen über handelsrelevante geistige Eigentumsrechte, stehen in einem Spannungsverhältnis, in dem derzeit der Handel die Oberhand inne hat

Genetische Ressourcen: Biodiversitätskonvention und TRIPS-Abkommen

"In dieser Analyse wird die Bedeutung genetischer Ressourcen im Übereinkommen über biologische Vielfalt von 1992 (Biodiversitätskonvention) und im Übereinkommen über handelsbezogene Rechte des geistigen Eigentums von 1995 (TRIPS-Abkommen) untersucht. Diese beiden internationalen Regelwerke, so die zentrale These der Autorin, lösen den Konflikt um genetische Ressourcen nicht, sie tragen vielmehr zu dessen Verstärkung bei. Deshalb wird eine mögliche zukünftige Vorgehensweise entwickelt, die versucht, die Interessenlagen der Beteiligten besser zu berücksichtigen, um so zu einer Lösung der Konflikte um genetische Ressourcen beizutragen." (Autorenreferat

CheckAge - Screening-Verfahren für die Bewertung alter(n)sgerechter Arbeitsplätze

Der CheckAge „Alter(n)sgerechte Arbeitsplätze“ ist ein Screening-Verfahren, das es ermöglicht, altersSPEZIFISCHE Potentiale und Handlungsbedarf zur alter(n)s-gerechten Arbeitsgestaltung im Unternehmen aufzudecken. Er dient als Orientierungshilfe und kann von Personen mit ergonomischen Grundkenntnissen durchgeführt werden. CheckAge eignet sich für Arbeitsplätze, vorwiegend im produktionsnahen Bereich, bei denen Belastungen durch Körperhaltung, Aktionskräfte, Lastenhandhabung und repetitive Tätigkeiten auftreten. Der Mehrwert des CheckAge „Alter(n)sgerechte Arbeitsplätze“ besteht in der Möglichkeit, neben einer altersNEUTRALEN Bewertung  auch altersSPEZIFISCHE Faktoren zu berücksichtigen. Der CheckAge besteht aus dem Bewertungsbogen (zwei A4 Seiten) und dem Maßnahmenblatt zum Maßnahmencontrolling. Vorliegender aw&I Report unterstützt die Anwendung mit Erläuterungen zu altersbedingten Fähigkeitsänderungen, Bewertungshilfen und Vorschlägen für Verbesserungsmaßnahmen

The Human Blood Transcriptome in a Large Population Cohort and Its Relation to Aging and Health

Background: The blood transcriptome is expected to provide a detailed picture of an organism’s physiological state with potential outcomes for applications in medical diagnostics and molecular and epidemiological research.We here present the analysis of blood specimens of 3,388 adult individuals, together with phenotype characteristics such as disease history, medication status, lifestyle factors, and body mass index (BMI). The size and heterogeneity of this data challenges analytics in terms of dimension reduction, knowledge mining, feature extraction, and data integration. Methods: Self-organizing maps (SOM)-machine learning was applied to study transcriptional states on a population-wide scale. This method permits a detailed description and visualization of the molecular heterogeneity of transcriptomes and of their association with different phenotypic features. Results: The diversity of transcriptomes is described by personalized SOM-portraits, which specify the samples in terms of modules of co-expressed genes of different functional context. We identified two major blood transcriptome types where type 1 was found more in men, the elderly, and overweight people and it upregulated genes associated with inflammation and increased heme metabolism, while type 2 was predominantly found in women, younger, and normal weight participants and it was associated with activated immune responses, transcriptional, ribosomal, mitochondrial, and telomere-maintenance cell-functions. We find a striking overlap of signatures shared by multiple diseases, aging, and obesity driven by an underlying common pattern, which was associated with the immune response and the increase of inflammatory processes. Conclusions: Machine learning applications for large and heterogeneous omics data provide a holistic view on the diversity of the human blood transcriptome. It provides a tool for comparative analyses of transcriptional signatures and of associated phenotypes in population studies and medical applications

Relationship between determinants of arterial stiffness assessed by diastolic and suprasystolic pulse oscillometry: comparison of vicorder and vascular explorer

Pulse wave velocity (PWV) and augmentation index (AI) are independent predictors of cardiovascular health. However, the comparability of multiple oscillometric modalities currently available for their assessment was not studied in detail. In the present study, we aimed to evaluate the relationship between indices of arterial stiffness assessed by diastolic and suprasystolic oscillometry. In total, 56 volunteers from the general population (23 males; median age 70 years [interquartile range: 65–72 years]) were recruited into observational feasibility study to evaluate the carotid-femoral/aortic PWV (cf/aoPWV), brachial-ankle PWV (baPWV), and AI assessed by 2 devices: Vicorder (VI) applying diastolic, right-sided oscillometry for the determination of all 3 indices, and Vascular explorer (VE) implementing single-point, suprasystolic brachial oscillometry (SSBO) pulse wave analysis for the assessment of cfPWV and AI. Within- and between-device correlations of measured parameters were analyzed. Furthermore, agreement of repeated measurements, intra- and inter-observer concordances were determined and compared for both devices. In VI, both baPWVand cfPWVinter-correlatedwell and showed good level of agreement with bilateral baPWVmeasured byVE (baPWV[VI]– baPWV[VE]R: overall concordance correlation coefficient [OCCC]¼0.484, mean difference¼1.94 m/s; cfPWV[VI]–baPWV[- VE]R: OCCC¼0.493, mean difference¼1.0m/s). In contrast, SSBO derived aortic PWA (cf/aoPWA[VE]) displayed only weak correlation with cfPWV(VI) (r¼0.196; P¼0.04) and ipsilateral baPWV (cf/ aoPWV[VE]R–baPWV[VE]R: r¼0.166; P¼0.08). cf/aoPWA(VE) correlated strongly with AI(VE) (right-sided: r¼0.725, P 0.9 for 2-point-PWV modes and right-sided AI(VE). Intra- and inter-observer concordances were similarly high except for AI yielding a trend toward better reproducibility in VE (interobserver–OCCC[VI] vs [VE]¼0.774 vs 0.844; intraobserver OCCC[VI] vs [VE]¼0.613 vs 0.769). Both diastolic oscillometry-derived PWV modes, and AI measured either with VI or VE, are comparable and reliable alternatives for the assessment of arterial stiffness. Aortic PWV assessed by SSBO in VE is not related to the corresponding indices determined by traditional diastolic oscillometry

Revisited Upper Reference Limits for Highly Sensitive Cardiac Troponin T in Relation to Age, Sex, and Renal Function

(1) Background: Highly sensitive cardiac troponin T (hs-cTnT) plays an essential role in the diagnosis of myocardial injury. The upper reference limit of the respective assay is generally applied, irrespective of age, renal function, or sex. We aimed to identify age-adjusted and sex-adjusted upper reference limits in relation to renal function in a large population-based cohort without cardiac diseases. (2) Methods: We included 5428 subjects of the population-based LIFE-Adult cohort, free of diagnosed cardiac diseases. Sex-adjusted and age-adjusted 99th percentiles for hs-cTnT in subjects with preserved renal function were obtained. (3) Results: The hs-cTnT values were higher in men of all age groups. In both sexes, an increasing age positively correlated with higher hs-cTnT values. Hs-cTnT weakly correlated with serum creatinine. The three-dimensional analysis of age, creatinine, and hs-cTnT showed no relevant additional effect of creatinine on hs-cTnT. In men aged above 60 and women above 70, the calculated 99th percentiles clearly exceeded the commonly applied thresholds. (4) Conclusion: Age and sex have a major impact on the serum concentration of hs-cTnT, while renal function does not. We propose to consider age-adjusted and sex-adjusted reference values

Osteocytes Serve as a Reservoir for Intracellular Persisting Staphylococcus aureus Due to the Lack of Defense Mechanisms

Chronic staphylococcal osteomyelitis can persist for long time periods causing bone destruction. The ability of Staphylococcus aureus to develop chronic infections is linked to its capacity to invade and replicate within osteoblasts and osteocytes and to switch to a dormant phenotype called small colony variants. Recently, osteocytes were described as a main reservoir for this pathogen in bone tissue. However, the mechanisms involved in the persistence of S. aureus within these cells are still unknown. Here, we investigated the interaction between S. aureus and osteoblasts or osteocytes during infection. While osteoblasts are able to induce a strong antimicrobial response and eliminate intracellular S. aureus , osteocytes trigger signals to recruit immune cells and enhance inflammation but fail an efficient antimicrobial activity to clear the bacterial infection. Moreover, we found that extracellular signals from osteocytes enhance intracellular bacterial clearance by osteoblasts. Even though both cell types express Toll-like receptor (TLR) 2, the main TLR responsible for S. aureus detection, only osteoblasts were able to increase TLR2 expression after infection. Additionally, proteomic analysis indicates that reduced intracellular bacterial killing activity in osteocytes is related to low antimicrobial peptide expression. Nevertheless, high levels of lipid mediators and cytokines were secreted by osteocytes, suggesting that they can contribute to inflammation. Taken together, our results demonstrate that osteocytes contribute to severe inflammation observed in osteomyelitis and represent the main niche for S. aureus persistence due to their poor capacity for intracellular antimicrobial response

Interleukin-6-dependent survival of multiple myeloma cells involves the Stat3-mediated induction of micro-RNA-21 through a highly conserved enhancer

Signal transducer and activator of transcription 3 (Stat3) is implicated in the pathogenesis of many malignancies and essential for IL-6–dependent survival and growth of multiple myeloma cells. Here, we demonstrate that the gene encoding oncogenic microRNA-21 (miR-21) is controlled by an upstream enhancer containing 2 Stat3 binding sites strictly conserved since the first observed evolutionary appearance of miR-21 and Stat3. MiR-21 induction by IL-6 was strictly Stat3 dependent. Ectopically raising miR-21 expression in myeloma cells in the absence of IL-6 significantly reduced their apoptosis levels. These data provide strong evidence that miR-21 induction contributes to the oncogenic potential of Stat3

Simultaneous Mass Spectrometry-Based Apolipoprotein Profiling and Apolipoprotein E Phenotyping in Patients with ASCVD and Mild Cognitive Impairment

Apolipoprotein E (apoE) occurs on the majority of plasma lipoproteins and plays a major role in the lipid metabolism in the periphery and in the central nervous system. ApoE is a polymorphic protein with three common isoforms, apoE2, apoE3 and apoE4, derived from respective alleles '2, '3 and '4. The aim of this study was to develop a sample pretreatment protocol combined with rapid mass spectrometry (MS)-based assay for simultaneous apolipoprotein profiling and apoE phenotype identification. This assay was validated in 481 samples from patients with stable atherosclerotic cardiovascular disease (ASCVD) and applied to study association with mild cognitive impairment (MCI) in the LIFE Adult study, including overall 690 study subjects. Simultaneous quantification of 8–12 major apolipoproteins including apoA-I, apoB-100 and apoE could be performed within 6.5 min. Phenotyping determined with the developed MS assay had good agreement with the genotyping by real-time fluorescence PCR (97.5%). ApoE2 isoform was associated with the highest total apoE concentration compared to apoE3 and apoE4 (p < 0.001). In the subgroup of diabetic atherosclerotic cardiovascular disease (ASCVD) patients, apoE2 isoform was related to higher apoC-I levels (apoE2 vs. apoE3, p < 0.05), while in the subgroup of ASCVD patients under statin therapy apoE2 was related to lower apoB-100 levels (apoE2 vs. apoE3/apoE4, p < 0.05). A significant difference in apoE concentration observed between mild cognitive impairment (MCI) subjects and controls was confirmed for each apoE phenotype. In conclusion, this study provides evidence for the successful implementation of an MS-based apoE phenotyping assay, which can be used to assess phenotype effects on plasma lipid and apolipoprotein levels

COVID-19 patients share common, corticosteroid-independent features of impaired host immunity to pathogenic molds

Patients suffering from coronavirus disease-2019 (COVID-19) are susceptible to deadly secondary fungal infections such as COVID-19-associated pulmonary aspergillosis and COVID-19-associated mucormycosis. Despite this clinical observation, direct experimental evidence for severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2)-driven alterations of antifungal immunity is scarce. Using an ex-vivo whole blood stimulation assay, we challenged blood from twelve COVID-19 patients with Aspergillus fumigatus and Rhizopus arrhizus antigens and studied the expression of activation, maturation, and exhaustion markers, as well as cytokine secretion. Compared to healthy controls, T-helper cells from COVID-19 patients displayed increased expression levels of the exhaustion marker PD-1 and weakened A. fumigatus - and R. arrhizus -induced activation. While baseline secretion of proinflammatory cytokines was massively elevated, whole blood from COVID-19 patients elicited diminished release of T-cellular (e.g., IFN-γ, IL-2) and innate immune cell-derived (e.g., CXCL9, CXCL10) cytokines in response to A. fumigatus and R. arrhizus antigens. Additionally, samples from COVID-19 patients showed deficient granulocyte activation by mold antigens and reduced fungal killing capacity of neutrophils. These features of weakened anti-mold immune responses were largely decoupled from COVID-19 severity, the time elapsed since diagnosis of COVID-19, and recent corticosteroid uptake, suggesting that impaired anti-mold defense is a common denominator of the underlying SARS-CoV-2 infection. Taken together, these results expand our understanding of the immune predisposition to post-viral mold infections and could inform future studies of immunotherapeutic strategies to prevent and treat fungal superinfections in COVID-19 patients