Nitric oxide mediates metabolic functions in the bivalve Arctica islandica under hypoxia

The free radical nitric oxide (NO) is a powerful metabolic regulator in vertebrates and invertebrates. At cellular concentrations in the nanomolar range, and simultaneously reduced internal oxygen partial pressures (pO2), NO completely inhibits cytochrome-c-oxidase (CytOx) activity and hence mitochondrial- and whole-tissue respiration. The infaunal clam Arctica islandica regulates pO2 of hemolymph and mantle cavity water to mean values of <5 kPa, even in a completely oxygen-saturated environment of 21 kPa. These low internal pO2 values support a longer NO lifespan and NO accumulation in the body fluids and can thus trigger a depression of metabolic rate in the clams. Measurable amounts of NO formation were detected in hemocyte cells (~110 pmol NO 100−1 hemocytes h-1 at 6 kPa), which was not prevented in the presence of the NO synthase inhibitor L-NAME, and in the gill filaments of A. islandica. Adding a NO donor to intact gills and tissue homogenate significantly inhibited gill respiration and CytOx activity below 10 kPa. Meanwhile, the addition of the NO-oxidation product nitrite did not affect metabolic rates. The high nitrite levels found in the hemolymph of experimental mussels under anoxia do not indicate cellular NO production, but could be an indication of nitrate reduction by facultative anaerobic bacteria associated with tissue and/or hemolymph biofilms. Our results suggest that NO plays an important role in the initiation of metabolic depression during self-induced burrowing and shell closure of A. islandica. Furthermore, NO appears to reduce mitochondrial oxygen radical formation during surfacing and cellular reoxygenation after prolonged periods of hypoxia and anoxia

Project DECIDE, part 1: increasing the amount of valid advance directives in people with Alzheimer’s disease by offering advance care planning - a prospective double-arm intervention study

Finanziert im Rahmen der DEAL-Verträge durch die Universitätsbibliothek SiegenBackground Everybody has the right to decide whether to receive specific medical treatment or not and to provide their free, prior and informed consent to do so. As dementia progresses, people with Alzheimer’s dementia (PwAD) can lose their capacity to provide informed consent to complex medical treatment. When the capacity to consent is lost, the autonomy of the affected person can only be guaranteed when an interpretable and valid advance directive exists. Advance directives are not yet common in Germany, and their validity is often questionable. Once the dementia diagnosis has been made, it is assumed to be too late to write an advance directive. One approach used to support the completion of advance directives is ‘Respecting Choices’®—an internationally recognised, evidence-based model of Advance Care Planning (ACP), which, until now, has not been evaluated for the target group of PwAD. This study’s aims include (a) to investigate the proportion of valid advance directives in a memory clinic population of persons with suspected AD, (b) to determine the predictors of valid advance directives, and (c) to examine whether the offer of ACP can increase the proportion of valid advance directives in PwAD. Method We intend to recruit at least N = 250 participants from two memory clinics in 50 consecutive weeks. Of these, the first 25 weeks constitute the baseline phase (no offer of ACP), the following 25 weeks constitute the intervention phase (offer of ACP). The existence and validity of an advance directive will be assessed twice (before and after the memory clinic appointment). Moreover, potential predictors of valid advance directives are assessed. Discussion The results of this study will enhance the development of consent procedures for advance directives of PwAD based on the ACP/Respecting Choices (R) approach. Therefore, this project contributes towards increasing the autonomy and inclusion of PwAD and the widespread acceptance of valid advance directives in PwAD

Comparative analysis of the lambda-interferons IL-28A and IL-29 regarding their transcriptome and their antiviral properties against hepatitis C virus.

Specific differences in signaling and antiviral properties between the different Lambda-interferons, a novel group of interferons composed of IL-28A, IL-28B and IL-29, are currently unknown. This is the first study comparatively investigating the transcriptome and the antiviral properties of the Lambda-interferons IL-28A and IL-29. Expression studies were performed by microarray analysis, quantitative PCR (qPCR), reporter gene assays and immunoluminometric assays. Signaling was analyzed by Western blot. HCV replication was measured in Huh-7 cells expressing subgenomic HCV replicon. All hepatic cell lines investigated as well as primary hepatocytes expressed both IFN-λ receptor subunits IL-10R2 and IFN-λR1. Both, IL-28A and IL-29 activated STAT1 signaling. As revealed by microarray analysis, similar genes were induced by both cytokines in Huh-7 cells (IL-28A: 117 genes; IL-29: 111 genes), many of them playing a role in antiviral immunity. However, only IL-28A was able to significantly down-regulate gene expression (n = 272 down-regulated genes). Both cytokines significantly decreased HCV replication in Huh-7 cells. In comparison to liver biopsies of patients with non-viral liver disease, liver biopsies of patients with HCV showed significantly increased mRNA expression of IL-28A and IL-29. Moreover, IL-28A serum protein levels were elevated in HCV patients. In a murine model of viral hepatitis, IL-28 expression was significantly increased. IL-28A and IL-29 are up-regulated in HCV patients and are similarly effective in inducing antiviral genes and inhibiting HCV replication. In contrast to IL-29, IL-28A is a potent gene repressor. Both IFN-λs may have therapeutic potential in the treatment of chronic HCV

ECMO for COVID-19 patients in Europe and Israel

Since March 15th, 2020, 177 centres from Europe and Israel have joined the study, routinely reporting on the ECMO support they provide to COVID-19 patients. The mean annual number of cases treated with ECMO in the participating centres before the pandemic (2019) was 55. The number of COVID-19 patients has increased rapidly each week reaching 1531 treated patients as of September 14th. The greatest number of cases has been reported from France (n = 385), UK (n = 193), Germany (n = 176), Spain (n = 166), and Italy (n = 136) .The mean age of treated patients was 52.6 years (range 16–80), 79% were male. The ECMO configuration used was VV in 91% of cases, VA in 5% and other in 4%. The mean PaO2 before ECMO implantation was 65 mmHg. The mean duration of ECMO support thus far has been 18 days and the mean ICU length of stay of these patients was 33 days. As of the 14th September, overall 841 patients have been weaned from ECMO support, 601 died during ECMO support, 71 died after withdrawal of ECMO, 79 are still receiving ECMO support and for 10 patients status n.a. . Our preliminary data suggest that patients placed on ECMO with severe refractory respiratory or cardiac failure secondary to COVID-19 have a reasonable (55%) chance of survival. Further extensive data analysis is expected to provide invaluable information on the demographics, severity of illness, indications and different ECMO management strategies in these patients

Large-Scale Recombinant Production of the SARS-CoV-2 Proteome for High-Throughput and Structural Biology Applications

The highly infectious disease COVID-19 caused by the Betacoronavirus SARS-CoV-2 poses a severe threat to humanity and demands the redirection of scientific efforts and criteria to organized research projects. The international COVID19-NMR consortium seeks to provide such new approaches by gathering scientific expertise worldwide. In particular, making available viral proteins and RNAs will pave the way to understanding the SARS-CoV-2 molecular components in detail. The research in COVID19-NMR and the resources provided through the consortium are fully disclosed to accelerate access and exploitation. NMR investigations of the viral molecular components are designated to provide the essential basis for further work, including macromolecular interaction studies and high-throughput drug screening. Here, we present the extensive catalog of a holistic SARS-CoV-2 protein preparation approach based on the consortium’s collective efforts. We provide protocols for the large-scale production of more than 80% of all SARS-CoV-2 proteins or essential parts of them. Several of the proteins were produced in more than one laboratory, demonstrating the high interoperability between NMR groups worldwide. For the majority of proteins, we can produce isotope-labeled samples of HSQC-grade. Together with several NMR chemical shift assignments made publicly available on covid19-nmr.com, we here provide highly valuable resources for the production of SARS-CoV-2 proteins in isotope-labeled form

Einfluss von Mycophenolatmofetil auf die Pilokarpin-induzierte Epileptogenese im Mausmodell

Zielstellung der Arbeit war es, die Rolle, die Immunzell-vermittelten Prozesse im ZNS und die Unterschiede zwischen epileptischen Tieren und Tieren der Kontroll-Gruppe zu zeigen. Die Erkenntnisse zeigen, dass im ZNS epileptischer Mäuse nach erfolgter Pilokarpin-Injektion mehr CD3+T-Zellen vorhanden sind, was durch einen Anstieg der CD8+ T-Zellen begründet ist. Durch die immunmodulatorische Intervention mit Mycophenolatmofetil konnte die Antwort des Immunsystems beeinflusst werden. Durch MMF wird die T-Zell-Gensonde Cd3g gesenkt, was den immunsuppressiven Effekt des Medikaments zeigt

Age dependent patterns of antioxidants in Arctica islandica from six regionally separate populations with different life spans

We compared six biogeographically and climatically distinct population of extremely long-lived ocean quahog Arctica islandica, for age-dependent differences in metabolic rates and antioxidant capacities (superoxide dismutase, catalase activity and total glutathione concentration). Different geographic locations, covering a temperature and salinity gradient of 3.7–9.3 °C and 20–35 ppt from the Norwegian coast, White Sea, Iceland, Kattegat, Kiel Bay and German Bight. The bivalve shells were used as age recorders by counting annual growth bands. Maximum lifespan in different populations varied between 30 and 192 y. The exceptionally long lifespan of A. islandica cannot be exclusively explained by a better-established antioxidant defense system. Extreme longevity observed in some North Atlantic populations seems to be grounded in its very low lifetime mass specific respiration, in combination with stable maintenance of antioxidant protection over life in mature specimens. The shorter-lived populations have the highest metabolic rates and show no metabolic response (Q10) when warmed to higher temperature. Low and fluctuating salinity in Baltic exerts a stress, which enhances respiration rates and shortens longevity

Mitochondrial respiration and aging: Marine bivalves as model organisms for aging research

Bivalves show age rings like trees, thus in contrast to other model organisms for ageing like rats or fruit flies which have to be reared in the laboratory to know the age, we can investigate the natural aging process as we can determine the age of each bivalve we catch from the wild. Mitochondria are supposed to play a major role in the aging process as they supply energy for maintenance and repair but also produce reactive oxygen (ROS) species which can lead to damage and disturbance of cellular structures and processes. We measured mitochondrial respiration and ROS generation in mitochondria as well as antioxidant capacities and oxidative tissue damage of various bivalve species with different maximum life spans and of different lifestyle (burrowing-swimming). The results show a decrease of mitochondrial respiration with age in all investigated species. The magnitude of the decrease generally correlated with the amount of generated ROS but not always with the lifespan of the different species. The results implicate that different lifestyles lead to mitochondrial adaptations which alter mitochondrial ROS generation. Factors influencing the aging process leading to different maximum life spans are discussed