The Mitochondrion as Potential Interface in Early-Life Stress Brain Programming

Mitochondria play a central role in cellular energy-generating processes and are master regulators of cell life. They provide the energy necessary to reinstate and sustain homeostasis in response to stress, and to launch energy intensive adaptation programs to ensure an organism’s survival and future well-being. By this means, mitochondria are particularly apt to mediate brain programming by early-life stress (ELS) and to serve at the same time as subcellular substrate in the programming process. With a focus on mitochondria’s integrated role in metabolism, steroidogenesis and oxidative stress, we review current findings on altered mitochondrial function in the brain, the placenta and peripheral blood cells following ELS-dependent programming in rodents and recent insights from humans exposed to early life adversity (ELA). Concluding, we propose a role of the mitochondrion as subcellular intersection point connecting ELS, brain programming and mental well-being, and a role as a potential site for therapeutic interventions in individuals exposed to severe ELS

Methode und Ergebnis einer Gliederung des Landes Sachsen- Anhalt in hydrologische Regionen

In Fortsetzung vorangegangener, naturräumlicher Gliederungen des Landes-Sachsen-Anhalts wird mit dem objektiven Verfahren einer multivariaten Clusteranalyse eine Unterteilung des Bundeslandes in hydrologische Regionen vorgenommen. Basis der Unterteilung sind die Oberflächenwasserkörper entsprechend EU-Wasserrahmenrichtlinie und modellierte Komponenten des Wasserhaushaltes. Neben einer kurzen Erläuterung des Prinzips der Clusteranalyse wird die Vorgehensweise und Parameterwahl zur Erzeugung der Gliederung dargestellt. Einer anschließenden Betrachtung der Güte des Verfahrens folgt eine Auswertung nach Abflussregimen, die aus gemessenen Abflusszeitreihen der Pegel in den Regionen berechnet wurden. Nicht zuletzt werden die signifikanten Haupteigenschaften des Wasserhaushaltes für die hydrologischen Regionen übersichtlich beschrieben und verglichen.In continuation of former geographical classifications of the natural landscapes of Saxony-Anhalt a multivariate cluster analysis was performed as an objective method for the classification of the federal state into hydrological regions. The surface water bodies specified in the European Water Framework Directive and their modeled components of water balance were the basis of this division. The approach and parameter choice for the hydrological classification and a short explanation of the principles of the cluster analysis are given. Furthermore, the quality of the procedure was validated and runoff regimes were calculated from measured runoff time series of the gauging stations in the regions. Finally, significant main properties of the water balance are described clearly andcompared to the hydrological regions

Methylation at the CpG island shore region upregulates Nr3c1 promoter activity after early-life stress

Early-life stress (ELS) induces long-lasting changes in gene expression conferring an increased risk for the development of stress-related mental disorders. Glucocorticoid receptors (GR) mediate the negative feedback actions of glucocorticoids (GC) in the paraventricular nucleus (PVN) of the hypothalamus and anterior pituitary and therefore play a key role in the regulation of the hypothalamic-pituitary-adrenal (HPA) axis and the endocrine response to stress. We here show that ELS programs the expression of the GR gene (Nr3c1) by site-specific hypermethylation at the CpG island (CGI) shore in hypothalamic neurons that produce corticotropin-releasing hormone (Crh), thus preventing Crh upregulation under conditions of chronic stress. CpGs mapping to the Nr3c1 CGI shore region are dynamically regulated by ELS and underpin methylation-sensitive control of this region's insulation-like function via Ying Yang 1 (YY1) binding. Our results provide new insight into how a genomic element integrates experience-dependent epigenetic programming of the composite proximal Nr3c1 promoter, and assigns an insulating role to the CGI shore.European Union Directorate General for Research & Innovation through the CRESCENDO Consortium (O.F.X.A. and D.S) and the NINA Initial Training Program (D.S. and O.F.X.A

Aberrant phase separation of FUS leads to lysosome sequestering and acidification

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that leads to the death of upper and lower motor neurons. While most cases of ALS are sporadic, some of the familial forms of the disease are caused by mutations in the gene encoding for the RNA-binding protein FUS. Under physiological conditions, FUS readily phase separates into liquid-like droplets in vivo and in vitro. ALS-associated mutations interfere with this process and often result in solid-like aggregates rather than fluid condensates. Yet, whether cells recognize and triage aberrant condensates remains poorly understood, posing a major barrier to the development of novel ALS treatments. Using a combination of ALS-associated FUS mutations, optogenetic manipulation of FUS condensation, chemically induced stress, and pH-sensitive reporters of organelle acidity, we systematically characterized the cause-effect relationship between the material state of FUS condensates and the sequestering of lysosomes. From our data, we can derive three conclusions. First, regardless of whether we use wild-type or mutant FUS, expression levels (i.e., high concentrations) play a dominant role in determining the fraction of cells having soluble or aggregated FUS. Second, chemically induced FUS aggregates recruit LAMP1-positive structures. Third, mature, acidic lysosomes accumulate only at FUS aggregates but not at liquid-condensates. Together, our data suggest that lysosome-degradation machinery actively distinguishes between fluid and solid condensates. Unraveling these aberrant interactions and testing strategies to manipulate the autophagosome-lysosome axis provides valuable clues for disease intervention

Seaweed-based Packaging Solutions

Introduction The use of single-use packaging materials has increased dramatically in recent decades in parallel with increasing trends in convenience and fast-food. Most of these packaging materials are made of non-biodegradable, petroleum-based polymers that have degradative impacts on the environment and contribute to the global plastic pollution crisis. Finding alternative packaging materials is an important step towards building a bio-based circular economy. Sustainable land-based macroalgae cultivation can provide a solution, as it eliminates land-use pressure on coastal areas, doesn’t interfere with recreational activities or agriculture, reduces seasonal limitations, allows for complete control over product quality, and ensures consistent quality and traceability. Here, we present the success story of land-based macroalgae production for sustainable packaging solutions in the food industry via the Mak-Pak and Mak-Pak Scale-Up projects. Materials and Methods An initial screening of local macroalgae species was conducted based on detailed knowledge of growth rates, seasonality, geographic range, edibility, iodine content, biochemical properties, bioactivity, robustness and ease of cultivation. Different combinations of selected macroalgae were tested to develop a biodegradable, edible packaging prototype that was rated by consumer tests. In a follow-up project, we are focusing on eliminating the biggest bottleneck: scaling-up biomass production. We have partnered with a local, innovative farmer to sustainably scale-up and optimize biomass production for our sustainable, biodegradable macroalgae-based packaging material for the food industry. Results Several species of suitable macroalgae were selected based on the screening protocol and a method for using different combinations of selected species is described in a patent application for the packaging prototype. The packaging prototype was positively reviewed in consumer tests, where the consumers were pleasantly surprised by the neutral taste and smell. We could also show that certain components of the macroalgae that are important for packaging functionality (e.g. antioxidant activity) could be optimized during land-based production in artificial seawater. Currently we are in the early stages of scaling-up production and selecting strains to optimize growth rates and robustness, where we can complete the life cycle of one selected species from single cells to mature gametophytes within 6 weeks. With controlled induction of reproduction, we can continually provide material for transplantation to large-scale systems. Discussion The Mak-Pak and Mak-Pak Scale-Up projects have been featured in numerous news articles, exhibitions, and podcasts throughout Germany, Europe and even New Zealand. Our experience has shown that there is a lot of public interest in macroalgae-based packaging solutions. Consumers have become aware of the plastic pollution crisis and are open to alternatives to plastic packaging. Consequently, we have recently seen rapid changes in packaging trends in the cosmetic and food industries. Here we show that it is possible to produce a biodegradable, edible packaging from macroalgae biomass for the food-industry. Not only is this a success story for sustainable aquaculture, but also for macroalgae cultivation in general. This project has increased public awareness of macroalgae and contributed to a dialogue about the diversity of products and services that macroalgae can provide as we strive towards a sustainable, circular economy. However, optimization of the raw material production as well as the packaging itself is still underway. Furthermore, limitations in the food-industry require that our raw material meets high quality standards. In other industries where the quality of the raw material is not a limiting factor, there is enormous potential for macroalgae-based packaging solutions

Long-term decoding of movement force and direction with a wireless myoelectric implant

Objective. The ease of use and number of degrees of freedom of current myoelectric hand prostheses is limited by the information content and reliability of the surface electromyography (sEMG) signals used to control them. For example, cross-talk limits the capacity to pick up signals from small or deep muscles, such as the forearm muscles for distal arm amputations, or sites of targeted muscle reinnervation (TMR) for proximal amputations. Here we test if signals recorded from the fully implanted, induction-powered wireless Myoplant system allow long-term decoding of continuous as well as discrete movement parameters with better reliability than equivalent sEMG recordings. The Myoplant system uses a centralized implant to transmit broadband EMG activity from four distributed bipolar epimysial electrodes. Approach. Two Rhesus macaques received implants in their backs, while electrodes were placed in their upper arm. One of the monkeys was trained to do a cursor task via a haptic robot, allowing us to control the forces exerted by the animal during arm movements. The second animal was trained to perform a center-out reaching task on a touchscreen. We compared the implanted system with concurrent sEMG recordings by evaluating our ability to decode time-varying force in one animal and discrete reach directions in the other from multiple features extracted from the raw EMG signals. Main results. In both cases, data from the implant allowed a decoder trained with data from a single day to maintain an accurate decoding performance during the following months, which was not the case for concurrent surface EMG recordings conducted simultaneously over the same muscles. Significance. These results show that a fully implantable, centralized wireless EMG system is particularly suited for long-term stable decoding of dynamic movements in demanding applications such as advanced forelimb prosthetics in a wide range of configurations (distal amputations, TMR).German Federal Ministry for Education and Reseach (BMBF) grant No, 16SV3695, 16SV3699, 16SV3697 and 01GQ1005C, DFG Deutsche Forschungsgemeinschaft grant No. GA1475-C

Percutaneous dilatational tracheotomy in high-risk ICU patients

BACKGROUND Percutaneous dilatational tracheotomy (PDT) has become an established procedure in intensive care units (ICU). However, the safety of this method has been under debate given the growing number of critically ill patients with high bleeding risk receiving anticoagulation, dual antiplatelet therapy (DAPT) or even a combination of both, i.e. triple therapy. Therefore, the purpose of this study, including such a high proportion of patients on antithrombotic therapy, was to investigate whether PDT in high-risk ICU patients is associated with elevated procedural complications and to analyse the risk factors for bleeding occurring during and after PDT. METHODS PDT interventions conducted in ICUs at 12 European sites between January 2016 and October 2019 were retrospectively analysed for procedural complications. For subgroup analyses, patient stratification into clinically relevant risk groups based on anticoagulation and antiplatelet treatment regimens was performed and the predictors of bleeding occurrence were analysed. RESULTS In total, 671 patients receiving PDT were included and stratified into four clinically relevant antithrombotic treatment groups: (1) intravenous unfractionated heparin (iUFH, prophylactic dosage) (n = 101); (2) iUFH (therapeutic dosage) (n = 131); (3) antiplatelet therapy (aspirin and/or P2Y12 receptor inhibitor) with iUFH (prophylactic or therapeutic dosage) except for triple therapy (n = 290) and (4) triple therapy (DAPT with iUFH in therapeutic dosage) (n = 149). Within the whole cohort, 74 (11%) bleedings were reported to be procedure-related. Bleeding occurrence during and after PDT was independently associated with low platelet count (OR 0.73, 95% CI 0.56, 0.92, p = 0.009), chronic kidney disease (OR 1.75, 95{\%} CI 1.01, 3.03, p = 0.047) and previous stroke (OR 2.13, 95{\%} CI 1.1, 3.97, p = 0.02). CONCLUSION In this international, multicenter study bronchoscopy-guided PDT was a safe and low-complication airway management option, even in a cohort of high risk for bleeding on cardiovascular ICUs. Low platelet count, chronic kidney disease and previous stroke were identified as independent risk factors of bleeding during and after PDT but not triple therapy

Nachhaltigen Verpackungslösung aus Makroalgen für den Lebensmittel-Handel

Haben Sie schon einmal darüber nachgedacht, dass Meeresalgen eine Lösung für die weltweite Plastikverschmutzungskrise bieten könnten? Die Verwendung von Einweg-Verpackungsmaterialien hat in den letzten Jahrzehnten parallel zu den zunehmenden Trends in Sachen Convenience und Fast-Food dramatisch zugenommen. Die meisten dieser Verpackungsmaterialien bestehen aus biologisch nicht abbaubaren, erdölbasierten Polymeren, die sich negativ auf die Umwelt auswirken und zur globalen Plastikverschmutzungskrise beitragen. Die Plastikverschmutzung in den Ozeanen zerstört die Ökosysteme und bedroht in der Folge unsere eigene Gesundheit, die Lebensmittelsicherheit und den Küstentourismus. Die Suche nach alternativen Verpackungsmaterialien ist ein wichtiger Schritt zum Aufbau einer biobasierten Kreislaufwirtschaft und zum Erreichen unserer Nachhaltigkeitsziele. Unsere Ozeane könnten eine Lösung in Form von Makroalgen bieten. Das Mak-Pak Scale-Up Projekt konzentriert sich auf die Skalierung und Optimierung der Produktion von Meeresalgen, um nachhaltiges, biologisch abbaubares und/oder essbares Verpackungsmaterial auf Makroalgenbasis für die Fast-Food-Industrie zu schaffen, das potenziell Einweg-Plastikverpackungen ersetzen könnte. Dieser Vortrag stellt das Mak-Pak Scale-Up Projekt vor, einschließlich des Hintergrunds, der wichtigsten Errungenschaften, der aktuellen Aktivitäten und der Zukunftspläne im Rahmen der UN-Nachhaltigkeitsziele und der Kreislaufwirtschaft