Microbiology managers: managerial training in the RItrain project

Leaders of research infrastructures (RIs) in Europe who are scientists require competencies in management. RItrain has addressed this issue by identifying skills required, locating relevant courses and finding gaps, whilst establishing a Master of Management programme. We describe how one contributing microbiology RI determined the most relevant skills.The RItrain project is funded by the European Commission, grant agreement number 654156.info:eu-repo/semantics/publishedVersio

Bayesian estimation of physical and geometrical parameters for nanocapacitor array biosensors

8siMassively parallel nanosensor arrays fabricated with low-cost CMOS technology represent powerful platforms for biosensing in the Internet-of-Things (IoT) and Internet-of-Health (IoH) era. They can efficiently acquire “big data” sets of dependable calibrated measure-ments, representing a solid basis for statistical analysis and parameter estimation. In this paper we propose Bayesian estimation methods to extract physical parameters and interpret the statistical variability in the measured outputs of a dense nanocapacitor array biosensor. Firstly, the physical and mathematical models are presented. Then, a simple 1D-symmetry structure is used as a validation test case where the estimated parameters are also known a-priori. Finally, we apply the methodology to the simultaneous extraction of multiple physical and geometrical parameters from measurements on a CMOS pixelated nanocapacitor biosensor platform.reservedmixedStadlbauer, Benjamin; Cossettini, Andrea; Morales E., José A.; Pasterk, Daniel; Scarbolo, Paolo; Taghizadeh, Leila; Heitzinger, Clemens; Selmi, LucaStadlbauer, Benjamin; Cossettini, Andrea; Morales E., José A.; Pasterk, Daniel; Scarbolo, Paolo; Taghizadeh, Leila; Heitzinger, Clemens; Selmi, Luc

Loss of Sirt3 accelerates arterial thrombosis by increasing formation of neutrophil extracellular traps and plasma tissue factor activity

BACKGROUND: Sirtuin 3 (Sirt3) is a mitochondrial, nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase that reduces oxidative stress by activation of superoxide dismutase 2 (SOD2). Oxidative stress enhances arterial thrombosis. This study investigated the effects of genetic Sirt3 deletion on arterial thrombosis in mice in an inflammatory setting and assessed the clinical relevance of these findings in patients with ST-elevation myocardial infarction (STEMI). Methods and Results: Using a laser-induced carotid thrombosis model with lipopolysaccharide (LPS) challenge, in vivo time to thrombotic occlusion in Sirt3-/- mice (n = 6) was reduced by half compared to Sirt3+/+ wildtype (WT, n = 8, p<0.01) controls. Ex vivo analyses of whole blood using rotational thromboelastometry (ROTEM) revealed accelerated clot formation and increased clot stability in Sirt3-/- compared to WT blood. ROTEM of cell-depleted plasma showed accelerated clotting initiation in Sirt3-/- mice, whereas overall clot formation and firmness remained unaffected. Ex vivo LPS-induced neutrophil extracellular trap (NET) formation was increased in Sirt3-/- bone marrow (BM)-derived neutrophils. Plasma tissue factor (TF) levels and activity were elevated in Sirt3-/- mice, whereas plasma levels of other coagulation factors and TF expression in arterial walls remained unchanged. SOD2 expression in BM-derived Sirt3-/- neutrophils was reduced. In STEMI patients, transcriptional levels of Sirt3 and its target SOD2 were lower in CD14+ leukocytes compared with healthy donors (n = 10 each, p<0.01). CONCLUSIONS: Sirt3 loss-of-function enhances experimental thrombosis in vivo via an increase of NETs and elevation of TF suggesting thrombo-protective effects of endogenous Sirt3. Acute coronary thrombosis in STEMI patients is associated with lower expression levels of SIRT3 and SOD2 in CD14+ leukocytes. Therefore, enhancing SIRT3 activity by pan-sirtuin activating NAD+-boosters may provide a novel therapeutic target to prevent or treat thrombotic arterial occlusion in myocardial infarction or stroke

Biobanking for Europe

Biobanks are well-organized resources comprising biological samples and associated information that are accessible to scientific investigation. Across Europe, millions of samples with related data are held in different types of collections. While individual collections can be well organized and accessible, the resources are subject to fragmentation, insecurity of funding and incompleteness. To address these issues, a Biobanking and BioMolecular Resources Infrastructure (BBMRI) is to be developed across Europe, thereby implementing a European &#39;roadmap&#39; for research infrastructures that was developed by a forum of EU member states and that has been received by the European Commission. In this review, we describe the work involved in preparing for the construction of BBMRI in a European and global context

Intravenously administered APAC, a dual AntiPlatelet AntiCoagulant, targets arterial injury site to inhibit platelet thrombus formation and tissue factor activity in mice

Introduction: Arterial thrombosis is the main underlying mechanism of acute atherothrombosis. Combined antiplatelet and anticoagulant regimens prevent thrombosis but increase bleeding rates. Mast cell-derived heparin proteoglycans have local antithrombotic properties, and their semisynthetic dual AntiPlatelet and AntiCoagulant (APAC) mimetic may provide a new efficacious and safe tool for arterial thrombosis. We investigated the in vivo impact of intravenous APAC (0.3-0.5 mg/kg; doses chosen according to pharmacokinetic studies) in two mouse models of arterial thrombosis and the in vitro actions in mouse platelets and plasma.Materials and methods: Platelet function and coagulation were studied with light transmission aggregometry and clotting times. Carotid arterial thrombosis was induced either by photochemical injury or surgically exposing vascular collagen after infusion of APAC, UFH or vehicle. Time to occlusion, targeting of APAC to the vascular injury site and platelet deposition on these sites were assessed by intra-vital imaging. Tissue factor activity (TF) of the carotid artery and in plasma was captured.Results: APAC inhibited platelet responsiveness to agonist stimulation (collagen and ADP) and prolonged APTT and thrombin time. After photochemical carotid injury, APAC-treatment prolonged times to occlusion in comparison with UFH or vehicle, and decreased TF both in carotid lysates and plasma. Upon binding from circulation to vascular collagen-exposing injury sites, APAC reduced the in situ platelet deposition.Conclusions: Intravenous APAC targets arterial injury sites to exert local dual antiplatelet , anticoagulant actions and attenuates thrombosis upon carotid injuries in mice. Systemic APAC provides local efficacy, high-lighting APAC as a novel antithrombotic to reduce cardiovascular complications.Peer reviewe