Opportunities for Dutch Biorefineries

Deze Roadmap Bioraffinage beschrijft een aantal mogelijke routes naar de ontwikkeling en implementatie van een bioraffinage-gerelateerde Bio-based Economy in Nederland. De Roadmap combineert korte- en middellange termijn mogelijkheden (commerciële implementatie, demonstratie plants, pilot plants en gerelateerd toegepast onderzoek) met strategisch onderzoek voor de langere termijn. Tevens zijn vier z.g. Moonshots uitgewerkt, als voorziene bioraffinagestrategieën met een grote potentie voor de Nederlandse economi

Financieel-economische aspecten van Biobrandstofproductie : deskstopstudie naar de invloed van co-productie van bio-based producten op de financiële haalbaarheid van biobrandstoffen

Door uitvoering van een deskstop studie heeft WUR, in samenwerking met ECN, onderzocht of co-productie van biobrandstoffen en bio-based producten leidt tot meer marktcompetitieve biobrandstofproductie. De centrale vraagstelling van de studie was of aangetoond kan worden dat “co-productie” resulteert in realisatie van meer marktcompetitieve waardeketens voor grootschalige en duurzame inzet van biomassa in de biobased economy. De studie naar de financiële haalbaarheid van een twaalftal biobrandstofketens laten zien dat co-productie van biobrandstoffen tezamen met bio-based producten een goede methode is om additionele waarde toe te kennen aan de totale biomassa-product-keten. De co-producten die tezamen met biobrandstoffen geproduceerd kunnen worden zijn zeer divers. In het algemeen bestaat er voor deze co-producten een omvangrijke afzetmarkt, en gaat het om producten die op dit moment grotendeels uit aardolie vervaardigd worden. Technologieën voor productie en toepassing van hoogwaardige co-producten die naast biobrandstoffen uit biomassa geproduceerd kunnen worden bevinden zich in verschillende stadia van ontwikkeling

Manipulating adenovirus hexon hypervariable loops dictates immune neutralisation and coagulation factor X-dependent cell interaction in vitro and in vivo

Adenoviruses are common pathogens, mostly targeting ocular, gastrointestinal and respiratory cells, but in some cases infection disseminates, presenting in severe clinical outcomes. Upon dissemination and contact with blood, coagulation factor X (FX) interacts directly with the adenovirus type 5 (Ad5) hexon. FX can act as a bridge to bind heparan sulphate proteoglycans, leading to substantial Ad5 hepatocyte uptake. FX “coating” also protects the virus from host IgM and complement-mediated neutralisation. However, the contribution of FX in determining Ad liver transduction whilst simultaneously shielding the virus from immune attack remains unclear. In this study, we demonstrate that the FX protection mechanism is not conserved amongst Ad types, and identify the hexon hypervariable regions (HVR) of Ad5 as the capsid proteins targeted by this host defense pathway. Using genetic and pharmacological approaches, we manipulate Ad5 HVR interactions to interrogate the interplay between viral cell transduction and immune neutralisation. We show that FX and inhibitory serum components can co-compete and virus neutralisation is influenced by both the location and extent of modifications to the Ad5 HVRs. We engineered Ad5-derived HVRs into the rare, native non FX-binding Ad26 to create Ad26.HVR5C. This enabled the virus to interact with FX at high affinity, as quantified by surface plasmon resonance, FX-mediated cell binding and transduction assays. Concomitantly, Ad26.HVR5C was also sensitised to immune attack in the absence of FX, a direct consequence of the engineered HVRs from Ad5. In both immune competent and deficient animals, Ad26.HVR5C hepatic gene transfer was mediated by FX following intravenous delivery. This study gives mechanistic insight into the pivotal role of the Ad5 HVRs in conferring sensitivity to virus neutralisation by IgM and classical complement-mediated attack. Furthermore, through this gain-of-function approach we demonstrate the dual functionality of FX in protecting Ad26.HVR5C against innate immune factors whilst determining liver targeting

Crystal structures of Λ-[Ru(phen)2dppz]2+ with oligonucleotides containing TA/TA and AT/AT steps show two intercalation modes

The ruthenium complex [Ru(phen)2(dppz)] (where phen is a phenanthroline and dppz a dipyridyl–phenazine ligand) is known as a ‘light switch’ complex because its luminescence in solution is significantly enhanced in the presence of DNA. This property is poised to serve in diagnostic and therapeutic applications, but its binding mode with DNA needs to be elucidated further. Here, we describe the crystal structures of the L enantiomer bound to two oligonucleotide duplexes. The dppz ligand intercalates symmetrically and perpendicularly from the minor groove of the d(CCGGTACCGG)2 duplex at the central TA/TA step, but not at the central AT/AT step of d(CCGGATCCGG)2. In both structures, however, a second ruthenium complex links the duplexes through the combination of a shallower angled intercalation into the C1C2/G9G10 step at the end of the duplex, and semi-intercalation into the G3G4 step of an adjacent duplex. The TA/TA specificity of the perpendicular intercalation arises from the packing of phenanthroline ligands against the adenosine residue

Mechanical Support in Early Cardiogenic Shock: What Is the Role of Intra-aortic Balloon Counterpulsation?

Purpose of Review: We aim to summarize recent insights and provide an up-to-date overview on the role of intra-aortic balloon pump (IABP) counterpulsation in cardiogenic shock (CS). Recent Findings: In the largest randomized controlled trial (RCT) of patients with CS after acute myocardial infarction

Cellular origin and microRNA profiles of circulating extracellular vesicles in different stages of diabetic nephropathy

Background: Diabetic nephropathy (DN) is a major complication of diabetes and the main cause of end-stage renal disease. Extracellular vesicles (EVs) are small cell-derived vesicles that can alter disease progression by microRNA (miRNA) transfer. Methods: In this study, we aimed to characterize the cellular origin and miRNA content of EVs in plasma samples of type 2 diabetes patients at various stages of DN. Type 2 diabetes patients were classified in three groups: normoalbuminuria, microalbuminuria and macroalbuminuria. The concentration and cellular origin of plasma EVs were measured by flow cytometry. A total of 752 EV miRNAs were profiled in 18 subjects and differentially expressed miRNAs were validated. Results: Diabetic patients with microalbuminuria and/or macroalbuminuria showed elevated concentrations of total EVs and EVs from endothelial cells, platelets, leucocytes and erythrocytes compared with diabetic controls. miR-99a-5p was upregulated in macroalbuminuric patients compared with normoalbuminuric and microalbuminuric patients. Transfection of miR-99a-5p in cultured human podocytes downregulated mammalian target of rapamycin (mTOR) protein expression and downregulated the podocyte injury marker vimentin. Conclusions: Type 2 diabetes patients with microalbuminuria and macroalbuminuria display differential EV profiles. miR-99a-5p expression is elevated in EVs from macroalbuminuria and mTOR is its validated mRNA target

First-Line Support by Intra-Aortic Balloon Pump in Non-Ischaemic Cardiogenic Shock in the Era of Modern Ventricular Assist Devices

Objectives: Little is known about circulatory support in cardiogenic shock (CS) from other causes than the acute coronary syndrome or after cardiotomy. We evaluated the effects of first-line intra-aortic balloon pump (IABP) support in this subpopulation of CS patients. Methods: A retrospective study was performed in 27 patients with CS from end-stage cardiomyopathy supported firstly by IABP in the years 2011-2016. Results: At 24 h, lactate decreased from 3.2 (2.1-6.8) to 1.8 (1.2-2.2) mmol/L (p < 0.001). Eighteen patients (67%) defined as IABP responders were successfully bridged to either recovery (n = 7), left ventricular assist device (n = 5), or heart transplantation (n = 6). IABP failed in 9 patients (non-responders, 33%) who either died (n = 7) or needed support by extracorporeal membrane oxygenation (n = 2). At 24 h of IABP support, urinary output was higher (2,660 [1,835-4,440] vs. 1,200 [649-2,385] mL; p = 0.02) and fluid balance more negative (-1,564 [-2,673 to -1,086] vs. -500 [-930 to +240] mL; p < 0.001) in responders than non-responders. Overall survival at 1 year was 63%. Conclusion: In most patients, first-line support by IABP in end-stage cardiomyopathy is associated with improvement in organ perfusion and clinical stabilisation for at least 24 h allowing time for decision making on next therapies

Eligibility of cardiac arrest patients for extracorporeal cardiopulmonary resuscitation and their clinical characteristics:a retrospective two-centre study

BACKGROUND AND IMPORTANCE: Sudden cardiac arrest has a high incidence and often leads to death. A treatment option that might improve the outcomes in refractory cardiac arrest is Extracorporeal Cardiopulmonary Resuscitation (ECPR).OBJECTIVES: This study investigates the number of in-hospital cardiac arrest (IHCA) and out-of-hospital cardiac arrest (OHCA) patients eligible to ECPR and identifies clinical characteristics that may help to identify which patients benefit the most from ECPR.DESIGN, SETTINGS AND PARTICIPANTS: A retrospective two-centre study was conducted in Rotterdam, the Netherlands. All IHCA and OHCA patients between 1 January 2017 and 1 January 2020 were screened for eligibility to ECPR. The primary outcome was the percentage of patients eligible to ECPR and patients treated with ECPR. The secondary outcome was the comparison of the clinical characteristics and outcomes of patients eligible to ECPR treated with conventional Cardiopulmonary Resuscitation (CCPR) vs. those of patients treated with ECPR.MAIN RESULTS: Out of 1246 included patients, 412 were IHCA patients and 834 were OHCA patients. Of the IHCA patients, 41 (10.0%) were eligible to ECPR, of whom 20 (48.8%) patients were actually treated with ECPR. Of the OHCA patients, 83 (9.6%) were eligible to ECPR, of whom 23 (27.7%) were actually treated with ECPR. In the group IHCA patients eligible to ECPR, no statistically significant difference in survival was found between patients treated with CCPR and patients treated with ECPR (hospital survival 19.0% vs. 15.0% respectively, 4.0% survival difference 95% confidence interval -21.3 to 28.7%). In the group OHCA patients eligible to ECPR, no statistically significant difference in-hospital survival was found between patients treated with CCPR and patients treated with ECPR (13.3% vs. 21.7% respectively, 8.4% survival difference 95% confidence interval -30.3 to 10.2%).CONCLUSION: This retrospective study shows that around 10% of cardiac arrest patients are eligible to ECPR. Less than half of these patients eligible to ECPR were actually treated with ECPR in both IHCA and OHCA.</p