Biocatalytic access to betazole by one-pot multienzymatic system in continuous flow

As an alternative to classical synthetic approaches for the production of betazole drug, a one-pot biocatalytic system to this pharmaceutical molecule from its alcohol precursor has been developed. An ꙍ-transaminase, an alcohol dehydrogenase and a water-forming NADH oxidase for in-situ cofactor recycling have been combined to catalyse this reaction yielding 75% molar conversion in batch reaction with soluble enzymes. This multienzyme system was then co-immobilised through a newly established protocol for sequential functionalization of a methacrylate-based porous carrier to enable tailored immobilisation chemistries for each enzyme. This pluri-catalytic system has been set up in a continuous flow packed-bed reactor, yielding a space-time yield up to 2.59 g L-1 h-1 with 15 min residence with constant supply of oxygen for in-situ cofactor recycling through a segmented air-liquid flow. The addition of an in-line catch-and-release column afforded >80% product recovery

ECHO360 Active Learning Platform in Health Sciences education: How, when and why to use it?

The ECHO360 Active Learning Platform (ALP) is an online active learning platform allowing the creation of interactive multimedia content for anytime student learning, with the potential for comprehensive analytics. This ALP has previously been shown to enhance student participation and engagement during in-class activities however it can be challenging to use at first. To enhance the uptake of ECHO360 ALP in and out of the classroom a simplified guide with clear instructions on the most useful aspects of the platform was developed and shared with staff, successfully creating a community of instructors. A student guide was also prepared which showcased the methods for gaining the most from its use in and out of lectures. These resources are available in the appendix

Sulfation pathways during neurodevelopment

Sulfate is an important nutrient that modulates a diverse range of molecular and cellular functions in mammalian physiology. Over the past 2 decades, animal studies have linked numerous sulfate maintenance genes with neurological phenotypes, including seizures, impaired neurodevelopment, and behavioral abnormalities. Despite sulfation pathways being highly conserved between humans and animals, less than one third of all known sulfate maintenance genes are clinically reportable. In this review, we curated the temporal and spatial expression of 91 sulfate maintenance genes in human fetal brain from 4 to 17 weeks post conception using the online Human Developmental Biology Resource Expression. In addition, we performed a systematic search of PubMed and Embase, identifying those sulfate maintenance genes linked to atypical neurological phenotypes in humans and animals. Those findings, together with a search of the Online Mendelian Inheritance in Man database, identified a total of 18 candidate neurological dysfunction genes that are not yet considered in clinical settings. Collectively, this article provides an overview of sulfate biology genes to inform future investigations of perturbed sulfate homeostasis associated with neurological conditions

Assessing the value of seasonal hydrological forecasts for improving water resource management:insights from a pilot application in the UK

Improved skill of long-range weather forecasts have motivated an increasing effort towards developing seasonal hydrological forecasting systems across Europe. Among other purposes, such forecasting systems are expected to support better water management decisions. In this paper we evaluate the potential use of a real-time optimisation system (RTOS) informed by seasonal forecasts in a water supply system in the UK. For this purpose, we simulate the performances of the RTOS fed by ECMWF seasonal forecasting systems (SEAS5) over the past ten years, and we compare them to a benchmark operation that mimics the common practices for reservoir operation in the UK. We also attempt to link the improvement of system performances, i.e. the forecast value, to the forecast skill (measured by the mean error and the Continuous Ranked Probability Skill Score) as well as other factors such as bias correction, the decision maker priorities, hydrological conditions and level of uncertainty consideration. We find that some of these factors control the forecast value much more strongly than the forecast skill. For the (realistic) scenario where the decision-maker prioritises water resource availability over energy cost reductions, we identify clear operational benefits from using seasonal forecasts, provided that forecast uncertainty is explicitly considered. However, when comparing the use of ECMWF-SEAS5 products to ensemble streamflow predictions (ESP), which are more easily derived from historical weather data, we find that ESP remains a hard-to-beat reference not only in terms of skill but also in terms of value

Small-angle neutron scattering and Molecular Dynamics structural study of gelling DNA nanostars

DNA oligomers with properly designed sequences self-assemble into well defined constructs. Here, we exploit this methodology to produce bulk quantities of tetravalent DNA nanostars (each one composed by 196 nucleotides) and to explore the structural signatures of their aggregation process. We report small-angle neutron scattering experiments focused on the evaluation of both the form factor and the temperature evolution of the scattered intensity at a nano star concentration where the system forms a tetravalent equilibrium gel. We also perform molecular dynamics simulations of one isolated tetramer to evaluate the form factor theoretically, without resorting to any approximate shape. The numerical form factor is found to be in very good agreement with the experimental one. Simulations predict an essentially temperature independent form factor, offering the possibility to extract the effective structure factor and its evolution during the equilibrium gelation.Comment: 9 pages, 5 figure

Novel implications of Lingo-1 signaling in the prefrontal cortex and hippocampus of perinatal phencyclidine treated rats in a neurodevelopmental model of schizophrenia

Abstract of a poster presentation

Investigation Between the S377G3 GATA-4 Polymorphism and Migraine

Migraine is a common and painful neurological disorder, with genetic and environmental components. Several conditions have been shown to be comorbid with migraine, notably a cardiac malformation affecting the interatrial septum and leading to patent foramen ovale (PFO). Mutations in the development regulatory gene GATA-4, located on human chromosome 8p23.1-p22, have been found to be responsible for some cases of congenital heart defects including PFO. To determine whether the GATA-4 gene is involved in migraine, the present study performed an association analysis of a common GATA-4 variant that results in a change of amino acid (S377G), in a large case/control population (275 unrelated Caucasian migraineurs versus 275 control individuals). The results showed that there was no significant association for this polymorphism between migraine and controls (χ² = 0.84, P = 0.66). Thus it appears that the GATA-4 (S377G) mutation does not play a significant role in common migraine susceptibility

Dairy products and inflammation: a review of the clinical evidence

Inflammation is a major biological process regulating the interaction between organisms and the environment, including the diet. Because of the increase in chronic inflammatory diseases, and in light of the immune-regulatory properties of breastfeeding, the ability of dairy products to modulate inflammatory processes in humans is an important but unresolved issue. Here, we report a systematic review of 52 clinical trials investigating inflammatory markers in relation to the consumption of dairy products. An inflammatory score (IS) was defined to quantitatively evaluate this interaction. The IS was significantly positive for the entire data set, indicating an anti-inflammatory activity in humans. When the subjects were stratified according to their health status, the IS was strongly indicative of an anti-inflammatory activity in subjects with metabolic disorders and of a pro-inflammatory activity in subjects allergic to bovine milk. Stratifying the data by product categories associated both low-fat and high-fat products, as well as fermented products, with an anti-inflammatory activity. Remarkably, the literature is characterized by a large gap in knowledge on bioavailability of bioactive nutrients. Future research should thus better combine food and nutritional sciences to adequately follow the fate of these nutrients along the gastrointestinal and metabolic axes.info:eu-repo/semantics/publishedVersio