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

breast conservation and sentinel lymph node biopsy after neoadjuvant systemic therapy

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Genetic Consideration of Schizotypal Traits: A Review

Schizotypal traits are of interest and importance in their own right and also have theoretical and clinical associations with schizophrenia. These traits comprise attenuated psychotic symptoms, social withdrawal, reduced cognitive capacity, and affective dysregulation. The link between schizotypal traits and psychotic disorders has long since been debated. The status of knowledge at this point is such schizotypal traits are a risk for psychotic disorders, but in and of themselves only confer liability, with other risk factors needing to be present before a transition to psychosis occurs. Investigation of schizotypal traits also has the possibility to inform clinical and research pursuits concerning those who do not make a transition to psychotic disorders. A growing body of literature has investigated the genetic underpinnings of schizotypal traits. Here, we review association, family studies and describe genetic disorders where the expression of schizotypal traits has been investigated. We conducted a thorough review of the existing literature, with multiple search engines, references, and linked articles being searched for relevance to the current review. All articles and book chapters in English were sourced and reviewed for inclusion. Family studies demonstrate that schizotypal traits are elevated with increasing genetic proximity to schizophrenia and some chromosomal regions have been associated with schizotypy. Genes associated with schizophrenia have provided the initial start point for the investigation of candidate genes for schizotypal traits; neurobiological pathways of significance have guided selection of genes of interest. Given the chromosomal regions associated with schizophrenia, some genetic disorders have also considered the expression of schizotypal traits. Genetic disorders considered all comprise a profile of cognitive deficits and over representation of psychotic disorders compared to the general population. We conclude that genetic variations associated with schizotypal traits require further investigation, perhaps with targeted phenotypes narrowed to assist in refining the clinical end point of significance

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

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