Development of a versatile laboratory experiment to teach the metabolic transformation of hydrolysis

In this paper we describe an easy, reliable, versatile and inexpensive laboratory experiment to teach the metabolic transformation of hydrolysis to Pharmacy students. The experiment does not require the sacrifice of any experimental animal, or any work with organs or tissues, and so can be implemented in a typical university chemistry laboratory. We used acetylsalicylic acid (ASA), hexyl salicylate (HS) and two enzymes, a lipase and an esterase. Since both ASS and HS liberate salicylic acid (SA) upon hydrolysis, students can evaluate the different enzymatic transformations by monitoring the amount of SA liberated. The learning outcomes are an enhanced student understanding of: (1) the process of hydrolysis; (2) the application of enzymatic transformations of molecules from food to xenobiotics; (3) the differences between the general specificity of substrate of both enzymes; (4) the concepts of the lipophilic pocket; (5) the catalytic triad and its regioselectivity in relation to the ester bond. A questionnaire was administered to participating students at three points in time: at the beginning of the module, after enzymatic hydrolysis was taught in class, and after the laboratory experiment. From an analysis of the questionnaire data we conclude that this practical helped Pharmacy students to understand these concepts

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

How can technology enhanced learning improve the efficiency and quality of help seeking and giving for programming

Programming tutorials are self-regulated learning activities where students are responsible for their own work pace and learning experience. They are working on programming assignments under supervision of teaching assistants (TAs), where help seeking is an essential skill. Especially, the ability to formulate specific questions contributes to higher test results. In addition, the likelihood of seeking help can be increased by electronic measures, as it is perceived as less threatening. During programming tutorials at the University of Twente the queue management system TA-help.me is used. In order to improve the quality of the learning process, this system was expanded by the following features: 1. Students had to choose a category to which their question belongs. 2. Students had to formulate their question or select a previously asked question. The extentions resulted from a Creative Technology Design process. For evaluation, quantitative data were gathered to measure the quality of the help seeking of students and the acceptance of the tool. Furthermore, TAs were interviewed to check if the tool improved the efficiency and quality of the help seeking and giving. The data indicate that the amount of improvident help seeking reduced, the categories were perceived as useful by the students. Furthermore, adding categories to the questions offered the TAs the opportunity to select topics and to spread their attention more effectively. Typing out the questions did, however, not increase the amount of more specific questions asked. Future research includes how to guide students to ask better questions

Challenge-Based Modular On-demand Digital Education: A pilot

A blueprint for challenge-based modular on-demand digital education (CMODE) was designed to: (a) provide students with a challenge-based learning environment that is learning-centered, rather than teaching-centered; (b) change the teacher’s role from lecturing and knowledge providing to guiding, coaching and motivating; and (c) to provide on-campus contact hours that are complementary to an online learning environment. These goals of CMODE are formulated to increase student motivation for learning by providing them with additional freedom and responsibility, while aiming to exploit the potential advantages of challenge-based and blended learning. Based on this blueprint, a pilot program was created in 2019 for the bachelor Mechanical Engineering course ‘Dynamics and Control of Mechanical Systems’ at Eindhoven University of Technology. A practical challenge was created, which could be completed by handing in six deliverables. The online learning material consisted of six theory modules—aligned with the six challenge deliverables—that contained short weblectures, examples, quizzes and exercises. Finally, a new format for on-campus contact hours was implemented to improve complementarity with regards to the online learning environment. Using a questionnaire and the student evaluations, in combination with the exam and challenge grades, we evaluated how CMODE affected students’ learning and motivation. Preliminary results show better grades than the previous year, while students mention that they feel more motivated to stay on track with their learning

Comparative Genomic and Functional Analysis of Lactobacillus casei and Lactobacillus rhamnosus Strains Marketed as Probiotics

Four Lactobacillus strains were isolated from marketed probiotic products, including L. rhamnosus strains from Vifit (Friesland Campina) and Idoform (Ferrosan) and L. casei strains from Actimel (Danone) and Yakult (Yakult Honsa Co.). Their genomes and phenotypes were characterized and compared in detail with L. casei strain BL23 and L. rhamnosus strain GG. Phenotypic analysis of the new isolates indicated differences in carbohydrate utilization between L. casei and L. rhamnosus strains, which could be linked to their genotypes. The two isolated L. rhamnosus strains had genomes that were virtually identical to that of L. rhamnosus GG, testifying to their genomic stability and integrity in food products. The L. casei strains showed much greater genomic heterogeneity. Remarkably, all strains contained an intact spaCBA pilus gene cluster. However, only the L. rhamnosus strains produced mucus-binding SpaCBA pili under the conditions tested. Transcription initiation mapping demonstrated that the insertion of an iso-IS30 element upstream of the pilus gene cluster in L. rhamnosus strains but absent in L. casei strains had constituted a functional promoter driving pilus gene expression. All L. rhamnosus strains triggered an NF-¿B response via Toll-like receptor 2 (TLR2) in a reporter cell line, whereas the L. casei strains did not or did so to a much lesser extent. This study demonstrates that the two L. rhamnosus strains isolated from probiotic products are virtually identical to L. rhamnosus GG and further highlights the differences between these and L. casei strains widely marketed as probiotics, in terms of genome content, mucus-binding and metabolic capacities, and host signaling capabilitie

Fecundity selection does not vary along a large geographical cline of trait means in a passerine bird

Local environmental and ecological conditions are commonly expected to result in local adaptation, although there are few examples of variation in phenotypic selection across continent-wide spatial scales. We collected standardized data on selection with respect to the highly variable plumage coloration of pied flycatcher (Ficedula hypoleucaPall.) males from 17 populations across the species' breeding range. The observed selection on multiple male coloration traits via the annual number of fledged young was generally relatively weak. The main aim of the present study, however, was to examine whether the current directional selection estimates are associated with distance to the sympatric area with the collared flycatcher (Ficedula albicollisTemminck), a sister species with which the pied flycatcher is showing character displacement. This pattern was expected because plumage traits in male pied flycatchers are changing with the distance to these areas of sympatry. However, we did not find such a pattern in current selection on coloration. There were no associations between current directional selection on ornamentation and latitude or longitude either. Interestingly, current selection on coloration traits was not associated with the observed mean plumage traits of the populations. Thus, there do not appear to be geographical gradients in current directional fecundity selection on male plumage ornamentation. The results of the present study do not support the idea that constant patterns in directional fecundity selection would play a major role in the maintenance of coloration among populations in this species. By contrast, the tendency for relatively weak mosaic-like variation in selection among populations could reflect just a snapshot of temporally variable, potentially environment-dependent, selection, as suggested by other studies in this system. Such fine-grained variable selection coupled with gene flow could maintain extensive phenotypic variation across populations.Peer reviewe

A mathematical model for reactions during top-blowing in the AOD process:derivation of the model

Abstract In an earlier work, a fundamental mathematical model was proposed for side-blowing operation in the argon–oxygen decarburization (AOD) process. The purpose of this work is to present a new model, which focuses on the reactions during top-blowing in the AOD process. The model considers chemical reaction rate phenomena between the gas jet and the metal bath as well as between the gas jet and metal droplets. The rate expressions were formulated according to a law of mass action-based method, which accounts for the mass-transfer resistances in the liquid metal, gas, and slag phases. The generation rate of the metal droplets was related to the blowing number theory. This paper presents the description of the model, while validation and preliminary results are presented in the second part of this work