Chemical Profiling of Five Canadian Haskap Berry Varieties and the Roles of their Phenolic Extracts in Modulating Cellular Stress in Human Fibroblasts

Interest in plant phenolic structure(s) and their applications has grown due to their potent antioxidant and nutraceutical potential. Many plant species produce phenolics for a variety of functions, with high levels of these compounds often found in berry fruits. When applied to cells and organisms, berry fruit phenolics have shown anti-aging, anticancer, and anti-inflammatory activities. Haskap berries (Lonicera caerulea) are an edible honeysuckle species that contain very high levels of phenolics when compared to other commercial fruits. In this study, the chemical and physicochemical composition of five Canadian haskap berry varieties (Aurora, Blizzard, Honey Bee, Indigo Gem, and Tundra) was determined, with a focus on phenolic analysis and the in vitro health-promoting potential of these compounds. Total phenolic chromatographic indices (TPCI) using high performance liquid chromatography with photodiode array detection (HPLC-PDA) identified anthocyanins as the major phenolic subclass with cyanidin-3-O-glucoside, cyanidin-3,5-O-diglucoside, and cyanidin-3-O-rutinoside being the most prevalent. HPLC-tandem mass spectrometry (HPLC-MS/MS) was also employed to identify haskap phenolic structures including three previously unreported phenolic compounds. In vitro free radical scavenging assays showed that these haskap varieties had higher radical scavenging abilities than many other fruits (e.g. blueberry) with the Tundra variety demonstrating the highest capacity. These experiments led to selection of the Tundra variety for use in tissue culture assays due to its high phenolic content and free radical scavenging abilities. Phenolic extracts and fractions from Tundra haskap berries were produced using solid phase extraction, so as to separate phenolic subclasses for comparative cell line treatments in vitro. In tissue culture assays, phenolic extracts from the Tundra variety slowed the growth of fibroblasts isolated from healthy donors (2DD) and immortalized (NB1 hTERT) fibroblasts without inducing cell death, indicating potential biological impacts similar to resveratrol, a fruit phenolic known to promote cellular health. Tundra phenolic fractions also increased cellular protein and activity levels of Sirtuin-1 (SIRT1), decreased levels of the pro-inflammatory phospho-nuclear factor kappa B (phospho-NF-κB p65) and the phosphorylated mammalian target of rapamycin (phospho-mTOR), and increased nuclear factor erythroid 2 (Nrf2). These observations are significant as these activities have been linked to slowed aging, improved intracellular radical scavenging (resistance to oxidative stress), and decreased inflammatory responses. Tundra phenolic fraction activities were shown to rely primarily on SIRT1 by employing lentiviral and siRNA SIRT1 knockdown cells, with additional SIRT1-independent mechanism(s) related to Nrf2 upregulation. These fractions also showed the ability to decrease transcript levels of select pro-inflammatory cytokines and antioxidant enzymes, demonstrating further anti-inflammatory activities along with decreased requirements for cellular antioxidant mechanisms. These experimental results indicated that Saskatchewan-bred haskaps have the potential to promote health in vitro by mediating cellular stress responses and may be candidates for use as nutraceutical supplements

Learning effective amino acid interactions through iterative stochastic techniques

The prediction of the three-dimensional structures of the native state of proteins from the sequences of their amino acids is one of the most important challenges in molecular biology. An essential ingredient to solve this problem within coarse-grained models is the task of deducing effective interaction potentials between the amino acids. Over the years several techniques have been developed to extract potentials that are able to discriminate satisfactorily between the native and non-native folds of a pre-assigned protein sequence. In general, when these potentials are used in actual dynamical folding simulations, they lead to a drift of the native structure outside the quasi-native basin. In this study, we present and validate an approach to overcome this difficulty. By exploiting several numerical and analytical tools we set up a rigorous iterative scheme to extract potentials satisfying a pre-requisite of any viable potential: the stabilization of proteins within their native basin (less than 3-4 \AA$$ cRMS). The scheme is flexible and is demonstrated to be applicable to a variety of parametrizations of the energy function and provides, in each case, the optimal potentials.Comment: Revtex 17 pages, 10 eps figures. Proteins: Structure, Function and Genetics (in press

Quelles sont les interventions infirmières de prévention secondaire centrées sur l'environnement familial et social qui permettent de tendre vers un arrêt de la consommation de tabac chez les adolescents ?:: travail de Bachelor

Le tabac étant un problème de santé publique au niveau mondial, il n'est pas rare que les fumeurs adultes aient débuté leur consommation pendant l'adolescence. Cette revue de littérature analyse 9 articles de recherche scientifique trouvés sur deux bases de recherche : PubMed et CINAHL. Ces écrits scientifiques regroupent différents aspects généraux liés à ce stade du développement humain ainsi que les différents facteurs influençant qui pourraient mener un jeune à développer un tel comportement à risque. La majorité des adolescents étant scolarisés et passant la plupart de leur temps à l'école, ce lieu devient alors une arène pour expérimenter la vie. L'infirmière scolaire serait une ressource clé pour affronter la problématique liée au tabac dès ses débuts. Le modèle de soins infirmiers de McGill a été choisi pour développer cette problématique et ainsi investiguer quelles interventions infirmières de prévention secondaire pourraient éventuellement être instaurées dans les écoles secondaires suisses. Il en ressort de ces écrits de la méthode des 5A et le programme N-O-T+FIT seraient des outils que l'infirmière scolaire serait en mesure d'utiliser dans un système de santé scolaire semblable au système scolaire Suisse

Incidence of emergency department visits for electric rental scooters using detailed ridership data

INTRODUCTION: Electric scooter (e-scooter) rental usage has increased exponentially around the country, expanding to more than 120 cities by the end of 2018. Early attempts to capture the safety effects of widespread adoption of this technology have been hampered by lack of accurate ridership data. Here we describe a 17-month evolution of ridership characteristics in St. Louis, Missouri, and the frequency of e-scooter rental-related injuries serious enough to require an emergency department (ED) visit over this time frame; we also provide estimates of incidence rates of injuries based on company ridership data. METHODS: We performed a combination retrospective chart review and prospective questionnaire-based analysis of adult e-scooter rental-related ED visits in both downtown St. Louis Level 1 trauma centers during the first 17 months of e-scooter rental usage (August 2018-December 2019). The retrospective portion focused on demographics, alcohol use, helmet use, disposition, operative repair, and temporal and severity markers. The prospective portion focused on more detailed crash and rider data. Finally, we used ridership data from both e-scooter rental companies in St. Louis to estimate incidence and temporal trends. RESULTS: A total of 221 patients had e-scooter rental-related ED visits. The median age of our population was 31 years with 58.8% male and 53.8% White. There were no deaths. Ninety-two patients were found to have fractures with 38% requiring surgery. Of the 21 patients diagnosed with head injury, five had an intracranial bleed. Overall incidence of ED visits related to e-scooters was 2.1 per 10,000 trips and 2.2 per 10,000 miles with the number of ED visits by month closely correlated with the number of rides per month (Pearson correlation coefficient = 0.95). CONCLUSION: The number of e-scooter rental-related injuries seen in St. Louis trauma centers was relatively low and correlated closely with overall number of rides. The number of injuries decreased and were less severe from 2018 to 2019 with infrequent intracranial injuries and a large percentage of fractures requiring operative repair

A Database of Domain Definitions for Proteins with Complex Interdomain Geometry

Protein structural domains are necessary for understanding evolution and protein folding, and may vary widely from functional and sequence based domains. Although, various structural domain databases exist, defining domains for some proteins is non-trivial, and definitions of their domain boundaries are not available. Here, we present a novel database of manually defined structural domains for a representative set of proteins from the SCOP “multi-domain proteins” class. (http://prodata.swmed.edu/multidom/). We consider our domains as mobile evolutionary units, which may rearrange during protein evolution. Additionally, they may be visualized as structurally compact and possibly independently folding units. We also found that representing domains as evolutionary and folding units do not always lead to a unique domain definition. However, unlike existing databases, we retain and refine these “alternate” domain definitions after careful inspection of structural similarity, functional sites and automated domain definition methods. We provide domain definitions, including actual residue boundaries, for proteins that well known databases like SCOP and CATH do not attempt to split. Our alternate domain definitions are suitable for sequence and structure searches by automated methods. Additionally, the database can be used for training and testing domain delineation algorithms. Since our domains represent structurally compact evolutionary units, the database may be useful for studying domain properties and evolution

Repeat expansion in the budding yeast ribosomal DNA can occur independently of the canonical homologous recombination machinery

Major eukaryotic genomic elements, including the ribosomal DNA (rDNA), are composed of repeated sequences with well-defined copy numbers that must be maintained by regulated recombination. Although mechanisms that instigate rDNA recombination have been identified, none are directional and they therefore cannot explain precise repeat number control. Here, we show that yeast lacking histone chaperone Asf1 undergo reproducible rDNA repeat expansions. These expansions do not require the replication fork blocking protein Fob1 and are therefore independent of known rDNA expansion mechanisms. We propose the existence of a regulated rDNA repeat gain pathway that becomes constitutively active in asf1Δ mutants. Cells lacking ASF1 accumulate rDNA repeats with high fidelity in a processive manner across multiple cell divisions. The mechanism of repeat gain is dependent on highly repetitive sequence but, surprisingly, is independent of the homologous recombination proteins Rad52, Rad51 and Rad59. The expansion mechanism is compromised by mutations that decrease the processivity of DNA replication, which leads to progressive loss of rDNA repeats. Our data suggest that a novel mode of break-induced replication occurs in repetitive DNA that is dependent on high homology but does not require the canonical homologous recombination machinery

Light Yield in DarkSide-10: a Prototype Two-phase Liquid Argon TPC for Dark Matter Searches

As part of the DarkSide program of direct dark matter searches using liquid argon TPCs, a prototype detector with an active volume containing 10 kg of liquid argon, DarkSide-10, was built and operated underground in the Gran Sasso National Laboratory in Italy. A critically important parameter for such devices is the scintillation light yield, as photon statistics limits the rejection of electron-recoil backgrounds by pulse shape discrimination. We have measured the light yield of DarkSide-10 using the readily-identifiable full-absorption peaks from gamma ray sources combined with single-photoelectron calibrations using low-occupancy laser pulses. For gamma lines of energies in the range 122-1275 keV, we get consistent light yields averaging 8.887+-0.003(stat)+-0.444(sys) p.e./keVee. With additional purification, the light yield measured at 511 keV increased to 9.142+-0.006(stat) p.e./keVee.Comment: 10 pages, 7 figures, Accepted for publication in Astroparticle Physic

Valeurs et transmission de valeurs des enseignants en class : recherche sur les pratiques enseignantes

Les enseignants, dans leurs pratiques, sont chargés de transmettre des savoirs aux élèves. Cependant leur tâche ne s’arrête pas là : au-delà de leur mission d’instruction existe une certaine part d’éducation, de socialisation. Nous nous sommes intéressée à cette part là, en nous focalisant sur les valeurs personnelles et professionnelles transmises par les enseignants, afin de voir quelles valeurs sont chères aux enseignants, et comment celles-ci sont transmises dans leurs pratiques. À travers les propos de sept enseignants, nous avons pu voir que cela est loin d’être une pratique isolée et qu’il existe plusieurs manières de transmettre des valeurs, telles que de manières formelles ou de manières informelles. Nous avons aussi essayé de comprendre comment celles-ci s’articulent dans le quotidien, à travers les raisons sociales et des dispositifs choisis par les enseignants, leur façon d’être ou à travers des situations de gestion de confits