The Spindle Tree, Euonymus europaea L. (Celastraceae): A Newly Naturalized Shrub in Nova Scotia

Over 100 plants, including over 750 individual shoots, of Euonymus europaea L. are reported from the Town of Antigonish in northern Nova Scotia. Plants were found in five discrete areas separated by 200-1000 m. A few individuals at one site may represent human planting; however, over 90% of plants occur on waste ground or in dense shrubbery where natural colonization has occurred. Many individuals were observed in fruit in the fall of 2005, and over 95% of the plants had well developed buds and flowers in May and early June 2006. Euonymus europaea is considered a newly naturalized species for the flora of Nova Scotia

Producción cultural y la economía en el humor digital: observaciones de “Just for Laughs”

En el presente artículo, presento información relacionada a mi investigación del festival de comedia “Just for Laughs” que se llevó a cabo en Montreal, uno delos eventos más importantes que congrega actores, productores, agentes y cadenas televisoras que forman parte de la industria de la comedia. De modo particular, analizo la información de la conferencia de industria anual, “Just Comedy”, la cual se llevó a cabo durante el festival. Es aquí, en que los expertos del “sector de la industria” discuten las tendencias potenciales, ansiedades y frustraciones relacionadas a la precariedad de la labor cultural y el crecimiento de la tecnología digital. Tomo en cuenta el terreno cambiante de la labor cómica, la producción del humor digital y la facilitación relacionada a las teorías de la economía creativa, la labor cultural, así como la producción cultural. La presente investigación, presenta variaciones evidentes en relación a la producción cultural sobre el crecimiento de las tecnologías digitales, así como el desempeño adecuado hacia las demandas del consumo y difusión del internet – debido a las pruebas de estándares de producción baja, comerciales cortos, y el seguimiento tanto de las masas y audiencias en particular.&nbsp

An experimental model for calcium carbonate urolithiasis in goats

This article is also available at the journal website: https://onlinelibrary.wiley.com/doi/full/10.1111/jvim.15061Background: Calcium carbonate is a common urolith type in small ruminants with no high-yield experimental model to evaluate animal susceptibility or preventative measure response. Hypothesis: That novel plastic winged implants would allow accumulation and quantification of calcium carbonate calculus formation in goats on a high-calcium diet and identify individual variation between goats in the mass of calculi produced. Animals: Eight nonpregnant 3- and 4-year-old Boer-cross does, weighing 22.3–39.5 kg, determined to be healthy based on physical examination, were used in these experiments. Methods: Prospective cohort study for in vivo experimental model development. Implants were placed into the urinary bladder lumen in 8 goats over 2 evaluation periods. The alfalfa-based ration had a total ration Ca : P of 3.29 and 3.84 : 1, respectively. Urine was collected at 0, 28, 56, and 84 days in the 1st experiment; blood and urine at those timepoints in the 2nd experiment. For each evaluation period, the implants were removed 84 days after implantation and weighed. Accumulated calculi mass was calculated and compared between goats and was analyzed for composition. Results: Implant retention was 100% and 86% in the 2 studies. All goats with retained implants accumulated calcium carbonate at a mean implant gain per day across studies ranging from 0.44 to 57.45 mg. Two goats accumulated (0.44–7.65 mg/day and 33.64 & 57.45 mg/day) significantly more urolith material than the cohort across both studies (P5.047). No routine analytes on blood or urine were found to be explanatory for the difference observed. Conclusions and Clinical Importance: These findings form a basis for implant and diet selection for use in future studies of urolithiasis development and for studies regarding individual susceptibility to urolithiasis. KEYWORDS 3D printing, calculogenesis, urinary calculi, urolithFunding information: Department of Large Animal Clinical Sciences, Texas A&M University College of Veterinary Medicin

Application de la méthode de rétrodiffusion des électrons à la mesure en continu des faibles épaisseurs de revêtements légers sur métaux ou alliages légers

Le problème envisagé concerne la mesure en continu des faibles épaisseurs de revêtements organiques sur métaux ou alliages légers. Nous étudions les caractéristiques d'une jauge à rétrodiffusion β opérant sous atmosphère d'hélium. Nous montrons que le fait de travailler sous hélium améliore les résultats de façon très importante. L'influence de l'énergie de la source radio-active et du numéro atomique du revêtement sont examinés. Les résultats obtenus concernent également la précision, le temps de mesure ainsi que la surface de l'échantillon sous investigation

How the other half lives: CRISPR-Cas's influence on bacteriophages

CRISPR-Cas is a genetic adaptive immune system unique to prokaryotic cells used to combat phage and plasmid threats. The host cell adapts by incorporating DNA sequences from invading phages or plasmids into its CRISPR locus as spacers. These spacers are expressed as mobile surveillance RNAs that direct CRISPR-associated (Cas) proteins to protect against subsequent attack by the same phages or plasmids. The threat from mobile genetic elements inevitably shapes the CRISPR loci of archaea and bacteria, and simultaneously the CRISPR-Cas immune system drives evolution of these invaders. Here we highlight our recent work, as well as that of others, that seeks to understand phage mechanisms of CRISPR-Cas evasion and conditions for population coexistence of phages with CRISPR-protected prokaryotes.Comment: 24 pages, 8 figure

Allosteric inhibition of a stem cell RNA-binding protein by an intermediary metabolite

Gene expression and metabolism are coupled at numerous levels. Cells must sense and respond to nutrients in their environment, and specialized cells must synthesize metabolic products required for their function. Pluripotent stem cells have the ability to differentiate into a wide variety of specialized cells. How metabolic state contributes to stem cell differentiation is not understood. In this study, we show that RNA-binding by the stem cell translation regulator Musashi-1 (MSI1) is allosterically inhibited by 18-22 carbon omega-9 monounsaturated fatty acids. The fatty acid binds to the N-terminal RNA Recognition Motif (RRM) and induces a conformational change that prevents RNA association. Musashi proteins are critical for development of the brain, blood, and epithelium. We identify stearoyl-CoA desaturase-1 as a MSI1 target, revealing a feedback loop between omega-9 fatty acid biosynthesis and MSI1 activity. We propose that other RRM proteins could act as metabolite sensors to couple gene expression changes to physiological state

Structural basis for CRISPR RNA-guided DNA recognition by Cascade

The CRISPR (clustered regularly interspaced short palindromic repeats) immune system in prokaryotes uses small guide RNAs to neutralize invading viruses and plasmids. In Escherichia coli, immunity depends on a ribonucleoprotein complex called Cascade. Here we present the composition and low-resolution structure of Cascade and show how it recognizes double-stranded DNA (dsDNA) targets in a sequence-specific manner. Cascade is a 405-kDa complex comprising five functionally essential CRISPR-associated (Cas) proteins (CasA1B2C6D1E1) and a 61-nucleotide CRISPR RNA (crRNA) with 5′-hydroxyl and 2′,3′-cyclic phosphate termini. The crRNA guides Cascade to dsDNA target sequences by forming base pairs with the complementary DNA strand while displacing the noncomplementary strand to form an R-loop. Cascade recognizes target DNA without consuming ATP, which suggests that continuous invader DNA surveillance takes place without energy investment. The structure of Cascade shows an unusual seahorse shape that undergoes conformational changes when it binds target DNA.

Effect of Childhood Trauma on Adult Depression and Neuroendocrine Function: Sex-Specific Moderation by CRH Receptor 1 Gene

Variations of the corticotropin-releasing hormone receptor 1 (CRHR1) gene appear to moderate the development of depression after childhood trauma. Depression more frequently affects women than men. We examined sex differences in the effects of the CRHR1 gene on the relationship between childhood trauma and adult depression. We recruited 1,063 subjects from the waiting rooms of a public urban hospital. Childhood trauma exposure and symptoms of depression were assessed using dimensional rating scales. Subjects were genotyped for rs110402 within the CRHR1 gene. An independent sample of 78 subjects underwent clinical assessment, genotyping, and a dexamethasone/CRH test. The age range at recruitment was 18–77 years and 18–45, for the two studies respectively. In the hospital sample, the protective effect of the rs110402 A-allele against developing depression after childhood trauma was observed in men (N = 424), but not in women (N = 635). In the second sample, the rs110402 A-allele was associated with decreased cortisol response in the dexamethasone/CRH test only in men. In A-allele carriers with childhood trauma exposure women exhibited increased cortisol response compared men; there were no sex differences in A-allele carriers without trauma exposure. This effect may, however, not be related to gender differences per se, but to differences in the type of experienced abuse between men and women. CRHR × environment interactions in the hospital sample were observed with exposure to physical, but not sexual or emotional abuse. Physical abuse was the most common type of abuse in men in this cohort, while sexual abuse was most commonly suffered by women. Our results suggest that the CRHR1 gene may only moderate the effects of specific types of childhood trauma on depression. Gender differences in environmental exposures could thus be reflected in sex-specific CRHR1 × child abuse interactions

The Molecular Basis of Drug Resistance against Hepatitis C Virus NS3/4A Protease Inhibitors

Hepatitis C virus (HCV) infects over 170 million people worldwide and is the leading cause of chronic liver diseases, including cirrhosis, liver failure, and liver cancer. Available antiviral therapies cause severe side effects and are effective only for a subset of patients, though treatment outcomes have recently been improved by the combination therapy now including boceprevir and telaprevir, which inhibit the viral NS3/4A protease. Despite extensive efforts to develop more potent next-generation protease inhibitors, however, the long-term efficacy of this drug class is challenged by the rapid emergence of resistance. Single-site mutations at protease residues R155, A156 and D168 confer resistance to nearly all inhibitors in clinical development. Thus, developing the next-generation of drugs that retain activity against a broader spectrum of resistant viral variants requires a comprehensive understanding of the molecular basis of drug resistance. In this study, 16 high-resolution crystal structures of four representative protease inhibitors - telaprevir, danoprevir, vaniprevir and MK-5172 - in complex with the wild-type protease and three major drug-resistant variants R155K, A156T and D168A, reveal unique molecular underpinnings of resistance to each drug. The drugs exhibit differential susceptibilities to these protease variants in both enzymatic and antiviral assays. Telaprevir, danoprevir and vaniprevir interact directly with sites that confer resistance upon mutation, while MK-5172 interacts in a unique conformation with the catalytic triad. This novel mode of MK-5172 binding explains its retained potency against two multi-drug-resistant variants, R155K and D168A. These findings define the molecular basis of HCV N3/4A protease inhibitor resistance and provide potential strategies for designing robust therapies against this rapidly evolving virus

Staff training in physical interventions: a literature review

BackgroundRestrictive practices are used frequently by frontline staff in a variety of care contexts, including psychiatric hospitals, children’s services, and support services for older adults and individuals with intellectual and developmental disabilities. Physical restraint has been associated with emotional harm, physical injury to staff and consumers, and has even resulted in death of individuals in care environments. Various interventions have been implemented within care settings with the intention of reducing instances of restraint. One of the most common interventions is staff training that includes some physical intervention skills to support staff to manage crisis situations. Despite physical intervention training being used widely in care services, there is little evidence to support the effectiveness and application of physical interventions. This review will examine the literature regarding outcomes of staff training in physical interventions across care sectors.MethodA systematic search was conducted following PRISMA guidelines using Cochrane Database, Medline EBSCO, Medline OVID, PsychINFO, and the Web of Science. Main search keywords were staff training, physical intervention, physical restraint. The MMAT was utilised to provide an analytical framework for the included studies.Results and discussionSeventeen articles have been included in this literature review. The included studies take place in a range of care settings and comprise a wide range of outcomes and designs. The training programmes examined vary widely in their duration, course content, teaching methods, and extent to which physical skills are taught. Studies were of relatively poor quality. Many descriptions of training programmes did not clearly operationalise the knowledge and skills taught to staff. As such, it is difficult to compare course content across the studies. Few papers described physical interventions in sufficient detail. This review demonstrates that, although staff training is a ‘first response’ to managing health and safety in care settings, there is very little evidence to suggest that staff training in physical intervention skills leads to meaningful outcomes