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Hepatitis E virus (HEV) is a nonenveloped, single-stranded, positive-sense RNA virus within the family Hepeviridae, subfamily Orthohepevirinae, which is divided into 4 genera: Paslahepevirus, Rocahepevirus, Chirohepevirus, and Avihepevirus (1). Human [...]

Transitioning to university can be a daunting endeavour, with student success dependent on a myriad of effects (Pascarella & Terenzini, 2005). Understanding how to navigate university systems, who to meet, how to get help, how to study, and what goals to set can be hard to grasp (Valle et al., 2003). We provide an overview of the new interdisciplinary foundations course, which piloted in fall 2014, for first-year Faculty of Science students at McMaster University. This course provides a taste of research-based learning (Healey, Jenkins, & Lea, 2014) and develops essential skills that are important for an undergraduate degree and future academic or career plans, exposes students to a wide range of departments and programs in the Faculty of Science, and invites students to reflect on their academic journey and how it may be changing as a result of the course. This customized approach intentionally teaches students how to locate and use institutional resources and the expectations that the institution has of its students, while offering opportunities to create networks of support essential for student success and retention (Kuh, Cruce, Shoup, Kinzie, & Gonyea, 2008), and speaks to a number of considerations highlighted in the literature (e.g., Ambrose, Bridges, DiPietro, Lovett, & Norman, 2010). Other factors considered include balancing the needs of the Faculty, the resources available, and the goals, demands, and interests of the students. In this paper, we describe the course's design, structure and implementation, key components of the course, support from upper-level science students, and preliminary pedagogical results, which assess its impact on and perception by students.

Aims: Rat‐associated zoonotic pathogen transmission at the human–wildlife interface is a public health concern in urban environments where Norway rats (Rattus norvegicus) thrive on abundant anthropogenic resources and live in close contact with humans and other animal species. To identify potential factors influencing zoonotic pathogen occurrence in rats, we investigated associations between environmental and sociodemographic factors and Leptospira interrogans and Bartonella spp. infections in rats from Windsor, Ontario, Canada, while controlling for the potential confounding effects of animal characteristics (i.e., sexual maturity and body condition). Methods and Results: Between November 2018 and June 2021, 252 rats were submitted by collaborating pest control professionals. Kidney and spleen samples were collected for L. interrogans and Bartonella spp. PCR and sequencing, respectively. Of the rats tested by PCR, 12.7% (32/252) were positive for L. interrogans and 16.3% (37/227) were positive for Bartonella species. Associations between infection status and environmental and sociodemographic variables of interest were assessed via mixed multivariable logistic regression models with a random intercept for social group and fixed effects to control for sexual maturity and body condition in each model. The odds of L. interrogans infection were significantly higher in rats from areas with high building density (odds ratio [OR]: 3.76; 95% CI: 1.31–10.79; p = 0.014), high human population density (OR: 3.31; 95% CI: 1.20–9.11; p = 0.021), high proportion of buildings built in 1960 or before (OR: 11.21; 95% CI: 2.06–60.89; p = 0.005), and a moderate number of reports of uncollected garbage compared to a low number of reports (OR: 4.88; 95% CI: 1.01–23.63; p = 0.049). A negative association was observed between median household income and Bartonella spp. infection in rats (OR: 0.26; 95% CI: 0.08–0.89; p = 0.031). Conclusions: Due to the complexity of the ecology of rat‐associated zoonoses, consideration of environmental and sociodemographic factors is of critical importance to better understand the nuances of host–pathogen systems and inform how urban rat surveillance and intervention efforts should be distributed within cities. [ABSTRACT FROM AUTHOR]

Enzyme screening of crude sponge extracts prioritized a 2005 Papua New Guinea collection of Hyrtios sp. for further study. The MeOH extract contained puupehenone and four puupehenone analogues (1, 2, 3, 5, and 7) along with a new diastereomer, 20-epi-hydroxyhaterumadienone (4), and a new analogue, 15-oxo-puupehenoic acid (6). The drimane terpene core of 4 and 6 was rapidly dereplicated, and the modified Mosher's method identified 4, while 1D and 2D NMR techniques were used to solve 6. These compounds plus noteworthy repository natural products and standards were tested against three lipoxygenase isozymes, human 5-, 12-, and 15-lipoxygenases. Significant potency and selectivity profiles were exhibited in the human 5-lipoxygenase assay by puupehenone (1) and jaspaquinol (9) and structural factors responsible for activity identified.

Research has been conducted on the Drosophila melanogaster and its latitudinal geographic variation. The investigation of the starvation resistance and fat content in D. melanogaster from South Africa and India has been carried out and the results indicate that there is no evidence of cline in the starvation resistance or fat content in South Africa and that starvation resistance in India could have evolved in response to the climatic variations specific only for India.

1.Glucuronidation of amines has been shown to exhibit large species differences, where the activity is typically more pronounced in human than in many preclinical species such as rat, mouse, dog and monkey. The purpose of this work was to characterize the in vitro glucuronidation of GNE-924, a potent pan-PIM inhibitor, to form M1 using liver microsomes (LM) and intestinal microsomes (IM). 2.M1 formation kinetics varied highly across species and between liver and intestinal microsomes. In LM incubations, rat exhibited the highest rate of M1 formation (CLint,app) at 140 ± 10 µL/min/mg protein, which was approximately 30-fold higher than human. In IM incubations, mouse exhibited the highest CLint,app at 484 ± 40 µL/min/mg protein, which was >1000-fold higher than human. In addition, CLint,app in LM was markedly higher than IM in human and monkey. In contrast, CLint,app in IM was markedly higher than LM in dog and mouse. 3.Reaction phenotyping indicated that UGT1A1, UGT1A3, UGT1A9, UGT2B4 and the intestine-specific UGT1A10 contributed to the formation of M1. 4.This is one of the first reports showing that N-glucuronidation activity is significantly greater in multiple preclinical species than in humans, and suggests that extensive intestinal N-glucuronidation may limit the oral exposure of GNE-924. [ABSTRACT FROM AUTHOR]

Abstract: The presence of fluorine in an active pharmaceutical ingredient (API) can impart important pharmacological attributes with regards to metabolism, stability, and selectivity. As such, nearly one‐third of newly approved small molecule drugs contain at least one fluorine atom. 19F is 100% naturally abundant lending to virtually unimpeded detection of fluorine‐containing molecules, even in complex mixtures. Despite these promising characteristics, the thorough evaluation of a method for 19F qNMR (quantitative NMR) has been lacking. Herein we present experimental methodology and optimized parameters for uniform quantitative sampling of fluorine‐containing drugs and we compare results obtained using both gravimetric and absolute concentration methods for data reduction. [ABSTRACT FROM AUTHOR]

Extracts of plastic packaging, manufacturing, and delivery systems (or their materials of construction) are analyzed by chromatographic methods to establish the system's extractables profile. The testing strategy consists of multiple orthogonal chromatographic methods, for example, gas and liquid chromatography with multiple detection strategies. Although this orthogonal testing strategy is comprehensive, it is not necessarily complete and members of the extractables profile can elude detection and/or accurate identification/quantification. Because the chromatographic methods rarely indicate that some extractables have been missed, another means of assessing the completeness of the profiling activity must be established. If the extracts are aqueous and contain no organic additives (e.g., pH buffers), then they can be analyzed for their total organic carbon content (TOC). Additionally, the TOC of an extract can be calculated based on the extractables revealed by the screening analyses. The measured and calculated TOC can be reconciled to establish the completeness and accuracy of the extractables profile. If the reconciliation is poor, then the profile is either incomplete or inaccurate and additional testing is needed to establish the complete and accurate profile. Ten test materials and components of systems were extracted and their extracts characterized for organic extractables using typical screening procedures. Measured and calculated TOC was reconciled to establish the completeness of the revealed extractables profile. When the TOC reconciliation was incomplete, the profiling was augmented with additional analytical testing to reveal the missing members of the organic extractables profile. This process is illustrated via two case studies involving aqueous extracts of sterile filters., Lay Abstract: Plastic materials and systems used to manufacture, contain, store, and deliver pharmaceutical products are extracted and the extracts analyzed to establish the materials' (or systems') organic extractables profile. Such testing typically consists of multiple chromatographic approaches whose differences help to ensure that all organic extractables are revealed, measured, and identified. Nevertheless, this rigorous screening process is not infallible and certain organic extractables may elude detection. If the extraction medium is aqueous, the process of total organic carbon (TOC) reconciliation is proposed as a means of establishing when some organic extractables elude detection. In the reconciliation, the TOC of the extracts is both directly measured and calculated from the chromatographic data. The measured and calculated TOC is compared (or reconciled), and the degree of reconciliation is an indication of the completeness and accuracy of the organic extractables profiling. If the reconciliation is poor, then the extractables profile is either incomplete or inaccurate and additional testing must be performed to establish the complete and accurate profile. This article demonstrates the TOC reconciliation process by considering aqueous extracts of 10 different test articles. Incomplete reconciliations were augmented with additional testing to produce a more complete TOC reconciliation., (© PDA, Inc. 2014.)

Actinobacteria such as streptomycetes are renowned for their ability to produce bioactive natural products including nonribosomal peptides (NRPs) and polyketides (PKs). The advent of genome sequencing has revealed an even larger genetic repertoire for secondary metabolism with most of the small molecule products of these gene clusters still unknown. Here, we employed a "protein-first" method called PrISM (Proteomic Investigation of Secondary Metabolism) to screen 26 unsequenced actinomycetes using mass spectrometry-based proteomics for the targeted detection of expressed nonribosomal peptide synthetases or polyketide synthases. Improvements to the original PrISM screening approach (Nat. Biotechnol. 2009, 27, 951-956), for example, improved de novo peptide sequencing, have enabled the discovery of 10 NRPS/PKS gene clusters from 6 strains. Taking advantage of the concurrence of biosynthetic enzymes and the secondary metabolites they generate, two natural products were associated with their previously "orphan" gene clusters. This work has demonstrated the feasibility of a proteomics-based strategy for use in screening for NRP/PK production in actinomycetes (often >8 Mbp, high GC genomes) versus the bacilli (2-4 Mbp genomes) used previously.