Regulation of autoimmune-mediated neuroinflammation by endothelial cells.

The CNS has traditionally been considered an immune-privileged organ, but recent studies have identified a plethora of immune cells in the choroid plexus, meninges, perivascular spaces, and cribriform plate. Although those immune cells are crucial for the maintenance of CNS homeostasis and for neural protection against infections, they can lead to neuroinflammation in some circumstances. The blood and the lymphatic vasculatures exhibit distinct structural and molecular features depending on their location in the CNS, greatly influencing the compartmentalization and the nature of CNS immune responses.

Patient satisfaction with access to a student-run free-service dental clinic.

Background: The Student Health Initiative for the Needs of Edmonton (SHINE) dental clinic is a student-volunteer-operated clinic offering free oral care to low-income individuals. However, little is known about how SHINE impacts access to care. Drawing on Penchansky and Thomas' theory of access, this study assessed patient satisfaction to measure access.

Epidemiologic disparities in colon cancer screening and adherence during the COVID-19 pandemic: a retrospective cohort analysis.

Background: Colorectal cancer (CRC) is the second-leading cause of death in the USA. CRC screening remains underutilized, especially in underinsured populations. Screening has been heavily disrupted during the COVID-19 pandemic.

Patterns in schizomid flagellum shape from elliptical Fourier analysis.

The arachnid order Schizomida is a relatively understudied group of soil-dwelling predators found on all continents except Antarctica. While efforts to understand their biology are growing, there is still much to know about them. A curious aspect of their morphology is the male flagellum, a sexually dimorphic, tail-like structure which differs in shape across the order and functions in their courtship rituals.

Cell-Based Drug Discovery: Identification and Optimization of Small Molecules that Reduce -MYC Protein Levels in Cells.

Elevated expression of the -MYC oncogene is one of the most common abnormalities in human cancers. Unfortunately, efforts to identify pharmacological inhibitors that directly target MYC have not yet yielded a drug-like molecule due to the lack of any known small molecule binding pocket in the protein, which could be exploited to disrupt MYC function. We have recently described a strategy to target MYC indirectly, where a screening effort designed to identify compounds that can rapidly decrease endogenous -MYC protein levels in a amplified cell line led to the discovery of a compound series that phenocopies -MYC knockdown by siRNA.

Converging on the orb: denser taxon sampling elucidates spider phylogeny and new analytical methods support repeated evolution of the orb web.

High throughput sequencing and phylogenomic analyses focusing on relationships among spiders have both reinforced and upturned long-standing hypotheses. Likewise, the evolution of spider webs-perhaps their most emblematic attribute-is being understood in new ways. With a matrix including 272 spider species and close arachnid relatives, we analyze and evaluate the relationships among these lineages using a variety of orthology assessment methods, occupancy thresholds, tree inference methods and support metrics.

Exploring access in a volunteer free-service dental clinic.

Introduction: Marginalized, low-income individuals face many barriers to dental care, including but not limited to cost. The Student Health Initiative for the Needs of Edmonton (SHINE) dental clinic is a student-operated volunteer clinic offering free services to low-income individuals. This study aimed to explore the access to dental care needs of low-income groups, from community health brokers' perspectives.

High-Throughput Screening and Triage Assays Identify Small Molecules Targeting c-MYC in Cancer Cells.

While c-MYC is well established as a proto-oncogene, its structure and function as a transcription factor have made c-MYC a difficult therapeutic target. To identify small-molecule inhibitors targeting c-MYC for anticancer therapy, we designed a high-throughput screening (HTS) strategy utilizing cellular assays. The novel approach for the HTS was based on the detection of cellular c-MYC protein, with active molecules defined as those that specifically decreased c-MYC protein levels in cancer cells.

Interrogating Genomic-Scale Data to Resolve Recalcitrant Nodes in the Spider Tree of Life.

Genome-scale data sets are converging on robust, stable phylogenetic hypotheses for many lineages; however, some nodes have shown disagreement across classes of data. We use spiders (Araneae) as a system to identify the causes of incongruence in phylogenetic signal between three classes of data: exons (as in phylotranscriptomics), noncoding regions (included in ultraconserved elements [UCE] analyses), and a combination of both (as in UCE analyses). Gene orthologs, coded as amino acids and nucleotides (with and without third codon positions), were generated by querying published transcriptomes for UCEs, recovering 1,931 UCE loci (codingUCEs).

Using Lean Six Sigma methodologies to reduce risk of warfarin medication omission at hospital discharge.

Unintended omission of warfarin, an anticoagulant used to prevent and treat thromboembolic events, can lead to serious medical complications. These complications include increased medical costs, hospitalisations and significant patient harm, including increased risk of thrombosis and mortality. Chart review of discharged patients at our institution revealed an average of one patient/month with warfarin omitted from the discharge plan despite intention to continue therapy.

Nylanderia of the World Part III: Nylanderia in the West Indies.

The diversity of the formicine ant genus Nylanderia is currently underestimated and largely undescribed. This includes the faunas of tropical regions where species richness is typically high. Here, the taxonomy of the West Indian Nylanderia fauna is revised for the first time.

High-Throughput Cellular Thermal Shift Assays in Research and Drug Discovery.

Thermal shift assays (TSAs) can reveal changes in protein structure, due to a resultant change in protein thermal stability. Since proteins are often stabilized upon binding of ligand molecules, these assays can provide a readout for protein target engagement. TSA has traditionally been applied using purified proteins and more recently has been extended to study target engagement in cellular environments with the emergence of cellular thermal shift assays (CETSAs).

Identification via a Parallel Hit Progression Strategy of Improved Small Molecule Inhibitors of the Malaria Purine Uptake Transporter that Inhibit Parasite Proliferation.

Emerging resistance to current antimalarial medicines underscores the importance of identifying new drug targets and novel compounds. Malaria parasites are purine auxotrophic and import purines via the equilibrative nucleoside transporter type 1 (PfENT1). We previously showed that PfENT1 inhibitors block parasite proliferation in culture.

Monophyly, Taxon Sampling, and the Nature of Ranks in the Classification of Orb-Weaving Spiders (Araneae: Araneoidea).

We address some of the taxonomic and classification changes proposed by Kuntner et al. (2019) in a comparative study on the evolution of sexual size dimorphism in nephiline spiders. Their proposal to recircumscribe araneids and to rank the subfamily Nephilinae as a family is fundamentally flawed as it renders the family Araneidae paraphyletic.

Next-Generation Compound Delivery Platforms to Support Miniaturized Biology.

Recent advancements in science and engineering are revolutionizing our understanding of an individual's disease, and with this knowledge we are gaining an increasingly sophisticated understanding of how discovery can be transformed to deliver personalized medicines. To reach this future state, we must reengineer our approach to enable the use of more relevant human cellular models earlier in the drug discovery process. Stem cells and primary human cells represent more disease-relevant models than immortalized cell lines; however, due to both availability and cost, their use is limited in lead generation activities.

Phylogenomics, Diversification Dynamics, and Comparative Transcriptomics across the Spider Tree of Life.

Dating back to almost 400 mya, spiders are among the most diverse terrestrial predators [1]. However, despite considerable effort [1-9], their phylogenetic relationships and diversification dynamics remain poorly understood. Here, we use a synergistic approach to study spider evolution through phylogenomics, comparative transcriptomics, and lineage diversification analyses.

A phylotranscriptomic backbone of the orb-weaving spider family Araneidae (Arachnida, Araneae) supported by multiple methodological approaches.

The orb-weaving spider family Araneidae is extremely diverse (>3100 spp.) and its members can be charismatic terrestrial arthropods, many of them recognizable by their iconic orbicular snare web, such as the common garden spiders. Despite considerable effort to better understand their backbone relationships based on multiple sources of data (morphological, behavioral and molecular), pervasive low support remains in recent studies.

A High-Throughput Dose-Response Cellular Thermal Shift Assay for Rapid Screening of Drug Target Engagement in Living Cells, Exemplified Using SMYD3 and IDO1.

A persistent problem in early small-molecule drug discovery is the frequent lack of rank-order correlation between biochemical potencies derived from initial screens using purified proteins and the diminished potency and efficacy observed in subsequent disease-relevant cellular phenotypic assays. The introduction of the cellular thermal shift assay (CETSA) has bridged this gap by enabling assessment of drug target engagement directly in live cells based on ligand-induced changes in protein thermal stability. Initial success in applying CETSA across multiple drug target classes motivated our investigation into replacing the low-throughput, manually intensive Western blot readout with a quantitative, automated higher-throughput assay that would provide sufficient capacity to use CETSA as a primary hit qualification strategy.

Redescription of the Jamaican orb-weaving spider Chrysometa pecki Levi, 1986 (Araneae, Tetragnathidae), including the first description of the male.

The tetragnathid genus Chrysometa Simon, 1894 includes 138 species found in the Americas, ranging from the Caribbean to Chile (World Spider Catalog 2015). This genus was revised by Levi (1986), with more recent publications adding to the genus (Álvarez-Padilla 2007, Nogueira et al. 2011, Simó et al.

Atypical challenging and first case report of babesiosis in Ecuador.

Unlabelled: Babesia is known to be prevalent in the Eastern United States and other temperate countries but the prevalence of babesia is not well known in the tropical malaria-endemic countries because of the higher prevalence of malaria. A 72-year-old Hispanic male from Ecuador presenting with increasing left lower quadrant abdominal pain and distention for one year. He experienced nausea, vomiting, diarrhea, fever, chill, and myalgias.

A High-Content Imaging Screen for Cellular Regulators of β-Catenin Protein Abundance.

Abnormal accumulation of β-catenin protein, a key transcriptional activator required for Wnt signaling, is the hallmark of many tumor types, including colon cancer. In normal cells, β-catenin protein level is tightly controlled by a multiprotein complex through the proteosome pathway. Mutations in the components of the β-catenin degradation complex, such as adenomatous polyposis coli (APC) and Axin, lead to β-catenin stabilization and the constitutive activation of target genes.