Publications by authors named "Murdock S"

Gammaherpesviruses are DNA tumor viruses that establish lifelong latent infections in lymphocytes. For viruses such as Epstein-Barr virus and murine gammaherpesvirus 68, this is accomplished through a viral gene-expression program that promotes cellular proliferation and differentiation, especially of germinal center B cells. Intrinsic host mechanisms that control virus-driven cellular expansion are incompletely defined.

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Unlabelled: Gammaherpesviruses (GHV) are DNA tumor viruses that establish lifelong latent infections in lymphocytes. For viruses such as Epstein-Barr virus (EBV) and murine gammaherpesvirus 68 (MHV68), this is accomplished through a viral gene-expression program that promotes cellular proliferation and differentiation, especially of germinal center (GC) B cells. Intrinsic host mechanisms that control virus-driven cellular expansion are incompletely defined.

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The mechanisms by which large-scale microbial community function emerges from complex ecological interactions between individual taxa and functional groups remain obscure. We leveraged network analyses of 16S rRNA amplicon sequences obtained over a seven-month timeseries in seasonally anoxic Saanich Inlet (Vancouver Island, Canada) to investigate relationships between microbial community structure and water column NO cycling. Taxa separately broadly into three discrete subnetworks with contrasting environmental distributions.

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Absorption measurements allow the orientational order parameter of four dyes in the lyotropic chromonic liquid crystal di-sodium cromoglycate (DSCG) to be determined. The dye order parameters are small, except for dyes that intercalate between the DSCG molecules of the rod-like assemblies. The dye order parameters decrease with increasing temperature faster than the nematic order parameter of the DSCG assemblies.

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Leishmanial skin lesions are characterized by inflammatory hypoxia alongside the activation of hypoxia-inducible factors, HIF-1α and HIF-2α, and subsequent expression of the HIF-α target VEGF-A during infection. However, the factors responsible for HIF-α activation are not known. We hypothesize that hypoxia and proinflammatory stimuli contribute to HIF-α activation during infection.

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Human infants who suffer from intrauterine growth restriction (IUGR), which is a failure to attain their genetically predetermined weight, are at increased risk for postnatal learning and memory deficits. Hippocampal dentate gyrus (DG) granule neurons play an important role in memory formation; however, it is unknown whether IUGR affects embryonic DG neurogenesis, which could provide a potential mechanism underlying abnormal postnatal learning and memory function. Using a mouse model of the most common cause of IUGR, induced by hypertensive disease of pregnancy, we first assessed adult learning and memory function.

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Assessment of ecosystem health entails consideration of species interactions within and between size classes to determine their contributions to ecosystem function. Elucidating microbial involvement in these interactions requires tools to distil diverse microbial information down to relevant, manageable elements. We used covariance ratios (proportionality) between pairs of species and patterns of enrichment to identify "core communities" of likely interacting microbial (<64 µm), meiofaunal (64 µm to 1 mm) and macrofaunal (>1 mm) taxa within assemblages hosted by a foundation species, the hydrothermal vent tubeworm Ridgeia piscesae.

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Regulatory T (Treg) cell infiltration of solid tumors often correlates with poor prognosis, but their tumor-suppressive function lacks mechanistic understanding. Through a combination of transgenic mice, cell fate mapping, adoptive transfer, and co-injection strategies, we demonstrate that Treg cell ablation-dependent anti-tumor effects in murine breast cancer require intratumoral recruitment of CCR2 inflammatory monocytes, which primarily differentiate into tumor-associated macrophages (TAMs), and lead to reprogramming of their function in an IFN-γ-dependent manner. Furthermore, transcriptomic signatures from murine TAMs in Treg cell-ablated conditions correlate with increased overall survival in human breast cancer.

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Background: Peritoneal dialysis-associated peritonitis can uncommonly be caused by fungal infections. When they do present, they are associated with significant mortality and morbidity. We describe a case where a sample of peritoneal dialysate fluid grew Rhodotorula muciliginosa, a yeast organism present in the normal environment which has previously been reported as rarely causing peritonitis.

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Elucidation of the potential roles of single-celled eukaryotes (protists) in ecosystem function and trophodynamics in hydrothermal vent ecosystems is reliant on information regarding their abundance, distribution and preference for vent habitats. Using high-throughput 18S rRNA gene sequencing on a diverse suite of hydrothermally influenced and background water samples, we assess the diversity and distribution of protists and identify potential vent endemics. We found that 95% of the recovered sequences belong to operational taxonomic units (OTUs) with a cosmopolitan distribution across vent and non-vent habitats.

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In vitro analysis of covalent inhibitors requires special consideration, due to the time-dependent and typically irreversible nature of their target interaction. While many analyses are reported for the characterization of a final candidate, it is less clear which are most useful in the lead optimization phase of drug discovery. In the context of identifying covalent inhibitors of Bruton's tyrosine kinase (BTK), we evaluated multiple techniques for characterizing covalent inhibitors.

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Objectives: Bruton's tyrosine kinase (BTK) is a non-receptor tyrosine kinase required for intracellular signaling downstream of multiple immunoreceptors. We evaluated ABBV-105, a covalent BTK inhibitor, using in vitro and in vivo assays to determine potency, selectivity, and efficacy to validate the therapeutic potential of ABBV-105 in inflammatory disease.

Methods: ABBV-105 potency and selectivity were evaluated in enzymatic and cellular assays.

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Denitrifying may dominate nitrogen loss processes in marine habitats with intense redox gradients, but assessment of their importance is limited by the currently available primers for nitrite reductase genes. Nine new primers targeting the gene of denitrifying were designed and tested for use in sequencing and quantitative PCR on two microbial mat samples (vent 2 and vent 4) from the Calypso hydrothermal vent field, Bay of Plenty, New Zealand. Commonly used and primer sets nirS1F/nirS6R, cd3aF/R3cd, nirK1F/nirK5R, and F1aCu/R3Cu were also tested to determine what may be missed by the common single-primer approach to assessing denitrifier diversity.

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The action of Janus kinases (JAKs) is required for multiple cytokine signaling pathways, and as such, JAK inhibitors hold promise for treatment of autoimmune disorders, including rheumatoid arthritis, inflammatory bowel disease, and psoriasis. However, due to high similarity in the active sites of the four members (Jak1, Jak2, Jak3, and Tyk2), developing selective inhibitors within this family is challenging. We have designed and characterized substituted, tricyclic Jak3 inhibitors that selectively avoid inhibition of the other JAKs.

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Seafloor iron oxide deposits are a common feature of submarine hydrothermal systems. Morphological study of these deposits has led investigators to suggest a microbiological role in their formation, through the oxidation of reduced Fe in hydrothermal fluids. Fe-oxidizing bacteria, including the recently described Zetaproteobacteria, have been isolated from a few of these deposits but generally little is known about the microbial diversity associated with this habitat.

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Introduction: Pain is a major concern of patients before orthodontic treatment. Currently, the most frequently recommended treatments for pain after archwire placement or appliance adjustment are over-the-counter (OTC) analgesics. Although the overuse of OTC medications and their potential side effects are concerns, particularly for children, no study to date has investigated a nonpharmacologic option for pain management as an alternative for these analgesics.

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Contemporary structural biology has an increased emphasis on high-throughput methods. Biomolecular simulations can add value to structural biology via the provision of dynamic information. However, at present there are no agreed measures for the quality of biomolecular simulation data.

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Comparative molecular dynamics (MD) simulations enable us to explore the conformational dynamics of the active sites of distantly related enzymes. We have used the BioSimGrid (http://www.biosimgrid.

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Overview: Dental treatment modalities for ectodermal dysplasia (ED) vary markedly depending on the clinical manifestations, but to date there have been no studies exploring the potential economic impact of ED. On the basis of anecdotal and clinical reports, the authors postulate that costs of dental treatment for this condition can have a substantial financial impact on patients and their families.

Objective: The purpose of the authors' pilot study was to develop an economic model for various treatment modalities for ED with severe hypodontia.

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Biomolecular computer simulations are now widely used not only in an academic setting to understand the fundamental role of molecular dynamics on biological function, but also in the industrial context to assist in drug design. In this paper, two applications of Grid computing to this area will be outlined. The first, involving the coupling of distributed computing resources to dedicated Beowulf clusters, is targeted at simulating protein conformational change using the Replica Exchange methodology.

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BioSimGrid is a database for biomolecular simulations, or, a "Protein Data Bank extended in time" for molecular dynamics trajectories. We describe the implementation details: architecture, data schema, deposition, and analysis modules. We encourage the simulation community to explore BioSimGrid and work towards a common trajectory exchange format.

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