Publications by authors named "DA MacKenzie"

Purpose: The Environmental influences on Child Health Outcomes (ECHO) Cohort has enrolled over 60,000 children to examine how early environmental factors (broadly defined) are associated with key child health outcomes. The ECHO Cohort may be well-positioned to contribute to our understanding of rural environments and contexts, which has implications for rural health disparities research. The present study examined the outcome of child obesity to not only illustrate the suitability of ECHO Cohort data for these purposes but also determine how various definitions of rural and urban populations impact the presentation of findings and their interpretation.

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Limited studies have explored different extraction techniques that improve cannabis extraction with scale-up potential. Ultrasound-assisted and microwave-assisted extraction were evaluated to maximize the yield and concentration of cannabinoids and terpenes. A central composite rotatable design was used to optimize independent factors (sample-to-solvent ratio, extraction time, extraction temperature, and duty cycle).

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Efficient cannabis biomass extraction can increase yield while reducing costs and minimizing waste. Cold ethanol extraction was evaluated to maximize yield and concentrations of cannabinoids and terpenes at different temperatures. Central composite rotatable design was used to optimize two independent factors: sample-to-solvent ratio (1:2.

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Uranium is a naturally occurring element found in the environment as a mixture of isotopes with differing radioactive properties. Enrichment of mined material results in depleted uranium waste with substantially reduced radioactivity but retains the capacity for chemical toxicity. Uranium mine and milling waste are dispersed by wind and rain leading to environmental exposures through soil, air, and water contamination.

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Background: Osteoarthritis (OA) is a major problem globally. First-line management comprises education and self-management strategies. Online support groups may be a low-cost method of facilitating self-management.

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Communities in the western region of the United States experience environmental exposure to metal mixtures from living in proximity to numerous unremediated abandoned uranium mines. Metals including arsenic and uranium co-occur in and around these sites at levels higher than the United States Environmental Protection Agency maximum contaminant levels. To address the potential effect of these metals on the activation of CD4+ T-cells, we used RNA sequencing methods to determine the effect of exposure to sodium arsenite (1 μM and 10 μM), uranyl acetate (3 μM and 30 μM) or a mixture of sodium arsenite and uranyl acetate (1 μM sodium arsenite + 3 μM uranyl acetate).

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Serine-rich repeat proteins (SRRPs) have emerged as an important group of cell surface adhesins found in a growing number of Gram-positive bacteria. Studies focused on SRRPs from streptococci and staphylococci demonstrated that these proteins are -glycosylated on serine or threonine residues and exported via an accessory secretion (aSec) system. In pathogens, these adhesins contribute to disease pathogenesis and represent therapeutic targets.

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Lactobacillus reuteri is a gut symbiont inhabiting the gastrointestinal tract of numerous vertebrates. The surface-exposed serine-rich repeat protein (SRRP) is a major adhesin in Gram-positive bacteria. Using lectin and sugar nucleotide profiling of wild-type or L.

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, a Gram-positive bacterial species inhabiting the gastrointestinal tract of vertebrates, displays remarkable host adaptation. Previous mutational analyses of rodent strain 100-23C identified a gene encoding a predicted surface-exposed serine-rich repeat protein (SRRP) that was vital for biofilm formation in mice. SRRPs have emerged as an important group of surface proteins on many pathogens, but no structural information is available in commensal bacteria.

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Intestinal mucins trigger immune responses upon recognition by dendritic cells via protein-carbohydrate interactions. We used a combination of structural, biochemical, biophysical, and cell-based approaches to decipher the specificity of the interaction between mucin glycans and mammalian lectins expressed in the gut, including galectin (Gal)-3 and C-type lectin receptors. Gal-3 differentially recognized intestinal mucins with different O-glycosylation profiles, as determined by mass spectrometry (MS).

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The vertebrate gut symbiont exhibits strain-specific adhesion and health-promoting properties. Here, we investigated the role of the mucus adhesins, CmbA and MUB, upon interaction of ATCC PTA 6475 and ATCC 53608 strains with human monocyte-derived dendritic cells (moDCs). We showed that mucus adhesins increased the capacity of strains to interact with moDCs and promoted phagocytosis.

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Lung cancer has the highest mortality rate of any tissue-specific cancer in both men and women. Research continues to investigate novel drugs and therapies to mitigate poor treatment efficacy, but the lack of a good descriptive lung cancer animal model for preclinical drug evaluation remains an obstacle. Here we describe the development of an orthotopic lung cancer animal model which utilizes the human sodium iodide symporter gene (hNIS; SLC5A5) as an imaging reporter gene for the purpose of non-invasive, longitudinal tumor quantification.

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The mucus layer covering the gastrointestinal (GI) epithelium is critical in selecting and maintaining homeostatic interactions with our gut bacteria. However, the molecular details of these interactions are not well understood. Here, we provide mechanistic insights into the adhesion properties of the canonical mucus-binding protein (MUB), a large multi-repeat cell-surface adhesin found in inhabiting the GI tract.

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Bioorthogonal chemistry has been applied to study a multitude of biological processes in complex environments through incorporation and detection of small functional groups. However, few reactions are known to be compatible with each other to allow for studies of more than one biomolecule simultaneously. Here we describe a dual labeling method wherein two stereoelectronically contrasting nitrone tags are incorporated into bacteria peptidoglycan and detected via strain-promoted alkyne-nitrone cycloaddition (SPANC) simultaneously.

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Tocopherylquinone (TQ), the oxidation product of alpha-tocopherol (AT), is a bioactive molecule with distinct properties from AT. In this study, AT and TQ are investigated for their comparative effects on growth and androgenic activity in prostate cancer cells. TQ potently inhibited the growth of androgen-responsive prostate cancer cell lines (e.

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Enteropathogenic Escherichia coli (EPEC) is a major cause of diarrheal infant death in developing countries, and probiotic bacteria have been shown to provide health benefits in gastrointestinal infections. In this study, we have investigated the influence of the gut symbiont Lactobacillus reuteri on EPEC adherence to the human intestinal epithelium. Different host cell model systems including non-mucus-producing HT-29 and mucus-producing LS174T intestinal epithelial cell lines as well as human small intestinal biopsies were used.

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Background: Lactobacillus reuteri is a gut symbiont of a wide variety of vertebrate species that has diversified into distinct phylogenetic clades which are to a large degree host-specific. Previous work demonstrated host specificity in mice and begun to determine the mechanisms by which gut colonisation and host restriction is achieved. However, how L.

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Unnatural D-amino acids bearing endocyclic nitrones were developed for live-cell labelling of the bacterial peptidoglycan layer. Metabolic incorporation of D-Lys and D-Ala derivatives bearing different endocyclic nitrones was observed in E. coli, L.

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The Kinugasa reaction has become an efficient method for the direct synthesis of β-lactams from substituted nitrones and copper(I) acetylides. In recent years, the reaction scope has been expanded to include the use of water as the solvent, and with micelle-promoted [3+2] cycloadditions followed by rearrangement furnishing high yields of β-lactams. The high yields of stable products under aqueous conditions render the modified Kinugasa reaction amenable to metabolic labelling and bioorthogonal applications.

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The development and applications of strain-promoted alkyne-nitrone cycloaddition (SPANC) reactions have brought about new tools for rapid and specific functionalization of biomolecules in different settings. While a number of strain-promoted reactions have been successfully developed, SPANC reactions offer high reactivity with bimolecular rate constants of k2 that are as fast as 60M(-1)s(-1). SPANC reactions also offer stability of starting materials, particularly in the case of endocyclic nitrones, as well as stereoelectronic tunability of the nitrone moiety to optimize reactivity towards different alkyne reaction partners.

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The mucus layer covering the gastrointestinal tract is the first point of contact of the intestinal microbiota with the host. Cell surface macromolecules are critical for adherence of commensal bacteria to mucus but structural information is scarce. Here we report the first molecular and structural characterization of a novel cell-surface protein, Lar_0958 from Lactobacillus reuteri JCM 1112(T) , mediating adhesion of L.

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Lactobacillus salivarius is part of the vertebrate indigenous microbiota of the gastrointestinal tract, oral cavity, and milk. The properties associated with some L. salivarius strains have led to their use as probiotics.

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Although vertebrates harbor bacterial communities in their gastrointestinal tract whose composition is host-specific, little is known about the mechanisms by which bacterial lineages become selected. The goal of this study was to characterize the ecological processes that mediate host-specificity of the vertebrate gut symbiont Lactobacillus reuteri, and to systematically identify the bacterial factors that are involved. Experiments with monoassociated mice revealed that the ability of L.

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The mucus layer covering the gastrointestinal (GI) epithelium is critical in selecting and maintaining homeostatic interactions with our gut bacteria. However, the underpinning mechanisms of these interactions are not understood. Here, we provide structural and functional insights into the canonical mucus-binding protein (MUB), a multi-repeat cell-surface adhesin found in Lactobacillus inhabitants of the GI tract.

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