Publications by authors named "Alexander Coutts"

Nutrients introduced to the environment by finfish aquaculture pose environmental risks, which can be mitigated by robust environmental monitoring. Biological communities in soft sediments are good indicators of aquaculture derived environmental changes. Traditionally, monitoring programs have visually surveyed macrofauna communities.

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Background & Aims: The xenobiotic efflux pump P-glycoprotein is highly expressed on the apical membrane of the gastrointestinal tract, where it regulates the levels of intracellular substrates. P-glycoprotein is altered in disease, but the mechanisms that regulate the levels of P-glycoprotein are still being explored. The molecular motor myosin Vb (Myo5b) traffics diverse cargo to the apical membrane of intestinal epithelial cells.

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Modern anatomy education has benefitted from the development of a wide range of digital 3D resources in the past decades, but the impact of the COVID-19 pandemic has sparked an additional demand for high-quality online learning resources. Photogrammetry provides a low-cost technique for departments to create their own photo-realistic 3D models of cadaveric specimens. However, to ensure accessibility, the design of the resulting learning resources should be carefully considered.

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Most male pigs are surgically castrated to avoid puberty-derived boar taint and aggressiveness. However, this surgical intervention represents a welfare concern in swine production. Disrupting porcine is hypothesized to delay or abolish puberty by inducing variable hypogonadotropism and thus preventing the need for castration.

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Use of lab-in-the-field experiments has steadily increased, given benefits of studying relevant populations and their preferences. In the field, researchers must often relinquish the control of a standard laboratory, raising the specter of communication from past to future participants. Little is known about the consequences of such spillovers, and recent literature indicates variation in how authors deal with them.

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Background: The MEK1/2 inhibitor selumetinib was recently approved for neurofibromatosis type 1 (NF1)-associated plexiform neurofibromas, but outcomes could be improved and its pharmacodynamic evaluation in other relevant tissues is limited. The aim of this study was to assess selumetinib tissue pharmacokinetics (PK) and pharmacodynamics (PD) using a minipig model of NF1.

Methods: WT ( = 8) and NF1 ( = 8) minipigs received a single oral dose of 7.

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Article Synopsis
  • The study investigates the role of the molecular motor Myosin Vb (MYO5B) in maintaining cell polarity and its link to microvillus inclusion disease (MVID), which results from inactivating mutations in MYO5B.
  • It reveals that inclusions formed in Myo5b knockout mice originate from changes in the apical brush border due to bulk endocytosis, leading to mislocalized polarity and tight junction proteins.
  • Findings from both mouse models and genetically modified swine indicate that tight junction proteins like Claudin-2 cluster over inclusions in MVID, suggesting similar mechanisms are at play in both animal models and affected human patients.
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Ribonucleoprotein (RNP) granules are biomolecular condensates-liquid-liquid phase-separated droplets that organize and manage messenger RNA metabolism, cell signaling, biopolymer assembly, biochemical reactions and stress granule responses to cellular adversity. Dysregulated RNP granules drive neuromuscular degenerative disease but have not previously been linked to heart failure. By exploring the molecular basis of congenital dilated cardiomyopathy (DCM) in genome-edited pigs homozygous for an RBM20 allele encoding the pathogenic R636S variant of human RNA-binding motif protein-20 (RBM20), we discovered that RNP granules accumulated abnormally in the sarcoplasm, and we confirmed this finding in myocardium and reprogrammed cardiomyocytes from patients with DCM carrying the R636S allele.

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Background & Aims: Microvillus inclusion disease (MVID) is caused by inactivating mutations in the myosin VB gene (MYO5B). MVID is a complex disorder characterized by chronic, watery, life-threatening diarrhea that usually begins in the first hours to days of life. We developed a large animal model of MVID to better understand its pathophysiology.

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Neurofibromatosis Type 1 (NF1) is a genetic disease caused by mutations in (). NF1 patients present with a variety of clinical manifestations and are predisposed to cancer development. Many NF1 animal models have been developed, yet none display the spectrum of disease seen in patients and the translational impact of these models has been limited.

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