Publications by authors named "Bradley Harris"

Biological organisms engineer peptide sequences to fold into membrane pore proteins capable of performing a wide variety of transport functions. Synthetic de novo-designed membrane pores can mimic this approach to achieve a potentially even larger set of functions. Here we explore water, solute, and ion transport in three de novo designed β-barrel membrane channels in the 5-10 Å pore size range.

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  • Common genetic variation at the 11q23.1 locus is linked to colorectal cancer risk, complicating the understanding of its mechanisms due to complex gene interactions and expression patterns.
  • The study utilizes various sequencing methods and mouse models to identify key genes, especially highlighting rs3087967 as a crucial variant that influences the expression of 21 genes associated with tuft cell markers.
  • The findings suggest that the risk genotype at rs3087967 leads to a deficiency in tuft cells, which are important for tumor suppression, positioning these cells as protective elements in colorectal cancer development.
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Genome-wide association studies of colorectal cancer (CRC) have identified 170 autosomal risk loci. However, for most of these, the functional variants and their target genes are unknown. Here, we perform statistical fine-mapping incorporating tissue-specific epigenetic annotations and massively parallel reporter assays to systematically prioritize functional variants for each CRC risk locus.

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  • Two-dimensional (2D) materials, especially peptoids, have gained attention for their diverse applications from chemical sensing to biomedicine due to their unique properties like high stability and self-repair.
  • This study examined how different peptoid sequences affect their self-assembly into 2D crystalline sheets using techniques like Atomic Force Microscopy (AFM) and X-ray scattering.
  • Results indicated that peptoids with specific structural characteristics influence their growth behavior on surfaces, revealing variations in assembly rates and stability based on sequence composition and hydrophobic interactions.
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Peptoids (N-substituted glycines) are a class of biomimetic polymers that have attracted significant attention due to their accessible synthesis and enzymatic and thermal stability relative to their naturally occurring counterparts (polypeptides). While these polymers provide the promise of more robust functional materials via hierarchical approaches, they present a new challenge for computational structure prediction for material design. The reliability of calculations hinges on the accuracy of interactions represented in the force field used to model peptoids.

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  • Fatty acids are essential for various biological functions, including maintaining cell membranes, metabolism, and signaling.
  • FadL is the main protein responsible for the uptake of long-chain fatty acids in Gram-negative bacteria, with newly discovered capability to uptake fatty acids longer than 18 carbon atoms, enhancing bacterial survivability.
  • In-depth molecular simulations of FadL and its homologs reveal that some have improved structural adaptations for transporting long-chain polyunsaturated fatty acids, while one homolog lacks the necessary transport channels.
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Aeromonas salmonicida is a Gram-negative bacterium that can infect a wide host range of fish populations, including salmonids and non-salmonids as well as freshwater and marine life. Some strains of A. salmonicida cause the disease furunculosis, which can cause lethargy, intestinal inflammation, ulcers, haemorrhaging and death.

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  • Colorectal cancer (CRC) has a genetic risk factor located at 11q23.1, which influences gene expression through eQTL mechanisms affecting both local (cis) and distant (trans) targets.* -
  • Analysis of 32,361 healthy colonic epithelial cells revealed a specific gene network linked to the expression of tuft cells, with one module showing significant correlation with the gene POU2AF2.* -
  • The study identified 12 trans-eQTL targets related to the 11q23.1 region, suggesting that these genes are associated with tuft cell abundance, where lower expression correlates with fewer tuft cells in the tissue.*
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The binding interaction between the T-cell receptor (TCR) and peptide-major histocompatibility complex (pMHC) is modulated by several factors (known and unknown), however, investigations into effects of glycosylation are limited. A fully glycosylated computational model of the TCR bound to the pMHC is developed to investigate the effects of glycosylation on dissociation kinetics from the pMHC. Here, we examine the effects of N-glycosylation on TCR-pMHC bond strength using steered molecular dynamic simulations.

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Molecular dynamics (MD) simulations in the MARTINI model are used to study the assembly of 1-palmitoyl-2-oleoylphosphatidylcholine (POPC) molecules under spatial confinement, such as during solvent evaporation from ultrasmall (femtoliter quantity) droplets. The impact of surface polarity on molecular assembly is discussed in detail. To the best of our knowledge, this work represents the first of its kind.

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SARS-CoV-2 Spike is a key protein that mediates viral entry into cells and elicits antibody responses. Its importance in infection, diagnostics, and vaccinations has created a large demand for purified Spike for clinical and research applications. Spike is difficult to express, prompting modifications to the protein and expression platforms to improve yields.

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Colorectal cancer (CRC) is a common, multifactorial disease. While observational studies have identified an association between lower vitamin D and higher CRC risk, supplementation trials have been inconclusive and the mechanisms by which vitamin D may modulate CRC risk are not well understood. We sought to perform a weighted gene co-expression network analysis (WGCNA) to identify modules present after vitamin D supplementation (when plasma vitamin D level was sufficient) which were absent before supplementation, and then to identify influential genes in those modules.

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Highly detailed steered molecular dynamics simulations are performed on differently glycosylated receptor binding domains of the severe acute respiratory syndrome coronavirus-2 spike protein. The binding strength and the binding range increase with glycosylation. The interaction energy rises very quickly when pulling the proteins apart and only slowly drops at larger distances.

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  • Researchers aimed to understand how veterinary emergency and critical care clinicians define intravenous fluid bolus therapy (FBT) and what they consider a positive response.
  • An online survey was conducted with 222 veterinarians to collect data on their preferences for fluid types and monitoring methods during FBT.
  • Results showed that most clinicians preferred balanced isotonic crystalloids for FBT, with common monitoring parameters including heart rate and blood pressure; however, many believed a significant percentage of hypotensive patients do not respond positively to FBT.
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Identifying individual animals is crucial for many biological investigations. In response to some of the limitations of current identification methods, new automated computer vision approaches have emerged with strong performance. Here, we review current advances of computer vision identification techniques to provide both computer scientists and biologists with an overview of the available tools and discuss their applications.

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The integration of multiple tissues in physiological and ecological analyses can enhance methodological approaches, increase applications for data and extend interpretation of results. Previous investigations of the stress response in fish have focused primarily on cortisol levels in a single matrix-blood plasma-which confines interpretations of cortisol levels to a short temporal frame. Epidermal mucus has been proposed as an alternative or complement to plasma that may provide a view to cortisol levels over a different temporal window allowing comparative assessment.

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While self-assembly of molecules is relatively well-known and frequently utilized in chemical synthesis and material science, controlled assembly of molecules represents a new concept and approach. The present work demonstrates the concept of controlled molecular assembly using a non-spherical biomolecule, heparosan tetrasaccharide (MW = 1.099 kD).

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Building trust in science and evidence-based decision-making depends heavily on the credibility of studies and their findings. Researchers employ many different study designs that vary in their risk of bias to evaluate the true effect of interventions or impacts. Here, we empirically quantify, on a large scale, the prevalence of different study designs and the magnitude of bias in their estimates.

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Accurate characterization of oocyte development is essential to understanding foundational aspects of reproductive biology and successful management of Pacific halibut (Hippoglossus stenolepis). Here this study provides complete histological descriptions for eight oocyte developmental stages in addition to postovulatory follicles and demonstrates the potential for oocyte size frequency distribution to act as a proxy for ovarian developmental stage and future maturity assessments. Importantly, it provides the first histological evidence that Pacific halibut have a group-synchronous ovarian developmental pattern with determinate fecundity and support for their batch-spawning strategy.

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We develop fully glycosylated computational models of ACE2-Fc fusion proteins which are promising targets for a COVID-19 therapeutic. These models are tested in their interaction with a fragment of the receptor-binding domain (RBD) of the Spike Protein S of the SARS-CoV-2 virus, via atomistic molecular dynamics simulations. We see that some ACE2 glycans interact with the S fragments, and glycans are influencing the conformation of the ACE2 receptor.

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Spectral imaging approaches provide new possibilities for measuring and discriminating fluorescent molecules in living cells and tissues. These approaches often employ tunable filters and robust image processing algorithms to identify many fluorescent labels in a single image set. Here, we present results from a novel spectral imaging technology that scans the fluorescence excitation spectrum, demonstrating that excitation-scanning hyperspectral image data can discriminate among tissue types and estimate the molecular composition of tissues.

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Cross-contamination of epidermal mucus was assessed at three sampling locations on the bodies of Pacific halibut Hippoglossus stenolepis by inducing contact between fish coated with labelled synthetic mucus and non-treated fish. Results indicate a positive relationship between sampling site exposure and sample contamination and that mucous sample cross-contamination can be mitigated by sampling in a location protected from external contact.

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Species distribution models (SDMs) are commonly used to model the spatial structure of species in the marine environment, however, most fail to account for detectability of the target species. This can result in underestimates of occupancy, where nondetection is conflated with absence. The site occupancy model (SOM) overcomes this failure by treating occupancy as a latent variable of the model and incorporates a detection submodel to account for variability in detection rates.

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Hematoma formation after peripheral nerve block placement is a rare event. We report a case of a morbidly obese patient who was anticoagulated with apixaban and developed a massive thigh hematoma after an ultrasound-guided adductor canal block. Despite continuous visualization of the block needle, an unrecognized vascular injury occurred leading to a 14-cm hematoma in the anterolateral thigh.

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