Publications by authors named "Beattie D"

Pompe disease is a rare glycogen storage disease caused by mutations in the enzyme acid α-glucosidase (GAA) resulting in pathological accumulation of glycogen in muscle tissues leading to progressive weakness and respiratory dysfunction. Enzyme replacement therapy (ERT) with GAA is currently the sole treatment option for patients with Pompe disease. ERT burdens patients with frequent intravenous infusions while insufficiently halting disease progression due to incomplete ERT skeletal muscle distribution.

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is the causal agent of myrtle rust in over 480 species within the family Myrtaceae. Lineages of are structured by their hosts in the native range, and some have success in infecting newly encountered hosts. For example, the pandemic biotype has spread beyond South America, and proliferation of other lineages is an additional risk to biodiversity and industries.

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Glycogen is a large polymer of glucose that functions as an important means of storing energy and maintaining glucose homeostasis. Glycogen synthesis and degradation pathways are highly regulated and their dysregulation can contribute to disease. Glycogen storage diseases are a set of disorders that arise from improper glycogen metabolism.

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PRMT5, a type 2 arginine methyltransferase, has a critical role in regulating cell growth and survival in cancer. With the aim of developing MTA-cooperative PRMT5 inhibitors suitable for MTAP-deficient cancers, herein we report our efforts to develop novel "MTA-cooperative" compounds identified through a high-throughput biochemical screening approach. Optimization of hits was achieved through structure-based design with a focus on improvement of oral drug-like properties.

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Hypothesis: Naturally extracted polysaccharides, such as guar gum, are promising candidates for environmentally friendly flotation reagents. It is hypothesized that the kinetics of collision of sub- to millimeter gas bubbles with a hydrophobic graphite surface, and the stability of thin liquid film formed between the bubble and surface is affected by an adsorbed layer of guar gum.

Experiments: A combination of gravimetric (quartz crystal microbalance with dissipation) and imaging (atomic force microscopy) techniques was used to investigate the adsorption of guar gum on graphite surface, while high-speed camera imaging allowed for direct observation of the bubble collision process with guar gum-modified graphite surfaces with millisecond resolution.

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This review focuses on the current understanding regarding lipid crystallisation at oil-water interfaces. The main aspects of crystallisation in bulk lipids will be introduced, allowing for a more comprehensive overview of the crystallisation processes within emulsions. Additionally, the properties of an emulsion and the impact of lipid crystallisation on emulsion stability will be discussed.

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Glycogen synthase 1 (GYS1), the rate-limiting enzyme in muscle glycogen synthesis, plays a central role in energy homeostasis and has been proposed as a therapeutic target in multiple glycogen storage diseases. Despite decades of investigation, there are no known potent, selective small-molecule inhibitors of this enzyme. Here, we report the preclinical characterization of MZ-101, a small molecule that potently inhibits GYS1 in vitro and in vivo without inhibiting GYS2, a related isoform essential for synthesizing liver glycogen.

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Objectives: The study investigated the relationship between psychological distress, alcohol use, the three fears of compassion (i.e., to self, from others, and to others), facilitators and inhibitors of compassion (self-reassurance, shame, and self-criticizing), and the three flows of compassion (to self, to others, and from others) on moral injury (MI) in military veterans.

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Mid-air haptic feedback technology produces tactile sensations that are felt without the need for physical interactions. However, mid-air haptic experiences need to be congruent with visual cues to reflect user expectations. To overcome this, we investigate how to visually present properties of objects, so that what one feels is a more accurate prediction of what one sees.

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This study examined the prevalence of HIV risk factors and their association with intervention exposure among adolescent girls and young women (AGYW) living in six South African districts in which a combination HIV-prevention intervention was being implemented. A cross-sectional household survey was conducted from 2017 to 2018 among a representative sample of AGYW aged 15-24 years living in the six districts. We used an electronic questionnaire for self-reported demographic and behavioural questions and blood samples were taken to confirm HIV status in the laboratory.

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Due to increased reliance on glycolysis, which produces lactate, monocarboxylate transporters (MCTs) are often upregulated in cancer. MCT4 is associated with the export of lactic acid from cancer cells under hypoxia, so inhibition of MCT4 may lead to cytotoxic levels of intracellular lactate. In addition, tumor-derived lactate is known to be immunosuppressive, so MCT4 inhibition may be of interest for immuno-oncology.

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Background: Neoadjuvant long course chemoradiotherapy has become the standard treatment for locally advanced rectal cancer. It can reduce tumour bulk, downstage, reduce the risk of local recurrence, and increase the possibility of clear resection margins. The aim of our study is to evaluate all patients over a 9 year period who underwent neoadjuvant chemoradiotherapy for rectal cancer and entered our watch and wait programme.

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Hypothesis: Dairy proteins and mono- and diglycerides (MDG) are often used in unison to tailor the properties of dairy-based emulsions. However, there are significant gaps in our understanding of how proteins affect lipid crystallisation at the oil-water interface. We have used a unique combination of interfacially-sensitive techniques to elucidate the impact of dairy proteins on interfacial MDG crystal formation.

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Well-defined block copolymers have been widely used as emulsifiers, stabilizers, and dispersants in the chemical industry for at least 50 years. In contrast, nature employs amphiphilic proteins as polymeric surfactants whereby the spatial distribution of hydrophilic and hydrophobic amino acids within the polypeptide chains is optimized for surface activity. Herein, we report that polydisperse statistical copolymers prepared by conventional free-radical copolymerization can provide superior foaming performance compared to the analogous diblock copolymers.

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Article Synopsis
  • * Researchers modified previously established DNA-PKcs inhibitors by adding a basic group to improve distribution and metabolic stability, but this tweak also caused hERG activity, which can lead to heart issues.
  • * Further optimization was needed, resulting in a compound that has low hERG activity and maintains good selectivity and pharmacokinetics for potential therapeutic use.
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Metal-organic frameworks (MOFs) with ratiometric sensing properties are desirable for many applications due to their intrinsic self-calibration. We report the re-assessment of the sensing properties of a MOF, originally reported as containing europium(III) and 2-hydroxyterephtalic acid, and having fluorescent ratiometric iron(III) sensing properties. Synchrotron single-crystal X-ray diffraction and proton nuclear magnetic resonance (H NMR) spectroscopy revealed that the MOF is composed of 2-methoxyterephthalate, not 2-hydroxyterephthalate as originally reported.

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The synthesis of polycyclic aromatic hydrocarbons (PAHs) and related nanographenes requires the selective and efficient fusion of multiple aromatic rings. For this purpose, the Diels-Alder cycloaddition has proven especially useful; however, this approach currently faces significant limitations, including the lack of versatile strategies to access annulated dienes, the instability of the most commonly used dienes, and difficulties with aromatization of the [4 + 2] adduct. In this report we address these limitations the marriage of two powerful cycloaddition strategies.

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Despite the widespread use of copper catalysis for the formation of C-C bonds, debate about the mechanism persists. Reductive elimination from Cu(III) is often invoked as a key step, yet examples of its direct observation from isolable complexes remain limited to only a few examples. Here, we demonstrate that incorporation of bulky mesityl (Mes) groups into the α-positions of a phenanthrene-appended zirconacyclopentadiene, CpZr(2,5-Mes-phenanthro[9,10]C), enables efficient oxidative transmetalation to the corresponding, formal Cu(III) metallacyclopentadiene dimer.

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Water-in-oil-in-water (W/O/W) emulsions (double emulsions) have often been used for the encapsulation of bioactive compounds such as anthocyanins. Instability of both anthocyanins and double emulsions creates a need for a tailored composition of the aqueous phase. In this work, double emulsions with a gelled internal water phase were produced and monitored over a 20-day storage period.

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Agostic interactions are examples of σ-type interactions, typically resulting from interactions between C-H σ-bonds with empty transition metal d orbitals. Such interactions often reflect the first step in transition metal-catalysed C-H activation processes and thus are of critical importance in understanding and controlling σ bond activation chemistries. Herein, we report on the unusual electronic structure of linear electron-rich d Ni(i) complexes with symmetric bis(C-H) agostic interactions.

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Dairy emulsions contain an intrinsically heterogeneous lipid phase, whose components undergo crystallisation in a manner that is critical to dairy product formulation, storage, and sensory perception. Further complexity is engendered by the diverse array of interfacially-active molecules naturally present within the serum of dairy systems, and those that are added for specific formulation purposes, all of which interact at the lipid-serum interface and modify the impact of lipid crystals on dairy emulsion stability. The work described in this article addresses this complexity, with a specific focus on the impact of temperature cycling and the effect of emulsifier type on the formation and persistence of lipid crystals at lipid-solution interfaces.

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Article Synopsis
  • The study uses ATR FTIR to examine how the food protein β-lactoglobulin (BLG) and bile salts (TCA and GCA) interact with titanium dioxide nanoparticles, which could inform our understanding of digestion and bioavailability.
  • TCA shows weak retention on TiO nanoparticles, while GCA binds more strongly through two mechanisms, with one form being particularly resistant to removal.
  • BLG displays irreversible binding and structural changes depending on pH, suggesting that conditions in the stomach and small intestine affect its behavior, and coadsorption studies highlight how TCA and GCA’s binding can change in the presence of BLG.
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The existing literature on the rise velocities of air bubbles in aqueous surfactant solutions adsorbing at the water-air interface focuses mainly on large bubbles ( > 1.2 mm). In addition, due to the way the bubbles in rising bubble experiments are formed, their size is dependent on interfacial tension (the lower the interfacial tension the smaller the bubble).

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Article Synopsis
  • * The study involved 284 children diagnosed with CD, with a mean age of 8.3 years, and noted a higher occurrence of neurological problems in males and those diagnosed at an older age.
  • * Interestingly, the prevalence of these neurological problems in the studied children was lower compared to what adult CD studies reported, and it is similar to or lower than the prevalence in the general childhood population.
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It is well known that reversible addition-fragmentation chain transfer (RAFT) aqueous dispersion polymerization of 2-hydroxypropyl methacrylate (HPMA) enables the rational design of diblock copolymer worm gels. Moreover, such hydrogels can undergo degelation on cooling below ambient temperature as a result of a worm-to-sphere transition. However, only a subset of such block copolymer worms exhibit thermoresponsive behavior.

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