Publications by authors named "David Owen"

Background: Mental health disorders are currently the main contributor to poor quality of life and years lived with disability. Symptoms common to many mental health disorders lead to impairments or changes in the use of language, which are observable in the routine use of social media. Detection of these linguistic cues has been explored throughout the last quarter century, but interest and methodological development have burgeoned following the COVID-19 pandemic.

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Methicillin-resistant (MRSA), in which acquisition of [which encodes the cell wall peptidoglycan biosynthesis component penicillin-binding protein 2a (PBP2a)] confers resistance to β-lactam antibiotics, is of major clinical concern. We show that, in the presence of antibiotics, MRSA adopts an alternative mode of cell division and shows an altered peptidoglycan architecture at the division septum. PBP2a can replace the transpeptidase activity of the endogenous and essential PBP2 but not that of PBP1, which is responsible for the distinctive native septal peptidoglycan architecture.

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Rationale And Objectives: Placenta accreta spectrum (PAS) is associated with significant morbidity and mortality. Current radiomic analysis of PAS magnetic resonance (MR) images is often performed on a single imaging plane. However, depending on the chosen imaging plane, radiomic features extracted from the same patient may vary due to the differing orientations and anatomical contexts, potentially leading to inconsistent results.

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Detoxification of heme in depends on its crystallization into hemozoin. This pathway is a major target of antimalarial drugs. The crystalline structure of hemozoin was established by X-ray powder diffraction using a synthetic analog, β-hematin.

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Purpose: Segmentation of surgical scenes may provide valuable information for real-time guidance and post-operative analysis. However, in some surgical video frames there is unavoidable ambiguity, leading to incorrect predictions of class or missed detections. In this work, we propose a novel method that alleviates this problem by introducing a hierarchy and associated hierarchical inference scheme that allows broad anatomical structures to be predicted when fine-grained structures cannot be reliably distinguished.

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Article Synopsis
  • * A study focused on 15 α-L-fucosidases from the GH29 family utilized sequence similarity network analysis to evaluate their specificities for various fucosylated sugars and established their structural basis through advanced imaging techniques.
  • * The research combined experimental data with machine-learning models to categorize over 34,000 GH29 sequences into similarity clusters, paving the way for future identification of novel glycoside hydrolases with tailored functionalities.
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  • Cyclic β-amino acids (cβAAs) are important for creating compact and stable peptide structures, enhancing their resistance to breakdown and improving their ability to bind to target proteins.
  • An engineered tRNA allowed for the efficient incorporation of cβAAs into a macrocyclic peptide library, which was then tested against the SARS-CoV-2 main protease.
  • The peptides BM3 and BM7 demonstrated strong inhibitory effects and exceptional stability in serum, indicating that cβAAs play a crucial role in enhancing the functionality and longevity of peptides in a biological context.
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Persistent inflammation is described in people with HIV (PWH) on antiretroviral treatment (ART). Early ART initiation is associated with reduced inflammation. We aimed to evaluate neuroinflammation, using translocator protein (TSPO) [C]PBR28 PET neuroimaging in PWH who initiated ART during acute HIV (aPWH) versus chronic HIV infection (cPWH) versus a control population.

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The Golgi-localized golgins golgin-97 and golgin-245 capture transport vesicles arriving from endosomes via the protein TBC1D23. The amino-terminal domain of TBC1D23 binds to the golgins, and the carboxyl-terminal domain of TBC1D23 captures the vesicles, but how it recognizes specific vesicles was unclear. A search for binding partners of the carboxyl-terminal domain unexpectedly revealed direct binding to carboxypeptidase D and syntaxin-16, known cargo proteins of the captured vesicles.

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  • Brain perfusion and blood-brain barrier integrity are compromised early in Alzheimer's disease, leading to increased vascular issues.
  • Single nucleus RNA sequencing revealed that endothelial cells in Alzheimer's patients show gene expressions linked to AD susceptibility, particularly involving β-amyloid and impairments in vascular signaling.
  • The study suggests that targeting vascular inflammation and enhancing angiogenesis may help reduce vascular dysfunction and potentially slow down the onset or progression of Alzheimer's disease.
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The exquisite specificity of antibodies can be harnessed to effect targeted degradation of membrane proteins. Here, we demonstrate targeted protein removal utilising a protein degradation domain derived from the endogenous human protein Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9). Recombinant antibodies genetically fused to this domain drive the degradation of membrane proteins that undergo constitutive internalisation and recycling, including the transferrin receptor and the human cytomegalovirus latency-associated protein US28.

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Objective: Older people with multiple sclerosis (MS) have a less active radiological and clinical presentation, but many still attain significant levels of disability; but what drives worsening disability in this group?

Methods: We used data from the UK MS Register to characterize demographics and clinical features of late-onset multiple sclerosis (LOMS; symptom onset at ≥50 years), compared with adult-onset MS (AOMS; onset 18-49 years). We performed a pathology study of a separate MS cohort with a later onset (n = 18, mean age of onset 54 years) versus AOMS (n = 23, mean age of onset 29 years).

Results: In the Register cohort, there were 1,608 (9.

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Purpose: Total wrist arthrodesis (TWA) has been performed using various techniques. We aimed to provide pooled prevalence estimates of union and complications of TWA by technique. A secondary aim was to provide estimates of union and complication rates by treatment of the carpometacarpal joint (CMCJ) in TWA using plates.

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Article Synopsis
  • - The COVID Moonshot was a collaborative, open-science effort focused on finding a new drug to inhibit the SARS-CoV-2 main protease, which is crucial for the virus's survival.
  • - Researchers developed a novel noncovalent, nonpeptidic inhibitor that stands out from existing drugs targeting the same protease, employing advanced techniques like machine learning and high-throughput structural biology.
  • - Over 18,000 compound designs, 490 ligand-bound x-ray structures, and extensive assay data were generated and shared openly, creating a comprehensive and accessible knowledge base for future drug discovery efforts against coronaviruses.
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Despite recent advances in cryo-electron microscopy and artificial intelligence-based model predictions, a significant fraction of structure determinations by macromolecular crystallography still requires experimental phasing, usually by means of single-wavelength anomalous diffraction (SAD) techniques. Most synchrotron beamlines provide highly brilliant beams of X-rays of between 0.7 and 2 Å wavelength.

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Background: It is unknown whether total wrist arthrodesis (TWA) should be performed with or without arthrodesis of the carpometacarpal joint (CMCJ). The aim of this study is to compare CMCJ-spanning TWA plates using 3D printed wrist arthrodesis model with and without arthrodesis of the CMCJ.

Methods: Total wrist arthrodesis plates mounted to 3D printed models were tested under a 4-N bending load at 4 Hz for 50 000 cycles, increased by 15% every 10 000 cycles until failure.

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The placenta is a dynamic organ that must perform a remarkable variety of functions during its relatively short existence in order to support a developing fetus. These functions include nutrient delivery, gas exchange, waste removal, hormone production, and immune barrier protection. Proper placenta development and function are critical for healthy pregnancy outcomes, but the underlying genomic regulatory events that control this process remain largely unknown.

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Article Synopsis
  • Microglial activation is crucial in diseases that involve neuroinflammation and neurodegeneration, with PET scans using TSPO to detect inflammation in the brain, although interpreting these results can be tricky.* -
  • The study finds that while TSPO expression increases in activated microglia in mouse models, it doesn't change in human diseases, indicating a difference in how TSPO is regulated across species.* -
  • Genetic differences in TSPO expression linked to the transcription factor AP1 are noted, suggesting that human TSPO-PET signals are more about the presence of inflammatory cells rather than their activation state.*
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The placenta plays a critical role in fetal development. It serves as a multi-functional organ that protects and nurtures the fetus during pregnancy. However, despite its importance, the intricacies of placental structure and function in normal and diseased states have remained largely unexplored.

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Objective: Translocator protein (TSPO) targeting positron emission tomography (PET) imaging radioligands have potential utility in epilepsy to assess the efficacy of novel therapeutics for targeting neuroinflammation. However, previous studies in healthy volunteers have indicated limited test-retest reliability of TSPO ligands. Here, we examine test-retest measures using TSPO PET imaging in subjects with epilepsy and healthy controls, to explore whether this biomarker can be used as an endpoint in clinical trials for epilepsy.

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Electron diffraction from three dimensional crystals, as a technique for solving molecular structures, is rapidly increasing in popularity. The development of methodology and software has borrowed, to great effect, from macromolecular X-ray crystallography. However, standardization lags behind the development of the technique, and practitioners are forced to work with inadequate data formats that are unable to capture a full description of their experiments.

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Background: Major depressive disorder is a common mental disorder affecting 5% of adults worldwide. Early contact with health care services is critical for achieving accurate diagnosis and improving patient outcomes. Key symptoms of major depressive disorder (depression hereafter) such as cognitive distortions are observed in verbal communication, which can also manifest in the structure of written language.

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Objectives: To evaluate longitudinal placental perfusion using pseudo-continuous arterial spin-labeled (pCASL) MRI in normal pregnancies and in pregnancies affected by chronic hypertension (cHTN), who are at the greatest risk for placental-mediated disease conditions.

Methods: Eighteen normal and 23 pregnant subjects with cHTN requiring antihypertensive therapy were scanned at 3 T using free-breathing pCASL-MRI at 16-20 and 24-28 weeks of gestational age.

Results: Mean placental perfusion was 103.

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