Publications by authors named "Davies O"

Background: A growing population of patients is seeking treatments that not only affect their overlying features but also restore a more biologically youthful structure and function to the underlying tissue. These strategies are part of what is known as regenerative aesthetics (RA). As an emergent field, clarity regarding the precise definitions and aims of RA and methods to measure the regenerative capacity of RA treatments are lacking.

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Cables formed by head-to-tail polymerization of tropomyosin, localized along the length of sarcomeric and cytoskeletal actin filaments, play a key role in regulating a wide range of motile and contractile processes. The stability of tropomyosin cables, their interaction with actin filaments and the functional properties of the resulting co-filaments are thought to be affected by N-terminal acetylation of tropomyosin. Here, we present high-resolution structures of cables formed by acetylated and unacetylated Schizosaccharomyces pombe tropomyosin ortholog Tpm.

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Background: Peripheral nodal B-cell lymphomas (PNBCL) represent the most common presentation of lymphomas in dogs. Multiagent CHOP (C = cyclophosphamide, H = hydroxydaunorubicin [Doxorubicin], O = Oncovin, P = prednisolone)-based chemotherapy protocols have been widely accepted as gold standard 1st-line treatment. CHOP-25 and CHOP-19 are most commonly prescribed but have never been directly compared.

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BRCA2 is essential for DNA repair by homologous recombination in mitosis and meiosis. It interacts with recombinases RAD51 and DMC1 to facilitate the formation of nucleoprotein filaments on resected DNA ends that catalyse recombination-mediated repair. BRCA2's BRC repeats bind and disrupt RAD51 and DMC1 filaments, whereas its PhePP motifs bind recombinases and stabilise their nucleoprotein filaments.

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  • Skeletal muscle can release small particles (called SM-EVs) that help with muscle health and growth.
  • Researchers compared these particles from young (about 24 years old) and older (about 69 years old) humans to see how aging affects them.
  • They found that while the basic features of these particles didn't change much with age, older ones had more proteins linked to stress and possible damage, suggesting they play an important role in keeping muscles healthy as we get older.
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DNA double-strand break repair by homologous recombination has a specialised role in meiosis by generating crossovers that enable the formation of haploid germ cells. This requires meiosis-specific MEILB2-BRME1, which interacts with BRCA2 to facilitate loading of recombinases onto resected DNA ends. Here, we report the crystal structure of the MEILB2-BRME1 2:2 core complex, revealing a parallel four-helical assembly that recruits BRME1 to meiotic double-strand breaks in vivo.

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  • - The centromere, crucial for chromosome stability, relies on CENP-A-containing nucleosomes for proper microtubule attachment during cell division.
  • - The Mis18 complex, consisting of Mis18α, Mis18β, and Mis18BP1, plays a key role in maintaining centromere identity by facilitating CENP-A loading through its specific chaperone, HJURP.
  • - Research reveals the structure of the Mis18 complex and identifies key interactions needed for assembly and function, emphasizing that while Mis18α can associate with the centromere independently, Mis18β is essential for effective CENP-A loading.
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Cell culture-conditioned medium (CCM) is a valuable source of extracellular vesicles (EVs) for basic scientific, therapeutic and diagnostic applications. Cell culturing parameters affect the biochemical composition, release and possibly the function of CCM-derived EVs (CCM-EV). The CCM-EV task force of the Rigor and Standardization Subcommittee of the International Society for Extracellular Vesicles aims to identify relevant cell culturing parameters, describe their effects based on current knowledge, recommend reporting parameters and identify outstanding questions.

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  • Patients with psoriasis are more likely to experience liver function abnormalities, prompting a study on the effects of bimekizumab treatment on liver health.
  • In a review of 5 phase 3/3b trials over 2 years, researchers found that the rates of hepatic treatment-emergent adverse events (TEAEs) were low and stable, with most liver function parameters not changing significantly.
  • The study concluded that bimekizumab did not increase the risk of liver-related issues compared to placebo and other psoriasis treatments, although certain health conditions could affect liver function outcomes.
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  • The PI3K enzymes are important in regulating cell growth and differentiation, and variants in these enzymes are linked to cancer and related disorders.
  • Genetic variants in PI3K can lead to either undergrowth or overgrowth conditions, with differing impacts on protein interactions that influence cell activity.
  • The study uses molecular dynamics simulations to analyze these variants, revealing that variants causing undergrowth destabilize important protein interactions, while those linked to overgrowth enhance them, providing insights that could inform future therapies.
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The outer corona plays an essential role at the onset of mitosis by expanding to maximize microtubule attachment to kinetochores. The low-density structure of the corona forms through the expansion of unattached kinetochores. It comprises the RZZ complex, the dynein adaptor Spindly, the plus-end directed microtubule motor centromere protein E (CENP-E), and the Mad1/Mad2 spindle-assembly checkpoint proteins.

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The LINC complex transmits cytoskeletal forces into the nucleus to control the structure and movement of nuclear contents. It is formed of nuclear SUN and cytoplasmic KASH proteins, which interact within the nuclear lumen, immediately below the outer nuclear membrane. However, the symmetrical location of KASH molecules within SUN-KASH complexes in previous crystal structures has been difficult to reconcile with the steric requirements for insertion of their immediately upstream transmembrane helices into the outer nuclear membrane.

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Mineralization-competent cells, including hypertrophic chondrocytes, mature osteoblasts, and osteogenic-differentiated smooth muscle cells secrete media extracellular vesicles (media vesicles) and extracellular vesicles bound to the extracellular matrix (matrix vesicles). Media vesicles are purified directly from the extracellular medium. On the other hand, matrix vesicles are purified after discarding the extracellular medium and subjecting the cells embedded in the extracellular matrix or bone or cartilage tissues to an enzymatic treatment.

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  • The study investigates the long-term safety of bimekizumab (BKZ) for patients with moderate-to-severe plaque psoriasis over three years, based on data from multiple trials.
  • Out of 1,495 patients analyzed, the overall rate of treatment-emergent adverse events (TEAEs) was 175.5 per 100 patient-years, which decreased with longer treatment exposure.
  • Common TEAEs included mild cases of nasopharyngitis and oral candidiasis, with serious adverse events remaining rare, indicating that BKZ's safety profile is stable over time.
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In almost all sexually reproducing organisms, meiotic recombination and cell division require the synapsis of homologous chromosomes by a large proteinaceous structure, the synaptonemal complex (SC). While the SC's overall structure is highly conserved across eukaryotes, its constituent proteins diverge between phyla. Transverse filament protein, SYCP1, spans the width of the SC and undergoes amino-terminal head-to-head self-assembly in vitro through a motif that is unusually highly conserved across kingdoms of life.

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Achieving a good outcome for a person with Psoriatic Arthritis (PsA) is made difficult by late diagnosis, heterogenous clinical disease expression and in many cases, failure to adequately suppress inflammatory disease features. Single-centre studies have certainly contributed to our understanding of disease pathogenesis, but to adequately address the major areas of unmet need, multi-partner, collaborative research programmes are now required. HIPPOCRATES is a 5-year, Innovative Medicines Initiative (IMI) programme which includes 17 European academic centres experienced in PsA research, 5 pharmaceutical industry partners, 3 small-/medium-sized industry partners and 2 patient-representative organizations.

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