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Recognising and responding to acute deterioration in care home residents: a scoping review
No full textPatient perspectives of asthma treatment and belief barriers to implementing new guidelines: a qualitative analysis of an online forum
No full textLarge-Scale Pre-Trained Models Empowering Phrase Generalization in Temporal Sentence Localization
No full textAccuracy of continuous glucose monitoring during noncardiac surgery. Response to Br J Anaesth 2025; 135.
No full textMOLECULAR CHARACTERISATION OF ASTRIN TO UNDERSTAND HOW KINETOCHORE-MICROTUBULE ATTACHMENTS ARE REGULATED
No full textThe tetrameric Astrin-SKAP complex is required for proper chromosome alignment and segregation, and timely mitotic progression. Astrin C-terminus is crucial for Astrin-SKAP’s selective recruitment to end-on attached kinetochores and comprises a 70-aa conserved tail region that dynamically interacts with the Serine/Threonine phosphatase, PP1. The Astrin:PP1 interaction at the outer kinetochore serves as a positive feedback loop, promoting further Astrin enrichment at the outer kinetochore that is essential for stabilising end-on kinetochore-microtubule attachments, independent of biorientation. Characterising the evolutionarily conserved C-terminal region of human Astrin would help gain insights into how chromosome-microtubule attachments are monitored. In this work, I have expressed and biochemically characterised three His-tagged C-terminal Astrin fragments: His-Astrin-956-1193, His Astrin-851-1193, and His-Astrin-694-1193. Both His-Astrin956-1193, which encompasses two putative PP1-interacting short linear motifs (SLiMs) and the RVxF motif, and His Astrin851-1193, which comprises the minimal kinetochore-localising domain of Astrin, fold as alpha-helical structures in vitro. Analytical SEC experiments and preliminary pull-down assays suggest that His-Astrin851-1193 does not stably interact with a truncated NDC80 complex at least under the tested conditions. I have also explored conditions to study the kinetochore-localising and PP1-interacting Astrin C-terminal fragments using negative stain TEM. Preliminary analyses indicate that His-Astrin956-1193 and His-Astrin851-1193 tend to form soluble aggregates or higher-order structures under tested conditions. While earlier studies focussed on Astrin’s N-terminal region, my work establishes a foundation for biochemically characterising kinetochore localising Astrin C-terminal fragments and developing preliminary assays for studying Astrin:NDC80 interaction. To search for additional PP1-interacting SLiMs in Astrin, I generated mutants of the SLRR and putative FQ/ motifs adjacent to the previously reported PP1-interacting RVxF motif. Collaborative analyses of mutant Astrin localisation in metaphase HeLa cells, using live-cell microscopy, showed no significant changes in the kinetochore localisation of the Astrin-(A/D)LRR mutants compared to Astrin-WT. However, Alanine substitution of a putative FQ/ɸɸ motif enhanced Astrin’s kinetochore enrichment, and the dual loss of RVxF and FQ/ɸɸ motifs significantly reduced Astrin's kinetochore levels compared to the loss of RVxF motif alone. Although these studies require confirmation, with further repeats and in the absence of endogenous Astrin, they suggest that Astrin’s putative FQ/ɸɸ motif and RVxF motif may function synergistically to facilitate Astrin’s recruitment to end on attached kinetochores
The distributional impact of the UK Soft Drinks Industry Levy on dental care costs: An extended cost-effectiveness analysis
Get PDFA “COP da Verdade” e a ficção das finanças verdes
Get PDFO saneamento brasileiro virou vitrine da financeirização da sustentabilidade. Por trás do marketing “verde” – e de suas debêntures subsidiadas –, há uma escolha política: transformar direitos em ativos rentáveis. Alternativa: recuperar o sentido público da transição ecológica
Unitarity and the On-Shell Action of Worldline Quantum Field Theory
Get PDF A bstract We develop the on-shell action formalism within Worldline Quantum Field Theory (WQFT) to describe scattering of spinning compact bodies in General Relativity in the post-Minkowskian (PM) expansion. The real on-shell action is constructed from vacuum diagrams with causal (retarded) propagators from which scattering observables such as momentum impulse and spin kick follow via Poisson brackets of the initial scattering data. Furthermore, we explore the implications of unitarity at the level of the worldline and show how generalised unitarity techniques can be adapted to WQFT to efficiently compute multi-loop contributions. Our work establishes a concrete link between WQFT and amplitude-based methods, elucidating how unitarity cuts ensure equivalence between the on-shell action derived from either approach. Extending the state-of-the-art, we complete the full on-shell action — including dissipative terms — at (formal) 3PM order and up to quartic spin interactions on both massive bodies.</jats:p