The protein homeostasis (proteostasis) network includes quality control systems that coordinate protein synthesis, folding, localization, and degradation, and is deregulated in numerous diseases including cancer. Loss of proteostasis can activate lethal cellular stress responses, potentially opening a therapeutic window. Previous research demonstrated that MAL3-101, an inhibitor of heat shock protein 70-kD (HSP70) chaperones, selectively induces rhabdomyosarcoma (RMS) cell death via unfolded protein response (UPR) activation.
View Article and Find Full Text PDFBackground: Chronic subdural haematoma (CSDH) is common in the elderly, with approximately 40% of patients with CSDH taking anti-thrombotic medications. Surgery necessitates temporary cessation. The optimal time of postoperative antithrombotic resumption is not known, with the risk of recurrence balanced against the risk of thrombosis.
View Article and Find Full Text PDFGangliosides are sialic acid-containing glycosphingolipids integral to the cell membrane and are particularly abundant in the nervous system. Aberrant ganglioside metabolism contributes to pathological conditions including neurodegenerative diseases, lysosomal storage disorders, and cancer. Currently, tools to visualize and detect gangliosides are very limited and non-specific.
View Article and Find Full Text PDFClimate change contributes to widespread shifts in body size across taxa which can impact population and community dynamics. However, the reasons for variability in the direction and intensity of responses remain uncertain. Smaller body size improves thermoregulatory efficiency but can increase dehydration risk.
View Article and Find Full Text PDFCrystalline solids can become band insulators due to fully filled bands, or Mott insulators due to strong electronic correlations. While Mott insulators can theoretically occur in systems with an even number of electrons per unit cell, distinguishing them from band insulators experimentally has remained a longstanding challenge. In this work, we present a unique momentum-resolved signature of a dimerized Mott-insulating phase in the experimental spectral function of NbBr: the top of the highest occupied band along the out-of-plane direction k has a momentum-space separation Δk = 2π/d, whereas that of a band insulator is less than π/d, where d is the average interlayer spacing.
View Article and Find Full Text PDFIntroduction: Central serous chorioretinopathy (CSCR) is a common cause of acute, monocular vision loss amongst men aged 40-50 years. Diagnosis is typically multimodal, requiring advanced ophthalmic imaging. These techniques are not readily available in acute care settings.
View Article and Find Full Text PDFCurr Opin Struct Biol
June 2025
Raman microscopy offers a unique combination of chemical and spatial resolution with structural sensitivity. This makes it an ideal tool for studies of protein structural changes in heterogenous samples such as protein liquid-liquid phase separation (LLPS) and amyloid formation. These processes are characterized by the spontaneous assembly of proteins to form either microscopic liquid droplets or insoluble filaments stabilized by β-sheets.
View Article and Find Full Text PDFObjectives: Routine monitoring of renal and hepatic function during chemotherapy ensures that treatment-related organ damage has not occurred and clearance of subsequent treatment is not hindered; however, frequency and timing are not optimal. Model bias and data heterogeneity concerns have hampered the ability of machine learning (ML) to be deployed into clinical practice. This study aims to develop models that could support individualised decisions on the timing of renal and hepatic monitoring while exploring the effect of data shift on model performance.
View Article and Find Full Text PDFBackground: Patients with an elevated admission National Early Warning Score (NEWS) are more likely to die while in hospital. However, it is not known if this increased mortality risk is the same for all diagnoses. The aim of this study was to determine and compare the increased risk of in-hospital mortality associated with an elevated NEWS and different primary discharge diagnoses in unselected emergency admissions to a UK university teaching hospital.
View Article and Find Full Text PDFObjectives: Increasing operational pressures on emergency departments (ED) make it imperative to quickly and accurately identify patients requiring urgent clinical intervention. The widespread adoption of electronic health records (EHR) makes rich feature patient data sets more readily available. These large data stores lend themselves to use in modern machine learning (ML) models.
View Article and Find Full Text PDFTunable quantum materials hold great potential for applications. Of special interest are materials in which small lattice strain induces giant electronic responses. The kagome compounds AVSb (A = K, Rb, Cs) provide a testbed for electronic tunable states.
View Article and Find Full Text PDFInteraction between electrons and phonons in solids is a key effect defining the physical properties of materials, such as electrical and thermal conductivity. In transition metal dichalcogenides (TMDCs), the electron-phonon coupling results in the formation of polarons, quasiparticles that manifest themselves as discrete features in the electronic spectral function. In this study, we report the formation of polarons at the alkali-dosed MoSe surface, where Rashba-like spin splitting of the conduction band states is caused by an inversion-symmetry breaking electric field.
View Article and Find Full Text PDFSugar maples (Acer saccharum Marshall) develop elevated stem pressures in springtime through the compression and expansion of gas bubbles present within xylem fibres. The stability of this gas within the fibres is hypothesised to be due to the elevated sugar concentration of maple sap and the presence of an osmotic barrier between fibres and vessels. Without this osmotic barrier gas bubbles are predicted to dissolve rapidly.
View Article and Find Full Text PDFNat Commun
September 2024
Doping of a Mott insulator gives rise to a wide variety of exotic emergent states, from high-temperature superconductivity to charge, spin, and orbital orders. The physics underpinning their evolution is, however, poorly understood. A major challenge is the chemical complexity associated with traditional routes to doping.
View Article and Find Full Text PDFLinker histones play an essential role in chromatin packaging by facilitating compaction of the 11-nm fiber of nucleosomal "beads on a string." The result is a heterogeneous condensed state with local properties that range from dynamic, irregular, and liquid-like to stable and regular structures (the 30-nm fiber), which in turn impact chromatin-dependent activities at a fundamental level. The properties of the condensed state depend on the type of linker histone, particularly on the highly disordered C-terminal tail, which is the most variable region of the protein, both between species, and within the various subtypes and cell-type specific variants of a given organism.
View Article and Find Full Text PDFThe magnetic skyrmions generated in a centrosymmetric crystal were recently first discovered in Gd_{2}PdSi_{3}. In light of this, we observe the electronic structure by angle-resolved photoemission spectroscopy and unveil its direct relationship with the magnetism in this compound. The Fermi surface and band dispersions are demonstrated to have a good agreement with the density functional theory calculations carried out with careful consideration of the crystal superstructure.
View Article and Find Full Text PDFChronic subdural hematoma (CSDH) is increasingly common, particularly in the older and multimorbid population. Surgical proficiency in management is required in the early years of U.K.
View Article and Find Full Text PDFSpin-orbit coupling in noncentrosymmetric crystals leads to spin-momentum locking - a directional relationship between an electron's spin angular momentum and its linear momentum. Isotropic orthogonal Rashba spin-momentum locking has been studied for decades, while its counterpart, isotropic parallel Weyl spin-momentum locking has remained elusive in experiments. Theory predicts that Weyl spin-momentum locking can only be realized in structurally chiral cubic crystals in the vicinity of Kramers-Weyl or multifold fermions.
View Article and Find Full Text PDFDrug use in a sexualised context provides unique challenges both in specialised clinics (psychiatric and sexual health clinics) as well as general practice. Layered onto this leads some inequalities in health care to poorer outcomes in specific groups. This article aims to provide evidence based harm reduction strategies that can easily be applied in primary care to reduce complications, identify those at higher risk and deploy appropriate treatments.
View Article and Find Full Text PDFA chronic subdural haematoma (CSDH) is a collection of aged blood between the dura and the brain, typically treated with surgical evacuation. Many patients with CSDH have comorbidities requiring the use of antithrombotic medications. The optimal management of these medications in the context of CSDH remains unknown, as the risk of recurrence must be carefully weighed against the risk of vaso-occlusive events.
View Article and Find Full Text PDFHeart failure afflicts an estimated 6.5 million people in the United States, driven largely by incidents of coronary heart disease (CHD). CHD leads to heart failure due to the inability of adult myocardial tissue to regenerate after myocardial infarction (MI).
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