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High-speed imaging of non-photochemical laser-induced nucleation in aqueous cesium chloride
No full textThe contents of this archive are described in detail in the manuscript “High-speed imaging of non-photochemical laser-induced nucleation in aqueous cesium chloride” by Eleanor R. Barber and Andrew J. Alexander, published in Physical Chemistry Chemical Physics, 2025 (doi:10.1039/D4CP04147J). The designation Fn in the folders refer to specific figures in that work (e.g., F1 means Figure 1). The folders contain raw images and edited montages from recordings of nucleation of CsCl crystals from a supersaturated aqueous solution using a single, nanosecond laser pulse
Monitoring changes in the levels of newly synthesized proteins in response to Nutlin-3 treatment
Get PDFDeveloping methodological approaches for discovering novel pathways is a key challenge in the life science research. Biological pathways are regulated - in higher eukaryotes - by a vast diversity of linear peptide motifs that mediate combinatorial specificity in signal transduction pathways. The E3 ubiquitin ligase component (MDM2) is such a protein that interacts with target proteins containing linear motifs such as p53. Drug leads, such as Nutlin-3, that bind to the MDM2 hydrophobic pocket mimic p53 and can release p53 from MDM2 control and this can lead to cell death. However, these drug leads act allosterically, having agonist effects on MDM2’s functions and there are other proteins whose steady state levels can be altered by Nutlin-3. As cell density can alter the proliferation state of cell populations, we examined the impact of Nutlin-3 on levels of newly synthesized proteins using pulse-SILAC Mass spectrometry. The data demonstrate that at differing cell densities or population-wide proliferation rates, different newly synthesized proteins dominant the proteome landscape in aNutlin-3 dependent manner. These data further confirm that the cell state in a population of cells can in turn impact on the MDM2 signalling landscape. This methodology forms a blueprint for biomarker discovery using clinical samples that can detect changes in the synthesis rate of proteins in cell populations treated with specific agents. Broader implications highlight tools that can be used to study allosteric regulation of protein-drug combinations
Veterinary paraprofessional training and business environment needs assessment:Lessons learned
Get PDFThrough an innovative continuous professional development (CPD) training programme, “Growing your business through preventive livestock healthcare”, the Food and Agriculture Organization of the United Nations (FAO) has aimed to address private sector veterinary paraprofessionals’ skills gaps and support them to develop successful businesses providing preventive livestock health services to small-scale farmers and pastoralists. This document details the methodology of the needs assessment process and the key findings, including content on the legal frameworks, curricula, priority subjects, existing CPD, and design considerations
The prehistory of the idea that thinking is modelling
Get PDFThis paper examines early expositions of the idea that to think about an object is to construct and manipulate an internal model of that object. The origin of this idea is normally credited to Kenneth Craik (1943) but here I show that it is prefigured in the writings of two nineteenth century physicist-psychologists, Hermann von Helmholtz and Ernst Mach
Ancient genomics and the origin, dispersal, and development of domestic sheep
Get PDFThe origins and prehistory of domestic sheep (Ovis aries) are incompletely understood; to address this, we generated data from 118 ancient genomes spanning 12,000 years sampled from across Eurasia. Genomes from Central Türkiye ~8000 BCE are genetically proximal to the domestic origins of sheep but do not fully explain the ancestry of later populations, suggesting a mosaic of wild ancestries. Genomic signatures indicate selection by ancient herders for pigmentation patterns, hornedness, and growth rate. Although the first European sheep flocks derive from Türkiye, in a notable parallel with ancient human genome discoveries, we detected a major influx of Western steppe-related ancestry in the Bronze Age
Processing appositive relative clauses:Effects of information structure and sentence structure
Get PDFIn a self-paced reading experiment, we investigate the processing of complex sentences containing a matrix clause and a subordinate clause, specifically, an appositive relative clause (ARC), which has been posited to have distinct information structural properties. We test the predictions made by three long-standing ordering principles: the given-new principle (given before new information ordering facilitates processing), the clause structure principle (matrix clause before subordinate clause ordering facilitates processing) and the clause-type mapping of information principle (given information in subordinate clause and new information in matrix clause facilitates processing). Our results show that predictions made by the given-new principle and the clause structure principle hold for sentences with an ARC. We do not find evidence for the clause-type mapping of information principle. Instead, our findings suggest that the matrix clause in sentences with an ARC has a function usually associated with subordinate clauses, namely grounding, whereby its content serves as the thematic ground that supports understanding of what follows in the next clause. We suggest this is due to the matrix clause-like nature of ARCs with respect to both their syntactic structure and their expected information status
Deep sequencing of BCR heavy chain repertoires in myalgic encephalomyelitis/chronic fatigue syndrome
Get PDFMyalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a common and debilitating chronic illness of unknown aetiology. Chronic infection and autoimmune responses have been proposed as two mechanisms that potentially underlie the pathogenesis of ME/CFS. To explore these disease hypotheses, we characterised the antigen-specific receptors of B cells using adaptive immune receptor repertoire sequencing. We compared the B-cell receptor (BCR) repertoires of 25 patients with mild/moderate ME/CFS, 36 patients with severe ME/CFS, 21 healthy controls, and 28 patients with multiple sclerosis (MS) to identify signatures of infection or autoimmune responses. ME/CFS patients did not display increased clonality or differential somatic hypermutation compared to healthy controls and patients with MS. One of two immunoglobulin heavy variable (IGHV) genes, IGHV3-30, reported to be increased in ME/CFS patients in a previous study, was replicated in patients with mild/moderate disease in our cohort. However, there was no evidence of ongoing adaptive responses in IGHV3-30 repertoires from mild/moderate ME/CFS patients with increased IGHV3-30 usage. There were no detectable repertoire signatures associated with infection or autoimmunity in repertoires from ME/CFS patients, but we observed skewing of the ratio of IgM to IgG BCRs in patients with mild/moderate ME/CFS, a preliminary finding that presents an opportunity for follow-up work
Delirium and Cognitive Screening in National Hip Fracture Registries: Scoping Review Protocol [version 2; peer review: 2 approved]
Get PDFBackgroundDelirium and cognitive impairment are common in hip fracture populations and are associated with significant adverse patient outcomes. National hip fracture registries facilitate improvements in patient outcomes and care quality, such as reduced mortality and the development of specialist multidisciplinary services. However, there is substantial variation in the data collected and reported in relation to delirium and cognition, which impedes international comparison and may reduce quality of care.ObjectiveThis scoping review aims to identify delirium and cognition data items currently collected by hip fracture registries internationally, to identify associated registry guidance that exists for the administration of delirium and cognitive screening tools, and report outcomes of these data items across the most recently published annual reports of identified hip fracture registries.MethodsThis scoping review will be conducted in accordance with the Preferred Reporting Items for Systematic Reviews extension for Scoping Reviews (PRISMA-ScR). We will search the following databases: Medline Ovid; Embase; CINAHL EBSCOHost. Relevant websites such as the Fragility Fracture Network (FFN) will also be searched. Study selection and review will be carried out independently by two research team members, with discrepancies resolved by a third member of the research team. Data extraction and synthesis will be conducted by one reviewer and checked for accuracy and omissions by another. The scoping review findings will be informed and validated through engagement with the FFN Hip Fracture Audit Special Interest Group, who will share their knowledge, expertise, and research to achieve consensus over core aspects of the scoping review findings.ConclusionBy identifying existing heterogeneity in delirium and cognitive screening tool use and administration, it is hoped that administration and specific screening tool use will become standardised to optimise comparability across countries and ensure that high quality and reliable data are included across international registry reports
The type of carbon source not the growth rate it supports can determine diauxie in Saccharomyces cerevisiae
Get PDFHow cells choose between carbon sources is a classic example of cellular decision-making. Microbes often prioritise glucose, but there has been little investigation of whether other sugars are also preferred. Here we study budding yeast growing on mixtures of sugars with palatinose, a sucrose isomer that cells catabolise with the MAL regulon. We find that the decision-making involves more than carbon flux-sensing: yeast prioritise galactose over palatinose, but sucrose and fructose weakly if at all despite each allowing faster growth than palatinose. With genetic perturbations and transcriptomics, we show that the regulation is active with repression of the MAL genes via Gal4, the GAL regulon’s master regulator. We argue, using mathematical modelling, that cells enforce their preference for galactose through weakening the MAL regulon’s positive feedback. They do so through decreasing intracellular palatinose by repressing MAL11, the palatinose transporter, and expressing the isomaltases IMA1 and IMA5. Supporting these predictions, we show that deleting IMA1 abolishes diauxie. Our results demonstrate that budding yeast actively prioritises carbon sources other than glucose and that such priorities need not reflect differences in growth rates. They imply that carbon-sensing strategies even in model organisms are more complex than previously thought
Clinical outcomes and complications of tracheal resection and anastomosis in dogs and cats: 20 cases (2009-2022)
Get PDFOBJECTIVES: To report clinical presentation, short-term outcome and complications of tracheal resection and anastomosis in dogs and cats.MATERIALS AND METHODS: Clinical records of pets treated with tracheal resection and anastomosis in seven UK-based veterinary referral centres were retrospectively reviewed (2009 to 2022).RESULTS: Twenty client-owned pets (eight dogs; 12 cats) were included. Clinical signs comprised dyspnoea (n = 15), stridor (n = 5), subcutaneous emphysema (n = 3), pneumothorax and pneumomediastinum (n = 1), coughing (n = 3), regurgitation (n = 1) and exercise intolerance (n = 1). Indication for surgery was traumatic tracheal rupture (n = 5), tracheal avulsion (n = 7), neoplasia (n = 5) and stenosis (n = 3). Complications occurred in 15 patients (75%). Non-anastomotic complications occurred in nine patients and consisted of cough (n = 5), self-resolving laryngeal paralysis (n = 1), surgical site infection (n = 1) and septic shock (n = 2). Anastomotic complications occurred in seven patients and consisted of anastomotic dehiscence (n = 1), tracheal stenosis (n = 4) and fatal respiratory failure (n = 2). Revision surgery was performed in two dogs due to anastomotic dehiscence and stenosis, and tracheal stenting was performed in one cat due to stenosis. Sixteen patients survived to hospital discharge and 14 survived to latest follow-up (median: 119 days; range: 14 to 1744). Outcome was scored as excellent in five, good in seven, fair in two and poor in six patients.CLINICAL SIGNIFICANCE: Tracheal resection and anastomosis is the surgical technique of choice to reconstruct tracheal defects. Although more than half of the patients recovered well, high morbidity and mortality rates were documented. This may be due to the severe comorbidities affecting most tracheal resection and anastomosis patients, as well as the client's decision against further treatment when facing serious post-operative complications.</p
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