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MCC950 reduces autophagy and improves cognitive function by inhibiting NLRP3-dependent neuroinflammation in a rat model of Alzheimer's disease
No full textAlzheimer's disease (AD) is the seventh most common cause of mortality and one of the major causes of disability and vulnerability in the elderly. AD is characterized by gradual cognitive deterioration, the buildup of misfolded amyloid beta (Aβ) peptide, and the generation of neurofibrillary tangles. Despite enormous scientific progress, there is no effective cure for AD. Thus, exploring new treatment options to stop AD or at least slow down its progress is important. In this study, we investigated the potential therapeutic effects of MCC950 on NLRP3-mediated inflammasome-driven inflammation and autophagy in AD. Rats treated with streptozotocin (STZ) exhibited simultaneous activation of the NLRP3 inflammasome and autophagy, as confirmed by Western blot, immunofluorescence, and co-immunoprecipitation analyses. MCC950, a specific NLRP3 inhibitor, was intraperitoneally administered (50 mg/kg body weight) to rats with AD-like symptoms induced by intracerebroventricular STZ injections (3 mg/kg body weight). MCC950 effectively suppressed STZ-induced cognitive impairment and anxiety by inhibiting NLRP3-dependent neuroinflammation. Moreover, our findings indicate that MCC950 exerts neuroprotective effects by attenuating autophagy in neuronal cells. The inhibiting effects of MCC950 on inflammasome activation and autophagy were reproduced in vitro, provding further mechansistic insights into MCC950 therapeutic action. Our findings suggest that MCC950 impedes the progression of AD and may also improve cognitive function through the mitigation of autophagy and NLRP3 inflammasome inhibition. [Abstract copyright: Copyright © 2023 Elsevier Inc. All rights reserved.
AI-related data ethics oversight in UK policing
No full textThis paper considers the question of how police-related AI projects and data projects in general are normatively assessed in the UK. After locating data ethics in relation to policing ethics, I shall consider the workings of perhaps the leading regional data ethics committee in the UK. I go on to consider the approach of another committee that might in the future provide national data ethics advice for the police. Finally, I summarize the normative ethics frameworks in use in the two committees and their heavy reliance on the concepts of necessity and proportionality. I suggest that these concepts may have to be supplemented by systematic thinking about varieties of harm and the way in which severe harm may generate obligations to prevent it, where prevention may be assisted by AI models
Data to support : Magnetotransport of Sm2Ir2O7 across the pressure-induced quantum-critical phase boundary
No full textRare-earth pyrochlore iridates host two interlocking magnetic sublattices of corner-sharing tetrahedra and can harbour a unique combination of frustrated moments, exotic excitations and highly correlated electrons. They are also the �first systems predicted to display both topological Weyl semimetal and axion insulator phases. We have measured the transport and magnetotransport properties of single-crystal Sm2Ir2O7 up to and beyond the pressure-induced quantum critical point for all-in-all-out (AIAO) Ir order at p_c = 63 kbar previously identi�fied by resonant X-ray scattering and close to which Weyl semimetallic behavior has been previously predicted. Our fi�ndings overturn the accepted expectation that the suppression of AIAO order should lead to metallic conduction persisting down to zero temperature. Instead, the resistivity-minimum temperature, which tracks the decrease in the AIAO ordering temperature for pressures up to 30 kbar, begins to increase under further application of pressure, pointing to the presence of a second as-yet unidentifi�ed mechanism leading to non-metallic behavior. The magnetotransport does track the suppression of Ir magnetism, however, with a strong hysteresis observed only within the AIAO phase boundary, similar to that found for Ho2Ir2O7 and attributed to plastic deformation of Ir domains. Around pc we �find the emergence of a new type of electronic phase, characterized by a negative magnetoresistance with small hysteresis at the lowest temperatures, and hysteresis-free positive magnetoresistance above approximately 5 K. The temperature dependence of our low-temperature transport data are found to be best described by a model consistent with a Weyl semimetal across the entire pressure range
The endometrial microbiota and early pregnancy loss
Get PDFThe human endometrium is a dynamic entity that plays a pivotal role in mediating the complex interplay between the mother and developing embryo. Endometrial disruption can lead to pregnancy loss, impacting both maternal physical and psychological health. Recent research suggests that the endometrial microbiota may play a role in this, although the exact mechanisms are still being explored, aided by recent technological advancements and our growing understanding of host immune responses. Suboptimal or dysbiotic vaginal microbiota, characterized by increased microbial diversity and reduced Lactobacillus dominance, has been associated with various adverse reproductive events, including miscarriage. However, the mechanisms linking the lower reproductive tract microbiota with pregnancy loss remain unclear. Recent observational studies implicate a potential microbial continuum between the vaginal and endometrial niche in patients with pregnancy loss; however, transcervical sampling of the low biomass endometrium is highly prone to cross-contamination, which is often not controlled for. In this review, we explore emerging evidence supporting the theory that a dysbiotic endometrial microbiota may modulate key inflammatory pathways required for successful embryo implantation and pregnancy development. We also highlight that a greater understanding of the endometrial microbiota, its relationship with the local endometrial microenvironment, and potential interventions remain a focus for future research
Regio- and Enantioselective asymmetric transfer hydrogenation of one Carbonyl group in a diketone through steric hindrance
Get PDFOn the basis of steric hindrance, one carbonyl group in a diketone can be reduced in a regioselective manner, with high enantioselectivity. The methodology can be extended to ketones with varied length of hydrocarbon chain spacing, and the products can be converted by oxidation to hydroxy esters or lactones without loss of enantiopurity
From managerialism to shareholder primacy : the role of the Cohen Committee and the Bank of England
No full textReimaging ecclesia domestica following a time of pandemic : The John Hull Memorial Lecture
No full textThe Second Vatican Council helpfully reaffirmed the partnership among three primary agencies in the Christian education and the Christian formation of the young: school, church, and home. The primacy among these three agencies may emerge differently in different social contexts. The argument of the present paper is two-fold. First, it is argued that John Hull was the key influence during the 1970s in trying to shift the primary focus for the Church of England from the school to the local congregation. Second, it is argued that post- pandemic, the primary focus now needs shifting from the local congregation to the home, to the ecclesia domestica
Who is inspired to follow Bishop Barron? Applying psychological type and psychological temperament theory among lay Catholic participants at an event sponsored in London by the Word on Fire Institute
No full textThe present study draws on psychological type theory and psychological temperament theory to test the extent to which Bishop Barron’s ministry shaped by the Word on Fire Institute is reaching people less effectively reached by Catholic congregations. Data provided by 168 male and 292 female participants attending Bishop Barron’s day conference in central London during February 2023, who completed the Francis Psychological Type Scales, demonstrated that this event attracted significantly higher proportions of intuitive types and of thinking types, compared with Catholic churchgoers. However, like Catholic congregations, extraverts and perceiving types remained under-represented among the followers of Bishop Barron. The implications of these findings are discussed for the ongoing nurture of those attracted to Bishop Barron alongside inherited congregations
Review of Innovating Business for Sustainability – Regulatory Approaches in the Anthropocene edited by Sjåfjell, B., Liao, C. and Argyrou, A.
No full textDataset to support : Direct evidence from high-field magnetotransport for a dramatic change of quasiparticle character in van der Waals ferromagnet Fe3-xGeTe2
No full textMagnetometry and magnetoresistance (MR) data taken on the van der Waals ferromagnet Fe3−xGeTe2 (FGT) reveal three distinct contributions to the MR: a linear negative component, a contribution from closed Fermi-surface orbits, and a H2 enhancement linked to a non-coplanar spin arrangement. Contrary to earlier studies on FGT, by accounting for the field dependence of the anomalous Hall effect, we find that the ordinary Hall coefficient decreases markedly below 80,K, indicating a significant change in character of the electrons and holes on the Fermi surface at this temperature. The resulting altered ground state eventually causes the Hall coefficient to reverse sign at 35,K. Our Hall data support the proposal that Kondo-lattice behavior develops in this d-electron material below 80 K. Additional evidence comes from the negative linear component of the MR, which arises from electron-magnon scattering with an atypical temperature dependence attributable to the onset of Kondo screening