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Novel Ag(I) and Zn(II) complexes based on benzenesulfonamide ligand : synthesis, characterization, and biological evaluation as multitarget antidiabetic agents
Get PDFFunding: This work was supported by the Deanship of Scientific Research, Vice Presidency for Graduate Studies and Scientific Research, King Faisal University, Saudi Arabia (Project No. KFU250713).Three novel d10-metal complexes of the antidiabetic sulfonamide ligand (HPPS) were synthesized and characterized using elemental analysis, FTIR, NMR spectra, and single-crystal X-ray structure. The two Ag(I) complexes share the common cationic formula [Ag(HPPS)2]+, abbreviated as [1]. The structure of the /studied Ag(I) complexes could be represented by the formula [1]ClO4·2H2O and [1]NO3·CH3CN. Both complexes are mononuclear, where Ag(I) is tetra-coordinated with two neutral HPPS units as bidentate ligands via the pyrazole and pyridine N-atoms. In both cases, the coordination geometry around Ag(I) is a twisted form that is intermediate between tetrahedral and square planar geometry. The Zn(II) complex [Zn4(PPS)2Cl6(H2O)2]·2EtOH, 2, is tetra-nuclear in which the Zn(II) ions are tetra- and penta-coordinated. The anionic PPS- ligand acts as a bis-bidentate ligand, bridging both independent Zn(II) sites, which are then further bridged by chloride ions to adjacent zincs. The synthesized complexes were evaluated for their in vitro α-glucosidase and α-amylase inhibitory activities and glucose uptake. The results revealed that the synthesized Ag(I) and Zn(II) complexes showed remarkably excellent antidiabetic potential. Interestingly, α-glucosidase and α-amylase inhibitory activities and glucose uptake efficacy of Ag(I) and Zn(II) complexes highly surpassed their free ligand HPPS. Ag(I) complexes )[1]ClO4·2H2O and [1]NO3·CH3CN ( and Zn(II) complex )2( showed excellent inhibitory potential against α-glucosidase with IC50 values of 3.68, 5.22, and 3.93 µM, respectively (2.13, 1.5, and 2 times more potent than acarbose). Ag(I) complex, [1]ClO4·2H2O and Zn(II) complex, 2 (IC50 values of 2.78 and 4.93 µM) exhibited significant α-amylase inhibitory potential, 4.8- and 2.7- fold more potent than acarbose. Ag(I) and Zn(II) complexes showed 3.38- to 3.89-fold more glucose uptake efficacy than berberine with EC50 values of 12.01, 11.15, and 10.45 µM, for [1]ClO4·2H2O, [1]NO3·CH3CN and 2, respectively. Docking studies were conducted for the synthesized silver and zinc complexes using α-glucosidase protein (PDB:2QMJ) and α-amylase (PDB:1XCW) complexed with acarbose. Keywords: Ag(I) and Zn(II) complexes; Sulfonamide; α-Glucosidase; α-Amylase; Glucose uptake; Antidiabetic.Peer reviewe
Collegiality in the complex ecosystem of research in academia : an analysis of a research-intensive university in the UK
Get PDFFunding: The authors acknowledge support from the Wellcome Trust Institutional Research Fund and the University of St Andrews Restarting Interdisciplinary Research Fund.Recent work by researchers, higher education institutions and research funders highlights how current research culture can be damaging to individual experience, and the wider research endeavour, potentially constraining capacity to create useful knowledge that addresses key problems. Further, the erosion of academic values and freedoms has emerged as a key concern for researchers working within the UK and beyond. Many institutions are considering how they can support a positive research context where members feel their contributions are respected and where transparent processes support the development of trustworthy knowledge. This article addresses the question of how collegiality is experienced and implicated in the complex and interconnected issues characterising the contemporary research ecosystem. To explore this area, this article has three aims, (i) to define and review the concept of collegiality as part of research culture, (ii) consider how it is currently understood and experienced by members of a specific research community, (iii) consider the future potential for collegiality to contribute positively to researchers’ experience of their research culture. Drawing on quantitative and qualitative data from a Research Culture Survey we find that the historical understanding of collegiality no longer reflects its contemporary embodiment, partly due to the dual phenomena of increased neoliberal managerialism and increased staff diversity within higher education, and the attendant shift in how ‘collegial’ work is understood and experienced. We discuss how universities could nonetheless benefit from a renewed actualisation of collegiality within research culture.Peer reviewe
Rapid rise in atmospheric CO2 marked the end of the Late Palaeozoic Ice Age
Get PDFFunding: H.J. acknowledges funding from the Leverhulme Trust Early Career Fellowship (ECF-2023-199). H.J., R.W. and J.W.B.R. acknowledge funding from the European Research Council under the European Union’s Horizon 2020 research and innovation programme (grant agreement 805246). H.J., V.L., M.G., A.E., A.T. and L.A were in part supported by the European Commission’s Marie Sklodowska-Curie Innovative Training Network (‘BASELiNE-Earth’ ITN) under European Union’s Horizon 2020 research and innovation programme (grant agreement 643084). L.A. and M.V. were supported by the Italian Ministry for Universities and Research (MUR) through the project ‘Dipartimenti di Eccellenza 2023-27’ and by the European Union – Next Generation EU PRIN MUR 2022WEZR44. A.T. was supported by the Slovak Agency for Research and Development (APVV22-0523). W.W.’s and S.S.’s work was supported by NSFC (grant no. 42293280), and G.R.S’s work was supported by the Australian Research Council (ARC DP230100323).Atmospheric CO2 is thought to play a fundamental role in Earth’s climate regulation. Yet, for much of Earth’s geological past, atmospheric CO2 has been poorly constrained, hindering our understanding of transitions between cool and warm climates. Beginning ~370 million years ago in the Late Devonian and ending ~260 million years ago in the Permian, the Late Palaeozoic Ice Age was the last major glaciation preceding the current Late Cenozoic Ice Age and possibly the most intense glaciation witnessed by complex lifeforms. From the onset of the main phase of the Late Palaeozoic Ice Age in the mid-Mississippian ~330 million years ago, the Earth is thought to have sustained glacial conditions, with continental ice accumulating in high to mid-latitudes. Here we present an 80-million-year-long boron isotope record within a proxy framework for robust quantification of CO2. Our record reveals that the main phase of the Late Palaeozoic Ice Age glaciation was maintained by prolonged low CO2, unprecedented in Earth’s history. About 294 million years ago, atmospheric CO2 rose abruptly (4-fold), releasing the Earth from its penultimate ice age and transforming the Early Permian into a warmer world.Peer reviewe
A history of studies of reproductive isolation between Drosophila pseudoobscura and D. persimilis
Get PDFFunding: This work was primarily funded by the Natural Environment Research Council, NERC grant no. NE/V001566/1 to MGR.Drosophila pseudoobscura and D. persimilis are a sister species pair that have been used as a model for studies of reproductive isolation and speciation for almost 100 years owing to their close evolutionary history, well characterized genetic differences, and overlapping geographic distribution. There are extensive analyses of both pre- and post-zygotic isolation, including studies of courtship divergence, conspecific sperm precedence (CSP) and how reinforcement by natural selection may or may not act to strengthen isolation in sympatry. Post-zygotic analyses explore the underlying mechanics of reproductive isolation; how inversions may give rise to initial speciation events and misexpression of key genes typically found within inversion regions render hybrid offspring unfit or inviable. We aim here to present a history of studies of reproductive isolation between this species pair, looking at how the field has developed over the last century and identifying the open questions and gaps within the literature.Peer reviewe
Mindful moments : using meditation for student and staff wellbeing in the classroom
Get PDFThis article discusses the increasing concerns for student mental health within higher education and the specific need for anthropology to consider the effects of our teaching content on student wellbeing. I reflect on using mindfulness in the classroom as a coping strategy for the challenges faced during the Covid-19 pandemic, and how meditation helped to create a supportive, relaxed learning environment. Acknowledging the limits of this practice, I consider meditation to be one resource within a wider pedagogical toolkit that embraces student-centred learning. My argument does not intend to further burden teaching staff with the responsibilities for student welfare, but instead demonstrates how using pedagogies that prioritise wellbeing can increase student engagement, promote inclusivity and lead to positive transformations for students and staff.Peer reviewe
Emulation of the subjective experience of visual dorsal stream dysfunction : a description of three in depth case studies
Get PDFThese case studies explore the subjective visual experiences of individuals with cerebral visual impairment (CVI), specifically dorsal stream dysfunction (DSD) characterized by simultanagnosia. Through three in-depth case studies, this work documents the challenges these individuals face when navigating cluttered environments. The individuals were asked to describe their visual experiences while watching videos of varying complexity, with the future aim of creating a simulation of simultanagnosia. This process revealed a dynamic constriction of their attentional visual fields as scene complexity increased, and vice versa. Notably, the volunteers experienced a phenomenon where their vision could “get stuck” on specific items, with an apparent concurrent reduction in their ability to perceive and describe visual information as visual clutter increased. These consistent observations indicate that the symptoms of simultanagnosia are not simply limited to perceiving one or two objects at a time but can vary dynamically in response to environmental complexity. They enhance our understanding of how DSD impacts visual search and perceptual experiences, prompting us to propose the term “simultanagnostic vision” to describe this more nuanced and dynamic manifestation of CVI. The results are critical for developing effective interventions and optimizing support strategies for individuals affected by DSD, particularly children at sensitive developmental stages. Furthermore, we recommend deeper investigation into how different visual processing streams in the brain interconnect and influence each other, which may open new avenues for targeted therapeutic interventions.Peer reviewe
Unveiling the internal structure and formation history of the three planets transiting HIP 29442 (TOI-469) with CHEOPS
Get PDFFunding: A.C.C. acknowledges support from STFC consolidated grant numbers ST/R000824/1 and ST/V000861/1, and UKSA grant number ST/R003203/1. CHe acknowledges support from the European Union H2020-MSCA-ITN-2019 under Grant Agreement no. 860470 (CHAMELEON). PM acknowledges support from STFC research grant number ST/R000638/1. NCSa acknowledges funding by the European Union (ERC, FIERCE, 101052347). NAW acknowledges UKSA grant ST/R004838/1.Multiplanetary systems spanning the radius valley are ideal testing grounds for exploring the different proposed explanations for the observed bimodality in the radius distribution of close-in exoplanets. One such system is HIP 29442 (TOI-469), an evolved K0V star hosting two super-Earths and one sub-Neptune. We observed HIP 29442 with CHEOPS for a total of 9.6 days, which we modelled jointly with two sectors of TESS data to derive planetary radii of 3.410 ± 0.046, 1.551 ± 0.045, and 1.538 ± 0.049 R⊕ for planets b, c, and d, which orbit HIP 29442 with periods of 13.6, 3.5, and 6.4 days, respectively. For planet d this value deviates by more than 3σ from the median value reported in the discovery paper, leading us to conclude that caution is required when using TESS photometry to determine the radii of small planets with low per-transit signal-to-noise ratios and large gaps between observations. Given the high precision of these new radii, combining them with published RVs from ESPRESSO and HIRES provides us with ideal conditions to investigate the internal structure and formation pathways of the planets in the system. We introduced the publicly available code plaNETic, a fast and robust neural network-based Bayesian internal structure modelling framework. We then applied hydrodynamic models to explore the upper atmospheric properties of these inferred structures. Finally, we identified planetary system analogues in a synthetic population generated with the Bern model for planet formation and evolution. Based on this analysis, we find that the planets likely formed on opposing sides of the water iceline from a protoplanetary disk with an intermediate solid mass. We finally report that the observed parameters of the HIP 29442 system are compatible with a scenario where the second peak in the bimodal radius distribution corresponds to sub-Neptunes with a pure H/He envelope and with a scenario with water-rich sub-Neptunes.Peer reviewe
Impact of supranational non-financial disclosure legislation on CSR reporting - the case of the EU Directive 2014/95/EU
No full textWith regulation on corporate social responsibility (CSR) reporting becoming ever more prominent, it becomes increasingly important that legislators base their policy design on case-specific evidence and reliable measurement. In order to address this issue, this thesis aims to advance the methodology of CSR reporting measurement and the policy impact assessment of supranational CSR disclosure regulation. To this end, this thesis creates, tests, and validates a novel CSR reporting dictionary that can accurately measure CSR reporting in the context of Directive 2014/95/EU. This study further validates the newly developed assessment tool by using archived and quantitative communications data covering 549 French, German, Spanish and UK companies from 2014 to 2020. A difference-in-differences analysis is employed to determine the impact of Directive 2014/95/EU on CSR reporting in the sample countries, and the subsequent results are contextualised within Oliver's (1991) framework on strategic responses to institutional pressure. The findings show that the newly developed CSR reporting dictionary is highly valid and reliable across all four languages. Empirical results also reveal that Directive-affected companies significantly increased the scope and coverage of their overall and dimensional CSR reporting. However, in terms of reporting quality, the Directive appears to have no significant impact apart from an improvement in human rights disclosure and a deterioration in employee issues. Moreover, the inferences of this thesis indicate that, while companies from almost all countries comply, they exhibit unique strategic reporting responses to the regulatory shock depending on the country context. Finally, the evidence suggests that higher levels of institutional ownership decrease the effect of the Directive on CSR reporting quantity and coverage. Overall, this study contributes to the methodological and empirical knowledge on supranational non-financial disclosure regulation. It provides future researchers with a reliable multilanguage assessment tool for CSR reporting and highlights possible areas of improvement for policy design
Are current patient-reported outcome measures fit for purpose to evaluate unicompartmental knee arthroplasty?
Get PDFThe optimal procedure for isolated end-stage medial compartment knee osteoarthritis (OA) remains uncertain, with debate persisting between unicompartmental knee arthroplasty (UKA) and total knee arthroplasty (TKA). The aim of this narrative review is to evaluate current outcome measures in knee arthroplasty (KA) and explore how evolving patient populations and technological advancements may necessitate the use of different patient-reported outcome measures (PROMs) for evaluating UKA. While UKA offers potential advantages over TKA in early pain relief and functional outcomes, most randomised control trials using traditional PROMs have failed to show definitive superiority. The recent introduction of robotic assistance may have further enhanced the benefits of UKA. However, it remains uncertain whether the advantages outweigh the higher revision rates associated with UKA. Although traditional PROMs, such as the Oxford Knee Score or Knee Injury and Osteoarthritis Outcome Score, were designed for the KA population of 30 years ago, they continue to be employed today. The current KA population, particularly those undergoing UKA, are typically younger, physically fitter, and have higher functional demands than those for whom traditional PROMs were originally designed. As a result, these PROMs are now limited by ceiling effects. High-performance PROMs, such as the Forgotten Joint Score-12 or the metabolic equivalent of task score, have recently been utilised for high-demand patients and do not have postoperative ceiling effects. Return to work and sport are also important outcomes that are often overlooked for younger, high-demand patients. Future studies should aim to define the differences between UKA and TKA populations, identify patient factors that predict UKA success, and validate high-performance PROMs for UKA. This will provide deeper insights into the functional benefits of UKA and TKA, enabling patients and surgeons to make more informed decisions regarding implant selection.Peer reviewe
Mechanisms of cyclic-oligonucleotide-based anti-phage signalling systems in prokaryotic immunity
No full textCyclic oligonucleotide based anti-phage signalling systems (CBASS) are a diverse form of prokaryotic immunity, characterised by a core nucleotide cyclase and effector pair that, upon infection, produce secondary messengers and activate cell disrupting phenotypes, preventing phage replication. CBASS cyclases share ancestry with the eukaryotic innate immune pathway, cGAS-STING, and produce a diverse array of cyclic nucleotide molecules. This has both rapidly expanded the known arsenal of prokaryotic defence signals and identified a mechanism of immunity conserved across all domains of life.
Whilst the CBASS cyclase/effector pair alone offers immunity against select phage, diverse ancillary protein architectures are observed within CBASS to facilitate broader phage protection. Type II CBASS is characterised by the presence of ancillary proteins Cap2 and Cap3, which share homology with eukaryotic ubiquitin conjugation and deconjugation machinery, respectively. Type II ancillary genes have been demonstrated as essential for broad CBASS protection in vivo and were predicted to regulate the cyclase during infection, potentially through ubiquitin-like conjugation and post-translational modification. However, their critical roles within CBASS activation and regulation remained elusive.
During this project focussed on the type II CBASS system from Bacillus cereus, we determined that the monomeric wild-type cyclase adopts a low-activity conformation, subject to significant inhibition at cellularly relevant nucleotide concentrations. Following identification of the cyclase as the Cap2 conjugation substrate, we identified several major conjugation targets, including Phage shock protein A (PspA) and other cyclase monomers during different stages of infection. Prior to infection, the cyclase is spatially organised through conjugation to PspA, whilst cyclase homo-oligomerisation likely functions to structurally rearrange the cyclase active site, forming active oligomeric species. Additionally, we have elucidated that Cap2 conjugation is directly reversed by Cap3, facilitating re- conjugation and enhancing Cap2 conjugation target specificity through rapid non- target conjugate cleavage
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