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[Ni(NHC)2] as a scaffold for structurally characterized trans [H−Ni−PR2] and trans [R2P−Ni−PR2] complexes
Get PDFFunding: The authors thank the Royal Society (Newton Fellowship to SS), EPSRC, the Deutsche Forschungsgemeinschaft (DFG; RA720/7), the Julius-Maximilians-Universität Würzburg and Heriot–Watt University for financial support.The addition of PPh2H, PPhMeH, PPhH2, P(para-Tol)H2, PMesH2 and PH3 to the two-coordinate Ni0 N-heterocyclic carbene species [Ni(NHC)2] (NHC=IiPr2, IMe4, IEt2Me2) affords a series of mononuclear, terminal phosphido nickel complexes. Structural characterisation of nine of these compounds shows that they have unusual trans [H−Ni−PR2] or novel trans [R2P−Ni−PR2] geometries. The bis-phosphido complexes are more accessible when smaller NHCs (IMe4>IEt2Me2>IiPr2) and phosphines are employed. P−P activation of the diphosphines R2P−PR2 (R2=Ph2, PhMe) provides an alternative route to some of the [Ni(NHC)2(PR2)2] complexes. DFT calculations capture these trends with P−H bond activation proceeding from unconventional phosphine adducts in which the H substituent bridges the Ni−P bond. P−P bond activation from [Ni(NHC)2(Ph2P−PPh2)] adducts proceeds with computed barriers below 10 kcal mol−1. The ability of the [Ni(NHC)2] moiety to afford isolable terminal phosphido products reflects the stability of the Ni−NHC bond that prevents ligand dissociation and onward reaction.Peer reviewe
Mathematical modelling of p53 signalling during DNA damage response : a survey
Get PDFFunding: This research was funded by the EPSRC grant number EP/N014642/1.No gene has garnered more interest than p53 since its discovery over 40 years ago. In the last two decades, thanks to seminal work from Uri Alon and Ghalit Lahav, p53 has defined a truly synergistic topic in the field of mathematical biology, with a rich body of research connecting mathematic endeavour with experimental design and data. In this review we survey and distill the extensive literature of mathematical models of p53. Specifically, we focus on models which seek to reproduce the oscillatory dynamics of p53 in response to DNA damage. We review the standard modelling approaches used in the field categorising them into three types: time delay models, spatial models and coupled negative-positive feedback models, providing sample model equations and simulation results which show clear oscillatory dynamics. We discuss the interplay between mathematics and biology and show how one informs the other; the deep connections between the two disciplines has helped to develop our understanding of this complex gene and paint a picture of its dynamical response. Although yet more is to be elucidated, we offer the current state-of-the-art understanding of p53 response to DNA damage.Peer reviewe
Introduction - Corona a(e)ffects : radical affectivities of dissent and hope
Get PDFRight from the emergence of the ongoing COVID-19 pandemic, national governments and international institutions have been relentlessly qualifying it as an “unprecedented” event. We have been told that the virus sees no color or class and that equal sacrifices from each one of us are and continue to be necessary to contain its spread. We have been instructed to look at the virus in scientific, neutral terms as if we had equal chances of being affected by it—as if its routes, that is, did not follow the roots of sedimented histories of oppression, exploitation, dispossession, and structural violence. This forum departs from such narratives to look at how the current COVID-19 pandemic intersects with other pre-existing and enduring pandemics, such as those produced by racism, capitalism, and speciesism. In building on the emerging critiques by Indigenous, feminist, Black, and queer academics, movements, and activists, the contributions it hosts offer multimedia reflections on affects triggered or evoked by the current pandemic, such as rage, fear, despair, restraint, care, and hope. Coming from different parts of the globe and disciplinary approaches, authors convey the “Corona(virus) a(e)ffects” in multisensorial ways, combining written essays, poetry, videos, and photographs. By contextualizing the ongoing COVID-19 pandemic within a historical legacy of structural violence within and across species, this forum moves beyond deceitfully single-focus and temporally flat narrations. In so doing, it provides a space for the expression of radical affectivities of dissent and hope that its outburst has arguably made only more visible and pressing.Peer reviewe
Anaerobic decomposition dynamics of three kelp species from the North-east Atlantic : implications for blue carbon storage
Get PDFFunding: This work was conducted at the Scottish Association for Marine Science (SAMS) funded in part by the Scottish Blue Carbon Forum (SBCF), Scottish Government Marine Directorate, and the University of the Highlands and Islands forms part of Alasdair O’Dell’s PhD (O’Dell, 2022). DS was funded by a UKRI Future Leaders Fellowship (MR/S032827/1).Decomposition pathways of detritus are key processes in the contribution of macroalgal habitats to natural carbon sequestration of “blue carbon”. The anaerobic decomposition of three North-east Atlantic canopy-forming kelp species was investigated using ex-situ decomposition chambers. Thallus parts (stipes, holdfasts and blades) of Laminaria hyperborea, Saccharina latissima and Laminaria digitata were incubated in still seawater in temperature-controlled dark conditions. Refractory potential (Rp), first-order decomposition rate ‘k’ and associated half-life (t1/2) were calculated. Dissolved organic carbon (DOC) and dissolved inorganic carbon (DIC) were measured in the incubation water at 0, 7, 14 and 21 days and thermal gravimetric profiles were determined at each 26 decomposition stage. Oxygen depletion occurred within 24 hours. Approximately 5 times as much DOC was released than DIC. Holdfast material produced the most DIC, while blade material released greatest amounts of DOC. Saccharina latissima released less DOC than L. hyperborea and L.digitata. The refractory potential of fragments increased from Rp = 0.46 ± 0.05 (SD) to 0.50 ± 0.04 (SD) throughout the 21-day incubations. Saccharina latissima had the highest Rp throughout. First order decomposition rates, averaged across the three kelp species, gave half-lives (t1/2) for blade fragments of 27.8 ± 2.9 days, (k = 0.025 ± 0.002) and stipes (t1/2) as 113.2 ± 21.1 days (k = 0.006 ± 33 0.001). This experiment clarifies the fate of macroalgal carbon during early decomposition and thus the processes that govern blue carbon pathways of macroalgae highlighting the differences in species and thallus parts breakdown.Peer reviewe
What keeps me engaging? : A study of consumers' continuous social media brand engagement practices
Get PDFPurpose This study examines some pertinent individual-level factors and consequences of consumers' continuous social media brand engagement (SMBE) practices. Further, this study examines the moderating effect of other-efficacy to deepen the understanding. Design/methodology/approach Online survey data collected from 785 respondents, through a convenience sampling technique on Facebook, was analyzed through structural equation (SEM) modeling with AMOS 23.0. Findings The findings suggest that compatibility with lifestyle, perceived information quality and escapism, which significantly drive consumers' continuous engagement with brands on social media. However, perceived enjoyment does not. Other-efficacy duly moderates consumers' continuous SMBE practices. While continuous SMBE significantly drives consumer-based brand equity (CBBE), continuous SMBE does not have any significant relationship with consumers' subjective well-being (SWB). Research limitations/implications This study reports robust findings on the effects of individual-level factors that drive consumers' continuous SMBE practices. However, the study only focused on Facebook brand pages. This is a limitation for generalizability of results because the research did not take a holistic view of all types of social media. Practical implications The research suggests a need for managers to project their brands and share relevant and stimulating information throughout their continuous SMBE with consumers to build strong consumer–brand relationships. Managers should also engage consumers with interesting social media messages as well as both informative and transformative creative strategies to excite them. This will further give consumers a reason to continuously interact with the brand on social media platforms. Originality/value This study is one of the very few works to tease out pertinent factors that drive consumers' continuous SMBE practices. The paper integrates the consumer-level factors and moderating effects of other-efficacy through the lens of Social Cognitive Theory (SCT) and Uses and Gratification Theory (UGT) to make a significant contribution to the SMBE literature.Peer reviewe
Defining an ageing-related pathology, disease or syndrome : international consensus statement
Get PDFFunding: This project was supported by a Longevity Impetus Grant from Norn Group.Around the world, individuals are living longer, but an increased average lifespan does not always equate to an increased health span. With advancing age, the increased prevalence of ageing-related diseases can have a significant impact on health status, functional capacity and quality of life. It is therefore vital to develop comprehensive classification and staging systems for ageing-related pathologies, diseases and syndromes. This will allow societies to better identify, quantify, understand and meet the healthcare, workforce, well-being and socioeconomic needs of ageing populations, whilst supporting the development and utilisation of interventions to prevent or to slow, halt or reverse the progression of ageing-related pathologies. The foundation for developing such classification and staging systems is to define the scope of what constitutes an ageing-related pathology, disease or syndrome. To this end, a consensus meeting was hosted by the International Consortium to Classify Ageing-Related Pathologies (ICCARP), on February 19, 2024, in Cardiff, UK, and was attended by 150 recognised experts. Discussions and voting were centred on provisional criteria that had been distributed prior to the meeting. The participants debated and voted on these. Each criterion required a consensus agreement of ≥ 70% for approval. The accepted criteria for an ageing-related pathology, disease or syndrome were (1) develops and/or progresses with increasing chronological age; (2) should be associated with, or contribute to, functional decline or an increased susceptibility to functional decline and (3) evidenced by studies in humans. Criteria for an ageing-related pathology, disease or syndrome have been agreed by an international consortium of subject experts. These criteria will now be used by the ICCARP for the classification and ultimately staging of ageing-related pathologies, diseases and syndromes.Peer reviewe
A common human MLKL polymorphism confers resistance to negative regulation by phosphorylation
Get PDFFunding: The authors are grateful to the National Health and Medical Research Council for fellowship (J.M.H., 1142669; A.L.S., 2002965; J.M.M., 1172929; J.S., 1107149), grant (J.M.M., 1105023; K.R.M., 1092602; J.S., 1105023; J.M.H., 2011584) and infrastructure (IRIISS 9000719); Arthritis Australia support to K.R.M; K.E.L funding by Future Fellowships from the ARC (FT19010266). We acknowledge scholarship support for S.E.G (Australian Government Research Training Program Stipend Scholarship; Wendy Dowsett Scholarship), Y.M (Melbourne Research Scholarship; AINSE PGRA Scholarship), D.F (Australian Government Research Training Program Stipend Scholarship), A.V.J (Australian Government Research Training Program Stipend Scholarship), and S.C (Walter and Eliza Hall Handman PhD Scholarship). Victorian State Government Operational Infrastructure Support Scheme.Across the globe, 2-3% of humans carry the p.Ser132Pro single nucleotide polymorphism in MLKL, the terminal effector protein of the inflammatory form of programmed cell death, necroptosis. Here we show that this substitution confers a gain in necroptotic function in human cells, with more rapid accumulation of activated MLKLS132P in biological membranes and MLKLS132P overriding pharmacological and endogenous inhibition of MLKL. In mouse cells, the equivalent Mlkl S131P mutation confers a gene dosage dependent reduction in sensitivity to TNF-induced necroptosis in both hematopoietic and non-hematopoietic cells, but enhanced sensitivity to IFN-β induced death in non-hematopoietic cells. In vivo, MlklS131P homozygosity reduces the capacity to clear Salmonella from major organs and retards recovery of hematopoietic stem cells. Thus, by dysregulating necroptosis, the S131P substitution impairs the return to homeostasis after systemic challenge. Present day carriers of the MLKL S132P polymorphism may be the key to understanding how MLKL and necroptosis modulate the progression of complex polygenic human disease.Peer reviewe
Harmonious colourings of temporal matchings
Get PDFFunding: This work was supported by the Leverhulme Research Centre for Functional Materials Design.Graph colouring is a fundamental problem in computer science, with a large body of research dedicated to both the general colouring problem and restricted cases. Harmonious colourings are one such restriction, where each edge must contain a globally unique pair of colours, i.e. if an edge connects a vertex coloured x with a vertex coloured y, then no other pair of connected vertices can be coloured x and y. Finding such a colouring in the traditional graph setting is known to be NP-hard, even in trees. This paper considers the generalisation of harmonious colourings to Temporal Graphs, specifically (k,t)-Temporal matchings, a class of temporal graphs where the underlying graph is a matching (a collection of disconnected components containing pairs of vertices), each edge can appear in at most t timesteps, and each timestep can contain at most k other edges. We provide a complete overview of the complexity landscape of finding temporal harmonious colourings for (k,t)-matchings. We show that finding a Temporal Harmonious Colouring, a colouring that is harmonious in each timestep, is NP-hard for (k,t)-Temporal Matchings when k≥2,t≥4, or when k≥3 and t≥2. We further show that this problem is inapproximable for t≥2 and an unbounded value of k, and that the problem of determining the temporal harmonious chromatic number of a (2,3)-temporal matching can be determined in linear time. Finally, we strengthen this result by a set of upper and lower bounds of the temporal harmonious chromatic number both for individual temporal matchings and for the classes of (k,t)-temporal matchings, paths, and cycles.Peer reviewe
Salmonella pathogenicity islands in the genomic era
Get PDFFunding: J.S.P. was supported by a Sylvia and Charles Viertel Senior Medical Fellowship . B.P.H. was supported by NHMRC Investigator Grant ( GNT1196103 ). D.J.I. was supported by an NHMRC Investigator Grant ( GNT1195210 ).Serovars of Salmonella are significant bacterial pathogens and are leading contributors to the global burden of diarrhoeal disease. Salmonella pathogenicity islands (SPIs) are essential for the survival and success of this genus, enabling colonisation, invasion, and survival in hostile environments. While genomics has transformed efforts to understand the evolution, dissemination, and antimicrobial resistance of members, its use to explore virulence determinants that contribute to the pathogenicity of specific organisms and severity of infection remains varied. Here, we discuss the importance of SPIs to the evolution of Salmonella, the implications in the shift of identification of SPIs from molecular microbiology to genomic-based approaches, and examine current efforts to explore the distribution and prevalence of SPIs in large-scale datasets of Salmonella genomes.Peer reviewe
Demonstrating the reproductive consequences of cognition : learning from experience
Get PDFReproductive success and its consequences for fitness are key to determining how natural selection shapes cognitive abilities, and thus how and why cognition might change over evolutionary time. However, demonstrating reproductive costs or benefits owing to variation in cognitive ability is hugely challenging, in part because traits such as body size and condition make the largest contribution to reproductive success. Our ability to discriminate a role for ‘being smart’ in fitness is then already limited. Additionally, most animals have many ways to solve problems, only some of which will depend on their cognitive abilities. However, specific instances in key parts of animal’s life may depend heavily on their cognitive abilities, and without them the animal will not survive or reproduce. Retrieving food stores is one example and nest building might be another. For food-storing, spatial ability is key, while for nest building the pertinent ability is learning what works. The importance of animals learning from previous experience may be very common but is rarely considered explicitly in cognitive terms. Work on fitness consequences of cognition should develop from the presentation of discrete tasks testing specific abilities to encompass how learning from experience influences behavioural evolution more broadly.Peer reviewe
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