Multidisciplinary ecosystem to study lifecourse determinants and prevention of early-onset burdensome multimorbidity (MELD-B) - protocol for a research collaboration.

Background: Most people living with multiple long-term condition multimorbidity (MLTC-M) are under 65 (defined as 'early onset'). Earlier and greater accrual of long-term conditions (LTCs) may be influenced by the timing and nature of exposure to key risk factors, wider determinants or other LTCs at different life stages. We have established a research collaboration titled 'MELD-B' to understand how wider determinants, sentinel conditions (the first LTC in the lifecourse) and LTC accrual sequence affect risk of early-onset, burdensome MLTC-M, and to inform prevention interventions.

Getting the most out of maths: How to coordinate mathematical modelling research to support a pandemic, lessons learnt from three initiatives that were part of the COVID-19 response in the UK.

In March 2020 mathematics became a key part of the scientific advice to the UK government on the pandemic response to COVID-19. Mathematical and statistical modelling provided critical information on the spread of the virus and the potential impact of different interventions. The unprecedented scale of the challenge led the epidemiological modelling community in the UK to be pushed to its limits.

Selfish risk-seeking can provide an evolutionary advantage in a conditional public goods game.

While cooperation and risk aversion are considered to be evolutionarily advantageous in many circumstances, and selfish or risky behaviour can bring negative consequences for individuals and the community at large, selfish and risk-seeking behaviour is still often observed in human societies. In this paper we consider whether there are environmental and social conditions that favour selfish risk-seeking individuals within a community and whether tolerating such individuals may provide benefits to the community itself in some circumstances. We built an agent-based model including two types of agent-selfish risk-seeking and generous risk-averse-that harvest resources from the environment and share them (or not) with their community.

SARS-CoV-2 infection in UK university students: lessons from September-December 2020 and modelling insights for future student return.

In this paper, we present work on SARS-CoV-2 transmission in UK higher education settings using multiple approaches to assess the extent of university outbreaks, how much those outbreaks may have led to spillover in the community, and the expected effects of control measures. Firstly, we found that the distribution of outbreaks in universities in late 2020 was consistent with the expected importation of infection from arriving students. Considering outbreaks at one university, larger halls of residence posed higher risks for transmission.

The mechanism of DNA unwinding by the eukaryotic replicative helicase.

Accurate DNA replication is tightly regulated in eukaryotes to ensure genome stability during cell division and is performed by the multi-protein replisome. At the core an AAA+ hetero-hexameric complex, Mcm2-7, together with GINS and Cdc45 form the active replicative helicase Cdc45/Mcm2-7/GINS (CMG). It is not clear how this replicative ring helicase translocates on, and unwinds, DNA.

How group composition affects cooperation in fixed networks: can psychopathic traits influence group dynamics?

Static networks have been shown to foster cooperation for specific cost-benefit ratios and numbers of connections across a series of interactions. At the same time, psychopathic traits have been discovered to predict defective behaviours in game theory scenarios. This experiment combines these two aspects to investigate how group cooperation can emerge when changing group compositions based on psychopathic traits.

The effect of psychopathy on cooperative strategies in an iterated Prisoner's Dilemma experiment with emotional feedback.

As decision-making research becomes more popular, the inclusion of personality traits has emerged as a focal point for an exhaustive analysis of human behaviour. In this study, we investigate the impact of psychopathic traits on cooperation in an iterated Prisoner's Dilemma game with emotional facial feedback. Firstly, we observed how receiving a facial feedback after each decision affected players with different psychopathic trait scores, and how being informed about the opponent's identity influenced cooperative behaviour.

When to rely on maternal effects and when on phenotypic plasticity?

Existing insight suggests that maternal effects have a substantial impact on evolution, yet these predictions assume that maternal effects themselves are evolutionarily constant. Hence, it is poorly understood how natural selection shapes maternal effects in different ecological circumstances. To overcome this, the current study derives an evolutionary model of maternal effects in a quantitative genetics context.

Detachment, futile cycling, and nucleotide pocket collapse in myosin-V stepping.

Myosin-V is a highly processive dimeric protein that walks with 36-nm steps along actin tracks, powered by coordinated adenosine triphosphate (ATP) hydrolysis reactions in the two myosin heads. No previous theoretical models of the myosin-V walk reproduce all the observed trends of velocity and run length with adenosine diphosphate (ADP), ATP and external forcing. In particular, a result that has eluded all theoretical studies based upon rigorous physical chemistry is that run length decreases with both increasing [ADP] and [ATP].

Fitness consequences of maternal and grandmaternal effects.

Transgenerational effects are broader than only parental relationships. Despite mounting evidence that multigenerational effects alter phenotypic and life-history traits, our understanding of how they combine to determine fitness is not well developed because of the added complexity necessary to study them. Here, we derive a quantitative genetic model of adaptation to an extraordinary new environment by an additive genetic component, phenotypic plasticity, maternal and grandmaternal effects.

Equation-free analysis of two-component system signalling model reveals the emergence of co-existing phenotypes in the absence of multistationarity.

Phenotypic differences of genetically identical cells under the same environmental conditions have been attributed to the inherent stochasticity of biochemical processes. Various mechanisms have been suggested, including the existence of alternative steady states in regulatory networks that are reached by means of stochastic fluctuations, long transient excursions from a stable state to an unstable excited state, and the switching on and off of a reaction network according to the availability of a constituent chemical species. Here we analyse a detailed stochastic kinetic model of two-component system signalling in bacteria, and show that alternative phenotypes emerge in the absence of these features.

Spectral quantification of nonlinear behaviour of the nearshore seabed and correlations with potential forcings at Duck, N.C., U.S.A.

Local bathymetric, quasi-periodic patterns of oscillation are identified from 26 years of monthly profile surveys taken at two shore-perpendicular transects at Duck, North Carolina, USA. The data cover both the swash and surf zones. Singular Spectrum Analysis (SSA) and Multi-channel Singular Spectrum analysis (MSSA) methods are applied, on the shoreface, to three potential forcings: the monthly wave heights, the monthly mean water levels and the large scale atmospheric index known as the North Atlantic Oscillation.

The benefits of maternal effects in novel and in stable environments.

Natural selection favours phenotypes that match prevailing ecological conditions. A rapid process of adaptation is therefore required in changing environments. Maternal effects can facilitate such responses, but it is currently poorly understood under which circumstances maternal effects may accelerate or slow down the rate of phenotypic evolution.

Theoretical study of pattern formation during the catalytic oxidation of CO on Pt{100} at low pressures.

Theoretical studies have thus far been unable to model pattern formation during the reaction in this system on physically feasible length and time scales. In this paper, we derive a computational reaction-diffusion model for this system in which most of the input parameters have been determined experimentally. We model the surface on a mesoscopic scale intermediate between the microscopic size of CO islands and the macroscopic length scale of pattern formation.

Pattern formation during the oxidation of CO on Pt{100}: a mesoscopic model.

Constantly changing irregular patterns of carbon monoxide (CO) and oxygen are seen during CO oxidation on platinum crystals in the [100] orientation. Ours is the first reaction-diffusion model to reproduce this pattern formation on physically feasible length and time scales, faithfully incorporating the available experimental data. Numerical simulations show patterns made up of CO and oxygen fronts moving at similar speeds to those seen in experiments.

A kinetic model describing the processivity of myosin-V.

The precise details of how myosin-V coordinates the biochemical reactions and mechanical motions of its two head elements to engineer effective processive molecular motion along actin filaments remain unresolved. We compare a quantitative kinetic model of the myosin-V walk, consisting of five basic states augmented by two further states to allow for futile hydrolysis and detachments, with experimental results for run lengths, velocities, and dwell times and their dependence on bulk nucleotide concentrations and external loads in both directions. The model reveals how myosin-V can use the internal strain in the molecule to synchronize the motion of the head elements.

League tables and school effectiveness: a mathematical model.

'School performance tables', an alphabetical list of secondary schools along with aggregates of their pupils' performances in national tests, have been published in the UK since 1992. Inevitably, the media have responded by publishing ranked 'league tables'. Despite concern over the potentially divisive effect of such tables, the current government has continued to publish this information in the same form.