bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stackelberg evolutionary game theory: how to manage evolving systems
Authors: Stein Alexander , Salvioli Monica , Garjani Hasti , Dubbeldam Johan , Viossat Yannick , Brown Joel S. , Staňková Kateřina 
Published: March 2023

Stackelberg evolutionary game (SEG) theory combines classical and evolutionary game theory to frame interactions between a rational leader and evolving followers. In some of these interactions, the leader wants to preserve the evolving system (e.g. fisheries management), while in others, they try to drive the system to extinction (e.g. pest control). Often the worst strategy for the leader is to adopt a constant aggressive strategy (e.g. overfishing in fisheries management or maximum tolerable dose in cancer treatment). Taking into account the ecological dynamics typically leads to better outcomes for the leader and corresponds to the Nash equilibria in game-theoretic terms. However, the leader’s most profitable strategy is to anticipate and steer the eco-evolutionary dynamics, leading to the Stackelberg equilibrium of the game. We show how our results have the potential to help in fields where humans try to bring an evolutionary system into the desired outcome, such as, among others, fisheries management, pest management and cancer treatment. Finally, we discuss limitations and opportunities for applying SEGs to improve the management of evolving biological systems.
This article is part of the theme issue ‘Half a century of evolutionary games: a synthesis of theory, application and future directions’.
Evolutionary game theory and the adaptive dynamics approach: adaptation where individuals interact
Authors: Avila Piret , Mullon Charles 
Published: March 2023

Evolutionary game theory and the adaptive dynamics approach have made invaluable contributions to understanding how gradual evolution leads to adaptation when individuals interact. Here, we review some of the basic tools that have come out of these contributions to model the evolution of quantitative traits in complex populations. We collect together mathematical expressions that describe directional and disruptive selection in class- and group-structured populations in terms of individual fitness, with the aims of bridging different models and interpreting selection. In particular, our review of disruptive selection suggests there are two main paths that can lead to diversity: (i) when individual fitness increases more than linearly with trait expression; (ii) when trait expression simultaneously increases the probability that an individual is in a certain context (e.g. a given age, sex, habitat, size or social environment) and fitness in that context. We provide various examples of these and more broadly argue that population structure lays the ground for the emergence of polymorphism with unique characteristics. Beyond this, we hope that the descriptions of selection we present here help see the tight links among fundamental branches of evolutionary biology, from life history to social evolution through evolutionary ecology, and thus favour further their integration.
This article is part of the theme issue ‘Half a century of evolutionary games: a synthesis of theory, application and future directions’.
Hermaphroditic origins of anisogamy
Authors: Henshaw Jonathan M. , Bittlingmaier Markus , Schärer Lukas 
Published: March 2023

Anisogamy—the size dimorphism of gametes—is the defining difference between the male and female sexual strategies. Game-theoretic thinking led to the first convincing explanation for the evolutionary origins of anisogamy in the 1970s. Since then, formal game-theoretic models have continued to refine our understanding of when and why anisogamy should evolve. Such models typically presume that the earliest anisogamous organisms had separate sexes. However, in most taxa, there is no empirical evidence to support this assumption. Here, we present a model of the coevolution of gamete size and sex allocation, which allows for anisogamy to emerge alongside either hermaphroditism or separate sexes. We show that hermaphroditic anisogamy can evolve directly from isogamous ancestors when the average size of spawning groups is small and fertilization is relatively efficient. Sex allocation under hermaphroditism becomes increasingly female-biased as group size decreases and the degree of anisogamy increases. When spawning groups are very small, our model also predicts the existence of complex isogamous organisms in which individuals allocate resources equally to two large gamete types. We discuss common, but potentially unwarranted, assumptions in the literature that could be relaxed in future models.
This article is part of the theme issue ‘Half a century of evolutionary games: a synthesis of theory, application and future directions’.
Integration of Mendelian randomisation and systems biology models to identify novel blood-based biomarkers for stroke
Authors: Islam Tania , Rahman Md Rezanur , Khan Asaduzzaman , Moni Mohammad Ali 
Published: March 2023

AbstractStroke is the second largest cause of mortality in the world. Genome-wide association studies (GWAS) have identified some genetic variants associated with stroke risk, but their putative functional causal genes are unknown. Hence, we aimed to identify putative functional causal gene biomarkers of stroke risk. We used a summary-based Mendelian randomisation (SMR) approach to identify the pleiotropic associations of genetically regulated traits (i.e., gene expression and DNA methylation) with stroke risk. Using SMR approach, we integrated cis- expression quantitative loci (cis-eQTLs) and cis-methylation quantitative loci (cis-mQTLs) data with GWAS summary statistics of stroke. We also utilised heterogeneity in dependent instruments (HEIDI) test to distinguish pleiotropy from linkage from the observed associations identified through SMR analysis. Our integrative SMR analyses and HEIDI test revealed 45 candidate biomarker genes (FDR< 0.05;PHEIDI>0.01) that were pleiotropically or potentially causally associated with stroke risk. Of those candidate biomarker genes, 10 genes (HTRA1, PMF1, FBN2, C9orf84, COL4A1, BAG4, NEK6, SH2B3, SH3PXD2A, ACAD10) were differentially expressed in genome-wide blood transcriptomics data from stroke and healthy individuals (FDR<0.05). Functional enrichment analysis of the identified candidate biomarker genes revealed gene ontologies and pathways involved in stroke, including “cell aging”, “metal ion binding” and “oxidative damage”. Based on the evidence of genetically regulated expression of genes through SMR and directly measured expression of genes in blood, our integrative analysis suggests ten genes as blood biomarkers of stroke risk. Furthermore, our study provides a better understanding of the influence of DNA methylation on the expression of genes linked to stroke risk.
Volumetric and microstructural abnormalities of the amygdala in focal epilepsy with varied levels of SUDEP risk
Authors: Legouhy Antoine , Allen Luke A. , Vos Sjoerd B. , Oliveira Joana F. A. , Kassinopoulos Michalis , Winston Gavin P. , Duncan John S. , Ogren Jennifer A. , Scott Catherine , Kumar Rajesh , Lhatoo Samden D. , Thom Maria , Lemieux Louis , Harper Ronald M. , Zhang Hui , Diehl Beate 
Published: March 2023

AbstractAlthough the mechanisms of sudden unexpected death in epilepsy (SUDEP) are not yet well understood, generalised- or focal-to-bilateral tonic-clonic seizures (TCS) are a major risk factor. Previous studies highlighted alterations in structures linked to cardio-respiratory regulation; one structure, the amygdala, was enlarged in people at high risk of SUDEP and those who subsequently died. We investigated volume changes and the microstructure of the amygdala in people with epilepsy at varied risk for SUDEP since that structure can play a key role in triggering apnea and mediating blood pressure.The study included 53 healthy subjects and 143 patients with epilepsy, the latter separated into two groups according to whether TCS occur in years before scan. We used amygdala volumetry, derived from structural MRI, and tissue microstructure, derived from diffusion MRI, to identify differences between the groups. The diffusion metrics were obtained by fitting diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) models. The analyses were performed at the whole amygdala level and at the scale of amygdaloid nuclei.Patients with epilepsy showed larger amygdala volumes and lower neurite density indices (NDI) than healthy subjects; the left amygdala volumes were especially enhanced. Microstructural changes, reflected by NDI differences, were more prominent on the left side and localized in the lateral, basal, central, accessory basal and paralaminar amygdala nuclei; basolateral NDI lowering appeared bilaterally. No significant microstructural differences appeared between epilepsy patients with and without current TCS.The central amygdala nuclei, with prominent interactions from surrounding nuclei of that structure, project to cardiovascular regions and respiratory phase switching areas of the parabrachial pons, as well as to the periaqueductal gray. Consequently, they have the potential to modify blood pressure and heart rate, and induce sustained apnea or apneusis. The findings here suggest that lowered NDI, indicative of reduced dendritic density, could reflect an impaired structural organization influencing descending inputs that modulate vital respiratory timing and drive sites and areas critical for blood pressure control.
Low-frequency repetitive transcranial magnetic stimulation in patients with motor deficits after brain tumor resection: a randomised, double-blind, sham-controlled trial
Authors: Engelhardt Melina , Schneider Heike , Reuther Jan , Grittner Ulrike , Vajkoczy Peter , Picht Thomas , Rosenstock Tizian 
Published: March 2023

Structured abstractBackgroundSurgical resection of motor eloquent tumors poses the risk of causing postoperative motor deficits which leads to reduced quality of life in these patients. Currently, rehabilitative procedures are limited with physical therapy being the main treatment option.ObjectiveThe present study investigated the efficacy of repetitive navigated transcranial magnetic stimulation (rTMS) for treatment of motor deficits after supratentorial tumor resection.MethodsThis randomised, double-blind, sham-controlled trial recruited patients with a worsening of upper extremity motor function after tumor resection. They were randomly assigned to receive rTMS treatment (1Hz, 110% RMT, 15 minutes, 7 days) or sham stimulation to the motor cortex contralateral to the injury followed by physical therapy. Motor and neurological function as well as quality of life were assessed directly after the intervention, one month and three months postoperatively.ResultsThirty patients were recruited for this study. There was no significant difference between both groups in the primary outcome, the Fugl Meyer score three months postoperatively (Group difference [95%-CI]: 5.05 [-16.0; 26.1]; p=0.631). Patients in the rTMS group presented with better hand motor function (BMRC scores) one month postoperatively. Additionally, a subgroup of patients with motor eloquent ischemia showed lower NIHSS scores at all timepoints.ConclusionLow-frequency rTMS facilitated the recovery process stimulated hand muscles, but with limited generalization to other functional deficits. Long-term motor deficits were not impacted by rTMS. Due to the reduced life expectancy in this patient group a shortened recovery duration of functional deficits can still be of high clinical significance.
Characteristics of parkrun That Encourage New Participants to Return
Authors: Gilburn Andre S. 
Published: March 2023

AbstractPhysical activity is essential to combating the obesity epidemic. parkrun organise free weekly 5km events. Previous studies have identified characteristics of people that act as barriers to new registrants engaging in and returning to events. The current study identifies characteristics of parkrun events that are associated with the return rate of new participants. The return rate of adult first-time participants to parkrun was determined for all events in Scotland over a 1-year period between 2/2019 and 1/2020. A GLMM was used to determine factors associated with whether they returned to parkrun. Return rates were higher for smaller events and events with more other first-time participants. Older participants and male participants were more likely to return. Those that finished in a relatively slow time were disproportionately less likely to return. Events with routes that run alongside freshwater had higher return rates for women. New participants at parkrun are more likely to return if they attended a smaller event suggesting that parkrun should continue to create new events to make parkrun more efficient at retaining new participants. New participants also returned more readily if they attended an event with a high proportion of other adult new participants so specific recruitment events could be advertised to encourage new participants to attend their first event together. New events could be prioritised in proximity to those events that currently experience the highest attendances.
Mechanistic convergence of depression and suicidality on astrocyte fatty acid metabolism
Authors: Fitzgerald Eamon , O’Toole Nicholas , Pokhvisneva Irina , Turecki Gustavo , Nagy Corina , Meaney Michael J 
Published: March 2023

AbstractGenome-wide association studies (GWAS) show conceptual promise to identify novel mechanisms of major depressive disorder (MDD), but have not yet achieved this potential. One explanation is that MDD risk acts through complex expression networks, and GWAS-identified genes represent important components of these networks but in isolation are insufficient for their functional annotation. In this study, we aimed to identify and characterize the expression networks through which GWAS-identified MDD risk genes operate. We generated and characterized seeded co-expression networks of 252 MDD risk genes over 11 brain regions. We used principal component regression and Mendelian randomization to identify a relation between the networks of two such genes (FADS1andZKSCAN8) and suicidal ideation. These networks were primarily expressed in astrocytes, enriched for functions related to fatty acid metabolism, and could define MDD-altered astrocyte states. We then identifiedFGFR3toEPHA4signaling as a putative downstream effector of these astrocyte states on synaptic function. Finally through transcriptomic and genetic analyses, we identify PPARA as a putative therapeutic target of these mechanisms in MDD. Our study defines a tractable pathway to translate genetic findings into therapeutically actionable mechanisms.
Fate-mapping lymphocyte clones and their progenies from induced antigen-signals identifies temporospatial behaviours of T cells mediating tolerance
Authors: Takahashi Munetomo , So Tsz Y. , Williamson Kate , Hosseini Zhaleh , Kania Katarzyna , Ruhle Michelle , Mann Tiffeney , Schujis Martijn J. , Coupland Paul , Naisbitt Dean , Halim Timotheus Y.F. , Lyons Paul A. , Lio Pietro , Okkenhaug Klaus , Adams David J. , Smith Ken G.C. , Jodrell Duncan I. , Chapman Michael A. , Thaventhiran James E. D. 
Published: March 2023

AbstractTissue homeostasis is maintained by the behaviours of lymphocyte clones responding to antigenic triggers in the face of pathogen, environmental, and developmental challenges. Current methodologies for tracking the behaviour of specific lymphocytes identify clones of a defined antigen-receptor—antigen binding affinity. However, lymphocytes can receive antigenic signals from undefined or endogenous antigens, and the strength of each signal, even for the same lymphocyte, varies with accessory signalling, across tissues and across time. We present a novel fate-mapping mouse, that, by tracking lymphocyte clones and their progenies from induced antigen signals, overcomes these hurdles and provides novel insights into the maintenance of tissue homeostasis. We demonstrate the systems use by investigating the maintenance of localised T cell tolerance in tumour immunity. In a murine tumour model, our system reveals how Tregs differentiate to a reversible, tolerance inducing state within the tumour, and recirculate, while CD8+ T cells failing to recirculate, differentiate to an increasingly exhausted, tolerant state in the tumour. These contrasting T cell behaviours provide means by which immunity can tolerate a particular anatomical niche while maintaining systemic clonal protection. Our system can thus explore lymphocyte behaviours that cannot be tracked by previous methods and will therefore provide novel insights into the fundamental mechanisms underlying immunity’s role in tissue homeostasis.
Muscle of obese insulin-resistant humans exhibits losses in proteostasis and attenuated proteome dynamics that are improved by exercise training
Authors: Srisawat Kanchana , Stead Connor A , Hesketh Katie , Pogson Mark , Strauss Juliette A. , Cocks Matt , Siekmann Ivo , Phillips Stuart M. , Lisboa Paulo J. , Shepherd Sam , Burniston Jatin G 
Published: March 2023

AbstractWe examined muscle proteostasis in obese insulin-resistant (OIR) individuals to determine whether endurance exercise could positively influence proteome dynamics in this population. Male OIR (n = 3) and lean, healthy controls (LHC; n = 4) were recruited and underwent a 14-d measurement protocol of daily deuterium oxide (D2O) consumption and serial biopsies of vastus lateralis muscle. The OIR group then completed 10-weeks of high-intensity interval training (HIIT), encompassing 3 sessions per week of cycle ergometer exercise with 1 min intervals at 100 % maximum aerobic power (Wmax) interspersed by 1 min recovery periods. The number of intervals per session progressed from 4 to 8, and during weeks 8-10 the 14-d measurement protocol was repeated. The abundance and turnover rates of 880 and 301 proteins, respectively, were measured. OIR and LHC muscle exhibited 352 differences (p< 0.05, false discovery rate (p< 0.05) differences in protein turnover. OIR muscle was enriched with markers of metabolic stress, protein misfolding and components of the ubiquitin-proteasome system, and the turnover rate of many of these proteins was less compared to LHC muscle. HIIT altered the abundance of 53 proteins and increased the turnover rate of 22 proteins (p< 0.05) in OIR muscle and tended to restore proteostasis, evidenced by increasing muscle protein turnover rates and normalizing proteasome composition in OIR participants. In conclusion, obesity and insulin resistance are associated with compromised muscle proteostasis, which can be partially restored by endurance exercise.
Production of isotopically enriched high molecular weight hyaluronic acid and characterization by solid-state NMR
Authors: Rampratap Pushpa , Lasorsa Alessia , Perrone Barbara , van der Wel Patrick C.A. , Walvoort Marthe T.C. 
Published: March 2023

AbstractHyaluronic acid (HA) is a naturally occurring polysaccharide that is abundant in the extracellular matrix (ECM) of all vertebrate cells. HA-based hydrogels have attracted great interest for biomedical applications due to their high viscoelasticity and biocompatibility. In both ECM and hydrogel applications, high molecular weight (HMW)-HA can absorb a large amount of water to yield matrices with a high level of structural integrity. To understand the molecular underpinnings of structural and functional properties of HA-containing hydrogels, few techniques are available. Nuclear magnetic resonance (NMR) spectroscopy is a powerful tool for such studies, e.g.13C NMR measurements can reveal the structural and dynamical features of (HMW) HA. However, a major obstacle to13C NMR is the low natural abundance of13C, necessitating the generation of HMW-HA that is enriched with13C isotopes. Here we present a convenient method to obtain13C- and15N-enriched HMW-HA in good yield fromStreptococcus equisubsp. zooepidemicus. The labeled HMW-HA has been characterized by solution and magic angle spinning (MAS) solid-state NMR spectroscopy, as well as other methods. These results will open new ways to study the structure and dynamics of HMW-HA-based hydrogels, and interactions of HMW-HA with proteins and other ECM components, using advanced NMR techniques.
Bamboozle: A bioinformatic tool for identification and quantification of intraspecific barcodes
Authors: Pinder Matthew I M , Andersson Björn , Rengefors Karin , Blossom Hannah , Svensson Marie , Töpel Mats 
Published: March 2023

AbstractEvolutionary changes in populations of microbes, such as microalgae, cannot be traced using conventional metabarcoding loci as they lack intraspecific resolution. Consequently, selection and competition processes amongst strains of the same species cannot be resolved without elaborate isolation, culturing, and genotyping efforts. Bamboozle, a new bioinformatic tool introduced here, scans a species’ entire genome and identifies allele-rich barcodes that enable direct identification of different strains from a common population, and a single DNA sample, using amplicon sequencing. We demonstrate its usefulness by identifying hypervariable barcoding loci (<500 bp) from genomic data in two microalgal species, the diploid diatomSkeletonema marinoi, and the haploid chlorophyteChlamydomonas reinhardtii. Across the genomes, only 26 loci capable of resolving all available strains’ genotypes were identified, all of which are within protein-coding genes of variable metabolic function. Single nucleotide polymorphisms (SNPs) provided the most reliable genetic markers, and amongst 55 strains ofS. marinoi,three 500 bp loci contained, on average, 46 SNPs, 103 unique alleles, and displayed 100% heterozygosity. The prevalence of heterozygosity was identified as a novel opportunity to improve strain quantification and detect false positive artefacts during denoising of amplicon sequences. Finally, we illustrate how metabarcoding of a single genetic locus can be used to track strain abundances of 58 strains ofS. marinoiin an artificial selection experiment. As future genomics datasets become available and DNA sequencing technologies develop, Bamboozle has flexible user settings enabling optimal barcodes to be designed for other species and applications.
Gene coexpression analysis identifies genes associated with chlorophyll content and relative water content in pearl millet
Authors: Shinde Harshraj , Dudhate Ambika , Sathe Atul , Paserkar Neha , Wagh Sopan G. , Kadam Ulhas S. 
Published: March 2023

AbstractPearl millet is a significant crop tolerant to abiotic stresses and is a staple food of arid regions. However, its underlying mechanisms of stress tolerance is not fully understood. Plant survival is regulated by the ability to perceive a stress signal and induce appropriate physiological changes. Here, we screened for genes regulating physiological changes such as chlorophyll content (CC) and relative water content (RWC) in response to abiotic stress. Using ‘weighted gene co-expression network analysis’ (WGCNA) and clustering associated changes in physiological traits,i.e., CC and RWC with gene expression. A group of genes showing correlation with traits was identified as modules, and different color names were used to denote a particular module. In WGCNA, the darkgreen module (7082 genes) showed a significant positive correlation with CC, and the black (1393 genes) module was negatively correlated with CC and RWC. Analysis of the module positively correlated with CC highlighted ribosome synthesis and plant hormone signaling as the most significant pathways.Potassium transporter 8andmonothiol glutaredoxinwere reported as the topmost hub genes in the darkgreen module. InClustanalysis, 2987 genes were found to display a correlation with increasing CC and RWC. Further, the pathway analysis of these clusters identified ribosome and thermogenesis as positive regulators of RWC and CC, respectively. Our study provides novel insights into the molecular mechanisms regulating CC and RWC in pearl millet.