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Prof Robin Dunbar, Emeritus Professor of Evolutionary Psychology has been in conversation with Jim Al-Khalili on Radio 4's Life Scientific. This fascinating podcast gives takes us on a journey from his early beginnings in science, and his fascinating research and groundbreaking discoveries he's made deciphering the mysteries as to why humans and animals evolve the social habits to exist in friendship circles.
Platforms for studying cell-cell recognition by immune cells.
Immune cells interact directly with other cells and make decisions by integrating information from many different receptor-ligand interactions at these cell-cell interfaces. Since they encounter a huge variety of normal and abnormal cells, they experience many different combinations and concentrations of ligands. Understanding immune responses therefore requires platforms that enable ligands to be easily manipulated. We review and compare the available platforms, focusing on T-cell recognition. Although genetically modified antigen-presenting cells (APCs) offer the most physiological system, manipulating their ligands is difficult and slow. In contrast, solid surfaces or supported lipid bilayers allow easy manipulation of ligands but lack the biophysical properties of cells, such as softness, a glycocalyx, and/or ligand mobility. A recently developed CombiCell system enables easy manipulation of ligands while conserving key biophysical properties. By comparing the advantages and limitations of each platform, we provide a framework to choose the most suitable system to study signal integration in both basic and translational contexts.
Differential beta and gamma activity modulation during unimanual and bimanual motor learning.
Movement-related dynamics in the beta and gamma bands have been studied in relation to motor execution and learning during unimanual movements, but their roles in complex bimanual tasks remain largely unexplored. This study aimed to investigate how beta and gamma activity differs between unimanual and bimanual movements, and how these neural signatures evolve during the learning process. Our motor task incorporated varying levels of bimanual interaction: unimanual, bimanual-equal, and bimanual-unequal. Magnetoencephalography data were recorded in healthy participants (N = 43, 27 females) during task performance, and beta and gamma activity was quantified. As expected, increasing task complexity from unimanual to bimanual-equal, and then to bimanual-unequal movements resulted in slower and less accurate performance. Across all conditions, significant beta event-related desynchronization (ERD) and gamma event-related synchronization (ERS) were observed during movement, as well as beta ERS after movement. Bimanual movements exhibited greater beta ERD, beta ERS, and gamma ERS compared to unimanual movements. With practice, participants demonstrated faster and more accurate movements, accompanied by enhanced beta ERS responses. Furthermore, learning-related reductions in errors correlated with increases in beta ERS. These findings suggest the distinct behavioural and neural demands of unimanual versus bimanual movements and highlight the important role of beta activity in motor performance and learning.Significance statement Bimanual movements, which dominate daily motor behaviours, require finely tuned coordination between the two hands yet remain poorly understood at the neurophysiological level. Using magnetoencephalography, we tested neural responses to a novel movement task incorporating varying levels of bimanual interaction. We demonstrate that greater task complexity elicits enhanced movement-related brain activity in the beta and gamma frequency bands. Motor learning is associated with an increase in beta movement-related synchronization that correlates with improved movement accuracy. This study provides novel insights into how beta and gamma brain activity adapt to increasing movement complexity and motor learning.
AICAR confers prophylactic cardioprotection in doxorubicin-induced heart failure in rats.
Doxorubicin (DOX) is a widely used chemotherapeutic agent that can cause serious cardiotoxic side effects, leading to heart failure (HF). Impaired mitochondrial function is thought to be key factor driving progression into HF. We have previously shown in a rat model of DOX-HF that heart failure with reduced ejection fraction correlates with mitochondrial loss and dysfunction. Adenosine monophosphate-dependent kinase (AMPK) is a cellular energy sensor, regulating mitochondrial biogenesis and energy metabolism, including fatty acid oxidation. We hypothesised that AMPK activation could restore mitochondrial function and therefore be a novel cardioprotective strategy for the prevention of DOX-HF. Consequently, we set out to assess whether 5-aminoimidazole-4-carboxamide 1-β-D-ribofuranoside (AICAR), an activator of AMPK, could prevent cardiac functional decline in this chronic intravenous rat model of DOX-HF. In line with our hypothesis, AICAR improved cardiac systolic function. AICAR furthermore improved cardiac mitochondrial fatty acid oxidation, independent of mitochondrial number, and in the absence of observable AMPK-activation. In addition, we found that AICAR prevented loss of myocardial mass. RNAseq analysis showed that this may be driven by normalisation of pathways associated with ribosome function and protein synthesis, which are impaired in DOX-treated rat hearts. AICAR furthermore prevented dyslipidemia and excessive body-weight loss in DOX-treated rats, which may contribute to preservation of myocardial mass. Though it is unclear whether AICAR exerted its cardioprotective effect through cardiac or extra-cardiac AMPK-activation or via an AMPK-independent effect, these results show promise for the use of AICAR as a cardioprotective agent in DOX-HF to both preserve cardiac function and mass.
Targeting glucose metabolism with dichloroacetate (DCA) reduces zika virus replication in brain cortical progenitors at different stages of maturation.
The underlying threat of new Zika virus (ZIKV) outbreaks remains, as no vaccines or therapies have yet been developed. In vitro research has shown that glycolysis is a key factor to enable sustained ZIKV replication in neuroprogenitors. However, neither in vivo nor clinical investigation of glycolytic modulators as potential therapeutics for ZIKV-related fetal abnormalities has been conducted. Accordingly, we tested the therapeutic potential of metabolic modulators in relevant in vitro systems comprising two pools of neuroprogenitors (NPCs), which resemble early and late stages of pregnancy. Effective doses of metabolic modulators [3.0 μM] dimethyl fumarate (DMF), [3.2 mM] dichloroacetate (DCA), and [6.3 μM] VER-246608 were determined for these cells by their effect on lactate release, pyruvate dehydrogenase (PDH) activity and cell survival. The drugs were used in a 24h pre-treatment and kept throughout ZIKV infection of NPCs. Drug effects and ZIKV replication were assessed at 24- and 56-h post-infection. In early NPCs treated with DMF, DCA and VER-246608, there was a significant reduction in the extracellular release of ZIKV potentially by PDH-mediated increased mitochondrial oxidation of glucose. Out of the three drugs, only DCA was observed to reduce viral replication in late NPCs treated with DCA. Altogether, our findings suggest that reduction of anaerobic glycolysis could be of therapeutic potential against ZIKV-related fetal abnormalities and that clinical translation should consider the use of specific glycolytic modulators over different trimesters.
Neurodegenerative Disease and Association Football (NDAF): Systematic Review and Meta-Analysis.
There is increasing concern that head injuries in Association Football (or soccer) may lead to adverse health outcomes. The aim of this study was to determine whether head impacts or injuries are associated with an increased risk of neurodegenerative disease. We performed a systematic search using PubMed, Embase, and Ovid (up to April 2025). Studies included investigated neurodegenerative diseases in football in comparison to control athletic and general populations. Data were extracted according to PRISMA guidelines. Studies with an odds ratio (OR) were included in the meta-analysis. A total of ten studies were included in this review, of which nine were suitable for meta-analysis from eight cohorts. The risk for developing any neurodegeneration was 1.69 OR (95%CI 1.11 to 2.59; p = 0.01); for Dementia, it was 2.16 OR (95%CI 1.60 to 2.93; p < 0.01; for Motor Neurone Disease (MND), it was 1.39 OR (95%CI 0.67 to 2.53; p = 0.21); for Parkinson's Disease (PD), it was 1.14 OR (95%CI 0.55 to 2.89; p = 0.79). Heterogeneity was reduced following the removal of two studies and the revised risk scores for any neurodegenerative disease; Dementia increased, with that for MND reaching significance, 1.81 OR (95%CI 1.22 to 2.30; p = 0.01), but there remained no association with PD. Evidence suggests that professional football significantly increases the odds of neurodegenerative disease.
Teaching humanities in UK medical schools: towards community-building and coherence
Medical humanities teaching in UK medical schools has lacked cohesion, having developed opportunistically in different locations. Cohesion is necessary to develop an identifiable community of practice, but within that community there can be multiple readings of what ‘medical humanities’ are and how they may develop. This article details discussions held by medical humanities scholars teaching in UK medical schools at a workshop in January 2025 at the University of Oxford covering five key areas: the role of humanities scholars in medical schools, patients as partners in medical education, core curriculum teaching, intercalated teaching, and assessment. Our discussion highlights opportunities and challenges facing humanities teaching in UK medical schools today and calls for the creation of a community of medical humanities scholars working in UK medical education embracing diversity of opinion and practices. The article is specifically written as a synopsis of a brainstorming symposium.
User requirements for quantitative radiological reports in multiple sclerosis
Objectives: Quantitative radiological reports (QReports) can enhance clinical management of multiple sclerosis (MS) by including quantitative data from MRI scans. However, the lack of consensus on the specific information to include, on and clinicians’ preferences, hinders the adoption of these imaging analysis tools. This study aims to facilitate the clinical implementation of QReports by determining clinicians’ requirements regarding their use in MS management. Materials and methods: A four-phase Delphi panel approach was employed, involving neurologists and (neuro)radiologists across Europe. Initial interviews with experts helped develop a questionnaire addressing various QReport aspects. This questionnaire underwent refinement based on feedback and was distributed through the MAGNIMS network. A second questionnaire, incorporating additional questions, was circulated following a plenary discussion at the MAGNIMS workshop in Milan in November 2023. Responses from both questionnaire iterations were collected and analyzed, with adjustments made based on participant feedback. Results: The study achieved a 49.6% response rate, involving 78 respondents. Key preferences and barriers to QReport adoption were identified, highlighting the importance of integration into clinical workflows, cost-effectiveness, educational support for interpretation, and validation standards. Strong consensus emerged on including detailed lesion information and specific brain and spinal cord volume measurements. Concerns regarding report generation time, data protection, and reliability were also raised. Conclusion: While QReports show potential for improving MS management, incorporation of the key metrics and addressing the identified barriers related to cost, validation, integration, and clinician education is crucial for practical implementation. These recommendations for developers to refine QReports could enhance their utility and adoption in clinical practice. Key Points: Question A lack of consensus on essential features for quantitative magnetic resonance imaging reports limits their integration into multiple sclerosis management. Findings This study identified key preferences, including detailed lesion information, specific brain and spinal cord measurements, and rigorous validation for effective quantitative reports. Clinical relevance This study identified essential features and barriers for implementing quantitative radiological reports in multiple sclerosis management, aiming to enhance clinical workflows, improve disease monitoring, and ultimately provide better, data-driven care for patients through tailored imaging solutions.
Different types of social links contrastingly shape reproductive traits in a multi-level society of wild songbirds
Social environments can influence individuals’ health, reproductive success, welfare, and survival. These environments consist of diverse social connection types at multiple levels, which could influence different components of fitness in contrasting ways. Great tits (Parus major) exhibit a multilevel society with four major types of dyadic bonds: pair mates, breeding neighbours, flockmates, and spatial associates, all of which can influence fitness. Here, we show that these different types of dyadic bonds are differentially linked with reproductive success metrics in a wild great tit population, and that the consideration of spatial effects could provide further insights into these interrelationships. Specifically, more-social individuals had more fledglings, those that bonded more strongly with their pairmate laid earlier, and those with more spatial associates laid smaller clutches. These findings highlight the importance of considering multiple types of dyadic relationships when identifying the fitness consequences of sociality, and the need for work to experimentally test these relationships, particularly in spatially structured populations.
Detectable clonal mosaicism and its relationship to aging and cancer.
In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of >2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%. In cancer-free individuals, frequency increased with age, from 0.23% under 50 years to 1.91% between 75 and 79 years (P = 4.8 × 10(-8)). Mosaic abnormalities were more frequent in individuals with solid tumors (0.97% versus 0.74% in cancer-free individuals; odds ratio (OR) = 1.25; P = 0.016), with stronger association with cases who had DNA collected before diagnosis or treatment (OR = 1.45; P = 0.0005). Detectable mosaicism was also more common in individuals for whom DNA was collected at least 1 year before diagnosis with leukemia compared to cancer-free individuals (OR = 35.4; P = 3.8 × 10(-11)). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases.
Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index.
Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ∼ 2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10⁻⁸), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.
Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis.
By combining genome-wide association data from 8,130 individuals with type 2 diabetes (T2D) and 38,987 controls of European descent and following up previously unidentified meta-analysis signals in a further 34,412 cases and 59,925 controls, we identified 12 new T2D association signals with combined P<5x10(-8). These include a second independent signal at the KCNQ1 locus; the first report, to our knowledge, of an X-chromosomal association (near DUSP9); and a further instance of overlap between loci implicated in monogenic and multifactorial forms of diabetes (at HNF1A). The identified loci affect both beta-cell function and insulin action, and, overall, T2D association signals show evidence of enrichment for genes involved in cell cycle regulation. We also show that a high proportion of T2D susceptibility loci harbor independent association signals influencing apparently unrelated complex traits.
RIFINs displayed on malaria-infected erythrocytes bind KIR2DL1 and KIR2DS1.
Natural killer (NK) cells use inhibitory and activating immune receptors to differentiate between human cells and pathogens. Signalling by these receptors determines whether an NK cell becomes activated and destroys a target cell. In some cases, such as killer immunoglobulin-like receptors, immune receptors are found in pairs, with inhibitory and activating receptors containing nearly identical extracellular ligand-binding domains coupled to different intracellular signalling domains1. Previous studies showed that repetitive interspersed family (RIFIN) proteins, displayed on the surfaces of Plasmodium falciparum-infected erythrocytes, can bind to inhibitory immune receptors and dampen NK cell activation2,3, reducing parasite killing. However, no pathogen-derived ligand has been identified for any human activating receptor. Here we identified a clade of RIFINs that bind to inhibitory immune receptor KIR2DL1 more strongly than KIR2DL1 binds to the human ligand (MHC class I). This interaction mediates inhibitory signalling and suppresses the activation of KIR2DL1-expressing NK cells. We show that KIR2DL1-binding RIFINs are abundant in field-isolated strains from both Africa and Asia and reveal how the two RIFINs bind to KIR2DL1. The RIFIN binding surface of KIR2DL1 is conserved in the cognate activating immune receptor KIR2DS1. We find that KIR2DL1-binding RIFINs can also bind to KIR2DS1, resulting in the activation of KIR2DS1-expressing NK cells. This study demonstrates that activating killer immunoglobulin-like receptors can recruit NK cells to target a pathogen and reveals a potential role for activating immune receptors in controlling malaria infection.
Collaborative risk assessment and management planning in secure mental health services in England: protocol for a realist review.
INTRODUCTION: Secure mental health pathways are complex. They are typically based around secure hospitals, but also interface with justice agencies and other clinical services, including in the community. Consideration of risk is fundamental to clinical care and to decisions relating to a patient's stepwise journey through the pathway. Patient autonomy and involvement in decision-making are policy priorities for health services. However, improving collaboration in risk-related decisions in secure services is complicated by potential issues with insight and capacity and the necessary involvement of other agencies. In addition, although some collaborative approaches are feasible and effective, their impact, mechanisms and the contexts in which they work are not well understood. Therefore, using realist methodology, this review will outline what works, for whom, why and under what circumstances in terms of collaborative risk assessment and management in secure services. METHODS AND ANALYSIS: The review will consist of four stages: (1) Development of an initial programme theory to explain how and why collaborative risk assessment and management works for different groups of people, (2) search for evidence, (3) data selection and extraction and (4) evidence synthesis and development of a final programme theory. Our initial programme theory will be informed by an informal search of the literature and consultation with experts and patient and public involvement and engagement representatives. Following this, our formal literature search will include both the published and unpublished literature. During full text screening, each document will be assessed according to the principles of rigour and relevance and, if included, data will be extracted and synthesised to refine the programme theory. ETHICS AND DISSEMINATION: This protocol is for a review of published literature and so does not require ethical approval. The main output will be the final programme theory. Remaining gaps will inform planned future work to further refine the theory using mixed methods. Our dissemination strategy will be codeveloped with our public and patient involvement group and will include publishing findings in a peer-reviewed journal and presenting findings at relevant professional conferences, as well as engaging patient, carer and clinician groups directly.
Improving Outcomes in Survivors of Sepsis-The Transition from Secondary to Primary Care, and the Role of Primary Care: A Narrative Review.
Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. The number of patients with sepsis requiring critical care admission is increasing. At the same time, overall mortality from sepsis is declining. With increasing survival to hospital discharge, there are an increasing number of sepsis survivors whose care needs shift from the acute to chronic care settings. Recently, the phrase "post-sepsis syndrome" has emerged to encompass the myriad of complications in patients recovering from sepsis. The aim of this narrative review is to provide a contemporary summary of the available literature on post-sepsis care and highlight areas of ongoing research. There are many incentives for improving the quality of survivorship following sepsis, including individual health-related outcomes (e.g., increased survival, enhanced physical and psychological health) and wider socio-economic benefits (e.g., reduced economic burden on the healthcare systems, reduced physical and psychological burden on carers, ability for individuals (and carers) to return to workforce). Modifiable factors influencing long-term outcomes can be in-hospital or after discharge, when primary care physicians play a pivotal role. Despite national and international guidance being available, this area has been under-recognised historically, despite its profoundly negative impact on both patients and their families or caregivers. Contributing factors likely include the lack of a formally recognised "disease" or pathology, the presence of challenging-to-treat symptoms such as fatigue, weakness and cognitive impairment, and the prevailing assumption that ongoing rehabilitation merely requires time. Our review will focus on the following areas: screening for new cognitive and physical impairments; optimisation of pre-existing comorbidities; transition to primary care; and palliative care. Primary care physicians may have a crucial role to play in improving outcomes in sepsis survivors, and candidate interventions include education on common complications of post-sepsis syndrome.