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Involvement of matricellular proteins and immune receptors in the dynamic interaction between tumour and immune cells
No full textThis thesis was submitted for the award of Doctor of Philosophy and was awarded by Brunel University LondonBackground: Osteosarcoma (OS) is the most common primary malignant bone tumour in children and young adults, characterised by high metastatic potential and poor prognosis in advanced stages. Despite recent therapeutic advances, metastatic OS remains challenging to treat. Increasing evidence highlights the tumour microenvironment (TME), particularly immune cell components such as macrophages, as key modulators of tumour progression. Ovarian cancer (OC) is a significant cause of cancer-related deaths among women worldwide. It is a highly metastatic malignancy that shares similar molecular and immunological features with OS, including late-stage diagnosis, immune evasion, and extracellular matrix (ECM) remodelling. Matricellular proteins (MCPs) are non-structural extracellular matrix proteins that regulate cell– matrix interactions and signalling rather than providing structural support. They influence cell adhesion, migration, proliferation, and differentiation, and are often upregulated in cancer, promoting tumour growth, angiogenesis, and metastasis. Comparative analysis of OS and OC may reveal shared immune–metabolic pathways that contribute to tumour aggressiveness. This project investigates how MCPs and the interactions with immune cells influence tumour behaviour, survival, and metastatic progression within the TME. Using OC and OS as model systems, it integrates bioinformatic analyses, experimental validation, and functional assays to elucidate the molecular and immune mechanisms underpinning cancer progression and metastasis.
Methods: Publicly available transcriptomic datasets for OS (GSE42352, GSE12865) and ovarian cancer (GSE18520, GSE54388, GSE14407) were analysed to identify differentially expressed genes (DEGs). The UniProt tool was used for functional annotation, with an emphasis on immune receptor (IR), cell adhesion (CAD), and ECM pathways. Survival analyses were performed using the KM Plotter. Candidate genes were validated in vitro using RT-qPCR and Western blotting in OS cell lines (MG63, SaOS-2, MNNG, 143B) and THP-1 monocytes differentiated into M0, M1, and M2 macrophages via PMA and cytokine stimulation. In addition, MNNG and 143B cells were treated with the FPR3 agonist WKYMVm and antagonist WRW4 (10 μM and 50 μM) for 24 h to directly assess the functional impact of FPR3 signalling on OS cell motility. Proliferation and scratch migration assays were performed using tumour- and macrophage-conditioned media. Secretomes were subjected to ultracentrifugation to assess the roles of soluble and vesicle-bound factors. Co-culture experiments were conducted to examine the bidirectional effects of macrophage-tumour signalling.
Results: Initial bioinformatics analyses revealed a significant enrichment of DEGs associated with ECM remodelling, immune signalling, and poor survival in both OS and OC datasets. In OC, D24 (Cluster of Differentiation 24), DCN (Decorin), and OGN (Osteoglycin/Mimecan) were associated with adverse prognosis. In OS, SPP1 (osteopontin) and FPR3 (formyl peptide receptor 3) were upregulated, whereas LEPR (leptin receptor) was consistently downregulated across patient tissues, and it was a common gene among OC and OS. Functional assays demonstrated that M2- conditioned media enhanced the migration and proliferation of OS cells. Ultracentrifugation experiments suggested that vesicle-bound factors mediate these effects on the target cells. The reciprocal communication between osteosarcoma cells and macrophages establishes a pro-metastatic feedback loop. In vitro experiments using RT-qPCR and Western blotting revealed the differential expression of key genes involved in tumour progression and immune regulation across various osteosarcoma cell lines. Genes such as FPR3, LEPR, and SPP1 displayed variable mRNA and protein levels, indicating distinct molecular profiles between the cell lines. These differences highlight the heterogeneity of osteosarcoma and suggest that specific gene expression patterns may be linked to variations in tumour behaviour, immune interactions, and metastatic potential. Treatment of MNNG and 143B cells with the FPR3 agonist WKYMVm significantly increased migration velocity at both 10 μM and 50 μM, while the antagonist WRW4 effectively reduced migration, particularly at 50 μM. M2 macrophages showed high expression of CD163, FPR3, LEPR, and SPP1, reflecting their tumour-promoting, anti-inflammatory phenotype.THP-1 cells treated with OS-conditioned media upregulated CD163, consistent with M2 polarisation, whereas OS cell lines treated with macrophage supernatants displayed increased SPP1 and LEPR, particularly under M2 stimulation.
Conclusion: This study identified SPP1, FPR3, and LEPR as key immune-metabolic mediators in OS, highlighting their roles in tumour–macrophage crosstalk and metastasis. The combination of in silico and in vitro findings supports a model in which the TME, particularly M2 macrophages, enhances OS progression via dynamic signalling pathways. These findings provide a foundation for targeting tumour–immune interactions in future OS therapies and suggest new directions for precision medicine strategies in metastatic cancers. Notably, LEPR was also consistently downregulated in OC, indicating a shared immunometabolism mechanism that may contribute to metastatic progression across tumour types
Limited evidence for transgenerational chromosomal instability in families with elevated mutation pattern SBS16 in the germline
Get PDFAcknowledgments:
We thank all children of veterans for their participation in this project and, all families for their support, patience and involvement in the wider GCFT study. Our thanks go to Jose Seixo, Frances Daley, Siobhan Casha, Emily Al-Haddad for technical support. We are also extremely appreciative of the time given by Prof Dudley Goodhead OBE and Dr Mark Hill who have acted as independent experts to offer oversight for this project and for their useful comments on this manuscript. Chat GPT (basic) was used to improve grammar in places, no content was generated through the use of AI tools.Data availability statement:
The dataset generated during this current study are available as supplementary materials.Supplemental material is available online at: https://www.tandfonline.com/doi/full/10.1080/09553002.2026.2618529# .Purpose:
The transgenerational effects of preconception parental radiation exposure in humans remain unclear. We assessed genomic integrity in adult children of British nuclear test (NT) veterans—a community that has expressed long-standing concerns about adverse health effects, including in their offspring—to investigate for any constitutional chromosomal abnormalities and/or cytogenetic indicators of genomic instability that might be associated with paternal participation at NT sites.
Materials and Methods:
Peripheral blood samples were obtained from 86 adult children (45 from nuclear test (NT) and 41 control), all born to veterans from the British Army, Royal Air Force, or Royal Navy.
Results:
G-banded karyotyping revealed no constitutional chromosomal abnormalities in any NT sample, including those from families reporting adverse health outcomes. We next assessed for unstable aberrations using conventional Giemsa staining and found some evidence of instability. Specifically, a small subset of NT children (N = 4) showed elevated chromatid aberration frequencies (7.81 ± 4.01 per 100 cells) compared with controls (4.36 ± 0.62; N = 26). To investigate further, we analyzed matched veteran father–child pairs observing a weak association between fathers’ unstable aberration burden and chromatid aberrations in their children, suggesting a potential transgenerational effect. This positive trend was most pronounced in the small group of families (N = 8; 2 control and 6 NT) previously identified as being enriched for mutation signature SBS16 in the germline.
Conclusions:
Although based on a small sample size, this observation warrants further investigation to understand the significance of SBS16, if any, including whether it may serve as a potential transgenerational mutational signature of radiation exposure. Overall, and in the context of health concerns raised by NT families, none of the self-reported health-related variables showed any association with unstable aberration burden in either the veteran fathers or their adult children.This work was, in part, supported by the Nuclear Community Charity Fund (NCCF) through funds received by The Armed Forces Covenant Fund Trust under the Aged Veterans Fund Grants AVF15A and AVF16 and CHRC Funded Studentship
Evidence for Similar Collectivity of High Transverse-Momentum Particles in -Pb and Pb-Pb Collisions
Get PDFA version of the article is available at arXiv:2502.07525v2 [nucl-ex] (https://arxiv.org/abs/2502.07525). Comments: Replaced with the published version. Added the journal reference and the DOI. All the figures and tables can be found at https://cms-results.web.cern.ch/cms-results/public-results/publications/HIN-23-002 (CMS Public Pages). Report number: CMS-HIN-23-002, CERN-EP-2024-332. Journal reference: Phys. Rev. Lett. 135 (2025) 071903. Submission history: From: The CMS Collaboration: [v1] Tue, 11 Feb 2025 13:02:27 UTC (594 KB); [v2] Thu, 14 Aug 2025 12:59:32 UTC (596 KB).Data availability—
Release and preservation of data used by the CMS Collaboration as the basis for publications is guided by the CMS data preservation, re-use and open access policy [71]. CMS data availability statement, 10.7483/OPENDATA.CMS.1BNU.8V1W.Charged hadron elliptic anisotropies (2) are presented over a wide transverse momentum (T) range for proton-lead (Pb) and lead-lead (PbPb) collisions at nucleon-nucleon center-of-mass energies of 8.16 and 5.02 TeV, respectively. The data were recorded by the CMS experiment and correspond to integrated luminosities of 186 and 0.607 nb⁻¹ for the Pb and PbPb systems, respectively. A four-particle cumulant analysis is performed using subevents separated in pseudorapidity to effectively suppress noncollective effects. At high T (T > 8 GeV), significant positive 2 values that are similar between Pb and PbPb collisions at comparable charged particle multiplicities are observed. This observation suggests a common origin for the multiparticle collectivity for high-T particles in the two systems.SCOAP³
Design of the ECCE Detector for the Electron Ion Collider
Get PDFThe file archived on this institutional repository is a preprint version of the article submitted to Nuclear Instruments and Methods A is available at arXiv:2209.02580v3 [physics.ins-det], https://arxiv.org/abs/2209.02580 ([v3] Sat, 20 Jul 2024 16:48:46 UTC (40,987 KB)). It has not been certified by peer review.The EIC Comprehensive Chromodynamics Experiment (ECCE) detector has been designed to address the full scope of the proposed Electron Ion Collider (EIC) physics program as presented by the National Academy of Science and provide a deeper understanding of the quark–gluon structure of matter. To accomplish this, the ECCE detector offers nearly acceptance and energy coverage along with excellent tracking and particle identification. The ECCE detector was designed to be built within the budget envelope set out by the EIC project while simultaneously managing cost and schedule risks. This detector concept has been selected to be the basis for the EIC project detector.We acknowledge support from the Office of Nuclear Physics in the Office of Science in the Department of Energy, the National Science Foundation, USA, and the Los Alamos National Laboratory Directed Research and Development (LDRD) 20200022DR.
This research used resources of the Compute and Data Environment for Science (CADES) at the Oak Ridge National Laboratory, which is supported by the Office of Science of the U.S. Department of Energy under Contract No. DE-AC05-00OR22725. The work of AANL group are supported by the Science Committee of RA, in the frames of the research project # 21AG-1C028. And we gratefully acknowledge that support of Brookhaven National Lab and the Thomas Jefferson National Accelerator Facility which are operated under contracts DE-SC0012704 and DE-AC05-06OR23177 respectively
Students' Views on Their Academic Skills Development: How Can We Further Enhance Students' Development During Their Degree and Beyond?
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Data can be made available upon publication.Providing students with the right academic support throughout their studies is a crucial element for successful degree completion and graduate outcomes. The purpose of this study is to provide insights on how academic skills development for students can be enhanced. Data were data collected from students through one-to-one semi-structured interviews with Year 1 and Year 2 Psychology students. Through thematic analysis, three themes were generated in the Year 1 students' data: positive experiences and skills development, engagement, and negative experiences and repetition. For Year 2 students, the generated themes were similar: negative opinions and suggestions for improvement, extraneous effects, positive aspects, and transferable learning and skills development. This has improved our understanding of the student experience which will be used to further enhance the programme and its provision of academic skills
The Stigmatisation of Men Who Have Sex With Men in the Spread of Mpox: Are We Repeating the Mistakes of <scp>HIV</scp> ?
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The authors have nothing to report.Editorial.The 2022 mpox outbreak disproportionately affected men who have sex with men (MSM), leading to targeted public health interventions. While data supported prioritising MSM, this focus risks reviving stigmatisation reminiscent of the HIV/AIDS crisis. This editorial examines the roots of this narrative and its potential negative impact on affected communities. We argue that while high-risk groups should be addressed, public health efforts must avoid reinforcing prejudices and instead adopt inclusive strategies. Expanding prevention beyond MSM, promoting community empowerment, and fostering collaboration are essential to combat both the virus and the stigma it can generate
Research Skills and Academic Literacy in Multilingual Higher Education: The Case of Kazakhstan
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The data presented in this study is available on request from the corresponding author. The dataset is part of an ongoing research project and is therefore not publicly available.Developing research skills and academic literacy is essential for student success, yet their progression often varies across multilingual higher education systems. This study investigates these competencies among 692 bachelor’s and master’s students in Kazakhstan’s trilingual higher education context, where Kazakh, Russian, and English serve as languages of instruction. The contributions of multilingual academic practices, language of instruction, reading proficiency in three languages, peer collaboration, teacher facilitation, learner autonomy, and academic performance were examined using hierarchical regression and cumulative logit models. Results show that multilingual academic practices emerged as the strongest and most consistent predictor of both research skills (β = 0.56) and academic literacy (β = 0.69), explaining 38% and 49% of variance respectively and clearly outperforming medium of instruction, single-language reading proficiency, and programme level. Peer collaboration, teacher facilitation, and academic performance emerged as the most powerful predictors of students’ overall self-assessed research competence. The findings position multilingualism as both linguistic and cognitive resource, offering implications for curriculum design, staff training, and multilingual research-based learning in higher education. The study advances international scholarship on multilingual higher education.This research was funded by the Ministry of Science and Higher Education of the Republic of Kazakhstan (Grant No. AP26197733, Developing Research Skills through the Study of Communication Strategies for Effective Cross-Cultural Interaction in the Linguistic Space of Kazakhstan, 2025–2027)
Beyond satisfaction: A hierarchical model of three distinct guest experience types in peer-to-peer accommodation
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Data will be made available on request.This paper develops and empirically tests a hierarchical model of service quality in peer-to-peer (P2P) accommodation, focusing on guest experiences and behavioral intentions before and after the COVID-19 pandemic. A conceptual model was developed from Airbnb review comments and tested through a survey. Post-pandemic, 47 follow-up interviews informed an updated model, followed by a second survey to capture shifts in guest perceptions. The findings suggest that P2P accommodation guests allocate considerable processing resources to cognitive cues (deliberative route) and emotional ones (experiential route) in decision making. Also, the study indicates that quality evaluation leads to guest experiences, namely, congenial, affective and intellectual, which ultimately result in behavioral intentions. The study advances service quality theory in the sharing economy context, responds to recent calls in the literature for a deeper theorization of P2P accommodation experiences, and offers managerial insights for hosts and policy makers navigating post-pandemic recovery
Belief as Explanation: A motivation-based theory of agency and anthropomorphism in religious belief
No full textSupernatural agent beliefs are ubiquitous across cultures, yet many theories aimed at explaining this fact have not held up to scrutiny. The most famous of these, the Hyperactive Agency Detection Device (HADD), has garnered several strong critiques and no supportive empirical evidence in almost 30 years. Yet, HADD is routinely cited as an explanation of why supernatural agent beliefs exist. We explore these problems and propose a new theoretical perspective to replace HADD. We suggest the tendency to create supernatural agents comes from the use of mental state reasoning to explain phenomenon beyond our current causal understanding. This is a non-automatic and cognitively effortful process. We review evidence that suggests we anthropomorphise when we are motivated to explain things we cannot explain using simpler causal mechanisms—like complex weather events or why good things happen to bad people. We argue this fits better than HADD with the evidence on how we use mental state reasoning to think about supernatural minds. This perspective allows us to account for two underspecified problems in the current literature: the shrinking domain of religion with the growth of science, and how to connect the origin of supernatural beliefs to the cultural evolution of religions.John Templeton Foundation: [Grant Number 61928]
Data sources:
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