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    Comparative genomics of Rickettsiella bacteria reveal variable metabolic pathways potentially involved in symbiotic interactions with arthropods
    (2025-10-07) Floriano, Anna M; El-Filali, Adil; Amoros, Julien; Buysse, Marie; Jourdan-Pineau, Hélène; Sprong, Hein; Kohl, Robert; Dirks, Ron P; Schaap, Peter; Koehorst, Jasper; Nijsse, Bart; Bouchon, Didier; Daubin, Vincent; Vavre, Fabrice; Duron, Olivier
    Members of the Rickettsiella genus (order: Legionellales) are emerging as widespread bacteria associated with insects, arachnids, and crustaceans. While some Rickettsiella strains are highly virulent pathogens, others are maternally inherited endosymbionts that manipulate arthropod phenotypes, including the induction of defensive symbiosis and cytoplasmic incompatibility. However, the genomic diversity of Rickettsiella remains largely unexplored, and their genetic potential to induce complex phenotypes in arthropods is only partially understood. In this study, we sequenced five new Rickettsiella genomes isolated from three tick species. Through comparative genomics, we observed that Rickettsiella members share similar metabolic capabilities, and collectively lack virulence genes from pathogenic Legionellales. Additional analysis of Rickettsiella genomes revealed significant variability in metabolic properties related to endosymbiosis. Specifically, their capacity to biosynthesize certain B vitamins and heme varies, suggesting a functional role of some Rickettsiella strains in the nutrition of their arthropod hosts. Some Rickettsiella genomes harbour homologs of Wolbachia cif genes, the cause of Wolbachia-induced cytoplasmic incompatibility, suggesting that Rickettsiella may use a similar molecular mechanism to manipulate the reproduction of their arthropod hosts. Phylogenomics further revealed that tick-borne Rickettsiella exhibit distinct evolutionary origins within the genus, indicating that Rickettsiella have undergone repeated horizontal transfers between ticks and other arthropods.
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    The potential role of the MTHFR C677T polymorphism in the pathogenetic mechanisms of hormonal and metabolic response to antihyperglycemic therapy
    (2025-09-08) Tyzhnenko, T; Misіura, K; Plokhotnichenko, O; Pocherniaiev, A; Kolesnikova, A; Marakhovskyi, I; Gorshunska, M; Leshchenko, Z; Jansen, E; Biernot Pamuła, K
    Background. Type 2 diabetes mellitus (T2DM) is a multifactorial disease involving both environmental and genetic components. The methylenetetrahydrofolate reductase (MTHFR) gene, particularly the C677T poly morphism, influences folate metabolism and homocysteine levels and may affect metabolic processes and phar macological response. Metformin is the first-line antihyperglycemic agent for T2DM, but interindividual variability in treatment response remains a key issue. The purpose of the work is to identify and assess the potential impact of a pathogenetically significant single-nucleotide polymorphism of the MTHFR gene on the development of obesity and type 2 diabetes mellitus in the implementation of the hormonal and metabolic effects of pharmacological factors. Materials and methods. This study included 28 patients with T2DM and metabolic syndrome (body mass index ≥ 30 kg/m2). Clinical, biochemical, and anthropometric parameters were assessed. Genotyping of the MTHFR C677T polymorphism was performed using polymerase chain reaction and restriction fragment length polymorphism. The effects of metformin therapy were evaluated by analyzing glycemic control, lipid profile, liver function, adipokine levels, and oxidative stress markers, taking into account the patients’ MTHFR genotypes. Results. Metformin use was associated with improved lipid profile in all genotypes. In addition, a genotype-specific reduction in liver enzyme activity was observed: aspartate aminotransferase levels decreased significantly in T allele carriers, while alanine aminotransferase reduced in patients with the CC genotype. These results suggest both pleiotropic and genotype-de pendent hepatoprotective effects of metformin. No significant differences in MTHFR genotype distribution were found between metformin-treated and untreated groups. Conclusions. Metformin has beneficial metabolic effects in T2DM patients and may exert genotype-specific hepatoprotective properties. The C677T polymorphism of the MTHFR gene did not determine whether patients were prescribed metformin, but it may modulate liver-related biochemical respon ses to the drug. These findings support the relevance of pharmacogenetic approaches to optimize therapy in T2DM.
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    Re-evaluating CD57 as a marker of T cell senescence: implications for immune ageing and differentiation
    (2025-10-31) Autaa, Gaëlle; Korenkov, Daniil; van Beek, Josine; Pellegrin, Isabelle; Parfait, Béatrice; van Baarle, Debbie; Launay, Odile; Tartour, Eric; Appay, Victor
    Ageing is accompanied by a decline in immune function, associated with susceptibility to infections and malignancies, and reduced vaccine efficacy. These immunological changes, affect multiple components of the immune system, particularly T lymphocytes, which exhibit altered subset distributions and accumulate senescent features. CD57, a surface glycoprotein expressed on T cells, has emerged as a potential marker of terminal differentiation and senescence used for immunomonitoring in infection or cancer contexts. However, the use of CD57 as a marker of T cell senescence remains unclear. To investigate this, we analyzed CD57 expression on CD8 and CD4 T cells in healthy donors from two independent cohorts, considering cellular differentiation, age, cytomegalovirus status, and other senescence markers. Our findings reinforce the association between CD57 expression, T cell differentiation, and CMV seropositivity, but not with chronological age. Although CD57 is associated with altered proliferation and survival in all T cell differentiation subsets, it does not fully align with a senescent phenotype. Therefore, we propose that CD57 may be better appreciated as a marker of immunological age. Moreover, the interpretation of CD57 expression must account for CMV serostatus to avoid misleading conclusions, especially in oncology and ageing research.
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    Host factors associated with respiratory particle emission and virus presence within respiratory particles: a systematic review
    (2025-10-15) Horstink, Nils; Lassing, Kirsten; Knoester, Marjolein; Vermeulen, Lucie C; Rossen, John WA; Voss, Andreas; Lokate, Mariëtte
    INTRODUCTION: Understanding host factor-related mechanisms that drive variability in respiratory particle emission and virus presence in exhaled particles is essential to assess transmission risk and potentially identify individuals with elevated infectiousness. METHODS: We conducted a systematic review of human observational studies examining associations between host factors and either respiratory particle emission or virus presence in exhaled particles. Searches in PubMed, EMBASE, and Web of Science covered studies up to September 2024. Risk of bias was assessed using STROBE-based criteria. Findings were synthesized narratively, grouped by host factor and outcome type. RESULTS: Forty-four studies met inclusion criteria: 34 assessed host factors in relation to particle emission, and 11 examined viral presence in exhaled particles. Fine particle emission (<5 μm) was most consistently associated with older age ( 16), physical exercise ( 6), and active infection ( 6). No consistent associations were found for sex ( 21), body mass index (BMI;  10), or smoking ( 6). Viral presence-mainly influenza and SARS-CoV-2-was more strongly associated with time since symptom onset ( 8) and lower respiratory symptoms ( 3), based largely on genomic detection. Associations with other factors, including upper respiratory symptoms ( 6), swab viral load ( 11), age ( 6), sex ( 6), and BMI ( 2), were inconsistent or absent. Physical exercise was not evaluated in relation to viral presence. DISCUSSION: Fine respiratory particles (<5 μm) were the predominant size fraction detected and often contained higher concentrations of viral RNA. Age, physical exercise, and active infection were consistently associated with increased emission of these particles. The presence of respiratory viruses in exhaled air was more strongly linked to infection-related factors such as early symptom onset and lower respiratory involvement. These patterns suggest distinct mechanisms contributing to airborne transmission. Interpretation was limited by methodological heterogeneity and predominant reliance on PCR. Still, consistent associations with host factors suggest their potential as indicators for transmission risk. As evidence focused mainly on influenza and SARS-CoV-2, generalizability is limited. Standardized methods and further research are needed to strengthen outbreak preparedness.
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    Trust in institutions and misinformation susceptibility both independently explain vaccine skepticism
    (2025-10-28) Roozenbeek, Thom; van den Berg, Caspar; Lambooij, Mattijs S; van der Linden, Sander; Maertens, Rakoen; Ferreira, José A; van Dijk, Mart; Roozenbeek, Jon
    Herd immunity for preventable childhood infectious diseases such as measles and mumps has come under threat in numerous countries, due to declining vaccination rates. This decline underscores the urgent need to understand the underlying mechanisms of vaccine skepticism. Institutional (dis)trust and belief in (vaccine) misinformation have been proposed as important factors, but their interconnectedness and potential mutual influence have remained elusive. Importantly, higher trust has been hypothesized to serve as a "buffer" against the adverse effects of misinformation belief. In this preregistered study (N = 1356, probability sample of Dutch households), we address these questions using validated, high-quality measures of vaccine attitudes, trust, and misinformation susceptibility. We find that specific trust in the government with respect to vaccinations is a much stronger predictor of vaccine skepticism than general trust in institutions. Moreover, susceptibility to misinformation is significantly associated with vaccine skepticism under all model specifications. Contrary to expectations, we find no evidence for the "buffer" hypothesis, suggesting that, while correlated, misinformation susceptibility and trust are distinctly related to vaccine skepticism.

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