http://bura.brunel.ac.uk/handle/2438/8614 Thu, 21 May 2026 02:30:00 GMT 2026-05-21T02:30:00Z http://bura.brunel.ac.uk/handle/2438/33313 Title: Therapeutic activity of a hematopoietic stem cell-delivered cell-penetrating frataxin in Friedreich’s ataxia models Authors: Pido-Lopez, J; Moula, SE; Shaban, E; Stamatiou, K; Critchley, BJ; Whittaker, TE; Svensson, S; Anjomani Virmouni, S; Kalef-Ezra, E; Carr, L; Hassel, J; Thrasher, AJ; Kurian, MA; Blair, IA; Rojsajjakul, T; Santilli, G; Sala, A Abstract: Summary: Friedreich’s ataxia (FRDA) is an autosomal recessive neurodegenerative disease caused by a GAA repeat expansion in the frataxin (FXN) gene, leading to reduced frataxin, a protein essential for mitochondrial function. We developed a replacement strategy using a fusion protein containing secretion and cell-penetrating sequences fused to the frataxin precursor. In vitro studies confirmed secretion, cellular penetration, mitochondrial localization, and rescue of biochemical defects and apoptosis in cells from patients with FRDA. The therapeutic cDNA was cloned into a lentiviral vector and used to transduce hematopoietic stem and progenitor cells (HSPCs) from YG8sR mice, an FRDA model. Autologous transplantation of modified HSPCs produced stable peptide secretion in the bloodstream and delayed the onset of motor coordination symptoms, accompanied by improved biochemical and anatomical parameters. Patient-derived CD34+ HSPCs transduced with the vector differentiated normally into macrophages and secreted the peptide. These results support a cell and gene therapy strategy for long-term stabilization of FRDA. Description: Highlights: • Reduced levels of the mitochondrial protein frataxin cause FRDA • HSPCs have been engineered to secrete a cell-penetrating frataxin protein • Autologous transplantation of modified HSPCs ameliorates symptoms in FRDA mice • Patient HSPCs modified by gene therapy secrete the therapeutic frataxin protein; Data and code availability: • All data are available upon reasonable request to the lead contact, Arturo Sala (arturo.sala@brunel.ac.uk). • No custom code was generated in this study. • Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.; Supplemental information is available online at: https://www.sciencedirect.com/science/article/pii/S266637912600220X#appsec2 .; Acknowledgments: We thank Paola Vagnerelli for assistance and expertise with the microscopic analysis of cells; Robert Spaull for collection of patient samples; and Marta Zinicola and Andrea Schejtman for initial testing of the frataxin construct; and Elizabeth McCarthy (Microscopy facility manager, Brunel) for support with super-resolution microscopy. Wed, 13 May 2026 00:00:00 GMT http://bura.brunel.ac.uk/handle/2438/33313 2026-05-13T00:00:00Z http://bura.brunel.ac.uk/handle/2438/33311 Title: Depression Authors: Malhi, GS; Bell, E; Stavdal, A; Wu, C-Y; Naylor, A; Kumari, V Abstract: Depression is a common illness that affects people within every society around the world. It afflicts the young and the old and everyone in between, and as such poses an immense global burden. New interventions and a deeper understanding of this illness are emerging, but improving the use of existing treatments is equally important and might be a more efficient and effective strategy to addressing depression. Therefore, it is imperative that we improve the diagnosis of depression and its clinical management. Description: Supplementary Material is available online at: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(26)00201-1/fulltext#supplementary-material . Sat, 02 May 2026 00:00:00 GMT http://bura.brunel.ac.uk/handle/2438/33311 2026-05-02T00:00:00Z http://bura.brunel.ac.uk/handle/2438/33310 Title: Empirical validation of race-neutral normative brain morphometry models across ethnoracially diverse populations Authors: Ge, R; Yu, Y; New, F; Haas, SS; Sanford, N; Yu, K; Allen, P; Arslan, S; Avram, M; Borgwardt, S; Crossley, NA; de la Fuente-Sandoval, C; Fukunaga, M; Gao, J-H; Gonzalez-Valderrama, A; Hashimoto, R; Iasevoli, F; Keeser, D; Kubat, K; Kumari, V; Matsumoto, J; Mehta, UM; Nemoto, K; Pontillo, G; Raabe, FJ; Reyes-Madrigal, F; Roy, N; Şahin-Çevik, D; Sahin-Ilikoglu, T; Toulopoulou, T; Wagner, E; Yang, G; Zurita, M; Thompson, PM; Frangou, S Abstract: Normative models of brain morphometry quantify individual deviations from typical anatomical patterns and hold promise for enhancing clinical decision-making. However, their clinical utility depends critically on demonstrating generalizability across diverse ethnoracial populations. We previously developed sex-specific, race-neutral normative models for cortical thickness, surface area, and subcortical volumes using brain scans from a large international sample of healthy individuals, as part of the CentileBrain Project, a global initiative to provide open-access, neuroimaging reference models. The primary aim of the present study was to empirically evaluate the generalizability and accuracy of these pretrained models across multiple ethnoracial groups. To this end, we tested model performance in independent samples of healthy individuals from Africa, Asia, Europe, and the Americas, with ethnoracial classification defined either by self-identification or genetic ancestry (N = 4,862). We further compared performance against normative models developed exclusively from a single-population Chinese cohort. Across all groups, as well as in the pooled sample, the pretrained CentileBrain models demonstrated consistently high accuracy, with relative mean absolute error values below 10% for subcortical volume and surface area and below 5% for cortical thickness. Model performance was highly concordant across self-identified and ancestry-defined groups. In a separate analysis, the CentileBrain models performed comparably to a population-specific model when applied to an independent ancestry-matched sample. These findings provide empirical support for the generalizability of race-neutral normative models developed on large and diverse samples and underscore their potential utility for individualized neuroimaging assessment across ethnoracially diverse populations. Description: Data, Materials, and Software Availability: The pretrained CentileBrain Models are freely available at https://centilebrain.org/ while the deviation Z-scores of all samples used here can be access through https://doi.org/10.6084/m9.figshare.31100953. The original imaging data can be accessed through a number of repositories with a range of licensing conditions. Specifically, the ABCD dataset can be accessed through the US National Data Archive (https://nda.nih.gov/); the CHCP dataset can be accessed through the Science Data Bank website (https://doi.org/10.11922/sciencedb.01374); the Psy-ShareD dataset can be accessed by request at https://psyshared.com/; the SALD and SLIM datasets can be accessed through the International Data-sharing Initiative (https://fcon_1000.projects.nitrc.org/indi/retro/sald.html and https://fcon_1000.projects.nitrc.org/indi/retro/southwestuni_qiu_index.html); the UKB dataset can be access through the UK Biobank data-access protocol (https://www.ukbiobank.ac.uk/enable-your-research/apply-for-access). Data from BRAID-TWINS cohort (39), the Cognitive Genetics Collaborative Research Organization (25) and the Clinical Deep Phenotyping Working Group (https://www.psych.mpg.de/2948741/cdp-working-group) and South American datasets (38) can be made available through the cited original sources.; Supporting Information is available online at: https://www.pnas.org/doi/10.1073/pnas.2521055123#supplementary-materials . Tue, 12 May 2026 00:00:00 GMT http://bura.brunel.ac.uk/handle/2438/33310 2026-05-12T00:00:00Z http://bura.brunel.ac.uk/handle/2438/33299 Title: The impact of artificial sweeteners on bacterial physiology and the microbiome Authors: Staber, C; Krawiel, D; McCarthy, RR Abstract: Artificial sweeteners are non-nutritive compounds that have a profound sweetening effect with a negligible to zero calorific contribution. Global initiatives to reduce sugar consumption to tackle health conditions such as obesity have led to a significant increase in their consumption in recent decades. Artificial sweeteners have undergone extensive testing to determine whether their consumption could impact human health; however, their impact on the microbiome and microbial physiology has been comparatively overlooked. Recent work has demonstrated that artificial sweeteners (e.g., Ace-K, saccharin, and aspartame) can influence the oral and gut microbiome and that they can significantly affect bacterial behavior and growth. In this review, we will contextualize these findings and explore their relevance to human artificial sweetener consumption. Description: Highlights: • Artificial sweeteners have been shown to impact the human gut microbiome to varying levels, with saccharin having the most pronounced effect, influencing the human glycemic response via gut microbiome dysbiosis. • At environmentally relevant concentrations, a range of artificial sweeteners have been shown to impact bacterial conjugation and natural transformation. • Several artificial sweeteners have been shown to inhibit bacterial growth, including the growth of multidrug-resistant pathogens. • Certain artificial sweeteners, such as Ace-K and saccharin, have also shown antivirulence potential by inhibiting biofilm formation and increasing antibiotic susceptibility, highlighting their therapeutic potential.; Supplemental information is available online at: https://www.cell.com/cms/10.1016/j.tim.2026.01.010/attachment/8d35106f-6e32-4b22-9518-3f89debfe7a5/mmc1.docx (Document (189.36 KB). Mon, 13 Apr 2026 00:00:00 GMT http://bura.brunel.ac.uk/handle/2438/33299 2026-04-13T00:00:00Z