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Comprehensive analysis of pseudogene expression in human and macaque brains compared with other tissues

2026-08-13T02:01:18Z

Title: Comprehensive analysis of pseudogene expression in human and macaque brains compared with other tissues Authors: Jiang, Yunzhe; Yang, Yucheng T; Sisu, Cristina; He, Tianxing; Won, Hyejung; Gerstein, Mark Abstract: Although gene expression in the brain has been extensively investigated and compared to other tissues, the activity of pseudogenes has not been comprehensively surveyed. Here, leveraging large-scale RNA-seq data, we construct consistent pseudogene expression profiles in human and macaque brains and compare them to 29 other tissues. We further annotate pseudogenes with potential cellular roles based on co-clustering them with protein-coding genes. Notably, the majority of the expressed pseudogenes show elevated expression in the brain relative to other tissues, and these pseudogenes show broad and consistent expression patterns across brain subregions. Furthermore, spatiotemporal analyses reveal that pseudogenes in different brain subregions have greatly varying temporal trajectories (e.g., increasing vs. decreasing), in contrast to protein-coding genes that tend to be more uniform. Finally, we identify a set of pseudogenes exhibiting significant changes in neuropsychiatric disorders, some of which overlap with known brain eGenes (genes whose expression is associated with expression quantitative trait loci, eQTLs), as well as with genes implicated by genome-wide association studies (GWAS). Together, our study provides a public resource of pseudogene expression in human and macaque brains (in comparison to other tissues) and highlights aspects of pseudogene expression in brain development and pathogenesis. Description: Data availability: The publicly available datasets and corresponding metadata used in this study were downloaded from Synapse (https://www.synapse.org), as listed in the Supplementary Tables S1-S4. The expression data of the pseudogenes and protein-coding genes in human and macaque, quantified based on the computational framework in this study, have been deposited to Zenodo (10.5281/zenodo.16810204). Specifically, the deposited datasets include: FPKM-normalized expression matrices of pseudogenes and protein-coding genes in non-brain tissues from human (Supplementary Tables S6–S7), FPKM-normalized expression matrices in diverse brain regions from both human and macaque (Supplementary Tables S8–S11), and raw count matrices of pseudogenes and protein-coding genes in human brain samples diagnosed with psychiatric disorders (Supplementary Tables S14–S15). Each matrix contains genes as rows and tissue or brain region samples as columns.

“I’m a bit of a Snowflake. I Can’t Meet the Male Expectations.” How Adolescent Boys’ Perceived Competency Shapes Their Motivation for Physical Activity.

2026-08-13T02:01:10Z

Title: “I’m a bit of a Snowflake. I Can’t Meet the Male Expectations.” How Adolescent Boys’ Perceived Competency Shapes Their Motivation for Physical Activity. Authors: Kerner, Charlotte; Beddoe, Amelia; Hings, Rebecca Abstract: ... Description: ...

Ciprofloxacin Metabolites Drive Resistance Development and Biofilm Changes in Pseudomonas aeruginosa and Staphylococcus aureus

2026-08-09T07:31:02Z

Title: Ciprofloxacin Metabolites Drive Resistance Development and Biofilm Changes in Pseudomonas aeruginosa and Staphylococcus aureus Authors: Gallagher, Mairéad; Harkova, Lyuboslava G.; Krawiel, Dominika; McCarthy, Ronan R.; Cooke, Gordon; Kelleher, Fintan Abstract: Objectives: To investigate how two major ciprofloxacin metabolites, 2-oxo ciprofloxacin (M3) and N-formyl ciprofloxacin (M4), influence the resistance profiles and biofilm characteristics of Pseudomonas aeruginosa (PAO1) and Staphylococcus aureus (ATCC 25923). Methods: Both metabolites were synthesised, structurally validated, and co-cultured with bacterial strains at sub-inhibitory concentrations (SICs) over a 30-day period. Minimum inhibitory concentration (MIC) assays, crystal violet biofilm quantification, and genomic and transcriptomic analyses (whole genome and differential RNA sequencing) were employed to assess phenotypic and molecular adaptations. Results: Exposure to ciprofloxacin metabolites altered bacterial behaviour despite their weak intrinsic antimicrobial activity. In S. aureus, continuous exposure to M3 and M4 resulted in an eight and four-fold increase, respectively, in ciprofloxacin MIC values. In P. aeruginosa, although MIC values remained unchanged, prolonged exposure to both metabolites enhanced biofilm formation, M4 (p<0.0001) and M3 (p<0.0089)). Genomic sequencing of P. aeruginosa revealed a missense mutation (A290D) in the wspA gene following M3 exposure, which activates biofilm-promoting pathways via cyclic-di-GMP signalling. RNA sequencing identified 220 differentially expressed genes, including upregulation of quorum sensing regulators (rhlI, pqsH), nitric oxide cycle genes (nir, norCB), and the pel operon. Conclusions: Ciprofloxacin metabolites, though less potent than the parent antibiotic, can drive adaptive responses linked to resistance and persistence. Their capacity to induce stable genetic and transcriptomic shifts underscores their potential ecological and clinical significance as underexplored factors in AMR.

Generation of 3D Hemogenic Gastruloids From Mouse Embryonic Stem Cells

2026-08-09T08:23:18Z

Title: Generation of 3D Hemogenic Gastruloids From Mouse Embryonic Stem Cells Authors: Cicirò, Ylenia; Pina, Cristina; Ragusa, Denise Abstract: Embryonic blood formation encompasses the independent generation of different cell types in distinct cellular and anatomical environments, reflecting highly coordinated specific hierarchies of interacting tissues. Despite widespread use of embryonic stem cells (ESC) and induced pluripotent stem cell (iPSC)-based models to attempt to capture blood development in vitro and generate hematopoietic stem cells (HSC), a system that fully captures the spatial and temporal complexity of embryonic hematopoiesis is still lacking. In recent years, gastruloid models have emerged as powerful representations of early development, demonstrating self-organizing behaviors such as symmetry breaking, elongation, multi-axis formation, somitogenesis, and early organogenesis, with striking parallels to embryonic processes. Here, we present a protocol to generate hemogenic gastruloids (haemGx) from mouse ESC (mESC) that closely recapitulates the multi-stage, multi-niche process of blood formation and generates developmentally accurate hematopoietic progenitors. The haemGx model has been proven valuable in understanding embryonic hematopoiesis, as well as an in vitro model of forms of infant leukemia with an embryonic, in utero origin. Description: How to cite: Readers should cite both the Bio-protocol article and the original research article where this protocol was used: 1 .Cicirò, Y., Pina, C. and Ragusa, D. (2026). Generation of 3D Hemogenic Gastruloids From Mouse Embryonic Stem Cells. Bio-protocol 16(15): e5777. DOI: 10.21769/BioProtoc.5777. 2. Ragusa, D., Suen, C. W., Torregrosa Cortes, G., Pastorino, F., Johns, A., Cicirò, Y., Dijkhuis, L., van den Brink, S., Cilli, M., Byrne, C., et al. (2025). Dissecting infant leukemia developmental origins with a hemogenic gastruloid model. eLife. 14: e3. https://doi.org/10.7554/elife.102324.3.