Integrative analysis of spontaneous brain activity in Parkinson's disease: associations with gene expression, cell types, and receptor density.

The retina, our sensory organ for vision, displays distinct photoreceptor distributions and can have a specialized region for high visual acuity. The establishment of these spatial patterns during development depends on regionally restricted transcription factors and signaling pathways. Members of the T-box family of transcription factors, Tbx2, Tbx3, and Tbx5, show such restricted patterns of expression, with a dorsal high to ventral low pattern in the early retina. Their potential regulatory interactions and roles in patterning have not been fully explored. Here, we investigated their regulatory interactions by overexpression (OE) and knockdown (KD) approaches. We found that Tbx2, Tbx3, and Tbx5, directly or indirectly regulate each other as well as other early, patterned genes, including Fgf8, Cyp26a1, Cyp26c1, Cyp1b1, Raldh1, Ventroptin, and Bmp2. KD of any one of these Tbx genes increased rod photoreceptor density in a specific region of the retina, whereas Tbx2 loss additionally reduced the number of UV cones throughout the retina. Notably, KD of Tbx2, Tbx3, or Tbx5 consistently resulted in a smaller rod-free zone (RFZ), a domain within the high acuity area. These findings demonstrate that T-box transcription factors form a coordinated regulatory network that governs regional gene expression and photoreceptor patterning.

Letter to the editor: Comment on “Transposable element-associated structural variants and gene expression patterns in the hybrid of Megalobrama amblycephala♀ × Culter alburnus♂”

Identification, sequence characteristics, and expression patterns of Wnt genes in Eriocheir sinensis

Azadirachtin-induced oxidative stress in early life stages of the endangered horseshoe crab Tachypleus tridentatus: Implications for coastal conservation.

Molecular characterization and expression patterns of TLR22b gene in grass carp (Ctenopharyngodon idella) and association of single nucleotide polymorphisms with resistance/susceptibility to grass carp reovirus

BmADARa-mediated RNA editing regulates silk gland development and silk protein expression via miR-3315 targeting BmSuc1 in Bombyx mori.

Vitreous transcriptomic profiling reveals miR-4762 as a potential diagnostic biomarker and modulator of disease pathophysiology in Tubercular Uveitis.

Brains are complex structures comprising thousands to billions of neurons that belong to thousands of different neuronal types. These neurons often come from different progenitor domains and have very diverse developmental histories, yet they need to find their precise locations in the brain and integrate into appropriate circuits. While a large number of brain single-cell mRNA sequencing atlases have described the neuronal part list of the brain, spatial transcriptomic studies have lagged behind in offering the spatial information that is essential to understand brain structures. Here, we use a gene expression cartography algorithm called Novosparc to reconstruct the spatial distribution of gene expression and cell type localization in a complex, yet tractable, developing brain structure, the Drosophila optic lobe. We generate a three-dimensional atlas of this structure (https://larva3dnovosparc.ijm.fr); this atlas allowed us to identify spatially patterned transcription factors that define neuronal types. Importantly, we identify caveats in the algorithm and we discuss limitations of the current implementation that should guide future algorithmic improvements. Altogether, this work provides an invaluable tool to test gene expression patterns and paves the way for the generation of three-dimensional atlases of more complex brain structures, which will enhance our understanding of how neurons with diverse developmental lineages can integrate to form a functional brain.

Aluminum (Al), as a ubiquitous environmental pollutant, has been implicated in the pathogenesis and progression of various neurodegenerative diseases due to its neurotoxic properties. Recent studies indicate that aluminum exposure may induce aberrant epigenetic modifications, thereby disrupting gene expression patterns and cellular functions, ultimately leading to neuronal damage. This review focuses on examining the cross-hierarchical regulatory mechanisms of aluminum exposure on DNA methylation, histone modifications, noncoding RNAs, and RNA modifications. We point out an issue in current research-the isolated analysis of individual epigenetic modifications often neglects their network-based cascade effects. Future investigations should focus on integrating multi-omics approaches with dynamic modeling to elucidate the hierarchical transmission mechanisms underlying epigenetic crosstalk.

Genome-wide identification and functional validation of thermal tolerance genes in Mytilus coruscus using a yeast-based functional screening system.

A comprehensive transcriptomic and hormonal analysis reveals a hormetic effect of low-level lead exposure on plant growth

Cell type-specific transcriptional features associated with gray matter volume alterations in schizophrenia with predominantly negative symptoms.

Intermittent hypoxia (IH), a hallmark feature of obstructive sleep apnea (OSA), is associated with a range of physiological alterations that contribute to metabolic dysfunction and insulin resistance. IH induces adipose tissue inflammation and macrophages may play a key role in such homeostatic derangements. To examine the role of monocytes/macrophages in OSA, CD11b-diphtheria toxin receptor transgenic (DTR) mice were treated with diphtheria toxin (DT) to selectively eliminate these cells and assess changes in the metabolic function of IH-exposed mice. Transgenic homozygous male and female DTR mice were exposed to IH or room air (RA) for 6 weeks during which insulin sensitivity and other metabolic measures were assessed. Immunofluorescence analysis was performed for CD11b+ expression in metabolic tissues such as liver and visceral white adipose tissue (vWAT). Gene expression patterns associated with senescence-associated secretory phenotypes (SASPs) as well as adipokines and cytokines were evaluated. Depletion of CD11b+ cells in mice exposed to IH resulted in significant improvements in metabolic function and insulin sensitivity. Macrophage infiltration, assessed by F4/80 or CD11b immunostaining, was significantly reduced following CD11b ablation in IH exposed mice compared with controls in both males and females. Moreover, CD11b+ cell ablation led to a marked decrease in SASPs markers (p16 and Il-16) at both transcriptional and protein levels in vWAT and liver. Thus, depletion of CD11b+ cells in mice exposed to IH can significantly modulate the inflammatory response in multiple metabolic organs including visceral adipose tissues and markedly mitigate metabolic dysfunction. Targeted interventions aimed at some of the functional roles played by activated CD11b+ cells or SASPs within metabolic organs may improve metabolic regulation in OSA patients.

The construction of tissue shapes during embryonic development results from patterns of gene expression and mechanical forces fueled by chemical energy from ATP hydrolysis. We find that chemical energy is similarly patterned during apical constriction, which is widely used across the animal kingdom to fold epithelial tissues. Time-lapse imaging, spatial transcriptomics, and measurements of oxygen consumption rate reveal that mitochondrial density, potential, and ATP increase at the apical side of epithelial cells before actomyosin contraction and tissue folding, which is prevented by inhibiting oxidative phosphorylation. Mitochondrial enrichment and apical bias are conserved during apical constriction in flies, chicks, and mice, and these patterns can be used to predict computationally patterns of tissue folding. These findings highlight a spatial dimension of bioenergetics in development.

Advancements in sequencing technology enable the investigation of genomic information within its three-dimensional (3D) spatial structure, offering new insights into genome organization and function. However, the role of higher-order chromatin architecture in species divergence and speciation remains largely unexplored. Here we constructed 3D genome maps and performed comparative analyses across 11 phylogenetically diverse Populus species, revealing that evolutionary changes in 3D chromosomal architecture are closely associated with genomic differentiation. While chromatin compartments (A/B) are generally conserved across species, topologically associated domains exhibit substantial divergence. Integrating multi-omics data, we observed that genes located in dynamic 3D chromatin regions display distinct patterns of sequence conservation, gene expression and epigenetic modifications, emphasizing the interplay among spatial chromatin reorganization, transcriptional regulation and epigenetics during genome evolution. Structural variants are shown to play a key role in shaping interspecific 3D genome diversity. Notably, a ~76-bp insertion/deletion in HSFA2 3' UTR within divergent topologically associated domain boundaries modulates divergent heat-stress responses across species, underscoring the potential functional significance of 3D genome changes in adaptive evolution. Together, this study highlights the necessity of integrating 3D chromatin organization with genomic and epigenomic variation to dissect the molecular mechanisms underlying species divergence and ecological adaptation.

ABSTRACT Individuals with inborn errors of immunity often mount suboptimal responses to vaccination, yet the molecular determinants underlying their variable responses to mRNA vaccines remain poorly defined. The present study aimed to identify baseline immune transcriptional signatures predictive of humoral responses to the BNT162b2 (Comirnaty) mRNA vaccine in individuals with inborn errors of immunity. Twenty-one SARS-CoV-2-naïve participants with diverse inborn errors of immunity were stratified as high or low responders to the BNT162b2 vaccine based on anti-SARS-CoV-2 spike IgG titers at day 28 post-vaccination. Although vaccine-induced T cell responses were broadly comparable, low responders had significantly lower frequencies of switched memory B cells (p = .014). Transcriptional profiling revealed 41 differentially expressed genes between groups at baseline. Activated memory B cells and peripheral T follicular helper cells from high responders exhibited greater induction of activation and memory-related genes, including NFKB1, CD69, TIGIT, CD40L, and BATF, indicating greater intrinsic readiness to support coordinated antibody production. These findings demonstrate that distinct pre-vaccination gene expression patterns within specific immune subsets are associated with differential humoral responses to mRNA vaccination in individuals with inborn errors of immunity. More broadly, the study highlights that baseline molecular immune features substantially influence vaccine efficacy and suggests that pre-vaccination transcriptional profiling may enable more personalized vaccination strategies for individuals with impaired immunity.

ABSTRACT Benzo(a)pyrene (BaP), an environmental carcinogen, contributes to colon cancer pathogenesis through incompletely elucidated mechanisms. This study integrated network toxicology and multi-omics analyses to decipher BaP-associated molecular signatures and clinical relevance in colon cancer. Using TCGA-COAD data, 113 differentially expressed BaP-related targets were identified via CTD and Super-PRED databases. PPI networks, functional enrichment, and Cox/Lasso regression revealed key pathways (xenobiotic metabolism, p53 signaling, cell cycle) and six prognostic genes (CLK2, CRYAB, RPS6KA1, DPP7, CDC25C, GAST). A BaP-related risk model stratified patients into distinct survival groups. A nomogram accurately predicted 1-, 3-, and 5-year overall survival. High-risk scores correlated with advanced tumor stage, metastasis, and immunosuppressive microenvironments. Molecular docking demonstrated strong BaP binding to CLK2 and CRYAB. External validation (GSE39582, TNMplot) confirmed tumor-specific gene expression patterns. These findings delineate BaP-driven networks connecting xenobiotic stress, immune dysregulation, and tumor progression. The risk model provides a prognostic biomarker for personalized management and therapeutic targeting in colon cancer.

Alternative splicing in plants: emerging order from chaos.

Alcohol dependence currently lacks targeted pharmacotherapies, underscoring the urgent need for novel therapeutic targets. Existing research on disease-associated DNA methylation changes and their gene regulatory effects remains inconsistent. To resolve this uncertainty, we applied the Mendelian randomization to elucidate causal mechanisms connecting druggable genes, epigenetic regulation and alcohol dependence development. Integrating MR, colocalization and mediation analyses, we leveraged genome-wide association study (GWAS) (FinnGen), eQTL (eQTLGen) and methylation (GoDMC) data. We assessed causal gene-alcohol dependence relationships, shared causal variants via colocalization and methylation-mediated regulatory mechanisms. Our integrative analysis identified 10 drug-targetable genes showing significant expression alterations in alcohol dependence (FDR < 0.05), with three genes (CDK5R1, CAMKK2 and NRBP1) demonstrating evidence of shared causal variants through colocalization. Epigenetic regulation was particularly evident at two methylation sites (cg07437263 and cg05102552) that indirectly influenced alcohol dependence risk by modulating CDK5R1 (63.92% mediation) and NRBP1 (95.12% mediation) expression. These findings reveal DNA methylation as a critical regulatory mechanism governing neuronal gene expression patterns in alcohol dependence pathogenesis. The strong mediation effects observed for CDK5R1 and NRBP1, coupled with their colocalization evidence, position these genes as promising candidates for both biomarker development and targeted therapeutic interventions in alcohol dependence. This investigation spotlights the regulatory function of DNA methylation on CDK5R1 and NRBP1 in alcohol dependence. It implies that CDK5R1 and NRBP1 could serve as potential clinical biomarkers or therapeutic targets for the early management of alcohol dependence.