Stable genomic integration of exogenous transgenes is essential in neurodevelopmental and stem cell studies. Despite tools driving increasingly efficient genomic insertion with DNA vectors, transgenesis remains fundamentally hindered by the impossibility of distinguishing integrated from episomal transgenes. Here, we introduce an integration-coupled On genetic switch, iOn, which triggers gene expression upon incorporation into the host genome through transposition, thus enabling rapid and accurate identification of integration events following transfection with naked plasmids. In vitro, iOn permits rapid drug-free stable transgenesis of mouse and human pluripotent stem cells with multiple vectors. In vivo, we demonstrate faithful cell lineage tracing, assessment of regulatory elements, and mosaic analysis of gene function in somatic transgenesis experiments that reveal neural progenitor potentialities and interaction. These results establish iOn as a universally applicable strategy to accelerate and simplify genetic engineering in cultured systems and model organisms by conditioning transgene activation to genomic integration.

ATP1A3 , a mutated gene for AHC, RDP, and CAPOS, is also associated with polymicrogyria by different functional variants.

Astrocytes provide trophic and metabolic support to neurons and modulate circuit formation during development. In addition, astrocytes help maintain neuronal homeostasis through neurovascular coupling, blood–brain barrier maintenance, clearance of metabolites and nonfunctional proteins via the glymphatic system, extracellular potassium buffering, and regulation of synaptic activity. Thus, astrocyte dysfunction may contribute to a myriad of neurological disorders. Indeed, astrocyte dysfunction during development has been implicated in Rett disease, Alexander’s disease, epilepsy, and autism, among other disorders. Numerous disease model mice have been established to investigate these diseases, but important preclinical findings on etiology and pathophysiology have not translated into clinical interventions. A multidisciplinary approach is required to elucidate the mechanism of these diseases because astrocyte dysfunction can result in altered neuronal connectivity, morphology, and activity. Recent progress in neuroimaging techniques has enabled noninvasive investigations of brain structure and function at multiple spatiotemporal scales, and these technologies are expected to facilitate the translation of preclinical findings to clinical studies and ultimately to clinical trials. Here, we review recent progress on astrocyte contributions to neurodevelopmental and neuropsychiatric disorders revealed using novel imaging techniques, from microscopy scale to mesoscopic scale.

Although anthocyanins are major forms distributed in many plant foods and promising as chemopreventive source, many molecular data are obtained from anthocyanidins, showing their low bioavailability. This study aims to clarify the inhibitory effects of delphinidin glycosides on cell transformation comparing them to those of delphinidin. Screening data revealed that delphinidin 3-sambubioside could directly bind to MAPK/ERK kinase 1. Affinity assay data confirmed that delphinidin 3-sambubioside had higher binding affinity to MAPK/ERK kinase 1 than ERK1/2 and B-Raf. Colony assay data further demonstrated that delphinidin 3-sambubioside inhibited 12-O- tetradecanoylphorbol-13-acetate-induced phosphorylation of MAPK/ERK kinase 1 and sequentially suppressed cell transformation. All of these effects caused by delphinidin 3-sambubioside were weaker than those by its aglycon, delphinidin. Our data suggested that the weaker anti- transformation activity of delphinidin glycosides compared to that of their aglycon is due to lower binding affinity to the target molecule MAPK/ERK kinase 1.

Understanding brain evolution requires detailed comparative analyses of brain structures across species. However, high-resolution anatomical and connective data remain limited for most vertebrates beyond a few well-studied model organisms. To address this gap, we collected postmortem brain samples from a range of vertebrates, primarily small amniotes, and performed magnetic resonance imaging and histological staining. Here, we present the “Animal Brain Collection (ABC),” a freely accessible database that enables researchers to examine and compare cellular and tissue-level brain architectures across species. This resource provides a foundation for cross-species investigations of brain structure and development, offering new opportunities for research into the diversity and evolution of vertebrate brains.