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Extremely preterm birth (at <28 postconceptional weeks) leads to brain injury and represents the leading cause of childhood-onset neuropsychiatric diseases. No effective therapeutics exist to reduce the incidence and severity of brain injury of prematurity. Hypoxic events are the most important environmental factor, along with inflammation. Among other developmental processes, the second half of in utero fetal development coincides with the migration of cortical interneurons from the ganglionic eminences into the cortex; this process is thus prone to disruptions following extremely preterm birth. To date, no studies have directly investigated the migration of human cortical inhibitory neurons under hypoxic conditions. Using multi-day confocal live imaging in human forebrain assembloids (hFA) derived from human-induced pluripotent stem cells (hiPSCs) and ex vivo developing human brain tissue, we found a substantial reduction in the migration of hypoxic interneurons. Using transcriptomics, we identified adrenomedullin (ADM) as the gene with the highest fold change increase in expression. Based on previous literature about the protective role of supplemental ADM for other injuries, here, we demonstrated that addition of exogenous ADM to the hypoxic media restores the migration defects of interneurons. Lastly, we showed that one of the mechanisms of protection by ADM is through the activation of the cAMP/PKA pathway and subsequent pCREB-dependent rescued expression of a subset of GABA receptors, which are known to promote migration. Overall, in this manuscript, we provide the first direct evidence for hypoxia-induced deficits in the migration of human cortical interneurons and identify ADM as a possible target for therapeutic development.
Pubmed ID: 42138713
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Software package as distribution of ImageJ and ImageJ2 together with Java, Java3D and plugins organized into coherent menu structure. Used to assist research in life sciences.
View all literature mentionsOne of the largest financiers of research in Sweden that promotes scientific research, teaching and/or education beneficial to the Kingdom of Sweden. 20-30 percent of the Foundation''s grants relate to high-value research equipment for use within the technical, natural sciences and biomedical fields, and about 50 percent relate to major research projects and substantial scientific networks. Universities, academies and similar research and educational institutions are eligible for grants within the following fields: * Expensive scientific equipment * Fellowship programs initiated by the Foundation * Selected research projects of significant potential * Larger educational research projects Applications may be submitted by individual scientists, or research groups affiliated to a Swedish university or equivalent institution. An application may also be submitted by the management of a university, university college, scientific academy, or national research associations. Applications from private individuals without connection to a scientific institution are not considered.
View all literature mentionsFoundation to help all people lead healthy, productive lives, this funding and job resource is focused on health, poverty, and opportunity. They work with partner organizations worldwide to tackle critical problems in four program areas. Their Global Development Division works to help the world''s poorest people lift themselves out of hunger and poverty. Their Global Health Division aims to harness advances in science and technology to save lives in developing countries. Their United States Division works to improve U.S. high school and postsecondary education and support vulnerable children and families in Washington State. And their Global Policy & Advocacy Division seeks to build strategic relationships and promote policies that will help advance their work. Our approach to grantmaking in all four areas emphasizes collaboration, innovation, risk-taking, and, most importantly, results. The foundation is unable to make grants directly to individuals. The majority of our funding is proactive and made to U.S. tax-exempt organizations that are independently identified by our staff.
View all literature mentionsSoftware for single-cell flow cytometry analysis. Its functions include management, display, manipulation, analysis and publication of the data stream produced by flow and mass cytometers.
View all literature mentionsGovernment agency in Sweden established in 2001, with the responsibility to support and develop basic scientific research. Its objective is for Sweden to be a leading nation in scientific research.
View all literature mentionsA commercial antibody supplier which supplies primary and secondary antibodies, biochemicals, proteins, peptides, lysates, immunoassays and other kits.
View all literature mentionsSoftware for image processing, analysis, and editing. The software includes features such as touch capabilities, a customizable toolbar, 2D and 3D image merging, and Cloud access and options.
View all literature mentionsSoftware package for differential gene expression analysis based on the negative binomial distribution. Used for analyzing RNA-seq data for differential analysis of count data, using shrinkage estimation for dispersions and fold changes to improve stability and interpretability of estimates.
View all literature mentionsThis monoclonal targets HIF1-a
View all literature mentionsThis monoclonal targets Tubulin
View all literature mentionsThis polyclonal targets rat IgG HRP-linked
View all literature mentionsThis monoclonal targets RAMP2 (B-5)
View all literature mentionsThis monoclonal targets beta-Actin
View all literature mentionsThis monoclonal targets RAMP1
View all literature mentionsThis polyclonal targets GFP antibody
View all literature mentionsThis unknown targets Rabbit IgG (H+L)
View all literature mentionsThis polyclonal targets IgG
View all literature mentionsThis polyclonal secondary targets IgG
View all literature mentionsThis polyclonal targets Cleaved Caspase-3 (Asp175)
View all literature mentionsA software which acquires and processes data sets, primarily through the Xcalibur system.
View all literature mentionsNovoExpress software enables sample acquisition and analysis. User hands-on time is minimized with the walk-away autosampler functionality as well as batch analysis, statistics, and reporting.
View all literature mentionsOpen source Java based image processing software program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.
View all literature mentionsSoftware tool as set of analysis pipelines that process chromium single cell RNA-seq output to align reads, generate feature-barcode matrices and perform clustering and gene expression analysis by 10xGenomics.
View all literature mentionsA software tool which provides interactive visualization capability for the integrated analysis of high-dimensional gene expression data.
View all literature mentionsSoftware performing alignment of high-throughput RNA-seq data. Aligns RNA-seq reads to reference genome using uncompressed suffix arrays.
View all literature mentionsReal Time PCR detection system that combines optical technology with temperature control. Six channel, five colors and one FRET channel, real-time PCR instrument for singlexplex or multiplex reactions. Quickly set up runs and monitor amplification traces in real time on integrated LCD touch screen, or use included CFX Maestro Software to design experiment and analyze results from connected computer.
View all literature mentionsMultifunctional monochromator based microplate reader. Offers luminescence scanning to complement its existing 3D and ultra fast absorbance and fluorescence scanning capabilities. Allows for very low volume absorbance measurements. Provides double orbital shaking for more efficient reagent mixing, Optimal Read function for reliable cell-based measurements, and injector module for precisely controlled pipetting for triggering fast kinetic reactions and bulk dispensing.
View all literature mentionsSoftware environment and programming language for statistical computing and graphics. R is integrated suite of software facilities for data manipulation, calculation and graphical display. Can be extended via packages. Some packages are supplied with the R distribution and more are available through CRAN family.It compiles and runs on wide variety of UNIX platforms, Windows and MacOS.
View all literature mentionsJava toolset for working with next generation sequencing data in the BAM format.
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