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Evaluation of TRAP-sequencing technology with a versatile conditional mouse model

Gene expression profiling of various cell lineages has provided invaluable insights into the molecular mechanisms regulating cellular development and differentiation. However, in vivo molecular profiling of rare and interspersed cell populations, such as endothelial cells, has remained challenging. We have generated a versatile floxed translating ribosome affinity purification (TRAP) mouse model,

Crosstalk between astrocytes and microglia results in increased degradation of α-synuclein and amyloid-β aggregates

BACKGROUND: Alzheimer's disease (AD) and Parkinson's disease (PD) are characterized by brain accumulation of aggregated amyloid-beta (Aβ) and alpha-synuclein (αSYN), respectively. In order to develop effective therapies, it is crucial to understand how the Aβ/αSYN aggregates can be cleared. Compelling data indicate that neuroinflammatory cells, including astrocytes and microglia, play a central ro

Gene expression profiles of brain endothelial cells during embryonic development at bulk and single-cell levels

The blood-brain barrier is a dynamic interface that separates the brain from the circulatory system, and it is formed by highly specialized endothelial cells. To explore the molecular mechanisms defining the unique nature of vascular development and differentiation in the brain, we generated high-resolution gene expression profiles of mouse embryonic brain endothelial cells using translating ribos

Protocol for the derivation, culturing, and differentiation of human iPS-cell-derived neuroepithelial stem cells to study neural differentiation in vitro

Here, we present a revised protocol to derive neuroepithelial stem (NES) cells from human induced pluripotent stem cells. NES cells can be further differentiated into a culture of neurons (90%) and glia (10%). We describe how to derive and maintain NES cells in culture and how to differentiate them. In addition, we show the potential use of NES cells to study the role of reactive oxygen species in

Extreme altitude changes between night and day during marathon flights of great snipes

Summary Several factors affect the flight altitude of migratory birds, such as topography, ambient temperature, wind conditions, air humidity, predation avoidance, landmark orientation, and avoiding over-heating from direct sunlight.1, 2, 3, 4, 5, 6 Recent tracking of migratory birds over long distances has shown that migrants change flight altitude more commonly and dramatically than previously t

Detection of Copy Number Aberration and Tumor Fraction in Archival Cervical Specimens from Ovarian Cancer Patients using Shallow Whole Genome Sequencing.

Ovarian cancer, often called the silent killer due to its diffuse symptoms at early stage, poor prognosis after treatments and high mortality, is also a heterogeneous disease consisting of different histological subtypes with potentially different origins. About 90% of all cases derive from epithelial cells and high-grade serous ovarian carcinoma (HGSOC) is the most common and aggressive form of e

Transplantation of Human Neural Precursor Cells Reverses Syrinx Growth in a Rat Model of Post-Traumatic Syringomyelia

Posttraumatic syringomyelia (PTS) is a serious condition of progressive expansion of spinal cord cysts, affecting patients with spinal cord injury years after injury. To evaluate neural cell therapy to prevent cyst expansion and potentially replace lost neurons, we developed a rat model of PTS. We combined contusive trauma with subarachnoid injections of blood, causing tethering of the spinal cord

Vetenskap och beprövad erfarenhet : Slutrapport från ett forskningsprogram

Forskningsprogrammet "Vetenskap och beprövad erfarenhet" tilldelades anslag av Stiftelsen Riksbankens Jubileumsfond 2015. Vetenskap och beprövad erfarenhet är ett minst sagt viktigt begrepp. Via olika lagar påverkar det våra myndigheter, Det påverkar oss som yrkesutövare och som medborgare. Samtidigt är det något oklart med vad som avses. Vad menas med vetenskap? Vems eller vilkas beprövade erfare

Broadly Active Antiviral Compounds Disturb Zika Virus Progeny Release Rescuing Virus-Induced Toxicity in Brain Organoids

RNA viruses have gained plenty of attention during recent outbreaks of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Zika virus (ZIKV), and Ebola virus. ZIKV is a vector borne Flavivirus that is spread by mosquitoes and it mainly infects neuronal progenitor cells. One hallmark of congenital ZIKV disease is a reduced brain size in fetuses, leading to severe neurological defects. The

Prolyl oligopeptidase inhibition by KYP-2407 increases alpha-synuclein fibril degradation in neuron-like cells

Growing evidence emphasizes insufficient clearance of pathological alpha-synuclein (αSYN) aggregates in the progression of Parkinson's disease (PD). Consequently, cellular degradation pathways represent a potential therapeutic target. Prolyl oligopeptidase (PREP) is highly expressed in the brain and has been suggested to increase αSYN aggregation and negatively regulate the autophagy pathway. Inhi

Presynaptic dysfunction in CASK-related neurodevelopmental disorders

CASK-related disorders are genetically defined neurodevelopmental syndromes. There is limited information about the effects of CASK mutations in human neurons. Therefore, we sought to delineate CASK-mutation consequences and neuronal effects using induced pluripotent stem cell-derived neurons from two mutation carriers. One male case with autism spectrum disorder carried a novel splice-site mutati

Models of the blood-brain barrier using iPSC-derived cells

The blood-brain barrier (BBB) constitutes the interface between the blood and the brain tissue. Its primary function is to maintain the tightly controlled microenvironment of the brain. Models of the BBB are useful for studying the development and maintenance of the BBB as well as diseases affecting it. Furthermore, BBB models are important tools in drug development and support the evaluation of t

Three-dimensional single-cell imaging for the analysis of RNA and protein expression in intact tumour biopsies

Microscopy analysis of tumour samples is commonly performed on fixed, thinly sectioned and protein-labelled tissues. However, these examinations do not reveal the intricate three-dimensional structures of tumours, nor enable the detection of aberrant transcripts. Here, we report a method, which we name DIIFCO (for diagnosing in situ immunofluorescence-labelled cleared oncosamples), for the multimo

Copy number variants (CNVs) : a powerful tool for iPSC-based modelling of ASD

Patients diagnosed with chromosome microdeletions or duplications, known as copy number variants (CNVs), present a unique opportunity to investigate the relationship between patient genotype and cell phenotype. CNVs have high genetic penetrance and give a good correlation between gene locus and patient clinical phenotype. This is especially effective for the study of patients with neurodevelopment

"Det handlar om vår framtid" : Hur elevers scientific literacy kan utvecklas genom SNI-argumentation i kemiundervisning

En individ i dagens samhälle kommer ständigt i kontakt med olika frågor som är kopplade till naturvetenskap. Val ska göras, beslut ska fattas. Ska jag vaccinera mig? Ska jag köpa den där vattentäta jackan? Vilket elbolag ska jag välja? Vilken fisk ska jag köpa? Ska jag skänka pengar till eller engagera mig i en miljöorganisation? Medborgare i ett demokratiskt samhälle behöver kunskaper som gör att

Dyslexia Candidate Gene and Ciliary Gene Expression Dynamics During Human Neuronal Differentiation

Developmental dyslexia (DD) is a neurodevelopmental condition with complex genetic mechanisms. A number of candidate genes have been identified, some of which are linked to neuronal development and migration and to ciliary functions. However, expression and regulation of these genes in human brain development and neuronal differentiation remain uncharted. Here, we used human long-term self-renewin

hiPS-Derived Astroglia Model Shows Temporal Transcriptomic Profile Related to Human Neural Development and Glia Competence Acquisition of a Maturing Astrocytic Identity

Astrocyte biology has a functional and cellular diversity only observed in humans. The understanding of the regulatory network governing outer radial glia (RG), responsible for the expansion of the outer subventricular zone (oSVZ), and astrocyte cellular development remains elusive, partly since relevant human material to study these features is not readily available. A human-induced pluripotent s

Identification of cell surface markers and establishment of monolayer differentiation to retinal pigment epithelial cells

In vitro differentiation of human pluripotent stem cells into functional retinal pigment epithelial (RPE) cells provides a potentially unlimited source for cell based reparative therapy of age-related macular degeneration. Although the inherent pigmentation of the RPE cells have been useful to grossly evaluate differentiation efficiency and allowed manual isolation of pigmented structures, accurat