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Monitoring lung injury with particle flow rate in LPS- and COVID-19-induced ARDS
In severe acute respiratory distress syndrome (ARDS), extracorporeal membrane oxygenation (ECMO) is a life-prolonging treatment, especially among COVID-19 patients. Evaluation of lung injury progression is challenging with current techniques. Diagnostic imaging or invasive diagnostics are risky given the difficulties of intra-hospital transportation, contraindication of biopsies, and the potential
Normalisation of glucose metabolism by exendin-4 in the chronic phase after stroke promotes functional recovery in male diabetic mice
Background and Purpose: Glucagon-like peptide-1 (GLP-1) receptor activation decreases stroke risk in people with Type 2 diabetes (T2D), while animal studies have shown the efficacy of this strategy to counteract stroke-induced acute brain damage. However, whether GLP-1 receptor activation also improves recovery in the chronic phase after stroke is unknown. We investigated whether post-acute, chron
Anterior uveitis in patients with spondyloarthritis treated with secukinumab or tumour necrosis factor inhibitors in routine care : Does the choice of biological therapy matter?
Background: The effect of interleukin 17-inhibitors on anterior uveitis (AU) in spondyloarthritis (SpA) is poorly understood. This study aimed to compare the risk of AU during treatment with secukinumab versus tumour necrosis factor inhibitors (TNFi). Methods: Patients with SpA starting secukinumab or a TNFi 2015 through 2018 were identified in the Swedish Rheumatology Quality Register. Occurrence
Localization studies for parathyroid surgery
How to assess breathlessness in chronic obstructive pulmonary disease
Activity-related breathlessness is the most problematic symptom of chronic obstructive pulmonary disease (COPD), arising from complex interactions between periph- eral pathophysiology (both pulmonary and non-pulmonary) and central perceptual proces- sing. To capture information on the breathlessness experienced by people with COPD, many different instruments exist, which vary in applicability depe
Negative chain referral sampling : doing justice to subcultural diversity
This paper calls for renewed consideration of the way researchsubjects are selected in the study of subcultures. All too often,subcultural researchers limit themselves to the use of one or twoof the orthodox sampling designs, such as ‘conveniencesampling’ (selecting subjects who are readily available) or ‘chainreferral sampling’ (selecting a readily available subject who refersthe researcher to ot
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
Assembly of FN-silk with laminin-521 to integrate hPSCs into a three-dimensional culture for neural differentiation
Three-dimensional (3D) neural tissue cultures recapitulate the basic concepts during development and disease better than what can be obtained using conventional two-dimensional cultures. Here, we use a recombinant spider silk protein functionalized with a cell binding motif from fibronectin (FN-silk) in combination with a human recombinant laminin 521 (LN-521) to create a fully defined stem cell n
p53 controls genomic stability and temporal differentiation of human neural stem cells and affects neural organization in human brain organoids
In this study, we take advantage of human induced pluripotent stem (iPS) cell-derived neural stem cells and brain organoids to study the role of p53 during human brain development. We knocked down (KD) p53 in human neuroepithelial stem (NES) cells derived from iPS cells. Upon p53KD, NES cells rapidly show centrosome amplification and genomic instability. Furthermore, a reduced proliferation rate,
DNA methylation changes in Down syndrome derived neural iPSCs uncover co-dysregulation of ZNF and HOX3 families of transcription factors
BACKGROUND: Down syndrome (DS) is characterized by neurodevelopmental abnormalities caused by partial or complete trisomy of human chromosome 21 (T21). Analysis of Down syndrome brain specimens has shown global epigenetic and transcriptional changes but their interplay during early neurogenesis remains largely unknown. We differentiated induced pluripotent stem cells (iPSCs) established from two D
Oxidative DNA Damage Signalling in Neural Stem Cells in Alzheimer's Disease
The main pathological symptoms of Alzheimer's disease (AD) are β-amyloid (Aβ) lesions and intracellular neurofibrillary tangles of hyperphosphorylated tau protein. Unfortunately, existing symptomatic therapies targeting Aβ and tau remain ineffective. In addition to these pathogenic factors, oxidative DNA damage is one of the major threats to newborn neurons. It is necessary to consider in detail w
Humanized Stem Cell Models of Pediatric Medulloblastoma Reveal an Oct4/mTOR Axis that Promotes Malignancy
Medulloblastoma (MB), the most frequent malignant childhood brain tumor, can arise from cellular malfunctions during hindbrain development. Here we generate humanized models for Sonic Hedgehog (SHH)-subgroup MB via MYCN overexpression in primary human hindbrain-derived neuroepithelial stem (hbNES) cells or iPSC-derived NES cells, which display a range of aggressive phenotypes upon xenografting. iP
Single-cell study of neural stem cells derived from human iPSCs reveals distinct progenitor populations with neurogenic and gliogenic potential
We used single-cell RNA sequencing (seq) on several human induced pluripotent stem (iPS) cell-derived neural stem cell (NSC) lines and one fetal brain-derived NSC line to study inherent cell type heterogeneity at proliferating neural stem cell stage and uncovered predisposed presence of neurogenic and gliogenic progenitors. We observed heterogeneity in neurogenic progenitors that differed between
Ataxia in Patients With Bi-Allelic NFASC Mutations and Absence of Full-Length NF186
The etiology of hereditary ataxia syndromes is heterogeneous, and the mechanisms underlying these disorders are often unknown. Here, we utilized exome sequencing in two siblings with progressive ataxia and muscular weakness and identified a novel homozygous splice mutation (c.3020-1G > A) in neurofascin (NFASC). In RNA extracted from fibroblasts, we showed that the mutation resulted in inframe ski
Single cell analysis of autism patient with bi-allelic NRXN1-alpha deletion reveals skewed fate choice in neural progenitors and impaired neuronal functionality
We generated human iPS derived neural stem cells and differentiated cells from healthy control individuals and an individual with autism spectrum disorder carrying bi-allelic NRXN1-alpha deletion. We investigated the expression of NRXN1-alpha during neural induction and neural differentiation and observed a pivotal role for NRXN1-alpha during early neural induction and neuronal differentiation. Si