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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
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
Controversial evidence points to a possible involvement of methylmercury (MeHg) in the etiopathogenesis of autism spectrum disorders (ASD). In the present study, we used human neuroepithelial stem cells from healthy donors and from an autistic patient bearing a bi-allelic deletion in the gene encoding for NRXN1 to evaluate whether MeHg would induce cellular changes comparable to those seen in cell
Vi har undersökt orsaken till de pågående kon!ikterna mellan skogsägare och skogsvårdande myndigheter angående tillämpningen av artskyddsförordningen. Vi konstaterar att myndigheterna i ett internt projekt har utvecklat en tillämp-ning av artskyddsförordningen som saknar stöd i gängse rättskällor, som lagtext, förarbeten och praxis. Tillämpningen etablerades i internt framtagna riktlinjer för hand
Down syndrome (DS) or trisomy 21 (T21) is a leading genetic cause of intellectual disability. To gain insights into dynamics of molecular perturbations during neurogenesis in DS, we established a model using induced pluripotent stem cells (iPSC) with transcriptome profiles comparable to that of normal fetal brain development. When applied on iPSCs with T21, transcriptome and proteome signatures at
BACKGROUND: Mutations in mitochondrial aminoacyl tRNA synthetases form a subgroup of mitochondrial disorders often only perturbing brain function by affecting mitochondrial translation. Here we report two siblings with mitochondrial disease, due to compound heterozygous mutations in the mitochondrial tryptophanyl-tRNA synthetase (WARS2) gene, presenting with severe neurological symptoms but normal
Neurodegenerative disorders are an increasingly common and irreversible burden on society, often affecting the aging population, but their etiology and disease mechanisms are poorly understood. Studying monogenic neurodegenerative diseases with known genetic cause provides an opportunity to understand cellular mechanisms also affected in more complex disorders. We recently reported that loss-of-fu
Here we report that the low-voltage-dependent T-type calcium (Ca2+) channel Cav3.2, encoded by the CACNA1H gene, regulates neuronal differentiation during early embryonic brain development through activating caspase-3. At the onset of neuronal differentiation, neural progenitor cells exhibited spontaneous Ca2+ activity. This activity strongly correlated with the upregulation of CACNA1H mRNA. Cells
Neuroblastoma (NB) is an embryonic tumor of the peripheral nervous system and one of the most common solid cancers in infants. Mutations in the Anaplastic lymphoma tyrosine kinase (ALK) gene are common in NB. To study the contribution of ALK mutations in NB initiation and progression, we reprogrammed fibroblasts from two related NB patients carrying germline mutations in ALK (R1275Q) using non-int
Schizophrenia is a complex disorder with clinical manifestations in early adulthood. However, it may start with disruption of brain development caused by genetic or environmental factors, or both. Early deteriorating effects of genetic/environmental factors on neural development might be key to described disease causing mechanisms. Establishing cellular models with cells from affected individual u
Astrocytes have important functions in the brain and their deregulation may cause disease. Current ways to derive astrocytes from pluripotent stem cells are labor, time, and resource intensive, but in this issue of Stem Cell Reports, Li et al. present a faster method to produce functional astrocytes using transcription factors.
Cell-based models of the blood-brain barrier (BBB) are important for increasing the knowledge of BBB formation, degradation and brain exposure of drug substances. Human models are preferred over animal models because of interspecies differences in BBB structure and function. However, access to human primary BBB tissue is limited and has shown degeneration of BBB functions in vitro. Human induced p
In vitro modeling of complex diseases is now a possibility with the use of patient-derived induced pluripotent stem (iPS) cells. Their stem cell properties, including self-renewal and their potential to virtually differentiate into any cell type, emphasize their importance as a translational tool for modeling disorders that so far have been limited by the unavailability of primary cell lines, anim
In massive multiple-input multiple-output (MIMO) systems, the large size of channel state information (CSI) matrix significantly increases the computational complexity of uplink detection and size of required memory to store the channel data. To address these challenges, we propose to perform detection in the angular domain, where the channel information can be presented in a more condensed way. T
Introduction: In contrast to the intake of sugar-sweetened beverages (SSBs), the evidence linking added sugar intake to the risk of cardiometabolic disease (primarily referring to cardiovascular disease and type 2 diabetes (T2D)) is contradictory. Aim: The aim of this thesis is to elucidate the role of added sugar intake in the risk for cardiometabolic diseases. To obtain further understanding of
In vivo studies of human brain cellular function face challenging ethical and practical difficulties. Animal models are typically used but display distinct cellular differences. One specific example is astrocytes, recently recognized for contribution to neurological diseases and a link to the genetic risk factor apolipoprotein E (APOE). Current astrocytic in vitro models are questioned for lack of
The BRCA1 protein, one of the major players responsible for DNA damage response has recently been linked to Alzheimer's disease (AD). Using primary fibroblasts and neurons reprogrammed from induced pluripotent stem cells (iPSC) derived from familial AD (FAD) patients, we studied the role of the BRCA1 protein underlying molecular neurodegeneration. By whole-transcriptome approach, we have found wid
Caffeine is a widely consumed psychoactive substance, but little is known about the effects of caffeine stimulation on global gene expression changes in neurons. Here, we conducted gene expression profiling of human neuroepithelial stem cell-derived neurons, stimulated with normal consumption levels of caffeine (3 μM and 10 μM), over a period of 9 h. We found dosage-dependent activation of immedia
Xeno-free and fully defined conditions are key parameters for robust and reproducible generation of homogenous human induced pluripotent stem (hiPS) cells. Maintenance of hiPS cells on feeder cells or undefined matrices are susceptible to batch variances, pathogenic contamination and risk of immunogenicity. Utilizing the defined recombinant human laminin 521 (LN-521) matrix in combination with xen
