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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

SQSTM1/p62-Directed Metabolic Reprogramming Is Essential for Normal Neurodifferentiation

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

Barrier Properties and Transcriptome Expression in Human iPSC-Derived Models of the Blood-Brain Barrier

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

Integration Free Derivation of Human Induced Pluripotent Stem Cells Using Laminin 521 Matrix

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

Validity of the Brief Child and Family Phone Interview by comparison with Longitudinal Expert All Data diagnoses in outpatients

Background: The Brief Child and Family Phone Interview (BCFPI) is a standardized intake and follow-up interview used in child and adolescent mental health services (CAMHS). Although it has shown good validity compared with other measures using parent reports, it has not yet been compared with diagnoses derived from a Longitudinal Expert All Data (LEAD) procedure, which includes information from se

Generation of human iPS cell line CTL07-II from human fibroblasts, under defined and xeno-free conditions

CTL07-II is a healthy feeder-free and characterized human induced pluripotent stem (iPS) cell line. Cultured under xeno-free and defined conditions. The line is generated from healthy human fibroblasts with non-integrating Sendai virus vectors encoding the four Yamanaka factors, OCT4, SOX2, KLF4 and cMYC. The generated iPS cells are free from reprogramming vectors and their purity, karyotypic stab

Capture of neuroepithelial-like stem cells from pluripotent stem cells provides a versatile system for in vitro production of human neurons

Human embryonic stem cells (hESC) and induced pluripotent stem cells (iPSC) provide new prospects for studying human neurodevelopment and modeling neurological disease. In particular, iPSC-derived neural cells permit a direct comparison of disease-relevant molecular pathways in neurons and glia derived from patients and healthy individuals. A prerequisite for such comparative studies are robust pr

Progress towards Clinical Use of iPS Cell Derived Therapies

A decade has passed since Shinya Yamanaka published his landmarking publication on how to produce pluripotent stem-cell-like cells and the term induced pluripotent stem cells, iPS cells, was coined. This past decade has been a decade devoted to pluripotent cells, scrutinizing molecular mechanisms in cell identity, and optimizing derivation methods, culture conditions and characterization methods t

Relative importance of climatic variables, soil properties and plant traits to spatial variability in net CO2 exchange across global forests and grasslands

Compared to the well-known drivers of spatial variability in gross primary productivity (GPP), the relative importance of climatic variables, soil properties and plant traits to the spatial variability in net ecosystem exchange of CO2 between terrestrial ecosystem and atmosphere (NEE) is poorly understood. We used principal component regression to analyze data from 147 eddy flux sites to disentang

Struggling for an ideal dialogue. An analysis of the regional dialogue processes within Sweden's first National Forest Program

In 2018, a strategy for Sweden's first National Forest Program was launched. As part of its implementation, County Administrative Boards have initiated dialogue processes for drafting regional forest strategies. Stakeholder deliberation is ascribed the potential to promote trust and mutual understanding, lead to more robust decisions and smoother implementation. We examine the dialogue processes,

Experimental evaluation of feedforward tuning rules

This paper presents a practical comparison for some of the most relevant tuning rules for feedforward compensators that have been published in the recent years. The work is focused on the rejection of disturbances that affect the process output. The different tuning rules are evaluated in simulation and several performance indices are calculated in order to provide a quantitative comparison. All t

Customized Product Development Supported by Integrated Information

Information systems are key enablers for the integration and reliable management of the product development process. Fast, robust, and cost-efficient product adaptation is especially important in one-of-a-kind production. This paper presents an implementation of information supported tools of the product development (PD) design process for large power transformers. One-of-a-kind production is spec

Chronic stress and poor sleeping habits are associated with self-reported IBS and poor psychological well-being in the general population

OBJECTIVE: The present population-based study aimed to examine the association of chronic stress and sleeping difficulties with self-reported irritable bowel syndrome (IBS), gastrointestinal (GI) symptoms past 2 weeks, and psychological well-being.RESULTS: The Malmö Offspring Study included subjects from the general population to complete a questionnaire regarding sociodemographic factors, lifesty

Neoadjuvant Trastuzumab, Pertuzumab, and Docetaxel vs Trastuzumab Emtansine in Patients with ERBB2-Positive Breast Cancer : A Phase 2 Randomized Clinical Trial

Importance: Trastuzumab emtansine (T-DM1) is presently approved for treatment of advanced breast cancer and after incomplete response to neoadjuvant therapy, but the potential of T-DM1 as monotherapy is so far unknown. Objective: To assess pathologic complete response (pCR) to standard neoadjuvant therapy of combination docetaxel, trastuzumab, and pertuzumab (DTP) vs T-DM1 monotherapy in patients

Arctic-adapted dogs emerged at the Pleistocene–Holocene transition

Although sled dogs are one of the most specialized groups of dogs, their origin and evolution has received much less attention than many other dog groups. We applied a genomic approach to investigate their spatiotemporal emergence by sequencing the genomes of 10 modern Greenland sled dogs, an ~9500-year-old Siberian dog associated with archaeological evidence for sled technology, and an ~33,000-ye

The Politics and Ethics of Representation in Qualitative Research

This book offers insights on politics and ethics of representation that are relevant to researchers concerned with struggles for justice. It takes moments of discomfort in the qualitative research process as important sites of knowledge for exploring representational practices in critical research.The Politics and Ethics of Representation in Qualitative Research draws on experiences from research