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Neural Surface Antigens
Neural Surface Antigens: From Basic Biology towards Biomedical Applications focuses on the functionalrole of surface molecules in neural development, stem cell research, and translational biomedical paradigms.With an emphasis on human and rodent model systems, this reference covers fundamentals of neural stemcell biology and flow cytometric methodology. Addressing cell biologists as well as clinicians working in theneurosciences, the book was conceived by an international panel of experts to cover a vast array of particularsurface antigen families and subtypes. It provides insight into the basic biology and functional mechanisms ofneural cell surface signaling molecules influencing mammalian development, regeneration, and treatments. Introduces early phase clinical trials of neural stem cells Outlines characterization of surface molecule expression and methods for isolation which open unprecedented opportunities for functional study, quantitation & diagnostics Highlights the role of stem cells in neural surface antigen and biomarker analysis and applications
Transcriptomic Landscape and Functional Characterization of Human Induced Pluripotent Stem Cell-derived Limbal Epithelial Progenitor Cells
Abstract: Limbal stem cell deficiency (LSCD) is a complex, multifactorial disease affecting limbal epithelial progenitor cells (LEPC), which are essential for maintaining corneal stability and transparency. Human induced pluripotent stem cell-derived (hiPSC-) LEPC are a promising cell source for the treatment of LSCD. However, their similarity to native tissue-derived (T-) LEPC and their functional characterization has not been studied in detail. Here, we show that hiPSC-LEPC and T-LEPC have rather similar gene expression patterns, colony-forming ability, wound-healing capacity, and melanosome uptake. In addition, hiPSC-LEPC exhibited lower immunogenicity and reduced the proliferation of per...
Glycan Epitope and Integrin Expression Dynamics Characterize Neural Crest Epithelial-to-mesenchymal Transition (EMT) in Human Pluripotent Stem Cell Differentiation
Abstract: The neural crest gives rise to progeny as diverse as peripheral neurons, myelinating cells, cranial muscle, bone and cartilage tissues, and melanocytes. Neural crest derivation encompasses complex morphological change, including epithelial-to-mesenchymal transition (EMT) and migration to the eventual target locations throughout the body. Neural crest cultures derived from stem cells provide an attractive source for developmental studies in human model systems, of immediate biomedical relevance for neurocristopathies, neural cancer biology and regenerative medicine, if only appropriate markers for lineage and cell type definition and quality control criteria were available. Implemen...
Comprehensive Cell Surface Antigen Analysis Identifies Transferrin Receptor Protein-1 (CD71) as a Negative Selection Marker for Human Neuronal Cells
Abstract: Cell state-, developmental stage-, and lineage-specific combinatorial expression of cluster of differentiation (CD) molecules enables the identification of cellular subsets via multicolor flow cytometry. We describe an exhaustive characterization of neural cell types by surface antigens, exploiting human pluripotent stem cell-derived neural cell systems. Using multiwell screening approaches followed by detailed validation of expression patterns and dynamics, we exemplify a strategy for resolving cellular heterogeneity in stem cell paradigms. In addition to providing a catalog of surface antigens expressed in the neural lineage, we identified the transferrin receptor-1 (CD71) to be differentially expressed in neural stem cells and differentiated neurons. In this context, we describe a role for N-Myc proto-oncogene (MYCN) in maintaining CD71 expression in proliferating neural cells. We report that in vitro human stem cell-derived neurons lack CD71 surface expression and that the observed differential expression can be used to identify and enrich CD71− neuronal derivatives from heterogeneous cultures
The NAD+ Precursor Nicotinamide Riboside Rescues Mitochondrial Defects and Neuronal Loss in IPSC and Fly Models of Parkinson's Disease
Abstract: While mitochondrial dysfunction is emerging as key in Parkinson's disease (PD), a central question remains whether mitochondria are actual disease drivers and whether boosting mitochondrial biogenesis and function ameliorates pathology. We address these questions using patient-derived induced pluripotent stem cells and Drosophila models of GBA-related PD (GBA-PD), the most common PD genetic risk. Patient neurons display stress responses, mitochondrial demise, and changes in NAD+ metabolism. NAD+ precursors have been proposed to ameliorate age-related metabolic decline and disease. We report that increasing NAD+ via the NAD+ precursor nicotinamide riboside (NR) significantly ameliorates mitochondrial function in patient neurons. Human neurons require nicotinamide phosphoribosyltransferase (NAMPT) to maintain the NAD+ pool and utilize NRK1 to synthesize NAD+ from NAD+ precursors. Remarkably, NR prevents the age-related dopaminergic neuronal loss and motor decline in fly models of GBA-PD. Our findings suggest NR as a viable clinical avenue for neuroprotection in PD and other neurodegenerative diseases
Verteporfin-induced Proteotoxicity Impairs Cell Homeostasis and Survival in Neuroblastoma Subtypes Independent of YAP/TAZ Expression
Abstract: Neuroblastoma (NB) is a highly aggressive extracranial solid tumor in children. Due to its heterogeneity, NB remains a therapeutic challenge. Several oncogenic factors, including the Hippo effectors YAP/TAZ, are associated with NB tumorigenesis. Verteporfin (VPF) is an FDA-approved drug shown to directly inhibit YAP/TAZ activity. Our study aimed to investigate VPF's potential as a therapeutic agent in NB. We show that VPF selectively and efficiently impairs the viability of YAP/TAZ-expressing NB GI-ME-N and SK-N-AS cells, but not of non-malignant fibroblasts. To investigate whether VPF-mediated NB cell killing is YAP-dependent, we tested VPF potency in CRISPR-mediated YAP/TAZ knock...
Stem Cells: Current Challenges and New Directions
This volume looks at the state-of-the-science in stem cells, discusses the current challenges, and examines the new directions the field is taking. Dr. Turksen, editor-in-chief of the journal "Stem Cell Reviews and Reports," has assembled a volume of internationally-known scientists who cover topics that are both clinically and research-oriented. The contents range from sources of stem cells through their physiological role in health and disease, therapeutic applications in regenerative medicine, and ethics and society. An initial overview and a final summary bookend the contents into a cohesive and invaluable volume.
Development and Engineering of Dopamine Neurons
Theneurotransmitter dopamine has just celebrated its 50thbirthday. The discovery of dopamine as a neuronal entity in the late 1950s and the notion that it serves in neurotransmission has been a milestone in the field of neuroscience research. This milestone marked the beginning of an era that explored the brain as an integrated collection of neuronal systems that one could distinguish on basis of neurotransm- ter identities, and importantly, in which one started to be able to pinpoint the seat of brain disease. The mesodiencephalic dopaminergic (mdDA) system, previously designated as midbraindopaminergic system, has received much attention since its discovery. The initial identification of d...
