Insoluble aggregates containing TDP-43 are widely observed in the diseased brain, and defined as “TDP-43 pathology” in a spectrum of neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS), Alzheimer’s disease and ALS with frontotemporal dementia. Here we report that Betz cells of patients with TDP-43 pathology display a distinct set of intracellular defects especially at the site of nuclear membrane, mitochondria and endoplasmic reticulum (ER). Numerous TDP-43 mouse models have been generated to discern the cellular and molecular basis of the disease, but mechanisms of neuronal vulnerability remain unknown. In an effort to define the underlying causes of corticospinal motor neuron (CSMN) degeneration, we generated and characterized a novel CSMN reporter line with TDP-43 pathology, the prp-TDP-43A315T-UeGFP mice. We find that TDP-43 pathology related intracellular problems emerge very early in the disease. The Betz cells in humans and CSMN in mice both have impaired mitochondria, and display nuclear membrane and ER defects with respect to TDP-43 pathology.
In this study, we report the isolation and characterization of a population of multipotent keloid-derived mesenchymal-like stem cells (KMLSCs) from keloid scalp tissues. These KMLSCs expressed the typical mesenchymal stem cell marker proteins CD13, CD29, CD44, CD90, fibronectin, and vimentin when they were cultured in serum-containing medium and when subsequent exposure to various differentiation media resulted in their differentiation into adipocytes, osteoblasts, chondrocytes, smooth muscle cells, and angiogenic endothelial cells. When KMLSCs were cultured in neural stem culture conditions (i.e., in the presence of epidermal growth factor and fibroblast growth factor 2 in substrate-free conditions), they produced large numbers of neurospheres containing nestin-, CD133-, and SOX2-positive cells that expressed neural-crest stem cell markers. Subsequent exposure of these cells to different differentiation conditions resulted in cells that expressed neuronal cell-, astrocyte-, oligodendrocyte-, or Schwann cell-specific markers. Our study suggests that KMLSCs may be an alternative adult stem cell resource for regenerative tissue repair and auto-transplantation.
Quantitative determination of locations vulnerable to ground subsidence at mining regions is necessary for effective prevention. In this paper, a method of constructing subsidence susceptibility maps based on fuzzy relations is proposed and tested at an abandoned underground coal mine in Korea. An advantage of fuzzy combination operators over other methods is that the operation is mathematically and logically easy to understand and its implementation to GIS software is simple and straightforward. A certainty factor analysis was used for estimating the relative weight of eight major factors influencing ground subsidence. The relative weight of each factor was then converted into a fuzzy membership value and integrated as a subsidence hazard index using fuzzy combination operators, which produced coal mine subsidence susceptibility maps. The susceptibility maps were compared with the reported ground subsidence areas, and the results showed high accuracy between our prediction and the actual subsidence. Based on the root mean square error and accuracy in terms of success rates, fuzzy c-operator with a low c value and fuzzy algebraic product operator, specifically, are useful for ground subsidence prediction. Comparing the results of a fuzzy c-operator and a conventional logistic regression model, the performance of the fuzzy approach is comparative to that of a logistic regression model with improved computational. A field survey done in the area supported the method's reliability. A combination of certainty factor analysis and fuzzy relations with a GIS is an effective method to determine locations vulnerable to coal mine subsidence.
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