53 research outputs found

    Directed Induction of Functional Motor Neuron-Like Cells from Genetically Engineered Human Mesenchymal Stem Cells

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    Cell replacement using stem cells is a promising therapeutic approach to treat degenerative motor neuron (MN) disorders, such as amyotrophic lateral sclerosis and spinal cord injury. Human bone marrow-derived mesenchymal stem cells (hMSCs) are a desirable cell source for autologous cell replacement therapy to treat nervous system injury due to their plasticity, low immunogenicity, and a lower risk of tumor formation than embryonic stem cells. However, hMSCs are inefficient with regards to differentiating into MN-like cells. To solve this limitation, we genetically engineered hMSCs to express MN-associated transcription factors, Olig2 and Hb9, and then treat the hMSCs expressing Olig2 and Hb9 with optimal MN induction medium (MNIM). This method of induction led to higher expression (>30% of total cells) of MN markers. Electrophysiological data revealed that the induced hMSCs had the excitable properties of neurons and were able to form functional connections with muscle fibers in vitro. Furthermore, when the induced hMSCs were transplanted into an injured organotypic rat spinal cord slice culture, an ex vivo model of spinal cord injury, they exhibited characteristics of MNs. The data strongly suggest that induced Olig2/Hb9-expressing hMSCs were clearly reprogrammed and directed toward a MN-like lineage. We propose that methods to induce Olig2 and Hb9, followed by further induction with MNIM have therapeutic potential for autologous cell replacement therapy to treat degenerative MN disorders

    Consumer knowledge, food label use and grain consumption in the US

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    Responding to mounting evidence of the association between whole-grain consumption and a reduced risk of heart problems and other diseases, as well as an increased probability of body weight maintenance, the US Government has strongly encouraged its citizens to increase consumption of whole grains. However, compared against the 2005 Federal dietary recommendations, in 1994-1996 only 6% of Americans met the current recommended whole-grain consumption. To narrow this huge gap between actual and recommended consumption of whole grains, considerable changes in consumer behaviour will be needed. A demand system with two censored consumption equations and endogenous food label use and nutrition knowledge variables is estimated to investigate the factors that affect the consumption of whole and refined grains. Food label use and nutrition knowledge are found to play important roles in the consumption of refined- and whole-grain products, as are sociodemographic variables. The results can be used to help develop effective nutrition education messages and targeting strategies to promote consumption of whole grains in Americans' diets.

    Snx14 Regulates Neuronal Excitability, Promotes Synaptic Transmission, and Is Imprinted in the Brain of Mice

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    Genomic imprinting describes an epigenetic process through which genes can be expressed in a parent-of-origin-specific manner. The monoallelic expression of imprinted genes renders them particularly susceptible to disease causing mutations. A large proportion of imprinted genes are expressed in the brain, but little is known about their functions. Indeed, it has proven difficult to identify cell type-specific imprinted genes due to the heterogeneity of cell types within the brain. Here we used laser capture microdissection of visual cortical neurons and found evidence that sorting nexin 14 (Snx14) is a neuronally imprinted gene in mice. SNX14 protein levels are high in the brain and progressively increase during neuronal development and maturation. Snx14 knockdown reduces intrinsic excitability and severely impairs both excitatory and inhibitory synaptic transmission. These data reveal a role for monoallelic Snx14 expression in maintaining normal neuronal excitability and synaptic transmission
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