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TDP-43 proteinopathies have been observed in a wide range of neurodegenerative diseases. Mutations in the gene encoding TDP-43 (i.e., TDP) have been identified in amyotrophic lateral sclerosis (ALS) and in frontotemporal lobe degeneration associated with motor neuron disease. To study the consequences of TDP mutation in an intact system, we created(More)
Intrastriatal injection of the reversible succinate dehydrogenase inhibitor malonate results in both chemically induced hypoxia and striatal lesions that are similar to those seen in Huntington's disease and cerebral ischaemia. The mechanisms leading to neuronal death involve secondary excitotoxicity, the release of dopamine from nigrostriatal fibres and(More)
Transgenic RNAi, an alternative to the gene knockout approach, can induce hypomorphic phenotypes that resemble those of the gene knockout in mice. Conditional transgenic RNAi is an attractive choice of method for reverse genetics in vivo because it can achieve temporal and spatial silencing of targeted genes. Pol III promoters such as U6 are widely used to(More)
Entorhinal cortex lesion (ECL) leads to the activation of astrocytes and reactive axonal sprouting in the denervated fascia dentata. Previous studies indicated that CNTF or related cytokines are involved in the regulation of these processes. Therefore, we studied (1). whether the cytokine-associated STAT3 signaling pathway is activated in response to ECL(More)
RNA interference (RNAi) mediates gene silencing in many eukaryotes and has been widely used to investigate gene functions. A common method to induce sustained RNAi is introducing plasmids that synthesize short hairpin RNAs (shRNAs) using Pol III promoters. While these promoters synthesize shRNAs and elicit RNAi efficiently, they lack cell specificity.(More)
Amyotrophic lateral sclerosis (ALS or Lou Gehrig's disease) is a neurodegenerative disease characterized by motor neuron degeneration, paralysis and death. One cause of this disease is mutations in the Cu,Zn superoxide dismutase (SOD1) gene. As mutant SOD1 acquires a toxic property that kills motor neurons, by reducing the mutant protein the disease(More)
TAR DNA-binding protein 43 (TDP-43) is a major component in aggregates of ubiquitinated proteins in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Here we report that lipopolysaccharide (LPS)-induced inflammation can promote TDP-43 mislocalization and aggregation. In culture, microglia and astrocytes exhibited TDP-43(More)
To develop transgenic lines for conditional expression of desired genes in rats, we generated several lines of the transgenic rats carrying the tetracycline-controlled transactivator (tTA) gene. Using a vigorous, ubiquitous promoter to drive the tTA transgene, we obtained widespread expression of tTA in various tissues. Expression of tTA was sufficient to(More)
RNA interference (RNAi) is a recently discovered mechanism that is conserved in a wide range of eukaryotic species. Triggered by double-stranded RNA, RNAi identifies and destroys the mRNA that shares homology with the double-stranded RNA. Because of its specificity, RNAi has a high potential for being a powerful investigative and therapeutic tool. Indeed,(More)
Two-handed interaction is a very common paradigm that is gaining popularity in the fields of medical tele-operation, gaming, and large-scale design. In this paper, we validate Guiard's theory of bimanual control for the tasks of navigation and selection. We present the related literature and the theoretical models that motivate the research, in particular(More)