INCREASED OXIDATIVE DAMAGE TO DNA AND THE EFFECTS ON MITOCHONDRIAL PROTEIN IN ALZHEIMER\u27S DISEASE

Alzheimer\u27s disease (AD) is a progressive, irreversible, neurodegenerative disease. The key to understanding AD is to elucidate the pathogenesis of neuron degeneration in specific brain regions.We hypothesize that there is increased DNA oxidation in AD brain compared to age-matched control subjects, especially in mitochondrial DNA (mtDNA), and that the changes in DNA bases will affect protein expression in mitochondria and contribute to neurodegeneration in AD. To test this hypothesis:1) We quantified multiple oxidized bases in nuclear DNA (nDNA) and mtDNA of frontal, parietal, and temporal lobes and cerebellum from late-stage AD (LAD), mild cognitive impairment (MCI), and age-matched control subjects using gas chromatography/mass spectrometry with selective ion monitoring (GC/MS-SIM). Also, we quantified oxidized DNA bases in cortex of APP/PS1 transgenic mice. (a) nDNA and mtDNA were extracted from eight LAD and eight control subjects. We found levels of multiple oxidized bases were significantly higher in frontal, parietal, and temporal lobes and that mtDNA had approximately 10-fold higher levels of oxidized bases than nDNA. Eight-hydroxyguanine was approximately 10-fold higher than other oxidized base adducts in both LAD and control subjects. These results suggest that oxidative damage to mtDNA may contribute to the neurodegeneration of AD. (b) Mild Cognitive Impairment (MCI), the phase between normal aging and early dementia, is a common problem in the elderly with many subjects going on to develop AD. Results from eight amnestic MCI and six control subjects suggest oxidative damage to DNA occurs in the earliest detectable phase of AD. (c) Analysis of nDNA from the cortex of four groups (3m, 6m, 9m, 12m) of APP/PS1 and wild type mice showed elevations of 8-hydroxyguanine in 12 month old APP/PS1 mice.2) To analyze mitochondrial protein changes in LAD, 2D gels were run to separate proteins and MALDI-TOF mass spectrometry was used to identify proteins.Five mitochondrial proteins were significantly decreased in LAD. This proteomic study provides a proteome map of mitochondria in LAD brain and an insight into the pathogenesis of neuron degeneration in Alzheimer\u27s disease

Infectious cDNA Clone of the Modified Live Virus Vaccine Strain of \u3cem\u3eEquine Arteritis\u3c/em\u3e Virus

An isolated polynucleotide molecule includes a DNA sequence encoding an infectious RNA molecule encoding a modified live viral strain of an Equine arteritis virus, wherein the DNA sequence is SEQ ID NO:1 or a degenerate variant thereof. Also provided are transformed or transfected host cells including that sequence, vectors including the sequence, and isolated infectious RNA molecules encoded by the sequence. Further, a modified DNA sequence encoding an infectious RNA molecule encoding a modified live viral strain of an Equine arteritis virus is provided wherein the DNA sequence is SEQ ID NO:2 or a degenerate variant thereof, including a silent point mutation allowing distinguishing the modified sequence from the parent and other strains of Equine arteritis virus

Sitting Posture Recognition Using a Spiking Neural Network

To increase the quality of citizens' lives, we designed a personalized smart chair system to recognize sitting behaviors. The system can receive surface pressure data from the designed sensor and provide feedback for guiding the user towards proper sitting postures. We used a liquid state machine and a logistic regression classifier to construct a spiking neural network for classifying 15 sitting postures. To allow this system to read our pressure data into the spiking neurons, we designed an algorithm to encode map-like data into cosine-rank sparsity data. The experimental results consisting of 15 sitting postures from 19 participants show that the prediction precision of our SNN is 88.52%

Effect of Delay on Selection Dynamics in Long-Term Sphere Culture of Cancer Stem Cells

To quantitatively study the effect of delay on selection dynamics in long-term sphere culture of cancer stem cells (CSCs), a selection dynamic model with time delay is proposed. Theoretical results show that the ubiquitous time delay in cell proliferation may be one of the important factors to induce fluctuation, and numerical simulations indicate that the proposed selection dynamical model with time delay can provide a better fitting effect for the experiment of a long-term sphere culture of CSCs. Thus, it is valuable to consider the delay effect in the future study on the dynamics of nongenetic heterogeneity of clonal cell populations