Proceedings of the National Academy of Sciences of the United States of America
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Proc. Natl. Acad. Sci. U.S.A. · Feb 2009
Genome-wide association analysis reveals a SOD1 mutation in canine degenerative myelopathy that resembles amyotrophic lateral sclerosis.
Canine degenerative myelopathy (DM) is a fatal neurodegenerative disease prevalent in several dog breeds. Typically, the initial progressive upper motor neuron spastic and general proprioceptive ataxia in the pelvic limbs occurs at 8 years of age or older. If euthanasia is delayed, the clinical signs will ascend, causing flaccid tetraparesis and other lower motor neuron signs. ⋯ Microscopic examination of spinal cords from affected dogs revealed myelin and axon loss affecting the lateral white matter and neuronal cytoplasmic inclusions that bind anti-superoxide dismutase 1 antibodies. These inclusions are similar to those seen in spinal cord sections from ALS patients with SOD1 mutations. Our findings identify canine DM to be the first recognized spontaneously occurring animal model for ALS.
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Proc. Natl. Acad. Sci. U.S.A. · Feb 2009
Morphological and functional reorganization of rat medial prefrontal cortex in neuropathic pain.
Neuropathic pain is a chronic pain that results from lesion or dysfunction of the nervous system. Depression and cognitive decline are often coupled to chronic pain, suggesting the involvement of cortical areas associated with higher cognitive functions. ⋯ Interestingly, the NMDA/AMPA ratio of the synaptic current elicited in mPFC neurons by afferent fiber stimulation shows linear correlation with the rats' tactile threshold in the injured (but not in the contralateral) paw. Our results not only provide evidence that neuropathic pain leads to rearrangement of the mPFC, which may help defining the cellular basis for cognitive impairments associated with chronic pain, but also show pain-associated morphological changes in the cortex at single neuron level.
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Proc. Natl. Acad. Sci. U.S.A. · Feb 2009
Irreversible climate change due to carbon dioxide emissions.
The severity of damaging human-induced climate change depends not only on the magnitude of the change but also on the potential for irreversibility. This paper shows that the climate change that takes place due to increases in carbon dioxide concentration is largely irreversible for 1,000 years after emissions stop. ⋯ Thermal expansion of the warming ocean provides a conservative lower limit to irreversible global average sea level rise of at least 0.4-1.0 m if 21st century CO(2) concentrations exceed 600 ppmv and 0.6-1.9 m for peak CO(2) concentrations exceeding approximately 1,000 ppmv. Additional contributions from glaciers and ice sheet contributions to future sea level rise are uncertain but may equal or exceed several meters over the next millennium or longer.