Proceedings of the National Academy of Sciences of the United States of America
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Proc. Natl. Acad. Sci. U.S.A. · Jun 2013
Peripheral elevation of TNF-α leads to early synaptic abnormalities in the mouse somatosensory cortex in experimental autoimmune encephalomyelitis.
Sensory abnormalities such as numbness and paresthesias are often the earliest symptoms in neuroinflammatory diseases including multiple sclerosis. The increased production of various cytokines occurs in the early stages of neuroinflammation and could have detrimental effects on the central nervous system, thereby contributing to sensory and cognitive deficits. However, it remains unknown whether and when elevation of cytokines causes changes in brain structure and function under inflammatory conditions. ⋯ This synaptic instability occurred before T-cell infiltration and microglial activation in the central nervous system and was in conjunction with peripheral, but not central, production of TNF-α. Peripheral administration of a soluble TNF inhibitor prevented abnormal turnover of dendritic spines and axonal boutons in presymptomatic EAE mice. These findings indicate that peripheral production of TNF-α is a key mediator of synaptic instability in the primary somatosensory cortex and may contribute to sensory and cognitive deficits seen in autoimmune diseases.
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Proc. Natl. Acad. Sci. U.S.A. · Jun 2013
ReviewFrom perception to pleasure: music and its neural substrates.
Music has existed in human societies since prehistory, perhaps because it allows expression and regulation of emotion and evokes pleasure. In this review, we present findings from cognitive neuroscience that bear on the question of how we get from perception of sound patterns to pleasurable responses. ⋯ Recent data indicate that this dopaminergic system mediates pleasure associated with music; specifically, reward value for music can be coded by activity levels in the nucleus accumbens, whose functional connectivity with auditory and frontal areas increases as a function of increasing musical reward. We propose that pleasure in music arises from interactions between cortical loops that enable predictions and expectancies to emerge from sound patterns and subcortical systems responsible for reward and valuation.
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Proc. Natl. Acad. Sci. U.S.A. · May 2013
Historical ArticleClimate change frames debate over the extinction of megafauna in Sahul (Pleistocene Australia-New Guinea).
Around 88 large vertebrate taxa disappeared from Sahul sometime during the Pleistocene, with the majority of losses (54 taxa) clearly taking place within the last 400,000 years. The largest was the 2.8-ton browsing Diprotodon optatum, whereas the ∼100- to 130-kg marsupial lion, Thylacoleo carnifex, the world's most specialized mammalian carnivore, and Varanus priscus, the largest lizard known, were formidable predators. ⋯ Human involvement in the disappearance of some species remains possible but unproven. Mounting evidence points to the loss of most species before the peopling of Sahul (circa 50-45 ka) and a significant role for climate change in the disappearance of the continent's megafauna.
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Proc. Natl. Acad. Sci. U.S.A. · May 2013
Mycobacterial toxin MazF-mt6 inhibits translation through cleavage of 23S rRNA at the ribosomal A site.
The Mycobacterium tuberculosis genome contains an unusually high number of toxin-antitoxin modules, some of which have been suggested to play a role in the establishment and maintenance of latent tuberculosis. Nine of these toxin-antitoxin loci belong to the mazEF family, encoding the intracellular toxin MazF and its antitoxin inhibitor MazE. Nearly every MazF ortholog recognizes a unique three- or five-base RNA sequence and cleaves mRNA. ⋯ To gain further mechanistic insight, we demonstrated that MazF-mt6-mediated cleavage of rRNA can inhibit protein synthesis in the absence of mRNA cleavage. Finally, consistent with the position of 23S rRNA cleavage, MazF-mt6 destabilized 50S-30S ribosomal subunit association. Collectively, these results show that MazF toxins do not universally act as mRNA interferases, because MazF-mt6 inhibits protein synthesis by cleaving 23S rRNA in the ribosome active center.
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Human use of land has transformed ecosystem pattern and process across most of the terrestrial biosphere, a global change often described as historically recent and potentially catastrophic for both humanity and the biosphere. Interdisciplinary paleoecological, archaeological, and historical studies challenge this view, indicating that land use has been extensive and sustained for millennia in some regions and that recent trends may represent as much a recovery as an acceleration. ⋯ Contrasting two spatially explicit global reconstructions of land-use history shows that reconstructions incorporating adaptive changes in land-use systems over time, including land-use intensification, offer a more spatially detailed and plausible assessment of our planet's history, with a biosphere and perhaps even climate long ago affected by humans. Although land-use processes are now shifting rapidly from historical patterns in both type and scale, integrative global land-use models that incorporate dynamic adaptations in human-environment relationships help to advance our understanding of both past and future land-use changes, including their sustainability and potential global effects.