Nature communications
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Nature communications · Jan 2013
Enhanced dihydropyridine receptor calcium channel activity restores muscle strength in JP45/CASQ1 double knockout mice.
Muscle strength declines with age in part due to a decline of Ca(2+) release from sarcoplasmic reticulum calcium stores. Skeletal muscle dihydropyridine receptors (Ca(v)1.1) initiate muscle contraction by activating ryanodine receptors in the sarcoplasmic reticulum. Ca(v)1.1 channel activity is enhanced by a retrograde stimulatory signal delivered by the ryanodine receptor. ⋯ Here we show that JP45 and CASQ1 strengthen skeletal muscle contraction by modulating Ca(v)1.1 channel activity. Using muscle fibres from JP45 and CASQ1 double knockout mice, we demonstrate that Ca(2+) transients evoked by tetanic stimulation are the result of massive Ca(2+) influx due to enhanced Ca(v)1.1 channel activity, which restores muscle strength in JP45/CASQ1 double knockout mice. We envision that JP45 and CASQ1 may be candidate targets for the development of new therapeutic strategies against decay of skeletal muscle strength caused by a decrease in sarcoplasmic reticulum Ca(2+) content.
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Nature communications · Jan 2013
Evidence for distinct human auditory cortex regions for sound location versus identity processing.
Neurophysiological animal models suggest that anterior auditory cortex (AC) areas process sound identity information, whereas posterior ACs specialize in sound location processing. In humans, inconsistent neuroimaging results and insufficient causal evidence have challenged the existence of such parallel AC organization. ⋯ Our data show that TMS to posterior AC regions delays reaction times (RT) significantly more during sound location than identity discrimination, whereas TMS to anterior AC regions delays RTs significantly more during sound identity than location discrimination. This double dissociation provides direct causal support for parallel processing of sound identity features in anterior AC and sound location in posterior AC.
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Pirt is a membrane protein that is specifically expressed in the peripheral nervous system, where it has been shown to increase the sensitivity of the transient receptor potential vanilloid 1 channel and modulate its role in heat pain. The broad expression of Pirt among dorsal root ganglion neurons suggests it may modulate other transient receptor potentials, such as the menthol and cooling sensor TRPM8. ⋯ Pirt(-/-) mice exhibit decreased behavioural responses to cold and cool temperatures, and Pirt increases the sensitivity of TRPM8 to menthol and cool temperature. Our data suggest Pirt is an endogenous regulator of TRPM8.
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Nature communications · Jan 2013
Interferon-induced transmembrane protein-3 genetic variant rs12252-C is associated with severe influenza in Chinese individuals.
The SNP rs12252-C allele alters the function of interferon-induced transmembrane protein-3 increasing the disease severity of influenza virus infection in Caucasians, but the allele is rare. However, rs12252-C is much more common in Han Chinese. ⋯ More importantly, because the risk genotype occurs with such a high frequency, its effect translates to a large population-attributable risk of 54.3% for severe infection in the Chinese population studied compared with 5.4% in Northern Europeans. Interferon-induced transmembrane protein-3 genetic variants could, therefore, have a strong effect of the epidemiology of influenza in China and in people of Chinese descent.
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Nature communications · Jan 2013
Phantom pain is associated with preserved structure and function in the former hand area.
Phantom pain after arm amputation is widely believed to arise from maladaptive cortical reorganization, triggered by loss of sensory input. We instead propose that chronic phantom pain experience drives plasticity by maintaining local cortical representations and disrupting inter-regional connectivity. ⋯ We therefore propose that contrary to the maladaptive model, cortical plasticity associated with phantom pain is driven by powerful and long-lasting subjective sensory experience, such as triggered by nociceptive or top-down inputs. Our results prompt a revisiting of the link between phantom pain and brain organization.