Nature communications
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Nature communications · Jan 2012
Structural modelling and mutant cycle analysis predict pharmacoresponsiveness of a Na(V)1.7 mutant channel.
Sodium channel Na(V)1.7 is critical for human pain signalling. Gain-of-function mutations produce pain syndromes including inherited erythromelalgia, which is usually resistant to pharmacotherapy, but carbamazepine normalizes activation of Na(V)1.7-V400M mutant channels from a family with carbamazepine-responsive inherited erythromelalgia. Here we show that structural modelling and thermodynamic analysis predict pharmacoresponsiveness of another mutant channel (S241T) that is located 159 amino acids distant from V400M. ⋯ Atomic proximity and energetic coupling are paralleled by pharmacological coupling, as carbamazepine (30 μM) depolarizes S214T activation, as previously reported for V400M. Pharmacoresponsiveness of S241T to carbamazepine was further evident at a cellular level, where carbamazepine normalized the hyperexcitability of dorsal root ganglion neurons expressing S241T. We suggest that this approach might identify variants that confer enhanced pharmacoresponsiveness on a variety of channels.
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Nature communications · Jan 2012
Low-mass black holes as the remnants of primordial black hole formation.
Bridging the gap between the approximately ten solar mass 'stellar mass' black holes and the 'supermassive' black holes of millions to billions of solar masses are the elusive 'intermediate-mass' black holes. Their discovery is key to understanding whether supermassive black holes can grow from stellar-mass black holes or whether a more exotic process accelerated their growth soon after the Big Bang. Currently, tentative evidence suggests that the progenitors of supermassive black holes were formed as ∼10(4)-10(5) M(⊙) black holes via the direct collapse of gas. Ongoing searches for intermediate-mass black holes at galaxy centres will help shed light on this formation mechanism.
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Nature communications · Jan 2012
Distinct Nav1.7-dependent pain sensations require different sets of sensory and sympathetic neurons.
Human acute and inflammatory pain requires the expression of voltage-gated sodium channel Nav1.7 but its significance for neuropathic pain is unknown. Here we show that Nav1.7 expression in different sets of mouse sensory and sympathetic neurons underlies distinct types of pain sensation. Ablating Nav1.7 gene (SCN9A) expression in all sensory neurons using Advillin-Cre abolishes mechanical pain, inflammatory pain and reflex withdrawal responses to heat. ⋯ Surprisingly, responses to the hotplate test, as well as neuropathic pain, are unaffected when SCN9A is deleted in all sensory neurons. However, deleting SCN9A in both sensory and sympathetic neurons abolishes these pain sensations and recapitulates the pain-free phenotype seen in humans with SCN9A loss-of-function mutations. These observations demonstrate an important role for Nav1.7 in sympathetic neurons in neuropathic pain, and provide possible insights into the mechanisms that underlie gain-of-function Nav1.7-dependent pain conditions.
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Nature communications · Dec 2011
Low-power nano-optical vortex trapping via plasmonic diabolo nanoantennas.
Optical vortex trapping can allow the capture and manipulation of micro- and nanometre-sized objects such as damageable biological particles or particles with a refractive index lower than the surrounding material. However, the quest for nanometric optical vortex trapping that overcomes the diffraction limit remains. ⋯ Furthermore, a large radial trapping stiffness, ~0.69 pN nm(-1) W(-1), was measured at the position of the minimum potential, showing good agreement with numerical simulations. This subwavelength-scale nanoantenna system capable of low-power trapping represents a significant step toward versatile, efficient nano-optical manipulations in lab-on-a-chip devices.
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Nature communications · Jul 2011
Porous covalent electron-rich organonitridic frameworks as highly selective sorbents for methane and carbon dioxide.
Carbon dioxide capture from point sources like coal-fired power plants is considered to be a solution for stabilizing the CO(2) level in the atmosphere to avoid global warming. Methane is an important energy source that is often highly diluted by nitrogen in natural gas. For the separation of CO(2) and CH(4) from N(2) in flue gas and natural gas, respectively, sorbents with high and reversible gas uptake, high gas selectivity, good chemical and thermal stability, and low cost are desired. ⋯ These were prepared by simple condensation reactions between inexpensive, commercially available nitridic and electron-rich aromatic building units. The PECONF materials exhibit high and reversible CO(2) and CH(4) uptake and exceptional selectivities of these gases over N(2). The materials do not oxidize in air up to temperature of 400 °C.