Induction of an illusory shadow person

Stimulation of a site on the brain's left hemisphere prompts the creepy feeling that somebody is close by. The strange sensation that somebody is nearby when no one is actually present has been described by psychiatric and neurological patients, as well as by healthy subjects, but it is not understood how the illusion is triggered by the brain. Here we describe the repeated induction of this sensation in a patient who was undergoing presurgical evaluation for epilepsy treatment, as a result of focal electrical stimulation of the left temporoparietal junction: the illusory person closely 'shadowed' changes in the patient's body position and posture. These perceptions may have been due to a disturbance in the multisensory processing of body and self at the temporoparietal junction.     

Orai1 is an essential pore subunit of the CRAC channel

Stimulation of immune cells causes depletion of Ca2+ from endoplasmic reticulum (ER) stores, thereby triggering sustained Ca2+ entry through store-operated Ca2+ release-activated Ca2+ (CRAC) channels, an essential signal for lymphocyte activation and proliferation. Recent evidence indicates that activation of CRAC current is initiated by STIM proteins, which sense ER Ca2+ levels through an EF-hand located in the ER lumen and relocalize upon store depletion into puncta closely associated with the plasma membrane. We and others recently identified Drosophila Orai and human Orai1 (also called TMEM142A) as critical components of store-operated Ca2+ entry downstream of STIM. Combined overexpression of Orai and Stim in Drosophila cells, or Orai1 and STIM1 in mammalian cells, leads to a marked increase in CRAC current. However, these experiments did not establish whether Orai is an essential intracellular link between STIM and the CRAC channel, an accessory protein in the plasma membrane, or an actual pore subunit. Here we show that Orai1 is a plasma membrane protein, and that CRAC channel function is sensitive to mutation of two conserved acidic residues in the transmembrane segments. E106D and E190Q substitutions in transmembrane helices 1 and 3, respectively, diminish Ca2+ influx, increase current carried by monovalent cations, and render the channel permeable to Cs+. These changes in ion selectivity provide strong evidence that Orai1 is a pore subunit of the CRAC channel.     

An RNA gene expressed during cortical development evolved rapidly in humans

The developmental and evolutionary mechanisms behind the emergence of human-specific brain features remain largely unknown. However, the recent ability to compare our genome to that of our closest relative, the chimpanzee, provides new avenues to link genetic and phenotypic changes in the evolution of the human brain. We devised a ranking of regions in the human genome that show significant evolutionary acceleration. Here we report that the most dramatic of these 'human accelerated regions', HAR1, is part of a novel RNA gene (HAR1F) that is expressed specifically in Cajal-Retzius neurons in the developing human neocortex from 7 to 19 gestational weeks, a crucial period for cortical neuron specification and migration. HAR1F is co-expressed with reelin, a product of Cajal-Retzius neurons that is of fundamental importance in specifying the six-layer structure of the human cortex. HAR1 and the other human accelerated regions provide new candidates in the search for uniquely human biology.     

Free-electron-like dispersion in an organic monolayer film on a metal substrate

Thin films of molecular organic semiconductors are attracting much interest for use in electronic and optoelectronic applications. The electronic properties of these materials and their interfaces are therefore worth investigating intensively, particularly the degree of electron delocalization that can be achieved. If the delocalization is appreciable, it should be accompanied by an observable electronic band dispersion. But so far only limited experimental data on the intermolecular dispersion of electronic states in molecular materials is available, and the mechanism(s) of electron delocalization in molecular materials are also not well understood. Here we report scanning tunnelling spectroscopy observations of an organic monolayer film on a silver substrate, revealing a completely delocalized two-dimensional band state that is characterized by a metal-like parabolic dispersion with an effective mass of m* = 0.47m(e), where m(e) is the bare electron mass. This dispersion is far stronger than expected for the organic film alone, and arises as a result of strong substrate-mediated coupling between the molecules within the monolayer.     

Flushing submarine canyons

The continental slope is a steep, narrow fringe separating the coastal zone from the deep ocean. During low sea-level stands, slides and dense, sediment-laden flows erode the outer continental shelf and the continental slope, leading to the formation of submarine canyons that funnel large volumes of sediment and organic matter from shallow regions to the deep ocean(1). During high sea-level stands, such as at present, these canyons still experience occasional sediment gravity flows(2-5), which are usually thought to be triggered by sediment failure or river flooding. Here we present observations from a submarine canyon on the Gulf of Lions margin, in the northwest Mediterranean Sea, that demonstrate that these flows can also be triggered by dense shelf water cascading (DSWC)-a type of current that is driven solely by seawater density contrast. Our results show that DSWC can transport large amounts of water and sediment, reshape submarine canyon floors and rapidly affect the deep-sea environment. This cascading is seasonal, resulting from the formation of dense water by cooling and/or evaporation, and occurs on both high- and low-latitude continental margins(6-8). DSWC may therefore transport large amounts of sediment and organic matter to the deep ocean. Furthermore, changes in the frequency and intensity of DSWC driven by future climate change may have a significant impact on the supply of organic matter to deep-sea ecosystems and on the amount of carbon stored on continental margins and in ocean basins.     

Spider toxins activate the capsaicin receptor to produce inflammatory pain

Bites and stings from venomous creatures can produce pain and inflammation as part of their defensive strategy to ward off predators or competitors. Molecules accounting for lethal effects of venoms have been extensively characterized, but less is known about the mechanisms by which they produce pain. Venoms from spiders, snakes, cone snails or scorpions contain a pharmacopoeia of peptide toxins that block receptor or channel activation as a means of producing shock, paralysis or death. We examined whether these venoms also contain toxins that activate (rather than inhibit) excitatory channels on somatosensory neurons to produce a noxious sensation in mammals. Here we show that venom from a tarantula that is native to the West Indies contains three inhibitor cysteine knot (ICK) peptides that target the capsaicin receptor (TRPV1), an excitatory channel expressed by sensory neurons of the pain pathway. In contrast with the predominant role of ICK toxins as channel inhibitors, these previously unknown 'vanillotoxins' function as TRPV1 agonists, providing new tools for understanding mechanisms of TRP channel gating. Some vanillotoxins also inhibit voltage-gated potassium channels, supporting potential similarities between TRP and voltage-gated channel structures. TRP channels can now be included among the targets of peptide toxins, showing that animals, like plants (for example, chilli peppers), avert predators by activating TRP channels on sensory nerve fibres to elicit pain and inflammation.     

Sexual reproduction selects for robustness and negative epistasis in artificial gene networks

The mutational deterministic hypothesis for the origin and maintenance of sexual reproduction posits that sex enhances the ability of natural selection to purge deleterious mutations after recombination brings them together into single genomes. This explanation requires negative epistasis, a type of genetic interaction where mutations are more harmful in combination than expected from their separate effects. The conceptual appeal of the mutational deterministic hypothesis has been offset by our inability to identify the mechanistic and evolutionary bases of negative epistasis. Here we show that negative epistasis can evolve as a consequence of sexual reproduction itself. Using an artificial gene network model, we find that recombination between gene networks imposes selection for genetic robustness, and that negative epistasis evolves as a by-product of this selection. Our results suggest that sexual reproduction selects for conditions that favour its own maintenance, a case of evolution forging its own path.