Optical cuff for optogenetic control of the peripheral nervous system

OBJECTIVE: Nerves in the peripheral nervous system (PNS) contain axons with specific motor, somatosensory and autonomic functions. Optogenetics offers an efficient approach to selectively activate axons within the nerve. However, the heterogeneous nature of nerves and their tortuous route through the body create a challenging environment to reliably implant a light delivery interface. APPROACH: Here, we propose an optical peripheral nerve interface – an optocuff -, so that optogenetic modulation of peripheral nerves become possible in freely behaving mice. MAIN RESULTS: Using this optocuff, we demonstrate orderly recruitment of motor units with epineural optical stimulation of genetically targeted sciatic nerve axons, both in anaesthetized and in awake, freely behaving animals. Behavioural experiments and histology show the optocuff does not damage the nerve thus is suitable for long-term experiments. SIGNIFICANCE: These results suggest that the soft optocuff might be a straightforward and efficient tool to support more extensive study of the PNS using optogenetics

The nature of 500 micron risers I: SMA observations

We present SMA observations at resolutions from 0.35 to 3 arcsec of a sample of 34 candidate high redshift dusty star forming galaxies (DSFGs). These sources were selected from the HerMES Herschel survey catalogues to have SEDs rising from 250 to 350 to 500 μm, a population termed 500-risers. We detect counterparts to 24 of these sources, with four having two counterparts. We conclude that the remaining ten sources that lack detected counterparts are likely to have three or more associated sources which blend together to produce the observed Herschel source. We examine the role of lensing, which is predicted to dominate the brightest (F500 > 60 mJy) half of our sample. We find that while lensing plays a role, at least 35 per cent of the bright sources are likely to be multiple sources rather than the result of lensing. At fainter fluxes we find a blending rate comparable to, or greater than, the predicted 40 per cent. We determine far-IR luminosities and star formation rates for the non-multiple sources in our sample and conclude that, in the absence of strong lensing, our 500-risers are very luminous systems with LFIR > 1013 L⊙ and star formation rates >1000 M⊙ yr−1

The Herschel Stripe 82 Survey (HerS): maps and early catalog

We present the first set of maps and band-merged catalog from the Herschel Stripe 82 Survey (HerS). Observations at 250, 350, and 500μm were taken with the Spectral and Photometric Imaging Receiver instrument aboard the Herschel Space Observatory. HerS covers 79deg 2 along the SDSS Stripe 82 to an average depth of 13.0, 12.9, and 14.8mJybeam −1 (including confusion) at 250, 350, and 500μm, respectively. HerS was designed to measure correlations with external tracers of the dark matter density field—either point-like (i.e., galaxies selected from radio to X-ray) or extended (i.e., clusters and gravitational lensing)—in order to measure the bias and redshift distribution of intensities of infrared-emitting dusty star-forming galaxies and active galactic nuclei. By locating HerS in Stripe 82, we maximize the overlap with available and upcoming cosmological surveys. The band-merged catalog contains 3.3 × 10 4 sources detected at a significance of ?3σ (including confusion noise). The maps and catalog are available at http://www.astro.caltech.edu/hers/

The SCUBA-2 Cosmology Legacy Survey:850um maps, catalogues and number counts

We present a catalogue of nearly 3,000 submillimetre sources detected at 850um over ~5 square degrees surveyed as part of the James Clerk Maxwell Telescope (JCMT) SCUBA-2 Cosmology Legacy Survey (S2CLS). This is the largest survey of its kind at 850um, probing a meaningful cosmic volume at the peak of star formation activity and increasing the sample size of submillimetre galaxies selected at 850um by an order of magnitude. We describe the wide 850um survey component of S2CLS, which covers the key extragalactic survey fields: UKIDSS-UDS, COSMOS, Akari-NEP, Extended Groth Strip, Lockman Hole North, SSA22 and GOODS-North. The average 1-sigma depth of S2CLS is 1.2 mJy/beam, approaching the SCUBA-2 850um confusion limit, which we determine to be ~0.8 mJy/beam. We measure the single dish 850um number counts to unprecedented accuracy, reducing the Poisson errors on the differential counts to approximately 4% at S_850~3mJy. With several independent fields, we investigate field-to-field variance, finding that the number counts on 0.5-1 degree scales are generally within 50% of the S2CLS mean for S_850>3mJy, with scatter consistent with the Poisson and estimated cosmic variance uncertainties, although there is a marginal (2-sigma) density enhancement in the GOODS-North field. The observed number counts are in reasonable agreement with recent phenomenological and semi-analytic models. Finally, the large solid angle of S2CLS allows us to measure the bright-end counts: at S_850>10mJy there are approximately ten sources per square degree, and we detect the distinctive up-turn in the number counts indicative of the detection of local sources of 850um emission and strongly lensed high-redshift galaxies. Here we describe the data collection and reduction procedures and present calibrated maps and a catalogue of sources; these are made publicly available

Prostanoid receptor EP1 and Cox-2 in injured human nerves and a rat model of nerve injury: a time-course study

BACKGROUND: Recent studies show that inflammatory processes may contribute to neuropathic pain. Cyclooxygenase-2 (Cox-2) is an inducible enzyme responsible for production of prostanoids, which may sensitise sensory neurones via the EP1 receptor. We have recently reported that while macrophages infiltrate injured nerves within days of injury, they express increased Cox-2-immunoreactivity (Cox-2-IR) from 2 to 3 weeks after injury. We have now investigated the time course of EP1 and Cox-2 changes in injured human nerves and dorsal root ganglia (DRG), and the chronic constriction nerve injury (CCI) model in the rat. METHODS: Tissue sections were immunostained with specific antibodies to EP1, Cox-2, CD68 (human macrophage marker) or OX42 (rat microglial marker), and neurofilaments (NF), prior to image analysis, from the following: human brachial plexus nerves (21 to 196 days post-injury), painful neuromas (9 days to 12 years post-injury), avulsion injured DRG, control nerves and DRG, and rat CCI model tissues. EP1 and NF-immunoreactive nerve fibres were quantified by image analysis. RESULTS: EP1:NF ratio was significantly increased in human brachial plexus nerve fibres, both proximal and distal to injury, in comparison with uninjured nerves. Sensory neurones in injured human DRG showed a significant acute increase of EP1-IR intensity. While there was a rapid increase in EP1-fibres and CD-68 positive macrophages, Cox-2 increase was apparent later, but was persistent in human painful neuromas for years. A similar time-course of changes was found in the rat CCI model with the above markers, both in the injured nerves and ipsilateral dorsal spinal cord. CONCLUSION: Different stages of infiltration and activation of macrophages may be observed in the peripheral and central nervous system following peripheral nerve injury. EP1 receptor level increase in sensory neurones, and macrophage infiltration, appears to precede increased Cox-2 expression by macrophages. However, other methods for detecting Cox-2 levels and activity are required. EP1 antagonists may show therapeutic effects in acute and chronic neuropathic pain, in addition to inflammatory pain

Candidate high-z proto-clusters among the Planck compact sources, as revealed by Herschel-SPIRE

By determining the nature of all the Planck compact sources within 808.4 deg2 of large Herschel surveys, we have identified 27 candidate proto-clusters of dusty star forming galaxies (DSFGs) that are at least 3σ overdense in either 250, 350 or 500 μm sources. We find roughly half of all the Planck compact sources are resolved by Herschel into multiple discrete objects, with the other half remaining unresolved by Herschel. We find a significant difference between versions of the Planck catalogues, with earlier releases hosting a larger fraction of candidate proto-clusters and Galactic Cirrus than later releases, which we ascribe to a difference in the filters used in the creation of the three catalogues. We find a surface density of DSFG candidate proto-clusters of (3.3 ± 0.7) × 10−2 sources deg−2, in good agreement with previous similar studies. We find that a Planck colour selection of S857/S545 1. Our candidate proto-clusters are a factor of 5 times brighter at 353 GHz than expected from simulations, even in the most conservative estimates. Further observations are needed to confirm whether these candidate proto-clusters are physical clusters, multiple proto-clusters along the line of sight, or chance alignments of unassociated sources

Speciation in multidimensional evolutionary space

Adaptive Dynamics in two dimensional phenotype space is investigated by computer simulation. The model assumes Lotka-Voltera type competition and a stochastic mutation process. The carrying capacity has a single maximum in the origin of the strategy space and the competition coefficient decreases with strategy difference. Evolutionary branching, an asexual analogue of adaptive speciation, is observed with suitable parameters. The branching at the singular point, which is a fixed point of the directional evolution, may occur into two or three, but no more directions. Further branchings may occur after the initial separation. The probability of three-branching is studied as a function of several parameters. We conclude that the two-way branching is the predominant mode of adaptive speciation

Role of electrostatics at the catalytic metal binding site in xylose isomerase action: Ca2+-inhibition and metal competence in the double mutant D254E/D256E

The catalytic metal binding site of xylose isomerase from Arthrobacter B3728 was modified by protein engineering to diminish the inhibitory effect of Ca2+ and to study the competence of metals on catalysis. To exclude Ca2+ from Site 2 a double mutant D254E/D256E was designed with reduced space available for binding. In order to elucidate structural consequences of the mutation the binary complex of the mutant with Mg2+ as well as ternary complexes with bivalent metal ions and the open-chain inhibitor xylitol were crystallized for x-ray studies. We determined the crystal structures of the ternary complexes containing Mg2+, Mn2+, and Ca2+ at 2.2 to 2.5 \uc5 resolutions, and refined them to R factors of 16.3, 16.6, and 19.1, respectively. We found that all metals are liganded by both engineered glutamates as well as by atoms O1 and O2 of the inhibitor. The similarity of the coordination of Ca2+ to that of the cofactors as well as results with Be2+ weaken the assumption that geometry differences should account for the catalytic noncompetence of this ion. Kinetic results of the D254E/D256E mutant enzyme showed that the significant decrease in Ca2+ inhibition was accompanied by a similar reduction in the enzymatic activity. Qualitative argumentation, based on the protein electrostatic potential, indicates that the proximity of the negative side chains to the substrate significantly reduces the electrostatic stabilization of the transition state. Furthermore, due to the smaller size of the catalytic metal site, no water molecule, coordinating the metal, could be observed in ternary complexes of the double mutant. Consequently, the proton shuttle step in the overall mechanism should differ from that in the wild type. These effects can account for the observed decrease in catalytic efficiency of the D254E/D256E mutant enzyme