The search for novel analgesics: re-examining spinal cord circuits with new tools

In this perspective, we propose the absence of detailed information regarding spinal cord circuits that process sensory information remains a major barrier to advancing analgesia. We highlight recent advances showing that functionally discrete populations of neurons in the spinal cord dorsal horn play distinct roles in processing sensory information. We then discuss new molecular, electrophysiological, and optogenetic techniques that can be employed to understand how dorsal horn circuits process tactile and nociceptive information. We believe this information can drive the development of entirely new classes of pharmacotherapies that target key elements in spinal circuits to selectively modify sensory function and blunt pain

A model of ant route navigation driven by scene familiarity

In this paper we propose a model of visually guided route navigation in ants that captures the known properties of real behaviour whilst retaining mechanistic simplicity and thus biological plausibility. For an ant, the coupling of movement and viewing direction means that a familiar view specifies a familiar direction of movement. Since the views experienced along a habitual route will be more familiar, route navigation can be re-cast as a search for familiar views. This search can be performed with a simple scanning routine, a behaviour that ants have been observed to perform. We test this proposed route navigation strategy in simulation, by learning a series of routes through visually cluttered environments consisting of objects that are only distinguishable as silhouettes against the sky. In the first instance we determine view familiarity by exhaustive comparison with the set of views experienced during training. In further experiments we train an artificial neural network to perform familiarity discrimination using the training views. Our results indicate that, not only is the approach successful, but also that the routes that are learnt show many of the characteristics of the routes of desert ants. As such, we believe the model represents the only detailed and complete model of insect route guidance to date. What is more, the model provides a general demonstration that visually guided routes can be produced with parsimonious mechanisms that do not specify when or what to learn, nor separate routes into sequences of waypoints

Distinct forms of synaptic inhibition and neuromodulation regulate calretinin positive neuron excitability in the spinal cord dorsal horn

The dorsal horn (DH) of the spinal cord contains a heterogenous population of neurons that process incoming sensory signals before information ascends to the brain. We have recently characterized calretinin-expressing (CR+) neurons in the DH and shown that they can be divided into excitatory and inhibitory subpopulations. The excitatory population receives high-frequency excitatory synaptic input and expresses delayed firing action potential discharge, whereas the inhibitory population receives weak excitatory drive and exhibits tonic or initial bursting discharge. Here, we characterize inhibitory synaptic input and neuromodulation in the two CR+ populations, in order to determine how each is regulated. We show that excitatory CR+ neurons receive mixed inhibition from GABAergic and glycinergic sources, whereas inhibitory CR+ neurons receive inhibition, which is dominated by glycine. Noradrenaline and serotonin produced robust outward currents in excitatory CR+ neurons, predicting an inhibitory action on these neurons, but neither neuromodulator produced a response in CR+ inhibitory neurons. In contrast, enkephalin (along with selective mu and delta opioid receptor agonists) produced outward currents in inhibitory CR+ neurons, consistent with an inhibitory action but did not affect the excitatory CR+ population. Our findings show that the pharmacology of inhibitory inputs and neuromodulator actions on CR+ cells, along with their excitatory inputs can define these two subpopulations further, and this could be exploited to modulate discrete aspects of sensory processing selectively in the DH

Mode Switching and Subpulse Drifting in PSR B0826-34

We present high-quality observations of PSR B0826-34 at 1374 MHz. The emission from this pulsar exhibits strong bursts of pulses followed by long periods of `null' pulses. When it is strong, the radiation extends through the whole pulse period. We show for the first time that there is weak emission during the `null' phases, which should therefore be considered to be a different mode rather than a null. During this weak mode the profile is similar to that observed in the strong mode at low radio frequency. Using a phase-tracking method, the pattern of drifting subpulses during the strong mode is seen to be coherent across the whole profile. The drift rate is variable and includes positive and negative values. Thirteen subpulse bands have been directly observed, covering the whole longitude range. The subpulses and their spacings ($P_2$) are wider in one half of the profile than those in the other half. This difference, and the variation of observed $P_2$ within the two regions, can be accounted for if the magnetic pole is inclined to the rotation axis by about 0.5 degrees. These two regions appear to represent radiation from outer and inner cones. The intensity modulation of subpulses in all longitude ranges is related to the magnitude of the drift rate.Comment: 8 pages, 10 figures. Accepted for publication in MNRA

Community experiences of organised crime in Scotland

The research explored community experiences of serious organised crime in Scotland (SOC). The report provides information on the nature and extent of the impact of SOC on everyday life in the community, as well as offering suggestions for policy development. The study sought to answer the following questions: 1)What are the relationships that exist between SOC and communities in Scotland? 2)What are the experiences and perceptions of residents, stakeholders and organisations of the scope and nature of SOC within their local area? and 3)How does SOC impact on community wellbeing, and to what extent can the harms associated with SOC be mitigated

Unpulsed UBV Optical Emission from the Crab Pulsar

Based on observations of the Crab pulsar using the TRIFFID high speed imaging photometer in the UBV bands using the Special Astrophysical Observatory's 6m telescope in the Russian Caucasus, we report the detection of pronounced emission during the so-called `off' phase of emission. Following de-extinction, this unpulsed component of emission is shown to be consistent with a power law with an exponent of alpha = -0.60 +/- 0.37, the uncertainty being dominated by the error associated with the independent CCD photometry used to reference the TRIFFID data. This suggests a steeper power law form than that reported elsewhere in the literature for the total integrated spectrum, which is essentially flat with alpha ~ 0.1, although the difference in this case is only significant at the ~ 2 sigma level. Deeper reference integrated and TRIFFID phase-resolved photometry in these bands in conjunction with further observations in the UV and R region would constrain this fit further.Comment: 26 pages, 2 figures, uses aasms4.sty, accepted for publication in the Astrophysical Journa

1,10-Phenanthrolin-1-ium 2-carb­oxy-4,5-dichloro­benzoate

In the structure of the 1:1 proton-transfer compound of 1,10-phenanthroline with 4,5-dichloro­phthalic acid, C12H9N2 +·C8H3Cl2O4 −, determined at 130 K, the 1,10-phenanthrolinium cation and the hydrogen 4,5-dichloro­phthalate anion associate through a single N—H⋯Ocarbox­yl hydrogen bond giving discrete units which have no extension except through a number of weak cation C—H⋯Oanion associations and weak cation–anion aromatic ring π–π inter­actions [minimum centroid–centroid separation = 3.6815 (12) Å]. The anions are essentially planar "[maximum deviation 0.214 (1) Å (a carboxyl O)] with the syn-related H atom of the carboxyl group, forming a short intra­molecular O—H⋯Ocarbox­yl hydrogen bond

2-Carboxy­quinolinium–2,4,6-trinitro­benzene­sulfonate–quinolinium-2-carboxyl­ate (1/1/1)

The structure of the title adduct compound, C10H8NO2 +·C6H2N3O9S−·C10H7NO2, from the reaction of 2,4,6-trinitro­benzene­sulfonic acid (picrylsulfonic acid) with quinoline-2-carboxylic acid (quinaldic acid) in 2-propanol–water, has been determined at 130 (2) K. The cation and the adduct species form a twisted cyclic hydrogen-bonded R 2 2(10) pseudo-dimer which is extended into a one-dimensional chain structure through short head-to-tail carboxylic acid O—H⋯Ocarbox­yl associations [O⋯O = 2.4711 (19) Å]. The picrylsulfonate anions are attached peripherally by single N—H⋯Osulfonate hydrogen bonds [N⋯O = 2.8643 (19) Å]