KCNQ/M currents in sensory neurons: Significance for pain therapy

Neuronal hyperexcitability is a feature of epilepsy and both inflammatory and neuropathic pain. M currents [I-K(M)] play a key role in regulating neuronal excitability, and mutations in neuronal KCNQ2/3 subunits, the molecular correlates of I-K(M), have previously been linked to benign familial neonatal epilepsy. Here, we demonstrate that KCNQ/M channels are also present in nociceptive sensory systems. I-K(M) was identified, on the basis of biophysical and pharmacological properties, in cultured neurons isolated from dorsal root ganglia (DRGs) from 17-d-old rats. Currents were inhibited by the M-channel blockers linopirdine (IC50, 2.1 muM) and XE991 (IC50, 0.26 muM) and enhanced by retigabine (10 muM). The expression of neuronal KCNQ subunits in DRG neurons was confirmed using reverse transcription-PCR and single-cell PCR analysis and by immunofluorescence. Retigabine, applied to the dorsal spinal cord, inhibited C and Adelta fiber-mediated responses of dorsal horn neurons evoked by natural or electrical afferent stimulation and the progressive "windup" discharge with repetitive stimulation in normal rats and in rats subjected to spinal nerve ligation. Retigabine also inhibited responses to intrapaw application of carrageenan in a rat model of chronic pain; this was reversed by XE991. It is suggested that I-K(M) plays a key role in controlling the excitability of nociceptors and may represent a novel analgesic target

Tissue resolved, gene structure refined equine transcriptome.

BackgroundTranscriptome interpretation relies on a good-quality reference transcriptome for accurate quantification of gene expression as well as functional analysis of genetic variants. The current annotation of the horse genome lacks the specificity and sensitivity necessary to assess gene expression especially at the isoform level, and suffers from insufficient annotation of untranslated regions (UTR) usage. We built an annotation pipeline for horse and used it to integrate 1.9 billion reads from multiple RNA-seq data sets into a new refined transcriptome.ResultsThis equine transcriptome integrates eight different tissues from 59 individuals and improves gene structure and isoform resolution, while providing considerable tissue-specific information. We utilized four levels of transcript filtration in our pipeline, aimed at producing several transcriptome versions that are suitable for different downstream analyses. Our most refined transcriptome includes 36,876 genes and 76,125 isoforms, with 6474 candidate transcriptional loci novel to the equine transcriptome.ConclusionsWe have employed a variety of descriptive statistics and figures that demonstrate the quality and content of the transcriptome. The equine transcriptomes that are provided by this pipeline show the best tissue-specific resolution of any equine transcriptome to date and are flexible for several downstream analyses. We encourage the integration of further equine transcriptomes with our annotation pipeline to continue and improve the equine transcriptome

Cascaded Fresnel Lens Antenna for Scan Loss Mitigation in Millimeter-Wave Access Points

Millimeter wave lens antennas will be essential for future wireless access. Conventionally, they increase the gain in the boresight direction only. In this paper, cascaded Fresnel zone plate lenses are combined with a phased array to increase the gain at wide steering angles of ±52°. The side lenses are tilted to align with the maximum steering angle, and cascaded to increase the focusing gain. The inner lenses increase the gain by 2.45 dB at boresight, and by 3.19 dB at the maximum steering angle. When the side lenses are repositioned, the simulated focusing gain increases to 4.69 dB. Asymmetric amplitude distributions are proposed to prevent the main lobe from splitting. An 8-dement 7-lens prototype operating at 28 GHz achieved a gain from 12.96 dBi to 15.35 dBi with a bandwidth of at least 1.3 GHz for all measured beam directions. The maximum measured azimuthal beamwidth was 27°. A design procedure and a theoretical analysis of diffraction through the lenses are provided. By increasing the SNR, this beamfonning antenna could improve the coverage of 3-sector 5G microcell base stations, and support gigabit wireless links for vehicular, rail, and satellite communications

Organisational Identification of Academic Staff and Its Relationship to the Third Stream

A university is a organisation where academics study, research and teach students. The archetypal “academic” has an image and identity that is as clear as a doctor or fireman. However the nature of a university is changing, the university is now required to seek out new relationships with businesses and non traditional “customers”, delivering learning and knowledge in new ways, frequently driven by commercial demands. University senior management teams are motivated by government and funding to meet these demands and steer the university towards these new goals. These new areas of activity are often referred to as the “Third Stream” TS (teaching and research being streams 1 and 2). The new mission, strategies and definitions of third stream initiatives form a changing organisational identity for a university which may challenge widely held notions of a universities identity by its member staff, the academics. Dutton et. al. (1994, p1) state; “Strong organisational identification may translate into desirable outcomes”. If the university wants its members (the academics) to embrace the changing mission of a university and undertake actions in support of the new mission, university managers must understand the organisational members (the academics) relationship to the new identity and aim to engender a strong organisational identity

Conformal Transmitarray for Scan Loss Mitigation with Thinned Reconfiguration

A conformal transmitarray with thinned control is presented, operating at 28 GHz. Its side panels are rotated to align with the maximum steering angle, increasing the gain and reducing the scan loss. The transmitarray is fed by an 8-element linear phased array antenna. Beam focusing to +/- 53 degrees is demonstrated for two different directions, using combinations of crossed-slot unit cells. A unit cell placement rule is proposed to significantly reduce (i.e. thin) the required number of reconfigurable unit cells. A filling factor of 43% was achieved compared to a fully populated design. This reduces the cost and biasing complexity. By minimising scan loss, this antenna could improve the performance of 5G small-cell access points

Biomechanical determinants of knee joint loads associated with increased anterior cruciate ligament loading during cutting : a systematic review and technical framework

Background: Cutting actions are associated with non-contact ACL injuries in multidirectional sports due to the propensity to generate large multiplanar knee joint loads (KJLs) that have the capacity to increase ACL loading and strain. Numerous studies have investigated the biomechanical determinants of KJLs in cutting tasks. The aim of this systematic review was to comprehensively review the literature regarding biomechanical determinants of KJLs during cutting, in order to develop a cutting technical framework alongside training recommendations for practitioners regarding KJL mitigation. Methods: Databases (SPORTDiscus, Web of Science and PubMed) were systematically searched using a combination of the following terms: “Biomechanical determinants”, or “Knee abduction moment”, or “Technical determinants”, or “Knee loading”, or “Knee loads”, or “Mechanical determinants”, or “ACL strain”, or “Knee adduction moment”, or “Anterior tibial shear”, or “Knee internal rotation moment”, or “Knee valgus moment” AND “Change of direction”, or “Cutting manoeuvre”, or “Run and cut”, or “Run-and-cut”, or “Sidestepping”, or “Side-stepping”, or “Shuttle run”. Inclusion criteria were as follows: studies examining a cutting task < 110° with a preceding approach run that examined biomechanical determinants of KJLs using three-dimensional motion analysis. Results: The search returned 6404 possibly eligible articles, and 6 identified through other sources. Following duplicate removal, 4421 titles and abstracts were screened, leaving 246 full texts to be screened for inclusion. Twenty-three full texts were deemed eligible for inclusion and identified numerous determinants of KJLs; 11 trunk, 11 hip, 7 knee, 3 multiplanar KJLs, 5 foot/ankle and 7 identifying ground reaction forces (GRFs) as determinants of KJLs. Conclusion: Using the framework developed from the results, cutting KJLs can be mitigated through the following: reducing lateral foot-plant distances, thus lowering hip abduction and orientating the foot closer to neutral with a mid-foot or forefoot placement strategy; minimising knee valgus and hip internal rotation angles and motion at initial contact (IC) and weight acceptance (WA); avoiding and limiting lateral trunk flexion and attempt to maintain an upright trunk position or trunk lean into the intended direction; and finally, reducing GRF magnitude during WA, potentially by attenuation through increased knee flexion and emphasising a greater proportion of braking during the penultimate foot contact (PFC)

How large should whales be?

The evolution and distribution of species body sizes for terrestrial mammals is well-explained by a macroevolutionary tradeoff between short-term selective advantages and long-term extinction risks from increased species body size, unfolding above the 2g minimum size induced by thermoregulation in air. Here, we consider whether this same tradeoff, formalized as a constrained convection-reaction-diffusion system, can also explain the sizes of fully aquatic mammals, which have not previously been considered. By replacing the terrestrial minimum with a pelagic one, at roughly 7000g, the terrestrial mammal tradeoff model accurately predicts, with no tunable parameters, the observed body masses of all extant cetacean species, including the 175,000,000g Blue Whale. This strong agreement between theory and data suggests that a universal macroevolutionary tradeoff governs body size evolution for all mammals, regardless of their habitat. The dramatic sizes of cetaceans can thus be attributed mainly to the increased convective heat loss is water, which shifts the species size distribution upward and pushes its right tail into ranges inaccessible to terrestrial mammals. Under this macroevolutionary tradeoff, the largest expected species occurs where the rate at which smaller-bodied species move up into large-bodied niches approximately equals the rate at which extinction removes them.Comment: 7 pages, 3 figures, 2 data table

Quantitative estimates of sinking sea ice particulate organic carbon based on the biomarker IP<inf>25</inf>

Sea ice-derived particulate organic carbon (iPOC) represents an important contribution of carbon to Arctic ecosystems, yet our ability to obtain realistic quantitative estimates of iPOC outside the sea ice matrix is currently somewhat limited. To address this challenge, we applied a novel approach to quantifying iPOC within the water column under melting sea ice by first measuring the proportion of the sea ice diatom biomarker IP25 within iPOC in bottom ice samples obtained from Resolute Passage during spring 2012. We then compared this value with corresponding values obtained from a time series of water samples. Together, these reflected a period of ice melt and rapid release of iPOC, indicated by changing ice temperature and thickness, in addition to changes in the stable carbon isotope composition and concentration of iPOC, IP25 and chlorophyll a within bottom ice. Estimates of iPOC in seawater were highest (0.15 to 0.22 mg l-1) in the upper 2 m, coincident with the reduction of iPOC in sea ice near the beginning of sampling, with iPOC accounting for an estimated 84 to 125% of total POC (tPOC). Collectively, this biomarker approach yielded realistic estimates of %iPOC, both numerically and in the context of melting sea ice following a spring bloom in the Canadian Arctic. We describe some assumptions of this approach and consider the impacts of possible caveats on quantitative estimates of iPOC derived using this methodology

Cognitive-Behavior Therapy (CBT) for Panic Disorder: Relationship of Anxiety and Depression Comorbidity with Treatment Outcome

Research evaluating the relationship of comorbidity to treatment outcome for panic disorder has produced mixed results. The current study examined the relationship of comorbid depression and anxiety to treatment outcome in a large-scale, multi-site clinical trial for cognitive-behavior therapy (CBT) for panic disorder. Comorbidity was associated with more severe panic disorder symptoms, although comorbid diagnoses were not associated with treatment response. Comorbid generalized anxiety disorder (GAD) and major depressive disorder (MDD) were not associated with differential improvement on a measure of panic disorder severity, although only rates of comorbid GAD were significantly lower at posttreatment. Treatment responders showed greater reductions on measures of anxiety and depressive symptoms. These data suggest that comorbid anxiety and depression are not an impediment to treatment response, and successful treatment of panic disorder is associated with reductions of comorbid anxiety and depressive symptoms. Implications for treatment specificity and conceptual understandings of comorbidity are discussed