P2X7 Receptor Primes IL-1β and the NLRP3 Inflammasome in Astrocytes Subjected to Mechanical Strain

Inflammatory responses play a key role in many neural pathologies, with localized signaling from non-immune cells making critical contributions. The NLRP3 inflammasome is an important component of innate immune signaling and can link neural insult to chronic inflammation. Stimulation of the NLRP3 inflammasome is a two-stage process. The priming stage involves upregulation of the biosynthesis of the structural components while activation results in their assembly into the actual inflammasome complex and subsequent activation. The priming step can be rate limiting and can connect insult to chronic inflammation but our knowledge of the signals that regulate NLRP3 inflammasome priming in sterile inflammatory conditions is limited. This study examined the link between mechanical strain and inflammasome priming in neural systems. Transient non-ischemic elevation of intraocular pressure (IOP) increased mRNA for inflammasome components IL-1β, NLRP3, ASC, CASP1 and IL-6 in rat and mouse retinas. The P2X7 receptor was implicated in the in vivo mechanosensitive priming of IL-1β and IL-6 transcription and translation. In vitro experiments with optic nerve head astrocytes demonstrated enhanced expression of the IL-1β and IL-6 genes following stretching or swelling. The increase in IL-1β expression was inhibited by degradation of extracellular ATP with apyrase, blocking pannexin hemichannels with carbenoxolone, probenecid or 10Panx1 peptide, P2X7 receptor antagonists (BBG, A839977 or A740003) as well inhibition of the NFκB transcription factor with Bay 11-7082. The swelling-dependent fall in expression of the NFκB inhibitor IκB-α was reduced by treatment of cells with A839977 and in P2X7 knockout mice. In summary, our data suggest that mechanical trauma to the retina results in priming of the NLRP3 inflammasome components and upregulated IL-6 expression and release. This was dependent upon ATP release through pannexin hemichannels and autostimulation of the P2X7 receptor. Since the P2X7 receptor can also trigger inflammasome activation it appears to have a central role in linking mechanical strain to neuroinflammation

Abdominal functional electrical stimulation to improve respiratory function after spinal cord injury: a systematic review and meta-analysis

Objectives: Abdominal functional electrical stimulation (abdominal FES) is the application of a train of electrical pulses to the abdominal muscles, causing them to contract. Abdominal FES has been used as a neuroprosthesis to acutely augment respiratory function and as a rehabilitation tool to achieve a chronic increase in respiratory function after abdominal FES training, primarily focusing on patients with spinal cord injury (SCI). This study aimed to review the evidence surrounding the use of abdominal FES to improve respiratory function in both an acute and chronic manner after SCI. Settings: A systematic search was performed on PubMed, with studies included if they applied abdominal FES to improve respiratory function in patients with SCI. Methods: Fourteen studies met the inclusion criteria (10 acute and 4 chronic). Low participant numbers and heterogeneity across studies reduced the power of the meta-analysis. Despite this, abdominal FES was found to cause a significant acute improvement in cough peak flow, whereas forced exhaled volume in 1 s approached significance. A significant chronic increase in unassisted vital capacity, forced vital capacity and peak expiratory flow was found after abdominal FES training compared with baseline. Conclusions: This systematic review suggests that abdominal FES is an effective technique for improving respiratory function in both an acute and chronic manner after SCI. However, further randomised controlled trials, with larger participant numbers and standardised protocols, are needed to fully establish the clinical efficacy of this technique

Structures of the Ultra-High-Affinity Protein-Protein Complexes of Pyocins S2 and AP41 and Their Cognate Immunity Proteins from Pseudomonas aeruginosa

© 2015 The Authors. Published by Elsevier Ltd. How ultra-high-affinity protein-protein interactions retain high specificity is still poorly understood. The interaction between colicin DNase domains and their inhibitory immunity (Im) proteins is an ultra-high-affinity interaction that is essential for the neutralisation of endogenous DNase catalytic activity and for protection against exogenous DNase bacteriocins. The colicin DNase-Im interaction is a model system for the study of high-affinity protein-protein interactions. However, despite the fact that closely related colicin-like bacteriocins are widely produced by Gram-negative bacteria, this interaction has only been studied using colicins from Escherichia coli. In this work, we present the first crystal structures of two pyocin DNase-Im complexes from Pseudomonas aeruginosa, pyocin S2 DNase-ImS2 and pyocin AP41 DNase-ImAP41. These structures represent divergent DNase-Im subfamilies and are important in extending our understanding of protein-protein interactions for this important class of high-affinity protein complex. A key finding of this work is that mutations within the immunity protein binding energy hotspot, helix III, are tolerated by complementary substitutions at the DNase-Immunity protein binding interface. Im helix III is strictly conserved in colicins where an Asp forms polar interactions with the DNase backbone. ImAP41 contains an Asp-to-Gly substitution in helix III and our structures show the role of a co-evolved substitution where Pro in DNase loop 4 occupies the volume vacated and removes the unfulfilled hydrogen bond. We observe the co-evolved mutations in other DNase-Immunity pairs that appear to underpin the split of this family into two distinct groups

Relationship between ecosystem productivity and photosynthetically active radiation for northern peatlands

We analyzed the relationship between new ecosystem exchange of carbon dioxide (NEE) and irradiance (as photosynthetic photon flux density of PPFD), using published and unpublished data that have been collected during midgrowing season for carbon balance studies at seven peatlands in North America and Europe. NEE measurements included both eddy-correlation tower and clear, static chamber methods, which gave very similar results. Data were analyzed by site, as aggregated data set for all peatland type (bog, poor fen, rich fen, and all fens) and as a single aggregated data set for all peatlands. In all cases, a fit with a rectangular hyperbola (NEE = PPFD P max (PPFD + PMAX) + R) better described the NEE-PPFD relationships ,while bogs had lower respiration rates (R = -2.0 umol m-2 s-1 for bogs and -2.7 umol m-2 s-1 for fens) and lower NEE at moderate and high light levels (Pmax = 5.2 umol m-2 s-1) than the upland exosystems (closed canopy forest, grassland, and cropland) summarized by Ruimy et al. [1995]. Despite this low productivity, northern peatland soil carbon pools are generally 5-50 times larger than upland ecosystems because of slow rates of decomposition caused by litter quality and anaerobic, cold soils

Relationship between ecosystem productivity and photosynthetically-active radiation for northern peatlands

We analyzed the relationship between net ecosystem exchange of carbon dioxide (NEE) and irradiance (as photosynthetic photon flux density or PPFD), using published and unpublished data that have been collected during midgrowing season for carbon balance studies at seven peatlands in North America and Europe. NEE measurements included both eddy-correlation tower and clear, static chamber methods, which gave very similar results. Data were analyzed by site, as aggregated data sets by peatland type (bog, poor fen, rich fen, and all fens) and as a single aggregated data set for all peatlands. In all cases, a fit with a rectangular hyperbola (NEE = α PPFD Pmax/(α PPFD + Pmax) + R) better described the NEE-PPFD relationship than did a linear fit (NEE = β PPFD + R). Poor and rich fens generally had similar NEE-PPFD relationships, while bogs had lower respiration rates (R = −2.0μmol m−2s−1 for bogs and −2.7 μmol m−2s−1 for fens) and lower NEE at moderate and high light levels (Pmax = 5.2 μmol m−2s−1 for bogs and 10.8 μmol m−2s−1 for fens). As a single class, northern peatlands had much smaller ecosystem respiration (R = −2.4 μmol m−2s−1) and NEE rates (α = 0.020 and Pmax = 9.2μmol m−2s−1) than the upland ecosystems (closed canopy forest, grassland, and cropland) summarized by Ruimy et al. [1995]. Despite this low productivity, northern peatland soil carbon pools are generally 5–50 times larger than upland ecosystems because of slow rates of decomposition caused by litter quality and anaerobic, cold soils

Hemorrhagic Fever with Renal Syndrome in 4 US Soldiers, South Korea, 2005

Four US soldiers acquired hemorrhagic fever with renal syndrome while training near the Demilitarized Zone, South Korea, in 2005. Hantaan virus sequences were amplified by reverse transcription–PCR from patient serum samples and from lung tissues of striped field mice (Apodemus agrarius) captured at training sites. Epidemiologic investigations specified the ecology of possible sites of patient infection

Everyday self-defence: Hollaback narratives, habitus and resisting street harassment

Street harassment is recognised as an ‘everyday’ form of violence against women. Influenced by contemporary sociologies of everyday life, this article examines women responses to street harassment, drawing on over 500 first person narratives submitted to the website of Hollaback London. The narrative structure highlights women’s actions, which (like street harassment) have generally been considered inconsequential. Quantitative content analysis reveals the extent and variety of strategies employed by women, including speaking back, calling on others for help, physically fighting-back, walking away and an array of ‘small’, everyday actions and gestures that aim to resist harassment. I argue that these responses comprise everyday self-defence practice. Furthermore, the notion of narrative habitus is employed to argue that Hollaback narratives do not just describe harassment, but that reading narratives can generate dispositions for self-defence. Narrative analysis reveals the way that satire is employed to make space for women’s successful self-defence. I argue that Hollaback narratives do not just offer storylines or scripts for resisting street harassment but foster a style for doing so. Analysis considers the limits to narratively motivated self-defence. This research demonstrates that, in order to ‘see’ women’s resistance, we need to pay close attention to the everyday as the site of both gendered oppression and moments of liberation

Winter respiratory C losses provide explanatory power for net ecosystem productivity

Accurate predictions of net ecosystem productivity (NEPc) of forest ecosystems are essential for climate change decisions and requirements in the context of national forest growth and greenhouse gas inventories. However, drivers and underlying mechanisms determining NEPc (e.g., climate and nutrients) are not entirely understood yet, particularly when considering the influence of past periods. Here we explored the explanatory power of the compensation day (cDOY)defined as the day of year when winter net carbon losses are compensated by spring assimilationfor NEPc in 26 forests in Europe, North America, and Australia, using different NEPc integration methods. We found cDOY to be a particularly powerful predictor for NEPc of temperate evergreen needleleaf forests (R-2=0.58) and deciduous broadleaf forests (R-2=0.68). In general, the latest cDOY correlated with the lowest NEPc. The explanatory power of cDOY depended on the integration method for NEPc, forest type, and whether the site had a distinct winter net respiratory carbon loss or not. The integration methods starting in autumn led to better predictions of NEPc from cDOY then the classical calendar method starting 1 January. Limited explanatory power of cDOY for NEPc was found for warmer sites with no distinct winter respiratory loss period. Our findings highlight the importance of the influence of winter processes and the delayed responses of previous seasons' climatic conditions on current year's NEPc. Such carry-over effects may contain information from climatic conditions, carbon storage levels, and hydraulic traits of several years back in time.Peer reviewe

Epidemiology of traumatic spinal cord injury in Galicia, Spain: trends over a 20-year period

[Abstract] Study design: Observational study with prospective and retrospective monitoring. Objective: To describe the epidemiological and demographic characteristics of traumatic spinal cord injury (TSCI), and to analyze its epidemiological changes. Setting: Unidad de Lesionados Medulares, Complejo Hospitalario Universitario A Coruña, in Galicia (Spain). Methods: The study included patients with TSCI who had been hospitalized between January 1995 and December 2014. Relevant data were extracted from the admissions registry and electronic health record. Results: A total of 1195 patients with TSCI were admitted over the specified period of time; 76.4% male and 23.6% female. Mean patient age at injury was 50.20 years. Causes of injury were falls (54.2%), traffic accidents (37%), sports/leisure-related accidents (3.5%) and other traumatic causes (5.3%). Mean patient age increased significantly over time (from 46.40 to 56.54 years), and the number of cases of TSCI related to traffic accidents decreased (from 44.5% to 23.7%), whereas those linked to falls increased (from 46.9% to 65.6%). The most commonly affected neurological level was the cervical level (54.9%), increasing in the case of levels C1–C4 over time, and the most frequent ASIA (American Spinal Injury Association) grade was A (44.3%). The crude annual incidence rate was 2.17/100 000 inhabitants, decreasing significantly over time at an annual percentage rate change of −1.4%. Conclusions: The incidence rate of TSCI tends to decline progressively. Mean patient age has increased over time and cervical levels C1–C4 are currently the most commonly affected ones. These epidemiological changes will eventually result in adjustments in the standard model of care for TSCI

Biology ideology and pastiche hegemony

As knowledge about the biological foundation of the modern patriarchal gender order is increasingly challenged within late-modern social worlds enclaves persist in which men and women can attempt to recreate understandings of the "natural" basis of sex difference. Within "Power Gym," male boxers were able to symbolize their bodies and behaviors in such a manner. The language and logic of popular scientific discourses authored and authorized notions of an "innate" manhood. The ability to instrumentally deploy one's manliness in symbolically legitimate ways could then be represented and emotionally experienced as a man's biological right and obligation. Through scripted performances of "mimetic" violence and self-bullying, the boxers were able to experience this discursive naturalness and carve out a masculinity-validating social enclave. As such, they accessed a "patriarchal dividend" by securing a local pastiche hegemony in which discourses surrounding men's natural place as physically and psychologically dominant remained largely uncontested. Through the reflexive appropriation of "science," within appropriate subcultural codes, these men could negotiate taboos and restrictions that are characteristic of late-modern social worlds. When considered in this way, the power of "scientific" truth claims to explain and justify a certain level of violence, aggression, and behaviors coded as masculine, comes to the fore