Odontoblast TRPC5 channels signal cold pain in teeth

Teeth are composed of many tissues, covered by an inflexible and obdurate enamel. Unlike most other tissues, teeth become extremely cold sensitive when inflamed. The mechanisms of this cold sensation are not understood. Here, we clarify the molecular and cellular components of the dental cold sensing system and show that sensory transduction of cold stimuli in teeth requires odontoblasts. TRPC5 is a cold sensor in healthy teeth and, with TRPA1, is sufficient for cold sensing. The odontoblast appears as the direct site of TRPC5 cold transduction and provides a mechanism for prolonged cold sensing via TRPC5\u27s relative sensitivity to intracellular calcium and lack of desensitization. Our data provide concrete functional evidence that equipping odontoblasts with the cold-sensor TRPC5 expands traditional odontoblast functions and renders it a previously unknown integral cellular component of the dental cold sensing system

Towards understanding the myometrial physiome: approaches for the construction of a virtual physiological uterus

Premature labour (PTL) is the single most significant factor contributing to neonatal morbidity in Europe with enormous attendant healthcare and social costs. Consequently, it remains a major challenge to alleviate the cause and impact of this condition. Our ability to improve the diagnosis and treatment of women most at risk of PTL is, however, actually hampered by an incomplete understanding of the ways in which the functions of the uterine myocyte are integrated to effect an appropriate biological response at the multicellular whole organ system. The level of organization required to co-ordinate labouring uterine contractile effort in time and space can be considered immense. There is a multitude of what might be considered mini-systems involved, each with their own regulatory feedback cycles, yet they each, in turn, will influence the behaviour of a related system. These include, but are not exclusive to, gestational-dependent regulation of transcription, translation, post-translational modifications, intracellular signaling dynamics, cell morphology, intercellular communication and tissue level morphology. We propose that in order to comprehend how these mini-systems integrate to facilitate uterine contraction during labour (preterm or term) we must, in concert with biological experimentation, construct detailed mathematical descriptions of our findings. This serves three purposes: firstly, providing a quantitative description of series of complex observations; secondly, proferring a database platform that informs further testable experimentation; thirdly, advancing towards the establishment of a virtual physiological uterus and in silico clinical diagnosis and treatment of PTL

Synthesis of stoichiometrically controlled reactive aluminosilicate and calcium-aluminosilicate powders

Aluminosilicate and calcium-aluminosilicate powders are synthesised via an organic steric entrapment route under conditions permitting strict stoichiometric control, utilising polyvinyl alcohol and polyethylene glycol as polymeric carriers. Polyethylene glycol is superior to polyvinyl alcohol for synthesis of calcium-aluminosilicate powders via this method, producing a more controllable product which generated less fine ash during calcination. This paper presents detailed description of synthesis and characterisation of the powders produced through this approach, including new insight into the nanostructures within the calcined powders. Aluminium environments are a mixture of 4-, 5- and 6-coordinated, while silicon is tetrahedral and shows a broad range of connectivity states. The powders are X-ray amorphous, display a high degree of homogeneity, and thus offer potential for utilisation as precursors for synthesis of hydrous aluminosilicates in the quaternary CaO-Na2O-Al2O3-SiO2 system

CP violation Beyond the MSSM: Baryogenesis and Electric Dipole Moments

We study electroweak baryogenesis and electric dipole moments in the presence of the two leading-order, non-renormalizable operators in the Higgs sector of the MSSM. Significant qualitative and quantitative differences from MSSM baryogenesis arise due to the presence of new CP-violating phases and to the relaxation of constraints on the supersymmetric spectrum (in particular, both stops can be light). We find: (1) spontaneous baryogenesis, driven by a change in the phase of the Higgs vevs across the bubble wall, becomes possible; (2) the top and stop CP-violating sources can become effective; (3) baryogenesis is viable in larger parts of parameter space, alleviating the well-known fine-tuning associated with MSSM baryogenesis. Nevertheless, electric dipole moments should be measured if experimental sensitivities are improved by about one order of magnitude.Comment: 33 pages, 6 figure

Effect of nanosilica-based activators on the performance of an alkali-activated fly ash

This paper assesses the effect of the use of an alternative activator based on nanosilica/MOH (M = K+ or Na+) blended solutions on the performance of alkali-activated fly ash binders. Binders produced with commercial silicate activators display a greater degree of reaction, associated with increased contents of geopolymer gel; however, mortars produced with the alternative nanosilica-based activators exhibited lower water demand and reduced permeability, independent of the alkali cation used. Na-based activators promote higher compressive strength compared with K-based activators, along with a refined pore structure, although K-activated samples exhibit reduced water demand. Zeolite type products are the major crystalline phases formed within these binders. A wider range of zeolites is formed when using commercial silicate solutions compared with the alternative activators. These results suggest that there are variations in the availability of Si in the system, and consequently in the alkalinity, depending on the silicate source in the activator, which is important in determining the nanostructure of the geopolymer gel.This study was sponsored by the Ministerio de Ciencia e Innovacion of Spain (Project GEORES MAT2010-19934 and research scholarship BES-2008-002440), European regional development fund (FEDER), and the Universitat Politecnica de Valencia (Spain). The participation of SAB and JLP was funded by the Australian Research Council (ARC), including partial funding through the Particulate Fluids Processing Centre, a Special Research Centre of the ARC. A special acknowledgement is also due to the Centre of Electron Microscopy of the Universitat Politecnica de Valencia and Pedro Garces from the Universidad de Alicante for support in some experiments.Rodriguez Martinez, ED.; Bernal, SA.; Provis, JL.; Paya Bernabeu, JJ.; Monzó Balbuena, JM.; Borrachero Rosado, MV. (2013). Effect of nanosilica-based activators on the performance of an alkali-activated fly ash. Cement and Concrete Composites. 35(1):1-11. doi:10.1016/j.cemconcomp.2012.08.025S11135

Uncertainty in United States coastal wetland greenhouse gas inventorying

© The Author(s), 2018. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Environmental Research Letters 13 (2018): 115005, doi:10.1088/1748-9326/aae157.Coastal wetlands store carbon dioxide (CO2) and emit CO2 and methane (CH4) making them an important part of greenhouse gas (GHG) inventorying. In the contiguous United States (CONUS), a coastal wetland inventory was recently calculated by combining maps of wetland type and change with soil, biomass, and CH4 flux data from a literature review. We assess uncertainty in this developing carbon monitoring system to quantify confidence in the inventory process itself and to prioritize future research. We provide a value-added analysis by defining types and scales of uncertainty for assumptions, burial and emissions datasets, and wetland maps, simulating 10 000 iterations of a simplified version of the inventory, and performing a sensitivity analysis. Coastal wetlands were likely a source of net-CO2-equivalent (CO2e) emissions from 2006–2011. Although stable estuarine wetlands were likely a CO2e sink, this effect was counteracted by catastrophic soil losses in the Gulf Coast, and CH4 emissions from tidal freshwater wetlands. The direction and magnitude of total CONUS CO2e flux were most sensitive to uncertainty in emissions and burial data, and assumptions about how to calculate the inventory. Critical data uncertainties included CH4 emissions for stable freshwater wetlands and carbon burial rates for all coastal wetlands. Critical assumptions included the average depth of soil affected by erosion events, the method used to convert CH4 fluxes to CO2e, and the fraction of carbon lost to the atmosphere following an erosion event. The inventory was relatively insensitive to mapping uncertainties. Future versions could be improved by collecting additional data, especially the depth affected by loss events, and by better mapping salinity and inundation gradients relevant to key GHG fluxes. Social Media Abstract: US coastal wetlands were a recent and uncertain source of greenhouse gasses because of CH4 and erosion.Financial support was provided primarily by NASA Carbon Monitoring Systems (NNH14AY67I) and the USGS Land Carbon Program, with additional support from The Smithsonian Institution, The Coastal Carbon Research Coordination Network (DEB-1655622), and NOAA Grant: NA16NMF4630103

Galactic-Centre Gamma Rays in CMSSM Dark Matter Scenarios

We study the production of gamma rays via LSP annihilations in the core of the Galaxy as a possible experimental signature of the constrained minimal supersymmetric extension of the Standard Model (CMSSM), in which supersymmetry-breaking parameters are assumed to be universal at the GUT scale, assuming also that the LSP is the lightest neutralino chi. The part of the CMSSM parameter space that is compatible with the measured astrophysical density of cold dark matter is known to include a stau_1 - chi coannihilation strip, a focus-point strip where chi has an enhanced Higgsino component, and a funnel at large tanb where the annihilation rate is enhanced by the poles of nearby heavy MSSM Higgs bosons, A/H. We calculate the total annihilation rates, the fractions of annihilations into different Standard Model final states and the resulting fluxes of gamma rays for CMSSM scenarios along these strips. We observe that typical annihilation rates are much smaller in the coannihilation strip for tanb = 10 than along the focus-point strip or for tanb = 55, and that the annihilation branching ratios differ greatly between the different dark matter strips. Whereas the current Fermi-LAT data are not sensitive to any of the CMSSM scenarios studied, and the calculated gamma-ray fluxes are probably unobservably low along the coannihilation strip for tanb = 10, we find that substantial portions of the focus-point strips and rapid-annihilation funnel regions could be pressured by several more years of Fermi-LAT data, if understanding of the astrophysical background and/or systematic uncertainties can be improved in parallel.Comment: 33 pages, 12 figures, comments and references added, version to appear in JCA

Circulating microRNAs Reveal Time Course of Organ Injury in a Porcine Model of Acetaminophen-Induced Acute Liver Failure

Acute liver failure is a rare but catastrophic condition which can progress rapidly to multi-organ failure. Studies investigating the onset of individual organ injury such as the liver, kidneys and brain during the evolution of acute liver failure, are lacking. MicroRNAs are short, non-coding strands of RNA that are released into the circulation following tissue injury. In this study, we have characterised the release of both global microRNA and specific microRNA species into the plasma using a porcine model of acetaminophen-induced acute liver failure. Pigs were induced to acute liver failure with oral acetaminophen over 19h±2h and death occurred 13h±3h thereafter. Global microRNA concentrations increased 4h prior to acute liver failure in plasma (P<0.0001) but not in isolated exosomes, and were associated with increasing plasma levels of the damage-associated molecular pattern molecule, genomic DNA (P<0.0001). MiR122 increased around the time of onset of acute liver failure (P<0.0001) and was associated with increasing international normalised ratio (P<0.0001). MiR192 increased 8h after acute liver failure (P<0.0001) and was associated with increasing creatinine (P<0.0001). The increase in miR124-1 occurred concurrent with the pre-terminal increase in intracranial pressure (P<0.0001) and was associated with decreasing cerebral perfusion pressure (P<0.002)

Generalized Structural Description of Calcium–Sodium Aluminosilicate Hydrate Gels: The Cross-Linked Substituted Tobermorite Model

Structural models for the primary strength and durability-giving reaction product in modern cements, a calcium (alumino)silicate hydrate gel, have previously been based solely on non-cross-linked tobermorite structures. However, recent experimental studies of laboratory-synthesized and alkali-activated slag (AAS) binders have indicated that the calcium–sodium aluminosilicate hydrate [C-(N)-A-S-H] gel formed in these systems can be significantly cross-linked. Here, we propose a model that describes the C-(N)-A-S-H gel as a mixture of cross-linked and non-cross-linked tobermorite-based structures (the cross-linked substituted tobermorite model, CSTM), which can more appropriately describe the spectroscopic and density information available for this material. Analysis of the phase assemblage and Al coordination environments of AAS binders shows that it is not possible to fully account for the chemistry of AAS by use of the assumption that all of the tetrahedral Al is present in a tobermorite-type C-(N)-A-S-H gel, due to the structural constraints of the gel. Application of the CSTM can for the first time reconcile this information, indicating the presence of an additional activation product that contains highly connected four-coordinated silicate and aluminate species. The CSTM therefore provides a more advanced description of the chemistry and structure of calcium–sodium aluminosilicate gel structures than that previously established in the literature

Superantigens and Streptococcal Toxic Shock Syndrome

Superantigens produced by Streptococcus pyogenes have been implicated with streptococcal toxic shock syndrome (STSS). We analyzed 19 acute-phase serum samples for mitogenic activity from patients with severe streptococcal disease. The serum samples from two patients in the acute phase of STSS showed strong proliferative activity. Streptococcal mitogenic exotoxin (SME) Z-1 and streptococcal pyrogenic exotoxin (SPE)-J were identified in one patient with peritonitis who recovered after 2 weeks in intensive care. SMEZ-16 was found in a second patient who died on the day of admission. Sequential serum samples taken on day 3 after admission from patient 1 showed clearance of mitogenic activity but absence of neutralizing anti-SMEZ antibodies. Serum samples taken on day 9 from this patient showed evidence of seroconversion with high levels of anti-SMEZ antibodies that neutralized SMEZ-1 and 12 other SMEZ-variants. These results imply that a high level of SMEZ production by group A streptococcus is a causative event in the onset and subsequent severity of STSS