The Effect of Lactic Acid on Mast Cell Function

This study shows for the first time the effect that L-(+)-lactic acid has on mast cell activation. Lactic acid is a byproduct of anaerobic glycolysis and is associated with inflammatory environments such as wounds, tumors and, asthma. In this study, pre-treatment with lactic acid altered cytokine production by bone marrow-derived mast cells (BMMC). Specifically, lactic acid enhanced cytokine secretion following IgE cross-linking, but decreased IL-33 mediated cytokine production. These effects were altered by genetic background, since C57BL/6 mast cells demonstrated the aforementioned result, but lactic acid had no effect on IgE-mediated cytokine production in 129/SvJ mast cells. The affected cytokines included IL-6, TNF, MCP-1, MIP-1α, IL-13, and VEGF. Lactic acid pretreatment promoted a G0/G1 cell cycle arrest. Investigation into the IL-33 signaling pathway showed lactic acid decreased TAK1 and JNK phosphorylation, while increasing phosphorylated AKT levels. Blocking JNK and TAK1 with a small molecule inhibitor mimicked the effects of lactic acid. Interestingly, lactic acid significantly increased IL-33 mediated VEGF. An in vitro angiogenesis assay confirmed that mast cells were pro-angiogenic in a lactic acid-rich environment. Taken together, these data show that lactic acid impacts mast cell function, possibly promoting a pro-angiogenic, anti-inflammatory phenotype

Revisiting two-step Forbush decreases

Interplanetary coronal mass ejections (ICMEs) and their shocks can sweep out galactic cosmic rays (GCRs), thus creating Forbush decreases (FDs). The traditional model of FDs predicts that an ICME and its shock decrease the GCR intensity in a two-step profile. This model, however, has been the focus of little testing. Thus, our goal is to discover whether a passing ICME and its shock inevitably lead to a two-step FD, as predicted by the model. We use cosmic ray data from 14 neutron monitors and, when possible, high time resolution GCR data from the spacecraft International Gamma Ray Astrophysical Laboratory (INTEGRAL). We analyze 233 ICMEs that should have created two-step FDs. Of these, only 80 created FDs, and only 13 created two-step FDs. FDs are thus less common than predicted by the model. The majority of events indicates that profiles of FDs are more complicated, particularly within the ICME sheath, than predicted by the model. We conclude that the traditional model of FDs as having one or two steps should be discarded. We also conclude that generally ignored small-scale interplanetary magnetic field structure can contribute to the observed variety of FD profiles

Deep dielectric charging of regolith within the Moon\u27s permanently shadowed regions

Abstract Energetic charged particles, such as galactic cosmic rays (GCRs) and solar energetic particles (SEPs), can penetrate deep within the lunar surface, resulting in deep dielectric charging. This charging process depends on the GCR and SEP currents, as well as on the regolith\u27s electrical conductivity and permittivity. In permanently shadowed regions (PSRs) near the lunar poles, the discharging timescales are on the order of a lunation (∼20 days). We present the first predictions for deep dielectric charging of lunar regolith. To estimate the resulting subsurface electric fields, we develop a data-driven, one-dimensional, time-dependent model. For model inputs, we use GCR data from the Cosmic Ray Telescope for the Effects of Radiation on board the Lunar Reconnaissance Orbiter and SEP data from the Electron, Proton, and Alpha Monitor on the Advanced Composition Explorer. We find that during the recent solar minimum, GCRs create persistent electric fields up to ∼700 V/m. We also find that large SEP events create transient but strong electric fields (≥106 V/m) that may induce dielectric breakdown. Such breakdown would likely result in significant modifications to the physical and chemical properties of the lunar regolith within PSRs. Key Points Energetic charged particles deep dielectrically charge the lunar regolithWe model the resulting subsurface electric fieldsThe electric fields may be great enough to induce dielectric breakdown

Multipoint, high time resolution galactic cosmic ray observations associated with two interplanetary coronal mass ejections

[1] Galactic cosmic rays (GCRs) play an important role in our understanding of the interplanetary medium (IPM). The causes of their short timescale variations, however, remain largely unexplored. In this paper, we compare high time resolution, multipoint space-based GCR data to explore structures in the IPM that cause these variations. To ensure that features we see in these data actually relate to conditions in the IPM, we look for correlations between the GCR time series from two instruments onboard the Polar and INTEGRAL (International Gamma Ray Astrophysical Laboratory) satellites, respectively inside and outside Earth\u27s magnetosphere. We analyze the period of 18–24 August 2006 during which two interplanetary coronal mass ejections (ICMEs) passed Earth and produced a Forbush decrease (Fd) in the GCR flux. We find two periods, for a total of 10 h, of clear correlation between small-scale variations in the two GCR time series during these 7 days, thus demonstrating that such variations are observable using space-based instruments. The first period of correlation lasted 6 h and began 2 h before the shock of the first ICME passed the two spacecraft. The second period occurred during the initial decrease of the Fd, an event that did not conform to the typical one- or two-step classification of Fds. We propose that two planar magnetic structures preceding the first ICME played a role in both periods: one structure in driving the first correlation and the other in initiating the Fd

Lunar radiation environment and space weathering from the Cosmic Ray Telescope for the Effects of Radiation (CRaTER)

[1] The Cosmic Ray Telescope for the Effects of Radiation (CRaTER) measures linear energy transfer by Galactic Cosmic Rays (GCRs) and Solar Energetic Particles (SEPs) on the Lunar Reconnaissance Orbiter (LRO) Mission in a circular, polar lunar orbit. GCR fluxes remain at the highest levels ever observed during the space age. One of the largest SEP events observed by CRaTER during the LRO mission occurred on June 7, 2011. We compare model predictions by the Earth-Moon-Mars Radiation Environment Module (EMMREM) for both dose rates from GCRs and SEPs during this event with results from CRaTER. We find agreement between these models and the CRaTER dose rates, which together demonstrate the accuracy of EMMREM, and its suitability for a real-time space weather system. We utilize CRaTER to test forecasts made by the Relativistic Electron Alert System for Exploration (REleASE), which successfully predicts the June 7th event. At the maximum CRaTER-observed GCR dose rate (∼11.7 cGy/yr where Gy is a unit indicating energy deposition per unit mass, 1 Gy = 1 J/kg), GCRs deposit ∼88 eV/molecule in water over 4 billion years, causing significant change in molecular composition and physical structure (e.g., density, color, crystallinity) of water ice, loss of molecular hydrogen, and production of more complex molecules linking carbon and other elements in the irradiated ice. This shows that space weathering by GCRs may be extremely important for chemical evolution of ice on the Moon. Thus, we show comprehensive observations from the CRaTER instrument on the Lunar Reconnaissance Orbiter that characterizes the radiation environment and space weathering on the Moon

Performance comparison of two-point linkage methods using microsatellite markers flanking known disease locations

The Genetic Analysis Workshop 14 simulated data presents an interesting, challenging, and plausible example of a complex disease interaction in a dataset. This paper summarizes the ease of detection for each of the simulated Kofendrerd Personality Disorder (KPD) genes across all of the replicates for five standard linkage statistics. Using the KPD affection status, we have analyzed the microsatellite markers flanking each of the disease genes, plus an additional 2 markers that were not linked to any of the disease loci. All markers were analyzed using the following two-point linkage methods: 1) a MMLS, which is a standard admixture LOD score maximized over θ, α, and mode of inheritance, 2) a MLS calculated by GENEHUNTER, 3) the Kong and Cox LOD score as computed by MERLIN, 4) a MOD score (standard heterogeneity LOD maximized over θ, α, and a grid of genetic model parameters), and 5) the PPL, a Bayesian statistic that directly measures the strength of evidence for linkage to a marker. All of the major loci (D1–D4) were detectable with varying probabilities in the different populations. However, the modifier genes (D5 and D6) were difficult to detect, with similar distributions under the null and alternative across populations and statistics. The pooling of the four datasets in each replicate (n = 350 pedigrees) greatly improved the chance of detecting the major genes using all five methods, but failed to increase the chance to detect D5 and D6

Rapid subsurface warming and circulation changes of Antarctic coastal waters by poleward shifting winds

The southern hemisphere westerly winds have been strengthening and shifting poleward since the 1950s. This wind trend is projected to persist under continued anthropogenic forcing, but the impact of the changing winds on Antarctic coastal heat distribution remains poorly understood. Here we show that a poleward wind shift at the latitudes of the Antarctic Peninsula can produce an intense warming of subsurface coastal waters that exceeds 2°C at 200-700 m depth. The model simulated warming results from a rapid advective heat flux induced by weakened near-shore Ekman pumping and is associated with weakened coastal currents. This analysis shows that anthropogenically induced wind changes can dramatically increase the temperature of ocean water at ice sheet grounding lines and at the base of floating ice shelves around Antarctica, with potentially significant ramifications for global sea level rise. Key Points Twenty-first century winds drive Antarctic coastal warming and circulation changes The winds cause coastal isotherms to shoal and weaken coastal currents Fine model grid resolution is required to represent the coastal Ekman dynamic