Functional Interleukin-17 Receptor A is Expressed in Central Nervous System Glia and Upregulated in Experimental Autoimmune Encephalomyelitis

Background: Interleukin-17A (IL-17A) is the founding member of a novel family of inflammatory cytokines that plays a critical role in the pathogenesis of many autoimmune diseases, including multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). IL-17A signals through its receptor, IL-17RA, which is expressed in many peripheral tissues; however, expression of IL-17RA in the central nervous system (CNS) and its role in CNS inflammation are not well understood. Methods: EAE was induced in C57Bl/6 mice by immunization with myelin oligodendroglial glycoprotein. IL-17RA expression in the CNS was compared between control and EAE mice using RT-PCR, in situ hybridization, and immunohistochemistry. Cell-type specific expression was examined in isolated astrocytic and microglial cell cultures. Cytokine and chemokine production was measured in IL-17A treated cultures to evaluate the functional status of IL-17RA. Results: Here we report increased IL-17RA expression in the CNS of mice with EAE, and constitutive expression of functional IL-17RA in mouse CNS tissue. Specifically, astrocytes and microglia express IL-17RA in vitro, and IL-17A treatment induces biological responses in these cells, including significant upregulation of MCP-1, MCP-5, MIP-2 and KC chemokine secretion. Exogenous IL-17A does not significantly alter the expression of IL-17RA in glial cells, suggesting that upregulation of chemokines by glial cells is due to IL-17A signaling through constitutively expressed IL-17RA. Conclusion: IL-17RA expression is significantly increased in the CNS of mice with EAE compared to healthy mice, suggesting that IL-17RA signaling in glial cells can play an important role in autoimmune inflammation of the CNS and may be a potential pathway to target for therapeutic interventions. © 2009 Sarma et al; licensee BioMed Central Ltd.

Direct versus delayed pathways in strong-field non-sequential double ionization

We report full-dimensionality quantum and classical calculations of double ionization (DI) of laser-driven helium at 390 nm. Good agreement is observed. We identify the relative importance of the two main non-sequential DI pathways, the direct|with an almost simultaneous ejection of both electrons|and the delayed. We find that the delayed pathway prevails at small intensities independently of total electron energy but at high intensities the direct pathway predominates up to a certain upper-limit in total energy which increases with intensity. An explanation for this increase with intensity is provided.

Late Holocene climate change in central Sweden inferred from lacustrine stable isotope data

Stable isotopes (delta O-18 and delta C-13) of lacustrine carbonates (Chara spp. algae and Pisidium spp. molluscs) from a lake sedimentary sequence in central Sweden were analysed to infer changes in lake hydrology and climate during the late Holocene. Results from analysis of lake water isotopes (delta O-18 and delta H-2) show that Lake Blektjarnen water isotope composition is responsive to the balance between evaporation and input water (E/l ratio). A high E/l ratio results from a dry and probably warmer climate, decreasing the relative importance of precipitation input. Under such conditions evaporation and atmospheric equilibration probably enrich lake water in O-18 and C-13, respectively, which is reflected in the isotopic composition of the carbonates in the lake. From the relatively positive Chara delta O-18 values we infer that conditions were dry and warm between 4400 and 4000 cal. a BP, whereas more negative values indicate that conditions were wetter and probably cooler between 4000 and 3000 cal. a BP. A drier climate is inferred from more positive values between 2500 and 1000 cal. a BP. However, a successive depletion after ca. 1750 cal. a BP, also detected in several other delta O-18 records (carbonate and diatom), suggest increasingly wetter conditions in Scandinavia after that time, which is probably related to increased strength of the zonal flow.

Two-dimensional particle-in-cell simulation of the expansion of a plasma into a rarefied medium

The expansion of a dense plasma through a more rarefied ionized medium has been studied by means of two-dimensional particle-in-cell simulations. The initial conditions involve a density jump by a factor of 100, located in the middle of an otherwise equally dense electron-proton plasma with uniform proton and electron temperatures of 10 eV and 1 keV, respectively. Simulations show the creation of a purely electrostatic collisionless shock together with an ion-acoustic soliton tied to its downstream region. The shock front is seen to evolve in filamentary structures consistently with the onset of the ion-ion instability. Meanwhile, an un-magnetized drift instability is triggered in the core part of the dense plasma. Such results explain recent experimental laser-plasma experiments, carried out in similar conditions, and are of intrinsic relevance to non-relativistic shock scenarios in the solar and astrophysical systems.

Pilgrimstad revisited - a multi-proxy reconstruction of Early/Middle Weichselian climate and environment at a key site in central Sweden

The site Pilgrimstad in central Sweden has often been cited as a key locality for discussions of ice-free/ice-covered intervals during the Early and Middle Weichselian. Multi-proxy investigations of a recently excavated section at Pilgrimstad now provide a revised picture of the climatic and environmental development between similar to 80 and 36 ka ago. The combination of sedimentology, geochemistry, OSL and 14C dating, and macrofossil, siliceous microfossil and chironomid analyses shows: (i) a lower succession of glaciofluvial/fluvial, lacustrine and glaciolacustrine sediments; (ii) an upper lacustrine sediment sequence; and (iii) Last Glacial Maximum till cover. Microfossils in the upper lacustrine sediments are initially characteristic for oligo- to mesotrophic lakes, and macrofossils indicate arctic/sub-arctic environments and mean July temperatures > 8 degrees C. These conditions were, however, followed by a return to a low-nutrient lake and a cold and dry climate. The sequence contains several hiatuses, as shown by the often sharp contacts between individual units, which suggests that ice-free intervals alternated with possible ice advances during certain parts of the Early and Middle Weichselian.