Interferon-beta stabilizes barrier characteristics of the blood-brain barrier in four different species in vitro

BACKGROUND: Blood-brain barrier (BBB) breakdown is an early event in the pathogenesis of multiple sclerosis (MS). In a previous study we have found a direct stabilization of barrier characteristics after treatment of bovine brain capillary endothelial cells (BCECs) with human recombinant interferon-beta-1a (IFN-beta-1a) in an in vitro BBB model. In the present study we examined the effect of human recombinant IFN-beta-1a on the barrier properties of BCECs derived from four different species including humans to predict treatment efficacy of IFN-beta-1a in MS patients. METHODS: We used primary bovine and porcine BCECs, as well as human and murine BCEC cell lines. We investigated the influence of human recombinant IFN-beta-1a on the paracellular permeability for 3H-inulin and 14C-sucrose across monolayers of bovine, human, and murine BCECs. In addition, the transendothelial electrical resistance (TEER) was determined in in vitro systems applying porcine and murine BCECS. RESULTS: We found a stabilizing effect on the barrier characteristics of BCECs after pretreatment with IFN-beta-1a in all applied in vitro models: addition of IFN-beta-1a resulted in a significant decrease of the paracellular permeability across monolayers of human, bovine, and murine BCECs. Furthermore, the TEER was significantly increased after pretreatment of porcine and murine BCECs with IFN-beta-1a. CONCLUSION: Our data suggest that BBB stabilization by IFN-beta-1a may contribute to its beneficial effects in the treatment of MS. A human in vitro BBB model might be useful as bioassay for testing the treatment efficacy of drugs in MS.

Carbamyl Analogs of Phosphatidylcholines Synthesis, Interaction With Phospholipases and Permeability Behavior of their Liposomes

A novel class of phospholipase-resisting phosphatidylcholine analogs, in which the C-2 ester group or both C-1 and C-2 ester groups have been replaced by carbamyloxy functions (-NH-C-O-), have been synthesized. These lipids were not degraded by phospholipase A2 while complete hydrolysis occurred with phospholipase C. Ultrasonic irradiation of the aqueous dispersions of the phospholipids in the presence as well as in the absence of cholesterol resulted in the formation of closed bilayer structures as evidenced by negative staining electron microscopy and also by their ability to entrap [14C]glucose. The leakage rates of glucose at 37°C from liposomes of these compounds have also been measured. Liposomes consisting of 1,2-dipentadecanylcarbamyloxy-sn-glycero- 3-phosphorylcholine were found to be more leaky (2.1 %/h) as compared to the liposomes of 1-palmitoyl-2-pentadecanylcarbamyloxy-sn -glycero-3-phosphoryl- choline (O.5%/h). Moreover, inclusion of cholesterol (33 mol%) into the bilayers of the former phospholipid had no effect on the leakage rate (2.4%/h) while it effectively reduced permeability of the latter (O.22%/h). These phosphatidylcholines are useful for studying the possible role of phospholipases in the capture and lysis of liposomes in vivo.

Mean age of carbon in fine roots from temperate forests and grasslands with different management

Fine roots are the most dynamic portion of a plant's root system and a major source of soil organic matter. By altering plant species diversity and composition, soil conditions and nutrient availability, and consequently belowground allocation and dynamics of root carbon (C) inputs, land-use and management changes may influence organic C storage in terrestrial ecosystems. In three German regions, we measured fine root radiocarbon (14C) content to estimate the mean time since C in root tissues was fixed from the atmosphere in 54 grassland and forest plots with different management and soil conditions. Although root biomass was on average greater in grasslands 5.1 ± 0.8 g (mean ± SE, n = 27) than in forests 3.1 ± 0.5 g (n = 27) (p < 0.05), the mean age of C in fine roots in forests averaged 11.3 ± 1.8 yr and was older and more variable compared to grasslands 1.7 ± 0.4 yr (p < 0.001). We further found that management affects the mean age of fine root C in temperate grasslands mediated by changes in plant species diversity and composition. Fine root mean C age is positively correlated with plant diversity (r = 0.65) and with the number of perennial species (r = 0.77). Fine root mean C age in grasslands was also affected by study region with averages of 0.7 ± 0.1 yr (n = 9) on mostly organic soils in northern Germany and of 1.8 ± 0.3 yr (n = 9) and 2.6 ± 0.3 (n = 9) in central and southern Germany (p < 0.05). This was probably due to differences in soil nutrient contents and soil moisture conditions between study regions, which affected plant species diversity and the presence of perennial species. Our results indicate more long-lived roots or internal redistribution of C in perennial species and suggest linkages between fine root C age and management in grasslands. These findings improve our ability to predict and model belowground C fluxes across broader spatial scales.

Late Holocene summer temperatures in the central Andes reconstructed from the sediments of high-elevatin Laguna Chepical, Chile (32° S)

High-resolution reconstructions of climate variability that cover the past millennia are necessary to improve the understanding of natural and anthropogenic climate change across the globe. Although numerous records are available for the mid- and high-latitudes of the Northern Hemisphere, global assessments are still compromised by the scarcity of data from the Southern Hemisphere. This is particularly the case for the tropical and subtropical areas. In addition, high elevation sites in the South American Andes may provide insight into the vertical structure of climate change in the mid-troposphere. This study presents a 3000 yr-long austral summer (November to February) temperature reconstruction derived from the 210Pb- and 14C-dated organic sediments of Laguna Chepical (32°16' S, 70°30' W, 3050 m a.s.l.), a high-elevation glacial lake in the subtropical Andes of central Chile. Scanning reflectance spectroscopy in the visible light range provided the spectral index R570/R630, which reflects the clay mineral content in lake sediments. For the calibration period (AD 1901–2006), the R570/R630 data were regressed against monthly meteorological reanalysis data, showing that this proxy was strongly and significantly correlated with mean summer (NDJF) temperatures (R3 yr = −0.63, padj = 0.01). This calibration model was used to make a quantitative temperature reconstruction back to 1000 BC. The reconstruction (with a model error RMSEPboot of 0.33 °C) shows that the warmest decades of the past 3000 yr occurred during the calibration period. The 19th century (end of the Little Ice Age (LIA)) was cool. The prominent warmth reconstructed for the 18th century, which was also observed in other records from this area, seems systematic for subtropical and southern South America but remains difficult to explain. Except for this warm period, the LIA was generally characterized by cool summers. Back to AD 1400, the results from this study compare remarkably well to low altitude records from the Chilean Central Valley and southern South America. However, the reconstruction from Laguna Chepical does not show a warm Medieval Climate Anomaly during the 12–13th century, which is consistent with records from tropical South America. The Chepical record also indicates substantial cooling prior to 800 BC. This coincides with well-known regional as well as global glacier advances which have been attributed to a grand solar minimum. This study thus provides insight into the climatic drivers and temperature patterns in a region for which currently very few data are available. It also shows that since ca. AD 1400, long-term temperature patterns were generally similar at low and high altitudes in central Chile.

Holocene climatic change and the development of the lake-effect snowbelt in Michigan, USA

Lake-effect snow is an important constraint on ecological and socio-economic systems near the North American Great Lakes. Little is known about the Holocene history of lake-effect snowbelts, and it is difficult to decipher how lake-effect snowfall abundance affected ecosystem development. We conducted oxygen-isotope analysis of calcite in lake-sediment cores from northern Lower Michigan to infer Holocene climatic variation and assess snowbelt development. The two lakes experience the same synoptic-scale climatic systems, but only one of them (Huffman Lake) receives a significant amount of lake-effect snow. A 177-cm difference in annual snowfall causes groundwater inflow at Huffman Lake to be 18O-depleted by 2.3‰ relative to O'Brien Lake. To assess when the lake-effect snowbelt became established, we compared calcite-δ18O profiles of the last 11,500 years from these two sites. The chronologies are based on accelerator-mass-spectrometry 14C ages of 11 and 17 terrestrial-plant samples from Huffman and O'Brien lakes, respectively. The values of δ18O are low at both sites from 11,500 to 9500 cal yr BP when the Laurentide Ice Sheet (LIS) exerted a dominant control over the regional climate and provided periodic pulses of meltwater to the Great Lakes basin. Carbonate δ18O increases by 2.6‰ at O'Brien Lake and by 1.4‰ at Huffman Lake between 9500 and 7000 cal yr BP, suggesting a regional decline in the proportion of runoff derived from winter precipitation. The Great Lakes snowbelt probably developed between 9500 and 5500 cal yr BP as inferred from the progressive 18O-depletion at Huffman Lake relative to O'Brien Lake, with the largest increase of lake-effect snow around 7000 cal yr BP. Lake-effect snow became possible at this time because of increasing contact between the Great Lakes and frigid arctic air. These changes resulted from enhanced westerly flow over the Great Lakes as the LIS collapsed, and from rapidly rising Great Lakes levels during the Nipissing Transgression. The δ18O difference between Huffman and O'Brien lakes declines after 5500 cal yr BP, probably because of a northward shift of the polar vortex that brought increasing winter precipitation to the entire region. However, δ18O remains depleted at Huffman Lake relative to O'Brien Lake because of the continued production of lake-effect snow.

Effects of oligotrophication on primary production in peri-alpine lakes

During the second half of the 20th century untreated sewage released from housing and industry into natural waters led to a degradation of many freshwater lakes and reservoirs worldwide. In order to mitigate eutrophication, wastewater treatment plants, including Fe-induced phosphorus precipitation, were implemented throughout the industrialized world, leading to reoligotrophication in many freshwater lakes. To understand and assess the effects of reoligotrophication on primary productivity, we analyzed 28 years of 14C assimilation rates, as well as other biotic and abiotic parameters, such as global radiation, nutrient concentrations and plankton densities in peri-alpine Lake Lucerne, Switzerland. Using a simple productivity-light relationship, we estimated continuous primary production and discussed the relation between productivity and observed limnological parameters. Furthermore, we assessed the uncertainty of our modeling approach based on monthly 14C assimilation measurements using Monte Carlo simulations. Results confirm that monthly sampling of productivity is sufficient for identifying long-term trends in productivity and that conservation management has successfully improved water quality during the past three decades via reducing nutrients and primary production in the lake. However, even though nutrient concentrations have remained constant in recent years, annual primary production varies significantly from year to year. Despite the fact that nutrient concentrations have decreased by more than an order of magnitude, primary production has decreased only slightly. These results suggest that primary production correlates well to nutrients availability but meteorological conditions lead to interannual variability regardless of the trophic status of the lake. Accordingly, in oligotrophic freshwaters meteorological forcing may reduce productivity impacting on the entire food chain of the ecosystem.

Evidence for distinct modes of solar activity

The Sun shows strong variability in its magnetic activity, from Grand minima to Grand maxima, but the nature of the variability is not fully understood, mostly because of the insufficient length of the directly observed solar activity records and of uncertainties related to long-term reconstructions. Here we present a new adjustment-free reconstruction of solar activity over three millennia and study its different modes. Methods. We present a new adjustment-free, physical reconstruction of solar activity over the past three millennia, using the latest verified carbon cycle, 14C production, and archeomagnetic field models. This great improvement allowed us to study different modes of solar activity at an unprecedented level of details. Results. The distribution of solar activity is clearly bi-modal, implying the existence of distinct modes of activity. The main regular activity mode corresponds to moderate activity that varies in a relatively narrow band between sunspot numbers 20 and 67. The existence of a separate Grand minimum mode with reduced solar activity, which cannot be explained by random fluctuations of the regular mode, is confirmed at a high confidence level. The possible existence of a separate Grand maximum mode is also suggested, but the statistics is too low to reach a confident conclusion. Conclusions. The Sun is shown to operate in distinct modes – a main general mode, a Grand minimum mode corresponding to an inactive Sun, and a possible Grand maximum mode corresponding to an unusually active Sun. These results provide important constraints for both dynamo models of Sun-like stars and investigations of possible solar influence on Earth’s climate.

Dating groundwater in the Bohemian Cretaceous Basin: Understanding tracer variations in the subsurface

The northern section of the Bohemian Cretaceous Basin has been the site of intensive U exploitation with harmful impacts on groundwater quality. The understanding of groundwater flow and age distribution is crucial for the prediction of the future dispersion and impact of the contamination. State of the art tracer methods (3H, 3He, 4He, 85Kr, 39Ar and 14C) were, therefore, used to obtain insights to ageing and mixing processes of groundwater along a north–south flow line in the centre of the two most important aquifers of Cenomanian and middle Turonian age. Dating of groundwater is particularly complex in this area as: (i) groundwater in the Cenomanian aquifer is locally affected by fluxes of geogenic and biogenic gases (e.g. CO2, CH4, He) and by fossil brines in basement rocks rich in Cl and SO4; (ii) a thick unsaturated zone overlays the Turonian aquifer; (iii) a periglacial climate and permafrost conditions prevailed during the Last Glacial Maximum (LGM), and iv) the wells are mostly screened over large depth intervals. Large disagreements in 85Kr and 3H/3He ages indicate that processes other than ageing have affected the tracer data in the Turonian aquifer. Mixing with older waters (>50 a) was confirmed by 39Ar activities. An inverse modelling approach, which included time lags for tracer transport throughout the unsaturated zone and degassing of 3He, was used to estimate the age of groundwater. Best fits between model and field results were obtained for mean residence times varying from modern up to a few hundred years. The presence of modern water in this aquifer is correlated with the occurrence of elevated pollution (e.g. nitrates). An increase of reactive geochemical indicators (e.g. Na) and radiogenic 4He, and a decrease in 14C along the flow direction confirmed groundwater ageing in the deeper confined Cenomanian aquifer. Radiocarbon ages varied from a few hundred years to more than 20 ka. Initial 14C activity for radiocarbon dating was calibrated by means of 39Ar measurements. The 14C age of a sample recharged during the LGM was further confirmed by depleted stable isotope signatures and near freezing point noble gas temperature. Radiogenic 4He accumulated in groundwater with concentrations increasing linearly with 14C ages. This enabled the use of 4He to validate the dating range of 14C and extend it to other parts of this aquifer. In the proximity of faults, 39Ar in excess of modern concentrations and 14C dead CO2 sources, elevated 3He/4He ratios and volcanic activity in Oligocene to Quaternary demonstrate the influence of gas of deeper origin and impeded the application of 4He, 39Ar and 14C for groundwater dating.

Fossil and Non-Fossil Sources of Different Carbonaceous Fractions in Fine and Coarse Particles by Radiocarbon Measurement

Radiocarbon offers a unique possibility for unambiguous source apportionment of carbonaceous particles due to a direct distinction of non-fossil and fossil carbon. In this work, particulate matter of different size fractions was collected at 4 sites in Switzerland to examine whether fine and coarse carbonaceous particles exhibit different fossil and contemporary sources. Elemental carbon (EC) and organic carbon (OC) as well as water-soluble OC (WSOC) and water-insoluble OC (WINSOC) were separated and determined for subsequent 14C measurement. In general, both fossil and non-fossil fractions in OC and EC were found more abundant in the fine than in the coarse mode. However, a substantial fraction (~20 ± 5%) of fossil EC was found in coarse particles, which could be attributed to traffic-induced non-exhaust emissions. The contribution of biomass burning to coarse-mode EC in winter was relatively high, which is likely associated to the coating of EC with organic and/or inorganic substances emitted from intensive wood burning. Further, fossil OC (i.e. from vehicle emissions) was found to be smaller than non-fossil OC due to the presence of primary biogenic OC and/or growing in size of wood-burning OC particles during aging processes. 14C content in WSOC indicated that the second organic carbon rather stems from non-fossil precursors for all samples. Interestingly, both fossil and non-fossil WINSOC concentrations were found to be higher in fine particles than in coarse particles in winter, which is likely due to primary wood burning emissions and/or secondary formation of WINSOC.

Middle and Late Pleistocene humid periods recorded in palaeolake deposits of the Nafud desert, Saudi Arabia

Present climate in the Nafud desert of northern Saudi Arabia is hyper-arid and moisture brought by north-westerly winds scarcely reaches the region. The existence of abundant palaeolake sediments provides evidence for a considerably wetter climate in the past. However, the existing chronological framework of these deposits is solely based on radiocarbon dating of questionable reliability, due to potential post-depositional contamination with younger 14C. By using luminescence dating, we show that the lake deposits were not formed between 40 and 20 ka as suggested previously, but approximately ca 410 ka, 320 ka, 200 ka, 125 ka, and 100 ka ago. All of these humid phases are in good agreement with those recorded in lake sediments and speleothems from southern Arabia. Surprisingly, no Holocene lake deposits were identified. Geological characteristics of the deposits and diatom analysis suggest that a single, perennial lake covered the entire south-western Nafud ca 320 ka ago. In contrast, lakes of the 200 ka, 125 ka, and 100 ka humid intervals were smaller and restricted to interdune depressions of a pre-existing dune relief. The concurrent occurrence of humid phases in the Nafud, southern Arabia and the eastern Mediterranean suggests that moisture in northern Arabia originated either from the Mediterranean due to more frequent frontal depression systems or from stronger Indian monsoon circulation, respectively. However, based on previously published climate model simulations and palaecolimate evidence from central Arabia and the Negev desert, we argue that humid climate conditions in the Nafud were probably caused by a stronger African monsoon and a distinct change in zonal atmospheric circulation.

Radiocarbon impact in a nearby tree of a light-water VVER type nuclear power plant, Paks, Hungary

Tree-ring series were collected for radiocarbon analyses from the vicinity of Paks nuclear power plant (NPP) and a background area (Dunaföldvár) for a 10-yr period (2000–2009). Samples of holocellulose were prepared from the wood and converted to graphite for accelerator mass spectrometry (AMS) 14C measurement using the MICADAS at ETH Zürich. The 14C concentration data from these tree rings was compared to the background tree rings for each year. The global decreasing trend of atmospheric 14C activity concentration was observed in the annual tree rings both in the background area and in the area of the NPP. As an average of the past 10 yr, the excess 14C emitted by the pressurized-water reactor (PWR) NPP to the atmosphere shows only a slight systematic excess (~6‰) 14C in the annual rings. The highest 14C excess was 13‰ (in 2006); however, years with the same 14C level as the background were quite frequent in the tree-ring series.

Effects of sources and meteorology on particulate matter in the Western Mediterranean Basin: An overview of the DAURE campaign

DAURE (Determination of the Sources of Atmospheric Aerosols in Urban and Rural Environments in the Western Mediterranean) was a multidisciplinary international field campaign aimed at investigating the sources and meteorological controls of particulate matter in the Western Mediterranean Basin (WMB). Measurements were simultaneously performed at an urban-coastal (Barcelona, BCN) and a rural-elevated (Montseny, MSY) site pair in NE Spain during winter and summer. State-of-the-art methods such as 14C analysis, proton-transfer reaction mass spectrometry, and high-resolution aerosol mass spectrometry were applied for the first time in the WMB as part of DAURE. WMB regional pollution episodes were associated with high concentrations of inorganic and organic species formed during the transport to inland areas and built up at regional scales. Winter pollutants accumulation depended on the degree of regional stagnation of an air mass under anticyclonic conditions and the planetary boundary layer height. In summer, regional recirculation and biogenic secondary organic aerosols (SOA) formation mainly determined the regional pollutant concentrations. The contribution from fossil sources to organic carbon (OC) and elemental carbon (EC) and hydrocarbon-like organic aerosol concentrations were higher at BCN compared with MSY due to traffic emissions. The relative contribution of nonfossil OC was higher at MSY especially in summer due to biogenic emissions. The fossil OC/EC ratio at MSY was twice the corresponding ratio at BCN indicating that a substantial fraction of fossil OC was due to fossil SOA. In winter, BCN cooking emissions were identified as an important source of modern carbon in primary organic aerosol.

On the stratigraphic integrity of leaf-wax biomarkers in loess paleosols

Paleoenvironmental and paleoclimate reconstructions based on molecular proxies, such as those derived from leaf-wax biomarkers, in loess-paleosol sequences represent a promising line of investigation in Quaternary research. The main premise of such reconstructions is the synsedimentary deposition of biomarkers and dust, which has become a debated subject in recent years. This study uses two independent approaches to test the stratigraphic integrity of leaf-wax biomarkers: (i) long-chain n-alkanes and fatty acids are quantified in two sediment-depth profiles in glacial till on the Swiss Plateau, consisting of a Holocene topsoil and the underlying B and C horizons. Since glacial sediments are initially very poor in organic matter, significant amounts of leaf-wax biomarkers in the B and C horizons of those profiles would reflect postsedimentary root-derived or microbial contributions. (ii) Compound-specific radiocarbon measurements are conducted on n-alkanes and n-alkanoic (fatty) acids from several depth intervals in the loess section "Crvenka", Serbia, and the results are compared to independent estimates of sediment age. We find extremely low concentrations of plant-wax n-alkanes and fatty acids in the B and C horizons below the topsoils in the sediment profiles. Moreover, compound-specific radiocarbon analysis yields plant-wax 14C ages that agree well with published luminescence ages and stratigraphy of the Serbian loess deposit. Both approaches confirm that postsedimentary, root-derived or microbial contributions are negligible in the two investigated systems. The good agreement between the ages of odd and even homologues also indicates that reworking and incorporation of fossil leaf waxes is not particularly relevant either.

Diurnal cycle of fossil and nonfossil carbon using radiocarbon analyses during CalNex

Radiocarbon (14C) analysis is a unique tool to distinguish fossil/nonfossil sources of carbonaceous aerosols. We present 14C measurements of organic carbon (OC) and total carbon (TC) on highly time resolved filters (3–4 h, typically 12 h or longer have been reported) from 7 days collected during California Research at the Nexus of Air Quality and Climate Change (CalNex) 2010 in Pasadena. Average nonfossil contributions of 58% ± 15% and 51% ± 15% were found for OC and TC, respectively. Results indicate that nonfossil carbon is a major constituent of the background aerosol, evidenced by its nearly constant concentration (2–3 μgC m−3). Cooking is estimated to contribute at least 25% to nonfossil OC, underlining the importance of urban nonfossil OC sources. In contrast, fossil OC concentrations have prominent and consistent diurnal profiles, with significant afternoon enhancements (~3 μgC m−3), following the arrival of the western Los Angeles (LA) basin plume with the sea breeze. A corresponding increase in semivolatile oxygenated OC and organic vehicular emission markers and their photochemical reaction products occurs. This suggests that the increasing OC is mostly from fresh anthropogenic secondary OC (SOC) from mainly fossil precursors formed in the western LA basin plume. We note that in several European cities where the diesel passenger car fraction is higher, SOC is 20% less fossil, despite 2–3 times higher elemental carbon concentrations, suggesting that SOC formation from gasoline emissions most likely dominates over diesel in the LA basin. This would have significant implications for our understanding of the on-road vehicle contribution to ambient aerosols and merits further study.

Investigation of young water inflow in karst aquifers using SF6–CFC–3H/He–85Kr–39Ar and stable isotope components

Karst aquifers are known for their wide distribution of water transfer velocities. From this observation, a multiple geochemical tracer approach seems to be particularly well suited to provide a significant assessment of groundwater flows, but the choice of adapted tracers is essential. In this study, several common tracers in karst aquifers such as physicochemical parameters, major ions, stable isotopes, and d13C to more specific tracers such as dating tracers – 14C, 3H, 3H–3He, CFC-12, SF6 and 85Kr, and 39Ar – were used, in a fractured karstic carbonated aquifer located in Burgundy (France). The information carried by each tracer and the best sampling strategy are compared on the basis of geochemical monitoring done during several recharge events and over longer time periods (months to years). This study’s results demonstrate that at the seasonal and recharge event time scale, the variability of concentrations is low for most tracers due to the broad spectrum of groundwater mixings. The tracers used traditionally for the study of karst aquifers, i.e., physicochemical parameters and major ions, efficiently describe hydrological processes such as the direct and differed recharge, but require being monitored at short time steps during recharge events to be maximized. From stable isotopes, tritium, and Cl� contents, the proportion of the fast direct recharge by the largest porosity was estimated using a binary mixing model. The use of tracers such as CFC-12, SF6, and 85Kr in karst aquifers provides additional information, notably an estimation of apparent age, but they require good preliminary knowledge of the karst system to interpret the results suitably. The CFC-12 and SF6 methods efficiently determine the apparent age of baseflow, but it is preferable to sample the groundwater during the recharge event. Furthermore, these methods are based on different assumptions such as regional enrichment in atmospheric SF6, excess air, and flow models among others. 85Kr and 39Ar concentrations can potentially provide a more direct estimation of groundwater residence time. Conversely, the 3H–3He method is inefficient in the karst aquifer for dating due to 3He degassing.