Forcing mechanisms behind variations in TOC concentration of lake waters Forcing mechanisms behind variations in total organic carbon (TOC) concentration of lake waters during the past eight centuries – palaeolimnological evidence from southern Sweden Forcing mechanisms behind variations in TOC concentration of lake waters

International audienceDecadal-scale variations in total organic carbon (TOC) concentration in lake water since AD 1200 in two small lakes in southern Sweden were reconstructed based on visible-near infrared spectroscopy (VNIRS) of their recent sediment successions. In order to assess the impacts of local land-use changes and regional variations in 5 sulphur deposition and climate on the inferred changes in TOC concentration, the same sediment records were subjected to multi-proxy palaeolimnological analyses. Changes in lake-water pH were inferred from diatom analysis, whereas pollen-based land-use reconstructions (Landscape Reconstruction Algorithm) together with geo-chemical records provided information on catchment-scale environmental changes, 10 and comparisons were made with available records of climate and population density. Our long-term reconstructions reveal that TOC concentrations were generally high prior to AD 1900, with second-order variations coupled mainly to changes in agricultural land-use intensity. The last century showed significant changes, and unusually low TOC concentrations were recorded in 1930–1990, followed by a recent increase. Vari-15 ations in sulphur emissions, with an increase in the early 1900s to a peak around AD 1980 and a subsequent decrease, were most likely the main driver of these dynamics, although processes related to the introduction of modern forestry and recent increases in precipitation and temperature may have contributed. The increase in lake-water TOC concentration from around AD 1980 may therefore reflect a recovery process. Given 20 that the effects of sulphate deposition now subside, other forcing mechanisms related to land management and climate change will possibly become the main drivers of TOC concentration changes in boreal lake waters in the future

Historical TOC concentration minima during peak sulfur deposition in two Swedish lakes

International audienceDecadal-scale variations in total organic carbon (TOC) concentration in lake water since AD 1200 in two small lakes in southern Sweden were reconstructed based on visible–near-infrared spectroscopy (VNIRS) of their recent sediment successions. In order to assess the impacts of local land-use changes, regional variations in sulfur, and nitrogen deposition and climate variations on the inferred changes in TOC concentration, the same sediment records were subjected to multi-proxy palaeolimnological analyses. Changes in lake-water pH were inferred from diatom analysis , whereas pollen-based land-use reconstructions (Landscape Reconstruction Algorithm) together with geochemical records provided information on catchment-scale environmental changes, and comparisons were made with available records of climate and population density. Our long-term reconstructions reveal that inferred lake-water TOC concentrations were generally high prior to AD 1900, with additional variability coupled mainly to changes in forest cover and agricultural land-use intensity. The last century showed significant changes, and unusually low TOC concentrations were inferred at AD 1930–1990, followed by a recent increase , largely consistent with monitoring data. Variations in sulfur emissions, with an increase in the early 1900s to a peak around AD 1980 and a subsequent decrease, were identified as an important driver of these dynamics at both sites, while processes related to the introduction of modern forestry and recent increases in precipitation and temperature may have contributed, but the effects differed between the sites. The increase in lake-water TOC concentration from around AD 1980 may therefore reflect a recovery process. Given that the effects of sulfur deposition now subside and that the recovery of lake-water TOC concentrations has reached pre-industrial levels, other forcing mechanisms related to land management and climate change may become the main drivers of TOC concentration changes in boreal lake waters in the future

Two hundred years of land-use change in the South Swedish Uplands : comparison of historical map-based estimates with a pollen-based reconstruction using the landscape reconstruction algorithm

International audienceLong-term records of environmental history at decadal to millennial timescales enable an assessment of ecosystem variability and responses to past anthropogenic disturbances and are fundamental for the development of environmental management strategies. This study examines the local variability of land-use history in the South Swedish Uplands over the last 200 years based on pollen records from three lake-sediment successions. Temporal changes in the proportional cover of 14 plant taxa were quantified as percentages using the landscape reconstruction algorithm (LRA). The LRA-based estimates of the extent of four land-use categories (cropland, meadows/grassland, wetland, outland/woodland) were compared to corresponding estimates based on historical maps and aerial photographs from AD 1769–1823, 1837–1895, 1946 and 2005. Although the LRA approach tends to overestimate grassland cover by 10–30 % for the two earliest time periods, the reconstructed vegetation composition is generally in good agreement with estimates based on the historical records. Subsequently, the LRA approach was used to reconstruct the 200-year history of local land-use dynamics at 20-year intervals around two small lakes. The qualitative assessment of difference approach , which requires fewer assumptions and parameters than LRA for objective evaluation of between-site differences in plant abundances, provides consistent results in general. Significant differences exist in the land-use history between the sites. Local catchment characteristics, such as soil conditions and wetland cover, appear important for the development of human impact on the landscape. Quantifi-cations of past vegetation dynamics provide information on the amplitude, frequency and duration of the land-use changes and their effects on terrestrial and aquatic ecosystems , and should be taken into account when nature conservation strategies are developed

SC83288 is a clinical development candidate for the treatment of severe malaria

Severe malaria is a life-threatening complication of an infection with the protozoan parasite Plasmodium falciparum, which requires immediate treatment. Safety and efficacy concerns with currently used drugs accentuate the need for new chemotherapeutic options against severe malaria. Here we describe a medicinal chemistry program starting from amicarbalide that led to two compounds with optimized pharmacological and antiparasitic properties. SC81458 and the clinical development candidate, SC83288, are fast-acting compounds that can cure a P. falciparum infection in a humanized NOD/SCID mouse model system. Detailed preclinical pharmacokinetic and toxicological studies reveal no observable drawbacks. Ultra-deep sequencing of resistant parasites identifies the sarco/endoplasmic reticulum Ca(2+) transporting PfATP6 as a putative determinant of resistance to SC81458 and SC83288. Features, such as fast parasite killing, good safety margin, a potentially novel mode of action and a distinct chemotype support the clinical development of SC83288, as an intravenous application for the treatment of severe malaria

Towards an In Vitro Model of Plasmodium Hypnozoites Suitable for Drug Discovery

Contains fulltext : 96475.pdf (publisher's version ) (Open Access)BACKGROUND: Amongst the Plasmodium species in humans, only P. vivax and P. ovale produce latent hepatic stages called hypnozoites, which are responsible for malaria episodes long after a mosquito bite. Relapses contribute to increased morbidity, and complicate malaria elimination programs. A single drug effective against hypnozoites, primaquine, is available, but its deployment is curtailed by its haemolytic potential in glucose-6-phosphate dehydrogenase deficient persons. Novel compounds are thus urgently needed to replace primaquine. Discovery of compounds active against hypnozoites is restricted to the in vivo P. cynomolgi-rhesus monkey model. Slow growing hepatic parasites reminiscent of hypnozoites had been noted in cultured P. vivax-infected hepatoma cells, but similar forms are also observed in vitro by other species including P. falciparum that do not produce hypnozoites. METHODOLOGY: P. falciparum or P. cynomolgi sporozoites were used to infect human or Macaca fascicularis primary hepatocytes, respectively. The susceptibility of the slow and normally growing hepatic forms obtained in vitro to three antimalarial drugs, one active against hepatic forms including hypnozoites and two only against the growing forms, was measured. RESULTS: The non-dividing slow growing P. cynomolgi hepatic forms, observed in vitro in primary hepatocytes from the natural host Macaca fascicularis, can be distinguished from similar forms seen in P. falciparum-infected human primary hepatocytes by the differential action of selected anti-malarial drugs. Whereas atovaquone and pyrimethamine are active on all the dividing hepatic forms observed, the P. cynomolgi slow growing forms are highly resistant to treatment by these drugs, but remain susceptible to primaquine. CONCLUSION: Resistance of the non-dividing P. cynomolgi forms to atovaquone and pyrimethamine, which do not prevent relapses, strongly suggests that these slow growing forms are hypnozoites. This represents a first step towards the development of a practical medium-throughput in vitro screening assay for novel hypnozoiticidal drugs

Modern and fossil non-pollen palynomorphs from the Basque mountains (western Pyrenees, France): the use of coprophilous fungi to reconstruct pastoral activity

International audienceThis paper presents results from a modern dataset of non-pollen palynomorphs and its application to aca. 2,000 year peat record from the same area in the western Pyrenees (Basque Country, France). The modern dataset is composed of 35 surface samples (moss polsters) from a mountainous pasture-woodland landscape. Airborne fungal spores (ascospores and conidia), found dominant in the dataset, are linked to the degree of landscape openness and grazing pressure. The complete spectrum of 13 selected spore-types of dung-related Ascomycetes is positively linked with grazing pressure. However, different dung affinities between the spore-types have been identified. These are types clearly related to high grazing pressure and types with no or unclear dung indicative value. The modern dataset is used to aid interpretation of the local fossil pollen record as an independent 'proxy' to assess past pastoral dynamics. This study confirms the utility of modern nonpollen palynomorphs from terrestrial ecosystems in the reconstruction of historical local pastoral activities but also shows their limitation. It may be necessary to extend such study to wetland ecosystems and to investigate the spatial dimension of some fungal spores

Erratum: SC83288 is a clinical development candidate for the treatment of severe malaria

No abstract available

Inhibitory Effect of TNF-α on Malaria Pre-Erythrocytic Stage Development: Influence of Host Hepatocyte/Parasite Combinations

BACKGROUND: The liver stages of malaria parasites are inhibited by cytokines such as interferon-gamma or Interleukin (IL)-6. Binding of these cytokines to their receptors at the surface of the infected hepatocytes leads to the production of nitric oxide (NO) and radical oxygen intermediates (ROI), which kill hepatic parasites. However, conflicting results were obtained with TNF-alpha possibly because of differences in the models used. We have reassessed the role of TNF-alpha in the different cellular systems used to study the Plasmodium pre-erythrocytic stages. METHODS AND FINDINGS: Human or mouse TNF-alpha were tested against human and rodent malaria parasites grown in vitro in human or rodent primary hepatocytes, or in hepatoma cell lines. Our data demonstrated that TNF-alpha treatment prevents the development of malaria pre-erythrocytic stages. This inhibitory effect however varies with the infecting parasite species and with the nature and origin of the cytokine and hepatocytes. Inhibition was only observed for all parasite species tested when hepatocytes were pre-incubated 24 or 48 hrs before infection and activity was directed only against early hepatic parasite. We further showed that TNF-alpha inhibition was mediated by a soluble factor present in the supernatant of TNF-alpha stimulated hepatocytes but it was not related to NO or ROI. Treatment TNF-alpha prevents the development of human and rodent malaria pre-erythrocytic stages through the activity of a mediator that remains to be identified. CONCLUSIONS: Treatment TNF-alpha prevents the development of human and rodent malaria pre-erythrocytic stages through the activity of a mediator that remains to be identified. However, the nature of the cytokine-host cell-parasite combination must be carefully considered for extrapolation to the human infection

Multidisciplinary approach to reconstructing local pastoral activities: an example from the Pyrenean Mountains (Pays Basque)

International audienceIn this study archaeology, history and palaeoecology (modern and fossil data sets of pollen and nonpollen palynomorphs) were used to reconstruct small-scale pastoral activities in the Pyrenees Mountains during the last two millennia. Modern pollen assemblages from the major vegetation units (both natural andanthropogenic) are studied on one restricted watershed area. A correlative model (RDA) of 61 modern pollen spectra and 35 external variables distinguishes two groups of taxa, providing information on the nature and spatial extent of human impact on the landscape. The first pool indicates local pastoral activities, and the second one implies regional input from outside the studied watershed, and is not characteristic of a specific land use. These pools are described as 'Local Pastoral Pollen Indicators' (LPPI) for this particular mountain region on crystalline bedrock and 'Regional Human Activities Pollen Indicators' (RHAPI). The modern data set is used to aid interpretation of the local pollen sequence of Sourzay that covers the last 2000 calendar years BP, using RDA reconstructions, and best modern analogues as a means of comparing modern and fossil spectra. The study also demonstrates agreement between the independent interpretations of two fossil proxies, LPPI and coprophilous fungi