Mutations in one or more genes encoding complement‐regulatory proteins predispose to atypical hemolytic uremic syndrome (aHUS) and its recurrence following kidney transplantation. We evaluated plasma ...complement level and performed a screening for mutations in genes encoding complement Factors H and I (CFH, CFI) and membrane cofactor protein (MCP) in 24 kidney transplant recipients experiencing de novo thrombotic microangiopathy (TMA). Six patients presented with low C3 and/or low Factor B levels suggestive complement alternative pathway. A mutation in the CFH or CFI gene was found in 7/24 patients (29%), two of whom had a mutation in both genes. On the contrary, no mutation was identified in a control kidney transplant patients group (n = 25) without TMA. Patients with or without mutations were similar with regard to clinical features. Eight out of 24 patients lost their graft within 1 year of posttransplantation including six patients with a CFH mutation or a decrease of C3 or CFB in plasma. To conclude, kidney transplant patients with de novo TMA exhibit an unexpectedly high frequency of CFH and CFI mutations. These results suggest that genetic abnormalities may represent risk factors for de novo TMA after kidney transplantation and raise the question of the best therapeutic strategy.
Kidney transplant patients with de novo TMA exhibit an unexpectedly high frequency of mutations in genes encoding for complement regulatory proteins (Factor H and Factor I).
•We present a framework for identifying the optimal landscape configuration for multifunctionality.•The optimal configuration can be predicted from the response of individual services to local and ...landscape factors.•We show that services sharing the same optimal landscape configuration strategy form management bundles.
Increased pressure on land resources to provide multiple benefits calls for landscape strategies that optimize the supply of multiple ecosystem services (ES). Previous research into the drivers of landscape multifunctionality have focused on land use composition changes, but the spatial configuration of different land use types also drives ES supply. While the impact of landscape configuration on individual ES is well understood, the net outcome of these influences when considering many ES is not. Here we present the net-balance spatial interactions hypothesis, which posits that the strength and direction of local and surrounding landscape influences on the local supply of an individual ES will drive its optimal landscape configuration. Accordingly, the net balance of these influences across multiple prioritized ES will determine the optimal configuration for landscape multifunctionality. Further, ES that share the same optimal configuration strategy form a bundle that can be managed together. Using data from German grasslands we demonstrate that the net-balance spatial interactions hypothesis is applicable to land-use planning scenarios that aim to maximize multiple ES. It allows general rules to be applied when local, detailed ES data is not available, and can help identify the best option to minimize trade-offs in the face of multiple competing land-use objectives.
Hundreds of small RNAs of ∼22 nucleotides, collectively named microRNAs (miRNAs), have been discovered recently in animals and plants. Although their functions are being unravelled, their mechanism ...of biogenesis remains poorly understood. miRNAs are transcribed as long primary transcripts (pri-miRNAs) whose maturation occurs through sequential processing events: the nuclear processing of the pri-miRNAs into stem-loop precursors of ∼70 nucleotides (pre-miRNAs), and the cytoplasmic processing of pre-miRNAs into mature miRNAs. Dicer, a member of the RNase III superfamily of bidentate nucleases, mediates the latter step, whereas the processing enzyme for the former step is unknown. Here we identify another RNase III, human Drosha, as the core nuclease that executes the initiation step of miRNA processing in the nucleus. Immunopurified Drosha cleaved pri-miRNA to release pre-miRNA in vitro. Furthermore, RNA interference of Drosha resulted in the strong accumulation of pri-miRNA and the reduction of pre-miRNA and mature miRNA in vivo. Thus, the two RNase III proteins, Drosha and Dicer, may collaborate in the stepwise processing of miRNAs, and have key roles in miRNA-mediated gene regulation in processes such as development and differentiation.
Erdheim–Chester disease (ECD) pathophysiology remains largely unknown. Its treatment is not codified and usually disappointing. Interferon (IFN)-α therapy lacks efficacy for some life-threatening ...manifestations and has a poor tolerance profile. Because interleukin (IL)-1Ra synthesis is naturally induced after stimulation by IFN-α, we hypothesized that recombinant IL-1Ra (anakinra) might have some efficacy in ECD. We treated 2 patients who had poor tolerance or contraindication to IFN-α with anakinra as a rescue therapy and measured their serum C-reactive protein, IL-1β, IL-6, and monocytic membranous IL-1α (mIL-1α) levels before, under, and after therapy. Another untreated ECD patient and 5 healthy subjects were enrolled as controls. After treatment, fever and bone pains rapidly disappeared in both patients, as well as eyelid involvement in one patient. In addition, retroperitoneal fibrosis completely or partially regressed, and C-reactive protein, IL-6, and mIL-1α levels decreased to within the normal and control range. Beside injection-site reactions, no adverse event was reported. Therefore, our results support a central role of the IL-1 network, which seemed to be overstimulated in ECD. Its specific blockade using anakinra thereby opens new pathophysiology and therapeutic perspectives in ECD.
Land-use intensification is a major driver of biodiversity loss. However, understanding how different components of land use drive biodiversity loss requires the investigation of multiple trophic ...levels across spatial scales. Using data from 150 agricultural grasslands in central Europe, we assess the influence of multiple components of local- and landscape-level land use on more than 4,000 above- and belowground taxa, spanning 20 trophic groups. Plot-level land-use intensity is strongly and negatively associated with aboveground trophic groups, but positively or not associated with belowground trophic groups. Meanwhile, both above- and belowground trophic groups respond to landscape-level land use, but to different drivers: aboveground diversity of grasslands is promoted by diverse surrounding land-cover, while belowground diversity is positively related to a high permanent forest cover in the surrounding landscape. These results highlight a role of landscape-level land use in shaping belowground communities, and suggest that revised agroecosystem management strategies are needed to conserve whole-ecosystem biodiversity.
The ECLAIRs space telescope is the main French contribution to the payload of the SVOM Chinese-French mission, aiming at being the next gamma ray bursts multi-wavelength observatory. By detecting the ...very first lights of the gamma ray burst, the ECLAIRs telescope will be the initiator of the measurement process based on a complementary network of space and ground instruments. Since the beginning of 2006, this instrument has been developed within the SVOM international context. The whole architecture is based on a combination of 3 key solutions: the coded mask imaging, a compact ASIC-CdTe hybrid detector with thermal control, and an onboard powerful processor for gamma ray burst detection. Each of those elements has needed specific developments and optimized solutions in order to reach the expected performances.
The impact of local biodiversity loss on ecosystem functioning is well established, but the role of larger-scale biodiversity dynamics in the delivery of ecosystem services remains poorly understood. ...Here we address this gap using a comprehensive dataset describing the supply of 16 cultural, regulating and provisioning ecosystem services in 150 European agricultural grassland plots, and detailed multi-scale data on land use and plant diversity. After controlling for land-use and abiotic factors, we show that both plot-level and surrounding plant diversity play an important role in the supply of cultural and aboveground regulating ecosystem services. In contrast, provisioning and belowground regulating ecosystem services are more strongly driven by field-level management and abiotic factors. Structural equation models revealed that surrounding plant diversity promotes ecosystem services both directly, probably by fostering the spill-over of ecosystem service providers from surrounding areas, and indirectly, by maintaining plot-level diversity. By influencing the ecosystem services that local stakeholders prioritized, biodiversity at different scales was also shown to positively influence a wide range of stakeholder groups. These results provide a comprehensive picture of which ecosystem services rely most strongly on biodiversity, and the respective scales of biodiversity that drive these services. This key information is required for the upscaling of biodiversity-ecosystem service relationships, and the informed management of biodiversity within agricultural landscapes.
Future in astroparticle physics and observational cosmology Carr, J.
Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment,
03/2007, Volume:
572, Issue:
1
Journal Article, Conference Proceeding
Peer reviewed
This article is based on an introductory presentation at the 10th Pisa Meeting on Frontier Detectors for Frontier Physics at Elba in May 2006. A sample of results and expected future advances in the ...field of astroparticle physics are presented.
ANTARES: The first undersea neutrino telescope Ageron, M.; Anghinolfi, M.; Ardid, M. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
11/2011, Volume:
656, Issue:
1
Journal Article
Peer reviewed
Open access
The ANTARES Neutrino Telescope was completed in May 2008 and is the first operational Neutrino Telescope in the Mediterranean Sea. The main purpose of the detector is to perform neutrino astronomy ...and the apparatus also offers facilities for marine and Earth sciences. This paper describes the design, the construction and the installation of the telescope in the deep sea, offshore from Toulon in France. An illustration of the detector performance is given.
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