Multiscale investigations in a mesoscale catchment ? hydrological modelling in the Gera catchment

International audienceThe application of the hydrological process-oriented model J2000 (J2K) is part of a cooperation project between the Thuringian Environmental Agency (Thüringer Landesanstalt für Umwelt und Geologie ? TLUG) and the Department of Geoinformatics of the Friedrich-Schiller-University Jena focussing on the implementation of the EU water framework directive (WFD). In the first project phase J2K was parametrised and calibrated for a mesoscale catchment to quantify if it can be used as hydrological part of a multi-objective tool-box needed for the implementation of the WFD. The main objectives for that pilot study were: The development and application of a suitable distribution concept which provide the spatial data basis for various tasks and which reflects the specific physiogeographical variability and heterogeneity of river basins adequately. This distribution concept should consider the following constraints: The absolute number of spatial entities, which forms the basis for any distributive modelling should be as small as possible, but the spatial distributed factors, which controls quantitative and qualitative hydrological processes should not be generalised to much. The distribution concept of hydrological response units HRUs (Flügel, 1995) was selected and enhanced by a topological routing scheme (Staudenrausch, 2001) for the simulation of lateral flow processes. J2K should be calibrated for one subbasin of the pilot watershed only. Then the parameter set should be used on the other subbasins (referred as transfer basins) to investigate and quantify the transferability of a calibrated model and potential spatial dependencies of its parameter set. In addition, potential structural problems in the process description should be identified by the transfer to basins which show a different process dominance as the one which was used for calibration does. Model calibration and selection of efficiency criteria for the quantification of the model quality should be based on a comprehensive sensitivity and uncertainty analysis (Bäse, 2005) and multi-response validations with independent data sets (Krause and Flügel, 2005) carried out in advance in the headwater part of the calibration basin. To obtain good results in the transfer basins the calibrated parameter set could be adjusted slightly. This step was considered as necessary because of specific constraints which were not of significant importance in the calibration basin. This readjustment should be carried out on parameters which show a sensitive reaction on the identified differences in the environmental setup. Potential scaling problems of the process description, distribution concept or model structure should be identified by the comparison of the modelling results obtained in a small headwater region of the calibration basin with observed streamflow to find out if the selected efficiency measures show a significant change

Nicotinic acid adenine dinucleotide phosphate-mediated calcium signalling in effector T cells regulates autoimmunity of the central nervous system

Nicotinic acid adenine dinucleotide phosphate represents a newly identified second messenger in T cells involved in antigen receptor-mediated calcium signalling. Its function in vivo is, however, unknown due to the lack of biocompatible inhibitors. Using a recently developed inhibitor, we explored the role of nicotinic acid adenine dinucleotide phosphate in autoreactive effector T cells during experimental autoimmune encephalomyelitis, the animal model for multiple sclerosis. We provide in vitro and in vivo evidence that calcium signalling controlled by nicotinic acid adenine dinucleotide phosphate is relevant for the pathogenic potential of autoimmune effector T cells. Live two photon imaging and molecular analyses revealed that nicotinic acid adenine dinucleotide phosphate signalling regulates T cell motility and re-activation upon arrival in the nervous tissues. Treatment with the nicotinic acid adenine dinucleotide phosphate inhibitor significantly reduced both the number of stable arrests of effector T cells and their invasive capacity. The levels of pro-inflammatory cytokines interferon-gamma and interleukin-17 were strongly diminished. Consecutively, the clinical symptoms of experimental autoimmune encephalomyelitis were ameliorated. In vitro, antigen-triggered T cell proliferation and cytokine production were evenly suppressed. These inhibitory effects were reversible: after wash-out of the nicotinic acid adenine dinucleotide phosphate antagonist, the effector T cells fully regained their functions. The nicotinic acid derivative BZ194 induced this transient state of non-responsiveness specifically in post-activated effector T cells. Naïve and long-lived memory T cells, which express lower levels of the putative nicotinic acid adenine dinucleotide phosphate receptor, type 1 ryanodine receptor, were not targeted. T cell priming and recall responses in vivo were not reduced. These data indicate that the nicotinic acid adenine dinucleotide phosphate/calcium signalling pathway is essential for the recruitment and the activation of autoaggressive effector T cells within their target organ. Interference with this signalling pathway suppresses the formation of autoimmune inflammatory lesions and thus might qualify as a novel strategy for the treatment of T cell mediated autoimmune diseases

Review: ‘Gimme five’: future challenges in multiple sclerosis. ECTRIMS Lecture 2009

This article is based on the ECTRIMS lecture given at the 25th ECTRIMS meeting which was held in Düsseldorf, Germany, from 9 to 12 September 2009. Five challenges have been identified: (1) safeguarding the principles of medical ethics; (2) optimizing the risk/benefit ratio; (3) bridging the gap between multiple sclerosis and experimental autoimmune encephalitis; (4) promoting neuroprotection and repair; and (5) tailoring multiple sclerosis therapy to the individual patient. Each of these challenges will be discussed and placed in the context of current research into the pathogenesis and treatment of multiple sclerosis

The Activation Status of Neuroantigen-specific T Cells in the Target Organ Determines the Clinical Outcome of Autoimmune Encephalomyelitis

The clinical picture of experimental autoimmune encephalomyelitis (EAE) is critically dependent on the nature of the target autoantigen and the genetic background of the experimental animals. Potentially lethal EAE is mediated by myelin basic protein (MBP)–specific T cells in Lewis rats, whereas transfer of S100β- or myelin oligodendrocyte glycoprotein (MOG)–specific T cells causes intense inflammatory response in the central nervous system (CNS) with minimal disease. However, in Dark Agouti rats, the pathogenicity of MOG-specific T cells resembles the one of MBP-specific T cells in the Lewis rat. Using retrovirally transduced green fluorescent T cells, we now report that differential disease activity reflects different levels of autoreactive effector T cell activation in their target tissue. Irrespective of their pathogenicity, the migratory activity, gene expression patterns, and immigration of green fluorescent protein+ T cells into the CNS were similar. However, exclusively highly pathogenic T cells were significantly reactivated within the CNS. Without local effector T cell activation, production of monocyte chemoattractants was insufficient to initiate and propagate a full inflammatory response. Low-level reactivation of weakly pathogenic T cells was not due to anergy because these cells could be activated by specific antigen in situ as well as after isolation ex vivo

Knocking at the brain’s door: intravital two-photon imaging of autoreactive T cell interactions with CNS structures

Since the first applications of two-photon microscopy in immunology 10 years ago, the number of studies using this advanced technology has increased dramatically. The two-photon microscope allows long-term visualization of cell motility in the living tissue with minimal phototoxicity. Using this technique, we examined brain autoantigen-specific T cell behavior in experimental autoimmune encephalitomyelitis, the animal model of human multiple sclerosis. Even before disease symptoms appear, the autoreactive T cells arrive at their target organ. There they crawl along the intraluminal surface of central nervous system (CNS) blood vessels before they extravasate. In the perivascular environment, the T cells meet phagocytes that present autoantigens. This contact activates the T cells to penetrate deep into the CNS parenchyma, where the infiltrated T cells again can find antigen, be further activated, and produce cytokines, resulting in massive immune cell recruitment and clinical disease

Directed -in vitro- evolution of Precambrian and extant Rubiscos

Rubisco is an ancient, catalytically conserved yet slow enzyme, which plays a central role in the biosphere’s carbon cycle. The design of Rubiscos to increase agricultural productivity has hitherto relied on the use of in vivo selection systems, precluding the exploration of biochemical traits that are not wired to cell survival. We present a directed -in vitro- evolution platform that extracts the enzyme from its biological context to provide a new avenue for Rubisco engineering. Precambrian and extant form II Rubiscos were subjected to an ensemble of directed evolution strategies aimed at improving thermostability. The most recent ancestor of proteobacteria -dating back 2.4 billion years- was uniquely tolerant to mutagenic loading. Adaptive evolution, focused evolution and genetic drift revealed a panel of thermostable mutants, some deviating from the characteristic trade-offs in CO2-fixing speed and specificity. Our findings provide a novel approach for identifying Rubisco variants with improved catalytic evolution potential.This work was supported by the REPSOL Research contracts Rubolution (RC020401120018), Rubolution 2.0 (RC 020401140042), the CSIC project PIE-201780E043 and the Australian Research Council grant CE140100015

Climate fluctuations of tropical coupled system: The role of ocean dynamics

The tropical oceans have long been recognized as the most important region for large-scale ocean–atmosphere interactions, giving rise to coupled climate variations on several time scales. During the Tropical Ocean Global Atmosphere (TOGA) decade, the focus of much tropical ocean research was on understanding El Niño–related processes and on development of tropical ocean models capable of simulating and predicting El Niño. These studies led to an appreciation of the vital role the ocean plays in providing the memory for predicting El Niño and thus making seasonal climate prediction feasible. With the end of TOGA and the beginning of Climate Variability and Prediction (CLIVAR), the scope of climate variability and predictability studies has expanded from the tropical Pacific and ENSO-centric basis to the global domain. In this paper the progress that has been made in tropical ocean climate studies during the early years of CLIVAR is discussed. The discussion is divided geographically into three tropical ocean basins with an emphasis on the dynamical processes that are most relevant to the coupling between the atmosphere and oceans. For the tropical Pacific, the continuing effort to improve understanding of large- and small-scale dynamics for the purpose of extending the skill of ENSO prediction is assessed. This paper then goes beyond the time and space scales of El Niño and discusses recent research activities on the fundamental issue of the processes maintaining the tropical thermocline. This includes the study of subtropical cells (STCs) and ventilated thermocline processes, which are potentially important to the understanding of the low-frequency modulation of El Niño. For the tropical Atlantic, the dominant oceanic processes that interact with regional atmospheric feedbacks are examined as well as the remote influence from both the Pacific El Niño and extratropical climate fluctuations giving rise to multiple patterns of variability distinguished by season and location. The potential impact of Atlantic thermohaline circulation on tropical Atlantic variability (TAV) is also discussed. For the tropical Indian Ocean, local and remote mechanisms governing low-frequency sea surface temperature variations are examined. After reviewing the recent rapid progress in the understanding of coupled dynamics in the region, this study focuses on the active role of ocean dynamics in a seasonally locked east–west internal mode of variability, known as the Indian Ocean dipole (IOD). Influences of the IOD on climatic conditions in Asia, Australia, East Africa, and Europe are discussed. While the attempt throughout is to give a comprehensive overview of what is known about the role of the tropical oceans in climate, the fact of the matter is that much remains to be understood and explained. The complex nature of the tropical coupled phenomena and the interaction among them argue strongly for coordinated and sustained observations, as well as additional careful modeling investigations in order to further advance the current understanding of the role of tropical oceans in climate