Preface 3th Workshop "Large-scale Hydrological Modelling – Hydrological Modelling for the Assessment of Ecosystem Services and Landscape Functions", 25–27 November 2009, Dresden

No abstract available

Building an integrated modeling framework for assessing land-use change and its consequences for areal water balance in mountainous Southwest China

The opening up of China's industry towards market orientation has a distinct impact on natural resources as well as on social structures. The example of rubber introduction in Yunnan province (SW China) shows the mutual interdependencies between economy, natural resources, and social structures. We assess the impacts of rubber introduction and possible development paths in the study area. An integrated modeling framework (NabanFrame) is developed for the catchment of the Naban River (size 270 km2), a tributary to the Mekong River. NabanFrame comprises an agro-economic, ecological, and social model. Altogether they interact with a land-use change model via defined interfaces. Effects on the water cycle are considered by additionally integrating the spatially distributed rainfall-runoff and water balance model AKWA-M® in the model framework. Therefore, a reasonable parameterization is needed to assess the land-use changes on areal water fluxes. The authors conclude that the chosen hydrological model is able to assess the impacts of land conversion (from forest to rubber plantations) on catchment hydrology and address further adaptations to be implemented in the hydrological model.BMBF/LILA

Identification and model based assessment of the potential water retention caused by land-use changes

International audienceThe extreme summer flood in the Elbe River watershed initiated a debate on the role of forest conversion and afforestation as measures for preventive flood protection. To quantify the effect of forest conversion and afforestation on flood runoff from catchments reliable model calculations are essential. The article overviews the present state of our work and provides an example for a model- based assessment of potential water retention caused by land-use changes in a catchment in the Central Ore Mountains (Saxony, Germany). The potential of flood control by land-use management measures is highly dependant on the site-specific soil and relief conditions and the rainfall event characteristics. The pre-event soil moisture is distinctly lower under forest land-use. Furthermore, infiltration, percolation in the subsoil is increased. These effects exist for small/medium-scale events whereas they become marginal for extreme events

A modeling framework to assess water and nitrate balances in the Western Bug river basin, Ukraine

The objective of this study was to assess the utility of the eco-hydrological SWAT model (Soil and Water Assessment Tool, Arnold et al., 1998) for representing water balance and nitrate fluxes given limited input and calibration data. The investigated catchment is located in Western Ukraine with an area of approximately 2616 km². Land use is currently dominated by agriculture with significant areas of pasture, and has undergone a high degree of changes in land-use and agricultural practice since the end of the Soviet Union. Model application produced a fitted water balance (calibration: <i>R</i>² = 0.52, NS = 0.46; validation: <i>R</i>² = 0.47, NS = 0.51) and plausible ranges and dynamics of nitrate in stream loadings. Groundwater parameters were found to be highly sensitive. The results indicate that SWAT is an appropriate tool for water resource investigations in the Western Bug catchment, and can provide a useful tool for further eco-hydrologic research in the region (i.e. diffuse pollution impacts)

Skin infiltrating NK cells in cutaneous T-cell lymphoma are increased in number and display phenotypic alterations partially driven by the tumor

Cutaneous T-cell lymphomas (CTCL) are characterized by focal infiltration of malignant T cell clones in solitary skin lesions. Many CTCL patients experience an indolent disease, but some progress to advanced disease with high fatality. We hypothesized that natural killer (NK) cells participate in local control of tumor growth in CTCL skin. Immunohistochemistry and flow cytometry analysis of the density, localization, phenotype and function of NK cells in twenty-nine fresh or formalin-fixed skin biopsies from twenty-four CTCL patients and twenty-three biopsies from twenty healthy controls highlighted higher numbers of CD56+CD3- NK cells in CTCL skin. A reduced fraction of CTCL skin NK cells expressed the maturation marker CD57, the cytotoxic protein granzyme B and the activation marker CD69, indicating reduced tumor-killing abilities of the NK cells. Retained expression of immune checkpoint proteins or inhibitory proteins including PD1, TIM3, LAG3, CD73 and NKG2A and the activating receptors CD16 and NKp46 indicated maintained effector functions. Indeed, the capacity of NK cells to produce anti-tumor acting IFNγ upon PMA+ionomycin stimulation was similar in cells from CTCL and healthy skin. Co-cultures of primary human NK cells or the NK cell line NKL with CTCL cells resulted in reduced levels of granzyme B and CD69, indicating that close cellular interactions with CTCL cells induced the impaired functional NK cell phenotype. In conclusion, increased numbers of NK cells in CTCL skin exhibit a partially impaired phenotype in terms of activity. Enhancing NK cell activity with NK cell activating cytokines such as IL-15 or immune checkpoint blockade therefore represents a potential immunotherapeutic approach in CTCL.publishedVersio

Skin infiltrating NK cells in cutaneous T-cell lymphoma are increased in number and display phenotypic alterations partially driven by the tumor

Cutaneous T-cell lymphomas (CTCL) are characterized by focal infiltration of malignant T cell clones in solitary skin lesions. Many CTCL patients experience an indolent disease, but some progress to advanced disease with high fatality. We hypothesized that natural killer (NK) cells participate in local control of tumor growth in CTCL skin. Immunohistochemistry and flow cytometry analysis of the density, localization, phenotype and function of NK cells in twenty-nine fresh or formalin-fixed skin biopsies from twenty-four CTCL patients and twenty-three biopsies from twenty healthy controls highlighted higher numbers of CD56+CD3- NK cells in CTCL skin. A reduced fraction of CTCL skin NK cells expressed the maturation marker CD57, the cytotoxic protein granzyme B and the activation marker CD69, indicating reduced tumor-killing abilities of the NK cells. Retained expression of immune checkpoint proteins or inhibitory proteins including PD1, TIM3, LAG3, CD73 and NKG2A and the activating receptors CD16 and NKp46 indicated maintained effector functions. Indeed, the capacity of NK cells to produce anti-tumor acting IFNγ upon PMA+ionomycin stimulation was similar in cells from CTCL and healthy skin. Co-cultures of primary human NK cells or the NK cell line NKL with CTCL cells resulted in reduced levels of granzyme B and CD69, indicating that close cellular interactions with CTCL cells induced the impaired functional NK cell phenotype. In conclusion, increased numbers of NK cells in CTCL skin exhibit a partially impaired phenotype in terms of activity. Enhancing NK cell activity with NK cell activating cytokines such as IL-15 or immune checkpoint blockade therefore represents a potential immunotherapeutic approach in CTCL

Cellular mechanisms by which proinsulin C-peptide prevents insulin-induced neointima formation in human saphenous vein

AIMS/HYPOTHESIS: Endothelial cells (ECs) and smooth muscle cells (SMCs) play key roles in the development of intimal hyperplasia in saphenous vein (SV) bypass grafts. In diabetic patients, insulin administration controls hyperglycaemia but cardiovascular complications remain. Insulin is synthesised as a pro-peptide, from which C-peptide is cleaved and released into the circulation with insulin; exogenous insulin lacks C-peptide. Here we investigate modulation of human SV neointima formation and SV-EC and SV-SMC function by insulin and C-peptide. METHODS: Effects of insulin and C-peptide on neointima formation (organ cultures), EC and SMC proliferation (cell counting), EC migration (scratch wound), SMC migration (Boyden chamber) and signalling (immunoblotting) were examined. A real-time RT-PCR array identified insulin-responsive genes, and results were confirmed by real-time RT-PCR. Targeted gene silencing (siRNA) was used to assess functional relevance. RESULTS: Insulin (100 nmol/l) augmented SV neointimal thickening (70% increase, 14 days), SMC proliferation (55% increase, 7 days) and migration (150% increase, 6 h); effects were abrogated by 10 nmol/l C-peptide. C-peptide did not affect insulin-induced Akt or extracellular signal-regulated kinase signalling (15 min), but array data and gene silencing implicated sterol regulatory element binding transcription factor 1 (SREBF1). Insulin (1-100 nmol/l) did not modify EC proliferation or migration, whereas 10 nmol/l C-peptide stimulated EC proliferation by 40% (5 days). CONCLUSIONS/INTERPRETATION: Our data support a causative role for insulin in human SV neointima formation with a novel counter-regulatory effect of proinsulin C-peptide. Thus, C-peptide can limit the detrimental effects of insulin on SMC function. Co-supplementing insulin therapy with C-peptide could improve therapy in insulin-treated patients

Proinsulin C-peptide elicits disaggregation of insulin resulting in enhanced physiological insulin effects

Using surface plasmon resonance (SPR) and electrospray mass spectrometry (ESI-MS), proinsulin C-peptide was found to influence insulin-insulin interactions. In SPR with chip-bound insulin, C-peptide mixed with analyte insulin increased the binding, while alone C-peptide did not. A control peptide with the same residues in random sequence had little effect. In ESI-MS, C-peptide lowered the presence of insulin hexamer. The data suggest that C-peptide promotes insulin disaggregation. Insulin/insulin oligomer μM dissociation constants were determined. Compatible with these findings, type 1 diabetic patients receiving insulin and C-peptide developed 66% more stimulation of glucose metabolism than when given insulin alone. A role of C-peptide in promoting insulin disaggregation may be important physiologically during exocytosis of pancreatic β-cell secretory granulae and pharmacologically at insulin injection sites. It is compatible with the normal co-release of C-peptide and insulin and may contribute to the beneficial effect of C-peptide and insulin replacement in type 1 diabetics