ALBERT

Beschreibung: The objective of this study is to incorporate a time-dependent SCS CN method (SMA_CN) in Soil and Water Assessment Tool (SWAT) and compare its performance with the existing CN method in SWAT by simulating the hydrology of two agricultural watersheds in Indiana, United States. Results show that fusion of the SMA_CN method causes decrease in runoff volume and increase in profile soil moisture content, associated with larger groundwater contribution to the streamflow. In addition, the higher amount of moisture in the soil profile slightly elevates the actual evapotranspiration. The SMA-based SWAT configuration consistently produces improved goodness of fit scores and less uncertain outputs with respect to streamflow during both calibration and validation. The SMA_CN method exhibits better match with the observed data for all flow regimes, thereby addressing issues related to peak and low flow predictions by SWAT in many past studies. Comparison of the calibrated model outputs with field-scale soil moisture observations reveal that the SMA overhauling enables SWAT to represent soil moisture condition more accurately, with better response to the incident rainfall dynamics. While the results from the modification of the SCS method in SWAT are promising, more studies including watersheds with various physical and climatic settings are needed to validate the proposed approach. This article is protected by copyright. All rights reserved.

Beschreibung: We adapted Newton's Law of Cooling to model downstream water temperature change in response to stream-adjacent forest harvest on small and medium streams (average 327 ha in size) throughout the Oregon Coast Range, USA. The model requires measured stream gradient, width, depth and upstream control reach temperatures as inputs and contains two free parameters which were determined by fitting the model to measured stream temperature data. This model reproduces the measured downstream temperature responses to within 0.4 C ° for 15 of the 16 streams studied and provides insight into the physical sources of site-to-site variation among those responses. We also use the model to examine how the pre-to-post harvest change in daily maximum stream temperature depends on distance from the harvest reach. The model suggests that the pre-to-post harvest temperature change approximately 300  m downstream of the harvest will range from roughly 82% to less than 1% of that temperature change which occurred within the harvest reach, depending primarily on the downstream width, depth, and gradient. Using study-averaged values for these channel characteristics the model suggests that for a stream representative of those in the study, the temperature change approximately 300  m downstream of the harvest will be 56% of the temperature change which occurred within the harvest reach. This adapted Newton's Law of Cooling procedure represents a highly practical means for predicting stream temperature behavior downstream of timber harvests relative to conventional heat budget approaches, and is informative of the dominant processes affecting stream temperature. This article is protected by copyright. All rights reserved.

Beschreibung: Direct application of histone-deacetylase-inhibitors (HDACis) to dental pulp cells (DPCs) induces chromatin changes, promoting gene expression and cellular-reparative events. We have previously demonstrated that HDACis (Valproic acid, Trichostatin A) increase mineralization in dental papillae-derived cell-lines and primary DPCs by stimulation of dentinogenic gene expression. Here, we investigated novel genes regulated by the HDACi, suberoylanilide hydroxamic acid (SAHA), to identify new pathways contributing to DPC differentiation. SAHA significantly compromised DPC viability only at relatively high concentrations (5 μM); while low concentrations (1 μM) SAHA did not increase apoptosis. HDACi-exposure for 24 h induced mineralization-per-cell dose-dependently after 2 weeks; however, constant 14d SAHA-exposure inhibited mineralization. Microarray analysis (24 h and 14d) of SAHA exposed cultures highlighted that 764 transcripts showed a significant 〉2.0-fold change at 24 h, which reduced to 36 genes at 14d. 59% of genes were down-regulated at 24 h and 36% at 14d, respectively. Pathway analysis indicated SAHA increased expression of members of the matrix metalloproteinase (MMP) family. Furthermore, SAHA-supplementation increased MMP-13 protein expression (7d, 14 d) and enzyme activity (48 h, 14d). Selective MMP-13-inhibition (MMP-13i) dose-dependently accelerated mineralization in both SAHA-treated and non-treated cultures. MMP-13i-supplementation promoted expression of several mineralization-associated markers, however, HDACi-induced cell migration and wound healing were impaired. Data demonstrate that short-term low-dose SAHA-exposure promotes mineralization in DPCs by modulating gene pathways and tissue proteases. MMP-13i further increased mineralization-associated events, but decreased HDACi cell migration indicating a specific role for MMP-13 in pulpal repair processes. Pharmacological inhibition of HDAC and MMP may provide novel insights into pulpal repair processes with significant translational benefit. This article is protected by copyright. All rights reserved

Beschreibung: Digital elevation models (DEMs) that are used in hydrological applications must be processed to remove sinks, mainly topographic depressions. Flow enforcement techniques include filling methods, which raise elevations within depressions, breaching, which carves channels through blockages, and hybrid methods. Despite previous research demonstrating the large impact to DEMs and subsequent analyses of depression filling, it is common practice apply this technique to flow enforcement. This is partly due to the greater efficiency of depression filling tools compared to breaching counterparts, which often limits breaching to applications of small- to moderate-sized DEMs. A new hybrid flow enforcement algorithm is presented in this study. The method can be run in complete breaching, selective breaching (either breached or filled), or constrained breaching (partial breaching) modes, allowing for greater flexibility in how practitioners enforce continuous flow paths. Algorithm performance was tested with DEMs of varying topography, spatial extents, and resolution. The sites included three moderate sized DEMs (52,000,000 to 190,000,000 cells) and three massive DEMs of the Iberian Peninsula, and the Amazon and Nile River basins, the largest containing nearly one billion cells. In complete breaching mode, the new algorithm required 87% of the time needed by a filling method to process the test DEMs, while the selective breaching and constrained breaching modes, operating with maximum breach depth constraints, increased run times by 8% and 27% respectively. Therefore, the new algorithm offers comparable performance to filling and the ability to process massive topographic data sets, while giving practitioners greater flexibility and lowering DEM impact. This article is protected by copyright. All rights reserved.

Beschreibung: Mountain snowpacks provide most of the annual discharge of western U.S. rivers, but the future of water resources in the western U.S. is tenuous, as climatic changes have resulted in earlier spring melts that have exacerbated summer droughts. Compounding changes to the physical environment are biotic disturbances including the mountain pine beetle (MPB), which has decimated millions of acres of western North American forests. At the watershed scale, MPB disturbance increases the peak hydrograph, and at the stand scale the ‘gray’ phase of MPB canopy disturbance decreases canopy snow interception, increases snow albedo, increases net shortwave radiation and decreases net longwave radiation versus the ‘red’ phase. Fewer studies have been conducted on the red phase of MPB disturbance, and in the mixed coniferous stands that may follow MPB-damaged forests. We measured the energy balance of four snowpacks representing different stages of MPB damage, management, and recovery: a lodgepole pine stand, a MPB-infested stand in the red phase, a mixed coniferous stand (representing one successional trajectory), and a clearcut (representing reactive management) in the Tenderfoot Creek Experimental Forest in Montana, USA. Net longwave radiation was lower in the MPB-infested stand despite higher basal area and plant area index of the other forests, suggesting that the dessicated needles serve as a less effective thermal buffer against longwave radiative losses. Eddy covariance observations of sensible and latent heat flux indicate that they are of similar but opposite magnitude, on the order of 20 MJ m −2 during the melt period. Further analyses reveal that net turbulent energy fluxes were near zero due to the temperature and atmospheric vapor pressure encountered during the melt period. Future research should place snow science in the context of forest succession and management, and address important uncertainties regarding the timing and magnitude of needlefall events. This article is protected by copyright. All rights reserved.

Beschreibung: Deficiency in the retinoblastoma protein (Rb) favors leanness and a healthy metabolic profile in mice largely attributed to activation of oxidative metabolism in white and brown adipose tissues. Less is known about Rb modulation of skeletal muscle metabolism. This was studied here by transiently knocking down Rb expression in differentiated C2C12 myotubes using small interfering RNAs. Compared with control cells transfected with non-targeting RNAs, myotubes silenced for Rb (by 80–90%) had increased expression of genes related to fatty acid uptake and oxidation such as Cd36 and Cpt1b (by 61% and 42%, respectively), increased Mitofusin 2 protein content (∼2.5-fold increase), increased mitochondrial to nuclear DNA ratio (by 48%), increased oxygen consumption (by 65%) and decreased intracellular lipid accumulation. Rb silenced myotubes also displayed up-regulated levels of glucose transporter type 4 expression (∼5-fold increase), increased basal glucose uptake, and enhanced insulin-induced Akt phosphorylation. Interestingly, exercise in mice led to increased Rb phosphorylation (inactivation) in skeletal muscle as evidenced by immunohistochemistry analysis. In conclusion, the silencing of Rb enhances mitochondrial oxidative metabolism and fatty acid and glucose disposal in skeletal myotubes, and changes in Rb status may contribute to muscle physiological adaptation to exercise. This article is protected by copyright. All rights reserved

Beschreibung: MDA-9/Syntenin is a small PDZ domain containing scaffolding protein with diverse array of function regulating membrane trafficking, cell adhesion, neural and synaptic development, ubiquitination and exosome biogenesis. An appreciable number of studies also established a pivotal role of MDA-9/Syntenin in cancer development and progression. In this review, we will discuss the dynamic role of MDA-9/Syntenin in regulating normal and abnormal fate of various cellular processes. This article is protected by copyright. All rights reserved

Beschreibung: Because early-stage hepatocellular carcinoma (HCC) is difficult to diagnose using the existing techniques, identifying better biomarkers would likely improve the patients' prognoses. We performed a systematic review and meta-analysis of published studies to appraise the utility of microRNAs (miRNAs) for the early diagnosis of HCC. Pertinent literature was collected from the Medline, Embase, and Chinese National Knowledge Infrastructure databases. We analyzed 50 studies that included 3423 cases of HCC, 2403 chronic hepatic disease (CH) patients, and 1887 healthy controls in 16 articles. Summary receiver operating characteristic analyses of all miRNAs showed an area under the curve (AUC) of 0.82, with 75.8% sensitivity and 75.0% specificity in discriminating patients with HCC from healthy controls. miR-21 and miR-122 individually distinguished patients with HCC from healthy controls, with an AUC of 0.88 for miR-21 and 0.77 for miR-122. The sensitivity and specificity for miR-21 were 86.6% and 79.5%, respectively; those for miR-122 were 68.0% and 73.3%. We conclude that circulating miRNAs, particularly miR-21 and miR-122, are promising biomarkers for the early diagnosis of HCC. This article is protected by copyright. All rights reserved

Beschreibung: As a result of climate change/variation and its aggravation by human activities over the past several decades, the hydrological conditions in the middle Yellow River in China have dramatically changed, which has led to a sharp decrease of streamflow and the drying up of certain tributaries. This paper simulated and analysed the impact of sediment-trapping dams (STDs, a type of large-sized check dam used to prevent sediment from entering the Yellow River main stem) on hydrological processes, and the study area was located in the 3,246 km 2 Huangfuchuan (HFC) River basin. Changes in the hydrological processes were analysed, and periods of natural and disturbed states were defined. Subsequently, the number and distribution of the STDs were determined based on data collected from statistical reports and identified from remote sensing images, and the topological relationships between the STDs and high-resolution river reaches were established. A hydrological model, the Digital Yellow River Integrated Model, was used to simulate the STD impact on the hydrological processes, and the maximum STD impact was evaluated through a comparison between the simulation results with and without the STDs, which revealed that the interception effect of the STDs contributed to the decrease of the streamflow by approximately 39%. This paper also analysed the relationship between the spatial distribution of the STDs and rainfall in the HFC River basin and revealed that future soil and water conservation measures should focus on areas with a higher average annual rainfall and higher number of rainstorm hours. This article is protected by copyright. All rights reserved.

Beschreibung: We have synthesized a novel derivative of Digitoxin, termed “MonoD”, which demonstrates cytotoxic effects in lung cancer cells with much higher potency as compared to Digitoxin. Our data show that within one hour of MonoD treatment, H460 cells showed increased oxidative stress, increased formation of autophagic vacuoles and increased expression of pro-autophagic markers Beclin-1 and LC3-II. Cells pretreated with MnTBAP, a superoxide scavenger not only lowered superoxide production, but also had lower levels of LC3-II and Beclin-1. Prolonged treatment with MonoD induced apoptosis in lung cancer cells. We investigated MonoD-dependent regulation of Akt and Bcl2, proteins that are known regulators of both autophagy and apoptosis. Molecular and pharmacologic inhibitors of Bcl2 and Akt, when combined with MonoD, led to higher expression of LC3-II and Beclin-1 as compared to MonoD alone, suggesting a repressive effect for these proteins in MonoD-dependent autophagy. Pretreatment of cells with an autophagy inhibitor repressed the apoptotic potential of MonoD, confirming that early autophagic flux is important to drive apoptosis. Therapeutic entities such as MonoD that target multiple pathways such as autophagy and apoptosis may prove advantageous over current therapies that have unimodal basis for action and may drive sustained tumor regression, which is highly desirable. This article is protected by copyright. All rights reserved

Beschreibung: Distributed, continuous hydrologic models promote better understanding of hydrology and enable integrated hydrologic analyses by providing a more detailed picture of water transport processes across the varying landscape. However, such models are not widely used in routine modeling practices, due in part to the extensive data input requirements, computational demands, and complexity of routing algorithms. We developed a two-dimensional continuous hydrologic model, HYSTAR, using a time-area method within a grid-based spatial data model with the goal of providing an alternative way to simulate spatiotemporally varied watershed-scale hydrologic processes. The model calculates the direct runoff hydrograph by coupling a time-area routing scheme with a dynamic rainfall excess sub-model implemented here using a modified curve number method with an hourly time step, explicitly considering downstream ‘reinfiltration’ of routed surface runoff. Soil moisture content is determined at each time interval based on a water balance equation, and overland and channel runoff is routed on time-area maps, representing spatial variation in hydraulic characteristics for each time interval in a storm event. Simulating runoff hydrographs does not depend on unit hydrograph theory or on solution of the Saint Venant equation, yet retains the simplicity of a unit hydrograph approach and the capability of explicitly simulating two-dimensional flow routing. The model provided acceptable performance in predicting daily and monthly runoff for a 6-year period for a watershed in Virginia (USA) using readily available geographic information about the watershed landscape. Spatial and temporal variability in simulated effective runoff depth and time area maps dynamically show the areas of the watershed contributing to the direct runoff hydrograph at the outlet over time, consistent with the variable source area overland flow generation mechanism. The model offers a way to simulate watershed processes and runoff hydrographs using the time-area method, providing a simple, efficient, and sound framework that explicitly represents mechanisms of spatially and temporally varied hydrologic processes. This article is protected by copyright. All rights reserved.

Beschreibung: Given the importance of groundwater temperature to the biogeochemical health of aquatic ecosystems, a floodplain study was implemented to improve understanding of rural land use impacts on shallow groundwater (SGW) temperature. Study sites included a historic agricultural field (Ag) and bottomland hardwood forest (BHF), each with nine piezometers in an 80 × 80 m grid. Piezometers were equipped with pressure transducers to monitor SGW temperature and level at 30 minute intervals during the 2011, 2012, 2013, and 2014 water years. The study is one of the first to utilize long-term, continuous, automated, in situ monitoring to investigate rural land use impacts on shallow groundwater temperatures. Average SGW temperature during the study period was 11.1 and 11.2 °C at the Ag and BHF sites, respectively. However, temperature range at the Ag site was 72% greater than at the BHF site. Results indicate a greater responsiveness to seasonal climate fluctuations in Ag site SGW temperature related to absence of forest canopy. Patterns of intra-site groundwater temperature differences at both study sites illustrate the influence of stream-aquifer thermal conduction and occasional baseflow reversals. Considering similar surface soil temperature amplitudes and low average groundwater flow values at both sites, results suggest that contrasting rates of plant water use, groundwater recharge, and subsurface hydraulic conductivity are likely mechanistic causes for the observed SGW temperature differences. Results highlight the long-term impact of forest removal on subsurface hydrology and groundwater temperature regime. This article is protected by copyright. All rights reserved.

Beschreibung: Growing demand on groundwater resources and the semi-arid climate in the North China Plain (NCP) highlight the need for improved understanding of connections between regional climate change and groundwater recharge. Hydrologic time series of precipitation and groundwater levels were analyzed in three representative geographical zones throughout the NCP for the period of 1960-2008 using trend analysis and spectral analysis methods. A significant change point around 1975 is followed by a long term decline trend in precipitation time series, which coincides with the Pacific Decadal Oscillation (PDO) positive phase. However, the magnitudes of groundwater levels variability due to heavily pumping overwhelm the low-frequency signal of groundwater levels. Nonlinear trends that related to long-term climatic variability and anthropogenic activities are removed by using the Singular Spectrum Analysis (SSA) method. Spectral analyses of the detrended residuals demonstrate significant short-term oscillations at the frequencies of 2–7 years, which have strong correlations with the El Niño-Southern Oscillation (ENSO) modes. This study contributes to improved understanding of dynamic relationship between groundwater and climate variability modes in the NCP, and demonstrates the importance of reliable detrending methods for groundwater levels that are affected greatly by pumping. This article is protected by copyright. All rights reserved.

Beschreibung: On September 3, 1998, a glacial lake outburst flood (GLOF) that originated from Tam Pokhari occurred in the Hinku valley of the eastern Nepal Himalaya. This study analyzes the lake's geomorphic and hydrologic conditions prior to the outburst, and evaluates the conditions that could contribute to a future flood through photogrammetric techniques. We processed high-resolution Corona KH-4A (2.7 m) and ALOS PRISM (2.5 m) stereo-images taken before and after the GLOF event, and produced detailed topographic maps (2-m contour interval) and DEMs (5 m × 5 m). We (re-) constructed lake water surfaces before (4410 ± 5 m) and after (4356 ± 5 m) the outburst, and reliably estimated the lake water surface lowering (54 ± 5 m) and the water volume released (19.5 ± 2.2 × 10 6  m 3 ) from the lake, showing good agreement with the results obtained from ground-based measurements. The most relevant conditions that may have influenced the catastrophic drainage of Tam Pokhari in 1998 include the presence of: i) a narrow (75 ± 6 m), steep (up to 50°) and high (120 ± 5 m) moraine dam; ii) high lake level (8 ± 5 m of freeboard); and iii) a steep overhanging glacier (〉40°). The lake outburst substantially altered the immediate area, creating a low and wide (〉500 m) outwash plain below the lake, a wide lake outlet channel (~50 m) and a gentle channel slope (~3–5°). Our new data suggest that the likelihood of a future lake outburst is low. Our results demonstrate that the datasets produced by photogrammetric techniques provide an excellent representation of micro-landform features on moraine dams, lake water surfaces and the changes in both over time, thereby allowing highly accurate pre- and post-GLOF (volumetric) change analysis of glacial lakes. Furthermore, it enables precise measurement of several predictive variables of GLOFs that can be useful for identifying potentially dangerous glacial lakes or prioritizing them for detailed field investigations. This article is protected by copyright. All rights reserved.

Beschreibung: To overcome the drug resistance phenomenon induced by Imatibib (IM), in clinical practice, are often used second generation of tyrosine kinase inhibitors as Nilotinib (NIL) a such potent inhibitor of the BCR/ABL kinase and Dasatinib (DAS) a inhibitor of BCR/ABL kinase and inhibitor SrC family kinase. In this study we evaluated the in vivo effect of DAS, NIL and IM on intracellular calcium concentration, oxidative stress and apoptosis in peripheral blood leukocytes of 45 newly diagnosed patients with chronic myeloid leukaemia (CML-PBM). Our data demonstrated that treatment with DAS and NIL showed an higher modulating potential than IM on intracellular calcium concentration by inhibiting the thapsigargin, a sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA) inhibitor and Lithium (Li) an inositol 1,4,5-triphosphate (InsP3) receptor inhibitor activities. Moreover our data demonstrated that NIL and DAS have significantly increased apoptosis more than IM by involving both intracellular calcium signaling as well as oxidative stress. The acquisition of the oxidative stress and calcium channels receptors values data could help the hematologist to modulate and improve the treatment of chronic myeloid leukaemia (CML) pathology. This article is protected by copyright. All rights reserved

Beschreibung: Fucoidan, a natural component of seaweeds, is reported to have immunomodulatory and anti-tumor effects. The mechanisms underpinning these activities remain poorly understood. In this study, the cytotoxicity and anti-tumor activities of fucoidan were investigated in acute myeloid leukemia (AML) cells. The human AML cell lines NB4, KG1a, HL60 and K562 were treated with fucoidan and cell cycle, cell proliferation and expression of apoptotic pathways molecules were analyzed. Fucoidan suppressed the proliferation and induced apoptosis through the intrinsic and extrinsic pathways in the acute promyelocytic leukemia (APL) cell lines NB4 and HL60, but not in KG1a and K562 cells. In NB4 cells, apoptosis was caspase-dependent as it was significantly attenuated by pre-treatment with a pan-caspase inhibitor. P21/WAF1/CIP1 was significantly up-regulated leading to cell cycle arrest. Fucoidan decreased the activation of ERK1/2 and down-regulated the activation of AKT through hypo-phosphorylation of Thr(308) residue but not Ser(473). In vivo , a xenograft model using the NB4 cells was employed. Mice were fed with fucoidan and tumor growth was measured following inoculation with NB4 cells. Subsequently, splenic natural killer (NK) cell cytotoxic activity was also examined. Oral doses of fucoidan significantly delayed tumor growth in the xenograft model and increased cytolytic activity of NK cells. Taken together, these data suggest that the selective inhibitory effect of fucoidan on APL cells and its protective effect against APL development in mice warrant further investigation of fucoidan as a useful agent in treatment of certain types of leukemia. This article is protected by copyright. All rights reserved

Beschreibung: Virtual Reality (VR), a computer-generated virtual environment, has been increasingly used in the entertainment world becoming a very new evolving field, but VR technology has also found a variety of applications in the biomedical field. VR can offer to subjects a safe environment within which to carry on different interventions ranging from the rehabilitation of discharged patients directly at home, to the support of hospitalized patients during different procedures and also of oncological inpatient subjects. VR appears as a promising tool for support and monitoring treatments in cancer patients influencing psychological and physiological functions. The aim of this systematic review is to provide an overview of all the studies that used VR intervention on cancer patients and analyze their main findings. Nineteen studies across nearly a thousand articles were identified that explored effects of VR interventions on cancer patients. Although these studies varied greatly in setting and design, this review identified some overarching themes. Results found that VR improved patients' emotional well-being, and diminished cancer related psychological symptoms. The studies explored various relevant variables including different types of settings (i.e. during chemotherapy, during pain procedures, during hospitalization). Here, we point to the need of a global and multi-disciplinary approach aimed at analyzing the effects of VR taking advantage of the new technology systems like bio sensors as well as electroencephalogram monitoring pre-during and after intervention. Devoting more attention to bio physiological variables, standardized procedures, extending duration to longitudinal studies and adjusting for motion sickness related to VR treatment need to become standard of this research field. This article is protected by copyright. All rights reserved

Beschreibung: Although the importance to account for microrelief in the calculation of specific yields for shallow groundwater systems is well recognized, the microrelief influence is often treated very simplified, which can cause considerable errors. We provide a general one-dimensional expression that correctly represents the effect of a microrelief on the total specific yield that is composed of the soil and surface specific yield. The one-dimensional expression can be applied for different soil hydraulic parameterizations and soil surface elevation frequency distributions. Applying different van Genuchten parameters and a simple linear microrelief model, we demonstrate that the specific yield is influenced by the microrelief not only when surface storage directly contributes to specific yield by (partial) inundation but also when water levels are lower than the minimum surface elevation. Compared to a simplified representation of the soil specific yield, in which a mean soil surface is assumed for the calculation of soil specific yield, the correct representation can lead to lower as well as higher soil specific yields depending on the specific interaction of the soil water retention characteristics and the microrelief. The new equation can be used to obtain more accurate evapotranspiration estimates from water level fluctuations and to account for the effect of microtopographic subgrid variability on simulated water levels of spatially-distributed hydrological models. This article is protected by copyright. All rights reserved.

Beschreibung: Globally, Dissolved Inorganic Carbon (DIC) accounts for more than half the annual flux of carbon exported from terrestrial ecosystems via rivers. Here we assess the relative influences of biogeochemical and hydrological processes on DIC fluxes exported from a tropical river catchment characterized by distinct land cover, climate and geology transition from the wet tropical mountains to the low lying savanna plains. Processes controlling changes in river DIC were investigated using dissolved organic carbon (DOC), particulate organic carbon (POC) and DIC concentrations and stable isotope ratios of DIC (δ 13 C DIC ) at two time scales; seasonal and diel. The recently developed Isotopic Continuous Dissolved Inorganic Carbon Analyser (ISO-CADICA) was used to measure diel DIC concentration and δ 13 C DIC changes at a 15 minute temporal resolution. Results highlight the predominance of biologically mediated processes (photosynthesis and respiration) controlling diel changes in DIC. These resulted in DIC concentrations varying between 3.55-3.82 mg/L, and δ 13 C DIC values ranging from -19.7 ± 0.31 to -17.1 ± 0.08 ‰. In contrast, at the seasonal scale we observe wet season DIC variations predominantly from mixing processes, and dry season DIC variations due to both mixing processes and biological processes. The observed wet season increases in DIC concentrations (by 6.81 mg/L) and δ 13 C DIC values of river water (by 5.4 ‰) largely result from proportional increases in subsurface inflows from the savanna plains (C 4 vegetation) region relative to inflows from the rainforest (C 3 vegetation) highlands. The high DIC river load during the wet season results in the transfer of 97% of the annual river carbon load. Therefore, in this gaining river there are significant seasonal variations in both the hydrological and carbon cycles, and there is evidence of substantial coupling between the carbon cycles of the terrestrial and the fluvial environments. Recent identification of a substantial savanna carbon sink in wetter years in the recent past does not take into account the possibility of a substantial, rapid, lateral flux of carbon to rivers and back to the atmosphere. This article is protected by copyright. All rights reserved.

Beschreibung: Various remote-sensing methods are available to estimate soil moisture, but few address the fine spatial resolutions (e.g., 30 m grid cells) and root-zone depth requirements of agricultural and other similar applications. One approach that has been previously proposed to estimate fine-resolution soil moisture is to first estimate the evaporative fraction from an energy balance that is inferred from optical and thermal remote-sensing images (e.g., using the ReSET algorithm) and then estimate soil moisture through an empirical relationship to evaporative fraction. A similar approach has also been proposed to estimate the degree of saturation. The primary objective of this study is to evaluate these methods for estimating soil moisture and degree of saturation, particularly for a semiarid grassland with relatively dry conditions. Soil moisture was monitored at twenty-eight field locations in southeastern Colorado with herbaceous vegetation during the summer months of three years. In-situ soil moisture and degree of saturation observations are compared with estimates calculated from Landsat imagery using the ReSET algorithm. The in-situ observations suggest that the empirical relationships with evaporative fraction that have been proposed in previous studies typically provide overestimates of soil moisture and degree of saturation in this region. However, calibrated functions produce estimates with an accuracy that may be adequate for various applications. The estimates produced by this approach are more reliable for degree of saturation than for soil moisture, and the method is more successful at identifying temporal variability than spatial variability in degree of saturation for this region. This article is protected by copyright. All rights reserved.

Beschreibung: Groundwater movements in volcanic mountains and their effects on streamflow discharge and representative elementary area (REA) have remained largely unclear. We surveyed the discharge and chemical composition of spring and stream water in two catchments: the Hontani river (NR) catchment (6.6 km 2 ) and the Hosotani river (SR) catchment (4.0 km 2 ) at the southern part of Daisen volcano, Japan. Daisen volcano is a young volcano (17 × 10 3  years) at an early stage of erosion. Our study indicated that deep groundwater that moved through thick lava and pyroclastic flows and that could not be explained by shallow movements controlled by surface topography contributed dominantly to streamflow at larger catchment areas. At the NR catchment, the deep groundwater contribution clearly increased at a catchment boundary defined by an area of 3.0 km 2 and an elevation of 800 m. At the SR catchment, the contribution deep groundwater to the stream also increased suddenly at a boundary threshold of 2.0 km 2 and 700 m. Beyond these thresholds, the contributions of deep bedrock groundwater remained constant, indicating that the REA is between 2 and 3 km 2 at the observed area. These results indicate that the hydrological conditions of base flow were controlled mainly by the deep bedrock groundwater that moved through thick lava and pyroclastic flows in the undissected volcanic body of the upper part of the catchment. Our study demonstrates that deep and long groundwater movements via a deep bedrock layer including thick deposits of volcanic materials at the two catchments on Daisen volcano strongly determined streamflow discharge instead of the mixing of small-scale hydrological conditions. This article is protected by copyright. All rights reserved.

Beschreibung: We propose a novel technique for improving a long-term multi-step-ahead streamflow forecasts. A model based on wavelet decomposition and a multivariate Bayesian machine learning approach is developed for forecasting the streamflow three, six, nine and twelve months ahead simultaneously. The inputs of the model utilize only the past monthly streamflow records. They are decomposed into components formulated in terms of wavelet multiresolution analysis. It is shown that the model accuracy can be increased by using the wavelet boundary rule introduced in this study. A simulation study is performed to evaluate the effects of different wavelet boundary rules using synthetic and real streamflow data from the Yellowstone River in the Uinta Basin in Utah. The model based on the combination of wavelet and Bayesian machine learning regression techniques is compared to the wavelet and artificial neural networks based model. The robustness of the models is evaluated. This article is protected by copyright. All rights reserved.

Beschreibung: The combined use of water erosion models and geographic information systems (GIS) has facilitated soil loss estimation at the watershed scale. Tools such as the Geo-spatial interface for the Water Erosion Prediction Project (GeoWEPP) model provide a convenient spatially-distributed soil loss estimate but require discretization to identify hillslopes and channels. In GeoWEPP, the TOpographic PArameteriZation (TOPAZ) model is used as an automated procedure to extract a watershed boundary, hillslopes and channels from a digital elevation model (DEM). Previous studies in small watersheds have shown that the size of the hillslopes and the channel distribution affect the model estimates, but in large watersheds the effects on the soil loss estimates have yet to be tested. Therefore, the objective of this study was to evaluate the effect of discretization on the hillslope sediment yield estimates using GeoWEPP in two large watersheds (〉10 km 2 ). The watersheds were selected and discretized varying the TOPAZ parameters (CSA – Critical Source Area, and MSCL – Minimum Source Channel Length) in a 30-m resolution DEM. The drainage networks built with TOPAZ were compared among each other using the drainage density index. The results showed that the discretization affected hillslope sediment yield estimates and their spatial distribution more than total runoff. The drainage density index and the hillslope sediment yield were proportional but inversely related, thus soil loss estimates were highly affected by the spatial discretization. As a result of this analysis, a method to choose the CSA and MSCL values that generates the greatest fraction of hillslopes having profile lengths less than 200 m was developed. This slope length condition is particularly crucial when using the WEPP and GeoWEPP models, in order for them to produce realistic estimates of sheet and rill erosion. Finally, and as a result of this analysis, a more reliable method was developed for selecting the TOPAZ channel network parameters (CSA and MSCL).

Beschreibung: Linkages between the controls on surface storage and catchment streamflow response were examined in a wetland dominated basin in the Canadian Prairie Pothole region. Snowmelt, surface storage, water table elevation, atmospheric fluxes, and streamflow were monitored during spring snowmelt and summer in a 1 km 2 sub-catchment containing a semi-permanent pond complex connected via an intermittent stream. Snow accumulation in the basin in spring of the 2013 study year was the largest in the 24-year record. Rainfall totals in 2013 were close to the long term average, though June was an anomalously wet month. The water budget of the pond complex indicates that there was a significant subsurface contribution to surface storage. Activation of an effective transmission zone occurred between uplands and the stream network where the water table was located near the ground surface, which allowed significant lateral movement of subsurface water into the stream network. This was also important for maintaining and re-establishing surface connectivity and streamflow during rainfall events. The observed period of surface-water connectivity was one of the longest on record in the catchment due to unusually wet conditions; nevertheless, the results of this study have implications for how contributing area and runoff should be considered in monitoring and modelling studies in the region, as inclusion of more frequent and varied runoff processes will be essential to understanding changing streamflow regimes. This article is protected by copyright. All rights reserved.

Beschreibung: Stream-subsurface exchange plays a significant role in the fate and transport of contaminants in streams. It has been modeled explicitly by considering fundamental processes such as hydraulic exchange, colloid filtration, and contaminant interactions with streambed sediments and colloids. The models have been successfully applied to simulate the transport of inorganic metals and nutrients. In this study, laboratory experiments were conducted in a recirculating flume to investigate the exchange of a hydrophobic organic contaminant (HOC), p,p′ -DDE, between a stream and a quartz sand bed. A previously developed process-based multiphase exchange model was modified by accounting for the p,p′ -DDE kinetic adsorption to and desorption from the bed sediments/colloids and was applied to interpret the experimental results. Model input parameters were obtained by conducting independent small-scale batch experiments. Results indicate that the immobilization of p,p′ -DDE in the quartz sand bed can occur under representative natural stream conditions. The observed p,p′ -DDE exchange was successfully simulated by the process-based model. The model sensitivity analysis results show that the exchange of p,p′ -DDE can be sensitive to either the sediment sorption/desorption parameters or colloidal parameters depending on the experimental conditions tested. For the experimental conditions employed here, the effect of colloids on contaminant transport is expected to be minimal and the stream-subsurface exchange of p,p′ -DDE is dominated by the interaction of p,p′ -DDE with bed sediment. The work presented here contributes to a better mechanistic understanding of the complex transport process that HOCs undergo in natural streams, and to the development of reliable, predictive models for the assessment of impacted streams. This article is protected by copyright. All rights reserved.

Beschreibung: The physical and hydrological conditions in extracted peatlands often act as barriers to the regeneration of the keystone peat-forming genus Sphagnum . Although previous work has suggested that Sphagnum mosses regenerating on cutover peat surfaces quickly become vulnerable to water stress as the thickness of the regenerated layer increases, uncertainties regarding the storage and transmission properties of this layer and how these might evolve over time have made this assertion difficult to evaluate. This study investigates the hydrophysical properties and hydrological behaviour of regenerating Sphagnum layers ranging from 3-43 years in age using both field and laboratory methods. The 〉40 year old regenerated layers had significantly (p 〈 0.001) higher bulk density and retention capacity in the 5 cm thick basal layer directly overlying the cutover peat than the newer (〈10 year old) regenerated layers. Capillarity was a much stronger control on surficial water content (θ) than precipitation, which was poorly retained in the Sphagnum canopy, suggesting that regulation of water table position is an effective method of controlling θ as a means of optimizing productivity. In general, the θ sustained at a given water table position decreased as regenerated layer thickness increased. Analysis of water table position relative to the former cutover peat surface in different areas of the site suggests that the soil water dynamics of the 〉40 year old regenerated layers may be becoming increasingly similar to those of a natural bog peatland. This article is protected by copyright. All rights reserved.

Beschreibung: Nutrient concentrations in stream water, rainfall, throughfall, stem flow, surface flow and ground water were compared before, during, and after strip thinning (intensive 50%) in plantation forested watersheds in Tochigi, Japan. Influences were evaluated comparing four thinning-applied and two reference basins for one year before, six months during and one year after the thinning. Results show that this strip thinning significantly increased DTP, TP and DOC (DTP: 0.01 mg l -1 , TP: 0.04 mg l -1 , DOC: 0.53 mg l -1 ) during the thinning period and DTN and TN (DTN: 0.34 mg l -1 , TN: 0.46 mg l -1 ) after the thinning in stream waters relative to the unthinned basins. The increased phosphorus during thinning indicated ground disturbances by the strip thinning, with a concomitant increase in DOC. Changes in biotic and abiotic conditions resulted in increased nitrogen after the thinning, particularly in the dissolved pool. Changes in hydrological processes due to thinning, e.g. a change in flow distributions (less high nutrient stem flow and more low nutrient throughfall) and an increase in water discharge in stream water, possibly weakened the direct influences of thinning on nutrient concentrations. This article is protected by copyright. All rights reserved.

Beschreibung: Fabry disease (FD) is a hereditary X-linked metabolic lysosomal storage disorder due to insufficient amounts or a complete lack of the lysosomal enzyme α -galactosidase A ( α  − GalA). The loss of α -GalA activity leads to an abnormal accumulation of globotriaosylceramide (Gb3) in lysosomes and other cellular components of different tissues and cell types, affecting the cell function. However, whether these biochemical alterations also modify functional processes associated to the cell mitotic ability is still unknown. The goal of the present study was to characterize lineages of human dermal fibroblasts (HDFs) of FD patients and healthy controls focusing on Gb3 accumulation, expression of chloride channels that regulate proliferation, and proliferative activity. The biochemical and functional analyses indicate the existence of quantitative differences in some but not all the parameters of cytoskeletal organization, proliferation and differentiation processes. This article is protected by copyright. All rights reserved

Beschreibung: Soil water repellency can impact soil hydrology, overland flow generation and associated soil losses. However, current hydrological models do not take it into account, which creates a challenge in repellency-prone regions. This work focused on the adaptation for soil water repellency of a daily water balance model. Repellency is estimated from soil moisture content using site-specific empirical relations, and used to limit maximum soil moisture. This model was developed and tested using c. 2 years of data from one long-unburned and two recently burned eucalypt plantations in northern Portugal, all of which showed strong seasonal soil water repellency cycles. Results indicated important improvements for the burned plantations, with the Nash-Sutcliffe efficiency increasing from -0.55 and -0.49 to 0.55 and 0.65. For the unburned site, model performance was already good without the modification and efficiency only improved slightly from 0.71 to 0.74, mostly due to the better simulation of delayed soil wetting after dry periods. Results suggested that even a simple approach to simulate soil water repellency can markedly improve the performance of hydrological models in eucalypt forests, especially after fire. This article is protected by copyright. All rights reserved.

Beschreibung: Mucopolysaccharidosis type I (MPS I) is a rare autosomal recessive disease caused by alpha-L-iduronidase deficiency in which heparan and dermatan sulfate degradation is compromised. Besides primary lysosomal glycosaminoglycan accumulation, further changes in cellular functions have also been described in several murine MPS models. Herein, we evaluated alterations in hematopoiesis and its implications on the production of mature progeny in a MPS I murine model. Despite the significant increase in hematopoietic stem cells, a reduction in common myeloid progenitors and granulocyte-macrophage progenitor cells was observed in Idua -/- mice bone marrow. Furthermore, no alterations in number, viability nor activation of cell death mechanisms were observed in Idua -/- mice mature macrophages but they presented higher sensitivity to apoptotic induction after staurosporine treatment. In addition, changes in Ca 2+ signaling and a reduction in phagocytosis ability were also found. In summary, our results revealed significant intracellular changes in mature Idua -/- macrophages related to alterations in Idua -/- mice hematopoiesis, revealing a disruption in cell homeostasis. These results provide new insights into physiopathology of MPS I. This article is protected by copyright. All rights reserved

Beschreibung: This study describes the use of linearly modulated optically stimulated luminescence (LM-OSL) to distinguish surface-soil derived sediments from those derived from channel bank erosion. LM-OSL signals from quartz extracted from fifteen surface-soil and five channel bank samples were analysed and compared to signals from samples collected from two downstream river sites. Discriminant analysis showed that the detrapping probabilities of fast, first slow and second slow components of the LM-OSL signal can be used to differentiate between the samples collected from the channel bank and surface-soil sources. We show that for each of these source end members these components are all normally distributed. These distributions are then used to estimate the relative contribution of surface-soil derived and channel bank derived sediment to the river bed sediments. The results indicate that channel bank derived sediments dominate the sediment sources at both sites, with 90.1 ± 3% and 91.9 ± 1.9% contributions. These results are in agreement with a previous study which used measurements of 137 Cs and 210 Pb ex fallout radionuclides to estimate the relative contribution from these two sources. This result shows that LM-OSL may be a useful method, at least in the studied catchment, to estimate the relative contribution of surface soil and channel erosion to river sediments. However, further research in different settings is required to test the difference of OSL signals in distinguishing these sediment sources. And if generally acceptable, this technique may provide an alternative to the use of fallout radionuclides for source tracing. This article is protected by copyright. All rights reserved.

Beschreibung: The vadose zone plays a crucial role in the water cycle for storing water, providing water to vegetation and transporting solutes or degrading contaminants. Earth scientists have long acknowledged the importance of the vadose zone and numerous methods have been developed to better understand and predict hydrological processes within this “critical zone”. For several decades, stable isotopes ( 18 O and 2 H) of pore water are used as environmental tracers to gain insights into vadose zone water movement and other processes. To determine the pore water stable isotopic composition various sampling procedures have been developed. We present the procedure and the accompanied advantages and drawbacks of each method. We further discuss possible opportunities and limitations regarding the scale of interest and the pore space that is sampled. The methodological review reveals that the choice of the sampling method is crucial for the interpretation of pore water stable isotopes in the vadose zone, but a thorough comparison between the different methods is yet missing. Spiking experiments, where water of known isotopic composition is added to oven-dried soil, have shown to be questionable, since the extracted water is usually depleted compared to the standard water. A comparative study analyzing soil samples with the recently developed direct water-vapor equilibration method and the widely used cryogenic extraction shows deviations, which can only be partly explained, but discloses the need for a more thorough experimental comparative study. Especially promising are developments of continuous isotope measurements based on laser-based spectrometry that will open up new opportunities of analyzing pore water isotopes with higher temporal and spatial resolutions, revealing new insights into hydrological processes across various temporal and spatial scales. This article is protected by copyright. All rights reserved.

Beschreibung: In the Vietnamese Mekong Delta (VMD), water levels at some stations have increased. However, the factors that cause this rise in the VMD have not been identified. We considered four factors that may have contributed to the water level rise: (1) increased runoff from upstream, (2) sea-level rise, (3) land subsidence, and (4) decrease in flood mitigation function due to construction of high dykes. We analyzed daily maximum and minimum water levels, and mean daily water levels from 24 monitoring stations from 1987 to 2006. Using daily and annual water level differences, we classified the delta into two groups; one is dominated by flows from upstream, while the other is tide-dominated. We then tested the trends of annual maximum and minimum water levels using the Mann-Kendall test, and identified the slope of the trend using the method of Sen. The areas of dyke construction were estimated using the Enhanced Vegetation Index (EVI) and Land Surface Water Index (LSWI) from the Moderate Resolution Imaging Spectroradiometer (MODIS) data. Results show (1) river inflow has little impact on rising water levels in the VMD, (2) the influence of high dykes on water level rise could not be quantified in this study, (3) both maximum and minimum water levels significantly increased in the tide-dominated area. Trend of annual minimum water level can be considered as the sum sea-level rise and land subsidence. Therefore, we attribute 6.05 mm year −1 (80%) to land subsidence and 1.42 mm year −1 (20%) to sea level rise, indicating inundations have been severe in the VMD, caused primarily by land subsidence. This article is protected by copyright. All rights reserved.

Beschreibung: Groundwater is the principal water resource in semi-arid and arid environments. Therefore, quantitative estimates of its replenishment rate are important for managing groundwater systems. In dry regions, karst outcrops often show enhanced recharge rates compared to other surface and sub-surface conditions. Areas with exposed karst features like sinkholes or open shafts allow point recharge, even from single rainfall events. Using the example of the As Sulb plateau in Saudi Arabia, this study introduces a cost-effective and robust method for recharge monitoring and modelling in karst outcrops. The measurement of discharge of a representative small catchment (4.0·10 4  m 2 ) into a sinkhole, and hence the direct recharge into the aquifer, was carried out with a time lapse camera. During the monitoring period of two rainy seasons (autumn 2012 to spring 2014) four recharge events were recorded. Afterwards, recharge data as well as proxy data about the drying of the sediment cover are used to set up a conceptual water balance model. The model was run for 17 years (1971 to 1986 and 2012 to 2014). Simulation results show highly variable seasonal recharge-precipitation ratios between zero and 0.27. In addition to the amount of seasonal precipitation, this ratio is influenced by the interannual distribution of rainfall events. Overall, an average annual groundwater recharge for the doline (sinkhole) catchment on As Sulb plateau of 5.1 mm a −1 has estimated for the simulation period. This article is protected by copyright. All rights reserved.

Beschreibung: This paper presents an analytical model for describing the tidal effects in a two-dimensional leaky confined aquifer system in an estuarine delta where ocean and river meet. This system has an unconfined aquifer on top, a confined aquifer on the bottom with an aquitard in between the two. The unconfined and confined aquifers interact with each other through leakage. It was assumed that the aquitard storage was negligible, and that the leakage was linearly proportional to the head difference between the unconfined and confined aquifers. This model's solution was based on the separation of variables method. Two existing solutions that deal with the head fluctuation in one-dimensional or two-dimensional leaky confined aquifers are shown as special cases in the present solution. Based on this new solution, the dynamic effect of the water table's fluctuations can be clearly explored, as well as the influence of leakage on the behavior of fluctuations in groundwater levels in the leaky aquifer system. This article is protected by copyright. All rights reserved.

Beschreibung: A portable Wavelength Scanned-Cavity Ring-Down Spectrometer (Picarro L2120) fitted with a diffusion sampler (DS-CRDS) was used for the first time to continuously measure δ 18 O and δ 2 H of stream water. The experiment took place during a storm event in a wet tropical agricultural catchment in north-eastern Australia. At a temporal resolution of one minute, the DS-CRDS measured 2160 δ 18 O and δ 2 H values continuously over a period of 36 hours with a precision of ± 0.08 and 0.5 ‰ for δ 18 O and δ 2 H, respectively. Four main advantages in using high temporal resolution stream δ 18 O and δ 2 H data during a storm event are highlighted from this study. Firstly, they enabled us to separate components of the hydrograph, which was not possible using high temporal resolution electrical conductivity data that represented changes in solute transfers during the storm event rather than physical hydrological processes. The results from the hydrograph separation confirm fast groundwater contribution to the stream, with the first 5 hours of increases in stream discharge comprising over 70% pre-event water. Secondly, the high temporal resolution stream δ 18 O and δ 2 H data allowed us to detect a short-lived reversal in stream isotopic values (δ 18 O increase by 0.4 ‰ over 9 minutes), which was observed immediately after the heavy rainfall period. Thirdly, δ 18 O values were used to calculate a time lag of 20 minutes between the physical and chemical stream responses during the storm event. Finally, the hydrograph separation highlights the role of event waters in the runoff transfers of herbicides and nutrients from this heavily cultivated catchment to the Great Barrier Reef. This article is protected by copyright. All rights reserved.

Beschreibung: Quantifying the linkages between vegetation disturbance by fire and the changes in hydrologic processes leading to post-fire erosional response remains a challenge. We measured the influence of fire severity, defined as vegetation disturbance (using a satellite derived vegetation disturbance index, VDI), landscape features that organize hydrologic flow pathways (relief and elongation ratios), and pre-fire vegetation type on the probability of the occurrence of post-fire gully rejuvenation (GR). We combined field surveys across 270 burned low-order catchments (112 occurrences of GR) and geospatial analysis to generate a probabilistic model through logistic regression. VDI alone discriminated well between catchments where GR did and did not occur (area under curve = 0.78, model accuracy = 0.72). The strong effect of vegetation disturbance on GR suggests that vegetation exerts a primary influence on the occurrence of infiltration excess runoff and post-fire erosion and that major gully erosion will not occur until fire consumes above ground biomass. Other topographic and local factors also influenced GR response, including catchment elongation, percent pre-fire shrub, mid-slope riparian vegetation, armored headwaters, firehose effects, and concentration of severe burn in source areas. These factors highlight the need to consider vegetation effects in concert with local topography and site conditions to understand the propensity for flow accumulation leading to GR. We present a process-based conceptual hydrologic model where vegetation loss from fire decreases rainfall attenuation and surface roughness, leading to accelerated flow accumulation and erosion; these effects are also influenced by interactions between fire severity and landscape structure. The VDI metric provides a continuous measure of vegetation disturbance and, when placed in a hydrologic context, may improve quantitative analysis of burned-area susceptibility to erosive rainfall, hazard prediction, ecological effects of fire, landform evolution, and sensitivity to climate change. This article is protected by copyright. All rights reserved.

Beschreibung: There is considerable interest in naturalizing flow regime on managed rivers to slow the spread of saltcedar ( Tamarix ramosissima ) invasion in southwestern United States or to preserve riparian forests dominated by saltcedar and other species in northwestern China. However, little is known about the responses of established saltcedar in water sources to frequent intra-annual fluctuation of water table resulting from this new, more dynamic flow regime. This study investigates how saltcedar at a riparian site in the middle reaches of the Heihe River, northwest China responds in water sources use to intra-annual water table fluctuations. Stable oxygen isotope was employed to determine accurate depth at which saltcedar obtains its water supply, and soil moisture monitoring was used to determine sources of plant-available soil water. We found that the primary zone of water uptake by saltcedar was stable at 25-60 cm depth, but the water sources used by saltcedar switched between groundwater and soil moisture with the water table fluctuations. Saltcedar derived its water from groundwater when water table was at depth less than 60 cm, but switched to soil moisture at 25-60 cm depth when water table declined. It is supposed that the well-developed clay layer at 60–80 cm depth constrained lateral roots of saltcedar to the soil layers above 60 cm, while the fine-textured soils at this site, which was periodically re-saturated by rising groundwater before the stored soil moisture had become depleted, provided an important water reservoir for saltcedar when groundwater dropped below the primary zone of fine roots. The root distribution of saltcedar may also be related to local groundwater history. The quick decline in water table in the early 1980s when the riparian saltcedar had established may strand its roots in the shallow unsaturated zone. We suggested that raising the water table periodically instead of maintaining it invariably above the rooting depth could sustain desired facultative phreatophytes while maximizing water deliveries. This article is protected by copyright. All rights reserved.

Beschreibung: Chondrogenesis subtends the development of most skeletal elements and involves mesenchymal cell condensations differentiating into growth plate chondrocytes that proliferate, undergo hypertrophy and are replaced by bone. In the pediatric disorder Hereditary Multiple Exostoses, however, chondrogenesis occurs also at ectopic sites and causes formation of benign cartilaginous tumors –exostoses- near the growth plates. No treatment is currently available to prevent or reverse exostosis formation. Here, we asked whether chondrogenesis could be stopped by targeting the hedgehog pathway, one of its major regulators. Micromass cultures of limb mesenchymal cells were treated with increasing amounts of the hedgehog inhibitor HhAntag or vehicle. The drug effectively blocked chondrogenesis and did so in a dose-dependent manner as monitored by: alcian blue-positive cartilage nodule formation; gene expression of cartilage marker genes; and reporter activity in Gli1-LacZ cell cultures. HhAntag blocked chondrogenesis even when the cultures were co-treated with bone morphogenetic protein 2 (rhBMP-2), a strong pro-chondrogenic factor. Immunoblots showed that HhAntag action included modulation of canonical (pSmad1/5/8) and non-canonical (pp38) BMP signaling. In cultures co-treated with HhAntag plus rhBMP-2, there was a surprising strong up-regulation of pp38 levels. Implantation of rhBMP-2-coated beads near metacarpal elements in cultured forelimb explants induced formation of ectopic cartilage that however, was counteracted by HhAntag co-treatment. Collectively, our data indicate that HhAntag inhibits not only hedgehog signaling, but also modulates canonical and non-canonical BMP signaling and blocks basal and rhBMP2-stimulated chondrogenesis, thus representing a potentially powerful drug-based strategy to counter ectopic cartilage growth or induce its involution. This article is protected by copyright. All rights reserved

Beschreibung: ABSTRACT Cholangiocarcinoma (CCAs) may be defined as tumors that derived from the biliary tree with the differentiation in the biliary epithelial cells. This tumor is malignant, extremely aggressive with a poor prognosis. It can be treated surgically and its pathogenesis is poorly understood. The tumor microenvironment (TME) is a very important factor in the regulation of tumor angiogenesis, invasion, and metastasis. Besides cancer stem cells (CSCs) can modulate tumor growth, stroma formation and migratory capability. The initial stage of tumorigenesis is characterized by genetic mutations and epigenetic alterations due to intrinsic factors which lead to the generation of oncogenes thus inducing tumorigenesis. CSCs may result from precancerous stem cells, cell de-differentiation, normal stem cells or an epithelial-mesenchymal transition (EMT). CSCs have been found in the cancer niche, and EMT may occur early within the tumor microenvironment. Previous studies have demonstrated evidence of cholangiocarcinoma stem cells (CD133, CD24, EpCAM, CD44, and others) and the presence of these markers has been associated with malignant potential. The interaction between TME and cholangiocarcinoma stem cells via signaling mediators may create an environment that accommodates tumor growth, yielding resistance to cytotoxic insults (chemotherarapeutic). While progress has been made in the understanding of the mechanisms, the interactions in the tumorigenic process still remain a major challenge. Our review, addresses recent concepts of TME-CSCs interaction and will emphasize the importance of early detection with the use of novel diagnostic mechanisms such as CCA-CSC biomarkers and the importance of tumor stroma to define new treatments. This article is protected by copyright. All rights reserved

Beschreibung: ABSTRACT Early detection of colorectal cancer (CRC) remains a challenge. It has been highlighted that the pathological alterations within an organ and tissues might be reflected in serum or plasma proteomic/peptidic patterns. The aim of the study was to follow the changes in the plasma peptides associated to colorectal cancer progression by mass spectrometry. This study included 27 adenoma, 67 CRC (n = 33 I-II stage and n = 34 III-IV stage), 23 liver metastasis from CRC patients and 34 subjects disease-free as controls. For plasma peptides analysis, samples purification was performed on the Nanoporous Silica Chips technology followed by matrix-assisted laser desorption/ionisation-time of flight analysis. Since the high complexity of the obtained dataset, multivariate statistical analysis and discriminant pattern recognition were performed for study groups classification. Forty-four of 88 ionic species were successfully identified as fragments of peptides and proteins physiologically circulating in the blood and belonging to immune and coagulation systems and inflammatory mediators. Many peptides clustered into sets of overlapping sequences with ladder-like truncation clearly associated to proteolytic processes of both endo- and exoproteases activity. Comparing to controls, a different median ion intensity of the group-type fragments distribution was observed. Moreover, the degradation pattern obtained by proteolytic cleavage was different into study groups. This pattern was specific and characteristic of each group: controls, colon tumour disease (including adenoma and CRC) and liver metastasis, revealing a role as biomarker in early diagnosis and prognosis. Our findings highlighted peculiar changes in protease activity characteristic of CRC progression from pre-cancer lesion to metastatic disease. This article is protected by copyright. All rights reserved

Beschreibung: ABSTRACT The aim of this study was to verify the effects of running overtraining protocols performed in downhill, uphill and without inclination on the proteins related to hypertrophy signaling pathway in extensor digitorum longus (EDL) and soleus of C57BL/6 mice. We also performed histological and stereological analyses. Rodents were divided into control (CT; sedentary mice), overtrained by downhill running (OTR/down), overtrained by uphill running (OTR/up) and overtrained by running without inclination (OTR). The incremental load, exhaustive and grip force tests were used as performance evaluation parameters. 36h after the grip force test, EDL and soleus were removed and immediately used for immunoblotting analysis or stored at -80 ° C for histological and stereological analyses. For EDL, OTR/down decreased the protein kinase B (Akt) and tuberous sclerosis protein 2 (TSC2) phosphorylation (p), and increased myostatin, receptor-activated Smads (pSMAD2-3) and insulin receptor substrate-1 (pIRS-1; Ser307/636). OTR/down also presented low and high relative proportions of cytoplasm and connective tissue, respectively. OTR/up increased the mammalian target of rapamycin (pmTOR), 70-kDa ribosomal protein S6 kinase 1 (pS6K1) and pSMAD2-3, and decreased pTSC2. OTR decreased pTSC2 and increased pIRS-1 (Ser636). For soleus, OTR/down increased S6 ribosomal protein (pS6RP) and pSMAD2-3, and decreased pIRS-1 (Ser639). OTR/up decreased pS6K1, pS6RP and pIRS-1 (Ser639), and increased pTSC2 (Ser939) and pSMAD2-3. OTR increased pS6RP, 4E-binding protein-1 (p4E-BP1), pTSC2 (Ser939), and pSMAD2-3, and decreased pIRS-1 (Ser639). In summary, OTR/down inhibited the skeletal muscle hypertrophy with concomitant signs of atrophy in EDL. The effects of OTR/up and OTR depended on the analyzed skeletal muscle type. This article is protected by copyright. All rights reserved

Beschreibung: Pain can vary over the estrous cycle as a result of changes in estradiol concentration but the mechanism causing this variation is unclear. Because the thalamus is important in pain control, gene expression in the lateral thalamus (ventral posteromedial, ventral posterolateral, reticular thalamic nuclei) was screened at different phases of the estrous cycle. Gene expression changes in Sprague-Dawley rats were further analyzed by real-time PCR and ELISA and plasma estradiol levels were measured by RIAs at different phases of the estrous cycle. Our results indicated that both the RNA and protein expression of glutamate decarboxylase 1 and 2 (GAD1, GAD2), GABA(A) receptor-associated protein like 1 (GABARAPL1) and vesicular GABA transporter (VGAT) significantly increased in the lateral thalamus when plasma estradiol levels were elevated. Estradiol levels were elevated during the proestrus and estrus phases of the estrous cycle. Estrogen receptor α (ERα) was observed to be co-localized in thalamic cells and thalamic infusion of an ERα antagonist significantly reduced GAD1 and VGAT transcript. GAD1, GAD2 GABARAPL1 and VGAT have been shown to effect neuronal responses suggesting that modulation of pain during the estrous cycle can be dependent, in part, through estradiol induced changes in thalamic gene expression. This article is protected by copyright. All rights reserved

Beschreibung: Generation of fully functional hematopoietic multipotent progenitor (MPP) cells from human pluripotent stem cells (hPSCs) has a great therapeutic potential to provide an unlimited cell source for treatment of hematological disorders. We previously demonstrated that CD34 + CD31 + CD144 + population derived from hPSCs contain hemato-endothelial progenitors (HEPs) that give rise to hematopoietic and endothelial cells. Here, we report a differentiation system to generate definitive hematopoietic MPP cells from HEPs via endothelial monolayer. In the presence of angiogenic factors, HEPs formed an endothelial monolayer, from which hematopoietic clusters emerged through the process of endothelial-to-hematopoietic transition (EHT). EHT was significantly enhanced by hematopoietic growth factors. The definitive MPP cells generated from endothelial monolayer were capable of forming multilineage hematopoietic colonies, giving rise to T lymphoid cells, and differentiating into enucleated erythrocytes. Emergence of hematopoietic cells from endothelial monolayer occurred transiently. Hematopoietic potential was lost during prolonged culture of HEPs in endothelial growth conditions. Our study demonstrated that CD34 + CD31 + CD144 + HEPs gave rise to hematopoietic MPP cells via hemogenic endothelial cells that exist transiently. The established differentiation system provides a platform for future investigation of regulatory factors involved in de novo generation of hematopoietic MPP cells and their applications in transplantation. This article is protected by copyright. All rights reserved

Beschreibung: Epididymal sperm binding protein 1 (ELSPBP1) is secreted by the epididymal epithelium via epididymosomes and is specifically transferred to dead spermatozoa during epididymal transit. We identified biliverdin reductase A (BLVRA) as a partner of ELSPBP1 by immunoprecipitation followed by tandem mass spectrometry. Pull down assays showed that these two proteins interact in the presence of zinc ions. The BLVRA enzyme is known to convert biliverdin to bilirubin, both of which possess antioxidant activity. Assessment by real-time RT-PCR showed that BLVRA is highly expressed in the caput and the corpus epididymis, but is expressed at lower levels in the testis and the cauda epididymis. It is primarily found in the soluble fraction of the caput epididymal fluid, is barely detectable in the cauda fluid, and is detectable to a lesser extent in the epididymosome fraction of both caput and cauda fluids. Immunocytometry on epididymal sperm showed that BLVRA is found on all sperm recovered from the caput region, whereas it is undetectable on cauda sperm. biliverdin and bilirubin are found in higher concentrations in the caput epididymal fluid, as measured by mass spectrometry. Lipid peroxidation was limited by 1 μM of biliverdin, but not bilirubin when caput spermatozoa were challenged with 500 μM H 2 O 2 . Since immature spermatozoa are a source of reactive oxygen species, BLVRA may be involved in the protection of maturing spermatozoa. It is also plausible that BLVRA is implicated in haemic protein catabolism in the epididymal luminal environment. This article is protected by copyright. All rights reserved

Beschreibung: Secondary circulation is the component of three-dimensional (3-D) flow in river channels perpendicular to the primary flow direction. Secondary circulation calculated from ADCP transects is sensitive to the calculation method, and is affected by the transect angle relative to the mean flow direction and variations in the flow direction along a transect. To quantify bounds on transect alignment relative to river flow for field data collection and examine tidal time-scale variability in secondary circulation, the 3-D hydrodynamic model UnTRIM was applied to simulate the hydrodynamics in the lower reach of the Sacramento River (CA, USA). Secondary circulation was calculated using the Rozovskii and the zero net discharge methods on repeated transects extracted from the model results in regions of both relatively uniform and complex flows. When the depth-averaged flow direction along a transect varied by more than about 5 degrees, occurring when the transect was as little as 10 to 20 degrees out of normal to the mean flow direction, the Rozovskii method produced more realistic secondary circulation than the zero net discharge method. Analysis indicated that ADCP transects should be within 20 degrees of perpendicular to the mean flow direction when calculating secondary circulation. Secondary circulation strength around two tidally influenced bends generally increased with increasing flow and broke down near slack water. However, the strength of the secondary circulation was not only a function of the flow magnitude, but also depended on the direction of the water flow, and the transect location relative to the river curvature, which varied with the tidal flow direction. This article is protected by copyright. All rights reserved.

Beschreibung: Oxygen levels range from 2-9% in vivo . Atmospheric O 2 levels (21%) are known to induce cell proliferation defects and cellular senescence in primary cell cultures. However, the mechanistic basis of the deleterious effects of higher O 2 levels is not fully understood. On the other hand, immortalized cells including cancer cell lines, which evade cellular senescence are normally cultured at 21% O 2 and the effects of higher O 2 on these cells are understudied. Here we addressed this problem by culturing immortalized human bronchial epithelial (BEAS-2B) cells at ambient atmospheric, 21% O 2 and lower, 10% O 2 . Our results show increased inflammatory response at 21% O 2 but not at 10% O 2 . We found higher RelA binding at the NF-κB1/RelA target gene promoters as well as upregulation of several pro-inflammatory cytokines in cells cultured at 21% O 2 . RelA knockdown prevented the upregulation of the pro-inflammatory cytokines at 21% O 2 , suggesting NF-κB1/RelA as a major mediator of inflammatory response in cells cultured at 21% O 2 . Interestingly, unlike the 21% O 2 cultured cells, exposure of 10% O 2 cultured cells to H 2 O 2 did not elicit inflammatory response, suggesting increased ability to tolerate oxidative stress in cells cultured at lower O 2 levels. This article is protected by copyright. All rights reserved

Beschreibung: Acute inflammation is accompanied from its outset by the release of specialized pro-resolving mediators (SPMs), including resolvins, that orchestrate the resolution of local inflammation. We showed earlier that, in rats with subcutaneous inflammation of the back induced by carrageenan, stretching for 10 minutes twice daily reduced inflammation and improved pain, two weeks after carrageenan injection. In this study, we hypothesized that stretching of connective tissue activates local pro-resolving mechanisms within the tissue in the acute phase of inflammation. In rats injected with carrageenan and randomized to stretch vs. no stretch for 48 hours, stretching reduced inflammatory lesion thickness and neutrophil count, and increased resolvin (RvD1) concentrations within lesions. Furthermore, subcutaneous resolvin injection mimicked the effect of stretching. In ex vivo experiments, stretching of connective tissue reduced the migration of neutrophils and increased tissue RvD1 concentration. These results demonstrate a direct mechanical impact of stretching on inflammation-regulation mechanisms within connective tissue. This article is protected by copyright. All rights reserved

Beschreibung: Flooding associated with tropical storms can cause extreme perturbations in riverine and coastal ecosystems. Measuring isotope variability of tropical storm events can help investigate the impacts of flooding. We measured the water isotope composition (δD and δ 18 O) of rain and associated floodwater collected during two storms and subsequent major and minor flooding events in the subtropical coast of eastern Australia. Compared to baseline regional rainfall isotope values of -15.0 ± 1.9‰ for δD and -3.3 ± 0.2‰ for δ 18 O, floodwater had lower values with -33.8 ± 2.5‰ δD and -5.1 ± 0.4‰ δ 18 O for the major flood and -29.4 ± 1.0‰ δD and -4.6 ± 0.1‰ δ 18 O for the minor flood. The low isotope composition of the floodwater was associated with the transport of large quantities of suspended sediments, with sediment loads 30 to 70 times larger than during base flow conditions. Floods carried up to 35% of the annual phosphorus and up to 208% of the currently calculated average annual nitrogen load of the Brisbane River. The dramatic changes caused by a rapid increase in discharge from 2 to 2,015 m 3 s -1 over two days in the major flood would have major consequences in riverine and coastal ecosystems of the region. These changes could potentially be traced using the isotope composition of the floodwaters. This article is protected by copyright. All rights reserved.

Beschreibung: Large river floods are a key water source for many lakes in fluvial periglacial settings. Where permeable sediments occur, the distribution of permafrost may play an important role in the routing of floodwaters across a floodplain. This relationship is explored for lakes in the discontinuous permafrost of Yukon Flats, interior Alaska, using an analysis that integrates satellite-derived gradients in water surface elevation, knowledge of hydrogeology, and hydrologic modeling. We observed gradients in water surface elevation between neighboring lakes ranging from 0.001 to 0.004. These high gradients, despite a ubiquitous layer of continuous shallow gravel across the flats, are consistent with limited groundwater flow across lake basins resulting from the presence of permafrost. Permafrost impedes the propagation of floodwaters in the shallow subsurface and constrains transmission to “fill-and-spill” over topographic depressions (surface sills), as we observed for the Twelvemile-Buddy Lake pair following a May 2013 ice-jam flood on the Yukon River. Model results indicate that permafrost table deepening of 1–11 m in gravel, depending on watershed geometry and subsurface properties, could shift important routing of floodwater to lakes from overland flow (fill-and-spill) to shallow groundwater flow (“fill-and-seep”). Such a shift is possible in the next several hundred years of ground surface warming, and may bring about more synchronous water level changes between neighboring lakes following large flood events. This relationship offers a potentially useful tool, well-suited to remote sensing, for identifying long-term changes in shallow groundwater flow resulting from thawing of permafrost. This article is protected by copyright. All rights reserved.

Beschreibung: Imperviousness, considered as a critical indicator of the hydrologic impacts of urbanization, has gained increasing attention both in the research field and in practice. However, the effectiveness of imperviousness on rainfall-runoff dynamics has not been fully determined in a fine spatiotemporal scale. In this study, 69 drainage subareas 〈 1 ha of a typical residential catchment in Beijing were selected to evaluate the hydrologic impacts of imperviousness, under a typical storm event with a three-year return period. Two metrics, total impervious area (TIA) and effective impervious area (EIA), were identified to represent the impervious characteristics of the selected subareas. Three runoff variables, total runoff depth (TR), peak runoff depth (PR), and lag time (LT), were simulated by using a validated hydrologic model. Regression analyses were developed to explore the quantitative associations between imperviousness and runoff variables. Then, three scenarios were established to test the applicability of the results in considering the different infiltration conditions. Our results showed that runoff variables are significantly related to imperviousness. However, the hydrologic performances of TIA and EIA were scale-dependent. Specifically, with finer spatial scale and the condition heavy rainfall, TIA rather than EIA was found to contribute more to TR and PR. EIA tended to have a greater impact on LT and showed a negative relationship. Moreover, the relative significance of TIA and EIA was maintained under the different infiltration conditions. These findings may provide potential implications for landscape and drainage design in urban areas, which help to mitigate the runoff risk. This article is protected by copyright. All rights reserved.

Beschreibung: Bone morphogenetic proteins 2 and 4 (BMP2/4) are essential for osteoblast differentiation and osteogenesis. Generation of a BMP2/4 dual knock out ( ko/ko ) osteoblastic cell line is a valuable asset for studying effects of BMP2/4 on skeletal development. In this study, our goal was to create immortalized mouse deleted BMP2/4 osteoblasts by infecting adenoviruses with Cre recombinase and green fluorescent protein genes into immortalized murine floxed BMP2/4 osteoblasts. Transduced BMP2/4 ko/ko cells were verified by green immunofluorescence and PCR. BMP2/4 ko/ko osteoblasts exhibited small size, slow cell proliferation rate and cell growth was arrested in G1 and G2 phases. Expression of bone-relate genes was reduced in the BMP2/4 ko/ko cells, resulting in delay of cell differentiation and mineralization. Importantly, extracellular matrix remodeling was impaired in the BMP2/4 ko/ko osteoblasts as reflected by decreased Mmp-2 and Mmp-9 expressions. Cell differentiation and mineralization were rescued by exogenous BMP2 and/or BMP4. Therefore, we for the first time described establishment of an immortalized deleted BMP2/4 osteoblast line useful for study of mechanisms in regulating osteoblast lineages. This article is protected by copyright. All rights reserved

Beschreibung: Voltage-gated potassium Kv1.2 channels play pivotal role in maintaining of resting membrane potential and, consequently, regulation of cellular excitability of neurons. Endogenously generated electric field (EF) have been proven as an important regulator for cell migration and tissue repair. The mechanisms of ion channel involvement in EF-induced cell responses are extensively studied but largely are poorly understood. In this study we generated three COS-7 clones with different expression levels of Kv1.2 channel, and confirmed their functional variations with patch clamp analysis. Time-lapse imaging analysis showed that EF-induced cell migration response was Kv1.2 channel expression level depended. Inhibition of Kv1.2 channels with charybdotoxin (ChTX) constrained the sensitivity of COS-7 cells to EF stimulation more than their motility. Immunocytochemistry and pull-down analyses demonstrated association of Kv1.2 channels with actin-binding protein cortactin and its re-localization to the cathode-facing membrane at EF stimulation, which confirms the mechanism of EF-induced directional migration. This study displays that Kv1.2 channels represent an important physiological link in EF-induced cell migration. The described mechanism suggests a potential application of EF which may improve therapeutic performance in curing injuries of neuronal and/or cardiac tissue repair, post operational therapy and various degenerative syndromes. This article is protected by copyright. All rights reserved

Beschreibung: The presence or absence of snow and its seasonal variability have profound effects on the climate, energy balance, and ecology in high-latitude and high-altitude regions of the world. While the timing, amount and duration of snow and its water content is of fundamental importance for several natural processes, it is also a convincing indicator of climate change in seasonally snow covered regions. The reduction in the amount and duration of the snow pack that already may have begun to happen across large geographic areas risks affecting several of the important ecosystem services that snow provides. Despite its fundamental role, snow and especially its water content is one of the least monitored climate variables in many seasonally snow-covered regions. Therefore we add complimentary long-term snow depth data (1980–2015) and snow water equivalent (SWE) data (1986–2015) to an already well established field research infrastructure – the Krycklan Catchment Study in northern Sweden. By combining digitized snow data to the already available long-term daily precipitation, runoff, and water quality information the ambition is to provide a more holistic database. While the primary purpose of this data release is to make the data readily available to any interested user, it also shows that the length of seasonal winter snow cover has shortened, especially because of its later arrival in the autumn, at the study site over the 35 year monitoring period. This article is protected by copyright. All rights reserved.

Beschreibung: Dentin matrix protein 1 (DMP1) is found abundantly in the extracellular matrices of bone and dentin. Secretory DMP1 begins with a tripeptide of leucine-proline-valine (LPV) after the endoplasmic reticulum (ER)-entry signal peptide is cleaved. The goal of this study was to determine the role of the LPV motif in the secretion of DMP1. A series of DNA constructs was generated to express various forms of DMP1 with or without the LPV motif. These constructs were transfected into a preosteoblast cell line, the MC3T3-E1 cells, and the subcellular localization and secretion of various forms of DMP1 were examined by immunofluorescent staining and Western-blotting analyses. Immunofluorescent staining showed that the LPV-containing DMP1 variants were primarily localized in the Golgi complex, whereas the LPV-lacking DMP1 variants were found abundantly within the ER. Western-blotting analyses demonstrated that the LPV-containing DMP1 variants were rapidly secreted from the transfected cells, as they did not accumulate within the cells, and the amounts increased in the conditioned media over time. In contrast, the LPV-lacking DMP1 variants were predominantly retained within the cells, and only small amounts were secreted out of the cells over time. These results suggest that the LPV motif is essential for the efficient export of secretory DMP1 from the ER to the Golgi complex. This article is protected by copyright. All rights reserved

Beschreibung: Tree-ring-based reconstructions of paleo-hydrology have proved useful for better understanding the irregularities and extent of past climate changes, and therefore, for more effective water resources management. Despite considerable advances in the field, there still exist challenges that introduce significant uncertainties into paleo-reconstructions. This study outlines these challenges and address them by developing two themes: (1) the effect of temporal scaling on the strength of the relationship between the hydrologic variables, streamflow in this study, and tree growth rates, and (2) the reconstruction uncertainty of streamflow due to the dissimilarity or inconsistency in the pool of tree-ring chronologies (predictors in reconstruction) in a basin. Based on the insight gained, a methodology is developed to move beyond only relying on the annual hydrology-growth correlations, and to utilize additional information embedded in the annual time series at longer time scales (e.g, multi-year to decadal time scales). This methodology also generates an ensemble of streamflow reconstructions to formally account for uncertainty in the pool of chronology sites. The major headwater tributaries of the Saskatchewan River basin, the main source of surface water in the Canadian Prairie Provinces, are used as the case study. It is shown that the developed methodology explains the variance of streamflows to a larger extent than the conventional approach, and better preserves the persistence and variability of streamflows across time scales (Hurst-type behaviour). The resulting ensemble of paleo-hydrologic time series is able to more credibly pinpoint the timing and extent of past dry and wet periods, and provides a dynamic range of uncertainty in reconstruction. This range varies with time over the course of the reconstruction period, indicating that the utility of tree-ring chronologies for paleo-reconstruction differs for different time periods over the past several centuries in the history of the region. The proposed ensemble approach provides a credible range of multiple-century-long water availability scenarios that can be used for vulnerability assessment of the existing water infrastructure and improving water resources management. This article is protected by copyright. All rights reserved.

Beschreibung: Discharge in mountain streams may be a mixture of snowmelt, water from surface runoff, and deep return flow through valley bottom alluvia. We used δ 18 O and δ 2 H, solute concentrations, and 222 Rn to determine water sources of a headwater stream located at the McDonald Creek watershed, Glacier National Park, USA during summer recession flow period. We analyzed minimal water isotope ranges of -17.6 to -16.5‰ and -133 to -121‰ for δ 18 O and δ 2 H, respectively, potentially due to dominance of snow-derived water in the stream. Likewise, solute concentrations measured in the stream through the watershed showed minimal variation with little indication of sub-surface water input into the stream. However, we observed 222 Rn activities in the stream that ranged from 39 to 2,646 Bq/m 3 with the highest value measured in middle of the watershed associated with channel constriction corresponding to changes in local orientation of underlying rocks. Downstream from this point, 222 Rn activity decreased from 581 to 117 Bq/m 3 in a series of punctuated steps associated with small rapids and waterfalls that we hypothesized to cause radon degassing with a maximum predicted loss of 427 Bq/m 3 along a 400 m distance. Based on mass balance calculations using 222 Rn activity values, streamflow, and channel characteristics, we estimated that groundwater contributed between 0.3 and 29% of total flow. Overall, we estimated a 5.9% of groundwater contribution integrated for stream reach measured at McDonald Creek during recession flow period. Finally, a lower mean hyporheic flux of 14 m 3 /day was estimated compared to the groundwater flux of 70,710 m 3 /day. These assessments highlight the potential for radon as a conservative tracer that can be used to estimate sub-surface water contribution in mountain streams within a complex geologic setting. This article is protected by copyright. All rights reserved.

Beschreibung: Although 〉90 of the human genome is transcribed, only 〈2% is transcribed into protein-coding RNA (messenger RNA, mRNA). Many thousands of noncoding RNAs are transcribed and recognized as functional RNAs with diverse sizes, structures and biological functions. Based on size, noncoding RNA can be generally divided into two subgroups: short noncoding RNA (〈 200 nucleotides including microRNA or miRNA) and long noncoding RNA (lncRNA, 〉 200 nucleotides). It is now clear that these RNAs fulfil critical roles as transcriptional and post-transcriptional regulators and as guides of chromatin-modifying complexes. Although not translated into protein, noncoding RNAs can regulate cardiac function through diverse mechanisms and their dysregulation is increasingly linked with cardiovascular pathophysiology. Furthermore, a series of recent studies have discovered that noncoding RNAs can be found in the bloodstream and some species are remarkably stable. This has raised the possibility that such noncoding RNAs may be measured in body fluids and serve as novel diagnostic biomarkers. Here, we summarize the current knowledge of noncoding RNAs' function and biomarker potential in cardiac diseases, concentrating mainly on circulating miRNAs and lncRNAs. This article is protected by copyright. All rights reserved

Beschreibung: Increasing evidence indicates that long noncoding RNAs (lncRNAs) are involved in diverse biological process. Mouse maternal expressed gene 3 (Meg3), is an imprinted gene and essential for development. Here, we explored the relationship between Meg3 and the function of mouse beta cells in vitro and vivo . Real-time PCR analyses revealed Meg3 was more abundantly expressed in Balb/c mouse islets than exocrine glands. Moreover, the expression of Meg3 in islets was decreased in T1DM (NOD female mice) and T2DM (db/db mice) models. Meg3 expression was modulated dynamically by glucose in Min6 cells and isolated mouse islets. The function role of Meg3 was investigated in Min6 cells and normal mouse by knockdown of Meg3 using small interfering RNA. After suppression of Meg3 expression in vitro , insulin synthesis and secretion were impaired and the rate of beta cells apoptosis was increased. Moreover, knockdown of Meg3 in vivo led to the impaired glucose tolerance and decreased insulin secretion, consisted with the reduction of insulin positive cells areas by immunochemistry assays. Notably, islets from Meg3 interference groups showed significant decrease of Pdx-1 and MafA expression in mRNA and protein levels. These results indicate that Meg3 may function as a new regulator of maintaining beta cells identity via affecting insulin production and cell apoptosis. This article is protected by copyright. All rights reserved

Beschreibung: Vegetative filter strips (VFS) can effectively trap sediment in overland flow, but little information is available on its performance in controlling high-concentration sediment and the runoff hydraulics in VFS. Flume experiments were conducted to investigate the sediment deposition, hydraulics of overland flow and their relationships in simulating VFS under a great range of sediment concentrations with four levels of vegetation cover (bare slope and 4, 11 and 17%) and two flow rates (15 and 30 L min −1 ). Sediment concentrations varied from 30 to 400 kg m −3 and slope gradient was 9°. Both the deposited sediment load and deposition efficiency in VFS increased as the vegetation cover increased. Sediment concentration had a positive effect on the deposited load but no effect on deposition efficiency. A lower flow rate corresponded to greater deposition efficiency but had little effect on deposited load. Flow velocities decreased as vegetation cover increased. Sediment concentration had a negative effect on the mean velocity but no effect on surface velocity. Hydraulic resistance increased as the vegetation cover and sediment concentration increased. Sediment deposition efficiency had a much more pronounced relationship with overland flow hydraulics compared with deposited load, especially with the mean flow velocity, and there was a power relationship between them. Flow regime also affected the sediment deposition efficiency, and the efficiency was much higher under subcritical than supercritical flow. The results will be useful for the design of VFS and the control of sediment flowing into rivers in areas with serious soil erosion.

Beschreibung: Recent changes in land use and new industrial developments in river basins around the world have raised serious concerns regarding future water quality. Assessment of regional nutrient export from river basins are needed in order to identify main nutrient sources and hydrological variables involved. The Red Deer River catchment in Alberta, Canada has been chosen as a test case to assess total phosphorus export regionally. Agricultural and livestock activities in the catchment have increased manure production and the supply of fertilizer to crops. Oil and gas exploitation has also increased the risk of surface water and groundwater contamination. The rapid population growth has not only lead to increases in water consumption and wastewater discharges, but also to further construction of transportation infrastructure and the expansion of new urban developments. This has imposed hydraulic controls on waterways, affecting the catchment hydrology and changing the dynamics of sediment and nutrient transport. River ecosystems are not exempt from the negative effects of water quality deterioration. Downstream from the city of Red Deer, the physiology and reproduction habits of native fish species have changed due to high riverine productivity. Although improvements have been made to surface water quality standards by Alberta Environment, further research is needed in order to identify major nutrient sources and quantify nutrient export. The SPAtially Referenced Regression On Watershed (SPARROW) model has therefore been used in this study of the Red Deer River catchment to assess regional water quality, in order to describe the spatial and temporal patterns of the processes that affect water quality. The model is suitable for interpreting monitoring data sets that suffer from network sparseness, bias and basin heterogeneity. Ultimately, the model could provide improved information to environmental agencies to guide future water quality management practices and policies.

Beschreibung: Interleukin-24 (IL-24) is a unique IL-10 family cytokine that could selectively induce apoptosis in cancer cells without harming normal cells. Previous research demonstrated that intracellular IL-24 protein induces an endoplasmic reticulum (ER) stress response only in cancer cells, culminating in apoptosis. In this study, we developed a novel recombinant fusion protein to penetrate into cancer cells and locate on ER. It is composed of three distinct functional domains, IL-24, and the targeting domain of transactivator of transcription (TAT) and an ER retention four-peptide sequence KDEL (Lys-Asp-Glu-Leu) that link at its NH 2 and COOH terminal, respectively. The in vitro results indicated that TAT-IL-24-KDEL inhibited growth in bladder cancer cells, as well as in non-small cell lung cancer cell line and breast cancer cell line, but the normal human lung fibroblast cell line was not affected, indicating the cancer specificity of TAT-IL-24-KDEL. Western blot analysis showed that apoptosis activation was induced by TAT-IL-24-KDEL through the ER stress-mediated cell death pathway. Treatment with TAT-IL-24-KDEL significantly inhibited the growth of human H460 xenografts in nude mice, and the tumor growth inhibition was correlated with increased hematoxylin and eosin (H&E) staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. These findings suggest that the artificially designed recombinant fusion protein TAT-IL-24-KDEL may be highly effective in cancer therapy and worthy of further evaluation and development. This article is protected by copyright. All rights reserved

Beschreibung: MicroRNAs (miRNAs) are a group of small non-coding RNAs that are involved in regulating a range of developmental and physiological processes; their dysregulation has been associated with development of diseases including cancer. Circulating miRNAs and exosomal miRNAs have also been proposed as being useful in diagnostics as biomarkers for diseases and different types of cancer. In this review, miRNAs are discussed as biomarkers for cancer and other diseases, including viral infections, nervous system disorders, cardiovascular disorders, and diabetes. We summarize some of the clinical evidence for the use of miRNAs as biomarkers in diagnostics and provide some general perspectives on their use in clinical situations. The analytical challenges in using miRNAs in cancer and disease diagnostics are evaluated and discussed. Validation of specific miRNA signatures as biomarkers is a critical milestone in diagnostics. This article is protected by copyright. All rights reserved

Beschreibung: ABSTRACT Bacterial lipopolysaccharide (LPS)-stimulated hepatic stellate cells (HSCs) produce many cytokines including IFNβ, TNFα and IL6, strongly inhibit DNA synthesis, but induce apoptosis of a small number of hepatocytes. In vivo administration of LPS (up to 10 mg/ml) causes modest inflammation and weight loss in rats but not mortality. We determined whether LPS-stimulated HSCs instigate mechanisms of hepatocyte survival. Rats received 10 mg/kg LPS (i.p.) and determinations were made at 6h. In vitro , HSCs were treated with 100 ng/ml LPS till 24h. The medium was transferred to hepatocytes, and determinations were made at 0-12h. Controls were HSC-conditioned medium or medium-containing LPS. LPS treatment of rats caused autophagy in hepatocytes, a physiological process for clearance of undesirable material including injured or damaged organelles. This was accompanied by activation of c-Jun NH2 terminal kinase (JNK) and apoptosis of ∼4-5% of hepatocytes. In vitro , LPS-conditioned HSC medium (LPS/HSC) induced autophagy in hepatocytes but apoptosis of only ∼10% of hepatocytes. While LPS/HSC stimulated activation of JNK (associated with cell death), it also activated NFkB and ERK1/2 (associated with cell survival). LPS-stimulated HSCs produced IFNβ, and LPS/HSC-induced autophagy in hepatocytes and their apoptosis were significantly inhibited by anti-IFNβ antibody. Blockade of autophagy, on the other hand, strongly augmented hepatocyte apoptosis. While LPS-stimulated HSCs cause apoptosis of a subpopulation of hepatocytes by producing IFNβ, they also induce cell survival mechanisms, which may be of critical importance in resistance to liver injury during endotoxemia. This article is protected by copyright. All rights reserved

Beschreibung: ABSTRACT In cancer therapy, it is imperative to increase the efficacy and reduce side effects of chemotherapeutic drugs. Nanotechnology offers the unique opportunity to overcome these barriers. In particular, in the last few years DNA nanostructures have gained attention for their biocompatibility, easy customized synthesis and ability to deliver drugs to cancer cells. Here, an open-caged pyramidal DNA@Doxorubicin ( Py-Doxo ) nanostructure was constructed with 10 DNA sequences of 26–28 nucleotides for drug delivery to cancer cells. The synthesized DNA nanostructures are sufficiently stable in biological medium. Py-Doxo exhibited significantly enhanced cytotoxicity of the delivered doxorubicin to breast and liver cancer cells up to two fold compared to free doxorubicin. This study demonstrates the importance of the shape and structure of the designed transporter DNA nanostructures for biomedical applications. This article is protected by copyright. All rights reserved

Beschreibung: ABSTRACT Preserving the integrity of the DNA double helix is crucial for the maintenance of genomic stability. Therefore, DNA double-strand breaks represent a serious threat to cells. In this review, we describe the two major strategies used to repair double strand breaks: non-homologous end joining and homologous recombination, emphasizing the mutagenic aspects of each. We focus on emerging evidence that homologous recombination, long thought to be an error-free repair process, can in fact be highly mutagenic, particularly in contexts requiring large amounts of DNA synthesis. Recent investigations have begun to illuminate the molecular mechanisms by which error-prone double-strand break repair can create major genomic changes, such as translocations and complex chromosome rearrangements. We highlight these studies and discuss proposed models that may explain some of the more extreme genetic changes observed in human cancers and congenital disorders. This article is protected by copyright. All rights reserved

Beschreibung: As regulators in gene expression, microRNAs take part in most biological processes including cell differentiation, apoptosis, cell cycle and epithelial-to-mesenchymal transition (EMT). In order to evaluate their roles in EMT process, microRNA expression profile changes induced by EGF or TGF-β treatment on nasopharyngeal carcinoma cell HK-1 were analyzed, and miR-21, miR-148a, miR-505 and miR-1207-5p were found to be upregulated in growth factors-induced EMT process. miR-21 is already known as an oncogenic miRNA to promote metastasis, however, the exact functions of other three miRNAs in EMT are unclear. To our surprise, we found that miR-148a, miR-505 and miR-1207-5p can suppress EMT and metastasis phenotypes in HK-1 cells both in vitro and in vivo , which may relate to their inhibition on EMT and Wnt signaling molecules. MiRNAs confer robustness to biological processes by posttranscriptional repression of key transcriptional programs that are related to previous developmental stages or to alternative cell fates. Our findings indicate that miRNA feedback circuit is tuned to respond to growth factors-induced EMT, and we suggested a new negative feedback loop which may be an important element of the EMT process and confer biological robustness. This article is protected by copyright. All rights reserved

Beschreibung: Regulation is at the heart of biology. What bioregulatory mechanisms finely tune and coordinate our cell's numerous complicated biochemical processes, maintaining constancy of the cell internal environment when external conditions change and it differentiates during development? Knowledge of the biochemistry of small molecules in normal cells progressed greatly in the early 1900s. This article is protected by copyright. All rights reserved

Beschreibung: ABSTRACT Previous work has shown that acidosis prevents bone nodule formation by osteoblasts in vitro by inhibiting mineralisation of the collagenous matrix. The ratio of phosphate (P i ) to pyrophosphate (PP i ) in the bone microenvironment is a fundamental regulator of bone mineralisation. Both P i and PP i , a potent inhibitor of mineralisation, are generated from extracellular nucleotides by the actions of ecto-nucleotidases. This study investigated the expression and activity of ecto-nucleotidases by osteoblasts under normal and acid conditions. We found that osteoblasts express mRNA for a number of ecto-nucleotidases including NTPdase 1-6 (ecto-nucleoside triphosphate diphosphohydrolase) and NPP1-3 (ecto-nucleotide pyrophosphatase/phosphodiesterase). The rank order of mRNA expression in differentiating rat osteoblasts (day 7) was Enpp1  〉  NTPdase 4  〉  NTPdase 6  〉  NTPdase 5  〉 alkaline phosphatase 〉 ecto-5-nucleotidase 〉  Enpp3  〉  NTPdase 1  〉  NTPdase 3  〉  Enpp2  〉  NTPdase 2 . Acidosis (pH 6.9) upregulated NPP1 mRNA (2.8-fold) and protein expression at all stages of osteoblast differentiation compared to physiological pH (pH 7.4); expression of other ecto-nucleotidases was unaffected. Furthermore, total NPP activity was increased up to 53% in osteoblasts cultured in acid conditions (p 〈 0.001). Release of ATP, one of the key substrates for NPP1, from osteoblasts, was unaffected by acidosis. Further studies showed that mineralised bone formation by osteoblasts cultured from NPP1 knockout mice was increased compared with wildtypes (2.5-fold, p 〈 0.001) and was partially resistant to the inhibitory effect of acidosis. These results indicate that increased NPP1 expression and activity might contribute to the decreased mineralisation observed when osteoblasts are exposed to acid conditions. This article is protected by copyright. All rights reserved

Beschreibung: Connexin43 (Cx43) has been shown to regulate cell proliferation and its down-regulation is correlated with poor prognosis and survival in several types of human cancer. Cx43 expression levels are frequently down-regulated in human ovarian cancer, suggesting a potential role for Cx43 in regulating the progression of this disease. Epidermal growth factor (EGF) is a well-characterized hormone that stimulates ovarian cancer cell proliferation. Although EGF is able to regulate Cx43 expression in other cell types, it is unclear whether EGF can regulate Cx43 expression in ovarian cancer cells. Additionally, it remains unknown whether Cx43 is involved in EGF-stimulated ovarian cancer cell proliferation. In the present study, we demonstrate that treatment with EGF up-regulates Cx43 expression in two ovarian cancer cell lines, SKOV3 and OVCAR4. Although treatment with EGF activates both ERK1/2 and Akt signaling pathways, pharmacological inhibition and siRNA-mediated knockdown suggest that only the activation of Akt1 is required for EGF-induced Cx43 up-regulation. Functionally, Cx43 knockdown enhanced basal and EGF-induced cell proliferation, whereas the proliferative effects of EGF were reduced by Cx43 overexpression. Co-treatment with the gap junction inhibitor carbenoxolone did not alter the suppressive effects of Cx43 overexpression on EGF-induced cell proliferation, suggesting a gap junction-independent mechanism. This study reveals an important role for Cx43 as a negative regulator of EGF-induced human ovarian cancer cell proliferation. This article is protected by copyright. All rights reserved

Beschreibung: p53 and Notch-1 play important roles in breast cancer biology. Notch-1 inhibits p53 activity in cervical and breast cancer cells. Conversely, p53 inhibits Notch activity in T-cells but stimulates it in human keratinocytes. Notch co-activator MAML1 binds p53 and functions as a p53 co-activator. We studied the regulation of Notch signaling by p53 in MCF-7 cells and normal human mammary epithelial cells (HMEC). Results show that overexpression of p53 or activation of endogenous p53 with Nutlin-3 inhibits Notch-dependent transcriptional activity and Notch target expression in a dose-dependent manner. This effect could be partially rescued by transfection of MAML1 but not p300. Standard and quantitative co-immunoprecipitation experiments readily detected a complex containing p53 and Notch-1 in MCF-7 cells. Formation of this complex was inhibited by dominant negative MAML1 (DN-MAML1) and stimulated by wild-type MAML1. Standard and quantitative far-Western experiments showed a complex including p53, Notch-1 and MAML1. Chromatin immunoprecipitation (ChIP) experiments showed that p53 can associate with Notch-dependent HEY1 promoter and this association is inhibited by DN-MAML1 and stimulated by wild-type MAML1. Our data support a model in which p53 associates with the Notch transcriptional complex (NTC) in a MAML1-dependent fashion, most likely through a p53-MAML1 interaction. In our cellular models, the effect of this association is to inhibit Notch-dependent transcription. Our data suggest that p53-null breast cancers may lack this Notch-modulatory mechanism, and that therapeutic strategies that activate wild-type p53 can indirectly cause inhibition of Notch transcriptional activity. This article is protected by copyright. All rights reserved

Beschreibung: The White method is a simple but the most frequently applied approach to estimate groundwater evapotranspiration ( ET g ) from groundwater level diurnal signals. Due to a lack of direct measurements of ET g , it is difficult to evaluate the performance of the White method, particularly in field environments with variable groundwater fluctuations. A two-year field observation in a hyper-arid riparian tamarisk ( Tamarix spp.) stand with deep groundwater depth in the lower Tarim River basin of China was conducted to measure the surface evapotranspiration ( ET s ) and groundwater table. The performance of the White method and the influences of the variable groundwater fluctuations on the determinations of the specific yield ( S y ) and recharge rate of groundwater ( r ) in the White method were investigated. The results showed that the readily available S y determined by Loheide's method was feasible, but must be finely determined based on the soil textures in the layers in which the groundwater level fluctuated. A constant S y value for a defined porous medium could be assumed regardless of the discharge or recharge processes of groundwater. The time span of 0 A.M. to 6 A.M. for r estimation for the White method worked best than other time spans. A two-day moving average of r values further enhance ET g estimation . Slight effects of environmental or anthropogenic disturbances on the diurnal fluctuations of groundwater level did not influence the ET g estimations by the White method. Our results provide valuable references to the application of the White method for estimating daily ET g in desert riparian forests with deep groundwater depth. This article is protected by copyright. All rights reserved.

Beschreibung: This study analyzed age-related water use dynamics across three temperate conifer forest plantations (aged 11-, 39-, and 74-years old, as of 2013, henceforth referred to as TP02, TP74, and TP39, where the last two digits represent the year of planting) in southern Ontario, Canada from 2008 to 2013. Eddy covariance-measured mean evapotranspiration over the growing season (April-October) was 438 ± 19, 392 ± 19 and 323 ± 25 mm at TP39, TP74 and TP02 respectively. Daytime bulk surface conductance was highest and most variable at the TP39 site (8.5 ± 4.0 mm s −1 ), followed by the TP74 (7.0 ± 2.8 mm s −1 ) and TP02 (5.4 ± 2.5 mm s −1 ) sites. Evapotranspiration at all the forests was sensitive to air temperature and also tended to decrease with increasing atmospheric dryness. The youngest forest's evapotranspiration was most conservative, which led to an increase in water use efficiency throughout the study period, in particular during drought events. The oldest forest was the least restrictive in its water use during drought, which led to lower water use efficiency during such events as compared to the younger forests. The oldest forest was thinned in early 2012, where about 1/3 of trees were commercially harvested. No significant change in evapotranspiration or water use efficiency was observed at this site following thinning, however daytime bulk surface conductance declined. Our results suggested that changes in stand structure with forest ageing, such as reduction in stem density and increase in sapwood area, were responsible for differences in soil water demand during drought and non-drought periods, leading to differences in forest water use. Hence, forest age, due to its structural implications, is an important control on the stand-level water use efficiency and forests’ response to drought events. Our study suggested that younger forests may be best suited to maximize growth and carbon uptake efficiency under rising air temperatures and increasing precipitation variability as predicted by climate models for eastern North America. This article is protected by copyright. All rights reserved.

Beschreibung: Physically-based distributed and semi-distributed hydrological models have become some of the primary tools for water resources studies and management over the past decades owing to increased computational capabilities and advances in data measurements. Representation of the existing heterogeneity in nature still remains one of the main challenges in these models, and is accomplished primarily via watershed discretization, subdividing watersheds into hydrologically similar land parcels. Discretization decisions in distributed modeling studies are often ad hoc and determined with little or no quantitative analysis to support these decisions. In this work, we present a quantitative methodology for assessing alternative watershed discretization schemes in terms of their corresponding model performance in ungauged basins. The effect of the computational time spent for calibrating each scheme (calibration budget) is considered as part of the assessment. Here, these schemes differ in how they represent landscape attributes, and range from a simple lumped scheme to more complex ones by adding spatial land cover and then soil information. The methodology was demonstrated using the Modélisation Environmentale–Surface et Hydrologie (MESH) model as applied to the Nottawasaga river basin in Ontario, Canada. Results reveal that model performance in ungauged basins depends upon the location of the validation sub-basin (i.e. upstream or downstream) with respect to the calibration sub-basins. Also, using a more complex scheme did not necessarily lead to improved performance in validation, when constrained by calibration budget. Therefore, the calibration budget also should be considered as a factor in the assessment process. This methodology was also implemented using a shorter sub-period for calibration, which leads to substantial computational saving. Results of the sub-period test were promising and consistent particularly when sufficient budget is spent to calibrate the model. Other strategies utilized for reducing the computational burden of the proposed analyses are also discussed in this study. This article is protected by copyright. All rights reserved.

Beschreibung: Floods are the most frequent natural disaster, causing more loss of life and property than any other in the United States. Floods also strongly influence the structure and function of watersheds, stream channels, and aquatic ecosystems. The Pacific Northwest is particularly vulnerable to climatically-driven changes in flood frequency and magnitude, because snowpacks that strongly influence flood generation are near the freezing point and thus sensitive to small changes in temperature. To improve predictions of future flooding potential and inform strategies to adapt to these changes, we mapped the sensitivity of landscapes to changes in peak flows due to climate warming across Oregon and Washington. We first developed principal component based models for predicting peak flows across a range of recurrence intervals (2-, 10-, 25-, 50-, and 100-years) based on historical instantaneous peak flow data from 1000 gaged watersheds in Oregon and Washington. Key predictors of peak flows included drainage area and principal component scores for climate, land cover, soil, and topographic metrics. We then used these regression models to predict future peak flows by perturbing the climate variables based on future climate projections (2020s, 2040s, and 2080s) for the A1B emission scenario. For each recurrence interval, peak flow sensitivities were computed as the ratio of future to current peak flow magnitudes. Our analysis suggests that temperature induced changes in snowpack dynamics will result in large (〉30-40%) increases in peak flow magnitude in some areas, principally the Cascades, Olympics, and Blue Mountains and parts of the western edge of the Rocky Mountains. Flood generation processes in lower elevation areas are less likely to be affected, but some of these areas may be impacted by floodwaters from upstream. These results can assist land, water, and infrastructure managers in identifying watersheds and resources that are particularly vulnerable to increased peak flows and developing plans to increase their resilience. This article is protected by copyright. All rights reserved.

Beschreibung: Numerous studies investigated the influence of abiotic (meteorological conditions) and biotic factors (tree characteristics) on stemflow generation. Though these studies identified the variables that influence stemflow volumes in simply structured forests, the combination of tree characteristics that allows a robust prediction of stemflow volumes in species-rich forests is not well known. Many hydrological applications, however, require at least a rough estimate of stemflow volumes based on the characteristics of a forest stand. The need for robust predictions of stemflow motivated us to investigate the relationships between tree characteristics and stemflow volumes in a species-rich tropical forest located in central Panama. Based on a sampling setup consisting of 10 rainfall collectors, 300 throughfall samplers, and 60 stemflow collectors and cumulated data comprising 26 rain events, we derive three main findings. First, stemflow represents a minor hydrological component in the studied 1 ha forest patch (1.0 % of cumulated rainfall). Second, in the studied species-rich forest, single tree characteristics are only weakly related to stemflow volumes. The influence of multiple tree parameters (e.g. crown diameter, presence of large epiphytes, and inclination of branches) and the dependencies among these parameters require a multivariate approach to understand the generation of stemflow. Third, predicting stemflow in species-rich forests based on tree parameters is a difficult task. Although our best model can capture the variation in stemflow to some degree, a critical validation reveals that the model cannot provide robust predictions of stemflow. A reanalysis of data from previous studies in species-rich forests corroborates this finding. Based on these results and considering that for most hydrological applications stemflow is only one parameter among others to estimate, we advocate using the base model, i.e. the mean of the stemflow data, to quantify stemflow volumes for a given study area. Studies in species-rich forests that wish to obtain predictions of stemflow based on tree parameters probably need to conduct a much more extensive sampling than currently implemented by most studies. This article is protected by copyright. All rights reserved.

Beschreibung: This study analyzes the stable isotopic compositions of hydrogen and oxygen ( δ 2 H, δ 18 O) in montane meteoric waters including precipitation and stream water of central Taiwan to identify hydrological processes in montane catchments. Results of precipitation demonstrate that monsoon and altitude effects are two principal processes affecting δ and deuterium excess ( d E ) values of inland precipitation in central Taiwan. Furthermore, slope and intercept values of summer and winter local Meteoric Water Line (MWL) are modified by secondary evaporation effects such as moisture recycling and raindrop evaporation. Additionally, stream water's results indicate that differences in δ values among stream waters reflect isotopic altitude effect whereby lower values are more evident in stream water originating from high-elevation catchments than low-elevation catchments. Comparison of the isotopic results between precipitation and stream water indicates that summer precipitation containing recycled moisture is the most important water source for the studied stream waters and indicates that catchment effect and base-flow contribution are the two major hydrological processes affecting mountain stream hydrology. The hydrological processes identified by the isotopic study re-stress the important role of forests in mountain hydrology. This article is protected by copyright. All rights reserved.

Beschreibung: Groundwater ridging is the rapid rise of a shallow water table during a rainfall event, in an environment where, in the pre-event period, the capillary fringe extends to the ground surface. Groundwater ridging is widely cited to account for the observed significant appearance of pre-event water in a stream stormflow hydrograph. Various hypotheses have been advanced to explain the groundwater ridging mechanism; and most recently, from a field study site in South Africa, an energy hypothesis was proposed, which explains that groundwater ridging water table rise is as a result of rapid introduction and transmission of additional pressure head into the capillary fringe from an intense rainfall at the ground surface. However, there is need for further analysis and evidence from other field study sites to confirm and support this newly proposed energy hypothesis. The objectives of this paper are, therefore, to: review previous observations on groundwater ridging, from other study sites, in order to deduce evidence of the newly proposed energy hypothesis; present and evaluate a one-dimensional diffusion mathematical model that can simulate groundwater ridging water table rise, based on the newly proposed energy hypothesis; and evaluate the importance of a capillary fringe in streamflow generation. Analysis of previous observations from other study sites generally indicated that the rate of groundwater ridging water table rise is directly related to the rainfall intensity, hence, confirming and agreeing with the newly proposed energy hypothesis. Additionally, theoretical results by the mathematical model agreed fairly well with the field results observed under natural rainfall, confirming that the rapidly rainfall-induced energy is diffusively transmitted downwards through pore water, elevating the pressure head at every depth. The results in this study also support the concept of a three-end member stream stormflow hydrograph, and contribute to the explanation of how catchments can store water for long periods, but then release it rapidly during storm events. This article is protected by copyright. All rights reserved.

Beschreibung: ABSTRACT Aims Type 1 diabetes mellitus is associated with a high risk for bone fractures. Although bone mass is reduced, bone quality is also dramatically altered in this disorder. However, recent evidences suggest a beneficial effect of the glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) pathways on bone quality. The aims of the present study were to conduct a comprehensive investigation of bone strength at the organ and tissue level; and to ascertain whether enzyme resistant GIP or GLP-1 mimetic could be beneficial in preventing bone fragility in type 1 diabetes mellitus. Materials and methods Streptozotocin-treated mice were used as a model of type 1 diabetes mellitus. Control and streptozotocin-diabetic animals were treated for 21 days with an enzymatic-resistant GIP peptide ([D-Ala 2 ]GIP) or with liraglutide (each at 25 nmol/kg bw, ip). Bone quality was assessed at the organ and tissue level by microCT, qXRI, 3-point bending, qBEI, nanoindentation and Fourier-transform infrared microspectroscopy. Results [D-Ala 2 ]GIP and liraglutide treatment did prevent loss of whole bone strength and cortical microstructure in the STZ-injected mice. However, tissue material properties were significantly improved in STZ-injected animals following treatment with [D-Ala 2 ]GIP or liraglutide. Conclusions Treatment of STZ-diabetic mice with [D-Ala 2 ]GIP or liraglutide was capable of significantly preventing deterioration of the quality of the bone matrix. Further studies are required to further elucidate the molecular mechanisms involved and to validate whether these findings can be translated to human patients. This article is protected by copyright. All rights reserved

Beschreibung: Testicular germ cell tumors (TGCTs) are frequent solid malignant tumors and cause of death in men between 20–40 years of age. Genetic and environmental factors play an important role in the origin and development of TGCTs. Although the majority of TGCTs are responsive to chemotherapy, about 20% of patient presents incomplete response or tumors relapse. In addition, the current treatments cause acute toxicity and several chronic collateral effects, including sterility. The present mini-review collectively summarize the most recent findings on the new discovered molecular biomarkers such as tyrosine kinases, HMGAs, Aurora B kinase, and GPR30 receptor predictive of TGCTs and as emerging new possible molecular targets for therapeutic strategies. This article is protected by copyright. All rights reserved

Beschreibung: ABSTRACT Atrogin-1, an E3 ligase present in skeletal, cardiac and smooth muscle, down-regulates myocardin protein during skeletal muscle differentiation. Myocardin, the master regulator of smooth muscle cell (SMC) differentiation, induces expression of smooth muscle marker genes through its association with serum response factor (SRF), which binds to the CArG box in the promoter. Myocardin undergoes ubiquitylation and proteasomal degradation. Evidence suggests that proteasomal degradation of myocardin is critical for myocardin to exert its transcriptional activity, but there is no report about the E3 ligase responsible for myocardin ubiquitylation and subsequent transactivation. Here, we showed that overexpression of atrogin-1 increased contractility of cultured SMCs and mouse aortic tissues in organ culture. Overexpression of dominant-negative myocardin attenuated the increase in SMC contractility induced by atrogin-1. Atrogin-1 overexpression increased expression of the SM contractile markers while downregulated expression of myocardin protein but not mRNA. Atrogin-1 also ubiquitylated myocardin for proteasomal degradation in vascular SMCs. Deletion studies showed that atrogin-1 directly interacted with myocardin through its amino acids 284-345. Immunostaining studies showed nuclear localization of atrogin-1, myocardin and the Rpt6 subunit of the 26S proteasome. Atrogin-1 overexpression not only resulted in degradation of myocardin but also increased recruitment of RNA Polymerase II onto the promoters of myocardin target genes. In summary, our results have revealed the roles for atrogin-1 in the regulation of smooth muscle contractility through enhancement of myocardin ubiquitylation/degradation and its transcriptional activity. This article is protected by copyright. All rights reserved

Beschreibung: Cholesterol is an important component for cell physiology. It regulates the fluidity of cell membranes and determines the physical and biochemical properties of proteins. In the central nervous system, cholesterol controls synapse formation and function and supports the saltatory conduction of action potential. In recent years, the role of cholesterol in the brain has caught the attention of several research groups since a breakdown of cholesterol metabolism has been associated with different neurodevelopmental and neurodegenerative diseases, and interestingly also with psychiatric conditions. The aim of this review is to summarize the current knowledge about the connection between cholesterol dysregulation and various neurologic and psychiatric disorders based on clinical and preclinical studies. This article is protected by copyright. All rights reserved

Beschreibung: ABSTRACT Nestin (+) -cardiomyocytes were identified in the ischemically damaged human/rodent heart, albeit the cellular source and signaling events implicated in the appearance of the intermediate filament protein remained undefined. Expression of the enhanced green fluorescent protein (EGFP) driven by the second intron of the nestin gene identified a subpopulation of EGFP/nestin (+) cells that differentiated to a vascular phenotype in the peri-infarct/infarct region of post-MI mice albeit the transgene was not detected in nestin (+) -cardiomyocytes. α-MHC-driven expression of the reporter mCherry was detected in troponin-T (+) - and nestin (+) -cardiomyocytes in the peri-infarct/infarct region of post-MI mice. However, the cell cycle re-entry of nestin/mCherry (+) -cardiomyocytes was not observed. Nestin staining was identified in a paucity of neonatal rat ventricular cardiomyocytes (NNVM). Exposure to phorbol 12, 13-dibutyrate (PDBu) induced NNVM hypertrophy but did not promote nestin expression or Brdu incorporation. PDBu treatment of NNVMs phosphorylated p38 MAPK and HSP27 and HSP27 phosphorylation was abrogated by the p38 MAPK inhibitor SB203580. PDBu/SB203580 co-treatment significantly increased the percentage of NNVMs that expressed nestin and incorporated Brdu. In the heart of embryonic 10.5 day mice, nestin was detected in cycling troponin-T (+) -cardiomyocytes. Nestin was also detected in embryonic rat ventricular cardiomyocytes and depletion of the intermediate filament protein attenuated cell cycle re-entry. Thus, nestin expressed by pre-existing cardiomyocytes following ischemic damage recapitulated in part an embryonic phenotype and may provide the requisite phenotype to initiate cell cycle re-entry. However, the overt activation of the p38 MAPK pathway post-MI may in part limit the appearance and inhibit the cell cycle re-entry of nestin (+) -cardiomyocytes. This article is protected by copyright. All rights reserved

Beschreibung: The most popular practice for analyzing nonstationarity of flood series is to use a fixed single-type probability distribution incorporated with the time-varying moments. However, the type of probability distribution could be both complex because of distinct flood populations and time-varying under changing environments. To allow the investigation of this complex nature, the time-varying two-component mixture distributions (TTMD) method is proposed in this study by considering the time variations of not only the moments of its component distributions but also the weighting coefficients. Having identified the existence of mixed flood populations based on circular statistics, the proposed TTMD was applied to model the annual maximum flood series (AMFS) of two stations in the Weihe River basin (WRB), with the model parameters calibrated by the meta-heuristic maximum likelihood (MHML) method. The performance of TTMD was evaluated by different diagnostic plots and indexes and compared with stationary single-type distributions, stationary mixture distributions and time-varying single-type distributions. The results highlighted the advantages of TTMD with physically-based covariates for both stations. Besides, the optimal TTMD models were considered to be capable of settling the issue of nonstationarity and capturing the mixed flood populations satisfactorily. This article is protected by copyright. All rights reserved.

Beschreibung: While the effects of land use change in urban areas have been widely examined, the combined effects of climate and land use change on the quality of urban and urbanizing streams have received much less attention. We describe a modeling framework that is applicable to the evaluation of potential changes in urban water quality and associated hydrologic changes in response to ongoing climate and landscape alteration. The grid-based spatially distributed model, DHSVM-WQ, is an outgrowth of the Distributed Hydrology-Soil-Vegetation Model (DHSVM) that incorporates modules for assessing hydrology and water quality in urbanized watersheds at a high spatial and temporal resolution. DHSVM-WQ simulates surface runoff quality and in-stream processes that control the transport of nonpoint-source (NPS) pollutants into urban streams. We configure DHSVM-WQ for three partially urbanized catchments in the Puget Sound region to evaluate the water quality responses to current conditions and projected changes in climate and/or land use over the next century. Here we focus on total suspended solids (TSS) and total phosphorus (TP) from nonpoint sources (runoff), as well as stream temperature. The projection of future land use is characterized by a combination of densification in existing urban or partially urban areas, and expansion of the urban footprint. The climate change scenarios consist of individual and concurrent changes in temperature and precipitation. Future precipitation is projected to increase in winter and decrease in summer, while future temperature is projected to increase throughout the year. Our results show that urbanization has a much greater effect than climate change on both the magnitude and seasonal variability of streamflow, TSS and TP loads largely due to substantially increased streamflow, and particularly winter flow peaks. Water temperature is more sensitive to climate warming scenarios than to urbanization and precipitation changes. Future urbanization and climate change together are predicted to significantly increase annual mean streamflow (up to 55%), water temperature (up to 1.9 °C), TSS load (up to 182%), and TP load (up to 74%). This article is protected by copyright. All rights reserved.

Beschreibung: The resolution of a digital elevation model (DEM) is a crucial factor in watershed hydrologic and environmental modeling. DEM resolution can cause significant variability in the representation of surface topography, which further affects quantification of hydrologic connectivity and simulation of hydrologic processes. The objective of this study is to examine the effects of DEM resolution on (1) surface microtopographic characteristics, (2) hydrologic connectivity, and (3) the spatial and temporal variations of hydrologic processes. A puddle-to-puddle (P2P) modeling system was utilized for surface delineation and modeling of the P2P overland flow dynamics, surface runoff, infiltration, and unsaturated flow for nine DEM resolution scenarios of a field plot surface. Comparisons of the nine modeling scenarios demonstrated that coarser DEM resolutions tended to eliminate topographic features, reduce surface depression storage, and strengthen hydrologic connectivity and surface runoff. We found that reduction in maximum depression storage and maximum ponding area was as high as 97.56% and 76.36%, respectively, as the DEM grid size increased from 2 cm to 80 cm. The paired t-test and fractal analysis demonstrated the existence of a threshold DEM resolution (10 cm for the field plot), within which the DEM-based hydrologic modeling was effective and acceptable. The effects of DEM resolution were further evaluated for a larger surface in the Prairie Pothole Region (PPR) subjected to observed rainfall events. It was found that simulations based on coarser resolution DEMs (〉10 m) tended to overestimate ponded areas and underestimate runoff discharge peaks. The simulated peak discharge from the PPR surface reduced by approximately 50% as the DEM resolution changed from 2 m to 90 m. Fractal analysis results elucidated scale dependency of hydrologic and topographic processes. In particular, scale analysis highlighted a unique constant-threshold-power relationship between DEM scale and topographic and hydrologic parameters/variables. Not only does this finding allow one to identify threshold DEM, but also further develop functional relationships for scaling to achieve valid topographic characterization as well as effective and efficient hydrologic modeling. This article is protected by copyright. All rights reserved.

Beschreibung: This paper presents a methodology for hydrograph separation in mountain watersheds, which aims at identifying flow sources among ungauged headwater sub-catchments through a combination of observed streamflow and data on natural tracers including isotope and dissolved solids. Daily summer and bi-daily spring season water samples obtained at the outlet of the Juncal River Basin in the Andes of Central Chile were analyzed for all major ions as well as stable water isotopes, δ 18 O and δD. Additionally, various samples from rain, snow, surface streams and exfiltrating subsurface water (springs), were sampled throughout the catchment. A principal component analysis (PCA) was performed in order to address cross-correlation in the tracer dataset, reduce the dimensionality of the problem and to uncover patterns of variability. Potential sources were identified in a two-component U-space that explains 94% of the observed tracer variability at the catchment outlet. Hydrograph separation was performed through an Informative - Bayesian model. Our results indicate that the Juncal Norte Glacier headwater sub-catchment contributed at least 50% of summer flows at the Juncal River Basin outlet during the 2011–12 water year (a hydrologically dry period in the Region), even though it accounts for only 27% of the basin area. Our study confirms the value of combining solute and isotope information for estimating source contributions in complex hydrologic systems, and provides insights regarding experimental design in high-elevation semi-arid catchments. The findings of this study can be useful for evaluating modeling studies of the hydrological consequences of the rapid decrease in glacier cover observed in this region, by providing insights into the origin of river water in basins with little hydrometeorological information.

Beschreibung: The average flow of Silver Springs, one of the largest magnitude springs in central Florida, declined 32% from 2000 to 2012. The average groundwater head in the springshed declined 0.14 m, and the spring pool altitude increased 0.24 m during the same period. This paper presents a novel explanation of the spring flow recession curve for Silver Springs using Torricelli model, which uses the groundwater head at a sentinel well, the spring pool altitude, and the net recharge to groundwater. The effective springshed area and net recharge (defined as recharge minus groundwater pumping and evapotranspiration) were estimated based on the observed recession slopes for spring flow, groundwater head, and spring pool altitude. The results show that the effective springshed area continuously declined since 1989, and the net recharge declined since the 1970s with a significant drop in 2002. Subsequent to 2002, the net recharge increased modestly but not to the levels prior to the 1990s. The reduction in net recharge was caused by changes in hydroclimatic conditions including precipitation and temperature, along with groundwater withdrawals, which contributed to the declined spring flow.

Beschreibung: Alkaptonuria (AKU) is an ultra-rare autosomal genetic disorder caused by a defect in the activity of the enzyme homogentisate 1,2-dioxygenase (HGD) that leads to the accumulation of homogentisic acid (HGA) and its oxidized product, benzoquinone acetic acid (BQA), in the connective tissues causing a pigmentation called “ochronosis”. The consequent progressive formation of ochronotic aggregates generate a severe condition of oxidative stress and inflammation in all the affected areas. Experimental evidences have also proved the presence of serum amyloid A (SAA) in several AKU tissues and it allowed classifying AKU as a secondary amyloidosis. Although AKU is a multisystemic disease, the most affected system is the osteoarticular one and articular cartilage is the most damaged tissue. In this work, we have analyzed for the first time the cytoskeleton of AKU chondrocytes by means of immunofluorescence staining. We have shown the presence of SAA within AKU chondrocytes and finally we have demonstrated the co-localization of SAA with three cytoskeletal proteins: actin, vimentin and β-tubulin. Furthermore, in order to observe the ultrastructural features of AKU chondrocytes we have performed TEM analysis, focusing on the Golgi apparatus structure and, to demonstrate that pigmented areas in AKU cartilage are correspondent to areas of oxidation, 4-HNE presence has been evaluated by means of immunofluorescence. This article is protected by copyright. All rights reserved

Beschreibung: In this report, we present an analysis of several recycling protocols based on labeling of membrane proteins with specific monoclonal antibodies (mAbs). We analyzed recycling of membrane proteins that are internalized by clathrin-dependent endocytosis, represented by the transferrin receptor, and by clathrin-independent endocytosis, represented by the Major Histocompatibility Class I molecules. Cell surface membrane proteins were labeled with mAbs and recycling of mAb:protein complexes was determined by several approaches. Our study demonstrates that direct and indirect detection of recycled mAb:protein complexes at the cell surface underestimate the recycling pool, especially for clathrin-dependent membrane proteins that are rapidly reinternalized after recycling. Recycling protocols based on the capture of recycled mAb:protein complexes require the use of the Alexa Fluor 488 conjugated secondary antibodies or FITC-conjugated secondary antibodies in combination with inhibitors of endosomal acidification and degradation. Finally, protocols based on the capture of recycled proteins that are labeled with Alexa Fluor 488 conjugated primary antibodies and quenching of fluorescence by the anti-Alexa Fluor 488 displayed the same quantitative assessment of recycling as the antibody-capture protocols. This article is protected by copyright. All rights reserved

Beschreibung: Discharge simulation from snow-dominated catchments seems to be an easy task. Any spatially-explicit precipitation-runoff model coupled to a temperature-index snow model generally yields simulations that mimic well the observed daily discharges. The robustness of such models is, however, questionable: in presence of strong annual discharge cycles, small model residuals do not guarantee high explanatory power of the underlying model. This paper proposes a methodology for snow hydrological model identification within a limits-of-acceptability framework, where acceptable model simulations are the ones that reproduce a set of signatures within an a priori specified range. The signatures proposed here namely include the relationship between the air temperature regime and the discharge regime, a new snow hydrology signature that can be readily transferred to other Alpine settings. The discriminatory power of all analyzed signatures is assessed with a new measure of their discriminatory power in the model prediction domain. The value of the proposed snow hydrology signatures and of the limits-of-acceptability approach is demonstrated for the Dischma river in Switzerland, whose discharge shows a strong temporal variability of hydrologic forcing conditions over the last 30 years. The signature-based model identification for this case study leads to the surprising conclusion that the observed discharge data contains a multi-year period that cannot be reproduced with the model at hand. This model-data mismatch might well result from a yet to be identified problem with the discharge observations, which would have been difficult to detect in a classical residual-based model identification approach. Overall, the detailed results for this case study underline the robustness of the limits-of-acceptability approach in the presence of error-prone observations if it is applied in combination with relatively robust signatures. Future work will show whether snow hydrology signatures and their limits-of-acceptability can be regionalized to ungauged catchments, which would make this model selection approach particularly powerful for Alpine environments. This article is protected by copyright. All rights reserved.

Beschreibung: In the kidney, vitamin C is reabsorbed from the glomerular ultrafiltrate by sodium-vitamin C cotransporter isoform 1 (SVCT1) located in the brush border membrane of the proximal tubules. Although we know that vitamin C levels decrease with age, the adaptive physiological mechanisms used by the kidney for vitamin C reabsorption during aging remain unknown. In this study, we used an animal model of accelerated senescence (SAMP8 mice) to define the morphological alterations and aging-induced changes in the expression of vitamin C transporters in renal tissue. Aging induced significant morphological changes, such as periglomerular lymphocytic infiltrate and glomerular congestion, in the kidneys of SAMP8 mice, although no increase in collagen deposits was observed using 2-photon microscopy analysis and second harmonic generation. The most characteristic histological alteration was the dilation of intracellular spaces in the basolateral region of proximal tubule epithelial cells. Furthermore, a combination of laser microdissection, qRT-PCR and immunohistochemical analyses allowed us to determine that SVCT1 expression specifically increased in the proximal tubules from the outer strip of the outer medulla (segment S3) and cortex (segment S2) during aging and that these tubules also express GLUT1. We conclude that aging modulates vitamin C transporter expression and that renal over-expression of SVCT1 enhances vitamin C reabsorption in aged animals that may synthesize less vitamin C. This article is protected by copyright. All rights reserved

Beschreibung: Electrochemotherapy (ECT) is a medical strategy that allows an increased efficacy of chemotherapy agents after the application of permeabilizing electric pulses having appropriate characteristics (form, voltage, frequency). In the past ten years, the clinical efficacy of this therapeutic approach in several spontaneous models of tumors in animals has been shown. Moreover, some of the molecular and cellular mechanisms responsible for this phenomenon have been elucidated. Our group has been deeply involved in the development of new ECT protocols for companion animals, implementing the use of the technique as first line treatment, and evaluating different chemotherapy agents in laboratory animals as well as pets. This article summarizes the most important advances in veterinary ECT, including the development of novel equipment, therapeutic protocols and their translation to humans. This article is protected by copyright. All rights reserved

Beschreibung: Changes in land use and land cover are major drivers of hydrological alteration in the tropical Andes. However, quantifying their impacts is fraught with difficulties because of the extreme diversity in meteorological boundary conditions, which contrasts strongly with the lack of knowledge about local hydrological processes. Although local studies have reduced data scarcity in certain regions, the complexity of the tropical Andes poses a big challenge to regional hydrological prediction. This study analyses data generated from a participatory monitoring network of 25 headwater catchments covering three of the major Andean biomes ( páramo , jalca , and puna ), and link their hydrological responses to main types of human interventions (cultivation, afforestation and grazing). A paired catchment setup was implemented to evaluate the impacts of change using a “trading space-for-time” approach. Catchments were selected based on regional representativeness and contrasting land use types. Precipitation and discharge have been monitored and analysed at high temporal resolution for a time period between 1 and 5 years. The observed catchment responses clearly reflect the extraordinarily wide spectrum of hydrological processes of the tropical Andes. They range from perennially humid páramos in Ecuador and northern Peru with extremely large specific discharge and baseflows, to highly seasonal, flashy catchments in the drier punas of southern Peru and Bolivia. The impacts of land use are similarly diverse and their magnitudes are a function of catchment properties, original and replacement vegetation, and management type. Cultivation and afforestation consistently affect the entire range of discharges, particularly low flows. The impacts of grazing are more variable, but have the largest effect on the catchment hydrological regulation. Overall, anthropogenic interventions result in increased streamflow variability and significant reductions in catchment regulation capacity and water yield, irrespective of the hydrological properties of the original biome. This article is protected by copyright. All rights reserved.