Desmosomal cadherins mediate intercellular adhesion and control epithelial homeostasis. Recent studies show that proteinases play an important role in the pathobiology of cancer by targeting ...epithelial intercellular junction proteins such as cadherins. Here we describe the proinflammatory cytokine-induced activation of matrix metalloproteinase 9 and a disintegrin and metalloproteinase domain-containing protein 10, which promote the shedding of desmosomal cadherin desmoglein-2 (Dsg2) ectodomains in intestinal epithelial cells. Epithelial exposure to Dsg2 ectodomains compromises intercellular adhesion by promoting the relocalization of endogenous Dsg2 and E-cadherin from the plasma membrane while also promoting proliferation by activation of human epidermal growth factor receptor 2/3 signaling. Cadherin ectodomains were detected in the inflamed intestinal mucosa of mice with colitis and patients with ulcerative colitis. Taken together, our findings reveal a novel response pathway in which inflammation-induced modification of columnar epithelial cell cadherins decreases intercellular adhesion while enhancing cellular proliferation, which may serve as a compensatory mechanism to promote repair.
•Countrywide mapping of rare and heterogeneous shrub forest.•Approach is based on multi-sensor and open access predictor data.•Active learning and Object growing for bias correction.•Mapping accuracy ...was increased in a cost-effective way.
The continual increase of shrub forest in the Swiss Alps over the past few decades impacts biodiversity, forest succession and the protective function of forests. Therefore, up-to-date and area-wide information on its distribution is of great interest. To detect the shrub forest areas for the whole of Switzerland (41,285 km2), we developed an approach that uses Random Forest (RF), bias correction techniques and data from multiple remote sensing sources. Manual aerial orthoimage interpretation of shrub forest areas was conducted in a non-probabilistic way to derive initial training data. The multi-sensor and open access predictor data included digital terrain and vegetation height models obtained from Airborne Laser Scanning (ALS) and stereo-imagery, as well as Synthetic Aperture Radar (SAR) backscatter from Sentinel-1 and multispectral imagery from Sentinel-2. To mitigate the expected bias due to the training data sampling strategy, two techniques using RF probability estimates were tested to improve mapping accuracy. 1) an iterative and semi-automated active learning technique was used to generate further training data and 2) threshold-moving related object growing was applied. Both techniques facilitated the production of a shrub forest map for the whole of Switzerland at a spatial resolution of 10 m. An accuracy assessment was performed using independent data covering 7640 regularly distributed National Forest Inventory (NFI) plots. We observed the influence of the bias correction techniques and found higher accuracies after each performed iteration. The Mean Absolute Error (MAE) for the predicted shrub forest proportion was reduced from 6.04% to 2.68% while achieving a Mean Bias Error (MBE) of close to 0. The present study underscores the potential of combining multi-sensor data with bias correction techniques to provide cost-effective and accurate countrywide detection of shrub forest. Moreover, the map complements currently available NFI plot sample point data.
Land‐use intensification in grassland ecosystems (i.e. increased mowing frequency, intensified grazing) has a strong negative effect on biodiversity and ecosystem services. However, accurate ...information on grassland‐use intensity is difficult to acquire and restricted to the local or regional level. Recent studies have shown that mowing events can be mapped for large areas using satellite image time series. The transferability of such approaches, especially to mountain areas, has been little explored, however, and the relevance for ecological applications in biodiversity and conservation has hardly been investigated. Here, we used a rule‐based algorithm to produce annual maps for 2018–2021 of grassland‐management events, that is, mowing and/or grazing, for Switzerland using Sentinel‐2 and Landsat 8 satellite data. We assessed the detection of management events based on independent reference data, which we acquired from daily time series of publicly available webcams that are widely distributed across Switzerland. We further examined the relationships between the generated grassland‐use intensity measures and plant species richness and ecological indicator values derived from a nationwide field survey. The webcam‐based verification for 2020 and 2021 revealed that most detected management events were actual mowing/grazing events (≥78%), but that a substantial number of events were not detected (up to 57%), particularly grazing events at higher elevations. We found lower plant species richness and higher mean ecological indicator values for nutrients and mowing tolerance with more frequent management events and those starting earlier in the year. A large proportion of the variance was explained by our use‐intensity measures. Our findings therefore highlight that remotely assessed management events can characterise land‐use intensity at fine spatial and temporal resolutions across broad scales and can explain plant biodiversity patterns in grasslands.
We used a newly developed rule‐based algorithm to produce annual maps of grassland‐management events, i.e. mowing and/or grazing, for Switzerland using Sentinel‐2 and Landsat 8 satellite data. We assessed the detection of management events based on independent reference data, which we acquired from daily time series of publicly available webcams that are widely distributed across Switzerland. The derived maps confirmed anticipated spatial patterns of grassland‐use intensities and explained biodiversity patterns in Swiss grasslands well, demonstrating their great potential for diverse ecological applications and in biodiversity research.
Phenol contamination of soil and water has raised concerns among people living near phenol-producing factories and hazardous waste sites containing the chemical. Phenol, particularly in high ...concentrations, is an irritating and corrosive substance, making mucosal membranes targets of toxicity in humans. However, few data on the effects of phenol after oral exposure exist.
We used an in vitro model employing human intestinal epithelial cells (SK-CO15) cultured on permeable supports to examine effects of phenol on epithelial barrier function. We hypothesized that phenol disrupts epithelial barrier by altering tight junction (TJ) protein expression. The dose-response effect of phenol on epithelial barrier function was determined using transepithelial electrical resistance (TER) and FITC-dextran permeability measurements. We studied phenol-induced changes in cell morphology and expression of several tight junction proteins by immunofluorescence and Western blot analysis. Effects on cell viability were assessed by MTT, Trypan blue, propidium iodide and TUNEL staining.
Exposure to phenol resulted in decreased TER and increased paracellular flux of FITC-dextran in a dose-dependent manner. Delocalization of claudin-1 and ZO-1 from TJs to cytosol correlated with the observed increase in permeability after phenol treatment. Additionally, the decrease in TER correlated with changes in the distribution of a membrane raft marker, suggesting phenol-mediated effects on membrane fluidity. Such observations were independent of effects of phenol on cell viability as enhanced permeability occurred at doses of phenol that did not cause cell death. Overall, these findings suggest that phenol may affect transiently the lipid bilayer of the cell membrane, thus destabilizing TJ-containing microdomains.
Exacerbated by climate change, Europe has experienced series of hot and dry summer since the beginning of the 21st century. The importance of land conditions became an international concern with a ...dedicated sustainable development goal (SDG), the SDG 15. It calls for developing and finding innovative solutions to follow and evaluate impacts of changing land conditions induced by various driving forces. In Switzerland, drought risk will significantly increase in the coming decades with severe consequences on agriculture, energy production and vegetation. In this paper, we used a 35-year satellite-derived annual and seasonal times-series of normalized difference water index (NDWI) to follow vegetation water content evolution at different spatial and temporal scales across Switzerland and related them to temperature and precipitation to investigate possible responses of changing climatic conditions. Results indicate that there is a small and slow drying tendency at the country scale with a NDWI mean decreasing slope of −0.22%/year for the 23% significant pixels across Switzerland. This tendency is mostly visible below 2000 m above sea level (m.a.s.l.) and in all biogeographical regions. The Southern Alps regions appear to be more responsive to changing drying conditions with a significant and slight negative NDWI trend (−0.39%/year) over the last 35 years. Moreover, NDWI values are mostly a function of temperature at elevations below the tree line rather than precipitation. Findings suggest that multi-annual and seasonal NDWI can be a valuable indicator to monitor vegetation water content at different scales, but other components such as land cover type and evapotranspiration should be considered to better characterize NDWI variability. Satellite Earth Observations data can provide valuable complementary observations for national statistics on the ecological state of vegetation to support SDG 15 to monitor land affected by drying conditions.
HLA-DM catalyzes peptide dissociation and exchange in class II MHC molecules through a mechanism that has been proposed to involve the disruption of specific components of the conserved hydrogen bond ...network in MHC-peptide complexes. HLA-DR1 molecules with alanine substitutions at each of the six conserved H- bonding positions were expressed in cells, and susceptibility to DM catalytic activity was evaluated by measuring the release of CLIP. The mutants alphaN62A, alphaN69A, alphaR76A, and betaH81A DR1 were fully susceptible to DM-mediated CLIP release, and betaN82A resulted in spontaneous release of CLIP. Using recombinant soluble DR1 molecules, the amino acid betaN82 was observed to contribute disproportionately in stabilizing peptide complexes. Remarkably, the catalytic potency of DM with each beta-chain mutant was equal to or greater than that observed with wild-type DR1. Our results support the conclusion that no individual component of the conserved hydrogen bond network plays an essential role in the DM catalytic mechanism.
Human leukocyte antigen (HLA)-DM is a critical participant in antigen presentation that catalyzes the release of class II-associated invariant chain-derived peptides (CLIP) from newly synthesized ...class II histocompatibility molecules, freeing the peptide-binding site for acquisition of antigenic peptides. The mechanism for the selective release of CLIP but not other peptides is unknown. DM was found to enhance the rate of peptide dissociation to an extent directly proportional to the intrinsic rate of peptide dissociation from HLA-DR, regardless of peptide sequence. Thus, CLIP is rapidly released in the presence of DM, because its intrinsic rate of dissociation is relatively high. In antigen presentation, DM has the potential to markedly enhance the rate of peptide exchange, favoring the presentation of peptides with slower intrinsic rates of dissociation.
The MHC class Ib molecule HLA-E is the primary ligand for CD94/NKG2A-inhibitory receptors expressed on NK cells, and there is also evidence for TCR-mediated recognition of this molecule. HLA-E ...preferentially assembles with a homologous set of peptides derived from the leader sequence of class Ia molecules, but its capacity to bind and present other peptides remains to be fully explored. The peptide-binding motif of HLA-E was investigated by folding HLA-E in vitro in the presence of peptide libraries derived from a nonameric leader peptide sequence randomized at individual anchor positions. A high degree of selectivity was observed at four of five total anchor positions, with preference for amino acids present in HLA-E-binding peptides from class Ia leader sequences. Selectivity was also observed at the nonanchor P5 position, with preference for positively charged amino acids, suggesting that electrostatic interactions involving the P5 side chain may facilitate assembly of HLA-E peptide complexes. The observed HLA-E peptide-binding motif was strikingly similar to that previously identified for the murine class Ib molecule, Qa-1. Experiments with HLA-E tetramers bearing peptides substituted at nonanchor positions demonstrated that P5 and P8 are primary contact residues for interaction with CD94/NKG2 receptors. A conservative replacement of Arg for Lys at P5 completely abrogated binding to CD94/NKG2. Despite conservation of peptide-binding specificity in HLA-E and Qa-1, cross-species tetramer-staining experiments demonstrated that the interaction surfaces on CD94/NKG2 and the class Ib ligands have diverged between primates and rodents.
Afin de comprendre avec exactitude la manière dont Francis Bacon envisage la question de la prolongation de la vie humaine, il faut impérativement examiner l’assise théologique de la réflexion du ...philosophe à ce sujet. Il convient aussi de restituer l’intégration de cette réflexion dans les objectifs plus amples de la philosophie naturelle nouvelle. Enfin, il est nécessaire de comprendre les dimensions proprement morales de la question. Car la prolongation de la vie humaine n’est pas seulement, au sein de la philosophie naturelle nouvelle, un cas parmi d’autres des recherches qu’il faut désormais effectuer : en réalité, c’est elle qui lui donne et qui lui fixe son sens ; avec elle se joue l’effectivité de l’identité espérée entre science et puissance. Mais il faut encore préciser qu’il ne s’agit aucunement pour l’homme de vieillir pour vieillir : il s’agit pour lui de pouvoir vieillir bien. Les leçons que Bacon tire de la fable de Tithon sont ici véritablement décisives.
•A remote sensing based approach predicts habitat quality of protected dry grassland.•Models benefit from multiple Landsat-based phenology metrics, particularly in case of management.•Phenology ...metrics performed best for management intensity and nutrient content.•Model relationships of phenology metrics differ between management types.•Models provide in-depth information on conservation risks for managers and science.
Dry grasslands are species rich and ecologically valuable habitats that have experienced a massive decline in Switzerland during the last century due to agricultural intensification and land abandonment. Appropriate management is a key factor in maintaining habitat quality of the remaining most valuable sites and should thus be an essential part of monitoring studies. However, information on management is often missing and fine-scale patterns are difficult to assess, especially over large areas and for past decades.
The aim of this study was to predict habitat quality of protected dry grasslands in Switzerland. Using a nation-wide in-situ vegetation data set with plot-based species lists, we derived six habitat quality indicators (management tolerance, light availability, nutrient content, moisture content and species richness). We then tested how well satellite-based phenology metrics, in combination with environmental and climate data, can predict these dry grassland habitat quality indicators. We expected that the seasonal pattern of vegetation activity, based on the Normalized Difference Vegetation Index (NDVI), would represent local productivity and management patterns, two crucial indicators of dry grassland habitat quality. Linear regression analysis was conducted to assess the relative importance and ecological relationship of different NDVI metrics and other environmental and climate predictors for habitat quality. Variance partitioning was applied to assess model contributions of the three variable groups which represent different data sources for productivity and management.
Accuracies for the habitat quality prediction models ranged between 34% and 57% and significant correlations with multiple NDVI metrics were found. Including NDVI phenology improved all models by 7–12%. Single contributions of NDVI phenology were highest for management tolerance and nutrient content. However, we found high variation of contributions between management types. NDVI metrics were highly informative for the habitat qualities of abandoned sites, but grazing and mowing reduced or even cancelled their predictive power. Moreover, our results demonstrate the limitation of single-date NDVI values in predicting habitat quality of dry grasslands, in particular pastures and meadows. For monitoring applications of dry grasslands, we propose using a combination of NDVI metrics, as our results showed that they greatly improve prediction results of essential habitat qualities. The Landsat legacy dataset facilitates the assessment of habitat changes during past decades and can be complemented in the future with higher resolution data, such as Sentinel-2, to increase the temporal and spatial resolution so analyses are more appropriate for the typically limited size of dry grassland habitat sites in Switzerland.
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