Reduced sediment supply in a fast eroding landscape? A multi-proxy sediment budget of the upper Rhone basin, Central Alps

Alpine water and sediment supply influence the sediment budget of many important European fluvial systems such as the Rhine, Rhône and Po rivers. In the light of human induced climate change and landscape modification, it becomes increasingly important to understand the mechanisms of sediment production and supply in Alpine sediment systems. This study aims to investigate the modern sediment budget of the upper Rhône basin, one of the largest Alpine intramontane watersheds, located in the Central Alps of southwestern Switzerland. Major areas of sediment generation are fingerprinted by framework petrography, heavy mineral concentrations and bulk geochemistry. The relative contributions of the three major sources to the sediment of the trunk Rhône river are identified by compositional mixing modelling. Concentrations of the terrestrial cosmogenic nuclide 10Be measured in quartz separated from fluvial sediments provide spatially averaged denudation rates for selected tributary basins. Results from sediment fingerprinting and mixing modelling suggest that tributaries located in the North and the East of the catchment are generating most of the sediment transported by the Rhône river to its primary sedimentary sink in Lake Geneva. Despite having some of the highest denudation rates within the basin, tributaries located in the southern area of the Rhône basin are relatively underrepresented in the sediment budget of the Rhône river. These tributaries are severely affected by human activities, for example through sediment mining as well as water and sediment abstraction in large hydropower reservoirs. Together, these processes reduce the basin-wide sediment discharge by about 50%, thereby explaining most of the observed compositional pattern. In addition, there is evidence suggesting that large amounts of glaciogenic sediments are currently supplied by retreating glaciers. Glaciogenic material with its low 10Be concentrations can lead to a significant overestimation of denudation rates and thus limit the applicability of cosmogenic nuclide analysis in such glaciated settings

Biological activity differences between TGF-β1 and TGF-β3 correlate with differences in the rigidity and arrangement of their component monomers

[Image: see text] TGF-β1, -β2, and -β3 are small, secreted signaling proteins. They share 71–80% sequence identity and signal through the same receptors, yet the isoform-specific null mice have distinctive phenotypes and are inviable. The replacement of the coding sequence of TGF-β1 with TGF-β3 and TGF-β3 with TGF-β1 led to only partial rescue of the mutant phenotypes, suggesting that intrinsic differences between them contribute to the requirement of each in vivo. Here, we investigated whether the previously reported differences in the flexibility of the interfacial helix and arrangement of monomers was responsible for the differences in activity by generating two chimeric proteins in which residues 54–75 in the homodimer interface were swapped. Structural analysis of these using NMR and functional analysis using a dermal fibroblast migration assay showed that swapping the interfacial region swapped both the conformational preferences and activity. Conformational and activity differences were also observed between TGF-β3 and a variant with four helix-stabilizing residues from TGF-β1, suggesting that the observed changes were due to increased helical stability and the altered conformation, as proposed. Surface plasmon resonance analysis showed that TGF-β1, TGF-β3, and variants bound the type II signaling receptor, TβRII, nearly identically, but had small differences in the dissociation rate constant for recruitment of the type I signaling receptor, TβRI. However, the latter did not correlate with conformational preference or activity. Hence, the difference in activity arises from differences in their conformations, not their manner of receptor binding, suggesting that a matrix protein that differentially binds them might determine their distinct activities

Making stratigraphy in the Anthropocene: climate change impacts and economic conditions controlling the supply of sediment to Lake Geneva

The Anthropocene has been proposed as a profound, globally synchronous rupture in the history of the Earth System with its current state fundamentally different to that of the Holocene and driven by the geological force of human activity. Here, we show how stratigraphy is being made in a lake that is heavily impacted upon by climate change and human activities. For one of the largest inner-Alpine catchments in the European Alps, we draw attention to how sedimentation rates are a product of non-stationary, reflexive, human actions. In Lake Geneva, we identify both a human-induced climate change (HCC) signature and the effects of a recent economic shock on sediment extraction upon sediment loading to and sedimentation rates in the lake. The HCC signature thus reflects the nature of climate change impacts in this basin, where sediment accumulation rates evolve with climate, but where economic conditions contribute to shifts in the supply of sediment to the lake. Following social theory, we call this glocalization because of the combined importance and inseparability of human impacts across different spatial scales. The nature of human impacts on sediment delivery to the lake mean that the influence of humans is unlikely to be captured in the long-term depositional record

Bedrock sculpting under an active alpine glacier revealed from cosmic-ray muon radiography.

Mountain glaciers form landscapes with U-shaped valleys, roche moutonées and overdeepenings through bedrock erosion. However, little evidence for active glacial carving has been provided particularly for areas above the Equilibrium Line Altitude (ELA) where glaciers originate. This is mainly due to our lack of information about the shape of the bedrock underneath active glaciers in highly elevated areas. In the past years, the bedrock morphology underneath active glaciers has been studied by geophysical methods in order to infer the subglacial mechanisms of bedrock erosion. However, these comprise surveys on the glaciers' surface, from where it has been difficult to investigate the lateral boundary between the ice and the bedrock with sufficient resolution. Here we perform a muon-radiographic inspection of the Eiger glacier (Switzerland, European Alps) with the aid of cosmic-ray muon attenuation. We find a reach (600 × 300 m) within the accumulation area where strong lateral glacial erosion has cut nearly vertically into the underlying bedrock. This suggests that the Eiger glacier has profoundly sculpted its bedrock in its accumulation area. This also reveals that the cosmic-ray muon radiography is an ideal technology to reconstruct the shape of the bedrock underneath an active glacier

Mapping evolutionary process: a multi-taxa approach to conservation prioritization

Human-induced land use changes are causing extensive habitat fragmentation. As a result, many species are not able to shift their ranges in response to climate change and will likely need to adapt in situ to changing climate conditions. Consequently, a prudent strategy to maintain the ability of populations to adapt is to focus conservation efforts on areas where levels of intraspecific variation are high. By doing so, the potential for an evolutionary response to environmental change is maximized. Here, we use modeling approaches in conjunction with environmental variables to model species distributions and patterns of genetic and morphological variation in seven Ecuadorian amphibian, bird, and mammal species. We then used reserve selection software to prioritize areas for conservation based on intraspecific variation or species-level diversity. Reserves selected using species richness and complementarity showed little overlap with those based on genetic and morphological variation. Priority areas for intraspecific variation were mainly located along the slopes of the Andes and were largely concordant among species, but were not well represented in existing reserves. Our results imply that in order to maximize representation of intraspecific variation in reserves, genetic and morphological variation should be included in conservation prioritization

NMR Studies on Structure and Dynamics of the Monomeric Derivative of BS-RNase: New Insights for 3D Domain Swapping

Three-dimensional domain swapping is a common phenomenon in pancreatic-like ribonucleases. In the aggregated state, these proteins acquire new biological functions, including selective cytotoxicity against tumour cells. RNase A is able to dislocate both N- and C-termini, but usually this process requires denaturing conditions. In contrast, bovine seminal ribonuclease (BS-RNase), which is a homo-dimeric protein sharing 80% of sequence identity with RNase A, occurs natively as a mixture of swapped and unswapped isoforms. The presence of two disulfides bridging the subunits, indeed, ensures a dimeric structure also to the unswapped molecule. In vitro, the two BS-RNase isoforms interconvert under physiological conditions. Since the tendency to swap is often related to the instability of the monomeric proteins, in these paper we have analysed in detail the stability in solution of the monomeric derivative of BS-RNase (mBS) by a combination of NMR studies and Molecular Dynamics Simulations. The refinement of NMR structure and relaxation data indicate a close similarity with RNase A, without any evidence of aggregation or partial opening. The high compactness of mBS structure is confirmed also by H/D exchange, urea denaturation, and TEMPOL mapping of the protein surface. The present extensive structural and dynamic investigation of (monomeric) mBS did not show any experimental evidence that could explain the known differences in swapping between BS-RNase and RNase A. Hence, we conclude that the swapping in BS-RNase must be influenced by the distinct features of the dimers, suggesting a prominent role for the interchain disulfide bridges

On the phylogeny of Mustelidae subfamilies: analysis of seventeen nuclear non-coding loci and mitochondrial complete genomes

<p>Abstract</p> <p>Background</p> <p>Mustelidae, as the largest and most-diverse family of order Carnivora, comprises eight subfamilies. Phylogenetic relationships among these Mustelidae subfamilies remain argumentative subjects in recent years. One of the main reasons is that the mustelids represent a typical example of rapid evolutionary radiation and recent speciation event. Prior investigation has been concentrated on the application of different mitochondrial (mt) sequence and nuclear protein-coding data, herein we employ 17 nuclear non-coding loci (>15 kb), in conjunction with mt complete genome data (>16 kb), to clarify these enigmatic problems.</p> <p>Results</p> <p>The combined nuclear intron and mt genome analyses both robustly support that Taxidiinae diverged first, followed by Melinae. Lutrinae and Mustelinae are grouped together in all analyses with strong supports. The position of Helictidinae, however, is enigmatic because the mt genome analysis places it to the clade uniting Lutrinae and Mustelinae, whereas the nuclear intron analysis favores a novel view supporting a closer relationship of Helictidinae to Martinae. This finding emphasizes a need to add more data and include more taxa to resolve this problem. In addition, the molecular dating provides insights into the time scale of the origin and diversification of the Mustelidae subfamilies. Finally, the phylogenetic performances and limits of nuclear introns and mt genes are discussed in the context of Mustelidae phylogeny.</p> <p>Conclusion</p> <p>Our study not only brings new perspectives on the previously obscured phylogenetic relationships among Mustelidae subfamilies, but also provides another example demonstrating the effectiveness of nuclear non-coding loci for reconstructing evolutionary histories in a group that has undergone rapid bursts of speciation.</p

r84, a Novel Therapeutic Antibody against Mouse and Human VEGF with Potent Anti-Tumor Activity and Limited Toxicity Induction

Vascular endothelial growth factor (VEGF) is critical for physiological and pathological angiogenesis. Within the tumor microenvironment, VEGF functions as an endothelial cell survival factor, permeability factor, mitogen, and chemotactic agent. The majority of these functions are mediated by VEGF-induced activation of VEGF receptor 2 (VEGFR2), a high affinity receptor tyrosine kinase expressed by endothelial cells and other cell types in the tumor microenvironment. VEGF can also ligate other cell surface receptors including VEGFR1 and neuropilin-1 and -2. However, the importance of VEGF-induced activation of these receptors in tumorigenesis is still unclear. We report the development and characterization of r84, a fully human monoclonal antibody that binds human and mouse VEGF and selectively blocks VEGF from interacting with VEGFR2 but does not interfere with VEGF∶VEGFR1 interaction. Selective blockade of VEGF binding to VEGFR2 by r84 is shown through ELISA, receptor binding assays, receptor activation assays, and cell-based functional assays. Furthermore, we show that r84 has potent anti-tumor activity and does not alter tissue histology or blood and urine chemistry after chronic high dose therapy in mice. In addition, chronic r84 therapy does not induce elevated blood pressure levels in some models. The ability of r84 to specifically block VEGF∶VEGFR2 binding provides a valuable tool for the characterization of VEGF receptor pathway activation during tumor progression and highlights the utility and safety of selective blockade of VEGF-induced VEGFR2 signaling in tumors

Proteins on the catwalk: modelling the structural domains of the CCN family of proteins

The CCN family of proteins (CCN1, CCN2, CCN3, CCN4, CCN5 and CCN6) are multifunctional mosaic proteins that play keys roles in crucial areas of physiology such as angiogenesis, skeletal development tumourigenesis, cell proliferation, adhesion and survival. This expansive repertoire of functions comes through a modular structure of 4 discrete domains that act both independently and in concert. How these interactions with ligands and with neighbouring domains lead to the biological effects is still to be explored but the molecular structure of the domains is likely to play an important role in this. In this review we have highlighted some of the key features of the individual domains of CCN family of proteins based on their biological effects using a homology modelling approach