Quantitative reconstruction of late Holocene surface evolution on an alpine debris-flow fan

Debris-flow fans form a ubiquitous record of past debris-flow activity in mountainous areas, and may be useful for inferring past flow characteristics and consequent future hazard. Extracting information on past debris flows from fan records, however, requires an understanding of debris-flow deposition and fan surface evolution; field-scale studies of these processes have been very limited. In this paper, we document the patterns and timing of debris-flow deposition on the surface of the large and exceptionally active Illgraben fan in southwestern Switzerland. We use terrain analysis, radiocarbon dating of sediment fill in the Illgraben catchment, and cosmogenic 10Be and 36Cl exposure dating of debris-flow deposits on the fan to constrain the temporal evolution of the sediment routing system in the catchment and on the fan during the past 3200 years. We show that the fan surface preserves a set of debris-flow lobes that were predominantly deposited after the occurrence of a large rock avalanche near the fan apex at about 3200 years ago. This rock avalanche shifted the apex of the fan and impounded sediment within the Illgraben catchment. Subsequent evolution of the fan surface has been governed by both lateral and radial shifts in the active depositional lobe, revealed by the cosmogenic radionuclide dates and by cross-cutting geometrical relationships on the fan surface. This pattern of frequent avulsion and fan surface occupation provides field-scale evidence of the type of large-scale compensatory behavior observed in experimental sediment routing systems

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

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

Structure and rearrangements of rRNA genes in chloroplast DNA in two strains of Euglena gracilis

The organisation of the rRNA genes in the chloroplast genomes of two strains of Euglena gracilis were analyzed and compared. It was previously shown that the bacillaris strain contains three complete rrn (rRNA) operons (7) and that the Z-S strain contains one operon (21). Using heteroduplex analysis it was found that the bacillaris strain contains, apart from the three complete rrn operons, an extra 16S rRNA gene, an extra partial 23S rRNA gene sequence and an inverted duplication of a stretch within the 5S–16S spacer. In addition a short (<100 bp) inverted repeat sequence (13) which forms a stem/loop structure in single-stranded cpDNA was located between the 3′-end of the extra 16S rRNA gene and the partial 23 S rRNA sequence.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43440/1/11103_2004_Article_BF00016060.pd

A probabilistic sediment cascade model of sediment transfer in the Illgraben

We present a probabilistic sediment cascade model to simulate sediment transfer in a mountain basin (Illgraben, Switzerland) where sediment is produced by hillslope landslides and rockfalls and exported out of the basin by debris flows and floods. The model conceptualizes the fluvial system as a spatially lumped cascade of connected reservoirs representing hillslope and channel storages where sediment goes through cycles of storage and remobilization by surface runoff. The model includes all relevant hydrological processes that lead to runoff formation in an Alpine basin, such as precipitation, snow accumulation, snowmelt, evapotranspiration, and soil water storage. Although the processes of sediment transfer and debris flow generation are described in a simplified manner, the model produces complex sediment discharge behavior which is driven by the availability of sediment and antecedent wetness conditions (system memory) as well as the triggering potential (climatic forcing). The observed probability distribution of debris flow volumes and their seasonality in 2000–2009 are reproduced. The stochasticity of hillslope sediment input is important for reproducing realistic sediment storage variability, although many details of the hillslope landslide triggering procedures are filtered out by the sediment transfer system. The model allows us to explicitly quantify the division into transport and supply-limited sediment discharge events. We show that debris flows may be generated for a wide range of rainfall intensities because of variable antecedent basin wetness and snowmelt contribution to runoff, which helps to understand the limitations of methods based on a single rainfall threshold for debris flow initiation in Alpine basins

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

Elucidating variations in the nucleotide sequence of Ebola virus associated with increasing pathogenicity

Background Ebolaviruses cause a severe and often fatal haemorrhagic fever in humans, with some species such as Ebola virus having case fatality rates approaching 90%. Currently, the worst Ebola virus outbreak since the disease was discovered is occurring in West Africa. Although thought to be a zoonotic infection, a concern is that with increasing numbers of humans being infected, Ebola virus variants could be selected which are better adapted for human-to-human transmission. Results To investigate whether genetic changes in Ebola virus become established in response to adaptation in a different host, a guinea pig model of infection was used. In this experimental system, guinea pigs were infected with Ebola virus (EBOV), which initially did not cause disease. To simulate transmission to uninfected individuals, the virus was serially passaged five times in naïve animals. As the virus was passaged, virulence increased and clinical effects were observed in the guinea pig. An RNAseq and consensus mapping approach was then used to evaluate potential nucleotide changes in the Ebola virus genome at each passage. Conclusions Upon passage in the guinea pig model, EBOV become more virulent, RNA editing and also coding changes in key proteins become established. The data suggest that the initial evolutionary trajectory of EBOV in a new host can lead to a gain in virulence. Given the circumstances of the sustained transmission of EBOV in the current outbreak in West Africa, increases in virulence may be associated with prolonged and uncontrolled epidemics of EBOV

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