The vascular bone marrow niche influences outcome in chronic myeloid leukemia via the E-selectin - SCL/TAL1-CD44 axis.

The endosteal bone marrow niche and vascular endothelial cells provide sanctuaries for leukemic cells. In murine chronic myeloid leukemia (CML) CD44 on leukemia cells and E-selectin on bone marrow endothelium are essential mediators for the engraftment of leukemic stem cells. We hypothesized that non-adhesion of CML-initiating cells to E-selectin on the bone marrow endothelium may lead to superior eradication of leukemic stem cells in CML after treatment with imatinib than imatinib alone. Indeed, here we show that treatment with the E-selectin inhibitor GMI-1271 in combination with imatinib prolongs survival of mice with CML via decreased contact time of leukemia cells with bone marrow endothelium. Non-adhesion of BCR-ABL1(+) cells leads to an increase of cell cycle progression and an increase of expression of the hematopoietic transcription factor and proto-oncogene Scl/Tal1 in leukemia-initiating cells. We implicate SCL/TAL1 as an indirect phosphorylation target of BCR-ABL1 and as a negative transcriptional regulator of CD44 expression. We show that increased SCL/TAL1 expression is associated with improved outcome in human CML. These data demonstrate the BCR-ABL1-specific, cell-intrinsic pathways leading to altered interactions with the vascular niche via the modulation of adhesion molecules - which could be exploited therapeutically in the future

The Economic Impact of the Value Chain of a Marcellus Shale Well

The Economic Impact of the Value Chain of a Marcellus Shale Well Site examines the direct economic impact of a Marcellus Shale well located in Southwestern Pennsylvania. This study seeks to fill a critical information gap on the impact of gas drilling and extraction from Marcellus Shale deposits deep underground: an assessment of the economic impacts – emphasizing the direct economic impact, rather than just focusing on the perceived benefits and impacts affecting the region. Our analysis is based on extensive field research, including a site visit and interviews with industry participants. It is further cross-validated by examining similar costs for development of Marcellus Wells by a vertically-integrated exploration and production firm

Extent, intensity and drivers of mammal defaunation:a continental-scale analysis across the Neotropics

Neotropical mammal diversity is currently threatened by several chronic human-induced pressures. We compiled 1,029 contemporary mammal assemblages surveyed across the Neotropics to quantify the continental-scale extent and intensity of defaunation and understand their determinants based on environmental covariates. We calculated a local defaunation index for all assemblages—adjusted by a false-absence ratio—which was examined using structural equation models. We propose a hunting index based on socioenvironmental co-variables that either intensify or inhibit hunting, which we used as an additional predictor of defaunation. Mammal defaunation intensity across the Neotropics on average erased 56.5% of the local source fauna, with ungulates comprising the most ubiquitous losses. The extent of defaunation is widespread, but more incipient in hitherto relatively intact major biomes that are rapidly succumbing to encroaching deforestation frontiers. Assemblage-wide mammal body mass distribution was greatly reduced from a historical 95th-percentile of ~ 14 kg to only ~ 4 kg in modern assemblages. Defaunation and depletion of large-bodied species were primarily driven by hunting pressure and remaining habitat area. Our findings can inform guidelines to design transnational conservation policies to safeguard native vertebrates, and ensure that the “empty ecosystem” syndrome will be deterred from reaching much of the New World tropics

Co-Translational Protein Folding and Sorting in Chloroplasts

Cells depend on the continuous renewal of their proteome composition during the cell cycle and in order to replace aberrant proteins or to react to changing environmental conditions. In higher eukaryotes, protein synthesis is achieved by up to five million ribosomes per cell. With the fast kinetics of translation, the large number of newly made proteins generates a substantial burden for protein homeostasis and requires a highly orchestrated cascade of factors promoting folding, sorting and final maturation. Several of the involved factors directly bind to translating ribosomes for the early processing of emerging nascent polypeptides and the translocation of ribosome nascent chain complexes to target membranes. In plant cells, protein synthesis also occurs in chloroplasts serving the expression of a relatively small set of 60–100 protein-coding genes. However, most of these proteins, together with nucleus-derived subunits, form central complexes majorly involved in the essential processes of photosynthetic light reaction, carbon fixation, metabolism and gene expression. Biogenesis of these heterogenic complexes adds an additional level of complexity for protein biogenesis. In this review, we summarize the current knowledge about co-translationally binding factors in chloroplasts and discuss their role in protein folding and ribosome translocation to thylakoid membranes

Pyridinic-N groups and ultramicropore nanoreactors enhance CO\u3csub\u3e2\u3c/sub\u3e electrochemical reduction on porous carbon catalysts

Wood-based activated carbons, as received and modified by introduction of nitrogen and/or oxidation, were studied as CO2 electrochemical reduction reaction (CO2ERR) catalysts. The carbons have similar pore structures but they differ significantly in surface chemistry. An electrochemical reduction process applied to the surface before CO2 reduction increased their catalytic performance. On the carbons tested Faradaic efficiency for CO formation reached 40% and methane formation − 1.2% at −0.66 V vs. RHE. The high efficiency for the CO formation was linked mainly to positively charged carbon close to pyridinic nitrogen, which stabilizes CO2− intermediate in the pore system. On the other hand, the results indicate that quaternary nitrogen is less influential and it is less affected by the reduction process. N-oxides outside the ring (CN+O−) were also found as active sites for CO2ERR. Hydrogen evolution reaction and CO2ERR compete for these active sites. Owing to the specific texture of nanoporous carbon, Faradaic reactions might not be a unique mechanism of CH4 formation. It is also possible that CO, upon strong adsorption in ultramicropores of sizes less than 0.7 nm combines there with adsorbed H2 from water reduction resulting in the formation of methane. Thus, the ultramicropores can be considered as pseudo Fisher-Tropsch nanoreactors. The results also indicate that the acidic surface of the catalysts increases the overpotential of the maximum Faradaic efficiency of either CO or CH4 formation

Co-Translational Protein Folding and Sorting in Chloroplasts

Cells depend on the continuous renewal of their proteome composition during the cell cycle and in order to replace aberrant proteins or to react to changing environmental conditions. In higher eukaryotes, protein synthesis is achieved by up to five million ribosomes per cell. With the fast kinetics of translation, the large number of newly made proteins generates a substantial burden for protein homeostasis and requires a highly orchestrated cascade of factors promoting folding, sorting and final maturation. Several of the involved factors directly bind to translating ribosomes for the early processing of emerging nascent polypeptides and the translocation of ribosome nascent chain complexes to target membranes. In plant cells, protein synthesis also occurs in chloroplasts serving the expression of a relatively small set of 60–100 protein-coding genes. However, most of these proteins, together with nucleus-derived subunits, form central complexes majorly involved in the essential processes of photosynthetic light reaction, carbon fixation, metabolism and gene expression. Biogenesis of these heterogenic complexes adds an additional level of complexity for protein biogenesis. In this review, we summarize the current knowledge about co-translationally binding factors in chloroplasts and discuss their role in protein folding and ribosome translocation to thylakoid membranes

A high-resolution model of bat diversity and endemism for continental Africa

Bats are the second-most species-rich mammal group numbering more than 1270 species globally. Our knowledge of their geographic distributions and diversity patterns however is very limited – possibly the poorest among mammals – mainly due to their nocturnal and volant life history, and challenging fieldwork conditions in the tropics where most bat species occur. This knowledge gap obscures the geographic extent of ecosystem services provided by bats (i.e. pollination, seed dispersal and insect control), translates into inefficient conservation policies, and restricts macroecological analyses to coarse spatial resolutions. In contrast to the currently prevailing method of estimating species distributions using expert-drawn range maps, correlative species distribution models (SDMs) can provide estimates at very fine spatial grains and largely account for widespread sample bias as well as the prevalent Wallacean shortfall in species occurrence data. Very few such studies have hitherto been published that cover a large and complete taxonomic group with fine resolution at continental extent. Using an unparalleled amount of occurrence data, the MaxEnt algorithm and tailored solutions to specific modelling challenges, we created SDMs for nearly all 250 African bat species to explore emerging diversity patterns at a resolution of 1 km2. Predicted species richness generally increases towards the equator conforming to expectations. Within the tropical area of elevated richness, several pronounced richness peaks and lows stand out, hinting at a complex interplay of determining factors. Richness gradients are often steep, decreasing strongly away from streams, and especially so in savanna biomes. Species richness also seems positively associated with rugged terrain, in particular at lower elevations. Centres of endemism are found primarily at low latitudes near major elevational ranges. Overlap with hotspots of species richness is rather low, and confined to five or six topodiverse, relatively low lying areas between wester

Dynamic strength testing of 3D-reinforced T-joints

Focus of this paper is to show the performance of reinforced CRFP T-joints under dynamic loading in a specifically designed testing facility. Static strength tests have been performed as a cross reference. Samples were built out of noncrimp fabrics (NCF) and for a part of them Carbon fibres were used to reinforce the Tjoints on the NCF-skin by means of a tufting-stitching head mounted on an industrial robot. These so-called preforms were then infiltrated with RTM 6 Epoxy resin and cured in an autoclave process. The specimens were tested both dynamically and statically. Results show an increase in the ultimate strength and in the energy absorption in case of the dynamically tested samples

A comparison of macroecological and stacked species distribution models to predict future global terrestrial vertebrate richness

Aim: Predicting future changes in species richness in response to climate change is one of the key challenges in biogeography and conservation ecology. Stacked species distribution models (S‐SDMs) are a commonly used tool to predict current and future species richness. Macroecological models (MEMs), regression models with species richness as response variable, are a less computationally intensive alternative to S‐SDMs. Here, we aim to compare the results of two model types (S‐SDMS and MEMs), for the first time for more than 14,000 species across multiple taxa globally, and to trace the uncertainty in future predictions back to the input data and modelling approach used. Location: Global land, excluding Antarctica. Taxon: Amphibians, birds and mammals. Methods: We fitted S‐SDMs and MEMs using a consistent set of bioclimatic variables and model algorithms and conducted species richness predictions under current and future conditions. For the latter, we used four general circulation models (GCMs) under two representative concentration pathways (RCP2.6 and RCP6.0). Predicted species richness was compared between S‐SDMs and MEMs and for current conditions also to extent‐of‐occurrence (EOO) species richness patterns. For future predictions, we quantified the variance in predicted species richness patterns explained by the choice of model type, model algorithm and GCM using hierarchical cluster analysis and variance partitioning. Results: Under current conditions, species richness predictions from MEMs and S‐SDMs were strongly correlated with EOO‐based species richness. However, both model types over‐predicted areas with low and under‐predicted areas with high species richness. Outputs from MEMs and S‐SDMs were also highly correlated among each other under current and future conditions. The variance between future predictions was mostly explained by model type. Main conclusions: Both model types were able to reproduce EOO‐based patterns in global terrestrial vertebrate richness, but produce less collinear predictions of future species richness. Model type by far contributes to most of the variation in the different future species richness predictions, indicating that the two model types should not be used interchangeably. Nevertheless, both model types have their justification, as MEMs can also include species with a restricted range, whereas S‐SDMs are useful for looking at potential species‐specific responses