Essential Role of the \u3ci\u3eCrk\u3c/i\u3e Family-Dosage in DiGeorge-Like Anomaly and Metabolic Homeostasis

CRK and CRKL (CRK-like) encode adapter proteins with similar biochemical properties. Here, we show that a 50% reduction of the family-combined dosage generates developmental defects, including aspects of DiGeorge/del22q11 syndrome in mice. Like the mouse homologs of two 22q11.21 genes CRKL and TBX1, Crk and Tbx1 also genetically interact, thus suggesting that pathways shared by the three genes participate in organogenesis affected in the syndrome. We also show that Crk and Crkl are required during mesoderm development, and Crk/Crkl deficiency results in small cell size and abnormal mesenchyme behavior in primary embryonic fibroblasts. Our systems-wide analyses reveal impaired glycolysis, associated with low Hif1a protein levels as well as reduced histone H3K27 acetylation in several key glycolysis genes. Furthermore, Crk/Crkl deficiency sensitizes MEFs to 2deoxy-D-glucose, a competitive inhibitor of glycolysis, to induce cell blebbing. Activated Rapgef1, a Crk/Crkl-downstream effector, rescues several aspects of the cell phenotype, including proliferation, cell size, focal adhesions, and phosphorylation of p70 S6k1 and ribosomal protein S6. Our investigations demonstrate that Crk/Crkl-shared pathways orchestrate metabolic homeostasis and cell behavior through widespread epigenetic controls

Essential ocean variables for global sustained observations of biodiversity and ecosystem changes

International audience; Sustained observations of marine biodiversity and ecosystems focused on specific conservation and management problems are needed around the world to effectively mitigate or manage changes resulting from anthropogenic pressures. These observations, while complex and expensive, are required by the international scientific, governance and policy communities to provide baselines against which the effects of human pressures and climate change may be measured and reported, and resources allocated to implement solutions. To identify biological and ecological essential ocean variables (EOVs) for implementation within a global ocean observing system that is relevant for science, informs society, and technologically feasible, we used a driver-pressure-state-impact-response (DPSIR) model. We (1) examined relevant international agreements to identify societal drivers and pressures on marine resources and ecosystems, (2) evaluated the temporal and spatial scales of variables measured by 100+ observing programs, and (3) analysed the impact and scalability of these variables and how they contribute to address societal and scientific issues. EOVs were related to the status of ecosystem components (phytoplankton and zoo-plankton biomass and diversity, and abundance and distribution of fish, marine turtles, birds and mammals), and to the extent and health of ecosystems (cover and composition of hard coral, seagrass, mangrove and macroalgal canopy). Benthic invertebrate abundance and distribution and microbe diversity and biomass were identified as emerging EOVs to be developed based on emerging requirements and new technologies. The temporal scale at which any shifts in biological systems will be detected will vary across the EOVs, the properties being monitored and the length of the existing time-series. Global implementation to deliver useful products will require collaboration of the scientific and policy sectors and a significant commitment to improve human and infrastructure capacity across the globe, including the development of new, more automated observing technologies, and encouraging the application of international standards and best practices

Redox cycling metals: Pedaling their roles in metabolism and their use in the development of novel therapeutics

Essential metals, such as iron and copper, play a critical role in a plethora of cellular processes including cell growth and proliferation. However, concomitantly, excess of these metal ions in the body can have deleterious effects due to their ability to generate cytotoxic reactive oxygen species (ROS). Thus, the human body has evolved a very well-orchestrated metabolic system that keeps tight control on the levels of these metal ions. Considering their very high proliferation rate, cancer cells require a high abundance of these metals compared to their normal counterparts. Interestingly, new anti-cancer agents that take advantage of the sensitivity of cancer cells to metal sequestration and their susceptibility to ROS have been developed. These ligands can avidly bind metal ions to form redox active metal complexes, which lead to generation of cytotoxic ROS. Furthermore, these agents also act as potent metastasis suppressors due to their ability to up-regulate the metastasis suppressor gene, N-myc downstream regulated gene 1. This review discusses the importance of iron and copper in the metabolism and progression of cancer, how they can be exploited to target tumors and the clinical translation of novel anti-cancer chemotherapeutics

Benford's Law and psychological barriers in certain eBay auctions

Using generalizations of Benford's Law we test for the absence of psychological barriers at various price levels in eBay auctions for professional football tickets. Our empirical results indicate that this hypothesis cannot be rejected.

Benford's Law and Psychological Barriers in Certain eBay Auctions

Using generalizations of Benford’s Law we test for the absence of psychological barriers at various price levels in eBay auctions for professional football tickets. Our empirical results indicate that this hypothesis cannot be rejected.Psychological barriers, auction prices, Benford’s law

The effect of cerium incorporation on the catalytic performance of cobalt and manganese containing layer double oxides for acetone oxidation

Abstract BACKGROUND Acetone is a volatile organic compound (VOC) that is often associated with poor air quality. Acetone has chronic toxicity towards humans and has significant impact to the overall atmospheric air quality. In this study, several layer double oxides (with M2+ = Mg, Ni, Co or Mn and M3+= Al or Ce)were tested as catalyst in acetone oxidation. RESULTS MnAl-LDO was found to be the most efficient catalyst. 50% acetone conversion was achieved at 170 °C (T50%) and 90% conversion at 200 °C (T90%).The incorporation of Ce on MnCeAl-LDO did not improve its catalytic properties over MnAl-LDO (the T50% for MnCeAl-LDO was 12 °C higher than for MnAl-LDO). The good performance on MnAl-LDO was due to the presence of Mn3+. MnAl-LDO was not affect when water was introduced into the catalytic reaction setup. Less than 5 % fluctuation in the acetone conversion rate at 170 and 200 °C was detected in the presence of 5.5% water. The incorporation of Ce on CoCeAl-LDO improved its catalytic performance over CoAl-LDO (T50% of CoCeAl-LDO was 15 °C lower than CoAl-LDO).Our results showed that the good catalytic performance of CoCeAl-LDO was ascribed to the increased Co2+/Co3+ ratio and the abundance of lattice oxygen (Olatt). CONCLUSION MnAl-LDO has good catalytic properties for acetone oxidation, even under humid conditions. The LDO catalysts tested here can be developed into efficient catalysts for acetone oxidation and serve as functional materials for the reduction in acetone or VOC emission. This article is protected by copyright. All rights reserved

Fracture of a slope by percolating

A theoretical analysis based on a pseudo-three-phase media is presented, and the instability of a slope causing the debris flow is studied. The occurrence of fractures (or water films) in saturated soils in two cases is analyzed. The first case is that the water is forced to percolate through the soil upwards. A perturbation method is used in this case to obtain an approximate solution to explain the formation mechanism of cracks. The second case is about the cracks in liquefied soils. Numerical analysis and theoretical analysis are processed for this case. The formation of fractures in saturated grain accumulation under gravity is due to the blocking by redeposit of finer grains. The formation of fractures presents a sliding surface for landslides and debris flow

Experimental study on mechanical properties of methane-hydrate-bearing sediments

Mechanical properties of methane hydrate-bearing-sediments (MHBS) are basic parameters for safety analysis of hydrate exploration and exploitation. Young's modulus, cohesion, and internal friction angle of hydrate-bearing sediments synthesized in laboratory, are investigated using tri-axial tests. Stress-strain curves and strength parameters are obtained and discussed for different compositions and different hydrate saturation, followed by empirical expressions related to the cohesion, internal friction angle, and modulus of MHBS. Almost all tested MHBS samples exhibit plastic failure. With the increase of total saturation of ice and methane hydrate (MH), the specimens' internal friction angle decreases while the cohesion increases.Mechanical properties of methane hydrate-bearing-sediments (MHBS) are basic parameters for safety analysis of hydrate exploration and exploitation. Young's modulus, cohesion, and internal friction angle of hydrate-bearing sediments synthesized in laboratory, are investigated using tri-axial tests. Stress-strain curves and strength parameters are obtained and discussed for different compositions and different hydrate saturation, followed by empirical expressions related to the cohesion, internal friction angle, and modulus of MHBS. Almost all tested MHBS samples exhibit plastic failure. With the increase of total saturation of ice and methane hydrate (MH), the specimens' internal friction angle decreases while the cohesion increases