The challenge of unprecedented floods and droughts in risk management

Risk management has reduced vulnerability to floods and droughts globally1,2, yet their impacts are still increasing3. An improved understanding of the causes of changing impacts is therefore needed, but has been hampered by a lack of empirical data4,5. On the basis of a global dataset of 45 pairs of events that occurred within the same area, we show that risk management generally reduces the impacts of floods and droughts but faces difficulties in reducing the impacts of unprecedented events of a magnitude not previously experienced. If the second event was much more hazardous than the first, its impact was almost always higher. This is because management was not designed to deal with such extreme events: for example, they exceeded the design levels of levees and reservoirs. In two success stories, the impact of the second, more hazardous, event was lower, as a result of improved risk management governance and high investment in integrated management. The observed difficulty of managing unprecedented events is alarming, given that more extreme hydrological events are projected owing to climate change3

Circadian oscillator proteins across the kingdoms of life : Structural aspects 06 Biological Sciences 0601 Biochemistry and Cell Biology

Circadian oscillators are networks of biochemical feedback loops that generate 24-hour rhythms and control numerous biological processes in a range of organisms. These periodic rhythms are the result of a complex interplay of interactions among clock components. These components are specific to the organism but share molecular mechanisms that are similar across kingdoms. The elucidation of clock mechanisms in different kingdoms has recently started to attain the level of structural interpretation. A full understanding of these molecular processes requires detailed knowledge, not only of the biochemical and biophysical properties of clock proteins and their interactions, but also the three-dimensional structure of clockwork components. Posttranslational modifications (such as phosphorylation) and protein-protein interactions, have become a central focus of recent research, in particular the complex interactions mediated by the phosphorylation of clock proteins and the formation of multimeric protein complexes that regulate clock genes at transcriptional and translational levels. The three-dimensional structures for the cyanobacterial clock components are well understood, and progress is underway to comprehend the mechanistic details. However, structural recognition of the eukaryotic clock has just begun. This review serves as a primer as the clock communities move towards the exciting realm of structural biology

GAPDH Expression Predicts the Response to R-CHOP, the Tumor Metabolic Status, and the Response of DLBCL Patients to Metabolic Inhibitors.

Diffuse large B cell lymphoma (DLBCL) is a heterogeneous disease treated with anti-CD20-based immuno-chemotherapy (R-CHOP). We identified that low levels of GAPDH predict a poor response to R-CHOP treatment. Importantly, we demonstrated that GAPDH lymphomas use OxPhos metabolism and rely on mTORC1 signaling and glutaminolysis. Consistently, disruptors of OxPhos metabolism (phenformin) or glutaminolysis (L-asparaginase) induce cytotoxic responses in GAPDH B cells and improve GAPDH B cell-lymphoma-bearing mice survival, while they are low or not efficient on GAPDH B cell lymphomas. Ultimately, we selected four GAPDH DLBCL patients, who were refractory to all anti-CD20-based therapies, and targeted DLBCL metabolism using L-asparaginase (K), mTOR inhibitor (T), and metformin (M) (called KTM therapy). Three out of the four patients presented a complete response upon one cycle of KTM. These findings establish that the GAPDH expression level predicts DLBCL patients' response to R-CHOP treatment and their sensitivity to specific metabolic inhibitors

Organic acids under pressure: elastic properties, negative mechanical phenomena and pressure induced phase transitions in the lactic, maleic, succinic and citric acids

28 pags., 20 figs., 4 tabs.A detailed study of the behavior under pressure of four important organic acids using the first-principles solid-state methodology is presented. These organic acids are the L-(+)-lactic, maleic, succinic and citric acids. The citric acid monohydrate is also investigated. The computed crystal structures and associated X-ray diffraction patterns are in very good agreement with their experimental counterparts. The elastic tensors of these materials are determined using the finite deformation method and the mechanical stability of their structures is studied. A set of relevant elastic properties is obtained in terms of the computed elastic tensors. This set includes the bulk, shear and Young moduli, the Poisson’s ratio, the ductility, hardness and anisotropy indices and the bulk modulus pressure derivatives. In the solid state, these organic acids are shown to be stable, relatively weak and very anisotropic materials and, with the exception of citric acid monohydrate, all of them exhibit the negative Poisson’s ratio (NPR) phenomenon. The deformation of the crystal structures under isotropic pressures and anisotropic stresses is then evaluated and analyzed. The organic acids considered display the negative linear compressibility (NLC) phenomenon in several narrow pressure ranges. The presence of large NLC effects in these materials is mainly related to the onset of pressure induced phase transitions or sudden structural rearrangements. The lactic acid exhibits a large NLC effect under the effect of isotropic pressures due to the proximity of a pressure induced phase transition occurring at a pressure of P B 1.0 GPa. The maleic acid shows NLC under isotropic pressures of the order of P B 1.1 GPa but no phase transition is observed. Under anisotropic stresses directed along the minimum Poisson’s ratio direction, maleic acid also shows a large NLC effect at small external pressures of P B 0.1 GPa. Succinic acid displays small NLC effects in several pressure ranges under isotropic pressures but large NLC values under anisotropic stresses directed along the minimum NPR direction because it undergoes a pressure induced phase transition near P B 1.5 GPa. Finally, the citric acid shows small NLC values for negative isotropic pressures near 0.5 GPa and a large NLC effect under low anisotropic stresses (P B 0.1 GPa) which is accompanied by the breaking of one intramolecular hydrogen bond present in this material at zero pressureThe supercomputer time provided by the CTI-CSIC center is greatly acknowledgedPeer reviewe