Novel Binding Mode of a Potent and Selective Tankyrase Inhibitor

Tankyrases (TNKS1 and TNKS2) are key regulators of cellular processes such as telomere pathway and Wnt signaling. IWRs (inhibitors of Wnt response) have recently been identified as potent and selective inhibitors of tankyrases. However, it is not clear how these IWRs interact with tankyrases. Here we report the crystal structure of the catalytic domain of human TNKS1 in complex with IWR2, which reveals a novel binding site for tankyrase inhibitors. The TNKS1/IWR2 complex provides a molecular basis for their strong and specific interactions and suggests clues for further development of tankyrase inhibitors

Evaluation of water use for bioenergy at different scales

This perspective reviews water metrics for accounting total water demand to produce bioenergy at various spatial scales. Volumes of water abstracted, consumed, and altered are estimated to assess water requirements of a bioenergy product, providing useful tools for water resource management and planning at local, regional, and global scale. Blue‐water use accounting, integrated over time and space, provides the most direct measurements of the effects of bioenergy production on freshwater allocation among various end‐users, and on human and ecosystem health and well‐being. Measurement of total water demand for crop evapotranspiration, which includes both blue and green water, communicates vital information of how land and water productivity supports/constrains bioenergy expansion, and helps identify potential areas to increase the productivity of agriculture through improved soil and water conservation, changes in crop choice, and improved crop management. Life‐cycle water use accounting provides a useful comparison of water required for production and conversion of feedstock to various forms of energy, and opportunities to improve water use efficiency throughout the supply chain. In addition, life‐cycle water use may be used to account for water use avoided as a result of displacement of products by coproducts of biofuel production; though these applications must be interpreted with caution. Local or regional conditions and the objective of the analysis at hand determine which water accounting metrics are most relevant and the relative importance of water use impact compared to other impacts, such as impacts to soil quality and biodiversity

Physics at a 100 TeV pp collider: Higgs and EW symmetry breaking studies

This report summarises the physics opportunities for the study of Higgs bosons and the dynamics of electroweak symmetry breaking at the 100 TeV pp collider.Comment: 187 pages, 94 figures. Chapter 2 of the "Physics at the FCC-hh" Repor

Precision studies of observables in pp → W → lνl and pp → γ , Z → l+l− processes at the LHC

This report was prepared in the context of the LPCC Electroweak Precision Measurements at the LHC WG (https://lpcc.web.cern.ch/lpcc/index.php?page=electroweak_wg) and summarizes the activity of a subgroup dedicated to the systematic comparison of public Monte Carlo codes, which describe the Drell–Yan processes at hadron colliders, in particular at the CERN Large Hadron Collider (LHC). This work represents an important step towards the definition of an accurate simulation framework necessary for very high-precision measurements of electroweak (EW) observables such as the W boson mass and the weak mixing angle. All the codes considered in this report share at least next-to-leading-order (NLO) accuracy in the prediction of the total cross sections in an expansion either in the strong or in the EW coupling constant. The NLO fixed-order predictions have been scrutinized at the technical level, using exactly the same inputs, setup and perturbative accuracy, in order to quantify the level of agreement of different implementations of the same calculation. A dedicated comparison, again at the technical level, of three codes that reach next-to-next-to-leading-order (NNLO) accuracy in quantum chromodynamics (QCD) for the total cross section has also been performed. These fixed-order results are a well-defined reference that allows a classification of the impact of higher-order sets of radiative corrections. Several examples of higher-order effects due to the strong or the EW interaction are discussed in this common framework. Also the combination of QCD and EW corrections is discussed, together with the ambiguities that affect the final result, due to the choice of a specific combination recipe. All the codes considered in this report have been run by the respective authors, and the results presented here constitute a benchmark that should be always checked/reproduced before any high-precision analysis is conducted based on these codes. In order to simplify these benchmarking procedures, the codes used in this report, together with the relevant input files and running instructions, can be found in a repository at https://twiki.cern.ch/twiki/bin/view/Main/DrellYanComparison

Transient study of the oxygen reduction reaction on reduced Pt and Pt alloys microelectrodes: evidence for the reduction of pre-adsorbed oxygen species linked to dissolved oxygen

Using chronoamperometry at preconditioned oxide-free Pt microdisc electrodes in aqueous media, we investigated the oxygen reduction reaction (ORR) on the millisecond timescale and obtained results consistent with the reduction of oxygen species which adsorb on the electrode before the ORR is electrochemically driven. Furthermore these adsorbed species are clearly linked to oxygen in solution. At long times, the amperometric response is solely controlled by the diffusion of dissolved oxygen towards the microelectrode. However, at short times, typically below 50 ms, the reduction of pre-adsorbed oxygen produces a large extra current whose magnitude depends on the oxygen concentration in solution, deliberate electrode poisoning and the rest time before the potential step. Using sampled current voltammetry we show that this extra current affects the entire potential range of the ORR. Using microdisc electrodes made with Pt alloys we find that the amperometric response is sufficiently sensitive to distinguish oxygen coverage differences between Pt, Pt0.9Rh0.1 and Pt0.9Ir0.1 microdiscs. These unexpected and, to our knowledge, never previously reported results provide new insight into the oxygen reduction reaction on Pt. The existence over a wide potential range of irreversibly adsorbed oxygen species arising from dissolved oxygen and different from Pt oxide is particularly relevant to the development of oxygen reduction catalysts for low temperature fuel cells

Mammalian Frataxin: An Essential Function for Cellular Viability through an Interaction with a Preformed ISCU/NFS1/ISD11 Iron-Sulfur Assembly Complex

Frataxin, the mitochondrial protein deficient in Friedreich ataxia, a rare autosomal recessive neurodegenerative disorder, is thought to be involved in multiple iron-dependent mitochondrial pathways. In particular, frataxin plays an important role in the formation of iron-sulfur (Fe-S) clusters biogenesis.. Fe-S cluster biosynthesis