PARP1 catalytic variants reveal branching and chain length-specific functions of poly(ADP-ribose) in cellular physiology and stress response

Poly(ADP-ribosyl)ation regulates numerous cellular processes like genome maintenance and cell death, thus providing protective functions but also contributing to several pathological conditions. Poly(ADP-ribose) (PAR) molecules exhibit a remarkable heterogeneity in chain lengths and branching frequencies, but the biological significance of this is basically unknown. To unravel structure-specific functions of PAR, we used PARP1 mutants producing PAR of different qualities, i.e. short and hypobranched (PARP1\G972R), short and moderately hyperbranched (PARP1\Y986S), or strongly hyperbranched PAR (PARP1\Y986H). By reconstituting HeLa PARP1 knockout cells, we demonstrate that PARP1\G972R negatively affects cellular endpoints, such as viability, cell cycle progression and genotoxic stress resistance. In contrast, PARP1\Y986S elicits only mild effects, suggesting that PAR branching compensates for short polymer length. Interestingly, PARP1\Y986H exhibits moderate beneficial effects on cell physiology. Furthermore, different PARP1 mutants have distinct effects on molecular processes, such as gene expression and protein localization dynamics of PARP1 itself, and of its downstream factor XRCC1. Finally, the biological relevance of PAR branching is emphasized by the fact that branching frequencies vary considerably during different phases of the DNA damage-induced PARylation reaction and between different mouse tissues. Taken together, this study reveals that PAR branching and chain length essentially affect cellular functions, which further supports the notion of a ‘PAR code’

Silicon oxycarbonitride ceramic containing nickel nanoparticles from design to catalytic application

Nickel containing silicon oxycarbonitride ceramic nanocomposites are synthesized from hydrous nickel acetate and poly vinyl silazane Durazane 1800 or perhydropolysilazane NN120 20 A PHPS . A room temperature chemical reaction results in Ni containing polysilazane precursors which are transformed into ceramic nanocomposites with nickel nanoparticles 2 4 nm upon pyrolysis at elevated temperatures 700 1100 C under an argon atmosphere. The ceramic nanocomposites derived from the Durazane 1800 Ni precursor by the thermolysis process at 700 and 900 C manifest a microporous structure with a BET specific surface area of amp; 8764;361 and amp; 8764;232 m2 g amp; 8722;1, respectively. In contrast, all pyrolyzed samples derived from the PHPS Ni precursor exhibit a nonporous structure. The Ni SiOCN ceramic nanocomposites tested in a plug flow fixed bed reactor display significant catalytic activity in dry methane reforming to syngas. The highest CH4 reaction rate of 0.18 mol min amp; 8722;1 gNi amp; 8722;1 is observed at 800 C for the sample derived from the PHPS Ni precursor by pyrolysis at 900 C. All these make the materials developed in this work, i.e. nickel nanoparticles in situ formed in the SiOCN ceramic matrix, as promising candidates for heterogeneous catalysi

Sr Al Si co segregated regions in eutectic Si phase of Sr modified Al 10Si alloy

The additionof200ppmstrontiumtoanAl 10wt Sicastingalloychangesthemorphologyofthe eutecticsiliconphasefromcoarseplate liketofinefibrousnetworks.Inordertoclarifythis modificationmechanismthelocationofSrwithintheeutecticSiphasehasbeeninvestigatedbya combinationofhigh resolutionmethods.Whereasthree dimensionalatomprobetomographyallows us tovisualisethedistributionofSrontheatomicscaleandtoanalyseitslocalenrichment, transmissionelectronmicroscopyyieldsinformationaboutthecrystallographicnatureofsegregated regions.SegregationswithtwokindsofmorphologieswerefoundattheintersectionsofSitwin lamellae Sr Al Sico segregationsofrod likemorphologyandAl richregionsofsphericalmorphology. Both areresponsiblefortheformationofahighdensityofmultipletwinsandpromotetheanisotropic growth oftheeutecticSiphaseinspecificcrystallographicdirectionsduringsolidification.The experimentalfindingsarerelatedtothepreviouslypostulatedmechanismof impurityinduced twinnin

Medial Entorhinal Cortex Lesions Only Partially Disrupt Hippocampal Place Cells and Hippocampus-Dependent Place Memory

The entorhinal cortex provides the primary cortical projections to the hippocampus, a brain structure critical for memory. However, it remains unclear how the precise firing patterns of medial entorhinal cortex (MEC) cells influence hippocampal physiology and hippocampus-dependent behavior. We found that complete bilateral lesions of the MEC resulted in a lower proportion of active hippocampal cells. The remaining active cells had place fields, but with decreased spatial precision and decreased long-term spatial stability. In addition, MEC rats were as impaired in the water maze as hippocampus rats, while rats with combined MEC and hippocampal lesions had an even greater deficit. However, MEC rats were not impaired on other hippocampus-dependent tasks, including those in which an object location or context was remembered. Thus, the MEC is not necessary for all types of spatial coding or for all types of hippocampus-dependent memory, but it is necessary for the normal acquisition of place memory

A laboratory spectrometer for high throughput X-ray emission spectroscopy in catalysis research

We have built a laboratory spectrometer for X-ray emission spectroscopy. The instrument is employed in catalysis research. The key component is a von Hamos full cylinder optic with Highly Annealed Pyrolytic Graphite (HAPG) as a dispersive element. With this very efficient optic, the spectrometer subtends an effective solid angle of detection of around 1 msr, allowing for the analysis of dilute samples. The resolving power of the spectrometer is approximately E/ΔE = 4000, with an energy range of ∼2.3 keV–10 keV. The instrument and its characteristics are described herein. Further, a comparison with a prototype spectrometer, based on the same principle, shows the substantial improvement in the spectral resolution and energy range for the present setup. The paper concludes with a discussion of sample handling. A compilation of HAPG fundamentals and related publications are given in a brief Appendix.EC/FP7/615414/EU/Spectroscopic Studies of N2 Reduction: From Biological to Heterogeneous Catalysis/N2RE

Insights into structure and dynamics of (Mn,Fe)O_x-promoted Rh nanoparticles

The mutual interaction between Rh nanoparticles and manganese/iron oxide promoters in silica-supported Rh catalysts for hydrogenation of CO to higher alcohols was analyzed by applying a combination of integral techniques including temperature-programmed reduction (TPR), X-ray photoelectron spectroscopy (XPS), X-ray absorption (XAS) and Fourier transform infrared (FTIR) spectroscopy with local analysis by using high angle annular dark-field scanning transmission electron microscopy (HAADF-STEM) in combination with energy dispersive X-ray spectroscopy (EDX). The promoted catalysts show reduced CO adsorption capacity as evidenced by FTIR spectroscopy, which is attributed to a perforated core-shell structure of the Rh nano-particles in accordance with the microstructural analysis by electron microscopy. Iron and manganese occur in low formal oxidation states between 2+ and zero in the reduced catalysts as shown by TPR and XAS. Infrared spectroscopy measured in diffuse reflectance at reaction temperature and pressure indicates that partial coverage of the Rh particles is maintained at reaction temperature under operation and that the remaining accessible metal adsorption sites might be catalytically less relevant because hydrogenation of adsorbed carbonyl species at 523 K and 30 bar hydrogen essentially failed. It is concluded that Rh⁰ is poisoned due to adsorption of CO under reaction conditions of CO hydrogenation. The active sites are associated either with a (Mn,Fe)O_x (x<0.25) phase or species at the interface between Rh and its co-catalyst (Mn,Fe)O_x