Field trials to assess resistance to warfarin and difenacoum of house mice in relation to the occurrence of variants in the vkorc1-gene before and after the treatments

Endepols, S., Klemann, N., Song, Y., Kohn, M.H

Altimetry, gravimetry, GPS and viscoelastic modeling data for the joint inversion for glacial isostatic adjustment in Antarctica (ESA STSE Project REGINA)

The poorly known correction for the ongoing deformation of the solid Earth caused by glacial isostatic adjustment (GIA) is a major uncertainty in determining the mass balance of the Antarctic ice sheet from measurements of satellite gravimetry and to a lesser extent satellite altimetry. In the past decade, much progress has been made in consistently modeling ice sheet and solid Earth interactions; however, forward-modeling solutions of GIA in Antarctica remain uncertain due to the sparsity of constraints on the ice sheet evolution, as well as the Earth's rheological properties. An alternative approach towards estimating GIA is the joint inversion of multiple satellite data – namely, satellite gravimetry, satellite altimetry and GPS, which reflect, with different sensitivities, trends in recent glacial changes and GIA. Crucial to the success of this approach is the accuracy of the space-geodetic data sets. Here, we present reprocessed rates of surface-ice elevation change (Envisat/Ice, Cloud,and land Elevation Satellite, ICESat; 2003–2009), gravity field change (Gravity Recovery and Climate Experiment, GRACE; 2003–2009) and bedrock uplift (GPS; 1995–2013). The data analysis is complemented by the forward modeling of viscoelastic response functions to disc load forcing, allowing us to relate GIA-induced surface displacements with gravity changes for different rheological parameters of the solid Earth. The data and modeling results presented here are available in the PANGAEA database (https://doi.org/10.1594/PANGAEA.875745). The data sets are the input streams for the joint inversion estimate of present-day ice-mass change and GIA, focusing on Antarctica. However, the methods, code and data provided in this paper can be used to solve other problems, such as volume balances of the Antarctic ice sheet, or can be applied to other geographical regions in the case of the viscoelastic response functions. This paper presents the first of two contributions summarizing the work carried out within a European Space Agency funded study: Regional glacial isostatic adjustment and CryoSat elevation rate corrections in Antarctica (REGINA)

Evolution of Global Ocean Tide Levels Since the Last Glacial Maximum

This study addresses the evolution of global tidal dynamics since the Last Glacial Maximum focusing on the extraction of tidal levels that are vital for the interpretation of geologic sea-level markers. For this purpose, we employ a truly-global barotropic ocean tide model which considers the non-local effect of Self-Attraction and Loading. A comparison to a global tide gauge data set for modern conditions yields agreement levels of 65%–70%. As the chosen model is data-unconstrained, and the considered dissipation mechanisms are well understood, it does not have to be re-tuned for altered paleoceanographic conditions. In agreement with prior studies, we find that changes in bathymetry during glaciation and deglaciation do exert critical control over the modeling results with minor impact by ocean stratification and sea ice friction. Simulations of 4 major partial tides are repeated in time steps of 0.5–1 ka and augmented by 4 additional partial tides estimated via linear admittance. These are then used to derive time series from which the tidal levels are determined and provided as a global data set conforming to the HOLSEA format. The modeling results indicate a strengthened tidal resonance by M2, but also by O1, under glacial conditions, in accordance with prior studies. Especially, a number of prominent changes in local resonance conditions are identified, that impact the tidal levels up to several meters difference. Among other regions, resonant features are predicted for the North Atlantic, the South China Sea, and the Arctic Ocean

Adaptive introgressive hybridization with the Algerian mouse (Mus spretus) promoted the evolution of anticoagulant rodenticide resistance in European house mice (M. musculus domesticus)

Song, Y., Endepols, S., Klemann, N., Richter, D., Matuschka, F.-R., Shih, C.-H., Nachman, M.W., Kohn, M.H

Projeto MOVIDA: uma análise do processo de inclusão digital visando à inclusão social

Recursos físicos e conectividade não garantem a inclusão digital. A inclusão digital é um processo estabelecido dentro de uma sociedade mais ampla que busca satisfazer necessidades relacionadas com qualidade de vida. O presente artigo apresenta uma análise realizada a partir do Projeto MOVIDA sob o aspecto da inclusão digital, com o objetivo de verificar que tipo de inclusão social o mesmo propicia. Como metodologia foi realizado o levantamento de dados e a análise com base nas variáveis propostas por Warschauer (2006). Como principal resultado acredita-se que a metodologia utilizada favorece a análise dos impactos da inclusão digital no processo de inclusão social, a qual permitiu identificar os impactos no Projeto MOVIDA

High temperature behaviour of a CuO/Al2O3 oxygen carrier for Chemical-Looping Combustion

8 pages, 10 figures, 2 tables.- Available online April 13, 2011.Chemical-Looping Combustion (CLC) is a combustion technology with inherent CO2 separation and, therefore, without energy losses. CLC is based on the transfer of oxygen from the air to the fuel by means of an oxygen carrier (OC) in the form of a metal oxide. The OC circulates between two interconnected reactors, the fuel (FR) and the air reactor (AR). To scale up the CLC process for industrial application OCs materials suitable to work at high temperatures are needed. So far, Cu-based OCs had been proved to fulfil the requirements for an OC material, although operating temperatures lower than 1073 K are recommended. In this work, the behaviour of an impregnated Cu-based oxygen carrier (CuO-Al2O3) was studied in a continuous CLC unit of 500 Wth during long-term tests using methane as fuel gas and FR temperatures up to 1173 K and AR temperatures up to 1223 K. The behaviour of the oxygen carrier on the process performance was evaluated taking into account important aspects such as combustion efficiency, resistance to attrition, fluidization behaviour and preservation of the oxygen transport capacity and reactivity. It was found that both TFR and TAR had a great influence on the resistance to attrition of the particles. Stable operation for more than 60 h was only feasible at TFR =1073 K and TAR = 1173 K. However agglomeration or deactivation of the particles was never detected in any of the temperatures used. This is the first time that a CuO-Al2O3 OC, prepared by a commercial manufacturing method, and used at 1073K in the FR and 1173 K in the AR exhibits such a good properties: high reactivity together with high mechanical durability and absence of agglomeration. This result opens new possibilities for the application of Cu-based materials in industrial-scale CLC processes.This research was conducted with financial support from the Spanish Ministry of Science and Innovation (MICINN, Project CTQ2007-64400) and C.S.I.C. (200480E619).Peer reviewe

Integrated molecular landscape of Parkinson’s disease

Parkinson’s disease is caused by a complex interplay of genetic and environmental factors. Although a number of independent molecular pathways and processes have been associated with familial Parkinson’s disease, a common mechanism underlying especially sporadic Parkinson’s disease is still largely unknown. In order to gain further insight into the etiology of Parkinson’s disease, we here conducted genetic network and literature analyses to integrate the top-ranked findings from thirteen published genome-wide association studies of Parkinson’s disease (involving 13.094 cases and 47.148 controls) and other genes implicated in (familial) Parkinson’s disease, into a molecular interaction landscape. The molecular Parkinson’s disease landscape harbors four main biological processes—oxidative stress response, endosomal-lysosomal functioning, endoplasmic reticulum stress response, and immune response activation—that interact with each other and regulate dopaminergic neuron function and death, the pathological hallmark of Parkinson’s disease. Interestingly, lipids and lipoproteins are functionally involved in and influenced by all these processes, and affect dopaminergic neuron-specific signaling cascades. Furthermore, we validate the Parkinson’s disease -lipid relationship by genome-wide association studies data-based polygenic risk score analyses that indicate a shared genetic risk between lipid/lipoprotein traits and Parkinson’s disease. Taken together, our findings provide novel insights into the molecular pathways underlying the etiology of (sporadic) Parkinson’s disease and highlight a key role for lipids and lipoproteins in Parkinson’s disease pathogenesis, providing important clues for the development of disease-modifying treatments of Parkinson’s disease

Palaeo-sea-level and palaeo-ice-sheet databases: Problems, strategies, and perspectives

Sea-level and ice-sheet databases have driven numerous advances in understanding the Earth system. We describe the challenges and offer best strategies that can be adopted to build self-consistent and standardised databases of geological and geochemical information used to archive palaeo-sea-levels and palaeo-ice-sheets. There are three phases in the development of a database: (i) measurement, (ii) interpretation, and (iii) database creation. Measurement should include the objective description of the position and age of a sample, description of associated geological features, and quantification of uncertainties. Interpretation of the sample may have a subjective component, but it should always include uncertainties and alternative or contrasting interpretations, with any exclusion of existing interpretations requiring a full justification. During the creation of a database, an approach based on accessibility, transparency, trust, availability, continuity, completeness, and communication of content (ATTAC3) must be adopted. It is essential to consider the community that creates and benefits from a database. We conclude that funding agencies should not only consider the creation of original data in specific research-question-oriented projects, but also include the possibility of using part of the funding for IT-related and database creation tasks, which are essential to guarantee accessibility and maintenance of the collected data

Transcription-coupled nucleotide excision repair is coordinated by ubiquitin and SUMO in response to ultraviolet irradiation

Cockayne Syndrome (CS) is a severe neurodegenerative and premature aging autosomal-recessive disease, caused by inherited defects in the CSA and CSB genes, leading to defects in transcription-coupled nucleotide excision repair (TC-NER) and consequently hypersensitivity to ultraviolet (UV) irradiation. TC-NER is initiated by lesion-stalled RNA polymerase II, which stabilizes the interaction with the SNF2/SWI2 ATPase CSB to facilitate recruitment of the CSA E3 Cullin ubiquitin ligase complex. However, the precise biochemical connections between CSA and CSB are unknown. The small ubiquitin-like modifier SUMO is important in the DNA damage response. We found that CSB, among an extensive set of other target proteins, is the most dynamically SUMOylated substrate in response to UV irradiation. Inhibiting SUMOylation reduced the accumulation of CSB at local sites of UV irradiation and reduced recovery of RNA synthesis. Interestingly, CSA is required for the efficient clearance of SUMOylated CSB. However, subsequent proteomic analysis of CSA-dependent ubiquitinated substrates revealed that CSA does not ubiquitinate CSB in a UV-dependent manner. Surprisingly, we found that CSA is required for the ubiquitination of the largest subunit of RNA polymerase II, RPB1. Combined, our results indicate that the CSA, CSB, RNA polymerase II triad is coordinated by ubiquitin and SUMO in response to UV irradiation. Furthermore, our work provides a resource of SUMO targets regulated in response to UV or ionizing radiation

Exploring the drivers of global and local sea-level change over the 21st century and beyond

We present a new set of global and local sea-level projections at example tide gauge locations under the RCP2.6, RCP4.5 and RCP8.5 emissions scenarios. Compared to the CMIP5-based sealevel projections presented in IPCC AR5, we introduce a number of methodological innovations, including: (i) more comprehensive treatment of uncertainties; (ii) direct traceability between global and local projections; (iii) exploratory extended projections to 2300 based on emulation of individual CMIP5 models. Combining the projections with observed tide gauge records, we explore the contribution to total variance that arises from sea-level variability, different emissions scenarios and model uncertainty. For the period out to 2300 we further breakdown the model uncertainty by sea-level component and consider the dependence on geographic location, time horizon and emissions scenario. Our analysis highlights the importance of variability for sea-level change in the coming decades and the potential value of annual-to-decadal predictions of local sea-level change. Projections to 2300 show a substantial degree of committed sea-level rise under all emissions scenarios considered and highlights the reduced future risk associated with RCP2.6 and RCP4.5 compared to RCP8.5. Tide gauge locations can show large (> 50%) departures from the global average, in some cases even reversing the sign of the change. While uncertainty in projections of the future Antarctic ice dynamic response tends to dominate post2100, we see a substantial differences in the breakdown of model variance as a function of location, timescale and emissions scenario