Proposal for field sampling of plants and processing in the lab for environmental metabolic fingerprinting

Maier T, Kuhn J, Müller C. Proposal for field sampling of plants and processing in the lab for environmental metabolic fingerprinting. Plant Methods. 2010;6(1): 6.BACKGROUND: Samples for plant metabolic fingerprinting are prepared generally by metabolism quenching, grinding of plant material and extraction of metabolites in solvents. Further concentration and derivatisation steps follow in dependence of the sample nature and the available analytical platform. For plant material sampled in the field, several methods are not applicable, such as, e.g., collection in liquid nitrogen. Therefore, a protocol was established for sample pre-treatment, grinding, extraction and storage, which can be used for analysis of field-collected plant material, which is further processed in the laboratory. Ribwort plantain (Plantago lanceolata L., Plantaginaceae) was used as model plant. The quality criteria for method suitability were high reproducibility, extraction efficiency and handling comfort of each subsequent processing step. RESULTS: Highest reproducibility of results was achieved by sampling fresh plant material in a solvent mixture of methanol:dichloromethane (2:1), crushing the tissue with a hand-held disperser and storing the material until further processing. In the laboratory the material was extracted threefold at different pH. The gained extracts were separated with water (2:1:1 methanol:dichloromethane:water) and the aqueous phases used for analysis by LC-MS, because the polar metabolites were in focus. Chromatograms were compared by calculating a value Xi for similarities. Advantages and disadvantages of different sample pre-treatment methods, use of solvents and solvent mixtures, influence of pH, extraction frequency and duration, and storing temperature are discussed with regard to the quality criteria. CONCLUSIONS: The proposed extraction protocol leads to highly reproducible metabolic fingerprints and allows optimal handling of field-collected plant material and further processing in the laboratory, which is demonstrated for an exemplary field data-set. Calculation of Xi values is a useful tool to judge similarities between chromatograms

A facile wet chemistry approach towards unilamellar tin sulfide nanosheets from Li4xSn1-xS2 solid solutions

We report on the facile production of single-layered tin sulfide nanosheets by a direct solid-state reaction, followed by quantitative liquid exfoliation in water. The new solid solution of SnS2 and Li2S with composition Li4xSn1-xS2 serves as a versatile solid-state precursor with tunable relative lithium and tin content. The end member Li2SnS3, corresponding to the solid solution composition Li-3xLixSn1-xS2], crystallizes in the well-known A(2)BO(3) structure type with mixed Li/Sn layers alternating with pure Li layers in the cationic substructure, which is interleaved with sulfur layers. The bonding in the Li layers can be regarded as ionic, while the Sn-S bonds have substantial covalent character. The resulting inherent anisotropy allows for the facile production of unilamellar chalcogenide nanosheets with thicknesses below 1 nm and lateral sizes of tens of microns, simply by shaking the crystalline precursor in water. The quantitative exfoliation into single-layered nanosheets was confirmed using optical microscopy, AFM, TEM, as well as X-ray diffraction of freestanding films produced from the colloidal suspension by centrifugation. Upon annealing, the as-obtained nanosheets are converted into SnS2 without sacrificing their favorable dispersion properties in water. The presented method allows for the cheap and scalable production of unilamellar chalogenide nanosheets for various potential applications, such as in electronic devices, solar cells, sensors, or battery technology. We expect this method to be generic and transferable to the synthesis of other metal chalcogenides. The use of solid solutions as solid-state precursors, featuring a large compositional range and potential for doping with other metals, may ultimately allow for the controlled introduction of defect levels and rational band-gap engineering in nanosheet materials

Challenges and Rewards in Medicinal Chemistry Targeting Cardiovascular and Metabolic Diseases

Medicinal chemistry has been transformed by major technological and conceptual innovations over the last three decades: structural biology and bioinformatics, structure and property based molecular design, the concepts of multidimensional optimization (MDO), in silico and experimental high-throughput molecular property analysis. The novel technologies advanced gradually and in synergy with biology and Roche has been at the forefront. Applications in drug discovery programs towards new medicines in cardiovascular and metabolic diseases are highlighted to show impact and advancement: the early discovery of endothelin antagonists for endothelial dysfunction (Bosentan), 11-beta hydroxysteroid dehydrogenase (11?-HSD1) inhibitors for dysregulated cellular glucocorticoid tonus (type 2 diabetes and metabolic syndrome) and non-covalent hormone sensitive lipase (HSL) inhibitors to study the scope of direct inhibition of lipolysis in the conceptual frame of lipotoxicity and type 2 diabetes

Sedimentary sequences below the Ekström Ice Shelf, Dronning Maud Land, Antarctica: A pre-site survey for deep drilling (Sub-EIS-Obs)

During the last season and ongoing planning, pre-site surveys are operated at the Ekströmisen, Dronning Maud Land, close to the Neumayer-Station III, with the primary target to build a stratigraphic age framework of the under-shelf-ice-sediments. These sediments are overlying the Explora Wedge [1], [2], a syn- or postrift volcanic deposit, and dipping north- to north-eastward. Expected ages could range from Late Mesozoic to Quaternary. From new vibroseismic profiles we will select sites for short core seafloor sampling of the oldest and of the youngest sediment sequences to confine their age time span. After that, we could select one or several sites for potential deep drillings (several hundred-meter-deep) with the support of international partner, if we could rise interest. The deep drillings should recover the sediments overlying the Explora Escarpment, and should discover the nature of the Explora Wedge as well. We expect that the overlying sediment sequences could reveal the history of polar amplification and climate changes in this part of Antarctica, the build-up of the East Antarctic Ice Sheet during past warmer climates and its Cenozoic and future dynamic and variability. The plan for seasons 2017/18 and 2018/19 are the testing of different sea floor sampling techniques through Hot Water Drill (HWD) holes. To select the drill sites for this shallow coring additional high resolution seismic will be acquired as well. Having holes through the shelf ice and sampling the sea floor will provide the unique opportunity for further piggy bag experiments consisting of multi-disciplinary nature. Experiments and measuring setup for oceanography, sea and shelf ice physics, geophysics, geology, hydrography, and biogeochemistry could be planned to characterize the sea-ice and shelf ice system, underlying water column, and the sediments. Video characterization underneath the shelf ice and at the seafloor, sediment trap deployment, seafloor mapping with an AUV (Leng, DFKI, ROBEX) could lead as well to innovative new interdisciplinary observations and discoveries of the sub-ice environment and ecosystem [3]. References: [1] Eisen, O., Hofstede, C., Diez, A., Kristoffersen, Y., Lambrecht, A., Mayer, C., Blenkner, R. & Hilmarsson, S., (2015), On-ice vibroseis and snowstream¬er systems for geoscientific research, Polar Science, 51-65, 9, http://dx.doi.org/10.1016/j.polar.2014.10.003. [2] Kristoffersen, Y., Hofstede, C., Diez, A., Blenkner, R., Lambrecht, A., Mayer, C. & Eisen, O., (2014), Reassembling Gondwana: A new high quality constraint from vibroseis exploration of the sub-ice shelf geology of the East Antarctic continental margin, J. Geophys. Res. Solid Earth, 9171-9182, 119 [3] Kuhn, G. & Gaedicke, C., (2015), A plan for interdisciplinary process-studies and geoscientific observations beneath the Ekström Ice Shelf (Sub-EIS-Obs), Polarforschung, 99-102, 8

Editorial Message

We compare a range of computational methods for the prediction of sublimation thermodynamics (enthalpy, entropy and free energy of sublimation). These include a model from theoretical chemistry that utilizes crystal lattice energy minimization (with the DMACRYS program) and QSPR models generated by both machine learning (Random Forest and Support Vector Machines) and regression (Partial Least Squares) methods. Using these methods we investigate the predictability of the enthalpy, entropy and free energy of sublimation, with consideration of whether such a method may be able to improve solubility prediction schemes. Previous work has suggested that the major source of error in solubility prediction schemes involving a thermodynamic cycle via the solid state is in the modeling of the free energy change away from the solid state. Yet contrary to this conclusion other work has found that the inclusion of terms such as the enthalpy of sublimation in QSPR methods does not improve the predictions of solubility. We suggest the use of theoretical chemistry terms, detailed explicitly in the methods section, as descriptors for the prediction of the enthalpy and free energy of sublimation. A dataset of 158 molecules with experimental sublimation thermodynamics values and some CSD refcodes has been collected from the literature and is provided with their original source references

Assessing hospitals' clinical risk management: Development of a monitoring instrument

<p>Abstract</p> <p>Background</p> <p>Clinical risk management (CRM) plays a crucial role in enabling hospitals to identify, contain, and manage risks related to patient safety. So far, no instruments are available to measure and monitor the level of implementation of CRM. Therefore, our objective was to develop an instrument for assessing CRM in hospitals.</p> <p>Methods</p> <p>The instrument was developed based on a literature review, which identified key elements of CRM. These elements were then discussed with a panel of patient safety experts. A theoretical model was used to describe the level to which CRM elements have been implemented within the organization. Interviews with CRM practitioners and a pilot evaluation were conducted to revise the instrument. The first nationwide application of the instrument (138 participating Swiss hospitals) was complemented by in-depth interviews with 25 CRM practitioners in selected hospitals, for validation purposes.</p> <p>Results</p> <p>The monitoring instrument consists of 28 main questions organized in three sections: 1) Implementation and organizational integration of CRM, 2) Strategic objectives and operational implementation of CRM at hospital level, and 3) Overview of CRM in different services. The instrument is available in four languages (English, German, French, and Italian). It allows hospitals to gather comprehensive and systematic data on their CRM practice and to identify areas for further improvement.</p> <p>Conclusions</p> <p>We have developed an instrument for assessing development stages of CRM in hospitals that should be feasible for a continuous monitoring of developments in this important area of patient safety.</p

Protein-Binding Microarray Analysis of Tumor Suppressor AP2α Target Gene Specificity

Cheap and massively parallel methods to assess the DNA-binding specificity of transcription factors are actively sought, given their prominent regulatory role in cellular processes and diseases. Here we evaluated the use of protein-binding microarrays (PBM) to probe the association of the tumor suppressor AP2α with 6000 human genomic DNA regulatory sequences. We show that the PBM provides accurate relative binding affinities when compared to quantitative surface plasmon resonance assays. A PBM-based study of human healthy and breast tumor tissue extracts allowed the identification of previously unknown AP2α target genes and it revealed genes whose direct or indirect interactions with AP2α are affected in the diseased tissues. AP2α binding and regulation was confirmed experimentally in human carcinoma cells for novel target genes involved in tumor progression and resistance to chemotherapeutics, providing a molecular interpretation of AP2α role in cancer chemoresistance. Overall, we conclude that this approach provides quantitative and accurate assays of the specificity and activity of tumor suppressor and oncogenic proteins in clinical samples, interfacing genomic and proteomic assays

Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer.

To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.11, 10q24.33, 18q11.2 and 22q12.1), two for mucinous EOC (3q22.3 and 9q31.1) and one for endometrioid EOC (5q12.3). We then performed meta-analysis on the results for high-grade serous ovarian cancer with the results from analysis of 31,448 BRCA1 and BRCA2 mutation carriers, including 3,887 mutation carriers with EOC. This identified three additional susceptibility loci at 2q13, 8q24.1 and 12q24.31. Integrated analyses of genes and regulatory biofeatures at each locus predicted candidate susceptibility genes, including OBFC1, a new candidate susceptibility gene for low-grade and borderline serous EOC