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  • Cell Press  (35,015)
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  • 1
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    Nature Publishing Group
    In:  EPIC3Nature Climate Change, Nature Publishing Group, 12(3), pp. 249-255
    Publication Date: 2022-06-20
    Repository Name: EPIC Alfred Wegener Institut
    Type: Article , isiRev
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  • 2
    Publication Date: 2022-10-27
    Description: © The Author(s), 2022. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Stolp, Z. D., Kulkarni, M., Liu, Y., Zhu, C., Jalisi, A., Lin, S., Casadevall, A., Cunningham, K. W., Pineda, F. J., Teng, X., & Hardwick, J. M. Yeast cell death pathway requiring AP-3 vesicle trafficking leads to vacuole/lysosome membrane permeabilization. Cell Reports, 39(2), (2022): 110647, https://doi.org/10.1016/j.celrep.2022.110647.
    Description: Unicellular eukaryotes have been suggested as undergoing self-inflicted destruction. However, molecular details are sparse compared with the mechanisms of programmed/regulated cell death known for human cells and animal models. Here, we report a molecular cell death pathway in Saccharomyces cerevisiae leading to vacuole/lysosome membrane permeabilization. Following a transient cell death stimulus, yeast cells die slowly over several hours, consistent with an ongoing molecular dying process. A genome-wide screen for death-promoting factors identified all subunits of the AP-3 complex, a vesicle trafficking adapter known to transport and install newly synthesized proteins on the vacuole/lysosome membrane. To promote cell death, AP-3 requires its Arf1-GTPase-dependent vesicle trafficking function and the kinase Yck3, which is selectively transported to the vacuole membrane by AP-3. Video microscopy revealed a sequence of events where vacuole permeability precedes the loss of plasma membrane integrity. AP-3-dependent death appears to be conserved in the human pathogenic yeast Cryptococcus neoformans.
    Description: Funding sources: National Institutes of Health, United States grants AI144373 and NS127076 (J.M.H.), AI115016 and AI153414 (K.W.C.), and AI052733, AI152078, and HL059842 (A.C.); National Natural Science Foundation of China 31970550; and the Priority Academic Program Development of the Jiangsu Higher Education Institutes (X.T.).
    Keywords: Yeast ; Programmed cell death ; Vesicle trafficking ; AP-3 ; Vacuole ; Cryptococcus ; Yck3 ; Regulated cell death ; Lysosome ; Vacuolar membrane permeabilization
    Repository Name: Woods Hole Open Access Server
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  • 3
    Publication Date: 2022-05-27
    Description: © The Author(s), 2022. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Mazzotta, M. G., Reddy, C. M., & Ward, C. P. Rapid degradation of cellulose diacetate by marine microbes. Environmental Science & Technology Letters, 9(1), (2022): 37-41. https://doi.org/10.1021/acs.estlett.1c00843.
    Description: The persistence of cellulose diacetate (CDA), a biobased plastic used in textiles and single-use consumer products, in the ocean is currently unknown. Here, we probe the disintegration and degradation of CDA-based materials (25 μm films, 510 μm foam, and 97 g/m2 fabric) by marine microbes in a continuous flow seawater mesocosm. Photographic evidence and mass loss measurements demonstrate that CDA-based materials disintegrate in months. Disintegration is marked by the increasing esterase and cellulase activity of the biofilm community, suggesting that marine microbes degrade CDA. The natural abundance stable (13C) and radiocarbon (14C) isotopic signature of carbon dioxide respired during short-term bottle incubations confirms the rapid degradation of both acetyl and cellulosic components of CDA by seawater microbial communities. These findings challenge the paradigm set by governmental agencies and advocacy groups that CDA-based materials persist in the ocean for decades, and represent a positive step toward identifying high-utility, biobased plastics with low environmental persistence.
    Description: M.G.M., C.M.R., and C.P.W. thank Eastman Chemical Co. and Woods Hole Oceanographic Institution (WHOI) for scientific and financial support.
    Repository Name: Woods Hole Open Access Server
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  • 4
    Publication Date: 2022-05-27
    Description: © The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Xie, L., Liu, X., Caratenuto, A., Tian, Y., Chen, F., DeGiorgis, J. A., Wan, Y., & Zheng, Y. Environmentally friendly and efficient hornet nest envelope-based photothermal absorbers. Acs Omega, 6(50), (2021): 34555–34562, https://doi.org/10.1021/acsomega.1c04851.
    Description: Water shortage is a critical global issue that threatens human health, environmental sustainability, and the preservation of Earth’s climate. Desalination from seawater and sewage is a promising avenue for alleviating this stress. In this work, we use the hornet nest envelope material to fabricate a biomass-based photothermal absorber as part of a desalination isolation system. This system realizes an evaporation rate of 3.98 kg m–2 h–1 under one-sun illumination, with prolonged evaporation rates all above 4 kg m–2 h–1. This system demonstrates a strong performance of 3.86 kg m–2 h–1 in 3.5 wt % saltwater, illustrating its effectiveness in evaporation seawater. Thus, with its excellent evaporation rate, great salt rejection ability, and easy fabrication approach, the hornet nest envelope constitutes a promising natural material for solar water treatment applications.
    Description: The authors acknowledge the support from the National Science Foundation, USA, through grant number CBET-1941743 and the National Science Foundation under EPSCoR Cooperation Agreement OIA-1655221.
    Repository Name: Woods Hole Open Access Server
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  • 5
    Publication Date: 2022-08-30
    Description: Most tropical corals live in symbiosis with Symbiodiniaceae algae whose photosynthetic production of oxygen (O2) may lead to excess O2 in the diffusive boundary layer (DBL) above the coral surface. When flow is low, cilia-induced mixing of the coral DBL is vital to remove excess O2 and prevent oxidative stress that may lead to coral bleaching and mortality. Here, we combined particle image velocimetry using O2-sensitive nanoparticles (sensPIV) with chlorophyll (Chla)-sensitive hyperspectral imaging to visualize the microscale distribution and dynamics of ciliary flows and O2 in the coral DBL in relation to the distribution of Symbiodiniaceae Chla in the tissue of the reef building coral, Porites lutea. Curiously, we found an inverse relation between O2 in the DBL and Chla in the underlying tissue, with patches of high O2 in the DBL above low Chla in the underlying tissue surrounding the polyp mouth areas and pockets of low O2 concentrations in the DBL above high Chla in the coenosarc tissue connecting neighboring polyps. The spatial segregation of Chla and O2 is related to ciliary-induced flows, causing a lateral redistribution of O2 in the DBL. In a 2D transport-reaction model of the coral DBL, we show that the enhanced O2 transport allocates parts of the O2 surplus to areas containing less chla, which minimizes oxidative stress. Cilary flows thus confer a spatially complex mass transfer in the coral DBL, which may play an important role in mitigating oxidative stress and bleaching in corals.
    Repository Name: EPIC Alfred Wegener Institut
    Type: Article , NonPeerReviewed
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  • 6
    Publication Date: 2022-08-11
    Description: The methanogenic degradation of oil hydrocarbons can proceed through syntrophic partnerships of hydrocarbon-degrading bacteria and methanogenic archaea1,2,3. However, recent culture-independent studies have suggested that the archaeon ‘Candidatus Methanoliparum’ alone can combine the degradation of long-chain alkanes with methanogenesis4,5. Here we cultured Ca. Methanoliparum from a subsurface oil reservoir. Molecular analyses revealed that Ca. Methanoliparum contains and overexpresses genes encoding alkyl-coenzyme M reductases and methyl-coenzyme M reductases, the marker genes for archaeal multicarbon alkane and methane metabolism. Incubation experiments with different substrates and mass spectrometric detection of coenzyme-M-bound intermediates confirm that Ca. Methanoliparum thrives not only on a variety of long-chain alkanes, but also on n-alkylcyclohexanes and n-alkylbenzenes with long n-alkyl (C≥13) moieties. By contrast, short-chain alkanes (such as ethane to octane) or aromatics with short alkyl chains (C≤12) were not consumed. The wide distribution of Ca. Methanoliparum4,5,6 in oil-rich environments indicates that this alkylotrophic methanogen may have a crucial role in the transformation of hydrocarbons into methane.
    Repository Name: EPIC Alfred Wegener Institut
    Type: Article , NonPeerReviewed
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  • 7
    Publication Date: 2022-12-07
    Description: © The Author(s), 2022. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in James, B., de Vos, A., Aluwihare, L., Youngs, S., Ward, C., Nelson, R., Michel, A., Hahn, M., & Reddy, C. Divergent forms of pyroplastic: lessons learned from the M/V X-Press Pearl ship fire. ACS Environmental Au, 2(5), (2022): 467–479, https://doi.org/10.1021/acsenvironau.2c00020.
    Description: In late May 2021, the M/V X-Press Pearl container ship caught fire while anchored 18 km off the coast of Colombo, Sri Lanka and spilled upward of 70 billion pieces of plastic or “nurdles” (∼1680 tons), littering the country’s coastline. Exposure to combustion, heat, chemicals, and petroleum products led to an apparent continuum of changes from no obvious effects to pieces consistent with previous reports of melted and burned plastic (pyroplastic) found on beaches. At the middle of this continuum, nurdles were discolored but appeared to retain their prefire morphology, resembling nurdles that had been weathered in the environment. We performed a detailed investigation of the physical and surface properties of discolored nurdles collected on a beach 5 days after the ship caught fire and within 24 h of their arrival onshore. The color was the most striking trait of the plastic: white for nurdles with minimal alteration from the accident, orange for nurdles containing antioxidant degradation products formed by exposure to heat, and gray for partially combusted nurdles. Our color analyses indicate that this fraction of the plastic released from the ship was not a continuum but instead diverged into distinct groups. Fire left the gray nurdles scorched, with entrained particles and pools of melted plastic, and covered in soot, representing partial pyroplastics, a new subtype of pyroplastic. Cross sections showed that the heat- and fire-induced changes were superficial, leaving the surfaces more hydrophilic but the interior relatively untouched. These results provide timely and actionable information to responders to reevaluate cleanup end points, monitor the recurrence of these spilled nurdles, gauge short- and long-term effects of the spilled nurdles to the local ecosystem, and manage the recovery of the spill. These findings underscore partially combusted plastic (pyroplastic) as a type of plastic pollution that has yet to be fully explored despite the frequency at which plastic is burned globally.
    Description: This work was supported by the Postdoctoral Scholar Program at the Woods Hole Oceanographic Institution (WHOI), with funding provided by the Weston Howland Jr. Postdoctoral Scholarship. Additional support was provided by the WHOI Marine Microplastics Catalyst Program, the WHOI Marine Microplastics Innovation Accelerator Program, the WHOI Investment in Science Fund, the March Marine Initiative (a program of March Limited, Bermuda), The Seaver Institute, Gerstner Philanthropies, the Wallace Research Foundation, the Richard Saltonstall Charitable Foundation, the Harrison Foundation, Hollis and Ermine Lovell Charitable Foundation, and the Richard Grand Foundation. AdV was supported by funding from the Schmidt Foundation.
    Keywords: Microplastic ; Resin pellets ; Pollution ; Additives ; Open burning ; Weathering ; Maritime accident
    Repository Name: Woods Hole Open Access Server
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  • 8
    Publication Date: 2022-11-18
    Description: © The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Tian, Y., Liu, X., Li, J., Deng, Y., DeGiorgis, J. A., Zhou, S., Caratenuto, A., Minus, M. L., Wan, Y., Xiao, G., & Zheng, Y. Farm-waste-derived recyclable photothermal evaporator. Cell Reports Physical Science, 2(9), (2021): 100549, https://doi.org/10.1016./j.xcrp.2021.100549
    Description: Interfacial solar steam generation is emerging as a promising technique for efficient desalination. Although increasing efforts have been made, challenges exist for achieving a balance among a plethora of performance indicators—for example, rapid evaporation, durability, low-cost deployment, and salt rejection. Here, we demonstrate that carbonized manure can convert 98% of sunlight into heat, and the strong capillarity of porous carbon fibers networks pumps sufficient water to evaporation interfaces. Salt diffusion within microchannels enables quick salt drainage to the bulk seawater to prevent salt accumulation. With these advantages, this biomass-derived evaporator is demonstrated to feature a high evaporation rate of 2.81 kg m−2 h−1 under 1 sun with broad robustness to acidity and alkalinity. These advantages, together with facial deployment, offer an approach for converting farm waste to energy with high efficiency and easy implementation, which is particularly well suited for developing regions.
    Description: This project is supported by the National Science Foundation through grant no. CBET-1941743. This project is based upon work supported in part by the National Science Foundation under EPSCoR Cooperative Agreement no. OIA-1655221.
    Keywords: Biomass ; Recyclable ; Manure ; Farm waste ; Photothermal evaporation ; Desalination
    Repository Name: Woods Hole Open Access Server
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  • 9
    Publication Date: 2022-10-31
    Description: The statistical properties of seismicity are known to be affected by several factors such as the rheological parameters of rocks. We analysed the earthquake double-couple as a function of the faulting type. Here we show that it impacts the moment tensors of earthquakes: thrust- faulting events are characterized by higher double-couple components with respect to strike- slip- and normal-faulting earthquakes. Our results are coherent with the stress dependence of the scaling exponent of the Gutenberg-Richter law, which is anticorrelated to the double- couple. We suggest that the structural and tectonic control of seismicity may have its origin in the complexity of the seismogenic source marked by the width of the cataclastic damage zone and by the slip of different fault planes during the same seismic event; the sharper and concentrated the slip as along faults, the higher the double-couple. This phenomenon may introduce bias in magnitude estimation, with possible impact on seismic forecasting.
    Description: Published
    Description: 258
    Description: 2T. Deformazione crostale attiva
    Description: JCR Journal
    Keywords: double couple ; damage zone ; different fault type ; seismicity ; tectonics ; fault type ; seismicity ; 04.06. Seismology
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 10
    Publication Date: 2022-01-07
    Description: Microplastic (MP) pollution has been found in the Southern Ocean surrounding Antarctica, but many local regions within this vast area remain uninvestigated. The remote Weddell Sea contributes to the global thermohaline circulation, and one of the two Antarctic gyres is located in that region. In the present study, we evaluate MP (〉300 μm) concentration and composition in surface (n = 34) and subsurface water samples (n = 79, ∼11.2 m depth) of the Weddell Sea. All putative MP were analyzed by attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy. MP was found in 65% of surface and 11.4% of subsurface samples, with mean (±standard deviation (SD)) concentrations of 0.01 (±0.01 SD) MP m–3 and 0.04 (±0.1 SD) MP m–3, respectively, being within the range of previously reported values for regions south of the Polar Front. Additionally, we aimed to determine whether identified paint fragments (n = 394) derive from the research vessel. Environmentally sampled fragments (n = 101) with similar ATR-FTIR spectra to reference paints from the research vessel and fresh paint references generated in the laboratory were further subjected to micro-X-ray fluorescence spectroscopy (μXRF) to compare their elemental composition. This revealed that 45.5% of all recovered MP derived from vessel-induced contamination. However, 11% of the measured fragments could be distinguished from the reference paints via their elemental composition. This study demonstrates that differentiation based purely on visual characteristics and FTIR spectroscopy might not be sufficient for accurately determining sample contamination sources.
    Repository Name: EPIC Alfred Wegener Institut
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  • 11
    Publication Date: 2022-10-26
    Description: © The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Walsh, A. N., Reddy, C. M., Niles, S. F., McKenna, A. M., Hansel, C. M., & Ward, C. P. Plastic formulation is an emerging control of its photochemical fate in the ocean. Environmental Science & Technology, 55(18), (2021): 12383–12392, https://doi.org/10.1021/acs.est.1c02272.
    Description: Sunlight exposure is a control of long-term plastic fate in the environment that converts plastic into oxygenated products spanning the polymer, dissolved, and gas phases. However, our understanding of how plastic formulation influences the amount and composition of these photoproducts remains incomplete. Here, we characterized the initial formulations and resulting dissolved photoproducts of four single-use consumer polyethylene (PE) bags from major retailers and one pure PE film. Consumer PE bags contained 15–36% inorganic additives, primarily calcium carbonate (13–34%) and titanium dioxide (TiO2; 1–2%). Sunlight exposure consistently increased production of dissolved organic carbon (DOC) relative to leaching in the dark (3- to 80-fold). All consumer PE bags produced more DOC during sunlight exposure than the pure PE (1.2- to 2.0-fold). The DOC leached after sunlight exposure increasingly reflected the 13C and 14C isotopic composition of the plastic. Ultrahigh resolution Fourier transform ion cyclotron resonance mass spectrometry revealed that sunlight exposure substantially increased the number of DOC formulas detected (1.1- to 50-fold). TiO2-containing bags photochemically degraded into the most compositionally similar DOC, with 68–94% of photoproduced formulas in common with at least one other TiO2-containing bag. Conversely, only 28% of photoproduced formulas from the pure PE were detected in photoproduced DOC from the consumer PE. Overall, these findings suggest that plastic formulation, especially TiO2, plays a determining role in the amount and composition of DOC generated by sunlight. Consequently, studies on pure, unweathered polymers may not accurately represent the fates and impacts of the plastics entering the ocean.
    Description: Funding was provided by the Seaver Institute, the Gerstner Family Foundation, Woods Hole Oceanographic Institution, and the National Science Foundation Graduate Research Fellowship Program (A.N.W.). The Ion Cyclotron Resonance user facility at the National High Magnetic Field Laboratory is supported by the National Science Foundation Division of Chemistry and Division of Materials Research through DMR-1644779 and the State of Florida.
    Keywords: Plastic pollution ; Marine debris ; Additives ; Dissolved organic carbon ; Photochemical oxidation ; FT-ICR-MS ; Titanium dioxide
    Repository Name: Woods Hole Open Access Server
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  • 12
    Publication Date: 2022-05-27
    Description: © The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Gosselin, K. M., Nelson, R. K., Spivak, A. C., Sylva, S. P., Van Mooy, B. A. S., Aeppli, C., Sharpless, C. M., O’Neil, G. W., Arrington, E. C., Reddy, C. M., & Valentine, D. L. Production of two highly abundant 2-methyl-branched fatty acids by blooms of the globally significant marine cyanobacteria Trichodesmium erythraeum. ACS Omega, 6(35), (2021): 22803–22810, https://doi.org/10.1021/acsomega.1c03196.
    Description: The bloom-forming cyanobacteria Trichodesmium contribute up to 30% to the total fixed nitrogen in the global oceans and thereby drive substantial productivity. On an expedition in the Gulf of Mexico, we observed and sampled surface slicks, some of which included dense blooms of Trichodesmium erythraeum. These bloom samples contained abundant and atypical free fatty acids, identified here as 2-methyldecanoic acid and 2-methyldodecanoic acid. The high abundance and unusual branching pattern of these compounds suggest that they may play a specific role in this globally important organism.
    Description: This work was funded with grants from the National Science Foundation grants OCE-1333148, OCE-1333162, and OCE-1756254 and the Woods Hole Oceanographic Institution (IR&D). GCxGC analysis made possible by WHOI’s Investment in Science Fund.
    Keywords: Lipids ; Alkyls ; Bacteria ; Genetics ; Chromatography
    Repository Name: Woods Hole Open Access Server
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  • 13
    Publication Date: 2022-08-15
    Description: Anaerobic oxidation of ammonium (anammox) in oxygen minimum zones (OMZs) is a major pathway of oceanic nitrogen loss. Ammonium released from sinking particles has been suggested to fuel this process. During cruises to the Peruvian OMZ in April–June 2017 we found that anammox rates are strongly correlated with the volume of small particles (128–512 µm), even though anammox bacteria were not directly associated with particles. This suggests that the relationship between anammox rates and particles is related to the ammonium released from particles by remineralization. To investigate this, ammonium release from particles was modelled and theoretical encounters of free-living anammox bacteria with ammonium in the particle boundary layer were calculated. These results indicated that small sinking particles could be responsible for ~75% of ammonium release in anoxic waters and that free-living anammox bacteria frequently encounter ammonium in the vicinity of smaller particles. This indicates a so far underestimated role of abundant, slow-sinking small particles in controlling oceanic nutrient budgets, and furthermore implies that observations of the volume of small particles could be used to estimate N-loss across large areas.
    Repository Name: EPIC Alfred Wegener Institut
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  • 14
    Publication Date: 2022-05-26
    Description: © The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Reusch, S., Biswas, A., Hirst, W. G., & Reber, S. Affinity purification of label-free tubulins from xenopus egg extracts. STAR Protocols, 1(3), (2020): 100151, doi:10.1016/j.xpro.2020.100151.
    Description: Cytoplasmic extracts from unfertilized Xenopus eggs have made important contributions to our understanding of microtubule dynamics, spindle assembly, and scaling. Until recently, these in vitro studies relied on the use of heterologous tubulin. This protocol allows for the purification of physiologically relevant Xenopus tubulins in milligram yield, which are a complex mixture of isoforms with various post-translational modifications. The protocol is applicable to any cell or tissue of interest. For complete details on the use and execution of this protocol, please refer to Hirst et al. (2020).
    Description: This article was prompted by our stay at the Marine Biological Laboratory (MBL), Woods Hole, MA, in the summer of 2016 funded by the Princeton-Humboldt Strategic Partnership Grant together with the lab of Sabine Petry (Princeton University). We are grateful to the National Xenopus Resource (NXR) for supplying frogs. For mass spectrometry, we would like to acknowledge the assistance of Benno Kuropka and Chris Weise from the Core Facility BioSupraMol supported by the Deutsche Forschungsgemeinschaft (DFG). We thank the Protein Expression Purification and Characterization (PEPC) facility at the MPI-CBG; in particular, we thank Aliona Bogdanova and Barbara Borgonovo. We thank all former and current members of the Reber lab for discussions and helpful advice, in particular Christoph Hentschel and Soma Zsoter for technical assistance. S.R. acknowledges funding from the IRI Life Sciences (Humboldt-Universität zu Berlin, Excellence Initiative/DFG). W.H. was supported by the Alliance Berlin Canberra co-funded by a grant from the Deutsche Forschungsgemeinschaft (DFG) for the International Research Training Group (IRTG) 2290 and the Australian National University.
    Repository Name: Woods Hole Open Access Server
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  • 15
    Publication Date: 2022-05-26
    Description: © The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Widner, B., Kido Soule, M. C., Ferrer-González, F. X., Moran, M. A., & Kujawinski, E. B. Quantification of amine- and alcohol-containing metabolites in saline samples using pre-extraction benzoyl chloride derivatization and ultrahigh performance liquid chromatography tandem mass spectrometry (UHPLC MS/MS). Analytical Chemistry, 93(11), (2021): 4809-4817, https://doi.org/10.1021/acs.analchem.0c03769.
    Description: Dissolved metabolites serve as nutrition, energy, and chemical signals for microbial systems. However, the full scope and magnitude of these processes in marine systems are unknown, largely due to insufficient methods, including poor extraction of small, polar compounds using common solid-phase extraction resins. Here, we utilized pre-extraction derivatization and ultrahigh performance liquid chromatography electrospray ionization tandem mass spectrometry (UHPLC-ESI-MS/MS) to detect and quantify targeted dissolved metabolites in seawater and saline culture media. Metabolites were derivatized with benzoyl chloride by their primary and secondary amine and alcohol functionalities and quantified using stable isotope-labeled internal standards (SIL-ISs) produced from 13C6-labeled benzoyl chloride. We optimized derivatization, extraction, and sample preparation for field and culture samples and evaluated matrix-derived biases. We have optimized this quantitative method for 73 common metabolites, of which 50 cannot be quantified without derivatization due to low extraction efficiencies. Of the 73 metabolites, 66 were identified in either culture media or seawater and 45 of those were quantified. This derivatization method is sensitive (detection limits = pM to nM), rapid (∼5 min per sample), and high throughput.
    Description: Funding included the Gordon and Betty Moore Foundation (Award GBMF5503 to M.A.M. and E.B.K.), Simons Foundation International (Award 409923 to E.B.K.), and the National Science Foundation (Award 1656311 to M.A.M.).
    Repository Name: Woods Hole Open Access Server
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  • 16
    Publication Date: 2022-05-26
    Description: © The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Hirst, W. G., Kiefer, C., Abdosamadi, M. K., Schäffer, E., & Reber, S. In Vitro reconstitution and imaging of microtubule dynamics by fluorescence and label-free microscopy. STAR Protocols, 1(3), (2020): 100177, doi:10.1016/j.xpro.2020.100177.
    Description: Dynamic microtubules are essential for many processes in the lives of eukaryotic cells. To study and understand the mechanisms of microtubule dynamics and regulation, in vitro reconstitution with purified components has proven a vital approach. Imaging microtubule dynamics can be instructive for a given species, isoform composition, or biochemical modification. Here, we describe two methods that visualize microtubule dynamics at high speed and high contrast: (1) total internal reflection fluorescence microscopy and (2) label-free interference reflection microscopy.
    Description: We thank the AMBIO imaging facility (Charité, Berlin) and Nikon at MBL for imaging support. We thank all former and current members of the Reber lab for discussion and helpful advice, in particular Christoph Hentschel and Soma Zsoter for technical assistance. S.R. acknowledges funding by the IRI Life Sciences (Humboldt-Universität zu Berlin, Excellence Initiative/DFG). W.H. was supported by the Alliance Berlin Canberra co-funded by a grant from the Deutsche Forschungsgemeinschaft (DFG) for the International Research Training Group (IRTG) 2290 and the Australian National University. C.K. thanks the Deutsche Forschungsgesellschaft (DFG, JA 2589/1-1). C.K. and M.A. thank Steve Simmert and Tobias Jachowski former and current members of the Schäffer lab.
    Keywords: Biophysics ; Cell Biology ; Microscopy
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  • 17
    Publication Date: 2022-05-26
    Description: © The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Geisterfer, Z. M., Oakey, J., & Gatlin, J. C. . Microfluidic encapsulation of Xenopus laevis cell-free extracts using hydrogel photolithography. STAR Protocols, 1(3), (2020): 100221, doi:10.1016/j.xpro.2020.100221.
    Description: Cell-free extract derived from the eggs of the African clawed frog Xenopus laevis is a well-established model system that has been used historically in bulk aliquots. Here, we describe a microfluidic approach for isolating discrete, biologically relevant volumes of cell-free extract, with more expansive and precise control of extract shape compared with extract-oil emulsions. This approach is useful for investigating the mechanics of intracellular processes affected by cell geometry or cytoplasmic volume, including organelle scaling and positioning mechanisms. For complete details on the use and execution of this protocol, please refer to Geisterfer et al. (2020).
    Description: This work was made possible by an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under grant no. 2P20GM103432. It was also supported by additional funding provided by the NIGMS under grant no. R01GM113028, the NSF Faculty CAREER Program under award no. BBBE 1254608, Whitman Center fellowships at the Marine Biological Laboratory, and the Biomedical Scholars program of the Pew Charitable Trusts. We thank Drs. Aaron Groen and Tim Mitchison for their intellectual contributions and involvement in some of the pioneering experiments that set the foundation for this approach.
    Keywords: Biophysics ; Cell Biology ; Cell isolation ; Microscopy ; Model Organisms
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  • 18
    Publication Date: 2022-10-21
    Description: © The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Colson, B. C., & Michel, A. P. M. Flow-through quantification of microplastics using impedance spectroscopy. ACS Sensors, 6(1), (2021): 238–244, doi:10.1021/acssensors.0c02223.
    Description: Understanding the sources, impacts, and fate of microplastics in the environment is critical for assessing the potential risks of these anthropogenic particles. However, our ability to quantify and identify microplastics in aquatic ecosystems is limited by the lack of rapid techniques that do not require visual sorting or preprocessing. Here, we demonstrate the use of impedance spectroscopy for high-throughput flow-through microplastic quantification, with the goal of rapid measurement of microplastic concentration and size. Impedance spectroscopy characterizes the electrical properties of individual particles directly in the flow of water, allowing for simultaneous sizing and material identification. To demonstrate the technique, spike and recovery experiments were conducted in tap water with 212–1000 μm polyethylene beads in six size ranges and a variety of similarly sized biological materials. Microplastics were reliably detected, sized, and differentiated from biological materials via their electrical properties at an average flow rate of 103 ± 8 mL/min. The recovery rate was ≥90% for microplastics in the 300–1000 μm size range, and the false positive rate for the misidentification of the biological material as plastic was 1%. Impedance spectroscopy allowed for the identification of microplastics directly in water without visual sorting or filtration, demonstrating its use for flow-through sensing.
    Description: The authors thank the Richard Saltonstall Charitable Foundation and the National Academies Keck Futures Initiative (NAKFI DBS13) for their funding support.
    Keywords: Microplastics ; Plastics ; Impedance spectroscopy ; Dielectric properties ; Instrumentation ; Particle detection ; Flow-through ; Environmental sensing
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  • 19
    Publication Date: 2022-01-07
    Description: The female flowers (“cones”) of the hop plant (Humulus L.) produce compounds that contribute to the flavor and other properties of beer. Hop leaves and cones produce many of the same compounds, which also confer agronomic traits such as insect and disease resistance. Targeted and untargeted ultraperformance liquid chromatography-quadrupole time-of-flight–mass spectrometry with Waters MSE technology (UPLC-QTof-MSE) metabolomics were used to compare leaf phytochemical compositions of greenhouse-grown southwestern American wild Humulus neomexicanus (A. Nelson and Cockerell) Rydb. against a group of commercial hop cultivars consisting of both pure European Humulus lupulus L. and European–North American hybrids. Principal component analysis showed a clear distinction in chemical profiles between the two groups. H. neomexicanus leaves had a significantly higher content of total α acids (p = 4.4 × 10–9), total bitter acids (p = 2.6 × 10–6), cohumulone (p = 1.0 × 10–13), humulone + adhumulone (p = 9.1 × 10–4), and the prenylflavonoids xanthohumol (p = 0.013) and desmethylxanthohumol (p = 0.029) as well as significantly higher densities of glandular trichomes (p = 1.3 × 10–6), the biosynthetic site of those compounds. Most flavonol glycosides measured were also significantly more abundant in H. neomexicanus (p = 1.5 × 10–22 to 0.0027), whereas phenolic acids were consistently, but generally nonsignificantly (p 〉 0.05), more abundant in the cultivars. The higher bitter acid, prenylflavonoid, and flavonol glycoside content of H. neomexicanus leaves may help to confer more favorable insect and disease-resistance properties.
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  • 20
    Publication Date: 2022-01-07
    Description: Iron is an indispensable metabolic cofactor in both pro- and eukaryotes, which engenders a natural competition for the metal between bacterial pathogens and their human or animal hosts. Bacteria secrete siderophores that extract Fe3+ from tissues, fluids, cells, and proteins; the ligand gated porins of the Gram-negative bacterial outer membrane actively acquire the resulting ferric siderophores, as well as other iron-containing molecules like heme. Conversely, eukaryotic hosts combat bacterial iron scavenging by sequestering Fe3+ in binding proteins and ferritin. The variety of iron uptake systems in Gram-negative bacterial pathogens illustrates a range of chemical and biochemical mechanisms that facilitate microbial pathogenesis. This document attempts to summarize and understand these processes, to guide discovery of immunological or chemical interventions that may thwart infectious disease.
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  • 21
    Publication Date: 2022-01-07
    Description: While thousands of environmental metagenomes have been mined for the presence of novel biosynthetic gene clusters, such computational predictions do not provide evidence of their in vivo biosynthetic functionality. Using fluorescent in situ enzyme assay targeting carrier proteins common to polyketide (PKS) and nonribosomal peptide synthetases (NRPS), we applied fluorescence-activated cell sorting to tunicate microbiome to enrich for microbes with active secondary metabolic capabilities. Single-cell genomics uncovered the genetic basis for a wide biosynthetic diversity in the enzyme-active cells and revealed a member of marine Oceanospirillales harboring a novel NRPS gene cluster with high similarity to phylogenetically distant marine and terrestrial bacteria. Interestingly, this synthase belongs to a larger class of siderophore biosynthetic gene clusters commonly associated with pestilence and disease. This demonstrates activity-guided single-cell genomics as a tool to guide novel biosynthetic discovery.
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  • 22
    Publication Date: 2022-06-20
    Description: Between 2003-2016, the Greenland ice sheet (GrIS) was one of the largest contributors to sea level rise, as it lost about 255 Gt of ice per year. This mass loss slowed in 2017 and 2018 to about 100 Gt yr−1. Here we examine further changes in rate of GrIS mass loss, by analyzing data from the GRACE-FO (Gravity Recovery and Climate Experiment – Follow On) satellite mission, launched in May 2018. Using simulations with regional climate models we show that the mass losses observed in 2017 and 2018 by the GRACE and GRACE-FO missions are lower than in any other two year period between 2003 and 2019, the combined period of the two missions. We find that this reduced ice loss results from two anomalous cold summers in western Greenland, compounded by snow-rich autumn and winter conditions in the east. For 2019, GRACE-FO reveals a return to high melt rates leading to a mass loss of 223 ± 12 Gt month−1 during the month of July alone, and a record annual mass loss of 532 ± 58 Gt yr−1.
    Repository Name: EPIC Alfred Wegener Institut
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  • 23
    Publication Date: 2022-10-27
    Description: © The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Meaders, J. L., de Matos, S. N., & Burgess, D. R. A pushing mechanism for microtubule aster positioning in a large cell type. Cell Reports, 33(1), (2020): 108213, doi:10.1016/j.celrep.2020.108213.
    Description: After fertilization, microtubule (MT) sperm asters undergo long-range migration to accurately position pronuclei. Due to the large sizes of zygotes, the forces driving aster migration are considered to be from pulling on the astral MTs by dynein, with no significant contribution from pushing forces. Here, we re-investigate the forces responsible for sperm aster centration in sea urchin zygotes. Our quantifications of aster geometry and MT density preclude a pulling mechanism. Manipulation of aster radial lengths and growth rates, combined with quantitative tracking of aster migration dynamics, indicates that aster migration is equal to the length of rear aster radii, supporting a pushing model for centration. We find that dynein inhibition causes an increase in aster migration rates. Finally, ablation of rear astral MTs halts migration, whereas front and side ablations do not. Collectively, our data indicate that a pushing mechanism can drive the migration of asters in a large cell type.
    Description: We would like to thank Dr. Jesse Gatlin for sending us the Tau-mCherry fusion protein for imaging live MTs. We would also like to thank Dr. Timothy Mitchison, Dr. Christine Field, and Dr. James Pelletier for supplying us with CA4, p150-CC1, and EB1-GFP peptides, as well as for fruitful discussions. Finally, we would like to thank Dr. Charles Shuster and Leslie Toledo-Jacobo for constructive feedback when preparing the manuscript. We thank Bret Judson and the Boston College Imaging Core for infrastructure and support. This material is based upon work supported by NSF grant no. 124425 to D.R.B.
    Keywords: Dynein ; Aster ; Microtubule ; Centrosome ; Pronucleus ; Fertilization ; Aster position
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  • 24
    Publication Date: 2022-05-26
    Description: © The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in McLean, C., & Kujawinski, E. B. AutoTuner: high fidelity and robust parameter selection for metabolomics data processing. Analytical Chemistry, 92(8), (2020): 5724-5732, doi:10.1021/acs.analchem.9b04804.
    Description: Untargeted metabolomics experiments provide a snapshot of cellular metabolism but remain challenging to interpret due to the computational complexity involved in data processing and analysis. Prior to any interpretation, raw data must be processed to remove noise and to align mass-spectral peaks across samples. This step requires selection of dataset-specific parameters, as erroneous parameters can result in noise inflation. While several algorithms exist to automate parameter selection, each depends on gradient descent optimization functions. In contrast, our new parameter optimization algorithm, AutoTuner, obtains parameter estimates from raw data in a single step as opposed to many iterations. Here, we tested the accuracy and the run-time of AutoTuner in comparison to isotopologue parameter optimization (IPO), the most commonly used parameter selection tool, and compared the resulting parameters’ influence on the properties of feature tables after processing. We performed a Monte Carlo experiment to test the robustness of AutoTuner parameter selection and found that AutoTuner generated similar parameter estimates from random subsets of samples. We conclude that AutoTuner is a desirable alternative to existing tools, because it is scalable, highly robust, and very fast (∼100–1000× speed improvement from other algorithms going from days to minutes). AutoTuner is freely available as an R package through BioConductor.
    Description: We thank Titus Brown and Ben Temperton for advice on the algorithm validation, Arthur Eschenlauer for constructive feedback on the software design, Krista Longnecker for continuous support and discussions, Gabriel Leventhal for mathematics advice, the users of AutoTuner for debugging help through Github, and David Angeles-Albores and two anonymous reviewers for critical feedback on the manuscript. Funding support included the National GEM Consortium and NSF graduate research program fellowships (C.M.) and grants from the MIT Microbiome Center (Award 6936800, E.B.K.) and the Simons Foundation (Award ID #509034, E.B.K.).
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  • 25
    Publication Date: 2022-05-26
    Description: Author Posting. © American Chemical Society, 2020. This is an open access article published under an ACS AuthorChoice License. The definitive version was published in Chemical Research in Toxicology, 33(4), (2020): 860-879, doi:10.1021/acs.chemrestox.9b00476.
    Description: The Ah receptor (AHR) has been studied for almost five decades. Yet, we still have many important questions about its role in normal physiology and development. Moreover, we still do not fully understand how this protein mediates the adverse effects of a variety of environmental pollutants, such as the polycyclic aromatic hydrocarbons (PAHs), the chlorinated dibenzo-p-dioxins (“dioxins”), and many polyhalogenated biphenyls. To provide a platform for future research, we provide the historical underpinnings of our current state of knowledge about AHR signal transduction, identify a few areas of needed research, and then develop concepts such as adaptive metabolism, ligand structural diversity, and the importance of proligands in receptor activation. We finish with a discussion of the cognate physiological role of the AHR, our perspective on why this receptor is so highly conserved, and how we might think about its cognate ligands in the future.
    Description: This review is dedicated in memory of the career of Alan Poland, one of the truly great minds in pharmacology and toxicology. This work was supported by the National Institutes of Health Grants R35-ES028377, T32-ES007015, P30-CA014520, P42-ES007381, and U01-ES1026127, The UW SciMed GRS Program, and The Morgridge Foundation. The authors would like to thank Catherine Stanley of UW Media Solutions for her artwork.
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  • 26
    Publication Date: 2022-01-07
    Description: Marine macroalgae, seaweeds, are exceptionally prolific producers of halogenated natural products. Biosynthesis of halogenated molecules in seaweeds is inextricably linked to reactive oxygen species (ROS) signaling as hydrogen peroxide serves as a substrate for haloperoxidase enzymes that participate in the construction these halogenated molecules. Here, using red macroalga Asparagopsis taxiformis, a prolific producer of the ozone depleting molecule bromoform, we provide the discovery and biochemical characterization of a ROS-producing NAD(P)H oxidase from seaweeds. This discovery was enabled by our sequencing of Asparagopsis genomes, in which we find the gene encoding the ROS-producing enzyme to be clustered with genes encoding bromoform-producing haloperoxidases. Biochemical reconstitution of haloperoxidase activities establishes that fatty acid biosynthesis can provide viable hydrocarbon substrates for bromoform production. The ROS production haloperoxidase enzymology that we describe here advances seaweed biology and biochemistry by providing the molecular basis for decades worth of physiological observations in ROS and halogenated natural product biosyntheses.
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  • 27
    Publication Date: 2022-01-07
    Description: Fusarium oxysporum is a destructive root-infecting plant pathogen that causes significant yield losses in many economically important crop species. Hence, a deeper understanding of pathogen infection strategies is needed. With liquid chromatography-tandem mass spectrometry and gas chromatography-time of flight mass spectrometry platforms, we analyzed the metabolic changes in a time-course experiment with Arabidopsis accessions either resistant (Col-0) or susceptible (Ler-0) to isolates of Fusarium oxysporum forma specialis matthioli infection. We showed a concurrent effect of Fusarium-derived polyols and the mycotoxin beauvericin in the suppression of the immune response of susceptible hosts. A significant increase in oxidized glutathione in the resistant host was probably associated with effective reactive oxygen species-mediated resistance responses. Through a combination of targeted and untargeted metabolomics, we demonstrated the concurrent action of several Arabidopsis defense systems as well as the concurrent action of several virulence systems in the fungal attack of susceptible Arabidopsis.
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  • 28
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    Nature medicine 10 (2004), S. 896-898 
    ISSN: 1546-170X
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] The mechanisms responsible for the formation of arterial aneurysms remain mysterious. Key features include extensive inflammation of the adventitia, the outermost layer of arteries, and dilation of the media, the smooth muscle cell–rich middle layer that conveys mechanical stability and ...
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    Nature medicine 10 (2004), S. 902-903 
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    Topics: Biology , Medicine
    Notes: [Auszug] It has long been accepted that the more HDL cholesterol a person has, the better off he is. However, review of the data from the original Framingham study, which first solidly identified the importance of HDL, or of the data from the placebo group in another large study reveals that many heart ...
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    Nature medicine 10 (2004), S. 907-907 
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    Topics: Biology , Medicine
    Notes: [Auszug] The race is on Efforts to combat the spread of drug-resistant malaria in Africa received a blow this month from research in Science (305, 1124; 2004) that examines the origins of resistance, but hope emerged from another study in Nature (430, 900–904; 2004) that introduces a synthetic ...
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    Notes: [Auszug] Although post-translational modifications of protein antigens may be important componenets of some B cell epitopes, the determinants of T cell immunity are generally nonmodified peptides. Here we show that methylation of the Mycobacterium tuberculosis heparin-binding hemagglutinin (HBHA) by the ...
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    Nature medicine 10 (2004), S. 1001-1001 
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    Notes: [Auszug] Filter plates Millipore now offers its MultiScreenHTS-PH (phosphocellulose) filter plates for high-throughput kinase screening assays. The 96-well filter plates are automation compatible and follow a prevalidated protocol for high sensitivity, high specificity and reliable kinase assay screening. ...
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    Nature medicine 10 (2004), S. 882-882 
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    Source: Nature Archives 1869 - 2009
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    Notes: [Auszug] Come November, California might become the first state to fund stem cell research, in direct opposition to the federal government's policy. If voted in, Proposition 71 would allow the state to issue bonds for up to $3 billion over ten years for the research. But given the state's $10 ...
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    Nature medicine 10 (2004), S. 884-884 
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    Notes: [Auszug] When the US National Institutes of Health (NIH) closed a pioneering prion research lab last month, the timing seemed a bit off. British researchers had just identified a second case of variant Creutzfeldt-Jakob disease (vCJD) transmitted through a blood transfusion. The UK Medical Research Council ...
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    Nature medicine 10 (2004), S. 893-893 
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    Notes: [Auszug] Experimentation on humans has always been problematic, and until World War II, was often prohibited or confined to subjects believed to be subhuman. Most recently, international controversy has focused not so much on research with humans or animals, but on research with human embryos. There is no ...
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    Notes: [Auszug] Bronchus-associated lymphoid tissue (BALT) is occasionally found in the lungs of mice and humans; however, its role in respiratory immunity is unknown. Here we show that mice lacking spleen, lymph nodes and Peyer's patches generate unexpectedly robust primary B- and T-cell responses to influenza, ...
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  • 37
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    Notes: [Auszug] Several non-hypercalcemic analogs of 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) show antitumor activity in a subset of cancer patients. High vitamin D receptor (VDR) expression, which is associated with good prognosis but is lost during tumor progression. We show that the SNAIL transcription ...
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  • 38
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    Notes: [Auszug] Activation of the 5-lipoxygenase (5-LO) pathway leads to the biosynthesis of proinflammatory leukotriene lipid mediators. Genetic studies have associated 5-LO and its accessory protein, 5-LO-activating protein, with cardiovascular disease, myocardial infarction and stroke. Here we show that ...
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  • 39
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    Nature medicine 10 (2004), S. 762-762 
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    Notes: [Auszug] After months of deliberation, a task force set up to consider the future of the National Institute for Medical Research (NIMR)—one of Britain's leading centres for basic medical research—has recommended that the institute be moved from Mill Hill, on the outskirts of London, to a single site in ...
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  • 40
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    Nature medicine 10 (2004), S. 766-766 
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    Notes: [Auszug] Irving Weissman is not afraid to wade into the murky waters of stem cell politics. Whether he's in the lab or knee-deep in the Missouri river, he has always had a knack for hooking the big one. Irving Weissman may be most famous for his pioneering research and advocacy on stem cells. But ...
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    Nature medicine 10 (2004), S. 773-773 
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    Notes: [Auszug] The US Food and Drug Administration (FDA) is the granddaddy of government agencies mandated to protect the health of the public. It is respected globally. Polls indicate that most Americans regard its role in assuring safe foods, drugs and medical devices as necessary and positive. Progressive ...
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    Nature medicine 10 (2004), S. 765-765 
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    Notes: [Auszug] US proves unpopular at global AIDS summit For the few US government researchers who gathered in Bangkok for the XV International AIDS Conference, the meeting cannot have been a pleasant experience.... US AIDS coordinator Randall Tobias was often missing from sessions where he was scheduled to ...
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  • 43
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    Notes: [Auszug] Dystrophic epidermolysis bullosa (DEB) is a family of inherited mechano-bullous disorders that are caused by mutations in the type VII collagen gene and for which ex vivo gene therapy has been considered. To develop a simpler approach for treating DEB, we evaluated the feasibility of protein-based ...
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    Nature medicine 10 (2004), S. 783-784 
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    Notes: [Auszug] During type 1 diabetes, CD4+ and CD8 T+ cells contribute to the destruction of insulin-producing β-cells in the pancreas. Recent studies outline two approaches to combat this destruction. In the June issue of Immunity, Ogasawara et al. show that antibodies blocking NKG2D, a costimulatory ...
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  • 45
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    Notes: [Auszug] The trafficking of circulating stem and progenitor cells to areas of tissue damage is poorly understood. The chemokine stromal cell–derived factor-1 (SDF-1 or CXCL12) mediates homing of stem cells to bone marrow by binding to CXCR4 on circulating cells. SDF-1 and CXCR4 are expressed in ...
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  • 46
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    Notes: [Auszug] Staphylococcus aureus is a major human pathogen that is associated with diverse types of local and systemic infection characterized by inflammation dominated by polymorphonuclear leukocytes. Staphylococci frequently cause pneumonia, and these clinical isolates often have increased expression of ...
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  • 47
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    Notes: [Auszug] Noonan syndrome is a common human autosomal dominant birth defect, characterized by short stature, facial abnormalities, heart defects and possibly increased risk of leukemia. Mutations of Ptpn11 (also known as Shp2), which encodes the protein-tyrosine phosphatase Shp2, occur in ∼50% of ...
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    Nature medicine 10 (2004), S. 653-653 
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    Notes: [Auszug] On June 2, New York State Attorney General Eliot Spitzer sued GlaxoSmithKline (GSK) for repeated and persistent fraud, contending that the company failed to disclose information on the safety and efficacy of paroxetine for the treatment of depression in children. This lawsuit quickly prompted ...
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  • 49
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    Nature medicine 10 (2004), S. 656-656 
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    Notes: [Auszug] After months of controversy, the Mexican parliament has approved the creation of the National Institute of Genomic Medicine. The Senate agreed in late April to eliminate a clause banning the institute from using human embryonic cells or producing human clones for research purposes. “We ...
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    Nature medicine 10 (2004), S. 625-632 
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    Notes: [Auszug] Obesity is an increasingly prevalent human condition in developed societies. Despite major progress in the understanding of the molecular mechanisms leading to obesity, no safe and effective treatment has yet been found. Here, we report an antiobesity therapy based on targeted induction of ...
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  • 51
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    Notes: [Auszug] Loss of PTEN function leads to activation of phosphoinositide 3-kinase (PI3K) signaling and Akt. Clinical trials are now testing whether mammalian target of rapamycin (mTOR) inhibition is useful in treating PTEN-null cancers. Here, we report that mTOR inhibition induced apoptosis of epithelial ...
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    Notes: [Auszug] Lysophosphatidic acid (LPA) is a bioactive lipid with activity in the nervous system mediated by G-protein-coupled receptors. Here, we examined the role of LPA signaling in the development of neuropathic pain by pharmacological and genetic approaches, including the use of mice lacking the LPA1 ...
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  • 53
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    Notes: [Auszug] Leptin is an adipocyte-derived hormone that plays a key role in energy homeostasis, yet resistance to leptin is a feature of most cases of obesity in humans and rodents. In vitro analysis suggested that the suppressor of cytokine signaling-3 (Socs3) is a negative-feedback regulator of leptin ...
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    Nature medicine 10 (2004), S. 553-553 
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    Source: Nature Archives 1869 - 2009
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    Notes: [Auszug] Individualized healthcare, once a seemingly utopian fantasy, is steadily gaining ground as a rational approach to cancer treatment. But recent developments emphasize the need for basic scientific insight as therapies move from the lab to the clinic. In May 2003, the US Food and Drug Administration ...
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    Nature medicine 10 (2004), S. 556-556 
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    Notes: [Auszug] Australian biomedical researchers walked away disappointed from this year's federal government budget, amidst concerns that the nation's biomedical research will struggle to keep pace with the international community. The budget, released on 11 May, forecasts that annual funds for the National ...
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    Nature medicine 10 (2004), S. 558-558 
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    Notes: [Auszug] Pharmaceutical companies routinely sink millions of dollars into common diseases, hoping for a multibillion-dollar payoff from the next blockbuster drug. But for orphan diseases with a small market, there are few takers. An emerging model for medical research—exemplified by the Cystic ...
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    Nature medicine 10 (2004), S. 561-561 
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    Notes: [Auszug] Willett and Jain reply: The objective of our study was to examine the biological and clinical effects on rectal cancer of an initial bevacizumab infusion, before the initiation of radiation therapy and 5-fluorouracil. Six patients with clinical stage T3 or T4 rectal cancer completed the ...
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    Nature medicine 10 (2004), S. 577-578 
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    Notes: [Auszug] The epidermal growth factor receptor (EGFR or erbB1) has emerged in recent years as a viable therapeutic target in human cancer. This transmembrane receptor tyrosine kinase is frequently detectable in a wide range of human tumors. However, tumor EGFR levels are not correlated with the level of ...
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    Nature medicine 10 (2004), S. 582-583 
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    Notes: [Auszug] Thyroid hormone acts by binding to nuclear receptors to regulate transcription, thereby controlling multiple homeostatic processes, such as metabolic, central nervous system and hemodynamic function. Treatment of hypothyroidism requires weeks of hormone administration to normalize such functions, ...
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    Nature medicine 10 (2004), S. 555-555 
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    Notes: [Auszug] The much-disputed European directive on clinical trials went into effect on 1 May (Nat. Med. 9, 1336; 2003), but some experts are warning against the restricted access provided to its new clinical trial database. The database will include general information on a clinical trial, recommendations of ...
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    Nature medicine 10 (2004), S. 557-557 
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    Notes: [Auszug] Community groups protesting the proliferation of biodefense 'hot labs' conjure up scenarios of lax security, accidental infections and dangerous microbes escaping into the neighborhood to bolster their case. A previously unreleased report on inspections of existing labs suggests that only luck has ...
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    Nature medicine 10 (2004), S. 439-439 
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    Notes: [Auszug] China is set to launch a new Institute of Molecular Medicine (IMM) in partnership with an existing institute of the same name at the University of California in San Diego. The new institute, to be formally opened in November, will focus initially on translational research in cardiovascular science ...
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    Nature medicine 10 (2004), S. 570-573 
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    Notes: [Auszug] The question “When are research risks reasonable in relation to anticipated benefits?” is at the very heart of pressing disputes in the ethics of clinical research. Institutional review boards (IRBs) are criticized for inconsistent decision-making, a phenomenon that may be traced in ...
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    Nature medicine 10 (2004), S. 581-582 
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    Notes: [Auszug] Treating obesity is not rocket science—'just' eat less and exercise more. However, in this case common-sense knowledge seems not to be enough, because obesity is becoming more prevalent throughout the world. Obesity is a disease, not a cosmetic feature. It increases the risk of insulin ...
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    Nature medicine 10 (2004), S. 587-588 
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    Notes: [Auszug] Liver health depends on the efficient removal of unwanted cells, such as aged or virus-infected cells, mainly through apoptosis. In a physiologic setting, new cells generated by mitosis replace those that are eliminated, ensuring organ homeostasis. An alteration in this balance between cell death ...
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    Nature medicine 10 (2004), S. 435-435 
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    Notes: [Auszug] Nat. Med. 10, 143–145 (2004) The name of author Jeffrey S Mueller was spelled ...
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    Notes: [Auszug] The clinical outcome of spinal cord injury (SCI) depends in part on the extent of secondary damage, to which apoptosis contributes. The CD95 and tumor necrosis factor (TNF) ligand/receptor systems play an essential role in various apoptotic mechanisms. To determine the involvement of these ligands ...
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    Nature medicine 10 (2004), S. 422-428 
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    Notes: [Auszug] Over 7 million people worldwide die annually from erratic heart rhythms (cardiac arrhythmias), and many more are disabled. Yet there is no imaging modality to identify patients at risk, provide accurate diagnosis and guide therapy. Standard diagnostic techniques such as the electrocardiogram (ECG) ...
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    Notes: [Auszug] Three human coronaviruses are known to exist: human coronavirus 229E (HCoV-229E), HCoV-OC43 and severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV). Here we report the identification of a fourth human coronavirus, HCoV-NL63, using a new method of virus discovery. The virus ...
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    Nature medicine 10 (2004), S. 355-361 
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    Notes: [Auszug] Obesity and the related disorders of dyslipidemia and diabetes (components of syndrome X) have become global health epidemics. Over the past decade, the elucidation of key regulators of energy balance and insulin signaling have revolutionized our understanding of fat and sugar metabolism and their ...
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    Notes: [Auszug] Charcot-Marie-Tooth disease (CMT) is the most common hereditary peripheral neuropathy, affecting 1 in 2,500 people. The only treatment currently available is rehabilitation or corrective surgery. The most frequent form of the disease, CMT-1A, involves abnormal myelination of the peripheral nerves. ...
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    Nature medicine 10 (2004), S. 214-214 
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    Notes: [Auszug] In New York City, where space for people is at a premium, finding room for mice is no small task. Faced with cramped quarters for their research animals, six local research institutes—including Columbia University and Rockefeller University—are forming a new consortium to create a ...
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    Nature medicine 10 (2004), S. 216-216 
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    Notes: [Auszug] Advances in insect molecular biology have allowed the creation of genetically modified (GM) insects for infectious disease control to step out of the realm of science fiction. But experts say the technology must clear unique scientific and political challenges before it can become a real ...
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    Nature medicine 10 (2004), S. 218-218 
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    Notes: [Auszug] US budget for 2005 boosts biodefense, food security Biodefense, food security and biosurveillance will receive significant increases in funding under the proposed US budget for 2005. The US Department of Health and Human Services, which oversees the National Institutes of Health (NIH), the ...
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    Nature medicine 10 (2004), S. 227-228 
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    Notes: [Auszug] Bill McKibben has had enough. He has seen quite enough of the current fruits of the biological revolution to make him very, very worried. And those involved with biotechnology ought take note, because he is raising a worry that is rarely heard in boardrooms and legislative settings where cost and ...
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    Nature medicine 10 (2004), S. 234-235 
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    Notes: [Auszug] There are many ways to stop a cell from dividing. Disordered spindle function, for instance, may be a potent signal for apoptosis. Taxanes and vinca alkaloids arrest cell-cycle progression in mitosis by interacting directly with tubulin and interfering with microtubule spindle function. These two ...
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    Nature medicine 10 (2004), S. 238-239 
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    Notes: [Auszug] Acute myeloid leukemia-1 (AML-1, encoded by the runt-related X1 gene, RUNX1) is perhaps the most frequent target of chromosomal translocations in acute leukemia. The translocations create fusion proteins that repress AML-1-regulated genes. The transcription factor AML-1 is a putative tumor ...
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    Notes: [Auszug] The mammalian target of rapamycin, mTOR, regulates cell growth and proliferation. Here we show that the initiation factor of translation (eIF-4E), a downstream effector of mTOR, has oncogenic effects in vivo and cooperates with c-Myc in B-cell lymphomagenesis. We found that c-Myc overrides ...
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    Notes: [Auszug] Atherosclerosis, the leading cause of death in developed countries, has been linked to hypercholesterolemia for decades. More recently, atherosclerotic lesion progression has been shown to depend on persistent, chronic inflammation in the artery wall. Although several studies have implicated ...
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    Nature medicine 10 (2004), S. 120-120 
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    Notes: [Auszug] To the editor: I read your News Feature, “The color of money” (Nat Med. 9, 1340; 2003), with great interest. I have grappled with this issue for many years and am glad to see it discussed in an open forum. I'm sure such discussions will eventually lead to an appropriate system of ...
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    Nature medicine 10 (2004), S. 209-209 
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    Notes: [Auszug] Nat. Med. 10, 93–97 (2004) The panels in Figure 4a and b should be switched. The panel in Figure 4b should have been labeled 'a', and ...
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    Notes: [Auszug] Patients presenting with metastatic rhabdomyosarcoma (RMS), the most common soft-tissue sarcoma in children, have a very poor clinical prognosis. This is due, in large part, to our rudimentary knowledge of the molecular events that dictate metastatic potential. We used cDNA microarray analysis of ...
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    Nature medicine 10 (2004), S. 236-237 
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    Notes: [Auszug] Successful regeneration after axonal injury hinges on proper communication. Crushing or slicing alerts the axon to send an 'injury signal' to the cell body, which then upregulates expression of a number of regeneration-associated genes, including those encoding growth-associated protein-43, ...
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    Nature medicine 10 (2004), S. 241-241 
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    Notes: [Auszug] Immortal or mortal? It finally happened. Just six years after the creation of the first human embryonic stem cell line and seven years after the cloning of Dolly by nuclear transfer, researchers have generated a human embryonic stem cell line from a donor nucleus. In the 13 February Science, Woo ...
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    Notes: [Auszug] The primary cause of severe acute respiratory syndrome (SARS) is a newly discovered coronavirus. Replication of this SARS coronavirus (SCV) occurs mainly in the lower respiratory tract, and causes diffuse alveolar damage. Lack of understanding of the pathogenesis of SARS has prevented the rational ...
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    Notes: [Auszug] Within-patient HIV evolution reflects the strong selection pressure driving viral escape from cytotoxic T-lymphocyte (CTL) recognition. Whether this intrapatient accumulation of escape mutations translates into HIV evolution at the population level has not been evaluated. We studied over 300 ...
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    Notes: [Auszug] Embryonic development of multilineage hematopoiesis requires the precisely regulated expression of lineage-specific transcription factors, including AML-1 (encoded by Runx1; also known as CBFA-2 or PEBP-2αB). In vitro studies and findings in human diseases, including leukemias, ...
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    Nature medicine 10 (2004), S. 110-110 
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    Notes: [Auszug] More than 300 US soldiers in Iraq have been diagnosed with the parasitic skin disease leishmaniasis, which is expected to infect nearly 1,000 soldiers by the end of 2004. “This is probably the largest outbreak of leishmaniasis that the US military has ever seen,” says Lt. Col. Peter ...
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    Nature medicine 10.2004, 12s, S122-, (8 S.) 
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    Notes: [Auszug] The optimism of the early period of antimicrobial discovery has been tempered by the emergence of bacterial strains with resistance to these therapeutics. Today, clinically important bacteria are characterized not only by single drug resistance but also by multiple antibiotic resistance—the ...
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    Nature medicine 10.2004, 12s, S77-, (5 S.) 
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    Notes: [Auszug] The successful replication of a viral pathogen in a host is a complex process involving many interactions. These interactions develop from the coevolution of pathogen and host and often lead to a species specificity of the virus that can make interspecies transmissions difficult. Nevertheless, ...
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    Notes: [Auszug] Signaling by the calcium-dependent phosphatase calcineurin profoundly influences the growth and gene expression of cardiac and skeletal muscle. Calcineurin binds to calsarcins, a family of muscle-specific proteins of the sarcomeric Z-disc, a focal point in the pathogenesis of human ...
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    Nature medicine 10 (2004), S. 1390-1396 
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    Notes: [Auszug] We have developed a multiplexed reverse phase protein (RPP) microarray platform for simultaneous monitoring of site-specific phosphorylation of numerous signaling proteins using nanogram amounts of lysates derived from stimulated living cells. We first show the application of RPP microarrays to the ...
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    Nature medicine 10 (2004), S. 133-134 
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    Notes: [Auszug] The structure of gp41 was a long-sought and elusive goal for HIV biologists. The difficulties of working with a membrane protein, the strong tendency of gp41 to aggregate, and other hurdles stood in the way. When Chan et al. and Weissenhorn et al. finally produced the first structures in 1997, ...
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    Nature medicine 10 (2004), S. 1266-1266 
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    Notes: [Auszug] The UK's Human Fertilisation and Embryology Authority (HFEA) has come under fire for allowing, for the first time in Britain, genetic screening of embryos for a disease that will not affect the child at birth. Critics say the agency made the ethically charged decision without input from experts, ...
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    Nature medicine 10 (2004), S. 1267-1267 
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    Notes: [Auszug] New techniques that use RNA interference (RNAi) and osmotic pumps to deliver medicines are moving to clinical trials after proving successful in animal models of amyotrophic lateral sclerosis (ALS). If the methods are successful in humans, researchers say, the results may be applicable to other ...
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    Nature medicine 10 (2004), S. 1397-1397 
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    Notes: [Auszug] Nat. Med. 10, 1074–1080 (2004). In the online version of this article, the right axis of the graph in Figure 1a was missing its label. It should be labeled 'average litter size.' Also in the online version, the link for Figure 2 was incorrect. This has now been ...
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    Nature medicine 10 (2004), S. 1161-1162 
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    Notes: [Auszug] Sepsis affects approximately 750,000 people and accounts for over 200,000 deaths each year in the United States alone. Despite treatment with appropriate antibiotics, patients with sepsis often develop multiple organ failure, including shock, resulting from an overwhelming inflammatory response. ...
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    Nature medicine 10 (2004), S. 1165-1166 
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    Notes: [Auszug] Transplantation immunobiology for the past half century has been shaped by the pursuit of tolerance—acceptance of a foreign graft as self while maintaining responsiveness to other antigens. In 1953, Billingham, Brent and Medawar conceptualized transplantation tolerance and proved it is ...
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    Nature medicine 10 (2004), S. 1261-1261 
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    Notes: [Auszug] Nat. Med. 10, 1088–1094 In the Figure 4 legend, “CD11c+CD8+ T or CD11c−CD8+” should read “CD11c+CD8+ or CD11c−CD8+ T cells.” In b of the Figure 5 legend, “control IgG or” should be ...
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    Nature medicine 10 (2004), S. 1262-1262 
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    Notes: [Auszug] In a spin Beckman Coulter introduces the Allegra X-15R benchtop centrifuge, providing fast separations and optimal recovery in the large capacity 4 × 750-ml rotor. This new instrument spins the popular rotor at 5,250 g and also spins microplate carriers. Suitable for many applications, the ...
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