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  • 1
    Publication Date: 2022-05-25
    Description: © The Author(s), 2018. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Proceedings of the National Academy of Sciences.of the United States of America 115 (2018): 3398-3403, doi:10.1073/pnas.1715382115.
    Description: Plant nitrogen (N) use is a key component of the N cycle in terrestrial ecosystems. The supply of N to plants affects community species composition and ecosystem processes such as photosynthesis and carbon (C) accumulation. However, the availabilities and relative importance of different N forms to plants are not well understood. While nitrate (NO3−) is a major N form used by plants worldwide, it is discounted as a N source for Arctic tundra plants because of extremely low NO3− concentrations in Arctic tundra soils, undetectable soil nitrification, and plant-tissue NO3− that is typically below detection limits. Here we reexamine NO3− use by tundra plants using a sensitive denitrifier method to analyze plant-tissue NO3−. Soil-derived NO3− was detected in tundra plant tissues, and tundra plants took up soil NO3− at comparable rates to plants from relatively NO3−-rich ecosystems in other biomes. Nitrate assimilation determined by 15N enrichments of leaf NO3− relative to soil NO3− accounted for 4 to 52% (as estimated by a Bayesian isotope-mixing model) of species-specific total leaf N of Alaskan tundra plants. Our finding that in situ soil NO3− availability for tundra plants is high has important implications for Arctic ecosystems, not only in determining species compositions, but also in determining the loss of N from soils via leaching and denitrification. Plant N uptake and soil N losses can strongly influence C uptake and accumulation in tundra soils. Accordingly, this evidence of NO3− availability in tundra soils is crucial for predicting C storage in tundra.
    Description: his study was supported by the Kyoto University Foundation, the Sumitomo Foundation, Program for Next Generation World-Leading Researcher (Grant GS008) and Grant-in-Aid for Scientific Research (KAKENHI Grants 26252020, 26550004, 17H06297, and P09316) from the Japan Society for Promotion of Science, the National Natural Science Foundation of China (Grants 41730855, 41522301, and 41473081), the National Key Research and Development Program of China (Grants 2016YFA0600802 and 2017YFC0210101), and the 11th Recruitment Program of Global Experts (the Thousand Talents Plan) for Young Professionals granted by the central budget of China.
    Keywords: Arctic tundra plants ; Nitrogen dynamics ; Plant nitrate ; Soil nitrate ; Stable isotopes
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  • 2
    Publication Date: 2022-05-25
    Description: © The Author(s), 2018. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Proceedings of the National Academy of Sciences.of the United States of America 115 (2018): 6756–6761, doi:10.1073/pnas.1804351115.
    Description: The existence of a chemosynthetic subseafloor biosphere was immediately recognized when deep-sea hot springs were discovered in 1977. However, quantifying how much new carbon is fixed in this environment has remained elusive. In this study, we incubated natural subseafloor communities under in situ pressure/temperature and measured their chemosynthetic growth efficiency and metabolic rates. Combining these data with fluid flux and in situ chemical measurements, we derived empirical constraints on chemosynthetic activity in the natural environment. Our study shows subseafloor microorganisms are highly productive (up to 1.4 Tg C produced yearly), fast-growing (turning over every 17–41 hours), and physiologically diverse. These estimates place deep-sea hot springs in a quantitative framework and allow us to assess their importance for global biogeochemical cycles.
    Description: This research was funded by a grant of the Dimensions of Biodiversity program of the US National Science Foundation (NSF-OCE-1136727 to S.M.S. and J.S.S.). Funding for J.M. was further provided by doctoral fellowships from the Natural Sciences and Engineering Research Council of Canada (PGSD3-430487-2013, PGSM-405117-2011) and the National Aeronautics and Space Administration Earth Systems Science Fellowship (PLANET14F-0075), an award from the Canadian Meteorological and Oceanographic Society, and the WHOI Academic Programs Office.
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  • 3
    Publication Date: 2022-05-25
    Description: © The Author(s), 2018. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Proceedings of the National Academy of Sciences.of the United States of America 115 (2018): 7729-7734, doi:10.1073/pnas.1805428115.
    Description: Identifying physical processes responsible for historical coastal sea-level changes is important for anticipating future impacts. Recent studies sought to understand the drivers of interannual to multidecadal sea-level changes on the United States Atlantic and Gulf coasts. Ocean dynamics, terrestrial water storage, vertical land motion, and melting of land ice were highlighted as important mechanisms of sea-level change along this densely populated coast on these time scales. While known to exert an important control on coastal ocean circulation, variable river discharge has been absent from recent discussions of drivers of sea-level change. We update calculations from the 1970s, comparing annual river-discharge and coastal sea-level data along the Gulf of Maine, Mid-Atlantic Bight, South Atlantic Bight, and Gulf of Mexico during 1910–2017. We show that river-discharge and sea-level changes are significantly correlated (p〈0.01), such that sea level rises between 0.01 and 0.08 cm for a 1 km3 annual river-discharge increase, depending on region. We formulate a theory that describes the relation between river-discharge and halosteric sea-level changes (i.e., changes in sea level related to salinity) as a function of river discharge, Earth’s rotation, and density stratification. This theory correctly predicts the order of observed increment sea-level change per unit river-discharge anomaly, suggesting a causal relation. Our results have implications for remote sensing, climate modeling, interpreting Common Era proxy sea-level reconstructions, and projecting coastal flood risk.
    Description: C.G.P. and R.M.P. acknowledge support from NASA Contract NNH16CT01C (which also supported C.M.L.), NASA Jet Propulsion Laboratory Subcontract 1569246, and National Science Foundation Award 1558966. C.G.P. also acknowledges support from The Investment in Science Fund at Woods Hole Oceanographic Institution. A.C.K. and S.E.E. acknowledge NSF Awards OCE-1458921 and OCE-1458903, respectively.
    Keywords: Coastal sea level ; Coastal river plumes ; Coastal flood risk ; Climate modeling ; Physical oceanography
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  • 4
    Publication Date: 2022-05-25
    Description: Author Posting. © The Author(s), 2018. This is the author's version of the work. It is posted here by permission of National Academy of Sciences for personal use, not for redistribution. The definitive version was published in Proceedings of the National Academy of Sciences of the United States of America 115(52), (2018): E12275-E12284. doi: 10.1073/pnas.1805243115.
    Description: Diatoms are prominent eukaryotic phytoplankton despite being limited by the micronutrient iron in vast expanses of the ocean. As iron inputs are often sporadic, diatoms have evolved mechanisms such as the ability to store iron that enable them to bloom when iron is resupplied and then persist when low iron levels are reinstated. Two iron storage mechanisms have been previously described: the protein ferritin and vacuolar storage. To investigate the ecological role of these mechanisms among diatoms, iron addition and removal incubations were conducted using natural phytoplankton communities from varying iron environments. We show that among the predominant diatoms, Pseudo-nitzschia were favored by iron removal and displayed unique ferritin expression consistent with a long-term storage function. Meanwhile, Chaetoceros and Thalassiosira gene expression aligned with vacuolar storage mechanisms. Pseudo-nitzschia also showed exceptionally high iron storage under steady-state high and low iron conditions, as well as following iron resupply to iron-limited cells. We propose that bloom-forming diatoms use different iron storage mechanisms and that ferritin utilization may provide an advantage in areas of prolonged iron limitation with pulsed iron inputs. As iron distributions and availability change, this speculated ferritin-linked advantage may result in shifts in diatom community composition that can alter marine ecosystems and biogeochemical cycles.
    Description: We thank the captain and crew of the R/V Melville and the CCGS J. P. Tully as well as the participants of the IRNBRU (MV1405) cruise for the California-based data, particularly K. Ellis [University of North Carolina (UNC)], T. Coale (University of California, San Diego), F. Kuzminov (Rutgers), H. McNair [University of California, Santa Barbara (UCSB)], and J. Jones (UCSB). W. Burns (UNC), S. Haines (UNC), and S. Bargu (Louisiana State University) assisted with sample processing and analysis. This work was funded by the National Science Foundation Grants OCE-1334935 (to A.M.), OCE-1334632 (to B.S.T.), OCE-1333929 (to K.T.), OCE-1334387 (to M.A.B.), OCE-1259776 (to K.W.B), and DGE-1650116 (Graduate Research Fellowship to R.H.L).
    Description: 2019-06-11
    Keywords: phytoplankton ; iron limitation ; Pseudo-nitzschia ; ferritin ; metatranscriptomics
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  • 5
    Publication Date: 2022-05-25
    Description: © The Author(s), 2018. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Proceedings of the National Academy of Sciences of the United States of America 115 (2018): 8161-8166, doi:10.1073/pnas.1806296115.
    Description: Copper is an essential cofactor of cytochrome c oxidase (CcO), the terminal enzyme of the mitochondrial respiratory chain. Inherited loss-of-function mutations in several genes encoding proteins required for copper delivery to CcO result in diminished CcO activity and severe pathologic conditions in affected infants. Copper supplementation restores CcO function in patient cells with mutations in two of these genes, COA6 and SCO2, suggesting a potential therapeutic approach. However, direct copper supplementation has not been therapeutically effective in human patients, underscoring the need to identify highly efficient copper transporting pharmacological agents. By using a candidate-based approach, we identified an investigational anticancer drug, elesclomol (ES), that rescues respiratory defects of COA6-deficient yeast cells by increasing mitochondrial copper content and restoring CcO activity. ES also rescues respiratory defects in other yeast mutants of copper metabolism, suggesting a broader applicability. Low nanomolar concentrations of ES reinstate copper-containing subunits of CcO in a zebrafish model of copper deficiency and in a series of copper-deficient mammalian cells, including those derived from a patient with SCO2 mutations. These findings reveal that ES can restore intracellular copper homeostasis by mimicking the function of missing transporters and chaperones of copper, and may have potential in treating human disorders of copper metabolism.
    Description: This work was supported by National Institutes of Health Awards R01GM111672 (to V.M.G.), R01 DK110195 (to B.-E.K.), and DK 44464 (to J.D.G.); Welch Foundation Grant A-1810 (to V.M.G.); and Canadian Institutes of Health Research Operating Grant MOP 133562 (to S.C.L.).
    Keywords: Copper ; Mitochondria ; Elesclomol ; Cytochrome c oxidase
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  • 6
    Publication Date: 2022-05-26
    Description: © The Author(s), 2019. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Proceedings of the National Academy of Sciences.of the United States of America 116(36), (2019): 17934-17942, doi:10.1073/pnas.1910121116.
    Description: Plastid endosymbiosis has been a major force in the evolution of eukaryotic cellular complexity, but how endosymbionts are integrated is still poorly understood at a mechanistic level. Dinoflagellates, an ecologically important protist lineage, represent a unique model to study this process because dinoflagellate plastids have repeatedly been reduced, lost, and replaced by new plastids, leading to a spectrum of ages and integration levels. Here we describe deep-transcriptomic analyses of the Antarctic Ross Sea dinoflagellate (RSD), which harbors long-term but temporary kleptoplasts stolen from haptophyte prey, and is closely related to dinoflagellates with fully integrated plastids derived from different haptophytes. In some members of this lineage, called the Kareniaceae, their tertiary haptophyte plastids have crossed a tipping point to stable integration, but RSD has not, and may therefore reveal the order of events leading up to endosymbiotic integration. We show that RSD has retained its ancestral secondary plastid and has partitioned functions between this plastid and the kleptoplast. It has also obtained genes for kleptoplast-targeted proteins via horizontal gene transfer (HGT) that are not derived from the kleptoplast lineage. Importantly, many of these HGTs are also found in the related species with fully integrated plastids, which provides direct evidence that genetic integration preceded organelle fixation. Finally, we find that expression of kleptoplast-targeted genes is unaffected by environmental parameters, unlike prey-encoded homologs, suggesting that kleptoplast-targeted HGTs have adapted to posttranscriptional regulation mechanisms of the host.
    Description: We are grateful to Martin Kolisko and Fabien Burki for helpful discussion about and comments on the phylogenetic analysis; and Filip Husnik and Vittorio Boscaro for valuable comments on the manuscript. This work was supported by a grant from the National Science Foundation to R.J.G. and P.J.K. (PLR-1341362) and from the Natural Sciences and Engineering Research Council of Canada to P.J.K. (RGPIN-2014-03994).
    Description: 2020-02-19
    Keywords: plastid endosymbiosis ; kleptoplasty ; dinoflagellates ; plastid integration
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  • 7
    Publication Date: 2022-10-26
    Description: © The Author(s), 2019. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Diaz, J. M., Plummer, S., Hansel, C. M., Andeer, P. F., Saito, M. A., & McIlvin, M. R. NADPH-dependent extracellular superoxide production is vital to photophysiology in the marine diatom Thalassiosira oceanica. Proceedings of the National Academy of Sciences of the United States of America, 116 (33), (2019): 16448-16453, doi: 10.1073/pnas.1821233116.
    Description: Reactive oxygen species (ROS) like superoxide drive rapid transformations of carbon and metals in aquatic systems and play dynamic roles in biological health, signaling, and defense across a diversity of cell types. In phytoplankton, however, the ecophysiological role(s) of extracellular superoxide production has remained elusive. Here, the mechanism and function of extracellular superoxide production by the marine diatom Thalassiosira oceanica are described. Extracellular superoxide production in T. oceanica exudates was coupled to the oxidation of NADPH. A putative NADPH-oxidizing flavoenzyme with predicted transmembrane domains and high sequence similarity to glutathione reductase (GR) was implicated in this process. GR was also linked to extracellular superoxide production by whole cells via quenching by the flavoenzyme inhibitor diphenylene iodonium (DPI) and oxidized glutathione, the preferred electron acceptor of GR. Extracellular superoxide production followed a typical photosynthesis-irradiance curve and increased by 30% above the saturation irradiance of photosynthesis, while DPI significantly impaired the efficiency of photosystem II under a wide range of light levels. Together, these results suggest that extracellular superoxide production is a byproduct of a transplasma membrane electron transport system that serves to balance the cellular redox state through the recycling of photosynthetic NADPH. This photoprotective function may be widespread, consistent with the presence of putative homologs to T. oceanica GR in other representative marine phytoplankton and ocean metagenomes. Given predicted climate-driven shifts in global surface ocean light regimes and phytoplankton community-level photoacclimation, these results provide implications for future ocean redox balance, ecological functioning, and coupled biogeochemical transformations of carbon and metals.
    Description: This work was supported by a postdoctoral fellowship from the Ford Foundation (to J.M.D.), the National Science Foundation (NSF) under grants OCE 1225801 (to J.M.D.) and OCE 1246174 (to C.M.H.), a Junior Faculty Seed Grant from the University of Georgia Research Foundation (to J.M.D.), and a National Science Foundation Graduate Research Fellowship (to S.P.). The FIRe was purchased through a NSF equipment improvement grant (1624593).The authors thank Melissa Soule for assistance with LC/MS/MS analysis of peptide samples.
    Keywords: Reactive oxygen species ; Photosynthesis ; Oxidative stress ; Biogeochemistry
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  • 8
    Publication Date: 2022-10-26
    Description: Author Posting. © National Academy of Sciences, 2019. This article is posted here by permission of National Academy of Sciences for personal use, not for redistribution. The definitive version was published in Proceedings of the National Academy of Sciences 116(27), (2019): 13233-13238, doi: 10.1073/pnas.1904087116.
    Description: The overturning circulation of the global ocean is critically shaped by deep-ocean mixing, which transforms cold waters sinking at high latitudes into warmer, shallower waters. The effectiveness of mixing in driving this transformation is jointly set by two factors: the intensity of turbulence near topography and the rate at which well-mixed boundary waters are exchanged with the stratified ocean interior. Here, we use innovative observations of a major branch of the overturning circulation—an abyssal boundary current in the Southern Ocean—to identify a previously undocumented mixing mechanism, by which deep-ocean waters are efficiently laundered through intensified near-boundary turbulence and boundary–interior exchange. The linchpin of the mechanism is the generation of submesoscale dynamical instabilities by the flow of deep-ocean waters along a steep topographic boundary. As the conditions conducive to this mode of mixing are common to many abyssal boundary currents, our findings highlight an imperative for its representation in models of oceanic overturning.
    Description: The DynOPO project is supported by the UK Natural Environment Research Council (grants NE/K013181/1 and NE/K012843/1) and the US National Science Foundation (grants OCE-1536453 and OCE-1536779). A.C.N.G. acknowledges the support of the Royal Society and the Wolfson Foundation. S.L. acknowledges the support of award NA14OAR4320106 from the National Oceanic and Atmospheric Administration, US Department of Commerce. The statements, findings, conclusions, and recommendations are those of the authors, and do not necessarily reflect the views of the National Oceanic and Atmospheric Administration, or the US Department of Commerce. We are grateful to the scientific party, crew, and technicians on the RRS James Clark Ross for their hard work during data collection.
    Description: 2019-12-18
    Keywords: Ocean mixing ; Overturning circulation ; Submesoscale instabilities ; Turbulence
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  • 9
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    American Institute of Physics
    Publication Date: 2022-05-26
    Description: Author Posting. © American Institute of Physics, 2017. This article is posted here by permission of American Institute of Physics for personal use, not for redistribution. The definitive version was published in Physics Today 70, no. 11 (2017): 78, doi:10.1063/PT.3.3773.
    Description: With only a minimal flapping, the wandering albatross can circumnavigate the globe. During its peregrinations over the Southern Ocean, the seabird exploits wind shear—the gradient of wind speed—to extract energy for its sustained flight. That same maneuver, called dynamic soaring, is used by pilots of radio-controlled gliders. In flights that take advantage of the shear associated with wind blowing over mountain ridges, the gliders reach air speeds of an astonishing 500 mph. Engineers are currently developing autonomous unmanned vehicles that can use the technique to supplement different sources of energy for sustained flight over the oceans. Possible applications include environmental monitoring, surveillance, and search and rescue.
    Description: 2018-11-01
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  • 10
    Publication Date: 2022-05-26
    Description: © The Author(s), 2017. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Annual Review of Marine Science 9 (2017): 173-203, doi:10.1146/annurev-marine-010816-060733.
    Description: The events that followed the Tohoku earthquake and tsunami on March 11, 2011, included the loss of power and overheating at the Fukushima Daiichi nuclear power plants, which led to extensive releases of radioactive gases, volatiles, and liquids, particularly to the coastal ocean. The fate of these radionuclides depends in large part on their oceanic geochemistry, physical processes, and biological uptake. Whereas radioactivity on land can be resampled and its distribution mapped, releases to the marine environment are harder to characterize owing to variability in ocean currents and the general challenges of sampling at sea. Five years later, it is appropriate to review what happened in terms of the sources, transport, and fate of these radionuclides in the ocean. In addition to the oceanic behavior of these contaminants, this review considers the potential health effects and societal impacts.
    Description: K.B. was supported in part by the Gordon and Betty Moore Foundation and the Deerbrook Charitable Trust. P.M. was supported in part by the Generalitat de Catalunya through MERS (grant 2014 SGR 1356), the European Commission 7th Framework COMET-FRAME project (grant agreement 604974), and the Ministerio de Economía y Competitividad of Spain (project CTM2011-15152-E). S.C. was supported in part by the French program Investissement d'Avenir run by the National Research Agency (AMORAD project, grant ANR-11-RSNR-0002). D.O. was supported in part by the Center for Environmental Radioactivity (NFR Centers of Excellence grant 223268/F50). J.N.S. was supported in part by the Marine Environmental Observation, Prediction, and Response Network.
    Keywords: Cesium ; Caesium ; North Pacific ; Radioactivity ; Japan
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  • 11
    Publication Date: 2022-05-26
    Description: © The Author(s), 2017. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Proceedings of the National Academy of Sciences of the United States of America 114 (2017): 13114-13119, doi: 10.1073/pnas.1702143114.
    Description: During the Mid-Pleistocene Transition (MPT; 1,200–800 kya), Earth’s orbitally paced ice age cycles intensified, lengthened from ∼40,000 (∼40 ky) to ∼100 ky, and became distinctly asymmetrical. Testing hypotheses that implicate changing atmospheric CO2 levels as a driver of the MPT has proven difficult with available observations. Here, we use orbitally resolved, boron isotope CO2 data to show that the glacial to interglacial CO2 difference increased from ∼43 to ∼75 μatm across the MPT, mainly because of lower glacial CO2 levels. Through carbon cycle modeling, we attribute this decline primarily to the initiation of substantive dust-borne iron fertilization of the Southern Ocean during peak glacial stages. We also observe a twofold steepening of the relationship between sea level and CO2-related climate forcing that is suggestive of a change in the dynamics that govern ice sheet stability, such as that expected from the removal of subglacial regolith or interhemispheric ice sheet phase-locking. We argue that neither ice sheet dynamics nor CO2 change in isolation can explain the MPT. Instead, we infer that the MPT was initiated by a change in ice sheet dynamics and that longer and deeper post-MPT ice ages were sustained by carbon cycle feedbacks related to dust fertilization of the Southern Ocean as a consequence of larger ice sheets.
    Description: Research was supported by National Environmental Research Council (NERC) Studentship NE/I528626/1 (to T.B.C.); NERC Grant NE/P011381/1 (to T.B.C., M.P.H., G.L.F., E.J.R., and P.A.W.); NERC Fellowships NE/K00901X/1 (to M.P.H.), NE/I006346/1 (to G.L.F. and R.D.P), and NE/H006273/1 (to R.D.P.); Royal Society Wolfson Awards (to G.L.F. and P.A.W.); Australian Research Council Laureate Fellowship FL1201000050 (to E.J.R.); Swiss National Science Foundation Grant PP00P2-144811 (to S.L.J.); ETH Research Grant ETH-04 11-1 (to S.L.J.); European Research Council Consolidator Grant (ERC CoG) Grant 617462 (to H.P.); and NERC UK IODP Grant NE/F00141X/1 (to P.A.W.).
    Keywords: Boron isotopes ; MPT ; Geochemistry ; Carbon dioxide ; Paleoclimate
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  • 12
    Publication Date: 2022-05-26
    Description: Author Posting. © The Author(s), 2019. This is the author's version of the work. It is posted here by permission of National Academy of Sciences for personal use, not for redistribution. The definitive version was published in Proceedings of the National Academy of Sciences of the United States of America 116(25), (2019):12343-12352, doi:10.1073/pnas.1901080116.
    Description: Genes encoding cytochrome P450 (CYP; P450) enzymes occur widely in the Archaea, Bacteria, and Eukarya, where they play important roles in metabolism of endogenous regulatory molecules and exogenous chemicals. We now report that genes for multiple and unique P450s occur commonly in giant viruses in the Mimiviridae, Pandoraviridae, and other families in the proposed order Megavirales. P450 genes were also identified in a herpesvirus (Ranid herpesvirus 3) and a phage (Mycobacterium phage Adler). The Adler phage P450 was classified as CYP102L1, and the crystal structure of the open form was solved at 2.5 Å. Genes encoding known redox partners for P450s (cytochrome P450 reductase, ferredoxin and ferredoxin reductase, and flavodoxin and flavodoxin reductase) were not found in any viral genome so far described, implying that host redox partners may drive viral P450 activities. Giant virus P450 proteins share no more than 25% identity with the P450 gene products we identified in Acanthamoeba castellanii, an amoeba host for many giant viruses. Thus, the origin of the unique P450 genes in giant viruses remains unknown. If giant virus P450 genes were acquired from a host, we suggest it could have been from an as yet unknown and possibly ancient host. These studies expand the horizon in the evolution and diversity of the enormously important P450 superfamily. Determining the origin and function of P450s in giant viruses may help to discern the origin of the giant viruses themselves.
    Description: We thank Dr. David Nes (Texas Tech University) for providing sterols and Dr. Matthieu Legendre and Dr. Chantal Abergel (CNRS, Marseille) for access to the P. celtis sequences. Drs. Irina Arkhipova, Mark Hahn, Judith Luborsky, and Ann Bucklin commented on the manuscript. The research was supported by a USA-UK Fulbright Scholarship and a Royal Society grant (to D.C.L.), the Boston University Superfund Research Program [NIH Grant 5P42ES007381 (to J.J.S. and J.V.G.) and NIH Grant 5U41HG003345 (to J.V.G.)], the European Regional Development Fund and Welsh Government Project BEACON (S.L.K.), the Woods Hole Center for Oceans and Human Health [NIH Grant P01ES021923 and National Science Foundation Grant OCE-1314642 (to J.J.S.)], and NIH Grant R01GM53753 (to T.L.P.).
    Description: 2019-12-05
    Keywords: cytochrome P450 ; virus ; evolution ; domains of life ; redox partner
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  • 13
    Publication Date: 2022-05-26
    Description: Author Posting. © National Academy of Sciences, 2019. This article is posted here by permission of National Academy of Sciences for personal use, not for redistribution. The definitive version was published in Proceedings of the National Academy of Sciences 116 (35), (2019): 17187-17192, doi:10.1073/pnas.1903067116.
    Description: Mesoscale eddies are critical components of the ocean’s “internal weather” system. Mixing and stirring by eddies exerts significant control on biogeochemical fluxes in the open ocean, and eddies may trap distinctive plankton communities that remain coherent for months and can be transported hundreds to thousands of kilometers. Debate regarding how and why predators use fronts and eddies, for example as a migratory cue, enhanced forage opportunities, or preferred thermal habitat, has been ongoing since the 1950s. The influence of eddies on the behavior of large pelagic fishes, however, remains largely unexplored. Here, we reconstruct movements of a pelagic predator, the blue shark (Prionace glauca), in the Gulf Stream region using electronic tags, earth-observing satellites, and data-assimilating ocean forecasting models. Based on 〉2,000 tracking days and nearly 500,000 high-resolution time series measurements collected by 15 instrumented individuals, we show that blue sharks seek out the interiors of anticyclonic eddies where they dive deep while foraging. Our observations counter the existing paradigm that anticyclonic eddies are unproductive ocean “deserts” and suggest anomalously warm temperatures in these features connect surface-oriented predators to the most abundant fish community on the planet in the mesopelagic. These results also shed light on the ecosystem services provided by mesopelagic prey. Careful consideration will be needed before biomass extraction from the ocean twilight zone to avoid interrupting a key link between planktonic production and top predators. Moreover, robust associations between targeted fish species and oceanographic features increase the prospects for effective dynamic ocean management.
    Description: We thank D. McGillicuddy, G. Lawson, and G. Flierl for helpful discussions while developing this work and 2 anonymous reviewers whose feedback significantly improved the manuscript. We also thank C. Fischer and the OCEARCH team for their support of this research. This work was funded by awards to C.D.B. from the Martin Family Society of Fellows for Sustainability Fellowship at the Massachusetts Institute of Technology; the Grassle Fellowship and Ocean Venture Fund at the Woods Hole Oceanographic Institution; and the National Aeronatics and Space Administration (NASA) Earth and Space Science Fellowship. C.D.B. and P.G. acknowledge support from the NASA New Investigator Program Award 80NSSC18K0757, and P.G. acknowledges support from NSF Award OCE-1558809. This research is partially supported by funding to S.R.T. as part of the Audacious Project, a collaborative endeavor, housed at TED. We thank donors to the Woods Hole Oceanographic Institution (WHOI) ProjectWHOI crowdfunding campaign: The Secret Lives of Sharks. Computational support was provided by the Amazon Web Services Cloud Credits for Research program. Funding for the development of HYCOM has been provided by the National Ocean Partnership Program and the Office of Naval Research.
    Description: 2020-02-06
    Keywords: remote sensing ; oceanographic model ; satellite telemetry ; marine predator ; mesopelagic
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  • 14
    Publication Date: 2022-05-26
    Description: Author Posting. © National Academy of Sciences, 2019. This article is posted here by permission of National Academy of Sciences for personal use, not for redistribution. The definitive version was published in Proceedings of the National Academy of Sciences 116 (35), (2019): 17207-17212, doi:10.1073/pnas.1900325116.
    Description: It has been hypothesized that the overall size of—or efficiency of carbon export from—the biosphere decreased at the end of the Great Oxidation Event (GOE) (ca. 2,400 to 2,050 Ma). However, the timing, tempo, and trigger for this decrease remain poorly constrained. Here we test this hypothesis by studying the isotope geochemistry of sulfate minerals from the Belcher Group, in subarctic Canada. Using insights from sulfur and barium isotope measurements, combined with radiometric ages from bracketing strata, we infer that the sulfate minerals studied here record ambient sulfate in the immediate aftermath of the GOE (ca. 2,018 Ma). These sulfate minerals captured negative triple-oxygen isotope anomalies as low as ∼ −0.8‰. Such negative values occurring shortly after the GOE require a rapid reduction in primary productivity of 〉80%, although even larger reductions are plausible. Given that these data imply a collapse in primary productivity rather than export efficiency, the trigger for this shift in the Earth system must reflect a change in the availability of nutrients, such as phosphorus. Cumulatively, these data highlight that Earth’s GOE is a tale of feast and famine: A geologically unprecedented reduction in the size of the biosphere occurred across the end-GOE transition.
    Description: Olivia M. J. Dagnaud assisted during fieldwork. S. V. Lalonde and E. A. Sperling provided helpful comments on an early version of the manuscript. We thank N. J. Planavsky and an anonymous reviewer for their constructive feedback. M.S.W.H. was supported by an NSERC PGS-D and student research grants from National Geographic, the APS Lewis and Clark Fund, Northern Science Training Program, McGill University Graduate Research Enhancement and Travel Awards, Geological Society of America, Mineralogical Association of Canada, and Stanford University. P.W.C. acknowledges support from the University of Colorado Boulder, the Agouron Institute Geobiology postdoctoral Fellowship program, a Natural Sciences and Engineering Council of Canada Postgraduate Scholarship–Doctoral Program scholarship, and the NSTP. Y.P. was supported by the Strategic Priority Research Program of CAS (XDB26000000). T.J.H. thanks Maureen E. Auro for laboratory assistance and the NSF for supporting isotope research in the NIRVANA Labs.
    Description: 2020-02-12
    Keywords: Proterozoic ; primary productivity ; Great Oxidation Event ; triple-oxygen isotopes ; nutrient limitation
    Repository Name: Woods Hole Open Access Server
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  • 15
    Publication Date: 2022-05-26
    Description: Author Posting. © National Academy of Sciences, 2019. This article is posted here by permission of National Academy of Sciences for personal use, not for redistribution. The definitive version was published in Proceedings of the National Academy of Sciences 116(45), (2019): 22518-22525, doi:10.1073/pnas.1913714116.
    Description: The Ganges–Brahmaputra (G-B) River system transports over a billion tons of sediment every year from the Himalayan Mountains to the Bay of Bengal and has built the world’s largest active sedimentary deposit, the Bengal Fan. High sedimentation rates drive exceptional organic matter preservation that represents a long-term sink for atmospheric CO2. While much attention has been paid to organic-rich fine sediments, coarse sediments have generally been overlooked as a locus of organic carbon (OC) burial. However, International Ocean Discovery Program Expedition 354 recently discovered abundant woody debris (millimeter- to centimeter-sized fragments) preserved within the coarse sediment layers of turbidite beds recovered from 6 marine drill sites along a transect across the Bengal Fan (∼8°N, ∼3,700-m water depth) with recovery spanning 19 My. Analysis of bulk wood and lignin finds mostly lowland origins of wood delivered episodically. In the last 5 My, export included C4 plants, implying that coarse woody, lowland export continued after C4 grassland expansion, albeit in reduced amounts. Substantial export of coarse woody debris in the last 1 My included one wood-rich deposit (∼0.05 Ma) that encompassed coniferous wood transported from the headwaters. In coarse layers, we found on average 0.16 weight % OC, which is half the typical biospheric OC content of sediments exported by the modern G-B Rivers. Wood burial estimates are hampered by poor drilling recovery of sands. However, high-magnitude, low-frequency wood export events are shown to be a key mechanism for C burial in turbidites.
    Description: This work was funded by National Science Foundation Grants OCE-1401217 and COL-T354A55 to S.J.F. and OCE-1400805 to V.G. Graduate student participation in the project received support from University of Southern California Provost’s Fellowship to H.L. Samples were provided by the International Ocean Discovery Program. We are grateful for the efforts of the Expedition 354 Science Party, Carl Johnson, and Zongguang Liu. C.F.-L. and A.G. were supported by IODP-France. We thank Colin Osborne and Maria Vorontsova for helpful discussions.
    Description: 2020-04-21
    Keywords: carbon cycle ; wood ; lignin ; Himalaya ; Bengal Fan
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  • 16
    Publication Date: 2023-03-31
    Description: Coeval changes in atmospheric CO2 and 14C contents during the last deglaciation are often attributed to ocean circulation changes that released carbon stored in the deep ocean during the Last Glacial Maximum (LGM). Work is being done to generate records that allow for the identification of the exact mechanisms leading to the accumulation and release of carbon from the oceanic reservoir, but these mechanisms are still the subject of debate. Here we present foraminifera 14C data from five cores in a transect across the Chilean continental margin between ~540 and ~3,100 m depth spanning the last 20,000 years. Our data reveal that during the LGM, waters at ~2,000 m were 50% to 80% more depleted in Δ14C than waters at ~1,500 m when compared to modern values, consistent with the hypothesis of a glacial deep ocean carbon reservoir that was isolated from the atmosphere. During the deglaciation, our intermediate water records reveal homogenization in the Δ14C values between ~800 and ~1,500 m from ~16.5–14.5 ka cal BP to ~14–12 ka cal BP, which we interpret as deeper penetration of Antarctic Intermediate Water. While many questions still remain, this process could aid the ventilation of the deep ocean at the beginning of the deglaciation, contributing to the observed ~40 ppm rise in atmospheric pCO2.
    Repository Name: EPIC Alfred Wegener Institut
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  • 17
    Publication Date: 2022-10-26
    Description: © The Author(s), 2019. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Proceedings of the National Academy of Sciences.of the United States of America 116(36), (2019): 17666-17672. doi:10.1073/pnas.1907871116.
    Description: The conditions of methane (CH4) formation in olivine-hosted secondary fluid inclusions and their prevalence in peridotite and gabbroic rocks from a wide range of geological settings were assessed using confocal Raman spectroscopy, optical and scanning electron microscopy, electron microprobe analysis, and thermodynamic modeling. Detailed examination of 160 samples from ultraslow- to fast-spreading midocean ridges, subduction zones, and ophiolites revealed that hydrogen (H2) and CH4 formation linked to serpentinization within olivine-hosted secondary fluid inclusions is a widespread process. Fluid inclusion contents are dominated by serpentine, brucite, and magnetite, as well as CH4(g) and H2(g) in varying proportions, consistent with serpentinization under strongly reducing, closed-system conditions. Thermodynamic constraints indicate that aqueous fluids entering the upper mantle or lower oceanic crust are trapped in olivine as secondary fluid inclusions at temperatures higher than ∼400 °C. When temperatures decrease below ∼340 °C, serpentinization of olivine lining the walls of the fluid inclusions leads to a near-quantitative consumption of trapped liquid H2O. The generation of molecular H2 through precipitation of Fe(III)-rich daughter minerals results in conditions that are conducive to the reduction of inorganic carbon and the formation of CH4. Once formed, CH4(g) and H2(g) can be stored over geological timescales until extracted by dissolution or fracturing of the olivine host. Fluid inclusions represent a widespread and significant source of abiotic CH4 and H2 in submarine and subaerial vent systems on Earth, and possibly elsewhere in the solar system.
    Description: We are indebted to J. Eckert for his support with FE-EMPA; to K. Aquinho and E. Codillo for providing samples from Zambales; to K. Aquinho for Raman analysis of some of the samples from Zambales and Mt. Dent; to H. Dick for providing access to his thin section collection; to the curators of the IODP core repositories for providing access to Ocean Drilling Program (ODP) and Integrated Ocean Drilling Program (IODP) samples; and to the captains and crews of the many cruises without whom the collection of these samples would not have been possible. Reviews by Peter Kelemen and an anonymous referee greatly improved this manuscript. This study is supported with funds provided by the National Science Foundation (NSF-OCE Award 1634032 to F.K. and J.S.S.).
    Description: 2020-02-19
    Keywords: Abiotic methane ; Fluid inclusions ; Serpentinization ; Methane seeps ; Carbon cycling
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  • 18
    Publication Date: 2022-10-26
    Description: Author Posting. © The Author(s), 2019. This is the author's version of the work. It is posted here by permission of National Academy of Sciences for personal use, not for redistribution. The definitive version was published in Proceedings of the National Academy of Sciences of the United States of America 116(20), (2019):9925-9930, doi:10.1073/pnas.1818349116.
    Description: Microbial capacity to metabolize arsenic is ancient, arising in response to its pervasive presence in the environment, which was largely in the form of As(III) in the early anoxic ocean. Many biological arsenic transformations are aimed at mitigating toxicity; however, some microorganisms can respire compounds of this redox-sensitive element to reap energetic gains. In several modern anoxic marine systems concentrations of As(V) are higher relative to As(III) than what would be expected from the thermodynamic equilibrium, but the mechanism for this discrepancy has remained unknown. Here we present evidence of a complete respiratory arsenic cycle, consisting of dissimilatory As(V) reduction and chemoautotrophic As(III) oxidation, in the pelagic ocean. We identified the presence of genes encoding both subunits of the respiratory arsenite oxidase AioA and the dissimilatory arsenate reductase ArrA in the Eastern Tropical North Pacific (ETNP) oxygen-deficient zone (ODZ). The presence of the dissimilatory arsenate reductase gene arrA was enriched on large particles (〉30 um), similar to the forward bacterial dsrA gene of sulfate-reducing bacteria, which is involved in the cryptic cycling of sulfur in ODZs. Arsenic respiratory genes were expressed in metatranscriptomic libraries from the ETNP and the Eastern Tropical South Pacific (ETSP) ODZ, indicating arsenotrophy is a metabolic pathway actively utilized in anoxic marine water columns. Together these results suggest arsenic-based metabolisms support organic matter production and impact nitrogen biogeochemical cycling in modern oceans. In early anoxic oceans, especially during periods of high marine arsenic concentrations, they may have played a much larger role.
    Description: We thank John Baross and Rika Anderson for helpful discussions and feedback on this project. We also thank the chief scientists of the research cruise, Al Devol and Bess Ward, as well as the captain and crew of the R/V Thomas G. Thompson. This work was supported through a NASA Earth and Space Sciences Graduate Research Fellowship to J.K.S. and National Science Foundation Grant OCE-1138368 (to G.R.).
    Description: 2019-10-29
    Keywords: Oxygen deficient zones ; Arsenic ; Chemoautotrophy ; Dissimilatory arsenate reduction ; Marine metagenome
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  • 19
    Publication Date: 2022-10-26
    Description: Author Posting. © National Academy of Sciences, 2019. This article is posted here by permission of National Academy of Sciences for personal use, not for redistribution. The definitive version was published in Proceedings of the National Academy of Sciences 116 (24), (2019):11646-11651, doi:10.1073/pnas.1900371116.
    Description: Measurements show large decadal variability in the rate of CO2 accumulation in the atmosphere that is not driven by CO2 emissions. The decade of the 1990s experienced enhanced carbon accumulation in the atmosphere relative to emissions, while in the 2000s, the atmospheric growth rate slowed, even though emissions grew rapidly. These variations are driven by natural sources and sinks of CO2 due to the ocean and the terrestrial biosphere. In this study, we compare three independent methods for estimating oceanic CO2 uptake and find that the ocean carbon sink could be responsible for up to 40% of the observed decadal variability in atmospheric CO2 accumulation. Data-based estimates of the ocean carbon sink from pCO2 mapping methods and decadal ocean inverse models generally agree on the magnitude and sign of decadal variability in the ocean CO2 sink at both global and regional scales. Simulations with ocean biogeochemical models confirm that climate variability drove the observed decadal trends in ocean CO2 uptake, but also demonstrate that the sensitivity of ocean CO2 uptake to climate variability may be too weak in models. Furthermore, all estimates point toward coherent decadal variability in the oceanic and terrestrial CO2 sinks, and this variability is not well-matched by current global vegetation models. Reconciling these differences will help to constrain the sensitivity of oceanic and terrestrial CO2 uptake to climate variability and lead to improved climate projections and decadal climate predictions.
    Description: We thank Rebecca Wright and Erik Buitenhuis at University of East Anglia, Norwich, for providing updated runs from the NEMO-PlankTOM5 model. T.D. was supported by NSF Grant OCE-1658392. C.L.Q. thanks the UK Natural Environment Research Council for supporting the SONATA Project (Grant NE/P021417/1). P.L. was supported by the Max Planck Society for the Advancement of Science. J.H. was supported under Helmholtz Young Investigator Group Marine Carbon and Ecosystem Feedbacks in the Earth System (MarESys) Grant VH-NG-1301. S.B. and R.S. were supported by the H2020 project CRESCENDO “Coordinated Research in Earth Systems and Climate: Experiments, Knowledge, Dissemination and Outreach,” which received funding from the European Union’s Horizon 2020 research and innovation program under Grant No 641816. SOCAT is an international effort, endorsed by the International Ocean Carbon Coordination Project, the Surface Ocean-Lower Atmosphere Study, and the Integrated Marine Biosphere Research program, to deliver a uniformly quality-controlled surface ocean CO2 database. The many researchers and funding agencies responsible for the collection of data and quality control are thanked for their contributions to SOCAT.
    Description: 2019-11-28
    Keywords: Carbon dioxide ; Ocean carbon sink ; Terrestrial carbon sink ; Climate variability ; Carbon budget
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  • 20
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    American Geophysical Union (AGU)
    In:  EPIC3Journal of Geophysical Research: Oceans, American Geophysical Union (AGU), 124(8), pp. 5503-5528, ISSN: 2169-9275
    Publication Date: 2022-11-02
    Repository Name: EPIC Alfred Wegener Institut
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  • 21
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    American Geophysical Union (AGU)
    In:  EPIC3Geophysical Research Letters, American Geophysical Union (AGU), 45(23), pp. 12972-12981, ISSN: 0094-8276
    Publication Date: 2023-01-30
    Description: The Arctic Ocean is known to be contaminated by various persistent organic pollutants (POPs). The Fram Strait, the only deepwater passage to the Arctic Ocean (from the Atlantic Ocean), represents an unquantified gateway for POPs fluxes into and out of the Arctic. Polyethylene passive samplers were deployed in vertical profiles in the Fram Strait and in air and surface water in the Canadian Archipelago to determine the concentrations, profiles, and mass fluxes of dissolved polychlorinated biphenyls (PCBs) and organochlorine pesticides. In the Fram Strait, higher concentrations of ΣPCBs (1.3–3.6 pg/L) and dichlorodiphenyltrichloroethanes (ΣDDTs, 5.2–9.1 pg/L) were observed in the deepwater masses (below 1,000 m), similar to nutrient-like vertical profiles. There was net southward transport of hexachlorobenzene and hexachlorocyclohexanes (ΣHCHs) of 0.70 and 14 Mg/year but a net northward transport of ΣPCBs at 0.16 Mg/year through the Fram Strait.
    Repository Name: EPIC Alfred Wegener Institut
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  • 22
    Electronic Resource
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 29 (2000), S. 27-47 
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract Owing to the rapid development of in vivo applications for non-viral gene delivery vectors, it is necessary to have a better understanding of how the structure-activity relationships of these lipid-DNA complexes are affected by their environment. Indeed, research in gene therapy first focused on in vitro cell culture studies to determine the mechanisms involved in the delivery of DNA into the cell. New biophysical techniques such as electron microscopy and X-ray diffraction have been developed to discern the structure of the lipid-DNA complex. However, further studies have revealed discrepancies between optimal lipid-DNA formulations for in vitro transfection and for in vivo administration of these vectors. Furthermore, some immune stimulatory effects have been associated with in vivo lipid-DNA administration. This review summarizes the current state of knowledge on in vitro and in vivo lipid-DNA complex transfections. New prospects of vectors for in vivo gene transfer are also discussed.
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  • 23
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 29 (2000), S. 81-103 
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract Hundreds of acetyltransferases exist. All use a common acetyl donor-acetyl coenzyme A-and each exhibits remarkable specificity for acetyl acceptors, which include small molecules and proteins. Analysis of the primary sequences of these enzymes indicates that they can be sorted into several superfamilies. This review covers the three-dimensional structures of members of one of these superfamilies, now referred to in the literature as the GCN5-related N-acetyltransferases (GNAT), reflecting the importance of one functional category, the histone acetyltransferases. Despite the diversity of substrate specificities, members of the GNAT superfamily demonstrate remarkable similarity in protein topology and mode of acetyl coenzyme A binding, likely reflecting a conserved catalytic mechanism.
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  • 24
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 29 (2000), S. 49-79 
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract Protein kinase C homology-1 and -2, FYVE, and pleckstrin homology domains are ubiquitous in eukaryotic signal transduction and membrane-trafficking proteins. These domains regulate subcellular localization and protein function by binding to lipid ligands embedded in cell membranes. Structural and biochemical analysis of these domains has shown that their molecular mechanisms of membrane binding depend on a combination of specific and nonspecific interactions with membrane lipids. In vivo studies of green fluorescent protein fusions have highlighted the key roles of these domains in regulating protein localization to plasma and internal membranes in cells.
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  • 25
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 29 (2000), S. 1-26 
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract Although the force fields and interaction energies that control protein behavior can be inferred indirectly from equilibrium and kinetic measurements, recent developments have made it possible to quantify directly (a) the ranges, magnitudes, and time dependence of the interaction energies and forces between biological materials; (b) the mechanical properties of isolated proteins; and (c) the strength of single receptor-ligand bonds. This review describes recent results obtained by using the atomic force microscope, optical tweezers, the surface force apparatus, and micropipette aspiration to quantify short-range protein-ligand interactions and the long-range, nonspecific forces that together control protein behavior. The examples presented illustrate the power of force measurements to quantify directly the force fields and energies that control protein behavior.
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  • 26
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 29 (2000), S. 183-212 
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract Cys2His2 zinc fingers are one of the most common DNA-binding motifs found in eukaryotic transcription factors. These proteins typically contain several fingers that make tandem contacts along the DNA. Each finger has a conserved betabetaalpha structure, and amino acids on the surface of the alpha-helix contact bases in the major groove. This simple, modular structure of zinc finger proteins, and the wide variety of DNA sequences they can recognize, make them an attractive framework for attempts to design novel DNA-binding proteins. Several studies have selected fingers with new specificities, and there clearly are recurring patterns in the observed side chain-base interactions. However, the structural details of recognition are intricate enough that there are no general rules (a "recognition code") that would allow the design of an optimal protein for any desired target site. Construction of multifinger proteins is also complicated by interactions between neighboring fingers and the effect of the intervening linker. This review analyzes DNA recognition by Cys2His2 zinc fingers and summarizes progress in generating proteins with novel specificities from fingers selected by phage display.
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  • 27
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 29 (2000), S. 327-359 
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract This review describes how kinetic experiments using techniques with dramatically improved time resolution have contributed to understanding mechanisms in protein folding. Optical triggering with nanosecond laser pulses has made it possible to study the fastest-folding proteins as well as fundamental processes in folding for the first time. These include formation of alpha-helices, beta-sheets, and contacts between residues distant in sequence, as well as overall collapse of the polypeptide chain. Improvements in the time resolution of mixing experiments and the use of dynamic nuclear magnetic resonance methods have also allowed kinetic studies of proteins that fold too fast (〉 103 s-1) to be observed by conventional methods. Simple statistical mechanical models have been extremely useful in interpreting the experimental results. One of the surprises is that models originally developed for explaining the fast kinetics of secondary structure formation in isolated peptides are also successful in calculating folding rates of single domain proteins from their native three-dimensional structure.
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  • 28
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 29 (2000), S. 411-438 
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract ClC-type chloride channels are ubiquitous throughout the biological world. Expressed in nearly every cell type, these proteins have a host of biological functions. With nine distinct homologues known in eukaryotes, the ClCs represent the only molecularly defined family of chloride channels. ClC channels exhibit features of molecular architecture and gating mechanisms unprecedented in other types of ion channels. They form two-pore homodimers, and their voltage-dependence arises not from charged residues in the protein, but rather via coupling of gating to the movement of chloride ions within the pore. Because the functional characteristics of only a few ClC channels have been studied in detail, we are still learning which properties are general to the whole family. New approaches, including structural analyses, will be crucial to an understanding of ClC architecture and function.
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  • 29
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 29 (2000), S. 439-461 
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract In the past decade, a general design for sequence-specific minor groove ligands has evolved, based on the natural products distamycin and netropsin. By utilizing a basic set of design rules for connecting pyrrole, imidazole, and hydroxypyrrole modules, new ligands can be prepared to target almost any sequence of interest with both high affinity and specificity. In this review we present the design rules with a brief history of how they evolved. The structural basis for sequence-specific recognition is explained, together with developments that allow linking of recognition modules that enable targeting of long DNA sequences. Examples of the affinity and specificity that can be achieved with a number of variations on the basic design are given. Recently these molecules have been used to compete with proteins both in vitro and in vivo, and a brief description of the experimental results are given.
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  • 30
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 30 (2001), S. 129-155 
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract NMR spin relaxation spectroscopy is a powerful approach for characterizing intramolecular and overall rotational motions in proteins. This review describes experimental methods for measuring laboratory frame spin relaxation rate constants by high-resolution solution-state NMR spectroscopy, together with theoretical approaches for interpreting spin relaxation data in order to quantify protein conformational dynamics on picosecond-nanosecond time scales. Recent applications of these techniques to proteins are surveyed, and investigations of the contribution of conformational chain entropy to protein function are highlighted. Insights into the dynamical properties of proteins obtained from NMR spin relaxation spectroscopy are compared with results derived from other experimental and theoretical techniques.
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  • 31
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 30 (2001), S. 157-171 
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract The fusion of vesicles with target membranes is controlled by a complex network of protein-protein and protein-lipid interactions. Structures of the SNARE complex, synaptotagmin III, nSec1, domains of the NSF chaperone and its adaptor SNAP, and Rab3 and some of its effectors provide the framework for developing molecular models of vesicle fusion and for designing experiments to test these models.
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  • 32
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 30 (2001), S. 173-189 
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract Considerable recent progress has been made in the field of ab initio protein structure prediction, as witnessed by the third Critical Assessment of Structure Prediction (CASP3). In spite of this progress, much work remains, for the field has yet to produce consistently reliable ab initio structure prediction protocols. In this work, we review the features of current ab initio protocols in an attempt to highlight the foundations of recent progress in the field and suggest promising directions for future work.
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  • 33
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 30 (2001), S. 191-209 
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract Species and tissue-specific isozymes of phosphorylase display differences in regulatory properties consistent with their distinct roles in particular organisms and tissues. In this review, we compare crystallographic structures of regulated and unregulated phosphorylases, including maltodextrin phosphorylase (MalP) from Escherichia coli, glycogen phosphorylase from yeast, and mammalian isozymes from muscle and liver tissues. Mutagenesis and functional studies supplement the structural work and provide insights into the structural basis for allosteric control mechanisms. MalP, a simple, unregulated enzyme, is contrasted with the more complicated yeast and mammalian phosphorylases that have evolved regulatory sites onto the basic catalytic architecture. The human liver and muscle isozymes show differences structurally in their means of invoking allosteric activation. Phosphorylation, though common to both the yeast and mammalian enzymes, occurs at different sites and activates the enzymes by surprisingly different mechanisms.
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  • 34
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract Computer modeling has been developed and widely applied in studying molecules of biological interest. The force field is the cornerstone of computer simulations, and many force fields have been developed and successfully applied in these simulations. Two interesting areas are (a) studying enzyme catalytic mechanisms using a combination of quantum mechanics and molecular mechanics, and (b) studying macromolecular dynamics and interactions using molecular dynamics (MD) and free energy (FE) calculation methods. Enzyme catalysis involves forming and breaking of covalent bonds and requires the use of quantum mechanics. Noncovalent interactions appear ubiquitously in biology, but here we confine ourselves to review only noncovalent interactions between protein and protein, protein and ligand, and protein and nucleic acids.
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    Annual Review of Biophysics and Biomolecular Structure 30 (2001), S. 245-269 
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract Molecular chaperones are required to assist folding of a subset of proteins in Escherichia coli. We describe a conceptual framework for understanding how the GroEL-GroES system assists misfolded proteins to reach their native states. The architecture of GroEL consists of double toroids stacked back-to-back. However, most of the fundamentals of the GroEL action can be described in terms of the single ring. A key idea in our framework is that, with coordinated ATP hydrolysis and GroES binding, GroEL participates actively by repeatedly unfolding the substrate protein (SP), provided that it is trapped in one of the misfolded states. We conjecture that the unfolding of SP becomes possible because a stretching force is transmitted to the SP when the GroEL particle undergoes allosteric transitions. Force-induced unfolding of the SP puts it on a higher free-energy point in the multidimensional energy landscape from which the SP can either reach the native conformation with some probability or be trapped in one of the competing basins of attraction (i.e., the SP undergoes kinetic partitioning). The model shows, in a natural way, that the time scales in the dynamics of the allosteric transitions are intimately coupled to folding rates of the SP. Several scenarios for chaperonin-assisted folding emerge depending on the interplay of the time scales governing the cycle. Further refinement of this framework may be necessary because single molecule experiments indicate that there is a great dispersion in the time scales governing the dynamics of the chaperonin cycle.
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    Annual Review of Biophysics and Biomolecular Structure 31 (2002), S. 1-44 
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    Annual Review of Biophysics and Biomolecular Structure 30 (2001), S. 421-455 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Abstract The mammalian thioredoxins are a family of small (approximately 12 kDa) redox proteins that undergo NADPH-dependent reduction by thioredoxin reductase and in turn reduce oxidized cysteine groups on proteins. The two main thioredoxins are thioredoxin-1, a cytosolic and nuclear form, and thioredoxin-2, a mitochondrial form. Thioredoxin-1 has been studied more. It performs many biological actions including the supply of reducing equivalents to thioredoxin peroxidases and ribonucleotide reductase, the regulation of transcription factor activity, and the regulation of enzyme activity by heterodimer formation. Thioredoxin-1 stimulates cell growth and is an inhibitor of apoptosis. Thioredoxins may play a role in a variety of human diseases including cancer. An increased level of thioredoxin-1 is found in many human tumors, where it is associated with aggressive tumor growth. Drugs are being developed that inhibit thioredoxin and that have antitumor activity.
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    Annual Review of Biophysics and Biomolecular Structure 31 (2002), S. 177-206 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Abstract Early NMR structural studies of serum lipoproteins were based on 1H, 13C, 31P, and 2H studies of lipid components. From the early studies information on composition, lipid chain dynamics and order parameters, and monolayer organization resulted. More recently, selective or complete isotopic labeling techniques, combined with multidimensional NMR spectroscopy, have resulted in structural information of apoprotein fragments. Finally, use of heteronuclear three- and four-dimensional experiments have yielded solution structures and protein-lipid interactions of intact apolipoproteins C-I, C-II, and A-I.
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    Annual Review of Biophysics and Biomolecular Structure 31 (2002), S. 235-256 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Abstract During the course of their biological function, proteins undergo different types of structural rearrangements ranging from local to large-scale conformational changes. These changes are usually triggered by their interactions with small-molecular-weight ligands or other macromolecules. Because binding interactions occur at specific sites and involve only a small number of residues, a chain of cooperative interactions is necessary for the propagation of binding signals to distal locations within the protein structure. This process requires an uneven structural distribution of protein stability and cooperativity as revealed by NMR-detected hydrogen/deuterium exchange experiments under native conditions. The distribution of stabilizing interactions does not only provide the architectural foundation to the three-dimensional structure of a protein, but it also provides the required framework for functional cooperativity. In this review, the statistical thermodynamic linkage between protein stability, functional cooperativity, and ligand binding is discussed.
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    Annual Review of Biophysics and Biomolecular Structure 30 (2001), S. 271-306 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Abstract Proteins are designed to function in environments crowded by cosolutes, but most studies of protein equilibria are conducted in dilute solution. While there is no doubt that crowding changes protein equilibria, interpretations of the changes remain controversial. This review combines experimental observations on the effect of small uncharged cosolutes (mostly sugars) on protein stability with a discussion of the thermodynamics of cosolute-induced nonideality and critical assessments of the most commonly applied interpretations. Despite the controversy surrounding the most appropriate manner for interpreting these effects of thermodynamic nonideality arising from the presence of small cosolutes, experimental advantage may still be taken of the ability of the cosolute effect to promote not only protein stabilization but also protein self-association and complex formation between dissimilar reactants. This phenomenon clearly has potential ramifications in the cell, where the crowded environment could well induce the same effects.
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    Annual Review of Biophysics and Biomolecular Structure 30 (2001), S. 329-359 
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    Notes: Abstract Nuclear receptors (NRs) form a superfamily of ligand-inducible transcription factors composed of several domains. Recent structural studies focused on domain E, which harbors the ligand-binding site and the ligand-dependent transcription activation function AF-2. Structures of single representatives in an increasing number of various complexes as well as new structures of further NRs addressed issues such as discrimination of ligands, superagonism, isotype specificity, and partial agonism. Until today, one unique transcriptionally active form of domain E was determined; however, divergent tertiary structures of apo-forms and transcriptionally inactive forms are known. Thus, recent results link the transformation of NRs upon ligand binding to principles of protein folding. Furthermore, the ensemble of NR structures, including those of DNA-binding domains, provides one of the foundations for the understanding of interactions with transcription intermediary factors up to the characterization of the link between NR complexes and the basal transcriptional machinery at the structural level.
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    Annual Review of Biophysics and Biomolecular Structure 30 (2001), S. 397-420 
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    Notes: Abstract Microtubules are polymers that are essential for, among other functions, cell transport and cell division in all eukaryotes. The regulation of the microtubule system includes transcription of different tubulin isotypes, folding of alpha/beta-tubulin heterodimers, post-translation modification of tubulin, and nucleotide-based microtubule dynamics, as well as interaction with numerous microtubule-associated proteins that are themselves regulated. The result is the precise temporal and spatial pattern of microtubules that is observed throughout the cell cycle. The recent high-resolution analysis of the structure of tubulin and the microtubule has brought new insight to the study of microtubule function and regulation, as well as the mode of action of antimitotic drugs that disrupt normal microtubule behavior. The combination of structural, genetic, biochemical, and biophysical data should soon give us a fuller understanding of the exquisite details in the regulation of the microtubule cytoskeleton.
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    Annual Review of Biophysics and Biomolecular Structure 30 (2001), S. 457-475 
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    Notes: Abstract The past few years have seen exciting advances in understanding the structure and function of catalytic RNA. Crystal structures of several ribozymes have provided detailed insight into the folds of RNA molecules. Models of other biologically important RNAs have been constructed based on structural, phylogenetic, and biochemical data. However, many questions regarding the catalytic mechanisms of ribozymes remain. This review compares the structures and possible catalytic mechanisms of four small self-cleaving RNAs: the hammerhead, hairpin, hepatitis delta virus, and in vitro-selected lead-dependent ribozymes. The organization of these small catalysts is contrasted to that of larger ribozymes, such as the group I intron.
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    Annual Review of Biophysics and Biomolecular Structure 31 (2002), S. 73-95 
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    Notes: Abstract Active transport requires the alternation of substrate uptake and release with a switch in the access of the substrate binding site to the two sides of the membrane. Both the transfer and switch aspects of the photocycle have been subjects of magnetic resonance studies in bacteriorhodopsin. The results for ion transfer indicate that the Schiff base of the chromophore is hydrogen bonded before, during, and after its deprotonation. This suggests that the initial complex counterion of the Schiff base decomposes in such a way that the Schiff base carries its immediate hydrogen-bonding partner with it as it rotates during the first half of the photocycle. If so, bacteriorhodopsin acts as an inward-directed hydroxide pump rather than as an outward-directed proton pump. The studies of the access switch explore both protein-based and chromophore-based mechanisms. Combined with evidence from functional studies of mutants and other forms of spectroscopy, the results suggest that maintaining access to the extracellular side of the protein after photoisomerization involves twisting of the chromophore and that the decisive switch in access to the cytoplasmic side results from relaxation of the chromophore when the constraints on the Schiff base are released by decomposition of the complex counterion.
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    Annual Review of Biophysics and Biomolecular Structure 31 (2002), S. 151-175 
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    Notes: Abstract We review the physical properties of phosphatidylinositol 4,5-bisphosphate (PIP2) that determine both its specific interactions with protein domains of known structure and its nonspecific electrostatic sequestration by unstructured domains. Several investigators have postulated the existence of distinct pools of PIP2 within the cell to account for the myriad functions of this lipid. Recent experimental work indicates certain regions of the plasma membrane-membrane ruffles and nascent phagosomes-do indeed concentrate PIP2. We consider two mechanisms that could account for this phenomenon: local synthesis and electrostatic sequestration. We conclude by considering the hypothesis that proteins such as MARCKS bind a significant fraction of the PIP2 in a cell, helping to sequester it in lateral membrane domains, then release this lipid in response to local signals such as an increased concentration of Ca++/calmodulin or activation of protein kinase C.
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    Annual Review of Biophysics and Biomolecular Structure 31 (2002), S. 121-149 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Abstract The first crystal structures of intact T cell receptors (TCRs) bound to class I peptide-MHC (pMHCs) antigens were determined in 1996. Since then, further structures of class I TCR/pMHC complexes have explored the degree of structural variability in the TCR-pMHC system and the structural basis for positive and negative selection. The recent determination of class II and allogeneic class I TCR/pMHC structures, as well as those of accessory molecules (e.g., CD3), has pushed our knowledge of TCR/pMHC interactions into new realms, shedding light on clinical pathologies, such as graft rejection and graft-versus-host disease. Furthermore, the determination of coreceptor structures lays the foundation for a more comprehensive structural description of the supramolecular TCR signaling events and those assemblies that arise in the immunological synapse. While these telling photodocumentaries of the TCR/pMHC interaction are composed mainly from static crystal structures, a full description of the biological snapshots in T cell signaling requires additional analytical methods that record the dynamics of the process. To this end, surface plasmon resonance (SPR), isothermal titration calorimetry (ITC), and ultracentrifugation (UC) have furnished both affinities and kinetics of the TCR/pMHC association. In the past year, structural, biochemical, and molecular biological data describing TCR/pMHC interactions have sublimely coalesced into a burgeoning well of understanding that promises to deliver further insights into T cell recognition. The coming years will, through a more intimate union of structural and kinetic data, allow many pressing questions to be addressed, such as how TCR/pMHC ligation is affected by coreceptor binding and what is the mechanism of TCR signaling in both early and late stages of T cell engagement with antigen-presenting cells.
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    Annual Review of Biophysics and Biomolecular Structure 31 (2002), S. 207-233 
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    Notes: Abstract The structures of an increasing number of channels and other alpha-helical membrane proteins have been determined recently, including the KcsA potassium channel, the MscL mechanosensitive channel, and the AQP1 and GlpF members of the aquaporin family. In this chapter, the orientation and packing characteristics of bilayer-spanning helices are surveyed in integral membrane proteins. In the case of channels, alpha-helices create the sealed barrier that separates the hydrocarbon region of the bilayer from the permeation pathway for solutes. The helices surrounding the permeation pathway tend to be rather steeply tilted relative to the membrane normal and are consistently arranged in a right-handed bundle. The helical framework further provides a supporting scaffold for nonmembrane-spanning structures associated with channel selectivity. Although structural details remain scarce, the conformational changes associated with gating transitions between closed and open states of channels are reviewed, emphasizing the potential roles of helix-helix interactions in this process.
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    Annual Review of Biophysics and Biomolecular Structure 31 (2002), S. 275-302 
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    Notes: Abstract Using luminescent lanthanides, instead of conventional fluorophores, as donor molecules in resonance energy transfer measurements offers many technical advantages and opens up a wide range of new applications. Advantages include farther measurable distances (~100 A) with greater accuracy, insensitivity to incomplete labeling, and the ability to use generic relatively large labels, when necessary. Applications highlighted include the study of ion channels in living cells, protein-protein interaction in cells, DNA-protein complexes, and high-throughput screening assays to measure peptide dimerization associated with DNA transcription factors and ligand-receptor interactions.
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    Annual Review of Biophysics and Biomolecular Structure 31 (2002), S. 303-319 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Abstract Cryo-electron microscopy (cryo-EM) of biological molecules in single-particle (i.e., unordered, nonaggregated) form is a new approach to the study of molecular assemblies, which are often too large and flexible to be amenable to X-ray crystallography. New insights into biological function on the molecular level are expected from cryo-EM applied to the study of such complexes "trapped" at different stages of their conformational changes and dynamical interactions. Important molecular machines involved in the fundamental processes of transcription, mRNA splicing, and translation are examples for successful applications of the new technique, combined with structural knowledge gained by conventional techniques of structure determination, such as X-ray crystallography and NMR.
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    Annual Review of Biophysics and Biomolecular Structure 31 (2002), S. 443-484 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Abstract The recent report of the crystal structure of rhodopsin provides insights concerning structure-activity relationships in visual pigments and related G protein-coupled receptors (GPCRs). The seven transmembrane helices of rhodopsin are interrupted or kinked at multiple sites. An extensive network of interhelical interactions stabilizes the ground state of the receptor. The ligand-binding pocket of rhodopsin is remarkably compact, and several chromophore-protein interactions were not predicted from mutagenesis or spectroscopic studies. The helix movement model of receptor activation, which likely applies to all GPCRs of the rhodopsin family, is supported by several structural elements that suggest how light-induced conformational changes in the ligand-binding pocket are transmitted to the cytoplasmic surface. The cytoplasmic domain of the receptor includes a helical domain extending from the seventh transmembrane segment parallel to the bilayer surface. The cytoplasmic surface appears to be approximately large enough to bind to the transducin heterotrimer in a one-to-one complex. The structural basis for several unique biophysical properties of rhodopsin, including its extremely low dark noise level and high quantum efficiency, can now be addressed using a combination of structural biology and various spectroscopic methods. Future high-resolution structural studies of rhodopsin and other GPCRs will form the basis to elucidate the detailed molecular mechanism of GPCR-mediated signal transduction.
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    Annual Review of Biophysics and Biomolecular Structure 31 (2002), S. 485-516 
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    Notes: Abstract Integrins are a structurally elaborate family of heterodimers that mediate divalent cation-dependent cell adhesion in a wide range of biological contexts. The inserted (I) domain binds ligand in the subset of integrins in which it is present. Its structure has been determined in two alternative conformations, termed open and closed. In striking similarity to signaling G proteins, rearrangement of a Mg2+-binding site is linked to large conformational movements in distant backbone regions. Mutations have been used to stabilize either the closed or open structures. These show that the snapshots of the open conformation seen only in the presence of a ligand or a ligand mimetic represent a high-affinity, ligand-binding conformation, whereas those of the closed conformation correspond to a low-affinity conformation. The C-terminal alpha-helix moves 10 A down the side of the domain in the open conformation. Locking in the conformation of the preceding loop is sufficient to increase affinity for ligand 9000-fold. This C-terminal "bell-rope" provides a mechanism for linkage to conformational movements in other domains. The transition from the closed to open conformation has been implicated in fast (〈1 s) regulation of integrin affinity in response to activation signals from inside the cell. Recent integrin structures and functional studies reveal interactions between beta-propeller, I, and I-like domains in the headpiece, and a critical role for integrin EGF domains in the stalk region. These studies suggest that the headpiece of the integrin faces down toward the membrane in the inactive conformation and extends upward in a "switchblade"-like opening motion upon activation. These long-range structural rearrangements of the entire integrin molecule involving multiple interdomain contacts appear closely linked to conformational changes in the I domain, which result in increased affinity and competence for ligand binding.
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    Annual Review of Biophysics and Biomolecular Structure 32 (2003), S. 47-67 
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    Notes: Abstract Optical single transporter recording (OSTR) is an emerging technique for the fluorescence microscopic measurement of transport kinetics in membrane patches. Membranes are attached to transparent microarrays of cylindrical test compartments (TCs) ~0.1-100 mum in diameter and ~10-100 mum in depth. Transport across membrane patches that may contain single transporters or transporter populations is recorded by confocal microscopy. By these means transport of proteins through single nuclear pore complexes has been recorded at rates of 〈1 translocation/s. In addition to the high sensitivity in terms of measurable transport rates OSTR features unprecedented spatial selectivity and parallel processing. This article reviews the conceptual basis of OSTR and its realization. Applications to nuclear transport are summarized. The further development of OSTR is discussed and its extension to a diversity of transporters, including translocases and ATP-binding cassette (ABC) pumps, projected.
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    Annual Review of Biophysics and Biomolecular Structure 32 (2003), S. 93-114 
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    Notes: Abstract Since mid-1990, with cloning and identification of several families of natural killer (NK) receptors, research on NK cells began to receive appreciable attention. Determination of structures of NK cell surface receptors and their ligand complexes led to a fast growth in our understanding of the activation and ligand recognition by these receptors as well as their function in innate immunity. Functionally, NK cell surface receptors are divided into two groups, the inhibitory and the activating receptors. Structurally, they belong to either the immunoglobulin (Ig)-like receptor superfamily or the C-type lectin-like receptor (CTLR) superfamily. Their ligands are either members of class I major histocompatibility complexes (MHC) or homologs of class I MHC molecules. The inhibitory form of NK receptors provides the protective immunity through recognizing class I MHC molecules with self-peptides on healthy host cells. The activating, or the noninhibitory, NK receptors mediate the killing of tumor or virally infected cells through their specific ligand recognition. The structures of activating and inhibitory NK cell surface receptors and their complexes with the ligands determined to date, including killer immunoglobulin-like receptors (KIRs) and their complexes with HLA molecules, CD94, Ly49A, and its complex with H-2Dd, and NKG2D receptors and their complexes with class I MHC homologs, are reviewed here.
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    Annual Review of Biophysics and Biomolecular Structure 32 (2003), S. 161-182 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Abstract Recent years have witnessed a renaissance of fluorescence microscopy techniques and applications, from live-animal multiphoton confocal microscopy to single-molecule fluorescence spectroscopy and imaging in living cells. These achievements have been made possible not so much because of improvements in microscope design, but rather because of development of new detectors, accessible continuous wave and pulsed laser sources, sophisticated multiparameter analysis on one hand, and the development of new probes and labeling chemistries on the other. This review tracks the lineage of ideas and the evolution of thinking that have led to the actual developments, and presents a comprehensive overview of the field, with emphasis put on our laboratory's interest in single-molecule microscopy and spectroscopy.
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    Annual Review of Biophysics and Biomolecular Structure 32 (2003), S. 135-159 
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    Notes: Abstract The lamba integrase, or tyrosine-based family of site-specific recombinases, plays an important role in a variety of biological processes by inserting, excising, and inverting DNA segments. Flp, encoded by the yeast 2-mum plasmid, is the best-characterized eukaryotic member of this family and is responsible for maintaining the copy number of this plasmid. Over the past several years, structural and biochemical studies have shed light on the details of a common catalytic scheme utilized by these enzymes with interesting variations under different biological contexts. The emergence of new Flp structures and solution data provides insights not only into its unique mechanism of active site assembly and activity regulation but also into the specific contributions of certain protein residues to catalysis.
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    Annual Review of Biophysics and Biomolecular Structure 32 (2003), S. 285-310 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Abstract The past decade has witnessed increasingly detailed insights into the structural mechanism of the bacteriorhodopsin photocycle. Concurrently, there has been much progress within our knowledge pertaining to the lipids of the purple membrane, including the discovery of new lipids and the overall effort to localize and identify each lipid within the purple membrane. Therefore, there is a need to classify this information to generalize the findings. We discuss the properties and roles of haloarchaeal lipids and present the structural data as individual case studies. Lipid-protein interactions are discussed in the context of structure-function relationships. A brief discussion of the possibility that bacteriorhodopsin functions as a light-driven inward hydroxide pump rather than an outward proton pump is also presented.
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    Annual Review of Biophysics and Biomolecular Structure 32 (2003), S. 375-397 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Abstract G protein-coupled receptors (GPCRs) are integral membrane proteins that respond to environmental signals and initiate signal transduction pathways activating cellular processes. Rhodopsin is a GPCR found in rod cells in retina where it functions as a photopigment. Its molecular structure is known from cryo-electron microscopic and X-ray crystallographic studies, and this has reshaped many structure/function questions important in vision science. In addition, this first GPCR structure has provided a structural template for studies of other GPCRs, including many known drug targets. After presenting an overview of the major structural elements of rhodopsin, recent literature covering the use of the rhodopsin structure in analyzing other GPCRs will be summarized. Use of the rhodopsin structural model to understand the structure and function of other GPCRs provides strong evidence validating the structural model.
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    Annual Review of Biophysics and Biomolecular Structure 32 (2003), S. 399-424 
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    Notes: Abstract The coupling of high-performance mass spectrometry instrumentation with highly efficient chromatographic and electrophoretic separations has enabled rapid qualitative and quantitative analysis of thousands of proteins from minute samples of biological materials. Here, we review recent progress in the development and application of mass spectrometry-based techniques for the qualitative and quantitative analysis of global proteome samples derived from whole cells, tissues, or organisms. Techniques such as multidimensional peptide and protein separations coupled with mass spectrometry, accurate mass measurement of peptides from global proteome digests, and mass spectrometric characterization of intact proteins hold great promise for characterization of highly complex protein mixtures. Advances in chemical tagging and isotope labeling techniques have enabled quantitative analysis of proteomes, and highly specific isolation strategies have been developed aimed at selective analysis of posttranslationally modified proteins.
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    Annual Review of Biophysics and Biomolecular Structure 33 (2004), S. 387-413 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Residual dipolar couplings (RDCs) have recently emerged as a new tool in nuclear magnetic resonance (NMR) with which to study macromolecular structure and function in a solution environment. RDCs are complementary to the more conventional use of NOEs to provide structural information. While NOEs are local-distance restraints, RDCs provide long-range orientational information. RDCs are now widely utilized in structure calculations. Increasingly, they are being used in novel applications to address complex issues in structural biology such as the accurate determination of the global structure of oligonucleotides and the relative orientation of protein domains. This review briefly describes the theory and methods for obtaining RDCs and then describes the range of biological applications where RDCs have been used.
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    Annual Review of Biophysics and Biomolecular Structure 33 (2004), S. 269-295 
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    Notes: Views of how cell membranes are organized are presently changing. The lipid bilayer that constitutes these membranes is no longer understood to be a homogeneous fluid. Instead, lipid assemblies, termed rafts, have been introduced to provide fluid platforms that segregate membrane components and dynamically compartmentalize membranes. These assemblies are thought to be composed mainly of sphingolipids and cholesterol in the outer leaflet, somehow connected to domains of unknown composition in the inner leaflet. Specific classes of proteins are associated with the rafts. This review critically analyzes what is known of phase behavior and liquid-liquid immiscibility in model systems and compares these data with what is known of domain formation in cell membranes.
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    Annual Review of Cell and Developmental Biology 17 (2001), S. 53-86 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract The bacterial pathogen Salmonella enterica has evolved a very sophisticated functional interface with its vertebrate hosts. At the center of this interface is a specialized organelle, the type III secretion system, that directs the translocation of bacterial proteins into the host cell. Salmonella spp. encode two such systems that deliver a remarkable array of bacterial proteins capable of modulating a variety of cellular functions, including actin cytoskeleton dynamics, nuclear responses, and endocytic trafficking. Many of these bacterial proteins operate by faithful mimicry of host proteins, in some cases representing the result of extensive molecular tinkering and convergent evolution. The coordinated action of these type III secreted proteins secures the replication and survival of the bacteria avoiding overt damage to the host. The study of this remarkable pathogen is not only illuminating general paradigms in microbial pathogenesis but is also providing valuable insight into host cell functions.
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    Annual Review of Cell and Developmental Biology 17 (2001), S. 87-132 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract Vertebrate limb buds are embryonic structures for which much molecular and cellular data are known regarding the mechanisms that control pattern formation during development. Specialized regions of the developing limb bud, such as the zone of polarizing activity (ZPA), the apical ectodermal ridge (AER), and the non-ridge ectoderm, direct and coordinate the development of the limb bud along the anterior-posterior (AP), dorsal-ventral (DV), and proximal-distal (PD) axes, giving rise to a stereotyped pattern of elements well conserved among tetrapods. In recent years, specific gene functions have been shown to mediate the organizing and patterning activities of the ZPA, the AER, and the non-ridge ectoderm. The analysis of these gene functions has revealed the existence of complex interactions between signaling pathways operated by secreted factors of the HH, TGF-beta/BMP, WNT, and FGF superfamilies, which interact with many other genetic networks to control limb positioning, outgrowth, and patterning. The study of limb development has helped to establish paradigms for the analysis of pattern formation in many other embryonic structures and organs.
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    Annual Review of Cell and Developmental Biology 17 (2001), S. 133-157 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract Cells in the immune and nervous systems communicate through informational synapses. The two-dimensional chemistry underlying the process of synapse formation is beginning to be explored using fluorescence imaging and mechanical techniques. Early analysis of two-dimensional kinetic rates (kon and koff) and equilibrium constants (Kd) provides a number of biological insights. First, there are two regimes for adhesion-one disordered with slow kon and the other self-ordered with 104-fold faster kon. Despite huge variation in two-dimensional kon, the two-dimensional koff is like koff in solution, and two-dimensional koff is more closely related to intrinsic properties of the interaction than the two-dimensional kon. Thus difference in koff can be used to set signaling thresholds. Early signaling complexes are compartmentalized to generate synergistic signaling domains. Immune antigen receptor components have a role in neural synapse editing. This suggests significant parallels in informational synapse formation based on common two-dimensional chemistry and signaling strategies.
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    Annual Review of Cell and Developmental Biology 17 (2001), S. 159-187 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract Pollen tubes and root hairs are highly elongated, cylindrically shaped cells whose polarized growth permits them to explore the environment for the benefit of the entire plant. Root hairs create an enormous surface area for the uptake of water and nutrients, whereas pollen tubes deliver the sperm cells to the ovule for fertilization. These cells grow exclusively at the apex and at prodigious rates (in excess of 200 nm/s for pollen tubes). Underlying this rapid growth are polarized ion gradients and fluxes, turnover of cytoskeletal elements (actin microfilaments), and exocytosis and endocytosis of membrane vesicles. Intracellular gradients of calcium and protons are spatially localized at the growing apex; inward fluxes of these ions are apically directed. These gradients and fluxes oscillate with the same frequency as the oscillations in growth rate but not with the same phase. Actin microfilaments, which together with myosin generate reverse fountain streaming, undergo rapid turnover in the apical domain, possibly being regulated by key actin-binding proteins, e.g., profilin, villin, and ADF/cofilin, in concert with the ion gradients. Exocytosis of vesicles at the apex, also dependent on the ion gradients, provides precursor material for the continuously expanding cell wall of the growing cell. Elucidation of the interactions and of the dynamics of these different components is providing unique insight into the mechanisms of polarized growth.
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    Annual Review of Cell and Developmental Biology 17 (2001), S. 189-214 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract Developing organisms may contain billions of cells destined to differentiate in numerous different ways. One strategy organisms use to simplify the orchestration of development is the separation of cell populations into distinct functional units. Our expanding knowledge of boundary formation and function in different systems is beginning to reveal general principles of this process. Fields of cells are subdivided by the interpretation of morphogen gradients, and these subdivisions are then maintained and refined by local cell-cell interactions. Sharp and stable separation between cell populations requires special mechanisms to keep cells segregated, which in many cases appear to involve the regulation of cell affinity. Once cell populations become distinct, specialized cells are often induced along the borders between them. These boundary cells can then influence the patterning of surrounding cells, which can result in progressively finer subdivisions of a tissue. Much has been learned about the signaling pathways that establish boundaries, but a key challenge for the future remains to elucidate the cellular and molecular mechanisms that actually keep cell populations separated.
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    Annual Review of Cell and Developmental Biology 18 (2002), S. 25-51 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract The amyloid precursor protein and the proteases cleaving this protein are important players in the pathogenesis of Alzheimer's disease via the generation of the amyloid peptide. Physiologically, the amyloid precursor protein is implied in axonal vesicular trafficking and the proteases are implicated in developmentally important signaling pathways, most significantly those involving regulated intramembrane proteolysis or RIP. We discuss the cell biology behind the amyloid and tangle hypothesis for Alzheimer's disease, drawing on the many links to the fields of cell biology and developmental biology that have been established in the recent years.
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    Annual Review of Cell and Developmental Biology 18 (2002), S. 107-133 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract The type III mechanism of protein secretion is a pathogenic strategy shared by a number of gram-negative pathogens of plants and animals that has evolved in order to inject virulence proteins into the cytosol of target eukaryotic cells. The pathogens of the Yersinia genus represent a model system where much progress has been made in understanding this secretion pathway. Herein, we review what has been recently learned in yersiniae about the various environmental signals that induce type III secretion, how the synthesis of secretion substrates is regulated, and how such a diverse group of proteins is recognized as a substrate for secretion.
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    Annual Review of Cell and Developmental Biology 18 (2002), S. 135-161 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Abstract The host cytoskeleton plays important roles in the entry, replication, and egress of viruses. An assortment of viruses hijack cellular motor proteins to move on microtubules toward the cell interior during the entry process; others reverse this transport during egress to move assembling virus particles toward the plasma membrane. Polymerization of actin filaments is sometimes used to propel viruses from cell to cell, while many viruses induce the destruction of select cytoskeletal filaments apparently to effect efficient egress. Indeed, the tactics used by any given virus to achieve its infectious life cycle are certain to involve multiple cytoskeletal interactions. Understanding these interactions, and their orchestration during viral infections, is providing unexpected insights into basic virology, viral pathogenesis, and the biology of the cytoskeleton.
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    Annual Review of Cell and Developmental Biology 18 (2002), S. 193-219 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Abstract Spindle microtubules interact with mitotic chromosomes, binding to their kinetochores to generate forces that are important for accurate chromosome segregation. Motor enzymes localized both at kinetochores and spindle poles help to form the biologically significant attachments between spindle fibers and their cargo, but microtubule-associated proteins without motor activity contribute to these junctions in important ways. This review examines the molecules necessary for chromosome-microtubule interaction in a range of well-studied organisms, using biological diversity to identify the factors that are essential for organized chromosome movement. We conclude that microtubule dynamics and the proteins that control them are likely to be more important for mitosis than the current enthusiasm for motor enzymes would suggest.
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    Annual Review of Cell and Developmental Biology 18 (2002), S. 221-245 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract Chlamydiae, bacterial obligate intracellular pathogens, are the etiologic agents of several human diseases. A large part of the chlamydial intracellular survival strategy involves the formation of a unique organelle called the inclusion that provides a protected site within which they replicate. The chlamydial inclusion is effectively isolated from endocytic pathways but is fusogenic with a subset of exocytic vesicles that deliver sphingomyelin from the Golgi apparatus to the plasma membrane. A combination of host and parasite functions contribute to the biogenesis of this compartment. Establishment of the mature inclusion is accompanied by the insertion of multiple chlamydial proteins, suggesting that chlamydiae actively modify the inclusion to define its interactions with the eukaryotic host cell. Despite being sequestered within a membrane-bound vacuole, chlamydiae clearly communicate with and manipulate the host cell from within this privileged intracellular niche.
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    Annual Review of Cell and Developmental Biology 18 (2002), S. 463-493 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract Epithelial morphogenesis comprises the various processes by which epithelia contribute to organ formation and body shape. These complex and diverse events play a central role in animal development and regeneration. Recently, the characterization of some of the molecular mechanisms involved in epithelial morphogenesis has provided an abundance of new information on the role and regulation of the cytoskeleton, cell-cell adhesion, and cell-matrix adhesion in these processes. In this review, we discuss our current understanding of the molecular mechanisms driving cell shape changes, cell intercalation, fusion of epithelia, ingression, egression, and cell migration. Our discussion is mostly focused on results from Drosophila and mammalian tissue culture but also draws on the insights gained from other organisms.
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    Annual Review of Cell and Developmental Biology 18 (2002), S. 379-420 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract Golgi inheritance proceeds via sequential biogenesis and partitioning phases. Although little is known about Golgi growth and replication (biogenesis), ultrastructural and fluorescence analyses have provided a detailed, though still controversial, perspective of Golgi partitioning during mitosis in mammalian cells. Partitioning requires the fragmentation of the juxtanuclear ribbon of interconnected Golgi stacks into a multitude of tubulovesicular clusters. This process is choreographed by a cohort of mitotic kinases and an inhibition of heterotypic and homotypic Golgi membrane-fusion events. Our model posits that accurate partitioning occurs early in mitosis by the equilibration of Golgi components on either side of the metaphase plate. Disseminated Golgi components then coalesce to regenerate Golgi stacks during telophase. Semi-intact cell and cell-free assays have accurately recreated these processes and allowed their molecular dissection. This review attempts to integrate recent findings to depict a more coherent, synthetic molecular picture of mitotic Golgi fragmentation and reassembly. Of particular importance is the emerging concept of a highly regulated and dynamic Golgi structural matrix or template that interfaces with cargo receptors, Golgi enzymes, Rab-GTPases, and SNAREs to tightly couple biosynthetic transport to Golgi architecture. This structural framework may be instructive for Golgi biogenesis and may encode sufficient information to ensure accurate Golgi inheritance, thereby helping to resolve some of the current discrepancies between different workers.
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    Annual Review of Cell and Developmental Biology 20 (2004), S. 593-618 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: During brain development, neurons migrate great distances from proliferative zones to generate the cortical gray matter. A series of studies has identified genes that are critical for migration and targeting of neurons to specific brain regions. These genes encode three basic groups of proteins and produce three distinct phenotypes. The first group encodes cytoskeletal molecules and produces graded and dosage-dependent effects, with a significant amount of functional redundancy. This group also appears to play important roles during the initiation and ongoing progression of neuronal movement. The second group encodes signaling molecules for which homozygous mutations lead to an inverted cortex. In addition, this group is responsible for movement of neurons through anatomic boundaries to specific cortical layers. The third group encodes enzymatic regulators of glycosylation and appears to delineate where neuronal migration will arrest. There is significant cross-talk among these different groups of molecules, suggesting possible points of pathway convergence.
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    Annual Review of Cell and Developmental Biology 20 (2004), S. 725-757 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: The principles underlying regeneration in planarians have been explored for over 100 years through surgical manipulations and cellular observations. Planarian regeneration involves the generation of new tissue at the wound site via cell proliferation (blastema formation), and the remodeling of pre-existing tissues to restore symmetry and proportion (morphallaxis). Because blastemas do not replace all tissues following most types of injuries, both blastema formation and morphallaxis are needed for complete regeneration. Here we discuss a proliferative cell population, the neoblasts, that is central to the regenerative capacities of planarians. Neoblasts may be a totipotent stem-cell population capable of generating essentially every cell type in the adult animal, including themselves. The population properties of the neoblasts and their descendants still await careful elucidation. We identify the types of structures produced by blastemas on a variety of wound surfaces, the principles guiding the reorganization of pre-existing tissues, and the manner in which scale and cell number proportions between body regions are restored during regeneration.
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    Annual Review of Cell and Developmental Biology 20 (2004), S. 481-504 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Plant membrane trafficking shares many features with other eukaryotic organisms, including the machinery for vesicle formation and fusion. However, the plant endomembrane system lacks an ER-Golgi intermediate compartment, has numerous Golgi stacks and several types of vacuoles, and forms a transient compartment during cell division. ER-Golgi trafficking involves bulk flow and efficient recycling of H/KDEL-bearing proteins. Sorting in the Golgi stacks separates bulk flow to the plasma membrane from receptor-mediated trafficking to the lytic vacuole. Cargo for the protein storage vacuole is delivered from the endoplasmic reticulum (ER), cis-Golgi, and trans-Golgi. Endocytosis includes recycling of plasma membrane proteins from early endosomes. Late endosomes appear identical with the multivesiculate prevacuolar compartment that lies on the Golgi-vacuole trafficking pathway. In dividing cells, homotypic fusion of Golgi-derived vesicles forms the cell plate, which expands laterally by targeted vesicle fusion at its margin, eventually fusing with the plasma membrane.
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    Annual Review of Cell and Developmental Biology 20 (2004), S. 285-308 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: We review the current status of research in dorsal-ventral (D-V) patterning in vertebrates. Emphasis is placed on recent work on Xenopus, which provides a paradigm for vertebrate development based on a rich heritage of experimental embryology. D-V patterning starts much earlier than previously thought, under the influence of a dorsal nuclear -Catenin signal. At mid-blastula two signaling centers are present on the dorsal side: The prospective neuroectoderm expresses bone morphogenetic protein (BMP) antagonists, and the future dorsal endoderm secretes Nodal-related mesoderm-inducing factors. When dorsal mesoderm is formed at gastrula, a cocktail of growth factor antagonists is secreted by the Spemann organizer and further patterns the embryo. A ventral gastrula signaling center opposes the actions of the dorsal organizer, and another set of secreted antagonists is produced ventrally under the control of BMP4. The early dorsal -Catenin signal inhibits BMP expression at the transcriptional level and promotes expression of secreted BMP antagonists in the prospective central nervous system (CNS). In the absence of mesoderm, expression of Chordin and Noggin in ectoderm is required for anterior CNS formation. FGF (fibroblast growth factor) and IGF (insulin-like growth factor) signals are also potent neural inducers. Neural induction by anti-BMPs such as Chordin requires mitogen-activated protein kinase (MAPK) activation mediated by FGF and IGF. These multiple signals can be integrated at the level of Smad1. Phosphorylation by BMP receptor stimulates Smad1 transcriptional activity, whereas phosphorylation by MAPK has the opposite effect. Neural tissue is formed only at very low levels of activity of BMP-transducing Smads, which require the combination of both low BMP levels and high MAPK signals. Many of the molecular players that regulate D-V patterning via regulation of BMP signaling have been conserved between Drosophila and the vertebrates.
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    Annual Review of Cell and Developmental Biology 20 (2004), S. 455-480 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Macrophages are essential modulators of lipid metabolism and the innate immune system. Lipid and inflammatory pathways induced in activated macrophages are central to the pathogenesis of human diseases including atherosclerosis. Recent work has shown that expression of genes involved in lipid uptake and cholesterol efflux in macrophages is controlled by peroxisome proliferator-activated receptors (PPARs) and liver X receptors (LXRs). Other studies have implicated these same receptors in the modulation of macrophage inflammatory gene expression. Together, these observations position PPARs and LXRs at the crossroads of lipid metabolism and inflammation and suggest that these receptors may serve to integrate these pathways in the control of macrophage gene expression. In this review, we summarize recent work that has advanced our understanding of the roles of PPARs and LXRs in macrophage biology and discuss the implication of these results for cardiovascular physiology and disease.
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    Annual Review of Cell and Developmental Biology 20 (2004), S. 87-123 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: The endoplasmic reticulum (ER) and the Golgi comprise the first two steps in protein secretion. Vesicular carriers mediate a continuous flux of proteins and lipids between these compartments, reflecting the transport of newly synthesized proteins out of the ER and the retrieval of escaped ER residents and vesicle machinery. Anterograde and retrograde transport is mediated by distinct sets of cytosolic coat proteins, the COPII and COPI coats, respectively, which act on the membrane to capture cargo proteins into nascent vesicles. We review the mechanisms that govern coat recruitment to the membrane, cargo capture into a transport vesicle, and accurate delivery to the target organelle.
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    Annual Review of Cell and Developmental Biology 20 (2004), S. 427-453 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: The one-cell Caenorhabditis elegans embryo divides asymmetrically into a larger and smaller blastomere, each with a different fate. How does such asymmetry arise? The sperm-supplied centrosome establishes an axis of polarity in the embryo that is transduced into the establishment of anterior and posterior cortical domains. These cortical domains define the polarity of the embryo, acting upstream of the PAR proteins. The PAR proteins, in turn, determine the subsequent segregation of fate determinants and the plane of cell division. We address how cortical asymmetry could be established, relying on data from C. elegans and other polarized cells, as well as from applicable models. We discuss how cortical polarity influences spindle position to accomplish an asymmetric division, presenting the current models of spindle orientation and anaphase spindle displacement. We focus on asymmetric cell division as a function of the actin and microtubule cytoskeletons, emphasizing the cell biology of polarity.
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    Annual Review of Cell and Developmental Biology 20 (2004), S. 695-723 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: The study of the epithelium of the adult mammalian intestine touches upon many modern aspects of biology. The epithelium is in a constant dialogue with the underlying mesenchyme to control stem cell activity, proliferation in transit-amplifying compartments, lineage commitment, terminal differentiation and, ultimately, cell death. There are spatially distinct compartments dedicated to each of these events. The Wnt, TGF-beta, BMP, Notch, and Par polarity pathways are the major players in homeostatic control of the adult epithelium. Several hereditary cancer syndromes deregulate these same signaling cascades through mutational (in)activation. Moreover, these mutations often also occur in sporadic tumors. Thus symmetry exists between the roles that these signaling pathways play in physiology and in cancer of the intestine. This is particularly evident for the Wnt/APC pathway, for which the mammalian intestine has become one of the most-studied paradigms. Here, we integrate recent knowledge of the molecular inner workings of the prototype signaling cascades with their specific roles in intestinal epithelial homeostasis and in neoplastic transformation of the epithelium.
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    Annual Review of Materials Research 33 (2003), S. 557-579 
    ISSN: 1531-7331
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract Combinatorial methods provide a means for accelerating the discovery of fuel cell catalysts. The first example of parallel fuel cell catalysts screening was an indirect method that used fluorescent chemosensors to detect changes in pH in proximity to electrocatalyst spots. Serial direct electrochemical methods have been developed that use voltammetry, chronoamperometry, and scanning electrochemical microscopy. An array fuel cell screens catalysts simultaneously, using high-performance fuel cell components. Heuristic models based on mechanistic and spectroscopic studies provide guidance for library development, and detailed studies of discovered catalysts can help to refine these models. The remaining challenges are the development of high throughput synthetic methods that can enable the use of discovery level and focus level screening. Until these synthetic methods are developed, a greater emphasis should be placed on smaller libraries with design of experiment strategies leveraged with informatics and data mining.
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    Annual Review of Materials Research 33 (2003), S. 503-555 
    ISSN: 1531-7331
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract The past 10 years have witnessed a tremendous acceleration in research devoted to non-fluorinated polymer membranes, both as competitive alternatives to commercial perfluorosulfonic acid membranes operating in the same temperature range and with the objective of extending the range of operation of polymer fuel cells toward those more generally occupied by phosphoric acid fuel cells. Important requirements are adequate membrane mechanical strength at levels of functionalization (generally sulfonation) and hydration allowing high proton conductivity, and stability in the aggressive environment of a working fuel cell, in particular thermohydrolytic and chemical stability. This review provides an overview of progress made in the development of proton-conducting hydrocarbon and heterocyclic-based polymers for proton exchange and direct methanol fuel cells and describes the various approaches made to polymer modification/synthesis and salient properties of the materials formed, including those relating to proton transport and proton conductivity, e.g., water diffusion and electro-osmotic drag. The microstructure, deduced from small angle X-ray and neutron diffraction measurements of representative non-fluorinated polymers is compared with that of perfluorosulfonic acid membranes. Different degradation mechanisms and aging processes that can result in chemical and morphological alteration are considered, and recent characterization of membrane-electrode assemblies (MEAs) in direct methanol and hydrogen-air (oxygen) fuel cells completes this review of the state of the art. While several types of non-fluorinated polymer membrane have demonstrated lifetimes of 500-4000 h, only a limited number of systems exist that hold promise for long-term operation above 100oC.1
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    Annual Review of Materials Research 34 (2004), S. 83-122 
    ISSN: 1531-7331
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Semiconductor nanowires and nanotubes exhibit novel electronic and optical properties owing to their unique structural one-dimensionality and possible quantum confinement effects in two dimensions. With a broad selection of compositions and band structures, these one-dimensional semiconductor nanostructures are considered to be the critical components in a wide range of potential nanoscale device applications. To fully exploit these one-dimensional nanostructures, current research has focused on rational synthetic control of one-dimensional nanoscale building blocks, novel properties characterization and device fabrication based on nanowire building blocks, and integration of nanowire elements into complex functional architectures. Significant progress has been made in a few short years. This review highlights the recent advances in the field, using work from this laboratory for illustration. The understanding of general nanocrystal growth mechanisms serves as the foundation for the rational synthesis of semiconductor heterostructures in one dimension. Availability of these high-quality semiconductor nanostructures allows systematic structural-property correlation investigations, particularly of a size- and dimensionality-controlled nature. Novel properties including nanowire microcavity lasing, phonon transport, interfacial stability and chemical sensing are surveyed.
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    Annual Review of Materials Research 34 (2004), S. 1-40 
    ISSN: 1531-7331
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Highly strained semiconductors grow epitaxially on mismatched substrates in the Stranski-Krastanow growth mode, wherein islands are formed after a few monolayers of layer-by-layer growth. Elastic relaxation on the facet edges, renormalization of the surface energy of the facets, and interaction between neighboring islands via the substrate are the driving forces for self-organized growth. The dimensions of the defect-free islands are of the order lambaB, the de Broglie wavelength, and provide three-dimensional quantum confinement of carriers. Self-organized In(Ga)As/GaAs quantum dots, or quantum boxes, are grown by molecular beam expitaxy (MBE) or metal-organic vapor phase epitaxy (MOVPE) on GaAs, InP, and other substrates and are being incorporated in microelectronic and opto-electronic devices. The use of strain to produce self-organized quantum dots has now become a well-accepted approach and is widely used in III-V semiconductors and other material systems. Much progress has been made in the area of growth, where focus has been on size control, and on optical characterization, where the goal has been the application to lasers and detectors. The unique carrier dynamics in the dots, characterized by femtosecond pump-probe spectroscopy, has led to novel device applications. This article reviews the growth and electronic properties of InGaAs quantum dots and the characteristics of interband and intersublevel lasers and detectors and modulation devices.
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    Annual Review of Materials Research 34 (2004), S. 123-150 
    ISSN: 1531-7331
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Carbon nanotubes functionalized with biological molecules (such as protein peptides and nucleic acids) show great potential for application in bioengineering and nanotechnology. Fundamental understanding, description, and regulation of such bio-nano-systems will ultimately lead to a new generation of integrated systems that combine unique properties of the carbon nanotube (CNT) with biological recognition capabilities. In this review, we describe recent advances in understanding the interactions between deoxyribonucleic acids (DNA) and CNT, as well as relevant simulation techniques. We also review progress in simulating DNA noncovalent interactions with CNTs in an aqueous environment. Molecular dynamics simulations indicate that DNA molecules may be encapsulated inside or wrap around CNT owing to van der Waals attraction between DNA and CNT. We focus on the dynamics and energetics of DNA encapsulation inside nanotubes and discuss the mechanism of encapsulation and the effects of nanotube size, nanotube end-group, DNA base sequence, solvent temperature and pressure on the encapsulation process. Finally, we discuss the likely impact of DNA encapsulation on bioengineering and nanotechnology, as well as other potential applications.
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    Annual Review of Materials Research 34 (2004), S. 279-314 
    ISSN: 1531-7331
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Modeling and simulation are becoming increasingly accepted components of materials research. In this review we discuss application of modeling and simulation in the developing field of biomaterials. To restrict the discussion somewhat, we focus primarily on the structure and properties of biomaterials and do not discuss biochemical or biomedical applications. We start with a discussion of how atomistic-level simulation can be used to study molecules and collections of molecules. We then focus on mesoscale simulations of structure and properties, followed by a brief review of continuum-scale approaches. We end with some thoughts on the future of modeling and simulation in biomaterials applications.
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    Annual Review of Ecology, Evolution, and Systematics 35 (2004), S. 557-581 
    ISSN: 1543-592X
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: We review the evidence of regime shifts in terrestrial and aquatic environments in relation to resilience of complex adaptive ecosystems and the functional roles of biological diversity in this context. The evidence reveals that the likelihood of regime shifts may increase when humans reduce resilience by such actions as removing response diversity, removing whole functional groups of species, or removing whole trophic levels; impacting on ecosystems via emissions of waste and pollutants and climate change; and altering the magnitude, frequency, and duration of disturbance regimes. The combined and often synergistic effects of those pressures can make ecosystems more vulnerable to changes that previously could be absorbed. As a consequence, ecosystems may suddenly shift from desired to less desired states in their capacity to generate ecosystem services. Active adaptive management and governance of resilience will be required to sustain desired ecosystem states and transform degraded ecosystems into fundamentally new and more desirable configurations.
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    Annual Review of Ecology, Evolution, and Systematics 35 (2004), S. 285-322 
    ISSN: 1543-592X
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Studies of plant and animal assemblages from both the terrestrial and the marine fossil records reveal persistence for extensive periods of geological time, sometimes millions of years. Persistence does not require lack of change or the absence of variation from one occurrence of the assemblage to the next in geological time. It does, however, imply that assemblage composition is bounded and that variation occurs within those bounds. The principal cause for these patterns appears to be species-, and perhaps clade-level, environmental fidelity that results in long-term tracking of physical conditions. Other factors that influence persistent recurrence of assemblages are historical, biogeographic effects, the "law of large numbers," niche differentiation, and biotic interactions. Much research needs to be done in this area, and greater uniformity is needed in the approaches to studying the problem. However, great potential also exists for enhanced interaction between paleoecology and neoecology in understanding spatiotemporal complexity of ecological dynamics.
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    Annual Review of Ecology, Evolution, and Systematics 35 (2004), S. 523-556 
    ISSN: 1543-592X
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: The evolutionary succession of marine photoautotrophs began with the origin of photosynthesis in the Archean Eon, perhaps as early as 3.8 billion years ago. Since that time, Earth's atmosphere, continents, and oceans have undergone substantial cyclic and secular physical, chemical, and biological changes that selected for different phytoplankton taxa. Early in the history of eukaryotic algae, between 1.6 and 1.2 billion years ago, an evolutionary schism gave rise to "green" (chlorophyll b-containing) and "red" (chlorophyll c-containing) plastid groups. Members of the "green" plastid line were important constituents of Neoproterozoic and Paleozoic oceans, and, ultimately, one green clade colonized land. By the mid-Mesozoic, the green line had become ecologically less important in the oceans. In its place, three groups of chlorophyll c-containing eukaryotes, the dinoflagellates, coccolithophorids, and diatoms, began evolutionary trajectories that have culminated in ecological dominance in the contemporary oceans. Breakup of the supercontinent Pangea, continental shelf flooding, and changes in ocean redox chemistry may all have contributed to this evolutionary transition. At the same time, the evolution of these modern eukaryotic taxa has influenced both the structure of marine food webs and global biogeochemical cycles.
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    Annual Review of Ecology, Evolution, and Systematics 35 (2004), S. 199-227 
    ISSN: 1543-592X
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Species are routinely used as fundamental units of analysis in biogeography, ecology, macroevolution, and conservation biology. A large literature focuses on defining species conceptually, but until recently little attention has been given to the issue of empirically delimiting species. Researchers confronted with the task of delimiting species in nature are often unsure which method(s) is (are) most appropriate for their system and data type collected. Here, we review twelve of these methods organized into two general categories of tree- and nontree-based approaches. We also summarize the relevant biological properties of species amenable to empirical evaluation, the classes of data required, and some of the strengths and limitations of each method. We conclude that all methods will sometimes fail to delimit species boundaries properly or will give conflicting results, and that virtually all methods require researchers to make qualitative judgments. These facts, coupled with the fuzzy nature of species boundaries, require an eclectic approach to delimiting species and caution against the reliance on any single data set or method when delimiting species. No one definition has as yet satisfied all naturalists; yet every naturalist knows vaguely what he means when he speaks of a species. Darwin (1859/1964)
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    Annual Review of Ecology, Evolution, and Systematics 35 (2004), S. 175-197 
    ISSN: 1543-592X
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Mutualisms occur when interactions between species produce reciprocal benefits. However, the outcome of these interactions frequently shifts from positive, to neutral, to negative, depending on the environmental and community context, and indirect effects commonly produce unexpected mutualisms that have community-wide consequences. The dynamic, and context dependent, nature of mutualisms can transform consumers, competitors, and parasites into mutualists, even while they consume, compete with, or parasitize their partner species. These dynamic, and often diffuse, mutualisms strongly affect community organization and ecosystem processes, but the historic focus on pairwise interactions decoupled from their more complex community context has obscured their importance. In aquatic systems, mutualisms commonly support ecosystem-defining foundation species, underlie energy and nutrient dynamics within and between ecosystems, and provide mechanisms by which species can rapidly adjust to ecological variance. Mutualism is as important as competition, predation, and physical disturbance in determining community structure, and its impact needs to be adequately incorporated into community theory.
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    Annual Review of Ecology, Evolution, and Systematics 35 (2004), S. 467-490 
    ISSN: 1543-592X
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Spatial synchrony refers to coincident changes in the abundance or other time-varying characteristics of geographically disjunct populations. This phenomenon has been documented in the dynamics of species representing a variety of taxa and ecological roles. Synchrony may arise from three primary mechanisms:(a) dispersal among populations, reducing the size of relatively large populations and increasing relatively small ones; (b) congruent dependence of population dynamics on a synchronous exogenous random factor such as temperature or rainfall, a phenomenon known as the "Moran effect"; and (c) trophic interactions with populations of other species that are themselves spatially synchronous or mobile. Identification of the causes of synchrony is often difficult. In addition to intraspecific synchrony, there are many examples of synchrony among populations of different species, the causes of which are similarly complex and difficult to identify. Furthermore, some populations may exhibit complex spatial dynamics such as spiral waves and chaos. Statistical tests based on phase coherence and/or time-lagged spatial correlation are required to characterize these more complex patterns of spatial dynamics fully.
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    Annual Review of Ecology, Evolution, and Systematics 35 (2004), S. 435-466 
    ISSN: 1543-592X
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Ecologists and evolutionary biologists are broadly interested in how the interactions among organisms influence their abundance, distribution, phenotypes, and genotypic composition. Recently, we have seen a growing appreciation of how multispecies interactions can act synergistically or antagonistically to alter the ecological and evolutionary outcomes of interactions in ways that differ fundamentally from outcomes predicted by pairwise interactions. Here, we review the evidence for criteria identified to detect community-based, diffuse coevolution. These criteria include (a) the presence of genetic correlations between traits involved in multiple interactions, (b) interactions with one species that alter the likelihood or intensity of interactions with other species, and (c) nonadditive combined effects of multiple interactors. In addition, we review the evidence that multispecies interactions have demographic consequences for populations, as well as evolutionary consequences. Finally, we explore the experimental and analytical techniques, and their limitations, used in the study of multispecies interactions. Throughout, we discuss areas in particular need of future research.
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    Annual Review of Ecology, Evolution, and Systematics 35 (2004), S. 375-403 
    ISSN: 1543-592X
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Floral evolution has often been associated with differences in pollination syndromes. Recently, this conceptual structure has been criticized on the grounds that flowers attract a broader spectrum of visitors than one might expect based on their syndromes and that flowers often diverge without excluding one type of pollinator in favor of another. Despite these criticisms, we show that pollination syndromes provide great utility in understanding the mechanisms of floral diversification. Our conclusions are based on the importance of organizing pollinators into functional groups according to presumed similarities in the selection pressures they exert. Furthermore, functional groups vary widely in their effectiveness as pollinators for particular plant species. Thus, although a plant may be visited by several functional groups, the relative selective pressures they exert will likely be very different. We discuss various methods of documenting selection on floral traits. Our review of the literature indicates overwhelming evidence that functional groups exert different selection pressures on floral traits. We also discuss the gaps in our knowledge of the mechanisms that underlie the evolution of pollination syndromes. In particular, we need more information about the relative importance of specific traits in pollination shifts, about what selective factors favor shifts between functional groups, about whether selection acts on traits independently or in combination, and about the role of history in pollination-syndrome evolution.
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    Annual Review of Astronomy and Astrophysics 18 (1980), S. 43-75 
    ISSN: 0066-4146
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Physics
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    Annual Review of Astronomy and Astrophysics 18 (1980), S. 77-113 
    ISSN: 0066-4146
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    Topics: Physics
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    Annual Review of Astronomy and Astrophysics 18 (1980), S. 115-164 
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    Annual Review of Astronomy and Astrophysics 18 (1980), S. 439-488 
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    Topics: Physics
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    Annual Review of Astronomy and Astrophysics 18 (1980), S. 165-218 
    ISSN: 0066-4146
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    Topics: Physics
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    Annual Review of Astronomy and Astrophysics 18 (1980), S. 537-560 
    ISSN: 0066-4146
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    Topics: Physics
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