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  • American Meteorological Society
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  • 1
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    American Meteorological Society
    In:  EPIC3Journal of Climate, American Meteorological Society, 35(23), pp. 7811-7831, ISSN: 0894-8755
    Publication Date: 2023-06-23
    Description: Numerical simulations allow us to gain a comprehensive understanding of the underlying mechanisms of past, present, and future climate changes. The mid-Holocene (MH) and the last interglacial (LIG) were the two most recent warm episodes of Earth’s climate history and are the focus of paleoclimate research. Here, we present results of MH and LIG simulations with two versions of the state-of-the-art Earth system model AWI-ESM. Most of the climate changes in MH and LIG compared to the preindustrial era are agreed upon by the two model versions, including 1) enhanced seasonality in surface temperature that is driven by the redistribution of seasonal insolation; 2) a northward shift of the intertropical convergence zone (ITCZ) and tropical rain belt; 3) a reduction in annual mean Arctic sea ice concentration; 4) weakening and northward displacement of the Northern Hemisphere Hadley circulation, which is related to the decrease and poleward shift of the temperature gradient from the subtropical to the equator in the Northern Hemisphere; 5) a westward shift of the Indo-Pacific Walker circulation due to anomalous warming over the Eurasia and North Africa during boreal summer; and 6) an expansion and intensification of Northern Hemisphere summer monsoon rainfall, with the latter being dominated by the dynamic component of moisture budget (i.e., the strengthening of wind circulation). However, the simulated responses of the Atlantic meridional overturning circulation (AMOC) in the two models yield different results for both the LIG and the MH. AMOC anomalies between the warm interglacial and preindustrial periods are associated with changes in North Atlantic westerly winds and stratification of the water column at the North Atlantic due to changes in ocean temperature, salinity, and density.
    Repository Name: EPIC Alfred Wegener Institut
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  • 2
    Publication Date: 2023-02-25
    Description: Author Posting. © American Meteorological Society, 2022. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Physical Oceanography 52(11), (2022): 2841–2852, https://doi.org/10.1175/jpo-d-22-0025.1.
    Description: Prediction of rapid intensification in tropical cyclones prior to landfall is a major societal issue. While air–sea interactions are clearly linked to storm intensity, the connections between the underlying thermal conditions over continental shelves and rapid intensification are limited. Here, an exceptional set of in situ and satellite data are used to identify spatial heterogeneity in sea surface temperatures across the inner core of Hurricane Sally (2020), a storm that rapidly intensified over the shelf. A leftward shift in the region of maximum cooling was observed as the hurricane transited from the open gulf to the shelf. This shift was generated, in part, by the surface heat flux in conjunction with the along- and across-shelf transport of heat from storm-generated coastal circulation. The spatial differences in the sea surface temperatures were large enough to potentially influence rapid intensification processes suggesting that coastal thermal features need to be accounted for to improve storm forecasting as well as to better understand how climate change will modify interactions between tropical cyclones and the coastal ocean.
    Description: This research was made possible by the NOAA RESTORE Science Program (NA17NOS4510101 and NA19NOS4510194) and the NASA Physical Oceanography program (80NSSC21K0553 and WBS 281945.02.25.04.67) and NOAA IOOS program via GCOOS (NA16NOS0120018). The authors declare that they have no competing interests.
    Keywords: Seas/gulfs/bays ; Atmosphere–ocean interaction ; Currents ; Tropical cyclones ; Buoy observations ; In situ oceanic observations
    Repository Name: Woods Hole Open Access Server
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  • 3
    Publication Date: 2023-02-25
    Description: Author Posting. © American Meteorological Society, 2022. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Physical Oceanography 52(8), (2022): 1797–1815, https://doi.org/10.1175/JPO-D-21-0288.1.
    Description: Intruding slope water is a major source of nutrients to sustain the high biological productivity in the Gulf of Maine (GoM). Slope water intrusion into the GoM is affected by Gulf Stream warm-core rings (WCRs) impinging onto the nearby shelf edge. This study combines long-term mooring measurements, satellite remote sensing data, an idealized numerical ocean model, and a linear coastal-trapped wave (CTW) model to examine the impact of WCRs on slope water intrusion into the GoM through the Northeast Channel. Analysis of satellite sea surface height and temperature data shows that the slope sea region off the GoM is a hotspot of ring activities. A significant linear relationship is found between interannual variations of ring activities in the slope sea region off the GoM and bottom salinity at the Northeast Channel, suggesting the importance of WCRs in modulating variability of intruding slope water. Analysis of the mooring data reveals enhanced slope water intrusion through bottom-intensified along-channel flow following impingements of WCRs on the nearby shelf edge. Numerical simulations qualitatively reproduce the observed WCR impingement processes and associated episodic enhancement of slope water intrusion in the Northeast Channel. Diagnosis of the model result indicates that baroclinic CTWs excited by the ring–topography interaction are responsible for the episodically intensified subsurface along-channel inflow, which carries more slope water into the GoM. A WCR that impinges onto the shelf edge to the northeast of the Northeast Channel tends to generate stronger CTWs and cause stronger enhancement of the slope water intrusion into the GoM.
    Description: This study is supported by the National Science Foundation through Grant OCE-1634965.
    Keywords: Continental shelf/slope ; Channel flows ; Mesoscale processes ; In situ oceanic observations ; Satellite observations ; Numerical analysis/modeling
    Repository Name: Woods Hole Open Access Server
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  • 4
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    American Meteorological Society
    In:  EPIC3Journal of Climate, American Meteorological Society, pp. 1-40, ISSN: 0894-8755
    Publication Date: 2023-09-04
    Description: 〈jats:title〉Abstract〈/jats:title〉 〈jats:p〉Tipping points in the Earth system describe critical thresholds beyond which a single component, part of the system, or the system as a whole changes from one stable state to another. In the present-day Southern Ocean, the Weddell Sea constitutes an important dense-water formation site, associated with efficient deep-ocean carbon and oxygen transfer and low ice-shelf basal melt rates. Here, a regime shift will occur when continental shelves are continuously flushed with warm, oxygen-poor offshore waters from intermediate depth, leading to less efficient deep-ocean carbon and oxygen transfer and higher ice-shelf basal melt rates. We use a global ocean–biogeochemistry model including ice-shelf cavities and an eddy-permitting grid in the southern Weddell Sea to address the susceptibility of this region to such a system change for four 21〈jats:sup〉st〈/jats:sup〉-century emission scenarios. Assessing the projected changes in shelf–open ocean density gradients, bottom-water properties, and on-shelf heat transport, our results indicate that the Weddell Sea undergoes a regime shift by 2100 in the highest-emission scenario SSP5-8.5, but not yet in the lower-emission scenarios. The regime shift is imminent by 2100 in the scenarios SSP3-7.0 and SSP2-4.5, but avoidable under the lowest-emission scenario SSP1-2.6. While shelf-bottom waters freshen and acidify everywhere, bottom waters in the Filchner Trough undergo accelerated warming and deoxygenation following the system change, with implications for local ecosystems and ice-shelf basal melt. Additionally, deep-ocean carbon and oxygen transfer decline, implying that the local changes ultimately affect ocean circulation, climate, and ecosystems globally.〈/jats:p〉
    Repository Name: EPIC Alfred Wegener Institut
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  • 5
    Publication Date: 2023-04-26
    Description: Mechanisms behind the phenomenon of Arctic amplification are widely discussed. To contribute to this debate, the (AC)3 project was established in 2016 (www.ac3-tr.de/). It comprises modeling and data analysis efforts as well as observational elements. The project has assembled a wealth of ground-based, airborne, shipborne, and satellite data of physical, chemical, and meteorological properties of the Arctic atmosphere, cryosphere, and upper ocean that are available for the Arctic climate research community. Short-term changes and indications of long-term trends in Arctic climate parameters have been detected using existing and new data. For example, a distinct atmospheric moistening, an increase of regional storm activities, an amplified winter warming in the Svalbard and North Pole regions, and a decrease of sea ice thickness in the Fram Strait and of snow depth on sea ice have been identified. A positive trend of tropospheric bromine monoxide (BrO) column densities during polar spring was verified. Local marine/biogenic sources for cloud condensation nuclei and ice nucleating particles were found. Atmospheric–ocean and radiative transfer models were advanced by applying new parameterizations of surface albedo, cloud droplet activation, convective plumes and related processes over leads, and turbulent transfer coefficients for stable surface layers. Four modes of the surface radiative energy budget were explored and reproduced by simulations. To advance the future synthesis of the results, cross-cutting activities are being developed aiming to answer key questions in four focus areas: lapse rate feedback, surface processes, Arctic mixed-phase clouds, and airmass transport and transformation.
    Repository Name: EPIC Alfred Wegener Institut
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  • 6
    Publication Date: 2023-01-27
    Description: Author Posting. © American Meteorological Society, 2022. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Physical Oceanography 52(8), (2022): 1705-1730, https://doi.org/10.1175/jpo-d-21-0243.1.
    Description: Formation and evolution of barrier layers (BLs) and associated temperature inversions (TIs) were investigated using a 1-yr time series of oceanic and air–sea surface observations from three moorings deployed in the eastern Pacific fresh pool. BL thickness and TI amplitude showed a seasonality with maxima in boreal summer and autumn when BLs were persistently present. Mixed layer salinity (MLS) and mixed layer temperature (MLT) budgets were constructed to investigate the formation mechanism of BLs and TIs. The MLS budget showed that BLs were initially formed in response to horizontal advection of freshwater in boreal summer and then primarily maintained by precipitation. The MLT budget revealed that penetration of shortwave radiation through the mixed layer base is the dominant contributor to TI formation through subsurface warming. Geostrophic advection is a secondary contributor to TI formation through surface cooling. When the BL exists, the cooling effect from entrainment and the warming effect from detrainment are both significantly reduced. In addition, when the BL is associated with the presence of a TI, entrainment works to warm the mixed layer. The presence of BLs makes the shallower mixed layer more sensitive to surface heat and freshwater fluxes, acting to enhance the formation of TIs that increase the subsurface warming via shortwave penetration.
    Description: SK is supported by JSPS Overseas Research Fellowships. JS and SK are supported by NASA Grant 80NSSC18K1500. JTF and the mooring deployment were funded by NASA Grants NNX15AG20G and 80NSSC18K1494. DZ is supported by NASA Grant 80NSSC18K1499. This publication is partially funded by the Cooperative Institute for Climate, Ocean, and Ecosystem Studies (CICOES) under NOAA Cooperative Agreement NA20OAR4320271, Contribution 2021-1152. This is PMEL Contribution 5268.
    Description: 2023-01-27
    Keywords: Ocean ; North Pacific Ocean ; Tropics ; Entrainment ; Oceanic mixed layer ; Salinity
    Repository Name: Woods Hole Open Access Server
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  • 7
    Publication Date: 2023-02-01
    Description: Author Posting. © American Meteorological Society, 2022. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Physical Oceanography 52(8), (2022): 1927-1943, https://doi.org/10.1175/jpo-d-21-0124.1.
    Description: The Galápagos Archipelago lies on the equator in the path of the eastward flowing Pacific Equatorial Undercurrent (EUC). When the EUC reaches the archipelago, it upwells and bifurcates into a north and south branch around the archipelago at a latitude determined by topography. Since the Coriolis parameter (f) equals zero at the equator, strong velocity gradients associated with the EUC can result in Ertel potential vorticity (Q) having sign opposite that of planetary vorticity near the equator. Observations collected by underwater gliders deployed just west of the Galápagos Archipelago during 2013–16 are used to estimate Q and to diagnose associated instabilities that may impact the Galápagos Cold Pool. Estimates of Q are qualitatively conserved along streamlines, consistent with the 2.5-layer, inertial model of the EUC by Pedlosky. The Q with sign opposite of f is advected south of the Galápagos Archipelago when the EUC core is located south of the bifurcation latitude. The horizontal gradient of Q suggests that the region between 2°S and 2°N above 100 m is barotropically unstable, while limited regions are baroclinically unstable. Conditions conducive to symmetric instability are observed between the EUC core and the equator and within the southern branch of the undercurrent. Using 2-month and 3-yr averages, e-folding time scales are 2–11 days, suggesting that symmetric instability can persist on those time scales.
    Description: This work was supported by the National Science Foundation (Grants OCE-1232971 and OCE-1233282), the NASA Earth and Space Science Fellowship Program (Grant 80NSSC17K0443), and the Global Ocean Monitoring and Observing Program of the National Oceanographic and Atmospheric Administration (NA13OAR4830216). Color maps are from Thyng et al. (2016).
    Description: 2023-02-01
    Keywords: Currents ; In situ oceanic observations ; Instability ; Mixing ; Ocean dynamics ; Pacific Ocean ; Potential vorticity ; Tropics
    Repository Name: Woods Hole Open Access Server
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  • 8
    Publication Date: 2023-02-01
    Description: Author Posting. © American Meteorological Society, 2022. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of the Atmospheric and Oceanic Technology 39(8), (2022): 1183-1198, https://doi.org/10.1175/jtech-d-21-0068.1.
    Description: Horizontal kinematic properties, such as vorticity, divergence, and lateral strain rate, are estimated from drifter clusters using three approaches. At submesoscale horizontal length scales O(1–10)km, kinematic properties become as large as planetary vorticity f, but challenging to observe because they evolve on short time scales O(hourstodays). By simulating surface drifters in a model flow field, we quantify the sources of uncertainty in the kinematic property calculations due to the deformation of cluster shape. Uncertainties arise primarily due to (i) violation of the linear estimation methods and (ii) aliasing of unresolved scales. Systematic uncertainties (iii) due to GPS errors, are secondary but can become as large as (i) and (ii) when aspect ratios are small. Ideal cluster parameters (number of drifters, length scale, and aspect ratio) are determined and error functions estimated empirically and theoretically. The most robust method—a two-dimensional, linear least squares fit—is applied to the first few days of a drifter dataset from the Bay of Bengal. Application of the length scale and aspect-ratio criteria minimizes errors (i) and (ii), and reduces the total number of clusters and so computational cost. The drifter-estimated kinematic properties map out a cyclonic mesoscale eddy with a surface, submesoscale fronts at its perimeter. Our analyses suggest methodological guidance for computing the two-dimensional kinematic properties in submesoscale flows, given the recently increasing quantity and quality of drifter observations, while also highlighting challenges and limitations.
    Description: This research was supported by the Office of Naval Research (ONR) Departmental Research Initiative ASIRI under Grant N00014-13-1-0451 (SE and AM) and Grant N00014-13-1-0477 (VH and LC). The authors thank the captain and crew of the R/V Roger Revelle, and Andrew Lucas with the Multiscale Ocean Dynamics group at the Scripps Institution for Oceanography for providing the FastCTD data collected in 2015, which was supported by ONR Grant N00014-13-1-0489, as well as Eric D’Asaro for helpful discussions and Lance Braasch for assistance with the drifter dataset. AM and SE further thank NSF (Grant OCE-I434788) and ONR (Grant N00014-16-1-2470) for support. VH and LC were additionally supported by ONR Grants N00014-15-1-2286, N00014-14-1-0183, N00014-19-1-26-91 and NOAA Global Drifter Program (GDP) Grant NA15OAR4320071.
    Description: 2023-02-01
    Keywords: Indian Ocean ; Eddies ; Frontogenesis/frontolysis ; Fronts ; Lagrangian circulation/transport ; Ocean circulation ; Ocean dynamics
    Repository Name: Woods Hole Open Access Server
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  • 9
    Publication Date: 2023-02-01
    Description: Author Posting. © American Meteorological Society, 2022. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Climate 35(17), (2022): 5465-5482, https://doi.org/10.1175/jcli-d-21-0671.1.
    Description: Understanding the contribution of ocean circulation to glacial–interglacial climate change is a major focus of paleoceanography. Specifically, many have tried to determine whether the volumes and depths of Antarctic- and North Atlantic–sourced waters in the deep ocean changed at the Last Glacial Maximum (LGM; ∼22–18 kyr BP) when atmospheric pCO2 concentrations were 100 ppm lower than the preindustrial. Measurements of sedimentary geochemical proxies are the primary way that these deep ocean structural changes have been reconstructed. However, the main proxies used to reconstruct LGM Atlantic water mass geometry provide conflicting results as to whether North Atlantic–sourced waters shoaled during the LGM. Despite this, a number of idealized modeling studies have been advanced to describe the physical processes resulting in shoaled North Atlantic waters. This paper aims to critically assess the approaches used to determine LGM Atlantic circulation geometry and lay out best practices for future work. We first compile existing proxy data and paleoclimate model output to deduce the processes responsible for setting the ocean distributions of geochemical proxies in the LGM Atlantic Ocean. We highlight how small-scale mixing processes in the ocean interior can decouple tracer distributions from the large-scale circulation, complicating the straightforward interpretation of geochemical tracers as proxies for water mass structure. Finally, we outline promising paths toward ascertaining the LGM circulation structure more clearly and deeply.
    Description: S.K.H. was supported by the Investment in Science Fund at WHOI and the John E. and Anne W. Sawyer Endowed Fund in Support of Scientific Staff. F.J.P. was supported by a Stanback Postdoctoral Fellowship at Caltech.
    Description: 2023-02-01
    Keywords: Diapycnal mixing ; Meridional overturning circulation ; Ocean circulation
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  • 10
    Publication Date: 2023-02-17
    Description: Author Posting. © American Meteorological Society, 2022. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of the Atmospheric and Oceanic Technology 39(10), (2022): 1525–1539, https://doi.org/10.1175/jtech-d-21-0186.1.
    Description: The static and dynamic performances of the RBRargo3 are investigated using a combination of laboratory-based and in situ datasets from floats deployed as part of an Argo pilot program. Temperature and pressure measurements compare well to co-located reference data acquired from shipboard CTDs. Static accuracy of salinity measurements is significantly improved using 1) a time lag for temperature, 2) a quadratic pressure dependence, and 3) a unit-based calibration for each RBRargo3 over its full pressure range. Long-term deployments show no significant drift in the RBRargo3 accuracy. The dynamic response of the RBRargo3 demonstrates the presence of two different adjustment time scales: a long-term adjustment O(120) s, driven by the temperature difference between the interior of the conductivity cell and the water, and a short-term adjustment O(5–10) s, associated to the initial exchange of heat between the water and the inner ceramic. Corrections for these effects, including dependence on profiling speed, are developed.
    Keywords: Data processing/distribution ; In situ oceanic observations ; Profilers ; Oceanic
    Repository Name: Woods Hole Open Access Server
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  • 11
    Publication Date: 2023-02-28
    Description: Author Posting. © American Meteorological Society, 2022. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Physical Oceanography 52(12),(2022): 3199-3219, https://doi.org/10.1175/jpo-d-22-0009.1.
    Description: The abyssal overturning circulation is thought to be primarily driven by small-scale turbulent mixing. Diagnosed water-mass transformations are dominated by rough topography “hotspots,” where the bottom enhancement of mixing causes the diffusive buoyancy flux to diverge, driving widespread downwelling in the interior—only to be overwhelmed by an even stronger upwelling in a thin bottom boundary layer (BBL). These water-mass transformations are significantly underestimated by one-dimensional (1D) sloping boundary layer solutions, suggesting the importance of three-dimensional physics. Here, we use a hierarchy of models to generalize this 1D boundary layer approach to three-dimensional eddying flows over realistically rough topography. When applied to the Mid-Atlantic Ridge in the Brazil Basin, the idealized simulation results are roughly consistent with available observations. Integral buoyancy budgets isolate the physical processes that contribute to realistically strong BBL upwelling. The downward diffusion of buoyancy is primarily balanced by upwelling along the sloping canyon sidewalls and the surrounding abyssal hills. These flows are strengthened by the restratifying effects of submesoscale baroclinic eddies and by the blocking of along-ridge thermal wind within the canyon. Major topographic sills block along-thalweg flows from restratifying the canyon trough, resulting in the continual erosion of the trough’s stratification. We propose simple modifications to the 1D boundary layer model that approximate each of these three-dimensional effects. These results provide local dynamical insights into mixing-driven abyssal overturning, but a complete theory will also require the nonlocal coupling to the basin-scale circulation.
    Description: We acknowledge funding support from National Science Foundation Awards 1536515, 1736109, and 2149080. This material is based upon work supported by the National Science Foundation Graduate Research Fellowship Program under Grant 174530.
    Description: 2023-05-18
    Keywords: Abyssal circulation ; Diapycnal mixing ; Meridional overturning circulation ; Topographic effects ; Upwelling/downwelling ; Bottom currents/bottom water
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  • 12
    Publication Date: 2023-02-28
    Description: Author Posting. © American Meteorological Society, 2022. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Physical Oceanography 52(6), (2022): 1091–1110, https://doi.org/10.1175/JPO-D-21-0068.1.
    Description: Hundreds of full-depth temperature and salinity profiles collected by Deepglider autonomous underwater vehicles (AUVs) in the North Atlantic reveal robust signals in eddy isopycnal vertical displacement and horizontal current throughout the entire water column. In separate glider missions southeast of Bermuda, subsurface-intensified cold, fresh coherent vortices were observed with velocities exceeding 20 cm s−1 at depths greater than 1000 m. With vertical resolution on the order of 20 m or less, these full-depth glider slant profiles newly permit estimation of scaled vertical wavenumber spectra from the barotropic through the 40th baroclinic mode. Geostrophic turbulence theory predictions of spectral slopes associated with the forward enstrophy cascade and proportional to inverse wavenumber cubed generally agree with glider-derived quasi-universal spectra of potential and kinetic energy found at a variety of locations distinguished by a wide range of mean surface eddy kinetic energy. Water-column average spectral estimates merge at high vertical mode number to established descriptions of internal wave spectra. Among glider mission sites, geographic and seasonal variability implicate bottom drag as a mechanism for dissipation, but also the need for more persistent sampling of the deep ocean.
    Description: This work was funded by NSF Grant 1736217 and would not have been possible without the help of Kirk O’Donnell, James Bennett, Noel Pelland, and all contributors to Deepglider development. We additionally thank the captain crew of the R/V Atlantic Explorer and the BATS team at the Bermuda Institute of Ocean Sciences, particularly Rod Johnson, as well as Seakeepers International for their professionalism, capability, and generous assistance in deploying and recovering gliders.
    Keywords: North Atlantic Ocean ; Eddies ; Mesoscale processes ; Turbulence ; Energy transport ; In situ oceanic observations ; Oceanic variability
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  • 13
    Publication Date: 2023-02-28
    Description: © The Author(s), 2023. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Timmermans, M.-L., & Toole, J. The Arctic Ocean’s Beaufort Gyre. Annual Review of Marine Science, 15(1), (2023): 223-248, https://doi.org/10.1146/annurev-marine-032122-012034.
    Description: The Arctic Ocean's Beaufort Gyre is a dominant feature of the Arctic system, a prominent indicator of climate change, and possibly a control factor for high-latitude climate. The state of knowledge of the wind-driven Beaufort Gyre is reviewed here, including its forcing, relationship to sea-ice cover, source waters, circulation, and energetics. Recent decades have seen pronounced change in all elements of the Beaufort Gyre system. Sea-ice losses have accompanied an intensification of the gyre circulation and increasing heat and freshwater content. Present understanding of these changes is evaluated, and time series of heat and freshwater content are updated to include the most recent observations.
    Description: Support was provided by the National Science Foundation Office of Polar Programs and the Office of Naval Research.
    Keywords: Arctic Ocean ; Beaufort Gyre ; Circulation ; Sea ice ; Freshwater ; Ocean heat content
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  • 14
    Publication Date: 2023-03-02
    Description: Author Posting. © American Meteorological Society, 2022. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Physical Oceanography 52(12), (2022): 3221–3240, https://doi.org/10.1175/jpo-d-22-0010.1.
    Description: Small-scale mixing drives the diabatic upwelling that closes the abyssal ocean overturning circulation. Indirect microstructure measurements of in situ turbulence suggest that mixing is bottom enhanced over rough topography, implying downwelling in the interior and stronger upwelling in a sloping bottom boundary layer. Tracer release experiments (TREs), in which inert tracers are purposefully released and their dispersion is surveyed over time, have been used to independently infer turbulent diffusivities—but typically provide estimates in excess of microstructure ones. In an attempt to reconcile these differences, Ruan and Ferrari derived exact tracer-weighted buoyancy moment diagnostics, which we here apply to quasi-realistic simulations. A tracer’s diapycnal displacement rate is exactly twice the tracer-averaged buoyancy velocity, itself a convolution of an asymmetric upwelling/downwelling dipole. The tracer’s diapycnal spreading rate, however, involves both the expected positive contribution from the tracer-averaged in situ diffusion as well as an additional nonlinear diapycnal distortion term, which is caused by correlations between buoyancy and the buoyancy velocity, and can be of either sign. Distortion is generally positive (stretching) due to bottom-enhanced mixing in the stratified interior but negative (contraction) near the bottom. Our simulations suggest that these two effects coincidentally cancel for the Brazil Basin Tracer Release Experiment, resulting in negligible net distortion. By contrast, near-bottom tracers experience leading-order distortion that varies in time. Errors in tracer moments due to realistically sparse sampling are generally small (〈20%), especially compared to the O(1) structural errors due to the omission of distortion effects in inverse models. These results suggest that TREs, although indispensable, should not be treated as “unambiguous” constraints on diapycnal mixing.
    Description: We acknowledge funding support from National Science Foundation Awards 1536515 and 1736109. This material is based upon work supported by the National Science Foundation Graduate Research Fellowship Program under Grant 174530. This research is also supported by the NOAA Climate and Global Change Postdoctoral Fellowship Program, administered by UCAR’s Cooperative Programs for the Advancement of Earth System Science (CPAESS) under Award NA18NWS4620043B.
    Description: 2023-05-18
    Keywords: Diapycnal mixing ; Diffusion ; Upwelling/downwelling ; Bottom currents/bottom water ; Tracers
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  • 15
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    Annual Reviews
    In:  EPIC3Annual Review of Marine Science, Annual Reviews, 16(1), pp. 417-441, ISSN: 1941-1405
    Publication Date: 2024-03-01
    Description: The genus Phaeocystis is globally distributed, with blooms commonly occurring on continental shelves. This unusual phytoplankter has two major morphologies: solitary cells and cells embedded in a gelatinous matrix. Only colonies form blooms. Their large size (commonly 2 mm but up to 3 cm) and mucilaginous envelope allow the colonies to escape predation, but data are inconsistent as to whether colonies are grazed. Cultured Phaeocystis can also inhibit the growth of co-occurring phytoplankton or the feeding of potential grazers. Colonies and solitary cells use nitrate as a nitrogen source, although solitary cells can also grow on ammonium. Phaeocystis colonies might be a major contributor to carbon flux to depth, but in most cases, colonies are rapidly remineralized in the upper 300 m. The occurrence of large Phaeocystis blooms is often associated with environments with low and highly variable light and high nitrate levels, with Phaeocystis antarctica blooms being linked additionally to high iron availability. Emerging results indicate that different clones of Phaeocystis have substantial genetic plasticity, which may explain its appearance in a variety of environments. Given the evidence of Phaeocystis appearing in new systems, this trend will likely continue in the near future.
    Repository Name: EPIC Alfred Wegener Institut
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  • 16
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    Annual Reviews
    In:  EPIC3Annual Review of Marine Science, Annual Reviews, 16(1), pp. 513-536, ISSN: 1941-1405
    Publication Date: 2024-01-31
    Description: 〈jats:p〉 For decades, multiple-driver/stressor research has examined interactions among drivers that will undergo large changes in the future: temperature, pH, nutrients, oxygen, pathogens, and more. However, the most commonly used experimental designs—present-versus-future and ANOVA—fail to contribute to general understanding or predictive power. Linking experimental design to process-based mathematical models would help us predict how ecosystems will behave in novel environmental conditions. We review a range of experimental designs and assess the best experimental path toward a predictive ecology. Full factorial response surface, fractional factorial, quadratic response surface, custom, space-filling, and especially optimal and sequential/adaptive designs can help us achieve more valuable scientific goals. Experiments using these designs are challenging to perform with long-lived organisms or at the community and ecosystem levels. But they remain our most promising path toward linking experiments and theory in multiple-driver research and making accurate, useful predictions. 〈/jats:p〉
    Repository Name: EPIC Alfred Wegener Institut
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  • 17
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    American Meteorological Society
    In:  EPIC3Journal of Climate, American Meteorological Society, 37(6), pp. 2059-2080, ISSN: 0894-8755
    Publication Date: 2024-04-22
    Description: Heat stress is projected to intensify with global warming, causing significant socioeconomic impacts and threatening human health. Wet-bulb temperature (WBT), which combines temperature and humidity effects, is a useful indicator for assessing regional and global heat stress variability and trends. However, the variations of European WBT and their underlying mechanisms remain unclear. Using observations and reanalysis datasets, we demonstrate a remarkable warming of summer WBT during the period 1958–2021 over Europe. Specifically, the European summer WBT has increased by over 1.08C in the past 64 years. We find that the increase in European summer WBT is driven by both near-surface warming temperatures and increasing atmospheric moisture content. We identify four dominant modes of European summer WBT variability and investigate their linkage with the large-scale atmospheric circulation and sea surface temperature anomalies. The first two leading modes of the European WBT variability exhibit prominent interdecadal to long-term variations, mainly driven by a circumglobal wave train and concurrent sea surface temperature variations. The last two leading modes of European WBT variability mainly show interannual variations, indicating a direct and rapid response to large-scale atmospheric dynamics and nearby sea surface temperature variations. Further analysis shows the role of global warming and changes in midlatitude circulations in the variations of summer WBT. Our findings can enhance the understanding of plausible drivers of heat stress in Europe and provide valuable insights for regional decision-makers and climate adaptation planning.
    Repository Name: EPIC Alfred Wegener Institut
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  • 18
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    American Meteorological Society
    In:  EPIC3Journal of Climate, American Meteorological Society, 37(8), pp. 2505-2518, ISSN: 0894-8755
    Publication Date: 2024-04-29
    Description: A fundamental statistic of climate variability is its spatiotemporal correlation function. Its complex structure can be concisely summarized by a frequency-dependent measure of the effective spatial degrees of freedom (ESDOF). Here we present, for the first time, frequency-dependent ESDOF estimates of global natural surface temperature variability from purely instrumental measurements, using the HadCRUT4 dataset (1850-2014). The approach is based on a newly developed method for estimating the frequency-dependent spatial correlation function from gappy data fields. Results reveal a multicomponent structure of the spatial correlation function, including a large-amplitude short-distance component (with weak time scale dependence) and a small-amplitude long-distance component (with increasing relative amplitude toward the longer time scales). Two frequency-dependent ESDOF measures are applied, each responding mainly to either of the two components. Both measures exhibit a significant ESDOF reduction from monthly to multidecadal time scales, implying an increase of the effective spatial scale of natural surface temperature fluctuations. Moreover, it is found that a good approximation to the global number of equally spaced samples needed to estimate the variance of global mean temperature is given, at any frequency, by the greater one of the two ESDOF measures, decreasing from ;130 at monthly to ;30 at multidecadal time scales. Finally, the multicomponent structure of the correlation function together with the detected ESDOF scaling properties indicate that the ESDOF reduction toward the longer time scales cannot be explained simply by diffusion acting on stochastically driven anomalies, as it might be suggested f rom simple stochastic-diffusive energy balance models.
    Repository Name: EPIC Alfred Wegener Institut
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  • 19
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    American Meteorological Society
    In:  EPIC3Journal of Climate, American Meteorological Society, 34(18), pp. 7373-7388, ISSN: 0894-8755
    Publication Date: 2024-04-29
    Description: Climate variability occurs over wide ranges of spatial and temporal scales. It exhibits a complex spatial covariance structure, which depends on geographic location (e.g., tropics vs extratropics) and also consists of a superposition of (i) components with gradually decaying positive correlation functions and (ii) teleconnections that often involve anticorrelations. In addition, there are indications that the spatial covariance structure depends on frequency. Thus, a comprehensive assessment of the spatiotemporal covariance structure of climate variability would require an extensive set of statistical diagnostics. Therefore, it is often desirable to characterize the covariance structure by a simple summarizing metric that is easy to compute from datasets. Such summarizing metrics are useful, for example, in the context of comparisons between climate models or between models and observations. Here we introduce a frequency-dependent version of a simple measure of the effective spatial degrees of freedom. The measure is based on the temporal variance of the global average of some climate variable, and its novel aspect consists in its frequency dependence. We also provide a clear geometric interpretation of the measure. Its easy applicability is demonstrated using near-surface temperature and precipitation fields obtained from a paleoclimate model simulation. This application reveals a distinct scaling behavior of the spatial degrees of freedom as a function of frequency, ranging from monthly to millennial scales.
    Repository Name: EPIC Alfred Wegener Institut
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  • 20
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    American Meteorological Society
    In:  EPIC3Journal of Physical Oceanography, American Meteorological Society, 54(4), pp. 1003-1018, ISSN: 0022-3670
    Publication Date: 2024-04-25
    Description: Coastal upwelling, driven by alongshore winds and characterized by cold sea surface temperatures and high upper-ocean nutrient content, is an important physical process sustaining some of the oceans’ most productive ecosystems. To fully understand the ocean properties in eastern boundary upwelling systems, it is important to consider the depth of the source waters being upwelled, as it affects both the SST and the transport of nutrients toward the surface. Here, we construct an upwelling source depth distribution for parcels at the surface in the upwelling zone. We do so using passive tracers forced at the domain boundary for every model depth level to quantify their contributions to the upwelled waters. We test the dependence of this distribution on the strength of the wind stress and stratification using high-resolution regional ocean simulations of an idealized coastal upwelling system. We also present an efficient method for estimating the mean upwelling source depth. Furthermore, we show that the standard deviation of the upwelling source depth distribution increases with increasing wind stress and decreases with increasing stratification. These results can be applied to better understand and predict how coastal upwelling sites and their surface properties have and will change in past and future climates.
    Repository Name: EPIC Alfred Wegener Institut
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  • 21
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    American Meteorological Society
    In:  EPIC3Bulletin of the American Meteorological Society, American Meteorological Society, 104(9), pp. s1-s10, ISSN: 0003-0007
    Publication Date: 2024-05-08
    Description: 〈jats:title〉Abstract〈/jats:title〉 〈jats:p〉—J. BLUNDEN, T. BOYER, AND E. BARTOW-GILLIES〈/jats:p〉 〈jats:p〉Earth’s global climate system is vast, complex, and intricately interrelated. Many areas are influenced by global-scale phenomena, including the “triple dip” La Niña conditions that prevailed in the eastern Pacific Ocean nearly continuously from mid-2020 through all of 2022; by regional phenomena such as the positive winter and summer North Atlantic Oscillation that impacted weather in parts the Northern Hemisphere and the negative Indian Ocean dipole that impacted weather in parts of the Southern Hemisphere; and by more localized systems such as high-pressure heat domes that caused extreme heat in different areas of the world. Underlying all these natural short-term variabilities are long-term climate trends due to continuous increases since the beginning of the Industrial Revolution in the atmospheric concentrations of Earth’s major greenhouse gases.〈/jats:p〉 〈jats:p〉In 2022, the annual global average carbon dioxide concentration in the atmosphere rose to 417.1±0.1 ppm, which is 50% greater than the pre-industrial level. Global mean tropospheric methane abundance was 165% higher than its pre-industrial level, and nitrous oxide was 24% higher. All three gases set new record-high atmospheric concentration levels in 2022.〈/jats:p〉 〈jats:p〉Sea-surface temperature patterns in the tropical Pacific characteristic of La Niña and attendant atmospheric patterns tend to mitigate atmospheric heat gain at the global scale, but the annual global surface temperature across land and oceans was still among the six highest in records dating as far back as the mid-1800s. It was the warmest La Niña year on record. Many areas observed record or near-record heat. Europe as a whole observed its second-warmest year on record, with sixteen individual countries observing record warmth at the national scale. Records were shattered across the continent during the summer months as heatwaves plagued the region. On 18 July, 104 stations in France broke their all-time records. One day later, England recorded a temperature of 40°C for the first time ever. China experienced its second-warmest year and warmest summer on record. In the Southern Hemisphere, the average temperature across New Zealand reached a record high for the second year in a row. While Australia’s annual temperature was slightly below the 1991–2020 average, Onslow Airport in Western Australia reached 50.7°C on 13 January, equaling Australia's highest temperature on record.〈/jats:p〉 〈jats:p〉While fewer in number and locations than record-high temperatures, record cold was also observed during the year. Southern Africa had its coldest August on record, with minimum temperatures as much as 5°C below normal over Angola, western Zambia, and northern Namibia. Cold outbreaks in the first half of December led to many record-low daily minimum temperature records in eastern Australia.〈/jats:p〉 〈jats:p〉The effects of rising temperatures and extreme heat were apparent across the Northern Hemisphere, where snow-cover extent by June 2022 was the third smallest in the 56-year record, and the seasonal duration of lake ice cover was the fourth shortest since 1980. More frequent and intense heatwaves contributed to the second-greatest average mass balance loss for Alpine glaciers around the world since the start of the record in 1970. Glaciers in the Swiss Alps lost a record 6% of their volume. In South America, the combination of drought and heat left many central Andean glaciers snow free by mid-summer in early 2022; glacial ice has a much lower albedo than snow, leading to accelerated heating of the glacier. Across the global cryosphere, permafrost temperatures continued to reach record highs at many high-latitude and mountain locations.〈/jats:p〉 〈jats:p〉In the high northern latitudes, the annual surface-air temperature across the Arctic was the fifth highest in the 123-year record. The seasonal Arctic minimum sea-ice extent, typically reached in September, was the 11th-smallest in the 43-year record; however, the amount of multiyear ice—ice that survives at least one summer melt season—remaining in the Arctic continued to decline. Since 2012, the Arctic has been nearly devoid of ice more than four years old.〈/jats:p〉 〈jats:p〉In Antarctica, an unusually large amount of snow and ice fell over the continent in 2022 due to several landfalling atmospheric rivers, which contributed to the highest annual surface mass balance, 15% to 16% above the 1991–2020 normal, since the start of two reanalyses records dating to 1980. It was the second-warmest year on record for all five of the long-term staffed weather stations on the Antarctic Peninsula. In East Antarctica, a heatwave event led to a new all-time record-high temperature of −9.4°C—44°C above the March average—on 18 March at Dome C. This was followed by the collapse of the critically unstable Conger Ice Shelf. More than 100 daily low sea-ice extent and sea-ice area records were set in 2022, including two new all-time annual record lows in net sea-ice extent and area in February.〈/jats:p〉 〈jats:p〉Across the world’s oceans, global mean sea level was record high for the 11th consecutive year, reaching 101.2 mm above the 1993 average when satellite altimetry measurements began, an increase of 3.3±0.7 over 2021. Globally-averaged ocean heat content was also record high in 2022, while the global sea-surface temperature was the sixth highest on record, equal with 2018. Approximately 58% of the ocean surface experienced at least one marine heatwave in 2022. In the Bay of Plenty, New Zealand’s longest continuous marine heatwave was recorded.〈/jats:p〉 〈jats:p〉A total of 85 named tropical storms were observed during the Northern and Southern Hemisphere storm seasons, close to the 1991–2020 average of 87. There were three Category 5 tropical cyclones across the globe—two in the western North Pacific and one in the North Atlantic. This was the fewest Category 5 storms globally since 2017. Globally, the accumulated cyclone energy was the lowest since reliable records began in 1981. Regardless, some storms caused massive damage. In the North Atlantic, Hurricane Fiona became the most intense and most destructive tropical or post-tropical cyclone in Atlantic Canada’s history, while major Hurricane Ian killed more than 100 people and became the third costliest disaster in the United States, causing damage estimated at $113 billion U.S. dollars. In the South Indian Ocean, Tropical Cyclone Batsirai dropped 2044 mm of rain at Commerson Crater in Réunion. The storm also impacted Madagascar, where 121 fatalities were reported.〈/jats:p〉 〈jats:p〉As is typical, some areas around the world were notably dry in 2022 and some were notably wet. In August, record high areas of land across the globe (6.2%) were experiencing extreme drought. Overall, 29% of land experienced moderate or worse categories of drought during the year. The largest drought footprint in the contiguous United States since 2012 (63%) was observed in late October. The record-breaking megadrought of central Chile continued in its 13th consecutive year, and 80-year record-low river levels in northern Argentina and Paraguay disrupted fluvial transport. In China, the Yangtze River reached record-low values. Much of equatorial eastern Africa had five consecutive below-normal rainy seasons by the end of 2022, with some areas receiving record-low precipitation totals for the year. This ongoing 2.5-year drought is the most extensive and persistent drought event in decades, and led to crop failure, millions of livestock deaths, water scarcity, and inflated prices for staple food items.〈/jats:p〉 〈jats:p〉In South Asia, Pakistan received around three times its normal volume of monsoon precipitation in August, with some regions receiving up to eight times their expected monthly totals. Resulting floods affected over 30 million people, caused over 1700 fatalities, led to major crop and property losses, and was recorded as one of the world’s costliest natural disasters of all time. Near Rio de Janeiro, Brazil, Petrópolis received 530 mm in 24 hours on 15 February, about 2.5 times the monthly February average, leading to the worst disaster in the city since 1931 with over 230 fatalities.〈/jats:p〉 〈jats:p〉On 14–15 January, the Hunga Tonga-Hunga Ha'apai submarine volcano in the South Pacific erupted multiple times. The injection of water into the atmosphere was unprecedented in both magnitude—far exceeding any previous values in the 17-year satellite record—and altitude as it penetrated into the mesosphere. The amount of water injected into the stratosphere is estimated to be 146±5 Terragrams, or ∼10% of the total amount in the stratosphere. It may take several years for the water plume to dissipate, and it is currently unknown whether this eruption will have any long-term climate effect.〈/jats:p〉
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  • 22
    Publication Date: 2024-05-08
    Description: NORP-SORP Workshop on Polar Fresh Water: Sources, Pathways and Impacts of Freshwater in Northern and Southern Polar Oceans and Seas (SPICE-UP) What: Up to 60 participants at a time and more than twice as many registrants in total from 20 nations and across experience levels met to discuss the current status of research on freshwater in both polar regions, future directions, and synergies between the Arctic and Southern Ocean research communities When: 19–21 September 2022 Where: Online
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  • 23
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    American Meteorological Society
    In:  EPIC3Bulletin of the American Meteorological Society, American Meteorological Society, 104(9), pp. s271-s321, ISSN: 0003-0007
    Publication Date: 2024-05-08
    Repository Name: EPIC Alfred Wegener Institut
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  • 24
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    Annual Reviews
    In:  EPIC3Annual Review of Marine Science, Annual Reviews, 15(1), pp. 509-538, ISSN: 1941-1405
    Publication Date: 2024-05-10
    Description: The regular movements of waves and tides are obvious representations of the oceans’ rhythmicity. But the rhythms of marine life span across ecological niches and timescales, including short (in the range of hours) and long (in the range of days and months) periods. These rhythms regulate the physiology and behavior of individuals, as well as their interactions with each other and with the environment. This review highlights examples of rhythmicity in marine animals and algae that represent important groups of marine life across different habitats. The examples cover ecologically highly relevant species and a growing number of laboratory model systems that are used to disentangle key mechanistic principles. The review introduces fundamental concepts of chronobiology, such as the distinction between rhythmic and endogenous oscillator–driven processes. It also addresses the relevance of studying diverse rhythms and oscillators, as well as their interconnection, for making better predictions of how species will respond to environmental perturbations, including climate change. As the review aims to address scientists from the diverse fields of marine biology, ecology, and molecular chronobiology, all of which have their own scientific terms, we provide definitions of key terms throughout the article.
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  • 25
    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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  • 26
    Electronic Resource
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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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    Electronic Resource
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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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  • 28
    Electronic Resource
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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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  • 29
    Electronic Resource
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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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  • 30
    Electronic Resource
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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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    Electronic Resource
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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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    Electronic Resource
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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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    Electronic Resource
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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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    Electronic Resource
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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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    Electronic Resource
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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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  • 36
    Electronic Resource
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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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    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 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    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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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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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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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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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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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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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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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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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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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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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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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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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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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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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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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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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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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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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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    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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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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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
    Topics: Biology , Medicine
    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
    Topics: Biology , Medicine
    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 
    ISSN: 1081-0706
    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 
    ISSN: 1081-0706
    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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  • 90
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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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  • 91
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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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  • 92
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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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  • 94
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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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  • 95
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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
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Physics
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    Annual Review of Astronomy and Astrophysics 18 (1980), S. 115-164 
    ISSN: 0066-4146
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Physics
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