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  • American Physical Society  (191,756)
  • American Association for the Advancement of Science  (72,530)
  • American Meteorological Society
  • Annual Reviews
  • International Union of Crystallography (IUCr)
  • 2020-2022  (46,067)
  • 2005-2009  (129,583)
  • 2000-2004  (109,693)
  • 1935-1939  (15,881)
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  • 1
    Publication Date: 2020-10-16
    Description: We propose a version of the pure temporal epidemic type aftershock sequences (ETAS) model: the ETAS model with correlated magnitudes. As for the standard case, we assume the Gutenberg-Richter law to be the probability density for the magnitudes of the background events. Instead, the magnitude of the triggered shocks is assumed to be probabilistically dependent on that of the relative mother events. This probabilistic dependence is motivated by some recent works in the literature and by the results of a statistical analysis made on some seismic catalogs [Spassiani and Sebastiani, J. Geophys. Res. 121, 903 (2016)10.1002/2015JB012398]. On the basis of the experimental evidences obtained in the latter paper for the real catalogs, we theoretically derive the probability density function for the magnitudes of the triggered shocks proposed in Spassiani and Sebastiani and there used for the analysis of two simulated catalogs. To this aim, we impose a fundamental condition: averaging over all the magnitudes of the mother events, we must obtain again the Gutenberg-Richter law. This ensures the validity of this law at any event's generation when ignoring past seismicity. The ETAS model with correlated magnitudes is then theoretically analyzed here. In particular, we use the tool of the probability generating function and the Palm theory, in order to derive an approximation of the probability of zero events in a small time interval and to interpret the results in terms of the interevent time between consecutive shocks, the latter being a very useful random variable in the assessment of seismic hazard.
    Description: Published
    Description: 042134
    Description: 6T. Studi di pericolosità sismica e da maremoto
    Description: JCR Journal
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Type: article
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  • 2
    Publication Date: 2021-06-08
    Description: The Aegean water masses and circulation structure are studied via two large-scale surveys performed during the late winters of 1988 and 1990 by the R/V Yakov Gakkel of the former Soviet Union. The analysis of these data sheds light on the mechanisms of water mass formation in the Aegean Sea that triggered the outflow of Cretan Deep Water (CDW) from the Cretan Sea into the abyssal basins of the eastern Mediterranean Sea (the so-called Eastern Mediterranean Transient). It is found that the central Aegean Basin is the site of the formation of Aegean Intermediate Water, which slides southward and, depending on their density, renews either the intermediate or the deep water of the Cretan Sea. During the winter of 1988, the Cretan Sea waters were renewed mainly at intermediate levels, while during the winter of 1990 it was mainly the volume of CDW that increased. This Aegean water mass redistribution and formation process in 1990 differed from that in 1988 in two major aspects: (i) during the winter of 1990 the position of the front between the Black Sea Water and the Levantine Surface Water was displaced farther north than during the winter of 1988 and (ii) heavier waters were formed in 1990 as a result of enhanced lateral advection of salty Levantine Surface Water that enriched the intermediate waters with salt. In 1990 the 29.2 isopycnal rose to the surface of the central basin and a large volume of CDW filled the Cretan Basin. It is found that, already in 1988, the 29.2 isopycnal surface, which we assume is the lowest density of the CDW, was shallower than the Kassos Strait sill and thus CDW egressed into the Eastern Mediterranean.
    Description: Published
    Description: 1841-1859
    Description: JCR Journal
    Description: reserved
    Keywords: Aegean Sea ; Water Masses ; 03. Hydrosphere::03.03. Physical::03.03.03. Interannual-to-decadal ocean variability
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 3
    Publication Date: 2021-06-01
    Description: Five non-eddy-resolving oceanic general circulation models driven by atmospheric fluxes derived from the NCEP reanalysis are used to investigate the link between the Gulf Stream (GS) variability, the atmospheric circulation, and the Atlantic meridional overturning circulation (AMOC). Despite the limited model resolution, the temperature at the 200-m depth along the mean GS axis behaves similarly in most models to that observed, and it is also well correlated with the North Atlantic Oscillation (NAO), indicating that a northward (southward) GS shift lags a positive (negative) NAO phase by 0–2 yr. The northward shift is accompanied by an increase in the GS transport, and conversely the southward shift with a decrease in the GS transport. Two dominant time scales appear in the response of the GS transport to the NAO forcing: a fast time scale (less than 1 month) for the barotropic component, and a slower one (about 2 yr) for the baroclinic component. In addition, the two components are weakly coupled. The GS response seems broadly consistent with a linear adjustment to the changes in the wind stress curl, and evidence for baroclinic Rossby wave propagation is found in the southern part of the subtropical gyre. However, the GS shifts are also affected by basin-scale changes in the oceanic conditions, and they are well correlated in most models with the changes in the AMOC. A larger AMOC is found when the GS is stronger and displaced northward, and a higher correlation is found when the observed changes of the GS position are used in the comparison. The relation between the GS and the AMOC could be explained by the inherent coupling between the thermohaline and the wind-driven circulation, or by the NAO variability driving them on similar time scales in the models.
    Description: This research was supported by the PREDICATE project of the European Community, and for M. Bentsen by the Research Council of Norway through RegClim, NOClim, and the Programme of Supercomputing.
    Description: Published
    Description: 2119–2135
    Description: 3.7. Dinamica del clima e dell'oceano
    Description: JCR Journal
    Description: reserved
    Keywords: ocean modelling ; gulf stream variability ; 03. Hydrosphere::03.01. General::03.01.03. Global climate models
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 4
    Publication Date: 2020-11-19
    Description: A land surface model (LSM) has been included in the ECMWF Hamburg version 4 (ECHAM4) atmospheric general circulation model (AGCM). The LSM is an early version of the Organizing Carbon and Hydrology in Dynamic Ecosystems (ORCHIDEE) and it replaces the simple land surface scheme previously included in ECHAM4. The purpose of this paper is to document how a more exhaustive consideration of the land surface–vegetation processes affects the simulated boreal summer surface climate. To investigate the impacts on the simulated climate, different sets of Atmospheric Model Intercomparison Project (AMIP)-type simulations have been performed with ECHAM4 alone and with the AGCM coupled with ORCHIDEE. Furthermore, to assess the effects of the increase in horizontal resolution the coupling of ECHAM4 with the LSM has been implemented at different horizontal resolutions. The analysis reveals that the LSM has large effects on the simulated boreal summer surface climate of the atmospheric model. Considerable impacts are found in the surface energy balance due to changes in the surface latent heat fluxes over tropical and midlatitude areas covered with vegetation. Rainfall and atmospheric circulation are substantially affected by these changes. In particular, increased precipitation is found over evergreen and summergreen vegetated areas. Because of the socioeconomical relevance, particular attention has been devoted to the Indian summer monsoon (ISM) region. The results of this study indicate that precipitation over the Indian subcontinent is better simulated with the coupled ECHAM4–ORCHIDEE model compared to the atmospheric model alone.
    Description: Published
    Description: 255–278
    Description: 3.7. Dinamica del clima e dell'oceano
    Description: JCR Journal
    Description: partially_open
    Keywords: Land Atmosphere interactions ; Global climate models ; 01. Atmosphere::01.01. Atmosphere::01.01.02. Climate
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 5
    Publication Date: 2021-05-12
    Description: Producing probabilistic subseasonal forecasts of extreme events up to six weeks in advance is crucial for many economic sectors. In agribusiness, this time scale is particularly critical because it allows for mitigation strategies to be adopted for counteracting weather hazards and taking advantage of opportunities. For example, spring frosts are detrimental for many nut trees, resulting in dramatic losses at harvest time. To explore subseasonal forecast quality in boreal spring, identified as one of the most sensitive times of the year by agribusiness end users, we build a multisystem ensemble using four models involved in the Subseasonal to Seasonal Prediction project (S2S). Two-meter temperature forecasts are used to analyze cold spell predictions in the coastal Black Sea region, an area that is a global leader in the production of hazelnuts. When analyzed at the global scale, the multisystem ensemble probabilistic forecasts for near-surface temperature are better than climatological values for several regions, especially the tropics, even many weeks in advance; however, in the coastal Black Sea, skill is low after the second forecast week. When cold spells are predicted instead of near-surface temperatures, skill improves for the region, and the forecasts prove to contain potentially useful information to stakeholders willing to put mitigation plans into effect. Using a cost–loss model approach for the first time in this context, we show that there is added value of having such a forecast system instead of a business-as-usual strategy, not only for predictions released 1–2 weeks ahead of the extreme event, but also at longer lead times.
    Description: Published
    Description: 237–254
    Description: 4A. Oceanografia e clima
    Description: JCR Journal
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 6
    Publication Date: 2020-07-13
    Repository Name: EPIC Alfred Wegener Institut
    Type: Article , isiRev
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  • 7
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    American Association for the Advancement of Science
    In:  EPIC3Science, American Association for the Advancement of Science, 369(6499), pp. 65-70, ISSN: 1095-9203
    Publication Date: 2021-05-05
    Description: Species’ vulnerability to climate change depends on the most temperature-sensitive life stages, but for major animal groups such as fish, life cycle bottlenecks are often not clearly defined. We used observational, experimental, and phylogenetic data to assess stage-specific thermal tolerance metrics for 694 marine and freshwater fish species from all climate zones. Our analysis shows that spawning adults and embryos consistently have narrower tolerance ranges than larvae and nonreproductive adults and are most vulnerable to climate warming. The sequence of stage-specific thermal tolerance corresponds with the oxygen-limitation hypothesis, suggesting a mechanistic link between ontogenetic changes in cardiorespiratory (aerobic) capacity and tolerance to temperature extremes. A logarithmic inverse correlation between the temperature dependence of physiological rates (development and oxygen consumption) and thermal tolerance range is proposed to reflect a fundamental, energetic trade-off in thermal adaptation. Scenario-based climate projections considering the most critical life stages (spawners and embryos) clearly identify the temperature requirements for reproduction as a critical bottleneck in the life cycle of fish. By 2100, depending on the Shared Socioeconomic Pathway (SSP) scenario followed, the percentages of species potentially affected by water temperatures exceeding their tolerance limit for reproduction range from ~10% (SSP 1–1.9) to ~60% (SSP 5–8.5). Efforts to meet ambitious climate targets (SSP 1–1.9) could therefore benefit many fish species and people who depend on healthy fish stocks.
    Repository Name: EPIC Alfred Wegener Institut
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  • 8
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    American Association for the Advancement of Science
    In:  EPIC3Science, American Association for the Advancement of Science, 367(6474), pp. 156-156
    Publication Date: 2020-01-19
    Repository Name: EPIC Alfred Wegener Institut
    Type: Article , peerRev
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  • 9
    Publication Date: 2021-01-25
    Repository Name: EPIC Alfred Wegener Institut
    Type: Article , peerRev
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  • 10
    Publication Date: 2017-04-04
    Description: The continuous volcanic and seismic activity at Mount Etna makes this volcano an important laboratory for seismological and geophysical studies. We used repeated three-dimensional tomography to detect variations in elastic parameters during different volcanic cycles, before and during the October 2002–January 2003 flank eruption. Well-defined anomalous low P- to S-wave velocity ratio volumes were revealed. Absent during the pre-eruptive period, the anomalies trace the intrusion of volatile-rich (Q4 weight percent) basaltic magma, most of which rose up only a few months before the onset of eruption. The observed time changes of velocity anomalies suggest that four-dimensional tomography provides a basis for more efficient volcano monitoring and shortand midterm eruption forecasting of explosive activity.
    Description: Published
    Description: 821-823
    Description: reserved
    Keywords: NONE ; 04. Solid Earth::04.01. Earth Interior::04.01.02. Geological and geophysical evidences of deep processes ; 04. Solid Earth::04.06. Seismology::04.06.07. Tomography and anisotropy ; 04. Solid Earth::04.08. Volcanology::04.08.06. Volcano monitoring
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Type: article
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  • 11
    Publication Date: 2017-04-04
    Description: In this paper results from the application of an ocean data assimilation (ODA) system, combining a multivariate reduced-order optimal interpolator (OI) scheme with a global ocean general circulation model (OGCM), are described. The present ODA system, designed to assimilate in situ temperature and salinity observations, has been used to produce ocean reanalyses for the 1962–2001 period. The impact of assimilating observed hydrographic data on the ocean mean state and temporal variability is evaluated. A special focus of this work is on the ODA system skill in reproducing a realistic ocean salinity state. Results from a hierarchy of different salinity reanalyses, using varying combinations of assimilated data and background error covariance structures, are described. The impact of the space and time resolution of the background error covariance parameterization on salinity is addressed.
    Description: This work has been funded by the ENACT Project (Contract EVK2-CT2001-00117) for A. Bellucci and P. Di Pietro, and partially by the ENSEMBLES Project (Contract GOCE-CT-2003-505539) for A. Bellucci.
    Description: Published
    Description: 3785-3807
    Description: 3.7. Dinamica del clima e dell'oceano
    Description: JCR Journal
    Description: reserved
    Keywords: ocean modelling ; data assimilation ; reanalysis ; upper ocean variability ; temperature ; Salinity ; 03. Hydrosphere::03.01. General::03.01.04. Ocean data assimilation and reanalysis
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 12
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    American Association for the Advancement of Science
    Publication Date: 2017-04-04
    Description: BREVIA
    Description: Current emission inventories require an additional "unknown" source to balance the global atmospheric budgets of ethane (C2H6). Here, we provide evidence that a substantial part of the missing source can be attributed to natural gas seepage from petroliferous, geothermal, and volcanic areas. Such geologic sources also inject propane (C3H8) into the atmosphere. The analysis of a large data set of methane (CH4), ethane, and propane concentrations in surface gas emissions of 238 sites from different geographic and geologic areas, coupled with published estimates of geomethane emissions, suggests that Earth's degassing accounts for at least 17% and 10% of total ethane and propane emissions, respectively.
    Description: Published
    Description: 478
    Description: 3.8. Geofisica per l'ambiente
    Description: JCR Journal
    Description: reserved
    Keywords: Ethane ; Propane ; Geologic emissions ; Seepage ; 03. Hydrosphere::03.04. Chemical and biological::03.04.05. Gases
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  • 13
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    American Association for the Advancement of Science
    Publication Date: 2017-04-04
    Description: Episodes of nonvolcanic tremor and accompanying slow slip recently have been observed in the subduction zones of Japan and Cascadia. In Cascadia, such episodes typically last a few weeks, and differ from “normal” earthquakes in their source location and momentduration scaling. The three most recent episodes in the Puget Sound/Southern Vancouver Island portion of the Cascadia subduction zone have been exceptionally well recorded. In each episode, we see clear pulsing of tremor activity with periods of 12.4 and 24-25 hours, the same as the principal lunar and lunisolar tides. This indicates that the small stresses associated with the solid-earth and ocean tides influence the genesis of tremor much more effectively than they do “normal” earthquakes. Because the lithostatic stresses are 105 times larger than those associated with the tides, we argue that tremor occurs on very weak faults.
    Description: Published
    Description: 186 -189
    Description: 3.1. Fisica dei terremoti
    Description: JCR Journal
    Description: reserved
    Keywords: Nonvolcanic ; tremor ; 04. Solid Earth::04.06. Seismology::04.06.01. Earthquake faults: properties and evolution ; 04. Solid Earth::04.06. Seismology::04.06.02. Earthquake interactions and probability ; 04. Solid Earth::04.06. Seismology::04.06.03. Earthquake source and dynamics
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  • 14
    Publication Date: 2017-04-04
    Description: The effect of horizontal resolution on tropical variability is investigated within the modified SINTEX model, SINTEX-F, developed jointly at INGV, IPSL and at the Frontier Research System. The horizontal resolutions T30 and T106 are investigated in terms of the coupling characteristics, frequency and variability of the tropical ocean-atmosphere interactions. It appears that the T106 resolution is generally beneficial even if it does not eliminate all the major systematic errors of the coupled model. There is an excessive shift west of the cold tongue and ENSO variability, and high resolution has also a somewhat negative impact to the variability in the East Indian Ocean. A dominant two-year peak for the NINO3 variabilty in the T30 model is moderated in the T106 as it shifts to longer time scale. At high resolution new processes come into play, as the coupling of tropical instability waves, the resolution of coastal flows at the Pacific Mexican coasts and improved coastal forcing along the coast of South America. The delayed oscillator seems the main mechanism that generates the interannual variability in both models, but the models realize it in different ways. In the T30 model it is confined close to the equator, involving relatively fast equatorial and near-equatorial modes, in the high resolution, it involves a wider latitudinal region and slower waves. It is speculated that the extent of the region that is involved in the interannual variability may be linked to the time scale of the variability itself.
    Description: This research was partially supported by the Italy–USA Cooperation Program of the Italian Ministry of Environment and by the EU projects ENSEMBLES and DYNAMITE.
    Description: Published
    Description: 730-750
    Description: 3.7. Dinamica del clima e dell'oceano
    Description: JCR Journal
    Description: reserved
    Keywords: coupled models ; tropical variability ; ENSO system ; 03. Hydrosphere::03.01. General::03.01.03. Global climate models
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  • 15
    Publication Date: 2017-04-04
    Description: The Indian Summer Monsoon (ISM) is one of the main components of the Asian summer monsoon. It is well known that one of the starting mechanisms of a summer monsoon is the thermal contrast between land and ocean and that sea surface temperature (SST) and moisture are crucial factors for its evolution and intensity. The Indian Ocean, therefore, may play a very important role in the generation and evolution of the ISM itself. A coupled general circulation model, implemented with a high resolution atmospheric component, appears to be able to simulate the Indian summer monsoon in a realistic way. In particular, the features of the simulated ISM variability are similar to the observations. In this study, the relationships between ISM and Tropical Indian Ocean (TIO) SST anomalies are investigated, as well as the ability of the coupled model to capture those connections. The recent discovery of the Indian Ocean Dipole Mode (IODM) may suggest new perspectives in the relationship between ISM and TIO SST. A new statistical technique, the Coupled Manifold, is used to investigate the TIO SST variability and its relation with the Tropical Pacific Ocean (TPO). The analysis shows that the SST variability in the TIO contains a significant portion that is independent from the TPO variability. The same technique is used to estimate the amount of Indian rainfall variability that can be explained by the Tropical Indian Ocean SST. Indian Ocean SST anomalies are separated in a part remotely forced from the Tropical Pacific Ocean variability and a part independent from that. The relationships between the two SSTA components and the Indian monsoon variability are then investigated in detail.
    Description: Published
    Description: 3083-3105
    Description: 3.7. Dinamica del clima e dell'oceano
    Description: JCR Journal
    Description: reserved
    Keywords: Indian Ocean ; monsoon ; 01. Atmosphere::01.01. Atmosphere::01.01.02. Climate
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  • 16
    Publication Date: 2017-04-04
    Description: We perform an analysis on the dissipative Olami-Feder-Christensen model on a small world topology considering avalanche size differences. We show that when criticality appears, the probability density functions (PDFs) for the avalanche size differences at different times have fat tails with a q-Gaussian shape. This behavior does not depend on the time interval adopted and is found also when considering energy differences between real earthquakes. Such a result can be analytically understood if the sizes (released energies) of the avalanches (earthquakes) have no correlations. Our findings support the hypothesis that a self-organized criticality mechanism with long-range interactions is at the origin of seismic events and indicate that it is not possible to predict the magnitude of the next earthquake knowing those of the previous ones.
    Description: Published
    Description: 2.3. TTC - Laboratori di chimica e fisica delle rocce
    Description: JCR Journal
    Description: reserved
    Keywords: SOC, earthquakes interaction ; 05. General::05.01. Computational geophysics::05.01.04. Statistical analysis
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  • 17
    Publication Date: 2017-04-04
    Description: An assessment of the present European operational marine monitoring and forecasting systems shows how observations, atmospheric forcing fields and ocean models combine to make useful oceanographic products possible.
    Description: Published
    Description: 1081-1090
    Description: open
    Keywords: MARINE ENVIRONMENT ; 03. Hydrosphere::03.01. General::03.01.05. Operational oceanography
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  • 18
    Publication Date: 2017-04-04
    Description: Ensemble experiments are performed with five coupled atmosphere–ocean models to investigate the potential for initial-value climate forecasts on interannual to decadal time scales. Experiments are started from similar model-generated initial states, and common diagnostics of predictability are used. We find that variations in the ocean meridional overturning circulation (MOC) are potentially predictable on interannual to decadal time scales, a more consistent picture of the surface temperature impact of decadal variations in the MOC is now apparent, and variations of surface air temperatures in the North Atlantic Ocean are also potentially predictable on interannual to decadal time scales, albeit with potential skill levels that are less than those seen for MOC variations. This intercomparison represents a step forward in assessing the robustness of model estimates of potential skill and is a prerequisite for the development of any operational forecasting system.
    Description: Published
    Description: 1195-1203
    Description: JCR Journal
    Description: reserved
    Keywords: Decadal Climate ; North Atlantic ; 03. Hydrosphere::03.01. General::03.01.03. Global climate models ; 03. Hydrosphere::03.02. Hydrology::03.02.05. Models and Forecasts ; 03. Hydrosphere::03.03. Physical::03.03.03. Interannual-to-decadal ocean variability
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  • 19
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    American Meteorological Society
    In:  EPIC3Journal of Atmospheric and Oceanic Technology, American Meteorological Society, 25(2), pp. 149-166, ISSN: 0739-0572
    Publication Date: 2019-07-17
    Description: The accuracy of all types of Vaisala radiosondes and two types of Snow White chilled-mirror hygrosondes was assessed in an intensive in situ comparison with reference hygrometers. Fourteen nighttime reference comparisons were performed to determine a working reference for the radiosonde comparisons. These showed that the night version of the Snow White agreed best with the references [i.e., the NOAA frost-point hygrometer (FPH) and University of Colorado cryogenic frost-point hygrometer (CFH)], but that the daytime version had severe problems with contamination in the humid upper troposphere. Since the RS92 performance was superior to the other radiosondes and to the day version of the Snow White, it was selected to be the working reference. According to the reference comparison, the RS92 has no bias in the mid- and lower troposphere, with deviations 〈±5% in relative humidity (RH). In the upper troposphere, the RS92 has a 5% RH wet bias, which is partly due to the RS92 time lag error and the termination of the heating cycle. It was shown that the time lag effects relating to Vaisala radiosondes can be corrected. Because these were nighttime comparisons, they can be considered to be free from solar radiation effects. Neither the radiosondes nor the Snow White succeeded in reproducing reference class hygrometer profiles in the stratosphere. According to the 29 radiosonde intercomparisons, the RS92 and the modified RS90 (FN) had the best mutual agreement and no bias. The disagreement is largest (〈±10% RH) at low temperatures (T ≪ −30°C), where the FN underestimated (overestimated) in high (low) ambient RH. In comparison with the RS92, the RS90 had a semilinearly increasing wet bias with decreasing temperature, where the bias was 10% RH at −60°C. The RS80-A suffers from a large temperature-dependent dry bias in high RH conditions, being over 30% RH at −60°C and 5% RH near 0°C. The RS80-A dry bias can be almost totally removed with the correction algorithm by Leiterer et al., which was chosen as the best available. The other approach tested tends to overcorrect in high RH conditions when T 〈 −50°C. For T 〉 −30°C it is ineffective and does not correct the RS80-A dry bias in high ambient RH.
    Repository Name: EPIC Alfred Wegener Institut
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  • 20
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    American Meteorological Society
    Publication Date: 2021-05-19
    Description: In this study we show a teleconnection pattern relating Outgoing Longwave Radiation (OLR) anomalies over the western Pacific Ocean and sea surface temperature anomalies (SSTA) over the western Indian Ocean over two seasons (Sept-Oct-Nov and Dec-Jan-Feb) at zero lag from observations and atmospheric general circulation model (AGCM) integrations. This teleconnection pattern suggests that a positive SSTA in Sept-Oct-Nov (SON) and Dec-Jan-Feb (DJF) seasons over the western Indian Ocean increases the contemporaneous positive OLR anomalies over the western Pacific Ocean. This teleconnection pattern is also simulated by the Center for Ocean-Land- Atmosphere studies (COLA) AGCM forced with observed SST’s. From the experimental COLA AGCM runs (wherein the Pacific Ocean SST variability is suppressed except for the climatological annual cycle) it is diagnosed that the interannual variability of OLR over the western Pacific Ocean persists because of this teleconnection. In relation to this teleconnection pattern it is shown that there is a significant linear response of the SON and DJF equatorial zonal wind anomaly over the Pacific Ocean to contemporaneous SSTA over the western Indian Ocean which is comparable to that of the eastern and western Pacific Oceans. The experimental AGCM runs clearly show that this response of the equatorial zonal wind anomaly to the western Indian Ocean forcing shifts westward towards the Indian Ocean in the absence of Pacific SST variability.
    Description: Published
    Keywords: Sea surface temperature ; Atmospheric conditions ; Teleconnections
    Repository Name: AquaDocs
    Type: Journal Contribution , Refereed , Article
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  • 21
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    American Meteorological Society
    Publication Date: 2021-05-19
    Description: Skill in ensemble-mean dynamical seasonal climate hindcasts with a coupled land-atmosphere model and specified observed sea surface temperature is compared to that for long multi-decade integrations of the same model where the initial conditions are far removed from the seasons of validation. The evaluations are performed for surface temperature and compared among all seasons. Skill is found to be higher in the seasonal simulations than the multi-decadal integrations except during boreal winter. The higher skill is prominent even beyond the first month when the direct influence of the atmospheric initial state elevates model skill. Skill is generally found to be lowest during the winter season for the dynamical seasonal forecasts, equal to that of the long integrations, which show some of the highest skill during winter. The reason for the differences in skill during the non-winter months is attributed to the severe climate drift in the long simulations, manifest through errors in downward fluxes of water and energy over land and evident in soil wetness. The drift presses the land surface to extreme dry or wet states over much of the globe, into a range where there is little sensitivity of evaporation to fluctuations in soil moisture. Thus, the land-atmosphere feedback is suppressed, which appears to lessen the model’s ability to respond correctly over land to remote ocean temperature anomalies.
    Description: Center for Ocean-Land-Atmosphere Studies
    Description: Published
    Keywords: Atmosphere-ocean system
    Repository Name: AquaDocs
    Type: Journal Contribution , Refereed , Article
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  • 22
    Publication Date: 2021-05-19
    Description: In this paper, the circulations driven by deep heating and shallow heating are investigated through analytically solving a set of linear equations and examining circulations simulated by a dry primitive equation model. Special emphasis is placed on the low-level mass (moisture) convergence associated with the forced circulation and the maintenance of the shallow and deep heat sources. It is found that the forced circulation driven by shallow heating is more likely to be trapped horizontally near the heating area but relatively extended in the vertical. As a consequence, diabatic heating can not balance adiabatic cooling due to upward motion. At the levels slightly above the top of the heating, a negative vertical gradient of temperature perturbation appears. For the atmosphere driven by deep heating, however, the temperature perturbation cannot accumulate because the heating signals propagate away very fast, allowing an approximate equilibrium between the convective diabatic heating and adiabatic cooling due to upward motion. The converged moisture associated with circulation driven by shallow heating exceeds the amount needed to maintain the heat source. However, the circulation driven by deep heating does not feed back effectively to the moisture convergence, and thus can not be self-sustaining.
    Description: Center for Ocean-Land-Atmosphere Studies - Calverton
    Description: Published
    Keywords: Atmospheric circulation
    Repository Name: AquaDocs
    Type: Journal Contribution , Refereed , Article
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  • 23
    Publication Date: 2022-05-25
    Description: Author Posting. © Annual Reviews, 2003. This article is posted here by permission of Annual Reviews for personal use, not for redistribution. The definitive version was published in Annual Review of Environment and Resources 28 (2003): 521-558, doi:10.1146/annurev.energy.28.011503.163443.
    Description: Agriculture and industrial development have led to inadvertent changes in the natural carbon cycle. As a consequence, concentrations of carbon dioxide and other greenhouse gases have increased in the atmosphere and may lead to changes in climate. The current challenge facing society is to develop options for future management of the carbon cycle. A variety of approaches has been suggested: direct reduction of emissions, deliberate manipulation of the natural carbon cycle to enhance sequestration, and capture and isolation of carbon from fossil fuel use. Policy development to date has laid out some of the general principles to which carbon management should adhere. These are summarized as: how much carbon is stored, by what means, and for how long. To successfully manage carbon for climate purposes requires increased understanding of carbon cycle dynamics and improvement in the scientific capabilities available for measurement as well as for policy needs. The specific needs for scientific information to underpin carbon cycle management decisions are not yet broadly known. A stronger dialogue between decision makers and scientists must be developed to foster improved application of scientific knowledge to decisions. This review focuses on the current knowledge of the carbon cycle, carbon measurement capabilities (with an emphasis on the continental scale) and the relevance of carbon cycle science to carbon sequestration goals.
    Description: The National Center for Atmospheric Research is supported by the National Science Foundation.
    Keywords: Carbon sequestration ; Measurement techniques ; Climate ; Kyoto protocol
    Repository Name: Woods Hole Open Access Server
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    Annual Reviews
    Publication Date: 2022-05-25
    Description: Author Posting. © Annual Reviews, 2006. This article is posted here by permission of Annual Reviews for personal use, not for redistribution. The definitive version was published in Annual Review of Fluid Mechanics 38 (2006): 395-425, doi:10.1146/annurev.fluid.38.050304.092129.
    Description: Over the past four decades, the combination of in situ and remote sensing observations has demonstrated that long nonlinear internal solitary-like waves are ubiquitous features of coastal oceans. The following provides an overview of the properties of steady internal solitary waves and the transient processes of wave generation and evolution, primarily from the point of view of weakly nonlinear theory, of which the Korteweg-de Vries equation is the most frequently used example. However, the oceanographically important processes of wave instability and breaking, generally inaccessible with these models, are also discussed. Furthermore, observations often show strongly nonlinear waves whose properties can only be explained with fully nonlinear models.
    Description: KRH acknowledges support from NSF and ONR and an Independent Study Award from the Woods Hole Oceanographic Institution. WKM acknowledges support from NSF and ONR, which has made his work in this area possible, in close collaboration with former graduate students at Scripps Institution of Oceanography and MIT.
    Keywords: Solitary waves ; Nonlinear waves ; Stratified flow ; Physical Oceanography
    Repository Name: Woods Hole Open Access Server
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  • 25
    Publication Date: 2022-05-25
    Description: This paper is not subject to U.S. copyright. The definitive version was published in Journal of Atmospheric and Oceanic Technology 21 (2004): 1448–1461, doi:10.1175/1520-0426(2004)021〈1448:AOAPAD〉2.0.CO;2.
    Description: The accuracy of velocities measured by a pulse-coherent acoustic Doppler profiler (PCADP) in the bottom boundary layer of a wave-dominated inner-shelf environment is evaluated. The downward-looking PCADP measured velocities in eight 10-cm cells at 1 Hz. Velocities measured by the PCADP are compared to those measured by an acoustic Doppler velocimeter for wave orbital velocities up to 95 cm s−1 and currents up to 40 cm s−1. An algorithm for correcting ambiguity errors using the resolution velocities was developed. Instrument bias, measured as the average error in burst mean speed, is −0.4 cm s−1 (standard deviation = 0.8). The accuracy (root-mean-square error) of instantaneous velocities has a mean of 8.6 cm s−1 (standard deviation = 6.5) for eastward velocities (the predominant direction of waves), 6.5 cm s−1 (standard deviation = 4.4) for northward velocities, and 2.4 cm s−1 (standard deviation = 1.6) for vertical velocities. Both burst mean and root-mean-square errors are greater for bursts with ub ≥ 50 cm s−1. Profiles of burst mean speeds from the bottom five cells were fit to logarithmic curves: 92% of bursts with mean speed ≥ 5 cm s−1 have a correlation coefficient R2 〉 0.96. In cells close to the transducer, instantaneous velocities are noisy, burst mean velocities are biased low, and bottom orbital velocities are biased high. With adequate blanking distances for both the profile and resolution velocities, the PCADP provides sufficient accuracy to measure velocities in the bottom boundary layer under moderately energetic inner-shelf conditions.
    Description: This work was funded by the U.S. Geological Survey as part of the Southwest Washington Coastal Erosion Study
    Repository Name: Woods Hole Open Access Server
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  • 26
    Publication Date: 2022-05-25
    Description: Author Posting. © The Authors, 2006. This article is posted here by permission of American Physical Society for personal use, not for redistribution. The definitive version was published in Physical Review Letters 96 (2006): 018305, doi:10.1103/PhysRevLett.96.018305.
    Description: We study the liquid-crystalline phase behavior of a concentrated suspension of helical flagella isolated from Salmonella typhimurium. Flagella are prepared with different polymorphic states, some of which have a pronounced helical character while others assume a rodlike shape. We show that the static phase behavior and dynamics of chiral helices are very different when compared to simpler achiral hard rods. With increasing concentration, helical flagella undergo an entropy-driven first order phase transition to a liquid-crystalline state having a novel chiral symmetry.
    Description: M. S. and R. O. are supported by NIH Grant No. EB002583.
    Keywords: Entropy ; Molecular biophysics ; Liquid crystal phase transformations ; Symmetry ; Chirality
    Repository Name: Woods Hole Open Access Server
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  • 27
    Publication Date: 2022-05-25
    Description: First published online as a Review in Advance on October 24, 2005. (Some corrections may occur before final publication online and in print)
    Description: Author Posting. © Annual Reviews, 2005. This article is posted here by permission of Annual Reviews for personal use, not for redistribution. The definitive version was published in Annual Review of Physiology 68 (2006): 22.1-22.29, doi:10.1146/annurev.physiol.68.040104.105418.
    Description: Superfast muscles of vertebrates power sound production. The fastest, the swimbladder muscle of toadfish, generates mechanical power at frequencies in excess of 200 Hz. To operate at these frequencies, the speed of relaxation has had to increase approximately 50-fold. This increase is accomplished by modifications of three kinetic traits: (a) a fast calcium transient due to extremely high concentration of sarcoplasmic reticulum (SR)-Ca2+ pumps and parvalbumin, (b) fast off-rate of Ca2+ from troponin C due to an alteration in troponin, and (c) fast cross-bridge detachment rate constant (g, 50 times faster than that in rabbit fast-twitch muscle) due to an alteration in myosin. Although these three modifications permit swimbladder muscle to generate mechanical work at high frequencies (where locomotor muscles cannot), it comes with a cost: The high g causes a large reduction in attached force-generating cross-bridges, making the swimbladder incapable of powering low-frequency locomotory movements. Hence the locomotory and sound-producing muscles have mutually exclusive designs.
    Description: This work was made possible by support from NIH grants AR38404 and AR46125 as well as the University of Pennsylvania Research Foundation.
    Keywords: Parvalbumin ; Ca2+ release ; Ca2+ uptake ; Cross-bridges ; Adaptation ; Sound production ; Whitman Center
    Repository Name: Woods Hole Open Access Server
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    American Meteorological Society
    Publication Date: 2020-03-16
    Description: Author Posting. © American Meteorological Society, 2020. 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 33(4), (2020): 1535-1545, doi:10.1175/JCLI-D-19-0547.1.
    Description: In a transient warming scenario, the North Atlantic is influenced by a complex pattern of surface buoyancy flux changes that ultimately weaken the Atlantic meridional overturning circulation (AMOC). Here we study the AMOC response in the CMIP5 experiment, using the near-geostrophic balance of the AMOC on interannual time scales to identify the role of temperature and salinity changes in altering the circulation. The thermal wind relationship is used to quantify changes in the zonal density gradients that control the strength of the flow. At 40°N, where the overturning cell is at its strongest, weakening of the AMOC is largely driven by warming between 1000- and 2000-m depth along the western margin. Despite significant subpolar surface freshening, salinity changes are small in the deep branch of the circulation. This is likely due to the influence of anomalously salty water in the subpolar intermediate layers, which is carried northward from the subtropics in the upper limb of the AMOC. In the upper 1000 m at 40°N, salty anomalies due to increased evaporation largely cancel the buoyancy increase due to warming. Therefore, in CMIP5, temperature dynamics are responsible for AMOC weakening, while freshwater forcing instead acts to strengthen the circulation in the net. These results indicate that past modeling studies of AMOC weakening, which rely on freshwater hosing in the subpolar gyre, may not be directly applicable to a more complex warming scenario.
    Description: We acknowledge the World Climate Research Programme’s Working Group on Coupled Modelling, which is responsible for CMIP, and we thank the climate modeling groups (listed in Table 1 of this paper) for producing and making available their model output. We also thank John Marshall for helpful discussions on the driving mechanisms of the AMOC, and three anonymous reviewers whose comments greatly improved the manuscript. This work was supported by NASA Headquarters under the NASA Earth and Space Science Fellowship Program Award 80NSSC17K0372, and by National Science Foundation Award OCE-1433132.
    Description: 2020-07-20
    Keywords: North Atlantic Ocean ; Thermohaline circulation ; Water masses/storage ; Climate change ; Climate prediction ; Climate models
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    American Association for the Advancement of Science
    In:  EPIC3Science advances, American Association for the Advancement of Science, 7(44), pp. eabg9739
    Publication Date: 2021-12-05
    Description: Elemental carbon exists in different structural forms including graphite, diamond, fullerenes, and amorphous carbon. In nature, these materials are produced through abiotic chemical processes under high temperature and pressure but are considered generally inaccessible to biochemical synthesis or breakdown. Here, we identified and characterized elemental carbon isolated from consortia of anaerobic methanotrophic archaea (ANME) and sulfate-reducing bacteria (SRB), which together carry out the anaerobic oxidation of methane (AOM). Two different AOM consortia, ANME-1a/HotSeep-1 and ANME-2a/c/Seep-SRB, produce a black material with similar characteristics to disordered graphite and amorphous carbon. Stable isotope probing studies revealed that the carbon is microbially generated during AOM. In addition, we found that select methanogens also produce amorphous carbon with similar characteristics to the carbon from AOM consortia. Biogenic amorphous carbon may serve as a conductive element to facilitate electron transfer, or redox active functional groups associated with the carbon could act as electron donors and acceptors.
    Repository Name: EPIC Alfred Wegener Institut
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    American Association for the Advancement of Science
    In:  EPIC3Science, American Association for the Advancement of Science, 373(6550), pp. 118-121
    Publication Date: 2021-10-20
    Repository Name: EPIC Alfred Wegener Institut
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    American Association for the Advancement of Science
    In:  EPIC3Science advances, American Association for the Advancement of Science, 7(27), pp. eabj1453
    Publication Date: 2021-10-20
    Description: Methanogens are considered as one of the earliest life forms on Earth, and together with anaerobic methane-oxidizing archaea, they have crucial effects on climate stability. However, the origin and evolution of anaerobic alkane metabolism in the domain Archaea remain controversial. Here, we present evidence that methylotrophic methanogenesis was the ancestral form of this metabolism. Carbon dioxide–reducing methanogenesis developed later through the evolution of tetrahydromethanopterin S-methyltransferase, which linked methanogenesis to the Wood-Ljungdahl pathway for energy conservation. Anaerobic multicarbon alkane metabolisms in Archaea also originated early, with genes coding for the activation of short-chain or even long-chain alkanes likely evolving from an ethane-metabolizing ancestor. These genes were likely horizontally transferred to multiple archaeal clades including Candidatus (Ca.) Bathyarchaeia, Ca. Lokiarchaeia, Ca. Hadarchaeia, and the methanogenic Ca. Methanoliparia.
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    American Association for the Advancement of Science
    In:  EPIC3Science Advances, American Association for the Advancement of Science, 7(19), pp. eabe4939
    Publication Date: 2021-10-20
    Repository Name: EPIC Alfred Wegener Institut
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  • 33
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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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    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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    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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    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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    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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    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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    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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    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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    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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    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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    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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    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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    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract Computer modeling has been developed and widely applied in studying molecules of biological interest. The force field is the cornerstone of computer simulations, and many force fields have been developed and successfully applied in these simulations. Two interesting areas are (a) studying enzyme catalytic mechanisms using a combination of quantum mechanics and molecular mechanics, and (b) studying macromolecular dynamics and interactions using molecular dynamics (MD) and free energy (FE) calculation methods. Enzyme catalysis involves forming and breaking of covalent bonds and requires the use of quantum mechanics. Noncovalent interactions appear ubiquitously in biology, but here we confine ourselves to review only noncovalent interactions between protein and protein, protein and ligand, and protein and nucleic acids.
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    Annual Review of Biophysics and Biomolecular Structure 30 (2001), S. 245-269 
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract Molecular chaperones are required to assist folding of a subset of proteins in Escherichia coli. We describe a conceptual framework for understanding how the GroEL-GroES system assists misfolded proteins to reach their native states. The architecture of GroEL consists of double toroids stacked back-to-back. However, most of the fundamentals of the GroEL action can be described in terms of the single ring. A key idea in our framework is that, with coordinated ATP hydrolysis and GroES binding, GroEL participates actively by repeatedly unfolding the substrate protein (SP), provided that it is trapped in one of the misfolded states. We conjecture that the unfolding of SP becomes possible because a stretching force is transmitted to the SP when the GroEL particle undergoes allosteric transitions. Force-induced unfolding of the SP puts it on a higher free-energy point in the multidimensional energy landscape from which the SP can either reach the native conformation with some probability or be trapped in one of the competing basins of attraction (i.e., the SP undergoes kinetic partitioning). The model shows, in a natural way, that the time scales in the dynamics of the allosteric transitions are intimately coupled to folding rates of the SP. Several scenarios for chaperonin-assisted folding emerge depending on the interplay of the time scales governing the cycle. Further refinement of this framework may be necessary because single molecule experiments indicate that there is a great dispersion in the time scales governing the dynamics of the chaperonin cycle.
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    Annual Review of Biophysics and Biomolecular Structure 31 (2002), S. 1-44 
    ISSN: 1056-8700
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    Annual Review of Biophysics and Biomolecular Structure 30 (2001), S. 421-455 
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    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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    Notes: Abstract The structures of an increasing number of channels and other alpha-helical membrane proteins have been determined recently, including the KcsA potassium channel, the MscL mechanosensitive channel, and the AQP1 and GlpF members of the aquaporin family. In this chapter, the orientation and packing characteristics of bilayer-spanning helices are surveyed in integral membrane proteins. In the case of channels, alpha-helices create the sealed barrier that separates the hydrocarbon region of the bilayer from the permeation pathway for solutes. The helices surrounding the permeation pathway tend to be rather steeply tilted relative to the membrane normal and are consistently arranged in a right-handed bundle. The helical framework further provides a supporting scaffold for nonmembrane-spanning structures associated with channel selectivity. Although structural details remain scarce, the conformational changes associated with gating transitions between closed and open states of channels are reviewed, emphasizing the potential roles of helix-helix interactions in this process.
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    Annual Review of Biophysics and Biomolecular Structure 31 (2002), S. 275-302 
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    Notes: Abstract Using luminescent lanthanides, instead of conventional fluorophores, as donor molecules in resonance energy transfer measurements offers many technical advantages and opens up a wide range of new applications. Advantages include farther measurable distances (~100 A) with greater accuracy, insensitivity to incomplete labeling, and the ability to use generic relatively large labels, when necessary. Applications highlighted include the study of ion channels in living cells, protein-protein interaction in cells, DNA-protein complexes, and high-throughput screening assays to measure peptide dimerization associated with DNA transcription factors and ligand-receptor interactions.
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    Annual Review of Biophysics and Biomolecular Structure 31 (2002), S. 303-319 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Abstract Cryo-electron microscopy (cryo-EM) of biological molecules in single-particle (i.e., unordered, nonaggregated) form is a new approach to the study of molecular assemblies, which are often too large and flexible to be amenable to X-ray crystallography. New insights into biological function on the molecular level are expected from cryo-EM applied to the study of such complexes "trapped" at different stages of their conformational changes and dynamical interactions. Important molecular machines involved in the fundamental processes of transcription, mRNA splicing, and translation are examples for successful applications of the new technique, combined with structural knowledge gained by conventional techniques of structure determination, such as X-ray crystallography and NMR.
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    Annual Review of Biophysics and Biomolecular Structure 31 (2002), S. 443-484 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Abstract The recent report of the crystal structure of rhodopsin provides insights concerning structure-activity relationships in visual pigments and related G protein-coupled receptors (GPCRs). The seven transmembrane helices of rhodopsin are interrupted or kinked at multiple sites. An extensive network of interhelical interactions stabilizes the ground state of the receptor. The ligand-binding pocket of rhodopsin is remarkably compact, and several chromophore-protein interactions were not predicted from mutagenesis or spectroscopic studies. The helix movement model of receptor activation, which likely applies to all GPCRs of the rhodopsin family, is supported by several structural elements that suggest how light-induced conformational changes in the ligand-binding pocket are transmitted to the cytoplasmic surface. The cytoplasmic domain of the receptor includes a helical domain extending from the seventh transmembrane segment parallel to the bilayer surface. The cytoplasmic surface appears to be approximately large enough to bind to the transducin heterotrimer in a one-to-one complex. The structural basis for several unique biophysical properties of rhodopsin, including its extremely low dark noise level and high quantum efficiency, can now be addressed using a combination of structural biology and various spectroscopic methods. Future high-resolution structural studies of rhodopsin and other GPCRs will form the basis to elucidate the detailed molecular mechanism of GPCR-mediated signal transduction.
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    Annual Review of Biophysics and Biomolecular Structure 31 (2002), S. 485-516 
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    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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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Abstract The past decade has witnessed increasingly detailed insights into the structural mechanism of the bacteriorhodopsin photocycle. Concurrently, there has been much progress within our knowledge pertaining to the lipids of the purple membrane, including the discovery of new lipids and the overall effort to localize and identify each lipid within the purple membrane. Therefore, there is a need to classify this information to generalize the findings. We discuss the properties and roles of haloarchaeal lipids and present the structural data as individual case studies. Lipid-protein interactions are discussed in the context of structure-function relationships. A brief discussion of the possibility that bacteriorhodopsin functions as a light-driven inward hydroxide pump rather than an outward proton pump is also presented.
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    Annual Review of Biophysics and Biomolecular Structure 32 (2003), S. 375-397 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Abstract G protein-coupled receptors (GPCRs) are integral membrane proteins that respond to environmental signals and initiate signal transduction pathways activating cellular processes. Rhodopsin is a GPCR found in rod cells in retina where it functions as a photopigment. Its molecular structure is known from cryo-electron microscopic and X-ray crystallographic studies, and this has reshaped many structure/function questions important in vision science. In addition, this first GPCR structure has provided a structural template for studies of other GPCRs, including many known drug targets. After presenting an overview of the major structural elements of rhodopsin, recent literature covering the use of the rhodopsin structure in analyzing other GPCRs will be summarized. Use of the rhodopsin structural model to understand the structure and function of other GPCRs provides strong evidence validating the structural model.
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    Annual Review of Biophysics and Biomolecular Structure 32 (2003), S. 399-424 
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    Notes: Abstract The coupling of high-performance mass spectrometry instrumentation with highly efficient chromatographic and electrophoretic separations has enabled rapid qualitative and quantitative analysis of thousands of proteins from minute samples of biological materials. Here, we review recent progress in the development and application of mass spectrometry-based techniques for the qualitative and quantitative analysis of global proteome samples derived from whole cells, tissues, or organisms. Techniques such as multidimensional peptide and protein separations coupled with mass spectrometry, accurate mass measurement of peptides from global proteome digests, and mass spectrometric characterization of intact proteins hold great promise for characterization of highly complex protein mixtures. Advances in chemical tagging and isotope labeling techniques have enabled quantitative analysis of proteomes, and highly specific isolation strategies have been developed aimed at selective analysis of posttranslationally modified proteins.
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    Annual Review of Biophysics and Biomolecular Structure 33 (2004), S. 387-413 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Residual dipolar couplings (RDCs) have recently emerged as a new tool in nuclear magnetic resonance (NMR) with which to study macromolecular structure and function in a solution environment. RDCs are complementary to the more conventional use of NOEs to provide structural information. While NOEs are local-distance restraints, RDCs provide long-range orientational information. RDCs are now widely utilized in structure calculations. Increasingly, they are being used in novel applications to address complex issues in structural biology such as the accurate determination of the global structure of oligonucleotides and the relative orientation of protein domains. This review briefly describes the theory and methods for obtaining RDCs and then describes the range of biological applications where RDCs have been used.
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    Annual Review of Biophysics and Biomolecular Structure 34 (2005), S. 295-318 
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    Notes: Toroidal DNA condensates have attracted the attention of biophysicists, biochemists, and polymer physicists for more than thirty years. In the biological community, the quest to understand DNA toroid formation has been motivated by its relevance to gene packing in certain viruses and by the potential use of DNA toroids in artificial gene delivery (e.g., gene therapy). In the physical sciences, DNA toroids are appreciated as a superb model system for studying particle formation by the collapse of a semiflexible, polyelectrolyte polymer. This review focuses on experimental studies from the past few years that have significantly increased our understanding of DNA toroid structure and the mechanism of their formation. Highlights include structural studies that show the DNA strands within toroids to be packed in an ideal hexagonal lattice, and also in regions with a nonhexagonal lattice that are required by the topological constraints associated with winding DNA into a toroid. Recent studies of DNA toroid formation have also revealed that toroid size limits result from a complex interplay between kinetic and thermodynamic factors that govern both toroid nucleation and growth. The work discussed in this review indicates that it will ultimately be possible to obtain substantial control over DNA toroid dimensions.
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    Annual Review of Biophysics and Biomolecular Structure 34 (2005), S. 267-294 
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    Notes: With genome sequencing nearing completion for the model organisms used in biomedical research, there is a rapidly growing appreciation that proteomics, the study of covalent modification to proteins, and transcriptional regulation will likely dominate the research headlines in the next decade. Protein methylation plays a central role in both of these fields, as several different residues (Arg, Lys, Gln) are methylated in cells and methylation plays a central role in the "histone code" that regulates chromatin structure and impacts transcription. In some cases, a single lysine can be mono-, di-, or trimethylated, with different functional consequences for each of the three forms. This review describes structural aspects of methylation of histone lysine residues by two enzyme families with entirely different structural scaffolding (the SET proteins and Dot1p) and methylation of protein arginine residues by PRMTs.
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    Annual Review of Biophysics and Biomolecular Structure 34 (2005), S. 153-171 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Potassium (K+) channels are tetrameric membrane-spanning proteins that provide a selective pore for the conductance of K+ across the cell membranes. These channels are most remarkable in their ability to discriminate K+ from Na+ by more than a thousandfold and conduct at a throughput rate near diffusion limit. The recent progress in the structural characterization of K+ channel provides us with a unique opportunity to understand their function at the atomic level. With their ability to go beyond static structures, molecular dynamics simulations based on atomic models can play an important role in shaping our view of how ion channels carry out their function. The purpose of this review is to summarize the most important findings from experiments and computations and to highlight a number of fundamental mechanistic questions about ion conduction and selectivity that will require further work.
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    Annual Review of Biophysics and Biomolecular Structure 34 (2005), S. 91-118 
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Proteins have become accessible targets for chemical synthesis. The basic strategy is to use native chemical ligation, Staudinger ligation, or other orthogonal chemical reactions to couple synthetic peptides. The ligation reactions are compatible with a variety of solvents and proceed in solution or on a solid support. Chemical synthesis enables a level of control on protein composition that greatly exceeds that attainable with ribosome-mediated biosynthesis. Accordingly, the chemical synthesis of proteins is providing previously unattainable insight into the structure and function of proteins.
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    Annual Review of Biophysics and Biomolecular Structure 34 (2005), S. 415-440 
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: A powerful approach to understanding protein enzyme catalysis is to examine the structural context of essential amino acid side chains whose deletion or modification negatively impacts catalysis. In principle, this approach can be even more powerful for RNA enzymes, given the wide variety and subtlety of functionally modified nucleotides now available. Numerous recent success stories confirm the utility of this approach to understanding ribozyme function. An anomaly, however, is the hammerhead ribozyme, for which the structural and functional data do not agree well, preventing a unifying view of its catalytic mechanism from emerging. To delineate the hammerhead structure-function comparison, we have evaluated and distilled the large body of biochemical data into a consensus set of functional groups unambiguously required for hammerhead catalysis. By examining the context of these functional groups within available structures, we have established a concise set of disagreements between the structural and functional data. The number and relative distribution of these inconsistencies throughout the hammerhead reaffirms that an extensive conformational rearrangement from the fold observed in the crystal structure must be necessary for cleavage to occur. The nature and energetic driving force of this conformational isomerization are discussed.
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    Annual Review of Biophysics and Biomolecular Structure 33 (2004), S. 269-295 
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    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 Biophysics and Biomolecular Structure 34 (2005), S. 399-414 
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: The development of single-molecule detection and manipulation has allowed us to monitor the behavior of individual biological molecules and molecular complexes in real time. This approach significantly expands our capability to characterize complex dynamics of biological processes, allowing transient intermediate states and parallel kinetic pathways to be directly observed. Exploring this capability to elucidate complex dynamics, recent single-molecule experiments on RNA folding and catalysis have improved our understanding of the folding energy landscape of RNA and allowed us to better dissect complex RNA catalytic reactions, including translation by the ribosome.
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    Annual Review of Biophysics and Biomolecular Structure 34 (2005), S. 173-199 
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Water plays a central role in the structures and properties of biomoleculesĐ??proteins, nucleic acids, and membranesĐ??and in their interactions with ligands and drugs. Over the past half century, our understanding of water has been advanced significantly owing to theoretical and computational modeling. However, like the blind men and the elephant, different models describe different aspects of water's behavior. The trend in water modeling has been toward finer-scale properties and increasing structural detail, at increasing computational expense. Recently, our labs and others have moved in the opposite direction, toward simpler physical models, focusing on more global propertiesĐ??water's thermodynamics, phase diagram, and solvation properties, for exampleĐ??and toward less computational expense. Simplified models can guide a better understanding of water in ways that complement what we learn from more complex models. One ultimate goal is more tractable models for computer simulations of biomolecules. This review gives a perspective from simple models on how the physical properties of waterĐ??as a pure liquid and as a solventĐ??derive from the geometric and hydrogen bonding properties of water.
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    Annual Review of Biophysics and Biomolecular Structure 34 (2005), S. 379-398 
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Structural data on protein-DNA complexes provide clues for understanding the mechanism of protein-DNA recognition. Although the structures of a large number of protein-DNA complexes are known, the mechanisms underlying their specific binding are still only poorly understood. Analysis of these structures has shown that there is no simple one-to-one correspondence between bases and amino acids within protein-DNA complexes; nevertheless, the observed patterns of interaction carry important information on the mechanisms of protein-DNA recognition. In this review, we show how the patterns of interaction, either observed in known structures or derived from computer simulations, confer recognition specificity, and how they can be used to examine the relationship between structure and specificity and to predict target DNA sequences used by regulatory proteins.
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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 
    ISSN: 1081-0706
    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 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract Epithelial morphogenesis comprises the various processes by which epithelia contribute to organ formation and body shape. These complex and diverse events play a central role in animal development and regeneration. Recently, the characterization of some of the molecular mechanisms involved in epithelial morphogenesis has provided an abundance of new information on the role and regulation of the cytoskeleton, cell-cell adhesion, and cell-matrix adhesion in these processes. In this review, we discuss our current understanding of the molecular mechanisms driving cell shape changes, cell intercalation, fusion of epithelia, ingression, egression, and cell migration. Our discussion is mostly focused on results from Drosophila and mammalian tissue culture but also draws on the insights gained from other organisms.
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    Annual Review of Cell and Developmental Biology 18 (2002), S. 379-420 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract Golgi inheritance proceeds via sequential biogenesis and partitioning phases. Although little is known about Golgi growth and replication (biogenesis), ultrastructural and fluorescence analyses have provided a detailed, though still controversial, perspective of Golgi partitioning during mitosis in mammalian cells. Partitioning requires the fragmentation of the juxtanuclear ribbon of interconnected Golgi stacks into a multitude of tubulovesicular clusters. This process is choreographed by a cohort of mitotic kinases and an inhibition of heterotypic and homotypic Golgi membrane-fusion events. Our model posits that accurate partitioning occurs early in mitosis by the equilibration of Golgi components on either side of the metaphase plate. Disseminated Golgi components then coalesce to regenerate Golgi stacks during telophase. Semi-intact cell and cell-free assays have accurately recreated these processes and allowed their molecular dissection. This review attempts to integrate recent findings to depict a more coherent, synthetic molecular picture of mitotic Golgi fragmentation and reassembly. Of particular importance is the emerging concept of a highly regulated and dynamic Golgi structural matrix or template that interfaces with cargo receptors, Golgi enzymes, Rab-GTPases, and SNAREs to tightly couple biosynthetic transport to Golgi architecture. This structural framework may be instructive for Golgi biogenesis and may encode sufficient information to ensure accurate Golgi inheritance, thereby helping to resolve some of the current discrepancies between different workers.
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    Annual Review of Cell and Developmental Biology 20 (2004), S. 593-618 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: During brain development, neurons migrate great distances from proliferative zones to generate the cortical gray matter. A series of studies has identified genes that are critical for migration and targeting of neurons to specific brain regions. These genes encode three basic groups of proteins and produce three distinct phenotypes. The first group encodes cytoskeletal molecules and produces graded and dosage-dependent effects, with a significant amount of functional redundancy. This group also appears to play important roles during the initiation and ongoing progression of neuronal movement. The second group encodes signaling molecules for which homozygous mutations lead to an inverted cortex. In addition, this group is responsible for movement of neurons through anatomic boundaries to specific cortical layers. The third group encodes enzymatic regulators of glycosylation and appears to delineate where neuronal migration will arrest. There is significant cross-talk among these different groups of molecules, suggesting possible points of pathway convergence.
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    Annual Review of Cell and Developmental Biology 20 (2004), S. 725-757 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: The principles underlying regeneration in planarians have been explored for over 100 years through surgical manipulations and cellular observations. Planarian regeneration involves the generation of new tissue at the wound site via cell proliferation (blastema formation), and the remodeling of pre-existing tissues to restore symmetry and proportion (morphallaxis). Because blastemas do not replace all tissues following most types of injuries, both blastema formation and morphallaxis are needed for complete regeneration. Here we discuss a proliferative cell population, the neoblasts, that is central to the regenerative capacities of planarians. Neoblasts may be a totipotent stem-cell population capable of generating essentially every cell type in the adult animal, including themselves. The population properties of the neoblasts and their descendants still await careful elucidation. We identify the types of structures produced by blastemas on a variety of wound surfaces, the principles guiding the reorganization of pre-existing tissues, and the manner in which scale and cell number proportions between body regions are restored during regeneration.
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    Annual Review of Cell and Developmental Biology 20 (2004), S. 481-504 
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    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 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: We review the current status of research in dorsal-ventral (D-V) patterning in vertebrates. Emphasis is placed on recent work on Xenopus, which provides a paradigm for vertebrate development based on a rich heritage of experimental embryology. D-V patterning starts much earlier than previously thought, under the influence of a dorsal nuclear -Catenin signal. At mid-blastula two signaling centers are present on the dorsal side: The prospective neuroectoderm expresses bone morphogenetic protein (BMP) antagonists, and the future dorsal endoderm secretes Nodal-related mesoderm-inducing factors. When dorsal mesoderm is formed at gastrula, a cocktail of growth factor antagonists is secreted by the Spemann organizer and further patterns the embryo. A ventral gastrula signaling center opposes the actions of the dorsal organizer, and another set of secreted antagonists is produced ventrally under the control of BMP4. The early dorsal -Catenin signal inhibits BMP expression at the transcriptional level and promotes expression of secreted BMP antagonists in the prospective central nervous system (CNS). In the absence of mesoderm, expression of Chordin and Noggin in ectoderm is required for anterior CNS formation. FGF (fibroblast growth factor) and IGF (insulin-like growth factor) signals are also potent neural inducers. Neural induction by anti-BMPs such as Chordin requires mitogen-activated protein kinase (MAPK) activation mediated by FGF and IGF. These multiple signals can be integrated at the level of Smad1. Phosphorylation by BMP receptor stimulates Smad1 transcriptional activity, whereas phosphorylation by MAPK has the opposite effect. Neural tissue is formed only at very low levels of activity of BMP-transducing Smads, which require the combination of both low BMP levels and high MAPK signals. Many of the molecular players that regulate D-V patterning via regulation of BMP signaling have been conserved between Drosophila and the vertebrates.
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    Annual Review of Cell and Developmental Biology 20 (2004), S. 455-480 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Macrophages are essential modulators of lipid metabolism and the innate immune system. Lipid and inflammatory pathways induced in activated macrophages are central to the pathogenesis of human diseases including atherosclerosis. Recent work has shown that expression of genes involved in lipid uptake and cholesterol efflux in macrophages is controlled by peroxisome proliferator-activated receptors (PPARs) and liver X receptors (LXRs). Other studies have implicated these same receptors in the modulation of macrophage inflammatory gene expression. Together, these observations position PPARs and LXRs at the crossroads of lipid metabolism and inflammation and suggest that these receptors may serve to integrate these pathways in the control of macrophage gene expression. In this review, we summarize recent work that has advanced our understanding of the roles of PPARs and LXRs in macrophage biology and discuss the implication of these results for cardiovascular physiology and disease.
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    Annual Review of Cell and Developmental Biology 20 (2004), S. 87-123 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: The endoplasmic reticulum (ER) and the Golgi comprise the first two steps in protein secretion. Vesicular carriers mediate a continuous flux of proteins and lipids between these compartments, reflecting the transport of newly synthesized proteins out of the ER and the retrieval of escaped ER residents and vesicle machinery. Anterograde and retrograde transport is mediated by distinct sets of cytosolic coat proteins, the COPII and COPI coats, respectively, which act on the membrane to capture cargo proteins into nascent vesicles. We review the mechanisms that govern coat recruitment to the membrane, cargo capture into a transport vesicle, and accurate delivery to the target organelle.
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    Annual Review of Cell and Developmental Biology 20 (2004), S. 427-453 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: The one-cell Caenorhabditis elegans embryo divides asymmetrically into a larger and smaller blastomere, each with a different fate. How does such asymmetry arise? The sperm-supplied centrosome establishes an axis of polarity in the embryo that is transduced into the establishment of anterior and posterior cortical domains. These cortical domains define the polarity of the embryo, acting upstream of the PAR proteins. The PAR proteins, in turn, determine the subsequent segregation of fate determinants and the plane of cell division. We address how cortical asymmetry could be established, relying on data from C. elegans and other polarized cells, as well as from applicable models. We discuss how cortical polarity influences spindle position to accomplish an asymmetric division, presenting the current models of spindle orientation and anaphase spindle displacement. We focus on asymmetric cell division as a function of the actin and microtubule cytoskeletons, emphasizing the cell biology of polarity.
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    Annual Review of Cell and Developmental Biology 20 (2004), S. 695-723 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: The study of the epithelium of the adult mammalian intestine touches upon many modern aspects of biology. The epithelium is in a constant dialogue with the underlying mesenchyme to control stem cell activity, proliferation in transit-amplifying compartments, lineage commitment, terminal differentiation and, ultimately, cell death. There are spatially distinct compartments dedicated to each of these events. The Wnt, TGF-beta, BMP, Notch, and Par polarity pathways are the major players in homeostatic control of the adult epithelium. Several hereditary cancer syndromes deregulate these same signaling cascades through mutational (in)activation. Moreover, these mutations often also occur in sporadic tumors. Thus symmetry exists between the roles that these signaling pathways play in physiology and in cancer of the intestine. This is particularly evident for the Wnt/APC pathway, for which the mammalian intestine has become one of the most-studied paradigms. Here, we integrate recent knowledge of the molecular inner workings of the prototype signaling cascades with their specific roles in intestinal epithelial homeostasis and in neoplastic transformation of the epithelium.
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    Annual Review of Cell and Developmental Biology 21 (2005), S. 457-483 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: The field of lymphatic research has been recently invigorated by the identification of genes and mechanisms that control various aspects of lymphatic development. We are beginning to understand how, starting from a subgroup of embryonic venous endothelial cells, the whole lymphatic system forms in a stepwise manner. The generation of genetically engineered mice with defects in different steps of the lymphangiogenic program has provided models that are increasing our understanding of the lymphatic system in health and disease. This knowledge, in turn, should lead to the development of better diagnostic methods and treatments of lymphatic disorders and tumor metastasis.
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