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  • Taylor & Francis  (19,042)
  • American Meteorological Society
  • Annual Reviews
  • 2005-2009  (26,145)
  • 1965-1969  (9,044)
  • 1945-1949  (3,000)
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  • 1
    Unknown
    Mechanics of fluids : revised by John Ward-Smith (2006)
    London ; New York : Taylor & Francis
    Details
    Keywords: Fluid mechanics.
    Pages: x, 696 p.
    Edition: 8th ed
    ISBN: 0-203-01232-1
    URL: http://www.netLibrary.com/urlapi.asp?action=summary&v=1&bookid=145236
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    E-Book (German National Licenses)
  • 2
    Unknown
    Hydraulic canals : design, construction, regulation and maintenance (2006)
    London ; New York : Taylor & Francis
    Details
    Keywords: Canals, Design and construction. ; Canals, Maintenance and repair.
    Pages: xx, 389 p.
    ISBN: 0-203-01242-9
    URL: http://www.netLibrary.com/urlapi.asp?action=summary&v=1&bookid=144327
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  • 3
    Unknown
    Courtyard housing : past, present and future (2006)
    Abingdon [England] ; New York : Taylor & Francis
    Details
    Keywords: Courtyard houses.
    Pages: xix, 248 p., [8] p. of plates
    ISBN: 0-203-64672-X
    URL: http://www.netLibrary.com/urlapi.asp?action=summary&v=1&bookid=115425
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  • 4
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    Aegean Sea Water Masses during the Early Stages of the Eastern Mediterranean Climatic Transient (2007)
    American Meteorological Society
    Details
    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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  • 5
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    Gulf Stream Variability in Five Oceanic General Circulation Models (2008)
    American Meteorological Society
    Details
    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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  • 6
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    Effects of Land-Surface-Vegetation on theboreal summer surface climate of a GCM (2007)
    American Meteorological Society
    Details
    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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  • 7
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    Using Temperature–Salinity Relations in a Global Ocean Implementation of a Multivariate Data Assimilation Scheme (2008)
    American Meteorological Society
    Details
    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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  • 8
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    Atmospheric horizontal resolution affects tropical climate variability in coupled models (2008)
    American Meteorological Society
    Details
    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
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 9
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    The influence of Tropical Indian Ocean SST on the Indian summer monsoon (2007)
    American Meteorological Society
    Details
    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
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 10
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    Marine Environment and Security for the European Area (MERSEA) - Towards operational oceanography (2007)
    American Meteorological Society
    Details
    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
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 11
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    Interannual to Decadal Climate Predictability in the North Atlantic: A Multi-Model-Ensemble Study (2007)
    American Meteorological Society
    Details
    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
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 12
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    Tropospheric Comparisons of Vaisala Radiosondes and Balloon-Borne Frost-Point and Lyman-α Hygrometers during the LAUTLOS-WAVVAP Experiment (2008)
    American Meteorological Society
    In:  EPIC3Journal of Atmospheric and Oceanic Technology, American Meteorological Society, 25(2), pp. 149-166, ISSN: 0739-0572
    Details
    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
    Type: Article , isiRev
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  • 13
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    The Teleconnection between the Western Indian and the Western Pacific Oceans (2005)
    American Meteorological Society
    Details
    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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  • 14
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    The Role of the Land Surface Background State in Climate Predictability (2005)
    American Meteorological Society
    Details
    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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  • 15
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    A Shallow-CISK-Deep-Equilibrium Mechanism for The Interaction Between Large-Scale Convection and Large-Scale Circulations In The Tropics (2005)
    American Meteorological Society
    Details
    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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  • 16
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    Role of carbon cycle observations and knowledge in carbon management (2005)
    Annual Reviews
    Details
    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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  • 17
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    Long nonlinear internal waves (2006)
    Annual Reviews
    Details
    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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  • 18
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    Accuracy of a pulse-coherent acoustic Doppler profiler in a wave-dominated flow (2007)
    American Meteorological Society
    Details
    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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  • 19
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    Design and function of superfast muscles : new insights into the physiology of skeletal muscle (2005)
    Annual Reviews
    Details
    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
    Type: Article
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    MARGINAL ZONE B CELLS (2005)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 23 (2005), S. 161-196 
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    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Our views regarding the origins and functions of splenic marginal zone B cells have changed considerably over the past few years. Perspectives regarding the development and function of these cells vary considerably between investigators studying human and rodent immunology. Marginal zone B cells are now recognized to constitute a distinct naive B lymphoid lineage. Considerable progress has been made regarding the mechanisms involved in marginal zone B cell development in the mouse. Many of the molecular events that participate in the retention of this lineage of B cells in the marginal zone have been identified. Here, we discuss the functions of these cells in both innate and adaptive immunity. We also attempt to reconcile differing viewpoints regarding the generation and function of marginal zone B cells in rodents and primates.
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    ANTIGEN-SPECIFIC MEMORY B CELL DEVELOPMENT (2005)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 23 (2005), S. 487-513 
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    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Helper T (Th) cellĐ??regulated B cell immunity progresses in an ordered cascade of cellular development that culminates in the production of antigen-specific memory B cells. The recognition of peptide MHC class II complexes on activated antigen-presenting cells is critical for effective Th cell selection, clonal expansion, and effector Th cell function development (Phase I). Cognate effector Th cellĐ??B cell interactions then promote the development of either short-lived plasma cells (PCs) or germinal centers (GCs) (Phase II). These GCs expand, diversify, and select high-affinity variants of antigen-specific B cells for entry into the long-lived memory B cell compartment (Phase III). Upon antigen rechallenge, memory B cells rapidly expand and differentiate into PCs under the cognate control of memory Th cells (Phase IV). We review the cellular and molecular regulators of this dynamic process with emphasis on the multiple memory B cell fates that develop in vivo.
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    B CELL SIGNALING AND Tumorigenesis (2005)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 23 (2005), S. 415-445 
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    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: The proliferation and differentiation of lymphocytes are regulated by receptors localized on the cell surface. Engagement of these receptors induces the activation of intracellular signaling proteins that transmit the receptor signals to distinct targets and control the cellular responses. The first signaling proteins to be discovered in higher organisms were the products of oncogenes. For example, the kinases Src and Abelson (Abl) were originally identified as oncogenes and were later characterized as important proteins for signal transduction in various cell types, including lymphocytes. Now, as many cellular signaling molecules have been discovered and ordered into certain pathways, we can better understand why particular signaling proteins are associated with tumorigenesis. In this review, we discuss recent progress in unraveling the molecular mechanisms of signaling pathways that control the proliferation and differentiation of early B cells. We point out the concepts of auto-inhibition and subcellular localization as crucial aspects in the regulation of B cell signaling.
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    IMMUNOLOGY OF MULTIPLE SCLEROSIS * (2005)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 23 (2005), S. 683-747 
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    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Multiple sclerosis (MS) develops in young adults with a complex predisposing genetic trait and probably requires an inciting environmental insult such as a viral infection to trigger the disease. The activation of CD4+ autoreactive T cells and their differentiation into a Th1 phenotype are a crucial events in the initial steps, and these cells are probably also important players in the long-term evolution of the disease. Damage of the target tissue, the central nervous system, is, however, most likely mediated by other components of the immune system, such as antibodies, complement, CD8+ T cells, and factors produced by innate immune cells. Perturbations in immunomodulatory networks that include Th2 cells, regulatory CD4+ T cells, NK cells, and others may in part be responsible for the relapsing-remitting or chronic progressive nature of the disease. However, an important paradigmatic shift in the study of MS has occurred in the past decade. It is now clear that MS is not just a disease of the immune system, but that factors contributed by the central nervous system are equally important and must be considered in the future.
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    UNDERSTANDING PRESENTATION OF VIRAL ANTIGENS TO CD8+ T CELLS IN VIVO: The Key to Rational Vaccine Design * (2005)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 23 (2005), S. 651-682 
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    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: CD8+ T cells play a critical role in antiviral immunity by exerting direct antiviral activity against infected cells. Because of their ability to recognize all types of viral proteins, they offer the promise of providing broad immunity to viruses that evade humoral immunity by varying their surface proteins. Consequently, there is considerable interest in developing vaccines that elicit effective antiviral TCD8+ responses. Generating optimal vaccines ultimately requires rational design based on detailed knowledge of how TCD8+ are activated in vivo under natural circumstances. Here we review recent progress obtained largely by in vivo studies in mice to understand the mechanistic basis for activation of naive TCD8+ in virus infections. These studies point the way to detailed understanding and provide some key information for vaccine development, although much remains to be learned to enable truly rational vaccine design.
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    REGULATION OF LYMPHOID DEVELOPMENT, DIFFERENTIATION, AND FUNCTION BY THE NOTCH PATHWAY (2005)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 23 (2005), S. 945-974 
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    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: The Notch pathway is gaining increasing recognition as a key regulator of developmental choices, differentiation, and function throughout the hematolymphoid system. Notch controls the generation of hematopoietic stem cells during embryonic development and may affect their subsequent homeostasis. Commitment to the T??cell lineage and subsequent stages of early thymopoiesis is critically regulated by Notch. Recent data indicate that Notch can also direct the differentiation and activity of peripheral T and B cells. Thus, the full spectrum of Notch effects is just beginning to be understood. In this review, we discuss this explosion of knowledge as well as current controversies and challenges in the field.
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    CELL BIOLOGY OF ANTIGEN PROCESSING IN VITRO AND IN VIVO (2005)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 23 (2005), S. 975-1028 
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    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: The conversion of exogenous and endogenous proteins into immunogenic peptides recognized by T lymphocytes involves a series of proteolytic and other enzymatic events culminating in the formation of peptides bound to MHC class I or class II molecules. Although the biochemistry of these events has been studied in detail, only in the past few years has similar information begun to emerge describing the cellular context in which these events take place. This review thus concentrates on the properties of antigen-presenting cells, especially those aspects of their overall organization, regulation, and intracellular transport that both facilitate and modulate the processing of protein antigens. Emphasis is placed on dendritic cells and the specializations that help account for their marked efficiency at antigen processing and presentation both in vitro and, importantly, in vivo. How dendritic cells handle antigens is likely to be as important a determinant of immunogenicity and tolerance as is the nature of the antigens themselves.
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    THE B7 FAMILY REVISITED (2005)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 23 (2005), S. 515-548 
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    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: The discovery of new functions for the original B7 family members, together with the identification of additional B7 and CD28 family members, have revealed new ways in which the B7:CD28 family regulates T cell activation and tolerance. B7-1/B7-2:CD28 interactions not only promote initial T cell activation but also regulate self-tolerance by supporting CD4+CD25+ T regulatory cell homeostasis. CTLA-4 can exert its inhibitory effects in both B7-1/B7-2 dependent and independent fashions. B7-1 and B7-2 can signal bidirectionally by engaging CD28 and CTLA-4 on T cells and by delivering signals into B7-expressing cells. The five new B7 family members, ICOS ligand, PD-L1 (B7-H1), PD-L2 (B7-DC), B7-H3, and B7-H4 (B7x/B7-S1) are expressed on professional antigen-presenting cells as well as on cells within nonlymphoid organs, providing new means for regulating T cell activation and tolerance in peripheral tissues. The new CD28 families members, ICOS, PD-1, and BTLA, are inducibly expressed on T cells, and they have important roles in regulating previously activated T cells. PD-1 and BTLA also are expressed on B cells and may have broader immunoregulatory functions. The ICOS:ICOSL pathway appears to be particularly important for stimulating effector T cell responses and T cellĐ??dependent B cell responses, but it also has an important role in regulating T cell tolerance. In addition, the PD-1:PD-L1/PD-L2 pathway plays a critical role in regulating T cell activation and tolerance. In this review, we revisit the roles of the B7:CD28 family members in regulating immune responses, and we discuss their therapeutic potential.
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    TOWARD AN UNDERSTANDING OF NKT CELL BIOLOGY: Progress and Paradoxes (2005)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 26 (2005), S. 877-900 
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    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Natural killer T (NKT) cells constitute a conserved T cell sublineage with unique properties, including reactivity for a synthetic glycolipid presented by CD1d, expression of an invariant T cell antigen receptor (TCR) ʼ̛ chain, and unusual requirements for thymic selection. They rapidly produce many cytokines after stimulation and thus influence diverse immune responses and pathogenic processes. Because of intensive research effort, we have learned much about factors promoting the development and survival of NKT cells, regulation of their cytokine production, and the means by which they influence dendritic cells and other cell types. Despite this progress, knowledge of the natural antigen(s) they recognize and their physiologic role remain incomplete. The activation of NKT cells paradoxically can lead either to suppression or stimulation of immune responses, and we cannot predict which will occur. Despite this uncertainty, many investigators are hopeful that immune therapies can be developed based on NKT cell stimulation.
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    TEC FAMILY KINASES IN T LYMPHOCYTE DEVELOPMENT AND FUNCTION * (2005)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 23 (2005), S. 549-600 
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    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: The Tec family tyrosine kinases are now recognized as important mediators of antigen receptor signaling in lymphocytes. Three members of this family, Itk, Rlk, and Tec, are expressed in T cells and activated in response to T cell receptor (TCR) engagement. Although initial studies demonstrated a role for these proteins in TCR-mediated activation of phospholipase C-??, recent data indicate that Tec family kinases also regulate actin cytoskeletal reorganization and cellular adhesion following TCR stimulation. In addition, Tec family kinases are activated downstream of G proteinĐ??coupled chemokine receptors, where they play parallel roles in the regulation of Rho GTPases, cell polarization, adhesion, and migration. In all these systems, however, Tec family kinases are not essential signaling components, but instead function to modulate or amplify signaling pathways. Although they quantitatively reduce proximal signaling, mutations that eliminate Tec family kinases in T cells nonetheless qualitatively alter T cell development and differentiation.
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    DEVELOPMENT AND REGULATION OF CELL-MEDIATED IMMUNE RESPONSES TO THE BLOOD STAGES OF MALARIA: Implications for Vaccine Research (2005)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 23 (2005), S. 69-99 
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    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: The immune response to the malaria parasite is complex and poorly understood. Although antibodies and T cells can control parasite growth in model systems, natural immunity to malaria in regions of high endemicity takes several years to develop. Variation and polymorphism of antibody target antigens are known to impede immune responses, but these factors alone cannot account for the slow acquisition of immunity. In human and animal model systems, cell-mediated responses can control parasite growth effectively, but such responses are regulated by parasite load via direct effects on dendritic cells and possibly on T and B cells as well. Furthermore, high parasite load is associated with pathology, and cell-mediated responses may also harm the host. Inflammatory cytokines have been implicated in the pathogenesis of cerebral malaria, anemia, weight loss, and respiratory distress in malaria. Immunity without pathology requires rapid parasite clearance, effective regulation of the inflammatory antiparasite effects of cellular responses, and the eventual development of a repertoire of antibodies effective against multiple strains. Data suggest that this may be hastened by exposure to malaria antigens in low dose, leading to augmented cellular immunity and rapid parasite clearance.
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    TNF/TNFR FAMILY MEMBERS IN COSTIMULATION OF T CELL RESPONSES (2005)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 23 (2005), S. 23-68 
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    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Several members of the tumor necrosis factor receptor (TNFR) family function after initial T cell activation to sustain T cell responses. This review focuses on CD27, 4-1BB (CD137), OX40 (CD134), HVEM, CD30, and GITR, all of which can have costimulatory effects on T cells. The effects of these costimulatory TNFR family members can often be functionally, temporally, or spatially segregated from those of CD28 and from each other. The sequential and transient regulation of T cell activation/survival signals by different costimulators may function to allow longevity of the response while maintaining tight control of T cell survival. Depending on the disease condition, stimulation via costimulatory TNF family members can exacerbate or ameliorate disease. Despite these complexities, stimulation or blockade of TNFR family costimulators shows promise for several therapeutic applications, including cancer, infectious disease, transplantation, and autoimmunity.
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    THE NOD MOUSE: A Model of Immune Dysregulation (2005)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 23 (2005), S. 447-485 
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    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Autoimmunity is a complex process that likely results from the summation of multiple defective tolerance mechanisms. The NOD mouse strain is an excellent model of autoimmune disease and an important tool for dissecting tolerance mechanisms. The strength of this mouse strain is that it develops spontaneous autoimmune diabetes, which shares many similarities to autoimmune or type 1a diabetes (T1D) in human subjects, including the presence of pancreas-specific autoantibodies, autoreactive CD4+ and CD8+ T cells, and genetic linkage to disease syntenic to that found in humans. During the past ten years, investigators have used a wide variety of tools to study these mice, including immunological reagents and transgenic and knockout strains; these tools have tremendously enhanced the study of the fundamental disease mechanisms. In addition, investigators have recently developed a number of therapeutic interventions in this animal model that have now been translated into human therapies. In this review, we summarize many of the important features of disease development and progression in the NOD strain, emphasizing the role of central and peripheral tolerance mechanisms that affect diabetes in these mice. The information gained from this highly relevant model of human disease will lead to potential therapies that may alter the development of the disease and its progression in patients with T1D.
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    THE T CELL RECEPTOR: Critical Role of the Membrane Environment in Receptor Assembly and Function (2005)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 23 (2005), S. 101-125 
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    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Recent studies have demonstrated that cell membranes provide a unique environment for protein-protein and protein-lipid interactions that are critical for the assembly and function of the T cell receptor (TCR)-CD3 complex. Highly specific polar interactions among transmembrane (TM) domains that are uniquely favorable in the lipid environment organize the association of the three signaling dimers with the TCR. Each of these three assembly steps depends on the formation of a three-helix interface between one basic and two acidic residues in the membrane environment. The same polar TM residues that drive assembly also play a central role in quality control and export by directing the retention and degradation of free subunits and partial complexes, while membrane proximal cytoplasmic signals control recycling and degradation of surface receptors. Recent studies also suggest that interactions between the membrane and the cytoplasmic domains of CD3 proteins may be important for receptor triggering.
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    CYTOCHROME P450: Nature's Most Versatile Biological Catalyst (2005)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 45 (2005), S. 1-25 
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    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Notes: The author describes studies that led to the resolution and reconstitution of the cytochrome P450 enzyme system in microsomal membranes. The review indicates how purification and characterization of the cytochromes led to rigorous evidence for multiple isoforms of the oxygenases with distinct chemical and physical properties and different but somewhat overlapping substrate specificities. Present knowledge of the individual steps in the P450 and reductase reaction cycles is summarized, including evidence for the generation of multiple functional oxidants that may contribute to the exceptional diversity of the reactions catalyzed.
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    GLUTATHIONE TRANSFERASES (2005)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 45 (2005), S. 51-88 
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    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Notes: This review describes the three mammalian glutathione transferase (GST) families, namely cytosolic, mitochondrial, and microsomal GST, the latter now designated MAPEG. Besides detoxifying electrophilic xenobiotics, such as chemical carcinogens, environmental pollutants, and antitumor agents, these transferases inactivate endogenous ʼ̛,?‚-unsaturated aldehydes, quinones, epoxides, and hydroperoxides formed as secondary metabolites during oxidative stress. These enzymes are also intimately involved in the biosynthesis of leukotrienes, prostaglandins, testosterone, and progesterone, as well as the degradation of tyrosine. Among their substrates, GSTs conjugate the signaling molecules 15-deoxy-??12,14-prostaglandin J2 (15d-PGJ2) and 4-hydroxynonenal with glutathione, and consequently they antagonize expression of genes trans-activated by the peroxisome proliferator-activated receptor ?? (PPAR??) and nuclear factor-erythroid 2 p45-related factor 2 (Nrf2). Through metabolism of 15d-PGJ2, GST may enhance gene expression driven by nuclear factor-?”B (NF-?”B). Cytosolic human GST exhibit genetic polymorphisms and this variation can increase susceptibility to carcinogenesis and inflammatory disease. Polymorphisms in human MAPEG are associated with alterations in lung function and increased risk of myocardial infarction and stroke. Targeted disruption of murine genes has demonstrated that cytosolic GST isoenzymes are broadly cytoprotective, whereas MAPEG proteins have proinflammatory activities. Furthermore, knockout of mouse GSTA4 and GSTZ1 leads to overexpression of transferases in the Alpha, Mu, and Pi classes, an observation suggesting they are part of an adaptive mechanism that responds to endogenous chemical cues such as 4-hydroxynonenal and tyrosine degradation products. Consistent with this hypothesis, the promoters of cytosolic GST and MAPEG genes contain antioxidant response elements through which they are transcriptionally activated during exposure to Michael reaction acceptors and oxidative stress.
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    THE ROLE OF METABOLIC ACTIVATION IN DRUG-INDUCED HEPATOTOXICITY (2005)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 45 (2005), S. 177-202 
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    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Notes: The importance of reactive metabolites in the pathogenesis of drug-induced toxicity has been a focus of research interest since pioneering investigations in the 1950s revealed the link between toxic metabolites and chemical carcinogenesis. There is now a great deal of evidence that shows that reactive metabolites are formed from drugs known to cause hepatotoxicity, but how these toxic species initiate and propagate tissue damage is still poorly understood. This review summarizes the evidence for reactive metabolite formation from hepatotoxic drugs, such as acetaminophen, tamoxifen, diclofenac, and troglitazone, and the current hypotheses of how this leads to liver injury. Several hepatic proteins can be modified by reactive metabolites, but this in general equates poorly with the extent of toxicity. Much more important may be the identification of the critical proteins modified by these toxic species and how this alters their function. It is also important to note that the toxicity of reactive metabolites may be mediated by noncovalent binding mechanisms, which may also have profound effects on normal liver physiology. Technological developments in the wake of the genomic revolution now provide unprecedented power to characterize and quantify covalent modification of individual target proteins and their functional consequences; such information should dramatically improve our understanding of drug-induced hepatotoxic reactions.
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    NON-MICHAELIS-MENTEN KINETICS IN CYTOCHROME P450-CATALYZED REACTIONS (2005)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 45 (2005), S. 291-310 
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    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Notes: The cytochrome P450 monooxygenases (CYPs) are the dominant enzyme system responsible for xenobiotic detoxification and drug metabolism. Several CYP isoforms exhibit non-Michaelis-Menten, or "atypical," steady state kinetic patterns. The allosteric kinetics confound prediction of drug metabolism and drug-drug interactions, and they challenge the theoretical paradigms of allosterism. Both homotropic and heterotropic ligand effects are now widely documented. It is becoming apparent that multiple ligands can simultaneously bind within the active sites of individual CYPs, and the kinetic parameters change with ligand occupancy. In fact, the functional effect of any specific ligand as an activator or inhibitor can be substrate dependent. Divergent approaches, including kinetic modeling and X-ray crystallography, are providing new information about how multiple ligand binding yields complex CYP kinetics.
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    NITROXYL (HNO): Chemistry, Biochemistry, and Pharmacology (2005)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 45 (2005), S. 335-355 
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    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Notes: Recent discoveries of novel and potentially important biological activity have spurred interest in the chemistry and biochemistry of nitroxyl (HNO). It has become clear that, among all the nitrogen oxides, HNO is unique in its chemistry and biology. Currently, the intimate chemical details of the biological actions of HNO are not well understood. Moreover, many of the previously accepted chemical properties of HNO have been recently revised, thus requiring reevaluation of possible mechanisms of biological action. Herein, we review these developments in HNO chemistry and biology.
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    ACTIONS OF ADENOSINE AT ITS RECEPTORS IN THE CNS: Insights from Knockouts and Drugs (2005)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 45 (2005), S. 385-412 
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    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Notes: Adenosine and its receptors have been the topic of many recent reviews ( 1Đ??26 ). These reviews provide a good summary of much of the relevant literatureĐ??including the older literature. We have, therefore, chosen to focus the present review on the insights gained from recent studies on genetically modified mice, particularly with respect to the function of adenosine receptors and their potential as therapeutic targets. The information gained from studies of drug effects is discussed in this context, and discrepancies between genetic and pharmacological results are highlighted.
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    THE CARDIAC FIBROBLAST: Therapeutic Target in Myocardial Remodeling and Failure (2005)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 45 (2005), S. 657-687 
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    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Notes: Cardiac fibroblasts play a central role in the maintenance of extracellular matrix in the normal heart and as mediators of inflammatory and fibrotic myocardial remodeling in the injured and failing heart. In this review, we evaluate the cardiac fibroblast as a therapeutic target in heart disease. Unique features of cardiac fibroblast cell biology are discussed in relation to normal and pathophysiological cardiac function. The contribution of cardiac fibrosis as an independent risk factor in the outcome of heart failure is considered. Candidate drug therapies that derive benefit from actions on cardiac fibroblasts are summarized, including inhibitors of angiotensin-aldosterone systems, endothelin receptor antagonists, statins, anticytokine therapies, matrix metalloproteinase inhibitors, and novel antifibrotic/anti-inflammatory agents. These findings point the way to future challenges in cardiac fibroblast biology and pharmacotherapy.
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    HUMAN FLAVIN-CONTAINING MONOOXYGENASES (2006)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 46 (2006), S. 65-100 
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    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Notes: This review summarizes recent information concerning the pharmacological and toxicological significance of the human flavin-containing monooxygenase (FMO, EC 1.14.13.8). The human FMO oxygenates nucleophilic heteroatom-containing chemicals and drugs and generally converts them into harmless, polar, readily excreted metabolites. Sometimes, however, FMO bioactivates chemicals into reactive materials that can cause toxicity. Most of the interindividual differences of FMO are due to genetic variability and allelic variation, and splicing variants may contribute to interindividual and interethnic variability observed for FMO-mediated metabolism. In contrast to cytochrome P450 (CYP), FMO is not easily induced nor readily inhibited, and potential adverse drug-drug interactions are minimized for drugs prominently metabolized by FMO. These properties may provide advantages in drug design and discovery, and by incorporating FMO detoxication pathways into drug candidates, more drug-like materials may be forthcoming. Although exhaustive examples are not available, physiological factors can influence FMO function, and this may have implications for the clinical significance of FMO and a role in human disease.
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    Genetic Factors in Relation to Drugs (1965)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 5 (1965), S. 9-26 
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    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.pa.05.040165.000301
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    The Fate of Drugs in the Organism (1965)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 5 (1965), S. 405-428 
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    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.pa.05.040165.002201
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    Biochemical Mechanisms of Drug Action (1967)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 7 (1967), S. 15-38 
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    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.pa.07.040167.000311
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    Cancer Chemotherapy with Purine and Pyrimidine Analogues (1967)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 7 (1967), S. 101-124 
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    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.pa.07.040167.000533
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    The Autonomic Nervous System (1967)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 7 (1967), S. 185-202 
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    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.pa.07.040167.001153
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    Narcotic and Narcotic Antagonist Analgesics (1967)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 7 (1967), S. 277-300 
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    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.pa.07.040167.001425
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    A Personal Biography of Arthur Robertson Cushny, 1866-1926 (1968)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 8 (1968), S. 1-25 
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    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.pa.08.040168.000245
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    Pharmacology of the Coronary Circulation (1968)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 8 (1968), S. 95-112 
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    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.pa.08.040168.000523
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    Drug Action on Digestive System (1968)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 8 (1968), S. 171-186 
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    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
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    URL: http://dx.doi.org/10.1146/annurev.pa.08.040168.001131
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    Pharmacology of Reproduction and Fertility (1968)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 8 (1968), S. 467-490 
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    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
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    URL: http://dx.doi.org/10.1146/annurev.pa.08.040168.002343
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    Action of Drugs on Movement of Ocular Fluids (1969)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 9 (1969), S. 85-94 
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    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
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    URL: http://dx.doi.org/10.1146/annurev.pa.09.040169.000505
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    Drugs Affecting Smooth Muscle (1969)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 9 (1969), S. 147-172 
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    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
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    URL: http://dx.doi.org/10.1146/annurev.pa.09.040169.001051
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    Mechanisms of General Anesthesia by Non-Hydrogen-Bonding Molecules (1969)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 9 (1969), S. 259-272 
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    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
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    URL: http://dx.doi.org/10.1146/annurev.pa.09.040169.001355
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    Use of Cell Culture in Pharmacology (1969)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 9 (1969), S. 393-406 
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    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
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    URL: http://dx.doi.org/10.1146/annurev.pa.09.040169.002141
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    New Substances of Plant Origin which Increase Nonspecific Resistance (1969)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 9 (1969), S. 419-430 
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    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
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    URL: http://dx.doi.org/10.1146/annurev.pa.09.040169.002223
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    MAINTENANCE OF SERUM ANTIBODY LEVELS (2005)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 23 (2005), S. 367-386 
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    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: In vertebrates, serum antibodies are an essential component of innate and adaptive immunity and immunological memory. They also can contribute significantly to immunopathology. Their composition is the result of tightly regulated differentiation of B lymphocytes into antibody-secreting plasma blasts and plasma cells. The survival of antibody-secreting cells determines their contribution to the immune response in which they were generated and to long-lasting immunity, as provided by stable serum antibody levels. Short-lived plasma blasts and/or plasma cells secrete antibodies for a reactive immune response. Short-lived plasma blasts can become long-lived plasma cells, probably by competition with preexisting plasma cells for occupation of a limited number of survival niches in the body, in a process not yet fully understood. Limitation of the number of long-lived plasma cells allows the immune system to maintain a stable humoral immunological memory over long periods, to react to new pathogenic challenges, and to adapt the humoral memory in response to these antigens.
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    PENTRAXINS AT THE CROSSROADS BETWEEN INNATE IMMUNITY, INFLAMMATION, MATRIX DEPOSITION, AND FEMALE FERTILITY (2005)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 23 (2005), S. 337-366 
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    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: C reactive protein, the first innate immunity receptor identified, and serum amyloid P component are classic short pentraxins produced in the liver. Long pentraxins, including the prototype PTX3, are expressed in a variety of tissues. Some long pentraxins are expressed in the brain and some are involved in neuronal plasticity and degeneration. PTX3 is produced by a variety of cells and tissues, most notably dendritic cells and macrophages, in response to Toll-like receptor (TLR) engagement and inflammatory cytokines. PTX3 acts as a functional ancestor of antibodies, recognizing microbes, activating complement, and facilitating pathogen recognition by phagocytes, hence playing a nonredundant role in resistance against selected pathogens. In addition, PTX3 is essential in female fertility because it acts as a nodal point for the assembly of the cumulus oophorus hyaluronan-rich extracellular matrix. Thus, the prototypic long pentraxin PTX3 is a multifunctional soluble pattern recognition receptor at the crossroads between innate immunity, inflammation, matrix deposition, and female fertility.
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    NK CELL RECOGNITION (2005)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 23 (2005), S. 225-274 
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    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: The integrated processing of signals transduced by activating and inhibitory cell surface receptors regulates NK cell effector functions. Here, I review the structure, function, and ligand specificity of the receptors responsible for NK cell recognition.
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    NETWORK COMMUNICATIONS: Lymphotoxins, LIGHT, and TNF (2005)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 23 (2005), S. 787-819 
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    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Lymphotoxins (LT) provide essential communication links between lymphocytes and the surrounding stromal and parenchymal cells and together with the two related cytokines, tumor necrosis factor (TNF) and LIGHT (LT-related inducible ligand that competes for glycoprotein D binding to herpesvirus entry mediator on T cells), form an integrated signaling network necessary for efficient innate and adaptive immune responses. Recent studies have identified signaling pathways that regulate several genes, including chemokines and interferons, which participate in the development and function of microenvironments in lymphoid tissue and host defense. Disruption of the LT/TNF/LIGHT network alleviates inflammation in certain autoimmune disease models, but decreases resistance to selected pathogens. Pharmacological disruption of this network in human autoimmune diseases such as rheumatoid arthritis alleviates inflammation in a significant number of patients, but not in other diseases, a finding that challenges our molecular paradigms of autoimmunity and perhaps will reveal novel roles for this network in pathogenesis.
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    CATERPILLER: A Novel Gene Family Important in Immunity, Cell Death, and Diseases (2005)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 23 (2005), S. 387-414 
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    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: The newly discovered CATERPILLER (CLR) gene family encodes proteins with a variable but limited number of N-terminal domains, followed by a nucleotide-binding domain (NBD) and leucine-rich repeats (LRR). The N-terminal domain consists of transactivation, CARD, Pyrin, or BIR domains, with a minority containing undefined domains. These proteins are remarkably similar in structure to the TIR-NBD-LRR and CC-NBD-LRR disease resistance (R) proteins that mediate immune responses in plants. The NBD-LRR architecture is conserved in plants and vertebrates, but only remnants are found in worms and flies. The CLRs regulate inflammatory and apoptotic responses, and some act as sensors that detect pathogen products. Several CLR genes have been genetically linked to susceptibility to immunologic disorders. We describe prominent family members, including CIITA, CARD4/NOD1, NOD2/CARD15, CIAS1, CARD7/NALP1, and NAIP, in more detail. We also discuss implied roles of these proteins in diversifying immune detection and in providing a check-and-balance during inflammation.
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    MACROPHAGE RECEPTORS AND IMMUNE RECOGNITION (2005)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 23 (2005), S. 901-944 
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    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Macrophages express a broad range of plasma membrane receptors that mediate their interactions with natural and altered-self components of the host as well as a range of microorganisms. Recognition is followed by surface changes, uptake, signaling, and altered gene expression, contributing to homeostasis, host defense, innate effector mechanisms, and the induction of acquired immunity. This review covers recent studies of selected families of structurally defined molecules, studies that have improved understanding of ligand discrimination in the absence of opsonins and differential responses by macrophages and related myeloid cells.
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    MOLECULAR GENETICS OF T CELL DEVELOPMENT (2005)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 23 (2005), S. 601-649 
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    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: T cell development is guided by a complex set of transcription factors that act recursively, in different combinations, at each of the developmental choice points from T-lineage specification to peripheral T cell specialization. This review describes the modes of action of the major T-lineage-defining transcription factors and the signal pathways that activate them during intrathymic differentiation from pluripotent precursors. Roles of Notch and its effector RBPSuh (CSL), GATA-3, E2A/HEB and Id proteins, c-Myb, TCF-1, and members of the Runx, Ets, and Ikaros families are critical. Less known transcription factors that are newly recognized as being required for T cell development at particular checkpoints are also described. The transcriptional regulation of T cell development is contrasted with that of B cell development, in terms of their different degrees of overlap with the stem-cell program and the different roles of key transcription factors in gene regulatory networks leading to lineage commitment.
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    TYPE I INTERFERONS (ʼ̛/?‚) IN IMMUNITY AND AUTOIMMUNITY (2005)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 23 (2005), S. 307-335 
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    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: The significance of type I interferons (IFN-ʼ̛/?‚) in biology and medicine renders research on their activities continuously relevant to our understanding of normal and abnormal (auto) immune responses. This relevance is bolstered by discoveries that unambiguously establish IFN-ʼ̛/?‚, among the multitude of cytokines, as dominant in defining qualitative and quantitative characteristics of innate and adaptive immune processes. Recent advances elucidating the biology of these key cytokines include better definition of their complex signaling pathways, determination of their importance in modifying the effects of other cytokines, the role of Toll-like receptors in their induction, their major cellular producers, and their broad and diverse impact on both cellular and humoral immune responses. Consequently, the role of IFN-ʼ̛/?‚ in the pathogenesis of autoimmunity remains at the forefront of scientific inquiry and has begun to illuminate the mechanisms by which these molecules promote or inhibit systemic and organ-specific autoimmune diseases.
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    CHEMOKINES, SPHINGOSINE-1-PHOSPHATE, AND CELL MIGRATION IN SECONDARY LYMPHOID ORGANS (2005)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 23 (2005), S. 127-159 
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    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Secondary lymphoid organs serve as hubs for the adaptive immune system, bringing together antigen, antigen-presenting cells, and lymphocytes. Two families of G proteinĐ??coupled receptors play essential roles in lymphocyte migration through these organs: chemokine receptors and sphingosine-1-phosphate (S1P) receptors. Chemokines expressed by lymphoid stromal cells guide lymphocyte and dendritic cell movements during antigen surveillance and the initiation of adaptive immune responses. S1P receptor-1 is required for lymphocyte egress from thymus and secondary lymphoid organs and is downregulated by the immunosuppressive drug FTY720. Here, we review the steps associated with the initiation of adaptive immune responses in secondary lymphoid organs, highlighting the roles of chemokines and S1P.
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    MAST CELLS AS "TUNABLE" EFFECTOR AND IMMUNOREGULATORY CELLS: Recent Advances (2005)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 23 (2005), S. 749-786 
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    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: This review focuses on recent progress in our understanding of how mast cells can contribute to the initiation, development, expression, and regulation of acquired immune responses, both those associated with IgE and those that are apparently expressed independently of this class of Ig. We emphasize findings derived from in vivo studies in mice, particularly those employing genetic approaches to influence mast cell numbers and/or to alter or delete components of pathways that can regulate mast cell development, signaling, or function. We advance the hypothesis that mast cells not only can function as proinflammatory effector cells and drivers of tissue remodeling in established acquired immune responses, but also may contribute to the initiation and regulation of such responses. That is, we propose that mast cells can also function as immunoregulatory cells. Finally, we show that the notion that mast cells have primarily two functional configurations, off (or resting) or on (or activated for extensive mediator release), markedly oversimplifies reality. Instead, we propose that mast cells are "tunable," by both genetic and environmental factors, such that, depending on the circumstances, the cell can be positioned phenotypically to express a wide spectrum of variation in the types, kinetics, and/or magnitude of its secretory functions.
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    INTERLEUKIN-6: From Basic Science to MedicineĐ??40 Years in Immunology (2005)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 23 (2005), S. 1-21 
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    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: This essay summarizes my 40 years of research in immunology. As a young physician, I encountered a patient with Waldenstro?m's macroglobulinemia, and this inspired me to study the structure of IgM. I began to ask how antibody responses are regulated. In the late 1960s, the essential role of T cells in antibody production had been reported. In search of molecules mediating T cell helper function, I discovered activities in the culture supernatant of T cells that induced proliferation and differentiation of B cells. This led to my life's work: studying one of those factors, interleukin-6 (IL-6). To my surprise, IL-6 turned out to play additional roles, including myeloma growth factor and hepatocyte-stimulating factor activities. More importantly, it was involved in a number of diseases, such as rheumatoid arthritis and Castleman's disease. I feel exceptionally fortunate that my work not only revealed the framework of cytokine signaling, including identification of the IL-6 receptor, gp130, NF-IL6, STAT3, and SOCS-1, but also led to the development of a new therapy for chronic inflammatory diseases.
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    DNA DEGRADATION IN DEVELOPMENT AND PROGRAMMED CELL DEATH (2005)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 23 (2005), S. 853-875 
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    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Most mammalian cells have nuclei that contain DNA, which replicates during cell proliferation. DNA is destroyed by various developmental processes in mammals. It is degraded during programmed cell death that accompanies mammalian development. The nuclei of erythrocytes and eye lens fiber cells are also removed during their differentiation into mature cells. If DNA is not properly degraded in these processes, it can cause various diseases, including tissue atrophy, anemia, cataract, and autoimmune diseases, which indicates that DNA can be a pathogenic molecule. Here, I present how DNA is degraded during programmed cell death, erythroid cell differentiation, and lens cell differentiation. I discuss what might be or will be learned from understanding the molecular mechanisms of DNA degradation that occurs during mammalian development.
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    URL: http://dx.doi.org/10.1146/annurev.immunol.23.021704.115811
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    PROTEASOME INHIBITION IN MULTIPLE MYELOMA: Therapeutic Implication (2005)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 45 (2005), S. 465-476 
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    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Notes: Normal cellular functioning requires processing of proteins regulating cell cycle, growth, and apoptosis. The ubiquitin-proteasome pathway (UBP) modulates intracellular protein degradation. Specifically, the 26S proteasome is a multienzyme protease that degrades misfolded or redundant proteins; conversely, blockade of the proteasomal degradation pathways results in accumulation of unwanted proteins and cell death. Because cancer cells are more highly proliferative than normal cells, their rate of protein translation and degradation is also higher. This notion led to the development of proteasome inhibitors as therapeutics in cancer. The FDA recently approved the first proteasome inhibitor bortezomib (VelcadeĐ?„), formerly known as PS-341, for the treatment of newly diagnosed and relapsed/refractory multiple myeloma (MM). Ongoing studies are examining other novel proteasome inhibitors, in addition to bortezomib, for the treatment of MM and other cancers.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.pharmtox.45.120403.100037
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    MOLECULAR MECHANISMS OF RESISTANCE IN ANTIMALARIAL CHEMOTHERAPY: The Unmet Challenge (2005)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 45 (2005), S. 565-585 
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    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Notes: The enormous public health problem posed by malaria has been substantially worsened in recent years by the emergence and worldwide spread of drug-resistant parasites. The utility of two major therapies, chloroquine and the synergistic combination of pyrimethamine/sulfadoxine, is now seriously compromised. Although several genetic mechanisms have been described, the major source of drug resistance appears to be point mutations in protein target genes. Clinically significant resistance to these agents requires the accumulation of multiple mutations, which genetic studies of parasite populations suggest arise focally and sweep through the population. Efforts to circumvent resistance range from the use of combination therapy with existing agents to laboratory studies directed toward discovering novel targets and therapies. The prevention and management of drug resistance are among the most important practical problems of tropical medicine and public health. Leonard J. Bruce-Chwatt, 1972
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.pharmtox.45.120403.095946
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    PEROXISOME PROLIFERATOR-ACTIVATED RECEPTORS: How Their Effects on Macrophages Can Lead to the Development of a New Drug Therapy Against Atherosclerosis (2006)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 46 (2006), S. 1-39 
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    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Notes: Peroxisome proliferator-activated receptors (PPARs) alpha (ʼ̛), beta/delta (?‚/??), and gamma (??) are members of the nuclear receptor superfamily, which also includes the estrogen, androgen, and glucocorticoid receptors. Recent evidence suggests that PPARs regulate genes involved in lipid metabolism, glucose homeostasis, and inflammation in various tissues; however, the mechanisms involved are not completely understood. Anti-diabetic drugs, called glitazones, can selectively activate PPAR??, and hypolipidemic drugs, called fibrates, can weakly activate PPARʼ̛. Both classes of drugs can decrease insulin resistance and dyslipidemias, which also makes them attractive for treating the metabolic syndrome. The metabolic syndrome exhibits a constellation of risk factors for atherosclerosis that include obesity, insulin resistance, dyslipidemias, and hypertension. Interestingly, all three PPARs are present in macrophages and can therefore have a profound effect on several disease processes, including atherosclerosis. Macrophages are key players in atherosclerotic lesion development. Currently, the first line of defense in reducing the risk of atherosclerosis is aimed at lowering low-density lipoproteins (LDL) and raising high-density lipoproteins (HDL), but a large percentage of patients on statins still succumb to coronary artery disease. However, with the development of drugs selectively activating PPARs, a new arsenal of drugs specifically targeting to the macrophage/foam cell may potentially have a profound impact on how we treat cardiovascular disease.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.pharmtox.46.120604.141247
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    THE REGULATION AND PHARMACOLOGY OF ENDOTHELIAL NITRIC OXIDE SYNTHASE (2006)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 46 (2006), S. 235-276 
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    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Notes: Nitric oxide (NO) is a small, diffusible, lipophilic free radical gas that mediates significant and diverse signaling functions in nearly every organ system in the body. The endothelial isoform of nitric oxide synthase (eNOS) is a key source of NO found in the cardiovascular system. This review summarizes the pharmacology of NO and the cellular regulation of endothelial NOS (eNOS). The molecular intricacies of the chemistry of NO and the enzymology of NOSs are discussed, followed by a review of the biological activities of NO. This information is then used to develop a more global picture of the pharmacological control of NO synthesis by NOSs in both physiologic conditions and pathophysiologic states.
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    URL: http://dx.doi.org/10.1146/annurev.pharmtox.44.101802.121844
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    CYTOCHROME P450 AND XENOBIOTIC RECEPTOR HUMANIZED MICE * (2006)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 46 (2006), S. 41-64 
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    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Notes: Most xenobiotics that enter the body are subjected to metabolism that functions primarily to facilitate their elimination. Metabolism of certain xenobiotics can also result in the production of electrophilic derivatives that can cause cell toxicity and transformation. Many xenobiotics can also activate receptors that in turn induce the expression of genes encoding xenobiotic-metabolizing enzymes and xenobiotic transporters. However, there are marked species differences in the way mammals respond to xenobiotics, which are due in large part to molecular differences in receptors and xenobiotic-metabolizing enzymes. This presents a problem in extrapolating data obtained with rodent model systems to humans. There are also polymorphisms in xenobiotic-metabolizing enzymes that can impact drug therapy and cancer susceptibility. In an effort to generate more reliable in vivo systems to study and predict human response to xenobiotics, humanized mice are under development.
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    Drugs and Properties of Heart Muscle (1965)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 5 (1965), S. 99-118 
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    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.pa.05.040165.000531
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    Acetylcholine in Adrenergic Transmission (1965)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 5 (1965), S. 163-182 
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    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.pa.05.040165.001115
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    Neuromuscular Pharmacology (1965)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 5 (1965), S. 263-284 
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    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.pa.05.040165.001403
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    Radiopaque Diagnostic Agents (1965)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 5 (1965), S. 321-334 
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    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.pa.05.040165.001541
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    Autonomic Nervous System: Newer Mechanisms of Adrenergic Blockade (1966)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 6 (1966), S. 107-128 
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    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.pa.06.040166.000543
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    Perinatal Pharmacology (1966)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 6 (1966), S. 189-207 
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    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.pa.06.040166.001201
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    Renal Pharmacology (1966)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 6 (1966), S. 261-292 
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    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
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    URL: http://dx.doi.org/10.1146/annurev.pa.06.040166.001401
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    Anesthesia (1966)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 6 (1966), S. 379-404 
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    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
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    URL: http://dx.doi.org/10.1146/annurev.pa.06.040166.002115
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    Toxicological Safety of Irradiated Foods (1967)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 7 (1967), S. 357-380 
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    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.pa.07.040167.002041
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    Agents Which Block Adrenergic beta-Receptors (1968)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 8 (1968), S. 259-272 
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    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.pa.08.040168.001355
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    Extrarenal Excretion of Drugs and Chemicals (1968)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 8 (1968), S. 337-356 
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    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.pa.08.040168.002005
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    Fluorides and Man (1968)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 8 (1968), S. 395-408 
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    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.pa.08.040168.002143
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    Drugs and Enzyme Induction (1969)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 9 (1969), S. 21-36 
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    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.pa.09.040169.000321
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    HOW NEUTROPHILS KILL MICROBES (2005)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 23 (2005), S. 197-223 
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    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Neutrophils provide the first line of defense of the innate immune system by phagocytosing, killing, and digesting bacteria and fungi. Killing was previously believed to be accomplished by oxygen free radicals and other reactive oxygen species generated by the NADPH oxidase, and by oxidized halides produced by myeloperoxidase. We now know this is incorrect. The oxidase pumps electrons into the phagocytic vacuole, thereby inducing a charge across the membrane that must be compensated. The movement of compensating ions produces conditions in the vacuole conducive to microbial killing and digestion by enzymes released into the vacuole from the cytoplasmic granules.
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    URL: http://dx.doi.org/10.1146/annurev.immunol.23.021704.115653
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    ROLE OF C5A IN INFLAMMATORY RESPONSES (2005)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 23 (2005), S. 821-852 
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    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: The complement system not only represents an effective innate immune mechanism of host defense to eradicate microbial pathogens, but it is also widely involved in many forms of acute and chronic inflammatory diseases including sepsis, acute lung injury, ischemia-reperfusion injury, and asthma, to give just a few examples. The complement-activated product, C5a, displays powerful biological activities that lead to inflammatory sequelae. C5a is a strong chemoattractant and is involved in the recruitment of inflammatory cells such as neutrophils, eosinophils, monocytes, and T lymphocytes, in activation of phagocytic cells and release of granule-based enzymes and generation of oxidants, all of which may contribute to innate immune functions or tissue damage. Accumulating data suggest that C5a provides a vital bridge between innate and adaptive immune functions, extending the roles of C5a in inflammation. Herein, we review human and animal data describing the cellular and molecular mechanisms of C5a in the development of inflammatory disorders, sepsis, acute lung injury, ischemia-reperfusion injury, and asthma.
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    URL: http://dx.doi.org/10.1146/annurev.immunol.23.021704.115835
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    IPC: Professional Type 1 Interferon-Producing Cells and Plasmacytoid Dendritic Cell Precursors (2005)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 23 (2005), S. 275-306 
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    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Type 1 interferon-(ʼ̛, ?‚, ?)-producing cells (IPCs), also known as plasmacytoid dendritic cell precursors (pDCs), represent 0.2%Đ??0.8% of peripheral blood mononuclear cells in both humans and mice. IPCs display plasma cell morphology, selectively express Toll-like receptor (TLR)-7 and TLR9, and are specialized in rapidly secreting massive amounts of type 1 interferon following viral stimulation. IPCs can promote the function of natural killer cells, B cells, T cells, and myeloid DCs through type 1 interferons during an antiviral immune response. At a later stage of viral infection, IPCs differentiate into a unique type of mature dendritic cell, which directly regulates the function of T cells and thus links innate and adaptive immune responses. After more than two decades of effort by researchers, IPCs finally claim their place in the hematopoietic chart as the most important cell type in antiviral innate immunity. Understanding IPC biology holds future promise for developing cures for infectious diseases, cancer, and autoimmune diseases.
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    The Bionomics of Blow Flies (1965)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Entomology 10 (1965), S. 47-68 
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    ISSN: 0066-4170
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.en.10.010165.000403
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    STRUCTURAL AND SEQUENCE MOTIFS OF PROTEIN (HISTONE) METHYLATION ENZYMES (2005)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 34 (2005), S. 267-294 
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    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    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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    ION CONDUCTION AND SELECTIVITY IN K+ CHANNELS (2005)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 34 (2005), S. 153-171 
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    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    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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    URL: http://dx.doi.org/10.1146/annurev.biophys.34.040204.144655
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    CHEMICAL SYNTHESIS OF PROTEINS (2005)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 34 (2005), S. 91-118 
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    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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    USE OF EPR POWER SATURATION TO ANALYZE THE MEMBRANE-DOCKING GEOMETRIES OF PERIPHERAL PROTEINS: Applications to C2 Domains (2005)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 34 (2005), S. 71-90 
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    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Despite the central importance of peripheral membrane proteins to cellular signaling and metabolic pathways, the structures of protein-membrane interfaces remain largely inaccessible to high-resolution structural methods. In recent years a number of laboratories have contributed to the development of an electron paramagnetic resonance (EPR) power saturation approach that utilizes site-directed spin labeling to determine the key geometric parameters of membrane-docked proteins, including their penetration depths and angular orientations relative to the membrane surface. Representative applications to Ca2+-activated, membrane-docking C2 domains are described.
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    MEMBRANE-PROTEIN INTERACTIONS IN CELL SIGNALING AND MEMBRANE TRAFFICKING (2005)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 34 (2005), S. 119-151 
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    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Research in the past decade has revealed that many cytosolic proteins are recruited to different cellular membranes to form protein-protein and lipid-protein interactions during cell signaling and membrane trafficking. Membrane recruitment of these peripheral proteins is mediated by a growing number of modular membrane-targeting domains, including C1, C2, PH, FYVE, PX, ENTH, ANTH, BAR, FERM, and tubby domains, that recognize specific lipid molecules in the membranes. Structural studies of these membrane-targeting domains demonstrate how they specifically recognize their cognate lipid ligands. However, the mechanisms by which these domains and their host proteins are recruited to and interact with various cell membranes are only beginning to unravel with recent computational studies, in vitro membrane binding studies using model membranes, and cellular translocation studies using fluorescent protein-tagged proteins. This review summarizes the recent progress in our understanding of how the kinetics and energetics of membrane-protein interactions are regulated during the cellular membrane targeting and activation of peripheral proteins.
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    MODELING WATER, THE HYDROPHOBIC EFFECT, AND ION SOLVATION (2005)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 34 (2005), S. 173-199 
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    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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    PROTEIN-DNA RECOGNITION PATTERNS AND PREDICTIONS (2005)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 34 (2005), S. 379-398 
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    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.biophys.34.040204.144537
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    TOWARD PREDICTIVE MODELS OF MAMMALIAN CELLS (2005)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 34 (2005), S. 319-349 
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    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Progress in experimental and theoretical biology is likely to provide us with the opportunity to assemble detailed predictive models of mammalian cells. Using a functional format to describe the organization of mammalian cells, we describe current approaches for developing qualitative and quantitative models using data from a variety of experimental sources. Recent developments and applications of graph theory to biological networks are reviewed. The use of these qualitative models to identify the topology of regulatory motifs and functional modules is discussed. Cellular homeostasis and plasticity are interpreted within the framework of balance between regulatory motifs and interactions between modules. From this analysis we identify the need for detailed quantitative models on the basis of the representation of the chemistry underlying the cellular process. The use of deterministic, stochastic, and hybrid models to represent cellular processes is reviewed, and an initial integrated approach for the development of large-scale predictive models of a mammalian cell is presented.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.biophys.34.040204.144415
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  • 99
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    QUORUM SENSING: Cell-to-Cell Communication in Bacteria (2005)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 21 (2005), S. 319-346 
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    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Bacteria communicate with one another using chemical signal molecules. As in higher organisms, the information supplied by these molecules is critical for synchronizing the activities of large groups of cells. In bacteria, chemical communication involves producing, releasing, detecting, and responding to small hormone-like molecules termed autoinducers . This process, termed quorum sensing, allows bacteria to monitor the environment for other bacteria and to alter behavior on a population-wide scale in response to changes in the number and/or species present in a community. Most quorum-sensing-controlled processes are unproductive when undertaken by an individual bacterium acting alone but become beneficial when carried out simultaneously by a large number of cells. Thus, quorum sensing confuses the distinction between prokaryotes and eukaryotes because it enables bacteria to act as multicellular organisms. This review focuses on the architectures of bacterial chemical communication networks; how chemical information is integrated, processed, and transduced to control gene expression; how intra- and interspecies cell-cell communication is accomplished; and the intriguing possibility of prokaryote-eukaryote cross-communication.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.cellbio.21.012704.131001
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    MOLECULAR MECHANISMS OF STEROID HORMONE SIGNALING IN PLANTS (2005)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 21 (2005), S. 177-201 
    Details
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Brassinosteroids (BRs), the polyhydroxylated steroid hormones of plants, regulate the growth and differentiation of plants throughout their life cycle. Over the past several years, genetic and biochemical approaches have yielded great progress in understanding BR signaling. Unlike their animal counterparts, BRs are perceived at the plasma membrane by direct binding to the extracellular domain of the BRI1 receptor S/T kinase. BR perception initiates a signaling cascade, acting through a GSK3 kinase, BIN2, and the BSU1 phosphatase, which in turn modulates the phosphorylation state and stability of the nuclear transcription factors BES1 and BZR1. Microarray technology has been used extensively to provide a global view of BR genomic effects, as well as a specific set of target genes for BES1 and BZR1. These gene products thus provide a framework for how BRs regulate the growth of plants.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.cellbio.21.090704.151241
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