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  • Institute of Physics  (131,010)
  • American Institute of Physics  (79,595)
  • Cell Press  (29,371)
  • American Meteorological Society
  • Annual Reviews
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  • 2005-2009  (264,774)
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  • 1
    Publication Date: 2020-12-14
    Description: In this study we present an intercomparison of measurements of very low water vapor column content obtained with a Ground-Based Millimeter-wave Spectrometer (GBMS), Vaisala RS92k radiosondes, a Raman Lidar, and an IR Fourier Transform Spectrometer. These sets of measurements were carried out during the primary field campaign of the ECOWAR (Earth COoling by WAter vapor Radiation) project which took place on the Western Italian Alps from 3 to 16 March, 2007.
    Description: Published
    Description: 135-138
    Description: 1.8. Osservazioni di geofisica ambientale
    Description: N/A or not JCR
    Description: open
    Keywords: Precipitable Water Vapor ; ECOWAR ; IR and Millimeter-Wave Spectroscopy ; 01. Atmosphere::01.01. Atmosphere::01.01.01. Composition and Structure ; 01. Atmosphere::01.01. Atmosphere::01.01.02. Climate
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Type: article
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  • 2
    Publication Date: 2021-06-08
    Description: The Aegean water masses and circulation structure are studied via two large-scale surveys performed during the late winters of 1988 and 1990 by the R/V Yakov Gakkel of the former Soviet Union. The analysis of these data sheds light on the mechanisms of water mass formation in the Aegean Sea that triggered the outflow of Cretan Deep Water (CDW) from the Cretan Sea into the abyssal basins of the eastern Mediterranean Sea (the so-called Eastern Mediterranean Transient). It is found that the central Aegean Basin is the site of the formation of Aegean Intermediate Water, which slides southward and, depending on their density, renews either the intermediate or the deep water of the Cretan Sea. During the winter of 1988, the Cretan Sea waters were renewed mainly at intermediate levels, while during the winter of 1990 it was mainly the volume of CDW that increased. This Aegean water mass redistribution and formation process in 1990 differed from that in 1988 in two major aspects: (i) during the winter of 1990 the position of the front between the Black Sea Water and the Levantine Surface Water was displaced farther north than during the winter of 1988 and (ii) heavier waters were formed in 1990 as a result of enhanced lateral advection of salty Levantine Surface Water that enriched the intermediate waters with salt. In 1990 the 29.2 isopycnal rose to the surface of the central basin and a large volume of CDW filled the Cretan Basin. It is found that, already in 1988, the 29.2 isopycnal surface, which we assume is the lowest density of the CDW, was shallower than the Kassos Strait sill and thus CDW egressed into the Eastern Mediterranean.
    Description: Published
    Description: 1841-1859
    Description: JCR Journal
    Description: reserved
    Keywords: Aegean Sea ; Water Masses ; 03. Hydrosphere::03.03. Physical::03.03.03. Interannual-to-decadal ocean variability
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Type: article
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  • 3
    Publication Date: 2021-06-01
    Description: Five non-eddy-resolving oceanic general circulation models driven by atmospheric fluxes derived from the NCEP reanalysis are used to investigate the link between the Gulf Stream (GS) variability, the atmospheric circulation, and the Atlantic meridional overturning circulation (AMOC). Despite the limited model resolution, the temperature at the 200-m depth along the mean GS axis behaves similarly in most models to that observed, and it is also well correlated with the North Atlantic Oscillation (NAO), indicating that a northward (southward) GS shift lags a positive (negative) NAO phase by 0–2 yr. The northward shift is accompanied by an increase in the GS transport, and conversely the southward shift with a decrease in the GS transport. Two dominant time scales appear in the response of the GS transport to the NAO forcing: a fast time scale (less than 1 month) for the barotropic component, and a slower one (about 2 yr) for the baroclinic component. In addition, the two components are weakly coupled. The GS response seems broadly consistent with a linear adjustment to the changes in the wind stress curl, and evidence for baroclinic Rossby wave propagation is found in the southern part of the subtropical gyre. However, the GS shifts are also affected by basin-scale changes in the oceanic conditions, and they are well correlated in most models with the changes in the AMOC. A larger AMOC is found when the GS is stronger and displaced northward, and a higher correlation is found when the observed changes of the GS position are used in the comparison. The relation between the GS and the AMOC could be explained by the inherent coupling between the thermohaline and the wind-driven circulation, or by the NAO variability driving them on similar time scales in the models.
    Description: This research was supported by the PREDICATE project of the European Community, and for M. Bentsen by the Research Council of Norway through RegClim, NOClim, and the Programme of Supercomputing.
    Description: Published
    Description: 2119–2135
    Description: 3.7. Dinamica del clima e dell'oceano
    Description: JCR Journal
    Description: reserved
    Keywords: ocean modelling ; gulf stream variability ; 03. Hydrosphere::03.01. General::03.01.03. Global climate models
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Type: article
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  • 4
    Publication Date: 2020-11-19
    Description: A land surface model (LSM) has been included in the ECMWF Hamburg version 4 (ECHAM4) atmospheric general circulation model (AGCM). The LSM is an early version of the Organizing Carbon and Hydrology in Dynamic Ecosystems (ORCHIDEE) and it replaces the simple land surface scheme previously included in ECHAM4. The purpose of this paper is to document how a more exhaustive consideration of the land surface–vegetation processes affects the simulated boreal summer surface climate. To investigate the impacts on the simulated climate, different sets of Atmospheric Model Intercomparison Project (AMIP)-type simulations have been performed with ECHAM4 alone and with the AGCM coupled with ORCHIDEE. Furthermore, to assess the effects of the increase in horizontal resolution the coupling of ECHAM4 with the LSM has been implemented at different horizontal resolutions. The analysis reveals that the LSM has large effects on the simulated boreal summer surface climate of the atmospheric model. Considerable impacts are found in the surface energy balance due to changes in the surface latent heat fluxes over tropical and midlatitude areas covered with vegetation. Rainfall and atmospheric circulation are substantially affected by these changes. In particular, increased precipitation is found over evergreen and summergreen vegetated areas. Because of the socioeconomical relevance, particular attention has been devoted to the Indian summer monsoon (ISM) region. The results of this study indicate that precipitation over the Indian subcontinent is better simulated with the coupled ECHAM4–ORCHIDEE model compared to the atmospheric model alone.
    Description: Published
    Description: 255–278
    Description: 3.7. Dinamica del clima e dell'oceano
    Description: JCR Journal
    Description: partially_open
    Keywords: Land Atmosphere interactions ; Global climate models ; 01. Atmosphere::01.01. Atmosphere::01.01.02. Climate
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Type: article
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  • 5
    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)
    Type: article
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  • 6
    Publication Date: 2017-04-04
    Description: COST (Co-operation in the field of Scientific and Technical Research) is an important instrument supporting co-operation among scientists and researchers across Europe now joining 35 member countries. Scientific projects in the COST framework are called COST Actions and have the objectives embodied in their respective Memorandum of Understanding (MoU). The main objectives of the COST Actions within the European ionospheric and radio propagation community have been: to study the influence of upper atmospheric conditions on terrestrial and Earthspace communications, to develop methods and techniques to improve existing and generate new ionospheric and propagation models over Europe for telecommunication and navigation applications and to transfer the results to the appropriate national and international organizations, institutions and industry dealing with the modern communication systems. This paper summarises in brief the background and historical context of four ionospheric COST Actions and outlines their main objectives and results. In addition, the paper discusses the dissemination of the results and the collaboration among the participating institutions and researchers.
    Description: DRS Codem Systems Ball Aerospace Corporation University of Massachusetts Lowell
    Description: Published
    Description: Lowell, Massachusetts, U.S.A., April 29, 2007
    Description: 3.9. Fisica della magnetosfera, ionosfera e meteorologia spaziale
    Description: open
    Keywords: Physics of the Ionosphere ; 01. Atmosphere::01.02. Ionosphere::01.02.99. General or miscellaneous ; 05. General::05.07. Space and Planetary sciences::05.07.02. Space weather
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Type: Conference paper
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  • 7
    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)
    Type: article
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  • 8
    Publication Date: 2017-04-04
    Description: Volcanoes represent an important natural source of several trace elements to the atmosphere. For some species (e.g., As, Cd, Pb and Se) they may be the main natural source and thereby strongly influencing geochemical cycles from the local to the global scale. Mount Etna is one of the most actively degassing volcanoes in the world, and it is considered to be, on the long-term average, the major atmospheric point source of many environmental harmful compounds. Their emission occurs either through continuous passive degassing from open-conduit activity or through sporadic paroxysmal eruptive activity, in the form of gases, aerosols or particulate. To estimate the environmental impact of magma-derived trace metals and their depositions processes, rainwater and snow samples were collected at Mount Etna area. Five bulk collectors have been deployed at various altitudes on the upper flanks around the summit craters of the volcano; samples were collected every two week for a period of one year and analyzed for the main chemical-physical parameters (electric conductivity and pH) and for major and trace elements concentrations. Chemical analysis of rainwater clearly shows that the volcanic contribution is always prevailing in the sampling site closest to the summit crater (about 1.5 km). In the distal sites (5.5-10 km from the summit) and downwind of the summit craters, the volcanic contribution is also detectable but often overwhelmed by anthropogenic or other natural (seawater spray, geogenic dust) contributions. Volcanic contribution may derive from both dry and wet deposition of gases and aerosols from the volcanic plume, but sometimes also from leaching of freshly emitted volcanic ashes. In fact, in our background site (7.5 km in the upwind direction) volcanic contribution has been detected only following an ash deposition event. About 30 samples of fresh snow were collected in the upper part of the volcano, during the winters 2006 and 2007 to estimate deposition processes at high altitude during cold periods. Some of the samples were collected immediately after a major explosive event from the summit craters to understand the interaction between snow and fresh erupted ash. Sulphur, Chlorine and Fluorine, are the major elements that prevailingly characterize the volcanic contribution in atmospheric precipitation on Mount Etna, but high concentrations of many trace elements are also detected in the studied samples. In particular, bulk deposition samples display high concentration of Al, Fe, Ti, Cu, As, Rb, Pb, Tl, Cd, Cr, U and Ag, in the site most exposed to the volcanic emissions: median concentration values are about two orders of magnitude higher than those measured in our background site. Also in the snow samples the volcanic signature is clearly detectable and decreases with distance from the summit craters. Some of the analysed elements display very high enrichment values with respect to the average crust and, in the closest site to the summit craters, also deposition values higher than those measured in polluted urban or industrial sites.
    Description: Published
    Description: Vienna, Austria
    Description: 4.5. Degassamento naturale
    Description: open
    Keywords: Mt. Etna ; trace elements ; rainwater ; 01. Atmosphere::01.01. Atmosphere::01.01.07. Volcanic effects ; 03. Hydrosphere::03.03. Physical::03.03.01. Air/water/earth interactions ; 03. Hydrosphere::03.04. Chemical and biological::03.04.03. Chemistry of waters
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Type: Oral presentation
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  • 9
    Publication Date: 2017-04-04
    Description: Improving the constraints on the atmospheric fate and depletion rates of acidic compounds persistently emitted by non-erupting (quiescent) volcanoes is important for quantitatively predicting the environmental impact of volcanic gas plumes. Here, we present new experimental data coupled with modelling studies to investigate the chemical processing of acidic volcanogenic species during tropospheric dispersion. Diffusive tube samplers were deployed at Mount Etna, a very active open-conduit basaltic volcano in eastern Sicily, and Vulcano Island, a closed-conduit quiescent volcano in the Aeolian Islands (northern Sicily). Sulphur dioxide (SO2), hydrogen sulphide (H2S), hydrogen chloride (HCl) and hydrogen fluoride (HF) concentrations in the volcanic plumes (typically several minutes to a few hours old) were repeatedly determined at distances from the summit vents ranging from 0.1 to ~10 km, and under different environmental conditions. At both volcanoes, acidic gas concentrations were found to decrease exponentially with distance from the summit vents (e.g., SO2 decreases from ~10,000 μg/m3 at 0.1 km from Etna’s vents down to ~7 _μg/m3 at ~10km distance), reflecting the atmospheric dilution of the plume within the acid gas-free background troposphere. Conversely, SO2/HCl, SO2/HF, and SO2/H2S ratios in the plume showed no systematic changes with plume aging, and fit source compositions within analytical error. Assuming that SO2 losses by reaction are small during short-range atmospheric transport within quiescent (ash-free) volcanic plumes, our observations suggest that, for these short transport distances, atmospheric reactions for H2S and halogens are also negligible. The one-dimensional model MISTRA was used to simulate quantitatively the evolution of halogen and sulphur compounds in the plume of Mt. Etna. Model predictions support the hypothesis of minor HCl chemical processing during plume transport, at least in cloud-free conditions. Larger variations in the modelled SO2/HCl ratios were predicted under cloudy conditions, due to heterogeneous chlorine cycling in the aerosol phase. The modelled evolution of the SO2/H2S ratios is found to be substantially dependent on whether or not the interactions of H2S with halogens are included in the model. In the former case, H2S is assumed to be oxidized in the atmosphere mainly by OH, which results in minor chemical loss for H2S during plume aging and produces a fair match between modelled and measured SO2/H2S ratios. In the latter case, fast oxidation of H2S by Cl leads to H2S chemical lifetimes in the early plume of a few seconds, and thus SO2 to H2S ratios that increase sharply during plume transport. This disagreement between modelled and observed plume compositions suggests that more in-detail kinetic investigations are required for a proper evaluation of H2S chemical processing in volcanic plumes.
    Description: Published
    Description: 1441-1450
    Description: 1.2. TTC - Sorveglianza geochimica delle aree vulcaniche attive
    Description: 4.5. Degassamento naturale
    Description: JCR Journal
    Description: open
    Keywords: Mt. Etna ; volcanic gas plumes ; tropospheric processing ; 01. Atmosphere::01.01. Atmosphere::01.01.07. Volcanic effects
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Type: article
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  • 10
    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)
    Type: article
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  • 11
    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)
    Type: article
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  • 12
    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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  • 13
    Publication Date: 2017-04-04
    Description: After some short test surveys, during the 2004–2005 summer expedition in Antarctica, a geomagnetic French-Italian observatory was installed on the plateau (geographic coordinates: 75.1 S, 123.4 E; corrected geomagnetic coordinates: 88.9 S, 54.3 E; UT=LT−8) very close to the geomagnetic pole. In this paper we present some peculiarities of the daily variation as observed at this polar cap observatory during the years 2005 and 2006, taking into account the different Loyd seasons and different interplanetary magnetic field conditions. Some interesting results emerge from the analysis, confirming the dependence of the daily variation (and of the associated polar current systems) on the IMF Bz and By components. In particular the analysis showed that different Bz conditions correspond to different contribution to daily variation of ionospheric and field aligned currents, while particular By conditions lead to a time shift of the diurnal variation, indicating an asymmetry with respect to the noon meridian.
    Description: Published
    Description: 2045–2051
    Description: 3.9. Fisica della magnetosfera, ionosfera e meteorologia spaziale
    Description: 1.6. Osservazioni di geomagnetismo
    Description: JCR Journal
    Description: reserved
    Keywords: Geomagnetism and paleomagnetism (Time variations, diurnal to secular) ; Magnetospheric physics (Polar cap phenomena; Solar wind-magnetosphere interactions) ; 01. Atmosphere::01.03. Magnetosphere::01.03.99. General or miscellaneous
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 14
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    American Institute of Physics
    Publication Date: 2020-02-24
    Description: A high-resolution Fabry–Perot interferometer was inserted in a feedback loop which, by monitoring elements of the fringe pattern, keeps the position of the transmitting window fixed with respect to a given line, taking into account the instability of the radiation source which would produce a wander of the line itself and the noise affecting the tuning of the receiving interferometer. The system, in this preliminary form, is able to lock itself and maintain its position indefinitely for slow and moderately fast varying disturbances.
    Description: Published
    Description: 2940-2944
    Description: 1.7. Osservazioni di alta e media atmosfera
    Description: JCR Journal
    Description: reserved
    Keywords: FABRY-PEROT ; INTERFEROMETER ; SERVOMECHANISMS ; FEEDBACK ; 01. Atmosphere::01.01. Atmosphere::01.01.08. Instruments and techniques
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 15
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    American Meteorological Society
    In:  EPIC3Journal of Atmospheric and Oceanic Technology, American Meteorological Society, 25(2), pp. 149-166, ISSN: 0739-0572
    Publication Date: 2019-07-17
    Description: The accuracy of all types of Vaisala radiosondes and two types of Snow White chilled-mirror hygrosondes was assessed in an intensive in situ comparison with reference hygrometers. Fourteen nighttime reference comparisons were performed to determine a working reference for the radiosonde comparisons. These showed that the night version of the Snow White agreed best with the references [i.e., the NOAA frost-point hygrometer (FPH) and University of Colorado cryogenic frost-point hygrometer (CFH)], but that the daytime version had severe problems with contamination in the humid upper troposphere. Since the RS92 performance was superior to the other radiosondes and to the day version of the Snow White, it was selected to be the working reference. According to the reference comparison, the RS92 has no bias in the mid- and lower troposphere, with deviations 〈±5% in relative humidity (RH). In the upper troposphere, the RS92 has a 5% RH wet bias, which is partly due to the RS92 time lag error and the termination of the heating cycle. It was shown that the time lag effects relating to Vaisala radiosondes can be corrected. Because these were nighttime comparisons, they can be considered to be free from solar radiation effects. Neither the radiosondes nor the Snow White succeeded in reproducing reference class hygrometer profiles in the stratosphere. According to the 29 radiosonde intercomparisons, the RS92 and the modified RS90 (FN) had the best mutual agreement and no bias. The disagreement is largest (〈±10% RH) at low temperatures (T ≪ −30°C), where the FN underestimated (overestimated) in high (low) ambient RH. In comparison with the RS92, the RS90 had a semilinearly increasing wet bias with decreasing temperature, where the bias was 10% RH at −60°C. The RS80-A suffers from a large temperature-dependent dry bias in high RH conditions, being over 30% RH at −60°C and 5% RH near 0°C. The RS80-A dry bias can be almost totally removed with the correction algorithm by Leiterer et al., which was chosen as the best available. The other approach tested tends to overcorrect in high RH conditions when T 〈 −50°C. For T 〉 −30°C it is ineffective and does not correct the RS80-A dry bias in high ambient RH.
    Repository Name: EPIC Alfred Wegener Institut
    Type: Article , isiRev
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  • 16
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    American Meteorological Society
    Publication Date: 2021-05-19
    Description: In this study we show a teleconnection pattern relating Outgoing Longwave Radiation (OLR) anomalies over the western Pacific Ocean and sea surface temperature anomalies (SSTA) over the western Indian Ocean over two seasons (Sept-Oct-Nov and Dec-Jan-Feb) at zero lag from observations and atmospheric general circulation model (AGCM) integrations. This teleconnection pattern suggests that a positive SSTA in Sept-Oct-Nov (SON) and Dec-Jan-Feb (DJF) seasons over the western Indian Ocean increases the contemporaneous positive OLR anomalies over the western Pacific Ocean. This teleconnection pattern is also simulated by the Center for Ocean-Land- Atmosphere studies (COLA) AGCM forced with observed SST’s. From the experimental COLA AGCM runs (wherein the Pacific Ocean SST variability is suppressed except for the climatological annual cycle) it is diagnosed that the interannual variability of OLR over the western Pacific Ocean persists because of this teleconnection. In relation to this teleconnection pattern it is shown that there is a significant linear response of the SON and DJF equatorial zonal wind anomaly over the Pacific Ocean to contemporaneous SSTA over the western Indian Ocean which is comparable to that of the eastern and western Pacific Oceans. The experimental AGCM runs clearly show that this response of the equatorial zonal wind anomaly to the western Indian Ocean forcing shifts westward towards the Indian Ocean in the absence of Pacific SST variability.
    Description: Published
    Keywords: Sea surface temperature ; Atmospheric conditions ; Teleconnections
    Repository Name: AquaDocs
    Type: Journal Contribution , Refereed , Article
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  • 17
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    American Meteorological Society
    Publication Date: 2021-05-19
    Description: Skill in ensemble-mean dynamical seasonal climate hindcasts with a coupled land-atmosphere model and specified observed sea surface temperature is compared to that for long multi-decade integrations of the same model where the initial conditions are far removed from the seasons of validation. The evaluations are performed for surface temperature and compared among all seasons. Skill is found to be higher in the seasonal simulations than the multi-decadal integrations except during boreal winter. The higher skill is prominent even beyond the first month when the direct influence of the atmospheric initial state elevates model skill. Skill is generally found to be lowest during the winter season for the dynamical seasonal forecasts, equal to that of the long integrations, which show some of the highest skill during winter. The reason for the differences in skill during the non-winter months is attributed to the severe climate drift in the long simulations, manifest through errors in downward fluxes of water and energy over land and evident in soil wetness. The drift presses the land surface to extreme dry or wet states over much of the globe, into a range where there is little sensitivity of evaporation to fluctuations in soil moisture. Thus, the land-atmosphere feedback is suppressed, which appears to lessen the model’s ability to respond correctly over land to remote ocean temperature anomalies.
    Description: Center for Ocean-Land-Atmosphere Studies
    Description: Published
    Keywords: Atmosphere-ocean system
    Repository Name: AquaDocs
    Type: Journal Contribution , Refereed , Article
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    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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  • 19
    Publication Date: 2022-05-25
    Description: Author Posting. © Annual Reviews, 2003. This article is posted here by permission of Annual Reviews for personal use, not for redistribution. The definitive version was published in Annual Review of Environment and Resources 28 (2003): 521-558, doi:10.1146/annurev.energy.28.011503.163443.
    Description: Agriculture and industrial development have led to inadvertent changes in the natural carbon cycle. As a consequence, concentrations of carbon dioxide and other greenhouse gases have increased in the atmosphere and may lead to changes in climate. The current challenge facing society is to develop options for future management of the carbon cycle. A variety of approaches has been suggested: direct reduction of emissions, deliberate manipulation of the natural carbon cycle to enhance sequestration, and capture and isolation of carbon from fossil fuel use. Policy development to date has laid out some of the general principles to which carbon management should adhere. These are summarized as: how much carbon is stored, by what means, and for how long. To successfully manage carbon for climate purposes requires increased understanding of carbon cycle dynamics and improvement in the scientific capabilities available for measurement as well as for policy needs. The specific needs for scientific information to underpin carbon cycle management decisions are not yet broadly known. A stronger dialogue between decision makers and scientists must be developed to foster improved application of scientific knowledge to decisions. This review focuses on the current knowledge of the carbon cycle, carbon measurement capabilities (with an emphasis on the continental scale) and the relevance of carbon cycle science to carbon sequestration goals.
    Description: The National Center for Atmospheric Research is supported by the National Science Foundation.
    Keywords: Carbon sequestration ; Measurement techniques ; Climate ; Kyoto protocol
    Repository Name: Woods Hole Open Access Server
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    Annual Reviews
    Publication Date: 2022-05-25
    Description: Author Posting. © Annual Reviews, 2006. This article is posted here by permission of Annual Reviews for personal use, not for redistribution. The definitive version was published in Annual Review of Fluid Mechanics 38 (2006): 395-425, doi:10.1146/annurev.fluid.38.050304.092129.
    Description: Over the past four decades, the combination of in situ and remote sensing observations has demonstrated that long nonlinear internal solitary-like waves are ubiquitous features of coastal oceans. The following provides an overview of the properties of steady internal solitary waves and the transient processes of wave generation and evolution, primarily from the point of view of weakly nonlinear theory, of which the Korteweg-de Vries equation is the most frequently used example. However, the oceanographically important processes of wave instability and breaking, generally inaccessible with these models, are also discussed. Furthermore, observations often show strongly nonlinear waves whose properties can only be explained with fully nonlinear models.
    Description: KRH acknowledges support from NSF and ONR and an Independent Study Award from the Woods Hole Oceanographic Institution. WKM acknowledges support from NSF and ONR, which has made his work in this area possible, in close collaboration with former graduate students at Scripps Institution of Oceanography and MIT.
    Keywords: Solitary waves ; Nonlinear waves ; Stratified flow ; Physical Oceanography
    Repository Name: Woods Hole Open Access Server
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  • 21
    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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  • 22
    Publication Date: 2022-05-25
    Description: First published online as a Review in Advance on October 24, 2005. (Some corrections may occur before final publication online and in print)
    Description: Author Posting. © Annual Reviews, 2005. This article is posted here by permission of Annual Reviews for personal use, not for redistribution. The definitive version was published in Annual Review of Physiology 68 (2006): 22.1-22.29, doi:10.1146/annurev.physiol.68.040104.105418.
    Description: Superfast muscles of vertebrates power sound production. The fastest, the swimbladder muscle of toadfish, generates mechanical power at frequencies in excess of 200 Hz. To operate at these frequencies, the speed of relaxation has had to increase approximately 50-fold. This increase is accomplished by modifications of three kinetic traits: (a) a fast calcium transient due to extremely high concentration of sarcoplasmic reticulum (SR)-Ca2+ pumps and parvalbumin, (b) fast off-rate of Ca2+ from troponin C due to an alteration in troponin, and (c) fast cross-bridge detachment rate constant (g, 50 times faster than that in rabbit fast-twitch muscle) due to an alteration in myosin. Although these three modifications permit swimbladder muscle to generate mechanical work at high frequencies (where locomotor muscles cannot), it comes with a cost: The high g causes a large reduction in attached force-generating cross-bridges, making the swimbladder incapable of powering low-frequency locomotory movements. Hence the locomotory and sound-producing muscles have mutually exclusive designs.
    Description: This work was made possible by support from NIH grants AR38404 and AR46125 as well as the University of Pennsylvania Research Foundation.
    Keywords: Parvalbumin ; Ca2+ release ; Ca2+ uptake ; Cross-bridges ; Adaptation ; Sound production ; Whitman Center
    Repository Name: Woods Hole Open Access Server
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  • 23
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    American Institute of Physics
    Publication Date: 2022-05-26
    Description: Author Posting. © American Institute of Physics, 2009. This article is posted here by permission of American Institute of Physics for personal use, not for redistribution. The definitive version was published in Physics Today 62 n.11 (2009): 39-44.
    Description: Most species of large whales are endangered because for centuries whaling fleets have decimated their populations. In the late 1960s, marine-mammal biologists discovered that fishermen setting nets for tuna in the Pacific Ocean were killing more than 100,000 dolphins a year. The cause of marine-mammal conservation became so popular at the dawn of the environmental movement that one of the first environmental accomplishments of the US Congress was to enact the Marine Mammal Protection Act of 1972, which prohibits the killing or injuring of marine mammals. Today, small remnant populations of whales, such as the North Atlantic right whale, are threatened by entanglement in fishing gear and collisions by ships. Indeed, marine biologists have estimated that hundreds of thousands of marine mammals are killed each year in fishing gear. Inadvertent effects of human activities can pose a serious risk to coastal populations, as evidenced by the recent extinction of the Chinese river dolphin due to fishing, pollution, and overdevelopment of the Yangtze River. A few decades ago, conservation efforts focused on reducing the intentional hunting of marine mammals. Nowadays, when hunts for marine mammals are better controlled, the slow degradation of habitat from a combination of sources may have a bigger impact. For example, biologists have documented cases in which the effects of coastal development—including noise, pollution, and dredging—have caused marine mammals to abandon critical breeding habitat. Noise in particular is at issue in legal actions that have been brought against the US Navy for sonar exercises that may have caused whales to strand and die.
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  • 24
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    Annual Review of Immunology 23 (2005), S. 161-196 
    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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    Annual Review of Immunology 23 (2005), S. 487-513 
    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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    Annual Review of Immunology 23 (2005), S. 415-445 
    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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    Annual Review of Immunology 23 (2005), S. 683-747 
    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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    Annual Review of Immunology 23 (2005), S. 651-682 
    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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    Annual Review of Immunology 23 (2005), S. 945-974 
    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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    Annual Review of Immunology 23 (2005), S. 975-1028 
    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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    Annual Review of Immunology 23 (2005), S. 515-548 
    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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    Annual Review of Immunology 26 (2005), S. 877-900 
    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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    Annual Review of Immunology 23 (2005), S. 549-600 
    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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    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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    Annual Review of Immunology 23 (2005), S. 23-68 
    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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    Annual Review of Immunology 23 (2005), S. 447-485 
    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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    Annual Review of Immunology 23 (2005), S. 101-125 
    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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    Annual Review of Pharmacology 45 (2005), S. 1-25 
    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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    Annual Review of Pharmacology 45 (2005), S. 51-88 
    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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    Annual Review of Pharmacology 45 (2005), S. 177-202 
    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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    Annual Review of Pharmacology 45 (2005), S. 291-310 
    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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    Annual Review of Pharmacology 45 (2005), S. 335-355 
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    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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    Annual Review of Pharmacology 45 (2005), S. 385-412 
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    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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    Annual Review of Pharmacology 45 (2005), S. 657-687 
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    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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    Annual Review of Pharmacology 46 (2006), S. 65-100 
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    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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    Annual Review of Immunology 23 (2005), S. 367-386 
    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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    Annual Review of Immunology 23 (2005), S. 337-366 
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    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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    Annual Review of Immunology 23 (2005), S. 225-274 
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    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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    Annual Review of Immunology 23 (2005), S. 787-819 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    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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    Annual Review of Immunology 23 (2005), S. 387-414 
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    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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    Annual Review of Immunology 23 (2005), S. 901-944 
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    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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    Annual Review of Immunology 23 (2005), S. 601-649 
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    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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    Annual Review of Immunology 23 (2005), S. 307-335 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    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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    Annual Review of Immunology 23 (2005), S. 127-159 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    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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    Annual Review of Immunology 23 (2005), S. 749-786 
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    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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    Annual Review of Immunology 23 (2005), S. 1-21 
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    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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    Annual Review of Immunology 23 (2005), S. 853-875 
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    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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    Annual Review of Pharmacology 45 (2005), S. 465-476 
    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.
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    Annual Review of Pharmacology 45 (2005), S. 565-585 
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    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
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    Annual Review of Pharmacology 46 (2006), S. 1-39 
    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.
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    Annual Review of Pharmacology 46 (2006), S. 235-276 
    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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    Annual Review of Pharmacology 46 (2006), S. 41-64 
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    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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    Annual Review of Immunology 23 (2005), S. 197-223 
    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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    Annual Review of Immunology 23 (2005), S. 821-852 
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    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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    Annual Review of Immunology 23 (2005), S. 275-306 
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    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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    Annual Review of Biophysics and Biomolecular Structure 34 (2005), S. 267-294 
    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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    Annual Review of Biophysics and Biomolecular Structure 34 (2005), S. 153-171 
    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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    Annual Review of Biophysics and Biomolecular Structure 34 (2005), S. 91-118 
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Proteins have become accessible targets for chemical synthesis. The basic strategy is to use native chemical ligation, Staudinger ligation, or other orthogonal chemical reactions to couple synthetic peptides. The ligation reactions are compatible with a variety of solvents and proceed in solution or on a solid support. Chemical synthesis enables a level of control on protein composition that greatly exceeds that attainable with ribosome-mediated biosynthesis. Accordingly, the chemical synthesis of proteins is providing previously unattainable insight into the structure and function of proteins.
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    Annual Review of Biophysics and Biomolecular Structure 34 (2005), S. 71-90 
    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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    Annual Review of Biophysics and Biomolecular Structure 34 (2005), S. 119-151 
    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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    Annual Review of Biophysics and Biomolecular Structure 34 (2005), S. 173-199 
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Water plays a central role in the structures and properties of biomoleculesĐ??proteins, nucleic acids, and membranesĐ??and in their interactions with ligands and drugs. Over the past half century, our understanding of water has been advanced significantly owing to theoretical and computational modeling. However, like the blind men and the elephant, different models describe different aspects of water's behavior. The trend in water modeling has been toward finer-scale properties and increasing structural detail, at increasing computational expense. Recently, our labs and others have moved in the opposite direction, toward simpler physical models, focusing on more global propertiesĐ??water's thermodynamics, phase diagram, and solvation properties, for exampleĐ??and toward less computational expense. Simplified models can guide a better understanding of water in ways that complement what we learn from more complex models. One ultimate goal is more tractable models for computer simulations of biomolecules. This review gives a perspective from simple models on how the physical properties of waterĐ??as a pure liquid and as a solventĐ??derive from the geometric and hydrogen bonding properties of water.
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    Annual Review of Biophysics and Biomolecular Structure 34 (2005), S. 379-398 
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Structural data on protein-DNA complexes provide clues for understanding the mechanism of protein-DNA recognition. Although the structures of a large number of protein-DNA complexes are known, the mechanisms underlying their specific binding are still only poorly understood. Analysis of these structures has shown that there is no simple one-to-one correspondence between bases and amino acids within protein-DNA complexes; nevertheless, the observed patterns of interaction carry important information on the mechanisms of protein-DNA recognition. In this review, we show how the patterns of interaction, either observed in known structures or derived from computer simulations, confer recognition specificity, and how they can be used to examine the relationship between structure and specificity and to predict target DNA sequences used by regulatory proteins.
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    Annual Review of Biophysics and Biomolecular Structure 34 (2005), S. 319-349 
    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.
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    Annual Review of Cell and Developmental Biology 21 (2005), S. 319-346 
    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.
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    Annual Review of Cell and Developmental Biology 21 (2005), S. 177-201 
    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.
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    Annual Review of Cell and Developmental Biology 21 (2005), S. 381-410 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: ʼ̛?‚ heterodimeric integrins mediate dynamic adhesive cell-cell and cell-extracellular matrix (ECM) interactions in metazoa that are critical in growth and development, hemostasis, and host defense. A central feature of these receptors is their capacity to change rapidly and reversibly their adhesive functions by modulating their ligand-binding affinity. This is normally achieved through interactions of the short cytoplasmic integrin tails with intracellular proteins, which trigger restructuring of the ligand-binding site through long-range conformational changes in the ectodomain. Ligand binding in turn elicits conformational changes that are transmitted back to the cell to regulate diverse responses. The publication of the integrin ʼ̛V?‚3 crystal structure has provided the context for interpreting decades-old biochemical studies. Newer NMR, crystallographic, and EM data, reviewed here, are providing a better picture of the dynamic integrin structure and the allosteric changes that guide its diverse functions.
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    Annual Review of Cell and Developmental Biology 21 (2005), S. 105-131 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: This review surveys what is known about the structure and function of the subnuclear domains called Cajal bodies (CBs). The major focus is on CBs in mammalian cells but we provide an overview of homologous CB structures in other organisms. We discuss the protein and RNA components of CBs, including factors recently found to associate in a cell cycle-dependent fashion or under specific metabolic or stress conditions. We also consider the dynamic properties of both CBs and their molecular components, based largely on recent data obtained thanks to the advent of improved in vivo detection and imaging methods. We discuss how these data contribute to an understanding of CB functions and highlight major questions that remain to be answered. Finally, we consider the interesting links that have emerged between CBs and alterations in nuclear structure apparent in a range of human pathologies, including cancer and inherited neurodegenerative diseases. We speculate on the relationship between CB function and molecular disease.
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    Annual Review of Cell and Developmental Biology 21 (2005), S. 581-603 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Over the past decades, intravital microscopy (IVM), the imaging of cells in living organisms, has become a valuable tool for studying the molecular determinants of lymphocyte trafficking. Recent advances in microscopy now make it possible to image cell migration and cell-cell interactions in vivo deep within intact tissues. Here, we summarize the principal techniques that are currently used in IVM, discuss options and tools for fluorescence-based visualization of lymphocytes in microvessels and tissues, and describe IVM models used to explore lymphoid and non-lymphoid organs. The latter will be introduced according to the physiologic itinerary of developing and differentiating T and B lymphocytes as they traffic through the body, beginning with their development in bone marrow and thymus and continuing with their migration to secondary lymphoid organs and peripheral tissues.
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    Annual Review of Cell and Developmental Biology 21 (2005), S. 223-245 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: In eukaryotes, the entwined pathways of RNA transport and local translational regulation are key determinants in the spatio-temporal articulation of gene expression. One of the main advantages of this mechanism over transcriptional control in the nucleus lies in the fact that it endows local sites with independent decision-making authority, a consideration that is of particular relevance in cells with complex cellular architecture such as neurons. Localized RNAs typically contain codes, expressed within cis-acting elements, that specify subcellular targeting. Such codes are recognized by trans-acting factors, adaptors that mediate translocation along cytoskeletal elements by molecular motors. Most transported mRNAs are assumed translationally dormant while en route. In some cell types, especially in neurons, it is considered crucial that translation remains repressed after arrival at the destination site (e.g., a postsynaptic microdomain) until an appropriate activation signal is received. Several candidate mechanisms have been suggested to participate in the local implementation of translational repression and activation, and such mechanisms may target translation at the level of initiation and/or elongation. Recent data indicate that untranslated RNAs may play important roles in the local control of translation.
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    Annual Review of Cell and Developmental Biology 21 (2005), S. 297-318 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: RNA silencing refers to a broad range of phenomena sharing the common feature that large, double-stranded RNAs or stem-loop precursors are processed to ca. 21Đ??26 nucleotide small RNAs, which then guide the cleavage of cognate RNAs, block productive translation of these RNAs, or induce methylation of specific target DNAs. Although the core mechanisms are evolutionarily conserved, epigenetic maintenance of silencing by amplification of small RNAs and the elaboration of mobile, RNA-based silencing signals occur predominantly in plants. Plant RNA silencing systems are organized into a network with shared components and overlapping functions. MicroRNAs, and probably trans-acting small RNAs, help regulate development at the posttranscriptional level. Small interfering RNAs associated with transgene- and virus-induced silencing function primarily in defending against foreign nucleic acids. Another system, which is concerned with RNA-directed methylation of DNA repeats, seems to have roles in epigenetic silencing of certain transposable elements and genes under their control.
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    Annual Review of Materials Research 35 (2005), S. 315-350 
    ISSN: 1531-7331
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: There is a pressing need for cleaner fuels (free or aromatics and of minimal sulfur content) or ones that convert chemical energy directly to electricity, silently and without production of noxious oxides and particulates; chemical, petrochemical and pharmaceutical processes that may be conducted in a one-step, solvent-free manner and that use air as the preferred oxidant; and industrial processes that minimize consumption of energy, production of waste, or the use of corrosive, explosive, volatile, and nonbiodegradable materials. All these needs and other desiderata, such as the in situ production and containment of aggressive and hazardous reagents, and the avoidance of use of ecologically harmful elements, may be achieved by designing the appropriate heterogeneous inorganic catalyst, which ideally should be cheap, readily preparable and fully characterizable, preferably under in situ reaction conditions. A range of nanoporous and nanoparticle catalysts that meet most of the stringent demands of sustainable development and responsible (clean) technology is described. Specific examples that are highlighted include the production of adipic acid (precursor of polyamides and urethanes) without the use of concentrated nitric acid nor the production of greenhouse gases such as nitrous oxide; the production of caprolactam (precursor of nylon) without the use of oleum and hydroxylamine sulfate; and the terminal oxyfunctionalization of linear alkanes in air. The topic of biocatalysis and sustainable development is also briefly discussed for the epoxidation of terpenes and fatty acid methyl esters; for the generation of polymers, polylactides, and polyesters; and for the production of 1,3-propanediol from corn.
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    Annual Review of Materials Research 35 (2005), S. 571-615 
    ISSN: 1531-7331
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: The review highlights the state-of-the-art research regarding the application of modern in situ spectroscopic, microscopic, and electrochemical techniques to improve the understanding of the interaction of organic molecules with metal surfaces. We also consider the chemical and electrochemical processes that lead to a de-adhesion of polymers from metal surfaces. Spectroscopic techniques such as surface-enhanced infrared or Raman spectroscopy provide molecular understanding of organic molecules and water at buried metal surfaces. This information is complementary to adhesion studies by means of atomic force microscopy and de-adhesion studies of polymer layers from metals by means of a scanning Kelvin probe. Adhesion and de-adhesion mechanisms are discussed, especially those involving humid and corrosive environments, which are the predominant and most important for metal/polymer composites in engineering applications.
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    Annual Review of Materials Research 35 (2005), S. 239-314 
    ISSN: 1531-7331
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Chemical analysis at high spatial resolution is the domain of analytical transmission electron microscopy. Owing to rapid instrumental developments during the past decade, electron energy-loss spectroscopy offers now a spatial resolution close to 0.1 nm and an energy resolution close to 0.1 eV. This development has been accompanied by the introduction of numerous new techniques and methods for data acquisition and analysis, which are outlined in the present article. Recent results for a wide range of material systems are addressed. These comprise first-principles calculations, which have contributed to enormous progress in the calculation of near-edge fine structures, and fingerprinting methods, which are still important for the interpretation of experimental data.
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    Annual Review of Ecology, Evolution, and Systematics 36 (2005), S. 169-189 
    ISSN: 1543-592X
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Plant secondary metabolites (PSMs) significantly impact the nutritional ecology of terrestrial vertebrate herbivores. Herbivores have a wide range of mechanisms (herbivore offenses) to mitigate the negative effects of PSMs. We discuss several behavioral and physiological offenses used by terrestrial vertebrates. Several newly recognized herbivore offenses such as regulated absorption and regulation of toxin intake are presented. We give a detailed description of the biotransformation system with respect to PSMs. We also summarize recent findings of plantĐ??animal interactions for lizards, birds, and mammals. Finally, we discuss some new tools that can be applied to long-standing questions of plantĐ??vertebrate interactions.
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    Annual Review of Fluid Mechanics 37 (2005), S. 357-392 
    ISSN: 0066-4189
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: The objective of this review is to critically assess the different approaches developed in recent years to understand the dynamics of open flows such as mixing layers, jets, wakes, separation bubbles, boundary layers, and so on. These complex flows develop in extended domains in which fluid particles are continuously advected downstream. They behave either as noise amplifiers or as oscillators, both of which exhibit strong nonlinearities ( Huerre & Monkewitz 1990 ). The local approach is inherently weakly nonparallel and it assumes that the basic flow varies on a long length scale compared to the wavelength of the instability waves. The dynamics of the flow is then considered as a superposition of linear or nonlinear instability waves that, at leading order, behave at each streamwise station as if the flow were homogeneous in the streamwise direction. In the fully global context, the basic flow and the instabilities do not have to be characterized by widely separated length scales, and the dynamics is then viewed as the result of the interactions between Global modes living in the entire physical domain with the streamwise direction as an eigendirection. This second approach is more and more resorted to as a result of increased computational capability. The earlier review of Huerre & Monkewitz (1990) emphasized how local linear theory can account for the noise amplifier behavior as well as for the onset of a Global mode. The present survey first adopts the opposite point of view by demonstrating how fully global theory accounts for the noise amplifier behavior of open flows. From such a perspective, there is strong emphasis on the very peculiar nonorthogonality of linear Global modes, which in turn allows a novel interpretation of recent numerical simulations and experimental observations. The nonorthogonality of linear Global modes also imposes severe constraints on the extension of linear global theory to the fully nonlinear re??gime. When the flow is weakly nonparallel, this limitation is so severe that the linear Global mode theory is of little help. It is then much more appropriate to develop a fully nonlinear formulation involving the presence of a front separating the base state region from the bifurcated state region.
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    Annual Review of Fluid Mechanics 37 (2005), S. 71-98 
    ISSN: 0066-4189
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: The flow in turbomachines is unsteady due to the relative motion of the rows of blades. In the low-pressure turbine, the wakes from the upstream bladerows provide the dominant source of unsteadiness. Because much of the blade-surface boundary-layer flow is laminar, one of the most important consequences of this unsteadiness is the interaction of the wakes with the suction-side boundary layer of a downstream blade. This is important because the blade suctionĐ??side boundary layers are responsible for most of the loss of efficiency and because the combined effects of random (wake turbulence) and periodic disturbances (wake velocity defect and pressure fields) cause the otherwise laminar boundary layer to undergo transition and eventually become turbulent. This article summarizes the process of wake-induced boundary-layer transition in low-pressure turbines and the loss generation processes that result. Particular emphasis is placed on how the effects of wakes may be exploited to control loss generation and how this has enabled successful development of ultra-high-lift low-pressure turbines.
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    Annual Review of Fluid Mechanics 37 (2005), S. 295-328 
    ISSN: 0066-4189
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Chaotic advection and, more generally, ideas from dynamical systems, have been fruitfully applied to a diverse, and varied, collection of mixing and transport problems arising in engineering applications over the past 20 years. Indeed, the "dynamical systems approach" was developed, and tested, to the point where it can now be considered a standard tool for understanding mixing and transport issues in many disciplines. This success for engineering-type flows motivated an effort to apply this approach to transport and mixing problems in geophysical flows. However, there are fundamental difficulties arising in this endeavor that must be properly understood and overcome. Central to this approach is that the starting point for analysis is a velocity field (i.e., the "dynamical system"). In many engineering applications this can be obtained sufficiently accurately, either analytically or computationally, so that it describes particle trajectories for the actual flow. However, in geophysical flows (and we concentrate here almost exclusively on oceanographic flows), the wide range of dynamically significant time and length scales makes the justification of any velocity field, in the sense of reproducing particle trajectories for the actual flow, a much more difficult matter. Nevertheless, the case for this approach is compelling due to the advances in observational capabilities in oceanography (e.g., drifter deployments, remote sensing capabilities, satellite imagery, etc.), which reveal space-time structures that are highly suggestive of the structures one visualizes in the global, geometrical study of dynamical systems theory. This has been pursued in recent years through a combination of laboratory studies, kinematic models, and dynamically consistent models that have all been compared with observational data. During the course of these studies it has become apparent that a new type of dynamical system is necessary to consider in these studies (i.e., a finite time, aperiodically time-dependent velocity field defined as a data set), which requires the development of new analytical and computational tools, as well as the necessity to discard some of the standard ideas and results from dynamical systems theory. In this article we review a number of the key developments to date in this young, but rapidly developing, area at the interface between geophysical fluid dynamics and applied and computational mathematics. We also describe the wealth of new directions for research that this approach unlocks.
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    Annual Review of Fluid Mechanics 38 (2006), S. 225-249 
    ISSN: 0066-4189
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: The gas-lift technique comprises the injection of gas bubbles in vertical oil wells to increase production. It is based on a reduction of the tubing gravitational pressure gradient. Several fluid-flow phenomena influencing such vertical gas-liquid flows are discussed. These effects include the radial distribution of void fraction and of gas and liquid velocity, flow regime changes, and system stability problems. Associated consequences for gas-lift performance and related optimization approaches are also discussed.
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    Annual Review of Fluid Mechanics 38 (2006), S. 193-224 
    ISSN: 0066-4189
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: What mechanisms of flow control do animals use to enhance hydrodynamic performance? Animals are capable of manipulating flow around the body and appendages both passively and actively. Passive mechanisms rely on structural and morphological components of the body (i.e., humpback whale tubercles, riblets). Active flow control mechanisms use appendage or body musculature to directly generate wake flow structures or stiffen fins against external hydrodynamic loads. Fish can actively control fin curvature, displacement, and area. The vortex wake shed by the tail differs between eel-like fishes and fishes with a discrete narrowing of the body in front of the tail, and three-dimensional effects may play a major role in determining wake structure in most fishes.
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    Annual Review of Fluid Mechanics 38 (2006), S. 1-25 
    ISSN: 0066-4189
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Brooke Benjamin's original theories of fluid mechanical phenomena changed our basic understanding of cavitation bubbles, surface and internal waves, gravity currents, instabilities of shear flow over flexible surfaces, and swirling flows. For some types of finite-amplitude wave phenomena, he generated integral constraints and derived new partial differential equations; by establishing their general properties he showed how they have wide application. He developed a complementary approach based on functional analysis that was quite new to fluid mechanics. He demonstrated methods for deriving, without detailed calculation, the essential features of nonlinear and indeterminate flow problems that are otherwise intractable.
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    Annual Review of Fluid Mechanics 38 (2006), S. 65-86 
    ISSN: 0066-4189
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: The fluid mechanics of artificial blood pumps has been studied since the early 1970s in an attempt to understand and mitigate hemolysis and thrombus formation by the device. Pulsatile pumps are characterized by inlet jets that set up a rotational "washing" pattern during filling. Strong regurgitant jets through the closed artificial heart valves have Reynolds stresses on the order of 10,000 dynes/cm2 and are the most likely cause of red blood cell damage and platelet activation. Although the flow in the pump chamber appears benign, low wall shear stresses throughout the pump cycle can lead to thrombus formation at the wall of the smaller pumps (10Đ??50 cc). The local fluid mechanics is critical. There is a need to rapidly measure or calculate the wall shear stress throughout the device so that the results may be easily incorporated into the design process.
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    Annual Review of Fluid Mechanics 38 (2006), S. 309-338 
    ISSN: 0066-4189
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Electrophoretic separation of a mixture of chemical species is a fundamental technique of great usefulness in biology, health care, and forensics. In capillary electrophoresis (which has evolved from its predecessor, slab-gel electrophoresis), the sample migrates through a single microcapillary instead of through the network of pores in a gel. A fundamental design problem is to minimize dispersion in the separation direction. Molecular diffusion is inevitable and sets a theoretical limit on the best separation that can be achieved. But in practice, there are a number of effects arising out of the interplay between fluid flow, chemistry, thermal effects, and electric fields that result in enhanced dispersion. This paper reviews the subject of fluid flow in such capillary microchannels and examines the various causes of enhanced dispersion that limit the efficiency of separation.
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    Annual Review of Fluid Mechanics 38 (2006), S. 453-482 
    ISSN: 0066-4189
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Large-eddy simulation (LES) of turbulent combustion is a relatively new research field. Much research has been carried out over the past years, but to realize the full predictive potential of combustion LES, many fundamental questions still have to be addressed, and common practices of LES of nonreacting flows revisited. The focus of the present review is to highlight the fundamental differences between Reynolds-averaged Navier-Stokes (RANS) and LES combustion models for nonpremixed and premixed turbulent combustion, to identify some of the open questions and modeling issues for LES, and to provide future perspectives.
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    Annual Review of Genetics 39 (2005), S. 263-291 
    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Species of the genus Drosophila exhibit enormous variation in all of their reproductive behaviors: resource use and specialization, courtship signaling, sperm utilization, and female remating. The genetic bases of this variability and its evolution are poorly understood. At the same time, Drosophila comparative genomics now has developed to a point at which approaches previously only possible with D. melanogaster can be exploited to address these questions. We have taken advantage of the known phylogenetic relationships of this group of flies not only to place these behaviors in an evolutionary framework, but to provide a roadmap for future genetic studies.
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  • 95
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    Annual Review of Genetics 39 (2005), S. 359-407 
    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Life is the interplay between structure and energy, yet the role of energy deficiency in human disease has been poorly explored by modern medicine. Since the mitochondria use oxidative phosphorylation (OXPHOS) to convert dietary calories into usable energy, generating reactive oxygen species (ROS) as a toxic by-product, I hypothesize that mitochondrial dysfunction plays a central role in a wide range of age-related disorders and various forms of cancer. Because mitochondrial DNA (mtDNA) is present in thousands of copies per cell and encodes essential genes for energy production, I propose that the delayed-onset and progressive course of the age-related diseases results from the accumulation of somatic mutations in the mtDNAs of post-mitotic tissues. The tissue-specific manifestations of these diseases may result from the varying energetic roles and needs of the different tissues. The variation in the individual and regional predisposition to degenerative diseases and cancer may result from the interaction of modern dietary caloric intake and ancient mitochondrial genetic polymorphisms. Therefore the mitochondria provide a direct link between our environment and our genes and the mtDNA variants that permitted our forbears to energetically adapt to their ancestral homes are influencing our health today.
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  • 96
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    Annual Review of Genetics 39 (2005), S. 69-94 
    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Cell-cycle control of transcription seems to be a universal feature of proliferating cells, although relatively little is known about its biological significance and conservation between organisms. The two distantly related yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe have provided valuable complementary insight into the regulation of periodic transcription as a function of the cell cycle. More recently, genome-wide studies of proliferating cells have identified hundreds of periodically expressed genes and underlying mechanisms of transcriptional control. This review discusses the regulation of three major transcriptional waves, which roughly coincide with three main cell-cycle transitions (initiation of DNA replication, entry into mitosis, and exit from mitosis). I also compare and contrast the transcriptional regulatory networks between the two yeasts and discuss the evolutionary conservation and possible roles for cell cycle-regulated transcription.
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  • 97
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    Annual Review of Genetics 39 (2005), S. 409-429 
    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: The lysis-lysogeny decision of bacteriophage lambda (??) is a paradigm for developmental genetic networks. There are three key features, which characterize the network. First, after infection of the host bacterium, a decision between lytic or lysogenic development is made that is dependent upon environmental signals and the number of infecting phages per cell. Second, the lysogenic prophage state is very stable. Third, the prophage enters lytic development in response to DNA-damaging agents. The CI and Cro regulators define the lysogenic and lytic states, respectively, as a bistable genetic switch. Whereas CI maintains a stable lysogenic state, recent studies indicate that Cro sets the lytic course not by directly blocking CI expression but indirectly by lowering levels of CII which activates cI transcription. We discuss how a relatively simple phage like ?? employs a complex genetic network in decision-making processes, providing a challenge for theoretical modeling.
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  • 98
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    Annual Review of Genetics 39 (2005), S. 293-307 
    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Although the sex of most animals is determined by genetic information, sex-determining genes had been identified only in mammals, several flies, and the worm Caenorhabditis elegans until the recent discovery of DMY (DM-domain gene on the Y chromosome) in the sex-determining region on the Y chromosome of the teleost fish medaka, Oryzias latipes. Functional and expression analyses of DMY have shown it to be the master gene for male sex determination in the medaka. The only sex-determining genes found so far in vertebrates are Sry and DMY. Therefore, the medaka is expected to become a good experimental animal for investigating the precise mechanisms involved in primary sex determination in nonmammalian vertebrates. This article reviews the origin of DMY and the sexual development of gonads in the medaka. The putative functions of DMY are also discussed.
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  • 99
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    Annual Review of Genetics 39 (2005), S. 47-68 
    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Bacillus subtilis uses novel regulatory mechanisms in controlling expression of its genes of tryptophan synthesis and transport. These mechanisms respond to changes in the intracellular concentrations of free tryptophan and uncharged tRNATrp. The major B. subtilis protein that regulates tryptophan biosynthesis is the tryptophan-activated RNA-binding attenuation protein, TRAP. TRAP is a ring-shaped molecule composed of 11 identical subunits. Active TRAP binds to unique RNA segments containing multiple trinucleotide (NAG) repeats. Binding regulates both transcription termination and translation in the trp operon, and translation of other coding regions relevant to tryptophan metabolism. When there is a deficiency of charged tRNATrp, B. subtilis forms an anti-TRAP protein, AT. AT antagonizes TRAP function, thereby increasing expression of all the genes regulated by TRAP. Thus B. subtilis and Escherichia coli respond to identical regulatory signals, tryptophan and uncharged tRNATrp, yet they employ different mechanisms in regulating trp gene expression.
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  • 100
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    Annual Review of Biophysics and Biomolecular Structure 34 (2005), S. 295-318 
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Toroidal DNA condensates have attracted the attention of biophysicists, biochemists, and polymer physicists for more than thirty years. In the biological community, the quest to understand DNA toroid formation has been motivated by its relevance to gene packing in certain viruses and by the potential use of DNA toroids in artificial gene delivery (e.g., gene therapy). In the physical sciences, DNA toroids are appreciated as a superb model system for studying particle formation by the collapse of a semiflexible, polyelectrolyte polymer. This review focuses on experimental studies from the past few years that have significantly increased our understanding of DNA toroid structure and the mechanism of their formation. Highlights include structural studies that show the DNA strands within toroids to be packed in an ideal hexagonal lattice, and also in regions with a nonhexagonal lattice that are required by the topological constraints associated with winding DNA into a toroid. Recent studies of DNA toroid formation have also revealed that toroid size limits result from a complex interplay between kinetic and thermodynamic factors that govern both toroid nucleation and growth. The work discussed in this review indicates that it will ultimately be possible to obtain substantial control over DNA toroid dimensions.
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