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  • Signal Transduction  (102)
  • 03. Hydrosphere::03.04. Chemical and biological::03.04.06. Hydrothermal systems
  • 04. Solid Earth::04.04. Geology::04.04.08. Sediments: dating, processes, transport
  • 04. Solid Earth::04.04. Geology::04.04.10. Stratigraphy
  • 04. Solid Earth::04.06. Seismology::04.06.08. Volcano seismology
  • Acoustics
  • Applied geophysics
  • Binding Sites
  • Data analysis / ~ processing
  • Fluids
  • Schussler
  • Textbook of geophysics
  • American Association for the Advancement of Science (AAAS)  (153)
  • Elsevier  (23)
  • Springer  (4)
  • Cambridge U. Press
  • Cambridge Univ. Press
  • Kluwer
  • W.H. Freeman
  • 2020-2023
  • 2010-2014  (180)
  • 2000-2004
  • 1980-1984
  • 2013  (41)
  • 2010  (139)
Collection
Keywords
Publisher
Years
  • 2020-2023
  • 2010-2014  (180)
  • 2000-2004
  • 1980-1984
Year
  • 1
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    Towards an automatic monitoring system of infrasonic events at Mt. Etna: strategies for source location and modelling (2010)
    Springer
    Details
    Publication Date: 2020-11-16
    Description: Active volcanoes characterized by open conduit conditions generate sonic and infrasonic signals, whose investigation provides useful information for both monitoring purposes and studying the dynamics of explosive processes. In this work, we discuss the automatic procedures implemented for a real-time application to the data acquired by a permanent network of five infrasound stations running at Mt. Etna volcano. The infrasound signals at Mt. Etna consist in amplitude transients, called infrasound events. The adopted procedure uses a multi-algorithm approach for event detection, counting, characterization and location. It is designed for an efficient and accurate processing of infrasound records provided by single-site and array stations. Moreover, the source mechanism of these events can be investigated off-line or in near real-time by using three different models: i) Strombolian bubble; ii) resonating conduit and iii) Helmholtz resonator. The infrasound waveforms allow us to choose the most suitable model, to get quantitative information about the source and to follow the time evolution of the source parameters.
    Description: Published
    Description: 1215–1231
    Description: 6V. Pericolosità vulcanica e contributi alla stima del rischio
    Description: JCR Journal
    Description: open
    Keywords: infrasound ; monitoring system ; Mt. Etna ; 04. Solid Earth::04.06. Seismology::04.06.08. Volcano seismology
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Type: article
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  • 2
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    Carbon dioxide degassing and thermal energy release in the Monte Amiata volcanic-geothermal area (Italy) (2010)
    Elsevier
    Details
    Publication Date: 2021-01-07
    Description: The quaternary volcanic complex of Mount Amiata is located in southern Tuscany (Italy) and represents the most recent manifestation of the Tuscan Magmatic Province. The region is characterised by a large thermal anomaly and by the presence of numerous CO2-rich gas emissions and geothermal features, mainly located at the periphery of the volcanic complex. Two geothermal systems are located, at increasing depths, in the carbonate and metamorphic formations beneath the volcanic complex. The shallow volcanic aquifer is separated from the deep geothermal systems by a low permeability unit (Ligurian Unit). A measured CO2 discharge through soils of 1.8 109 mol a 1 shows that large amounts of CO2 move from the deep reservoir to the surface. A large range in d13CTDIC ( 21.07 to +3.65) characterises the waters circulating in the aquifers of the region and the mass and isotopic balance of TDIC allows distinguishing a discharge of 0.3 109 mol a 1 of deeply sourced CO2 in spring waters. The total natural CO2 discharge (2.1 109 mol a 1) is slightly less than minimum CO2 output estimated by an indirect method (2.8 109 mol a 1), but present-day release of 5.8 109 mol a 1 CO2 from deep geothermal wells may have reduced natural CO2 discharge. The heat transported by groundwater, computed considering the increase in temperature from the infiltration area to the discharge from springs, is of the same order of magnitude, or higher, than the regional conductive heat flow (〉200 mWm 2) and reaches extremely high values (up to 2700mWm 2) in the north-eastern part of the study area. Heat transfer occurs mainly by conductive heating in the volcanic aquifer and by uprising gas and vapor along fault zones and in those areas where low permeability cover is lacking. The comparison of CO2 flux, heat flow and geological setting shows that near surface geology and hydrogeological setting play a central role in determining CO2 degassing and heat transfer patterns.
    Description: Published
    Description: 860–875
    Description: 1.2. TTC - Sorveglianza geochimica delle aree vulcaniche attive
    Description: 2.4. TTC - Laboratori di geochimica dei fluidi
    Description: 4.5. Studi sul degassamento naturale e sui gas petroliferi
    Description: JCR Journal
    Description: reserved
    Keywords: Carbon dioxide degassing ; Monte Amiata ; 03. Hydrosphere::03.04. Chemical and biological::03.04.05. Gases ; 03. Hydrosphere::03.04. Chemical and biological::03.04.06. Hydrothermal systems ; 04. Solid Earth::04.04. Geology::04.04.12. Fluid Geochemistry ; 04. Solid Earth::04.08. Volcanology::04.08.06. Volcano monitoring
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 3
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    Seasonal cycles of seismic velocity variations detected using coda wave interferometry at Fogo volcano, São Miguel, Azores, during 2003–2004 (2010)
    Elsevier
    Details
    Publication Date: 2020-11-12
    Description: Fogo volcano is an active central volcano, with a lake filled caldera, in the central part of São Miguel Island, Azores, whose current activity is limited to hydrothermal manifestations such as active fumarolic fields, thermal and CO2 cold springs and soil diffuse degassing areas. It is affected by important active tectonic structures, with high seismic activity and practically continuous micro-seismicity. A recurrent feature from the seismicity observed in volcanic regions is the occurrence of clusters of similar earthquakes, whose origin can be attributed to the repeated action of a similar source mechanism at the same focal area. Doublets/multiplets were identified in this study within a catalogue of small magnitude (usually 〈 3) volcano tectonic events recorded in 2003–2004 by a selection of stations around Fogo volcano. All events have been cross-correlated and pairs whose waveforms exhibited a cross-correlation coefficient equal to or higher than 0.9 were analysed using the coda-wave interferometry technique. Subtle velocity variations found between events highlight a seasonal cycle of the velocity patterns, with lower velocity in winter time and higher velocity during summer months. Those results, together with quantitative differences between the same doublets at different stations, exhibit an excellent correlation with rainfall. A seasonal effect can also be broadly seen in the seismicity occurrence, and some of the swarms recorded over the two year period occur during the wettest season or close to episodes of abundant (above average) rainfall. Moreover, temporal and spatial analysis of several swarms highlighted the lack of any mainshock–aftershock sequence and organized migration of the hypocenters. This is suggestive of a very heterogeneous stress field. Vp/Vs is found to be lower than usually observed in volcanic areas, an occurrence likely related to the presence of steamy fluid associated with the geothermal system. Taken together, these observations suggest that pore pressurisation plays a major role in controlling a considerable part of the recorded seismicity. The geothermal fluids around Fogo massif have been identified as derived from meteoric water, which infiltrates through Fogo Lake and the volcano flanks and flows from south to north on the northern flank. All those elements seem to point to a role played by rainfall in triggering seismicity at São Miguel, possibly through pressure changes at depth in response to surface rain and/or an interaction with the geothermal system.
    Description: Published
    Description: 231-246
    Description: 1.4. TTC - Sorveglianza sismologica delle aree vulcaniche attive
    Description: JCR Journal
    Description: reserved
    Keywords: velocity changes ; rainfall ; volcano seismicity ; triggered seismicity ; Azores archipelago ; 04. Solid Earth::04.06. Seismology::04.06.08. Volcano seismology
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 4
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    Astronomical tuning of the La Vedova High Cliff section (Ancona, Italy)—Implications of the Middle Miocene Climate Transition for Mediterranean sapropel formation (2010)
    Elsevier
    Details
    Publication Date: 2021-01-25
    Description: Continuous marine successions covering the Middle Miocene Climate Transition (MMCT; ∼15–13.7 Ma) are scarce and the lack of a high-resolution magnetobiostratigraphic framework hampers the construction of astronomically tuned age models for this time interval. The La Vedova High Cliff section, exposed along the coast of the Cònero Riviera near Ancona (Italy), is one of the few Mediterranean sections covering the critical time interval of the MMCT. Starting from an initial magnetobiostratigraphic age model, a robust astronomical tuning was constructed for the interval between 14.2 and 13.5 Ma, using geochemical element data and time series analysis. A shift in δ18O of bulk sediment towards heavier values occurs between ∼13.92 and 13.78 Ma and could be related to the Mi3b oxygen isotope event, which reflects the rapid expansion of the East Antarctic Ice Sheet in the middle Miocene. The onset of the CM6 carbon excursion is reflected in the bulk record by a rapid increase in δ13C at 13.86 Ma. Our results confirm the proposition that these events coincide with a 405-kyr minimum in eccentricity and a node in obliquity related to the ∼1.2 Myr cycle. From 13.8 Ma onwards, distinct quadruplet cycles containing sapropelitic sediments were deposited. This may suggest a causal connection between the main middle Miocene cooling step and the onset of sapropel formation in the Mediterranean.
    Description: Published
    Description: 249–261
    Description: 2.2. Laboratorio di paleomagnetismo
    Description: JCR Journal
    Description: restricted
    Keywords: Middle Miocene ; Mediterranean ; astronomical tuning ; paleomagnetism ; biostratigraphy ; environmental changes ; orbital forcing ; sapropels ; 04. Solid Earth::04.04. Geology::04.04.10. Stratigraphy ; 04. Solid Earth::04.05. Geomagnetism::04.05.06. Paleomagnetism
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 5
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    Tornillos at Vulcano: Clues to the dynamics of the hydrothermal system (2010)
    Elsevier
    Details
    Publication Date: 2020-11-12
    Description: The number of tornillo events has recently increased at the Vulcano Island, Italy. While only 15 tornillos were recorded during 2004–2006, 584 events occurred in 2007–2008. They were located just below La Fossa Crater at depths ranging between 0.1 and 1 km b.s.l. During two intervals in 2007–2008 increases in the number of tornillos took place at the same time as temperature and geochemical anomalies were observed. The spectral content of the tornillos, generally characterized by one–two dominant spectral peaks near 6 and 10 Hz, varied over time, with changes also noted in the quality factors. The simplest source mechanism proposed for tornillos is the free eigenvibration of a fluid volume within a crack or a conduit. Based on this model, we propose a causal relationship between the temperature and geochemical anomalies and the increases in numbers of tornillos. As the amount of hydrothermal fluids increases during the anomalies, the upward flux of fluids grows. The consequent changes in the pressure, temperature and dynamics of the system of cracks and conduits result in the generation of tornillos. Based on the fluid-filled crack/conduit model, the shallow depths of the sources and the values of the quality factors, the fluid within the resonant crack/conduit was inferred to be an ash–gas or water droplet–gas mixture. Moreover, the observed variations in the wavefield can be caused by small changes in the location of the source, in the source mechanism, or in the medium in between the source and the seismic station. Finally, another peculiar feature of tornillos is the amplitude modulation that can be explained as a result of a beating phenomenon.
    Description: Published
    Description: 377-393
    Description: 3V. Proprietà chimico-fisiche dei magmi e dei prodotti vulcanici
    Description: JCR Journal
    Description: reserved
    Keywords: Tornillos ; Vulcano Island ; Hydrothermal system ; Volcano seismology ; 04. Solid Earth::04.06. Seismology::04.06.08. Volcano seismology
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 6
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    Mantle-derived carbon in Hercynian granites. Stable isotopes signatures and C/He associations in the thermomineral waters, N-Portugal (2010)
    Elsevier
    Details
    Publication Date: 2021-01-27
    Description: Na–HCO3–CO2-rich thermomineral waters issue in the N of Portugal, within the Galicia-Trás-os-Montes region, linked to a major NNE-trending fault, the so-called Penacova-Régua-Verin megalineament. Along this tectonic structure different occurrences of CO2-rich thermomineral waters are found: Chaves hot waters (67 °C) and also several cold (16.1 °C) CO2-rich waters. The δ2H and δ18O values of the thermomineral waters are similar to those of the local meteoric waters. The chemical composition of both hot and cold mineral waters suggests that water–rock reactions are mainly controlled by the amount of dissolved CO2 (g) rather than by the water temperature. Stable carbon isotope data indicate an external CO2 inorganic origin for the gas. δ13CCO2 values ranging between −7.2‰ and −5.1‰ are consistent with a two-component mixture between crustal and mantle-derived CO2. Such an assumption is supported by the 3He/4He ratios measured in the gas phase, are between 0.89 and 2.68 times the atmospheric ratio (Ra). These ratios which are higher than that those expected for a pure crustal origin (≈0.02 Ra), indicating that 10 to 30% of the He has originated from the upper mantle. Release of deep-seated fluids having a mantle-derived component in a region without recent volcanic activity indicates that extensive neo-tectonic structures originating during the Alpine Orogeny are still active (i.e., the Chaves Depression).
    Description: Published
    Description: 49-56
    Description: 4.5. Studi sul degassamento naturale e sui gas petroliferi
    Description: JCR Journal
    Description: reserved
    Keywords: CO2-rich thermomineral waters ; mantle volatiles ; isotopes ; Chaves geothermal system ; N-Portugal ; 03. Hydrosphere::03.02. Hydrology::03.02.02. Hydrological processes: interaction, transport, dynamics ; 03. Hydrosphere::03.02. Hydrology::03.02.03. Groundwater processes ; 03. Hydrosphere::03.04. Chemical and biological::03.04.03. Chemistry of waters ; 03. Hydrosphere::03.04. Chemical and biological::03.04.06. Hydrothermal systems ; 04. Solid Earth::04.08. Volcanology::04.08.01. Gases
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 7
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    Paleomagnetic investigations on the Pleistocene lacustrine sequence of Piànico-Sèllere (northern Italy) (2010)
    Elsevier
    Details
    Publication Date: 2017-04-04
    Description: The Piànico-Sèllere is a lacustrine succession from northern Italy that records a sequence of climatic transitions across two Pleistocene glacial stages. The intervening interglacial stage is represented by well-preserved varves with calcitic (summer) and clastic (winter) laminae. There is a tight coupling between climate-driven lithologic changes and magnetic susceptibility variations, and stable paleomagnetic components were retrieved from all investigated lithologies including the largely diamagnetic calcite varves. These components were used to delineate a sequence of magnetic polarity reversals that was interpreted as a record of excursions of the Earth’s magnetic field. Comparison of the magnetostratigraphic results with previously published data allows discussion of two possible models which have generated controversy regarding the age of the Piànico Formation. The data indicates that the Piànico Formation magnetostratigraphy correlates to geomagnetic field excursions across the Brunhes/Matuyama transition, and consequently the Piànico interglacial correlates to marine isotope stage 19. This correlation option is substantially consistent with K-Ar radiometric age estimates recently obtained from a tepha layer interbedded in the Piànico Formation. The alternative option, considering the Piànico interglacial correlative to marine isotope stage 11 within the Brunhes Chron as supported by tephrochronological dating reported in the literature, is not supported by the magnetostratigraphic results.
    Description: Published
    Description: 44-53
    Description: 3.2. Tettonica attiva
    Description: JCR Journal
    Description: open
    Keywords: Piànico Formation ; Pleistocene ; magnetostratigraphy ; polarity excursions ; Brunhes Chron ; Southern Alps ; 04. Solid Earth::04.04. Geology::04.04.02. Geochronology ; 04. Solid Earth::04.04. Geology::04.04.08. Sediments: dating, processes, transport ; 04. Solid Earth::04.04. Geology::04.04.10. Stratigraphy ; 04. Solid Earth::04.05. Geomagnetism::04.05.02. Geomagnetic field variations and reversals ; 04. Solid Earth::04.05. Geomagnetism::04.05.06. Paleomagnetism
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 8
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    The upper lithostratigraphic unit of ANDRILL AND-2A core (Southern McMurdo Sound, Antarctica): Local Pleistocene volcanic sources, paleoenvironmental implications and subsidence in the southern Victoria Land Basin (2010)
    Elsevier
    Details
    Publication Date: 2017-04-04
    Description: We report results from the study of the uppermost 37 m of the Southern McMurdo Sound (SMS) AND-2A drill core, corresponding to the lithostratigraphic unit 1 (LSU 1), the most volcanogenic unit within the core. We present data on the age, composition, volcanological and depositional features of the volcanic sedimentary and tephra deposits of LSU 1 and discuss their source, mechanisms of emplacement and environment of deposition. Sedimentary features and compositional data indicate shallow water sedimentation for the whole of LSU 1. Most of LSU 1 deposits are a mixture of near primary volcanic material with minor exotic clasts derived from the Paleozoic crystalline basement rocks. Among volcanic materials, glassy particles are the most abundant. They were produced by mildly explosive basaltic eruptions occurring in subaerial and subaqueous environments. The Dailey Islands group, 13 km south-southwest of the SMS drill-site, has been identified as a possible source for the volcanics on the basis of similarity in composition and age. 40Ar–39Ar laser step-heating analyses on a lava sample from Juergens Island yields an age of 775 ± 22 ka. Yet because of the minimal reworking features of vitriclasts, preservation of fragile structures in volcaniclastic sediments and evidence for volcanic seamounts to the north of the Dailey Islands, it is likely that some of the material originated also from vents close to the drill-site. Evidence for local volcanic sources and for deposition of sediments in a shallow marine environment provides indications about the local paleogeography and implications for the subsidence history of the southern Victoria Land Basin from Pleistocene to Recent.
    Description: Published
    Description: 142-161
    Description: 3.5. Geologia e storia dei vulcani ed evoluzione dei magmi
    Description: 3.8. Geofisica per l'ambiente
    Description: JCR Journal
    Description: reserved
    Keywords: Antarctica ; volcaniclastic sediments ; Erebus Volcanic Province ; paleoenvironment reconstruction ; Victoria Land Basin ; 04. Solid Earth::04.04. Geology::04.04.05. Mineralogy and petrology ; 04. Solid Earth::04.04. Geology::04.04.08. Sediments: dating, processes, transport
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 9
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    Mantle-derived carbon in Hercynian granites. 1 Stable isotopes signatures 2 and C/He associations in the thermomineral waters, N-Portugal (2010)
    Elsevier
    Details
    Publication Date: 2017-04-04
    Description: Na–HCO3–CO2-rich thermomineral waters issue in the N of Portugal, within the Galicia-Trás-os-Montes region, linked to a major NNE-trending fault, the so-called Penacova-Régua-Verin megalineament. Along this tectonic structure different occurrences of CO2-rich thermomineral waters are found: Chaves hot waters (67 °C) and also several cold (16.1 °C) CO2-rich waters. The δ2H and δ18O values of the thermomineral waters are similar to those of the local meteoric waters. The chemical composition of both hot and cold mineral waters suggests that water–rock reactions are mainly controlled by the amount of dissolved CO2 (g) rather than by the water temperature. Stable carbon isotope data indicate an external CO2 inorganic origin for the gas. δ13CCO2 values ranging between −7.2‰ and −5.1‰ are consistent with a two-component mixture between crustal and mantle-derived CO2. Such an assumption is supported by the 3He/4He ratios measured in the gas phase, are between 0.89 and 2.68 times the atmospheric ratio (Ra). These ratios which are higher than that those expected for a pure crustal origin (≈0.02 Ra), indicating that 10 to 30% of the He has originated from the upper mantle. Release of deep-seated fluids having a mantle-derived component in a region without recent volcanic activity indicates that extensive neo-tectonic structures originating during the Alpine Orogeny are still active (i.e., the Chaves Depression).
    Description: In press
    Description: 4.5. Studi sul degassamento naturale e sui gas petroliferi
    Description: JCR Journal
    Description: open
    Keywords: CO2-rich thermomineral waters ; mantle volatiles ; isotopes ; Chaves geothermal 9 system ; 03. Hydrosphere::03.02. Hydrology::03.02.02. Hydrological processes: interaction, transport, dynamics ; 03. Hydrosphere::03.02. Hydrology::03.02.03. Groundwater processes ; 03. Hydrosphere::03.04. Chemical and biological::03.04.03. Chemistry of waters ; 03. Hydrosphere::03.04. Chemical and biological::03.04.05. Gases ; 03. Hydrosphere::03.04. Chemical and biological::03.04.06. Hydrothermal systems
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  • 10
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    Distal Turbidites and Tsunamigenic Landslides of Stromboli Volcano (Aeolian Islands, Italy) (2010)
    Springer
    Details
    Publication Date: 2017-04-04
    Description: On 30 December 2002, a 25-30 × 106 m3 landslide on the NW flank of Stromboli volcano produced a tsunami that caused relevant damage to the Stromboli village and to the neighboring islands of the Aeolian archipelago. The NW flank of Stromboli has been the site of several, cubic kilometer-scale, landslides during the past 13 ka. In this paper we present sedimentological and compositional data of deep-sea cores recovered from a site located about 24 km north of the island. Our preliminary results indicate that: (i) turbidity currents were effectively generated by the large-scale failures and (ii) volcanogenic turbidity current deposits retain clues of the landslide source and slope failure dynamics. By analogy with Hawaii and the Canary islands we confirm that deep-sea sediments can be effectively used to assess the age and scale of past landslide events giving an important contribution to the tsunami hazard assessment of this region.
    Description: Unpublished
    Description: -
    Description: 3.5. Geologia e storia dei vulcani ed evoluzione dei magmi
    Description: 4.3. TTC - Scenari di pericolosità vulcanica
    Description: reserved
    Keywords: Landslide ; turbidite ; tsunami ; Stromboli ; 04. Solid Earth::04.04. Geology::04.04.04. Marine geology ; 04. Solid Earth::04.04. Geology::04.04.08. Sediments: dating, processes, transport ; 04. Solid Earth::04.08. Volcanology::04.08.08. Volcanic risk
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Type: book chapter
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  • 11
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    Anomalous fluid emission of a deep borehole in a seismically active area of Northern Apennines (Italy) (2010)
    Elsevier
    Details
    Publication Date: 2017-04-04
    Description: The Miano borehole of 1047 m depth is located close to the river Parma in the Northern Apennines, Italy. A measuring station is installed to observe the discharge of fluids continuously since November 2004. The upwelling fluid of this artesian well is a mixture of thermal water and methane as main components. In non-seismogenic areas, we would expect a relative constant fluid emission perhaps overlaid with long term variations from that kind of deep reservoirs during the time. However, the continuously record of the fluid emission, in particular the water discharge, the gas flow rate and the water temperature, show periods of stable values interrupted by anomalous periods of fluctuations in the recorded parameters. The anomalous variations of these parameters are of low amplitude in comparison to the total values but significant in their long-term trend. Meteorological influences of rain and barometric pressure were not detected in recorded data probably due to reservoir depth and relatively high reservoir overpressure. Influences due to the ambient temperature after the discharge were evaluated by statistical analysis. We consider that recorded changes in fluid emission parameters can be interpreted as a mixing process of different fluid components in depth by variations in pore pressure as result of seismogenic stress variation. Local seismicity was analyzed in comparison to fluid’s physico-chemical data. The analysis supports the idea of an influence to fluid transport conditions due to geodynamic processes exist. Water temperature data show frequent anomalies probably connected with possible precursory phenomena of local seismic events.
    Description: In press
    Description: 3.2. Tettonica attiva
    Description: JCR Journal
    Description: open
    Keywords: Fluids ; Earthquakes ; Continous monitoring ; 04. Solid Earth::04.04. Geology::04.04.12. Fluid Geochemistry
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  • 12
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    Mercury content and speciation in the Phlegrean Fields volcanic complex: Evidence from hydrothermal system and fumaroles (2010)
    Elsevier
    Details
    Publication Date: 2017-04-04
    Description: Mercury is outstanding among the global environmental pollutants of continuing concern. Although degassing of active volcanic areas represents an important natural source of mercury into the atmosphere, still little is known about the amount and behaviour of Hg in volcanic aquifers, especially regarding its chemical speciation. In order to assess the importance of mercury emissions from active volcanoes, thermal waters were sampled in the area surrounding La Solfatara, Pozzuoli bay. This is the most active zone of the Phlegrean Fields complex (coastal area north–west of Naples), with intense hydrothermal activity at present day. Studied groundwaters show total Hg (THg) concentrations range from 56 to 171 ng/l and are lower than the 1000 ng/l threshold value for human health protection fixed by the World Health Organization (WHO, 1993). We also carefully discriminated the different aqueous species of Hg in the collected water samples. Besides, original data on Hg determination in gaseous manifestations at La Solfatara crater are also reported. We measured volcanogenic mercury concentration and Hg/Stot ratio both in the volcanic plume and in fumarolic condensates in order to better constrain Hg reactivity once emitted into the atmosphere. Data on Hg/Stot reveal that there is no significant difference between Hg volcanic composition at the venting source (fumaroles) and in near-vent diluted volcanic plumes (1.6×10−5 and 1.9×10−5, respectively), suggesting that there is limited Hg chemical processing in volcanic fumarole plumes, at least on the timescales of a few seconds investigated here. Combining the mean fumaroles Hg/CO2 mass ratio of about 1.3×10−8 (molar ratio: 2.1×10−9) with the hydrothermal soil diffuse CO2 degassing of the area, the annual Hg flux from La Solfatara is estimated as 7 kg y−1 (0.007 t y−1). Current mercury emission from La Solfatara volcano represents a very small contribution to the estimated global volcanic budget for this element, and the estimated Hg flux is considerably lower than that estimated from open-conduit active basaltic volcanoes.
    Description: Published
    Description: 250–260
    Description: 1.2. TTC - Sorveglianza geochimica delle aree vulcaniche attive
    Description: 2.4. TTC - Laboratori di geochimica dei fluidi
    Description: 4.5. Studi sul degassamento naturale e sui gas petroliferi
    Description: JCR Journal
    Description: reserved
    Keywords: hydrothermal waters ; total mercury ; mercury speciation ; fumaroles ; 03. Hydrosphere::03.04. Chemical and biological::03.04.05. Gases ; 03. Hydrosphere::03.04. Chemical and biological::03.04.06. Hydrothermal systems ; 04. Solid Earth::04.04. Geology::04.04.12. Fluid Geochemistry ; 04. Solid Earth::04.08. Volcanology::04.08.06. Volcano monitoring
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  • 13
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    CO2 degassing at La Solfatara volcano (Phlegrean Fields): Processes affecting d13C and d18O of soil CO2 (2010)
    Elsevier
    Details
    Publication Date: 2017-04-04
    Description: The soil CO2 degassing is affected by processes of isotope exchange and fractionation during transport across the soil, which can deeply modify the pristine isotope composition. This has been observed in the Solfatara volcano, upon a field survey of 110 points, where the CO2 flux was measured, together with temperature, CO2 concentration and oxygen and carbon isotopes within the soil. Furthermore, in some selected sites, the measurements were made at different depths, in order to analyze vertical gradients. Oxygen isotope composition appears controlled by exchange with soil water (either meteoric or fumarolic condensate), due to the fast kinetic of the isotopic equilibrium between CO2 and water. Carbon isotope composition is reliably controlled by transport-driven fractionation, due to the differences in diffusion coefficients between 13C16O2 and 12C16O2. We model the processes affecting CO2 transport across the soil in La Solfatara volcano by means of the Dusty Gas Model applied to a multicomponent system, to evaluate the reciprocal effect on diffusion of involved gases, i.e. 12C16O2, 13C16O2, N2 and O2 in our case. Both numerical and simplified analytical solutions of the equations based on the Dusty Gas Model are given. The modeling results fit well with the experimental data and put in evidence an isotope fractionation of carbon up to about þ4:4& with respect to the source value in the soil gas. This fractionation is independent from the entity of the CO2 flux, and occurs as long as a concentration gradient exists within the soil. On these grounds, the Dusty Gas Model can be applied to whichever diffusing gas mixture to evaluate the extent of chemical and/or isotopic fractionation that can affect ascending gases upon diffusion in any geothermal, volcanic or tectonic area.
    Description: Published
    Description: 3521-3528
    Description: 1.2. TTC - Sorveglianza geochimica delle aree vulcaniche attive
    Description: JCR Journal
    Description: reserved
    Keywords: isotope exchange ; degassing ; 03. Hydrosphere::03.04. Chemical and biological::03.04.05. Gases ; 03. Hydrosphere::03.04. Chemical and biological::03.04.06. Hydrothermal systems ; 03. Hydrosphere::03.04. Chemical and biological::03.04.08. Instruments and techniques
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  • 14
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    Towards an Automatic Monitoring System of Infrasonic Events at Mt. Etna: Strategies for Source Location and Modeling (2010)
    Springer
    Details
    Publication Date: 2017-04-04
    Description: Active volcanoes characterized by open conduit conditions generate sonic and infrasonic signals, whose investigation provides useful information for both monitoring purposes and studying the dynamics of explosive processes. In this work, we discuss the automatic procedures implemented for a real-time application to the data acquired by a permanent network of five infrasound stations running at Mt. Etna volcano. The infrasound signals at Mt. Etna consist in amplitude transients, called infrasound events. The adopted procedure uses a multi-algorithm approach for event detection, counting, characterization and location. It is designed for an efficient and accurate processing of infrasound records provided by single-site and array stations. Moreover, the source mechanism of these events can be investigated off-line or in near real-time by using three different models: (1) Strombolian bubble; (2) resonating conduit and (3) Helmholtz resonator. The infrasound waveforms allow us to choose the most suitable model, to get quantitative information about the source and to follow the time evolution of the source parameters.
    Description: Published
    Description: 1215–1231
    Description: 1.4. TTC - Sorveglianza sismologica delle aree vulcaniche attive
    Description: JCR Journal
    Description: reserved
    Keywords: Infrasound ; monitoring system ; Mt. Etna volcano ; 04. Solid Earth::04.06. Seismology::04.06.08. Volcano seismology ; 04. Solid Earth::04.08. Volcanology::04.08.06. Volcano monitoring ; 04. Solid Earth::04.08. Volcanology::04.08.07. Instruments and techniques
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  • 15
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    Magma dynamics of 2007 Stromboli effusive eruption as revealed by high precision location of seismic events. (2010)
    Elsevier
    Details
    Publication Date: 2017-04-04
    Description: Stromboli is considered one of the most active volcanoes in the world, and its persistent but moderate explosive activity is only interrupted by occasional episodes of more vigorous activity accompanied by lava flows. A new effusive eruption began in late February, 2007 and was characterised by intense seismic activity throughout the whole period. The accurate seismic signals analysis showed the presence of families of events with similar waveform signatures (i.e. multiplets) located beneath the crater region. Since traditional location techniques do not allow obtaining reliable hypocentres, our analysis focused on high precision locations of the seismicity, in order to better define the source geometry of the events. Hypocentres, therefore, have been relocated considering two steps: the first, based on a robust probabilistic approach, is used to find the absolute position of the clusters; the second exploits a master-event concept for the relative location of the events. Finally, the shape of the clusters and the temporal migration of the foci were correlated with the eruptive phases. The results show that the occurrence of a cluster of events is related to the opening and closure of a vent opened in the Sciara del Fuoco slope and, in particular, to the intrusion of a dike injected by central conduit in a radial direction, whereas another cluster lies in a narrow vertical volume positioned under the crater area. The geometry of the clusters suggests a source region depicting the shallower feeding system. Overall, the results highlight that the high precision locations method is an efficient and quick tool to obtain a better understanding of the magmatic processes occurring during an ongoing eruption.
    Description: Published
    Description: 405-415
    Description: 1.4. TTC - Sorveglianza sismologica delle aree vulcaniche attive
    Description: JCR Journal
    Description: reserved
    Keywords: eruption ; high precision location ; seismic swarms ; magma dynamics ; 04. Solid Earth::04.06. Seismology::04.06.08. Volcano seismology
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 16
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    Geochemistry of fluids discharged over the seismic area of the Southern Apennines (Calabria region, Southern Italy): Implications for Fluid-Fault relationships (2010)
    Elsevier
    Details
    Publication Date: 2017-04-04
    Description: The first comprehensive geochemical data-set of the fluids circulating over a 14,000 km2-wide seismicprone area of the Southern Apennines, Calabria Region (Italy), is presented here. The geochemical investigations were carried out with the twofold aim of constraining the origin and interactions of the circulating fluids and to investigate possible relationships with local faults. Sixty samples of both thermal and cold waters were collected, from which the dissolved gases were extracted. The geochemical features of the water samples display different types and degrees of water–rock interactions, irrespective of the outlet temperature. The calculated equilibrium temperatures of the thermal waters (60–160 C) and the low heat flow of thewhole study area, are consistent with a heating process due to deep water circulation and rapid upflow through lithospheric structures. The composition of the dissolved gases reveals that crustal-originating gases (N2 and CO2-dominated) feed all the groundwaters. The 3He/4He ratios of the dissolved He, in the range of 0.03–0.22Rac for the thermal waters and 0.05–0.63Rac for the cold waters (Rac = He isotope ratio corrected for atmospheric contamination), are mainly the result of a two-component (radiogenic and atmospheric) mixing, although indications of mantle-derived He are found in some cold waters. As the study area had been hit by 18 of the most destructive earthquakes (magnitude ranging from 5.9 to 7.2) occurring over a 280-a time span (1626–1908) in the Southern Apennines, the reported results on the circulating fluids may represent the reference for a better inside knowledge of the fault-fluid relationships and for the development of long-term geochemical monitoring strategies for the area.
    Description: Published
    Description: 540–554
    Description: 3.2. Tettonica attiva
    Description: JCR Journal
    Description: open
    Keywords: Fluids ; Geochemistry ; Faults ; Seismicity ; 04. Solid Earth::04.02. Exploration geophysics::04.02.01. Geochemical exploration
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  • 17
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    Anomalous fluid emission of a deep borehole in a seismically active area of Northern Apennines (Italy) (2010)
    Elsevier
    Details
    Publication Date: 2017-04-04
    Description: The Miano borehole, 1047 m deep, is located close to the river Parma in the Northern Apennines, Italy. A measuring station has been installed to observe the discharge of fluids continuously since November 2004. The upwelling fluid of this artesian well is a mixture of thermal water and CH4 as main components. In non-seismogenic areas, a relatively constant fluid emission would be expected, perhaps overlaid with long term variations from that kind of deep reservoir over time. However, the continuous record of the fluid emission, in particular the water discharge, the gas flow rate and the water temperature, show periods of stable values interrupted by anomalous periods of fluctuations in the recorded parameters. The anomalous variations of these parameters are of low amplitude in comparison to the total values but significant in their long-term trend. Meteorological effects due to rain and barometric pressure were not detected in recorded data probably due to reservoir depth and relatively high reservoir overpressure. Influences due to the ambient temperature after the discharge were evaluated by statistical analysis. Our results suggest that recorded changes in fluid emission parameters can be interpreted as a mixing process of different fluid components at depth by variations in pore pressure as a result of seismogenic stress variation. Local seismicity was analyzed in comparison to the fluid physico-chemical data. The analysis supports the idea that an influence on fluid transport conditions due to geodynamic processes exists. Water temperature data show frequent anomalies probably connected with possible precursory phenomena of local seismic events.
    Description: Published
    Description: 555–571
    Description: 3.2. Tettonica attiva
    Description: JCR Journal
    Description: open
    Keywords: Fluids ; Seismicity ; 04. Solid Earth::04.02. Exploration geophysics::04.02.01. Geochemical exploration
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  • 18
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    Astrochronology of the Mediterranean Langhian between 15.29 and 14.17 Ma (2010)
    Elsevier
    Details
    Publication Date: 2017-04-04
    Description: An integrated high-resolution magnetobiocyclostratigraphy including radioisotopic dating and astronomical tuning is presented for the interval between 15.29 and 14.17 Ma in the marine La Vedova section in northern Italy. The natural remanent magnetization is carried by the iron sulphide greigite and the resultant magnetostratigraphy can be correlated straightforwardly to the interval ranging from C5Bn.2n to C5ADn in the Astronomically Tuned Neogene Time Scale (ATNTS2004). Spectral analysis on high-resolution magnetic susceptibility and geochemical proxy records in the depth domain and, using our magnetobiostratigraphic age model, in the time domain demonstrate that the various scales of cyclicity in the section are related to astronomical climate forcing. Starting from our initial age model, larger-scale cycles were first tuned to eccentricity. This first-order tuning was followed by tuning the basic cycle to precession and boreal summer insolation using inferred phase relations between maxima in Ca/Al, redox-sensitive elements and Ba, and minima in magnetic susceptibility, and maxima in precession and minima in obliquity and boreal summer insolation. Our astronomical ages for reversal boundaries are supported by analysis of sea floor spreading rates and should replace the existing ages in the ATNTS2004 lacking direct astronomical control. Two major steps in the geochemical proxy records, astronomically dated at 15.074 and 14.489 Ma, coincide with abrupt changes in sedimentation rate, and are the result of the combined effect of the ∼400-kyr eccentricity cycle superimposed upon a longer-term climatic or tectonic induced trend.
    Description: Published
    Description: 254–269
    Description: 2.2. Laboratorio di paleomagnetismo
    Description: JCR Journal
    Description: restricted
    Keywords: Middle Miocene ; Langhian ; Mediterranean ; astronomical tuning ; palaeomagnetism ; biostratigraphy ; environmental changes ; orbital forcing ; 04. Solid Earth::04.04. Geology::04.04.10. Stratigraphy ; 04. Solid Earth::04.05. Geomagnetism::04.05.06. Paleomagnetism
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  • 19
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    Repeating volcano-tectonic earthquakes at Mt. Etna volcano (Sicily, Italy) during 1999–2009 (2013)
    Elsevier
    Details
    Publication Date: 2017-04-04
    Description: Repeating volcano-tectonic (VT) earthquakes, taking place at Mt. Etna during 1999–2009,were detected and analyzed to investigate their behavior. We found 735 families amounting to 2479 VT earthquakes, representing ~38% of all the analyzed VT earthquakes. The number of VT earthquakes making up the families ranges from 2 to 23. Over 70% of the families comprise 2 or 3 VT earthquakes and only 20 families by more than 10 events. The occurrence lifetime is also highly variable ranging from some minutes to ten years. In particular, more than half of the families have a lifetime shorter than 0.5 day and only ~10% longer than 1 year. On the basis of these results, most of the detected families were considered “burst-type”, i.e., show swarm-like occurrence, and hence their origin cannot be explained by a temporally constant tectonic loading. Indeed, since the analyzed earthquakes take place in a volcanic area, the rocks are affected not only by tectonic stresses related to the fairly steady regional stress field but also by local stresses, caused by the volcano, such as magma batch intrusions/ movements and gravitational loading.We focused on the five groups of families characterized by the longest repeatability over time, namely high number of events and long lifetime, located in the north-eastern, eastern and southern flanks of the volcano. Unlike the first four groups, which similarly to most of the detected families show swarm-like VT occurrences, group “v”, located in the north-eastern sector, exhibits a more “tectonic” behavior with the events making up such a group spread over almost the entire analyzed period. It is clear how both occurrence and slip rates do not remain constant but vary over time, and such changes are time-related to the occurrence of the 2002–2003 eruption. Finally, by FPFIT algorithm a good agreement between directions identified by nodal planes and the earthquake epicentral distribution was generally found.
    Description: Published
    Description: 1223 – 1236
    Description: 1.4. TTC - Sorveglianza sismologica delle aree vulcaniche attive
    Description: JCR Journal
    Description: restricted
    Keywords: repeating earthquakes ; Etna ; 04. Solid Earth::04.06. Seismology::04.06.08. Volcano seismology
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  • 20
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    Multiple resolution seismic attenuation imaging at Mt. Vesuvius (2010)
    Elsevier
    Details
    Publication Date: 2019-03-05
    Description: A three-dimensional S wave attenuation tomography of Mt. Vesuvius has been obtained with multiple measurements of coda-normalized S-wave spectra of local small magnitude earthquakes.We used 6609 waveforms, relative to 826 volcano-tectonic earthquakes, located close to the crater axis in a depth range between 1 and 4 km (below the sea level), recorded at seven 3-component digital seismic stations. We adopted a two-point ray-tracing; rays were traced in an high resolution 3-D velocity model. The spatial resolution achieved in the attenuation tomography is comparable with that of the velocity tomography (we resolve 300m side cubic cells). We statistically tested that the results are almost independent from the radiation pattern. We also applied an improvement of the ordinary spectral-slope method to both P- and S-waves, assuming that the differences between the theoretical and the experimental high frequency spectral-slope are only due to the attenuation effects. Consequently we could check the codanormalization method also comparing the S attenuation image with the P attenuation image. The images were obtained inverting the spectral data with a multiple resolution approach. Results have shown the general coincidence of low attenuation with high velocity zones. The joint interpretation of velocity and attenuation images allows us to interpret the low attenuation zone intruding toward the surface until a depth of 500m below the sea level as related to the residual part of solidified magma from the last eruption. In the depth range between −700 and −2300 images are consistent with the presence of multiple acquifer layers. No evidence of magma patches greater than the minimum cell dimension (300m) has been found. A shallow P wave attenuation anomaly (beneath the southern flank of the volcano) is consitent with the presence of gas saturated rocks. The zone characterized by the maximum seismic energy release cohincides with a high attenuation and low velocity volume, interpreted as a cracked medium.
    Description: Published
    Description: 17–32
    Description: 3.1. Fisica dei terremoti
    Description: JCR Journal
    Description: reserved
    Keywords: Attenuation tomography ; Mt. Vesuvius ; Coda normalization method ; Spectral slope ; Multi resolution inversion ; 04. Solid Earth::04.06. Seismology::04.06.07. Tomography and anisotropy ; 04. Solid Earth::04.06. Seismology::04.06.08. Volcano seismology ; 04. Solid Earth::04.06. Seismology::04.06.09. Waves and wave analysis
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  • 21
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    Time-space variation of volcano-seismic events at La Fossa (Vulcano, Aeolian Islands, Italy): new insights into seismic sources in a hydrothermal system (2010)
    Springer
    Details
    Publication Date: 2020-02-24
    Description: We investigated the relationship between volcano-seismic events, recorded at La Fossa crater of Vulcano (Aeolian Islands, Italy) during 2004-2006, and the dynamics of the hydrothermal system. During the period of study, three episodes of increasing numbers of volcano-seismic events took place at the same time as geothermal and geochemical anomalies were observed. These geothermal and geochemical anomalies have been interpreted as resulting from an increasing deep magmatic component of the hydrothermal fluids. Three classes of seismic events (long period, high frequency and monochromatic events), characterised by different spectral content and various similarity of the waveforms, have been recognised. These events, clustered mainly below La Fossa crater area at depths of 0.5–1.1 km b.s.l., were space-distributed according to the classes. Based on their features, we can infer that such events at Vulcano are related to two different source mechanisms: (1) fracturing processes of rocks and (2) resonance of cracks (or conduits) filled with hydrothermal fluid. In the light of these source mechanisms, the increase in the number of events, at the same time as geochemical and geothermal anomalies were observed, was interpreted as the result of an increasing magmatic component of the hydrothermal fluids, implying an increase of their flux. Indeed, such variation caused an increase of both the pore pressure within the rocks of the volcanic system and the amount of ascending fluids. Increased pore pressures gave rise to fracturing processes, while the increased fluid flux favoured resonance and vibration processes in cracks and conduits. Finally, a gradual temporal variation of the waveform of the hybrid events (one of the subclasses of long period events) was observed, likely caused by heating and drying of the hydrothermal system.
    Description: Published
    Description: 803-816
    Description: 1.4. TTC - Sorveglianza sismologica delle aree vulcaniche attive
    Description: JCR Journal
    Description: reserved
    Keywords: Volcano seismology ; Vulcano Island ; 04. Solid Earth::04.06. Seismology::04.06.08. Volcano seismology
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  • 22
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    Fault plane orientations of microearthquakes at Mt. Etna from theinversion of P-wave rise times (2010)
    Elsevier
    Details
    Publication Date: 2017-04-04
    Description: A crucial point in the analysis of tectonic earthquakes occurring in a volcanic area is the inference of the orientation of the structures along which the ruptures occur. These structures represent zones of weakness which could favor the migration of melt toward the surface and the assessment of their geometry is a fundamental step toward efficient evaluation of volcanic risk. We analyzed a high-quality dataset of 171 lowmagnitude, tectonic earthquakes that occurred at Mt. Etna during the 2002–2003 eruption. We applied a recently developed technique aimed at inferring the source parameters (source size, dip and strike fault) and the intrinsic quality factor Qp of P waves from the inversion of rise times. The technique is based on numerically calibrated relationships among the rise time of first P waves and the source parameters for a circular crack rupturing at a constant velocity. For the most of the events the directivity source effect did not allow us to constrain the fault plane orientation. For a subset of 45 events with well constrained focal mechanisms we were able to constrain the “true” fault plane orientation. The level of resolution of the fault planes was assessed through a non linear analysis based on the random deviates technique. The significance of the retrieved fault plane solutions and the fit of the assumed source model to data were assessed through a χ-square test. Most of the retrieved fault plane solutions agree with the geometrical trend of known surface faults. The inferred source parameters and Qp are in agreement with the results of previous studies
    Description: Published
    Description: 247-256
    Description: 3.1. Fisica dei terremoti
    Description: JCR Journal
    Description: reserved
    Keywords: rise time ; directivity ; 04. Solid Earth::04.06. Seismology::04.06.08. Volcano seismology
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  • 23
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    High-resolution intra- and interbasinal correlation of the Danian–Selandian transition (Early Paleocene): The Bjala section (Bulgaria) and the Selandian GSSP at Zumaia (Spain) (2010)
    Elsevier
    Details
    Publication Date: 2017-04-04
    Description: The Danian–Selandian (D–S) boundary has been identified for the first time in the Black Sea coast at Bjala (Bulgaria) based on a new integrated bio-, magneto- and cyclostratigraphic study. Several correlation criteria as established for the basal Selandian GSSP from Zumaia (Basque Basin) are evaluated. Noteworthy, is the almost complete lack of calcareous nannoplankton species Braarudosphaera bigelowi in the Bulgarian sections, a sharp decrease of which was indicated as suitable criteria for defining the D–S boundary as it occurred both at Zumaia and in the classical locations of the North Sea basin. Conversely, the second evolutionary radiation of the calcareous nannofossil genus Fasciculithus together with the occurrence of Fasciculithus tympaniformis that define the NP4/NP5 zonal boundary seem to be reliable criteria to approximate the D–S boundary. In detail, however, the best approach is to integrate biostratigraphic data within a magnetostratigraphic and/or cyclostratigraphic framework. Refinements on the placement of chron C27n at Zumaia and robust bed-by-bed correlation between several Basque sections and Bjala indicates that the D–S boundary is located 30 precession cycles (~630 ky) above C27n. In addition to the precession-related marl–limestone couplets and 100-ky eccentricity bundles recognized in the studied sections, expression of the stable 405-ky long eccentricity allows direct tuning to the astronomical solutions. A correlation of the land-based sections with previously tuned data from ODP Site1262 from the Southern Atlantic is challenged. Our choice is consistent with original tuning at Zumaia but shifts one 100-ky cycle older previous tuning from Site 1262 along the interval above C27n. Under the preferred tuning scheme the D–S boundary can be given an age of 61.641± 0.040 Ma on the La04 orbital solution.
    Description: Published
    Description: 511-533
    Description: 2.2. Laboratorio di paleomagnetismo
    Description: JCR Journal
    Description: restricted
    Keywords: Paleocene ; Magnetostratigraphy ; Orbital tuning ; Calcareous nannofossils ; Selandian GSSP ; 04. Solid Earth::04.04. Geology::04.04.08. Sediments: dating, processes, transport ; 04. Solid Earth::04.04. Geology::04.04.10. Stratigraphy ; 04. Solid Earth::04.05. Geomagnetism::04.05.06. Paleomagnetism
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  • 24
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    Nannoplankton biostratigraphic calibration of the evaporitic events in the Neogene Fortuna Basin (SE Spain) (2010)
    Elsevier
    Details
    Publication Date: 2017-04-04
    Description: The Fortuna Basin is an example of a marginal Mediterranean basin with evaporitic sedimentation during the Late Tortonian and Messinian. This basin shows an early restriction event before the main Messinian Salinity Crisis (MSC) that allows the Tortonian Salinity Crisis (TSC) to be proposed as a tectonic uplift event isolating the eastern Betic basins. Four evaporitic events are present in the central part of the Fortuna Basin, from bottom to top: Los Baños Marls Formation (composed by Fenazar Conglomerate Bed, Lower Gypsum Member [Mb] and Sanel Mb), Tale Gypsum Formation (Fm), Chicamo Diatomites and Gypsum Cycles Fm, and Rambla Salada Gypsum Fm. The present work documents the first biostratigraphic dating based on calcareous nannoplankton of these events. The lowest occurrence (LO) of Amaurolithus primus is registered at the upper part of the Sanel Mb, below the Tale Gypsum Fm. The LOs of Amaurolithus delicatus and Reticulofenestra rotaria, which mark the base of the Messinian, occur in the lower part of the Chicamo Cycles Fm, above the Tale Gypsum Fm, the Triquetrorhabdulus rugosus-Nicklithus amplificus integrate form and the LO of Nicklithus cf. amplificus in the upper part of the Chicamo Cycles Fm. Taking into account these results, a new calibration of the available magnetostratigraphic data is presented: the Chicamo Cycles Fm were formed during the reverse chron C3Ar and the Tortonian-Messinian boundary should be found within the Tale Gypsum Fm or near the top of the Sanel Mb. The onset of the TSC, the first restriction phase of the Fortuna Basin, is represented by the Fenazar Conglomerate Bed, bottom of the Los Baños Fm, and not by the Tale Gypsum Fm, as previously considered.
    Description: Published
    Description: 201-217
    Description: 2.2. Laboratorio di paleomagnetismo
    Description: JCR Journal
    Description: restricted
    Keywords: Betic Cordillera ; Tortonian Salinity Crisis ; Calcareous nannoplankton ; Messinian ; Fortuna Basin ; 04. Solid Earth::04.04. Geology::04.04.08. Sediments: dating, processes, transport ; 04. Solid Earth::04.04. Geology::04.04.10. Stratigraphy ; 04. Solid Earth::04.05. Geomagnetism::04.05.06. Paleomagnetism
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  • 25
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    Late Matuyama climate forcing on sedimentation at the margin of the southern Alps (Italy) (2010)
    Elsevier
    Details
    Publication Date: 2017-04-04
    Description: The Pleistocene history of climate control on sedimentation in the Southern Alps-Po Plain system, northern Italy, was reconstructed using an integrated magnetostratigraphic, palynological, and petrographical approach on a 47-m-deep core. The core mainly consists of lacustrine sediments pertaining to the Bagaggera sequence, deposited at the foothills of the Southern Alps during the late Matuyama subchron (0.99-0.78 Ma). At that time, climate worsened globally and locally it caused the progradation of an alluvial fan unit onto the nearby Po Plain, triggering lake formation by damming of a tributary valley. These new data are used in conjunction with data from the literature to highlight and track the effects of climate forcing on sedimentation during the late Matuyama subchron in different orographic and geodynamic settings of the Southern Alps-Po Plain system as part of the greater Alpine area. We found that the episodes of alluvial fan and braidplam progradation observed in the southern foreland of the Alps during the late Matuyama global cooling seem broadly synchronous with the deposition of most of the so-called Gunz and Alterer Deckenschotter deposits in the northern forelands of the Alps as well as with the first major waxing of the Alpine valley glaciers, possibly around the Marine Isotope Stage 22 (~0.87 Ma).
    Description: Regione Lombardia, IREALP
    Description: Published
    Description: 832–846
    Description: 3.2. Tettonica attiva
    Description: JCR Journal
    Description: restricted
    Keywords: Paleomagnetism ; Climate Change ; Early Pleistocene ; Italy ; Stratigraphy ; Petrography ; Palynology ; 03. Hydrosphere::03.01. General::03.01.03. Global climate models ; 04. Solid Earth::04.04. Geology::04.04.02. Geochronology ; 04. Solid Earth::04.04. Geology::04.04.03. Geomorphology ; 04. Solid Earth::04.04. Geology::04.04.08. Sediments: dating, processes, transport ; 04. Solid Earth::04.04. Geology::04.04.10. Stratigraphy ; 04. Solid Earth::04.05. Geomagnetism::04.05.06. Paleomagnetism
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  • 26
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    Human migration into Europe during the late Early Pleistocene climate transition (2010)
    Elsevier
    Details
    Publication Date: 2017-04-04
    Description: A critical assessment of the available magnetostratigraphic and/or radiometric age constraints on key sites bearing hominin remains and/or lithic industries from southern Europe (Italy, France, Spain) leads us to propose that the main window of early hominin presence in southern Europe is broadly comprised between the Jaramillo subchron and the Brunhes–Matuyama boundary (i.e., subchron C1r.1r, 0.99–0.78 Ma). Within the dating uncertainties, this ~200 ky time window broadly coincides with the late Early Pleistocene global climate transition that contains marine isotope stage (MIS) 22 (~0.87Ma), the first prominent cold stage of the Pleistocene. We suggest that aridification in North Africa and Eastern Europe, particularly harsh during MIS22 times, triggered migration pulses of large herbivores, particularly elephants, from these regions into southern European refugia, and that hominins migrated with them. Finally, we speculate on common pathways of late Early Pleistocene dispersal of elephants and hominins from their home in savannah Africa to southern Europe, elephant and hominin buen retiro. In particular, we stress the importance of the Po Valley of northern Italy that became largely and permanently exposed only since MIS22, thus allowing possibly for the first time in the Pleistocene viable new migration routes for large mammals and hominins across northern Italy to southern France and Spain in the west.
    Description: Published
    Description: 79-93
    Description: 3.2. Tettonica attiva
    Description: JCR Journal
    Description: restricted
    Keywords: Pleistocene ; Magnetostratigraphy ; Hominins ; Migration ; Europe ; Galerian ; Jaramillo ; Brunhes-Matuyama ; 04. Solid Earth::04.04. Geology::04.04.02. Geochronology ; 04. Solid Earth::04.04. Geology::04.04.08. Sediments: dating, processes, transport ; 04. Solid Earth::04.04. Geology::04.04.10. Stratigraphy ; 04. Solid Earth::04.05. Geomagnetism::04.05.06. Paleomagnetism
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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    Changes in the VLP seismic source during the 2007 Stromboli eruption (2010)
    Elsevier
    Details
    Publication Date: 2017-04-04
    Description: Aim of this paper is to identify variations in Very-Long-Period (VLP) source associated with eruptive style changes at Stromboli volcano (Italy) and to retrieve information about the shallow plumbing system that sustains the eruptive activity. We have considered a dataset of 74493 VLP events recorded during the period from January through August 2007, when an effusive eruption occurred (February 27–April 2).We performed a polarization analysis of the entire dataset and divided the considered period into four sub-periods on the basis of polarization characteristics. We then located the events and selected a subset of these events by applying a location quality threshold. The high quality locations demonstrate that during the effusive eruption the VLP sources first moved downward and then moved southwestward. To retrieve information about the geometry of the structures where the source processes take place, we further consider a subset of events and estimate their source mechanisms by using a moment tensor source function (MTSF) inversion technique. Inversion of the waveforms of the VLP events that occurred on February 27 allows us to obtain information about the dynamics of different source centroids distributed along different portions of the shallow magmatic conduits. The structure defined by the locations and source mechanisms shows a greater complexity compared with previous studies and their time variations give an insight into the kinematics of the eruption.
    Description: Published
    Description: 162–171
    Description: 1.4. TTC - Sorveglianza sismologica delle aree vulcaniche attive
    Description: JCR Journal
    Description: reserved
    Keywords: stromboli ; very-long-period events ; seismic source mechanism ; volcano seismology ; 04. Solid Earth::04.06. Seismology::04.06.08. Volcano seismology ; 04. Solid Earth::04.08. Volcanology::04.08.06. Volcano monitoring
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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    Nebulin and N-WASP cooperate to cause IGF-1-induced sarcomeric actin filament formation (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-12-15
    Description: Insulin-like growth factor 1 (IGF-1) induces skeletal muscle maturation and enlargement (hypertrophy). These responses require protein synthesis and myofibril formation (myofibrillogenesis). However, the signaling mechanisms of myofibrillogenesis remain obscure. We found that IGF-1-induced phosphatidylinositol 3-kinase-Akt signaling formed a complex of nebulin and N-WASP at the Z bands of myofibrils by interfering with glycogen synthase kinase-3beta in mice. Although N-WASP is known to be an activator of the Arp2/3 complex to form branched actin filaments, the nebulin-N-WASP complex caused actin nucleation for unbranched actin filament formation from the Z bands without the Arp2/3 complex. Furthermore, N-WASP was required for IGF-1-induced muscle hypertrophy. These findings present the mechanisms of IGF-1-induced actin filament formation in myofibrillogenesis required for muscle maturation and hypertrophy and a mechanism of actin nucleation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Takano, Kazunori -- Watanabe-Takano, Haruko -- Suetsugu, Shiro -- Kurita, Souichi -- Tsujita, Kazuya -- Kimura, Sumiko -- Karatsu, Takashi -- Takenawa, Tadaomi -- Endo, Takeshi -- New York, N.Y. -- Science. 2010 Dec 10;330(6010):1536-40. doi: 10.1126/science.1197767.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, Graduate School of Science, Chiba University, 1-33 Yayoicho, Inageku, Chiba 263-8522, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21148390" target="_blank"〉PubMed〈/a〉
    Keywords: Actin Cytoskeleton/*metabolism ; Actins/*metabolism ; Animals ; COS Cells ; Cercopithecus aethiops ; Hypertrophy ; Insulin-Like Growth Factor I/*metabolism ; Mice ; Mice, Inbred ICR ; *Muscle Development ; Muscle Proteins/chemistry/*metabolism ; Muscle, Skeletal/metabolism/pathology ; Myofibrils/metabolism ; Phosphatidylinositol 3-Kinase/metabolism ; Protein Binding ; Protein Interaction Domains and Motifs ; Proto-Oncogene Proteins c-akt/metabolism ; RNA Interference ; Sarcomeres/*metabolism ; Signal Transduction ; Wiskott-Aldrich Syndrome Protein, Neuronal/chemistry/*metabolism ; src Homology Domains
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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    PRDM9 is a major determinant of meiotic recombination hotspots in humans and mice (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-01-02
    Description: Meiotic recombination events cluster into narrow segments of the genome, defined as hotspots. Here, we demonstrate that a major player for hotspot specification is the Prdm9 gene. First, two mouse strains that differ in hotspot usage are polymorphic for the zinc finger DNA binding array of PRDM9. Second, the human consensus PRDM9 allele is predicted to recognize the 13-mer motif enriched at human hotspots; this DNA binding specificity is verified by in vitro studies. Third, allelic variants of PRDM9 zinc fingers are significantly associated with variability in genome-wide hotspot usage among humans. Our results provide a molecular basis for the distribution of meiotic recombination in mammals, in which the binding of PRDM9 to specific DNA sequences targets the initiation of recombination at specific locations in the genome.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4295902/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4295902/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Baudat, F -- Buard, J -- Grey, C -- Fledel-Alon, A -- Ober, C -- Przeworski, M -- Coop, G -- de Massy, B -- 03S1/PHS HHS/ -- GM83098/GM/NIGMS NIH HHS/ -- HD21244/HD/NICHD NIH HHS/ -- HL085197/HL/NHLBI NIH HHS/ -- R01 GM083098/GM/NIGMS NIH HHS/ -- R01 HD021244/HD/NICHD NIH HHS/ -- R01 HL085197/HL/NHLBI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2010 Feb 12;327(5967):836-40. doi: 10.1126/science.1183439. Epub 2009 Dec 31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut de Genetique Humaine, UPR1142, CNRS, Montpellier, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20044539" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Amino Acid Sequence ; Animals ; Base Sequence ; Binding Sites ; DNA/chemistry/metabolism ; DNA Breaks, Double-Stranded ; DNA-Binding Proteins/chemistry/genetics/metabolism ; Genome ; Genome, Human ; Genotype ; Histone-Lysine N-Methyltransferase/chemistry/*genetics/*metabolism ; Humans ; Meiosis/*genetics ; Mice ; Mice, Inbred C57BL ; Molecular Sequence Data ; Phenotype ; *Recombination, Genetic ; Zinc Fingers/genetics
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    Beta2-adrenergic receptor redistribution in heart failure changes cAMP compartmentation (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-02-27
    Description: The beta1- and beta2-adrenergic receptors (betaARs) on the surface of cardiomyocytes mediate distinct effects on cardiac function and the development of heart failure by regulating production of the second messenger cyclic adenosine monophosphate (cAMP). The spatial localization in cardiomyocytes of these betaARs, which are coupled to heterotrimeric guanine nucleotide-binding proteins (G proteins), and the functional implications of their localization have been unclear. We combined nanoscale live-cell scanning ion conductance and fluorescence resonance energy transfer microscopy techniques and found that, in cardiomyocytes from healthy adult rats and mice, spatially confined beta2AR-induced cAMP signals are localized exclusively to the deep transverse tubules, whereas functional beta1ARs are distributed across the entire cell surface. In cardiomyocytes derived from a rat model of chronic heart failure, beta2ARs were redistributed from the transverse tubules to the cell crest, which led to diffuse receptor-mediated cAMP signaling. Thus, the redistribution of beta(2)ARs in heart failure changes compartmentation of cAMP and might contribute to the failing myocardial phenotype.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nikolaev, Viacheslav O -- Moshkov, Alexey -- Lyon, Alexander R -- Miragoli, Michele -- Novak, Pavel -- Paur, Helen -- Lohse, Martin J -- Korchev, Yuri E -- Harding, Sian E -- Gorelik, Julia -- 084064/Wellcome Trust/United Kingdom -- BB/D020875/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- G0500373/Medical Research Council/United Kingdom -- Biotechnology and Biological Sciences Research Council/United Kingdom -- Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2010 Mar 26;327(5973):1653-7. doi: 10.1126/science.1185988. Epub 2010 Feb 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cardiac Medicine, National Heart and Lung Institute, Imperial College London, Dovehouse Street, London SW3 6LY, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20185685" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Compartmentation ; Cell Membrane/*metabolism/ultrastructure ; Chronic Disease ; Cyclic AMP/*metabolism ; Cyclic AMP-Dependent Protein Kinases/metabolism ; Cytosol/metabolism ; Fluorescence Resonance Energy Transfer ; Heart Failure/*metabolism/*pathology ; Male ; Mice ; Mice, Knockout ; Mice, Transgenic ; Microscopy/methods ; Myocytes, Cardiac/*metabolism/ultrastructure ; Rats ; Rats, Sprague-Dawley ; Receptors, Adrenergic, beta-1/genetics/metabolism ; Receptors, Adrenergic, beta-2/genetics/*metabolism ; Sarcolemma/*metabolism/ultrastructure ; Signal Transduction
    Print ISSN: 0036-8075
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    The ligase PIAS1 restricts natural regulatory T cell differentiation by epigenetic repression (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-10-23
    Description: CD4(+)Foxp3(+) regulatory T (T(reg)) cells are important for maintaining immune tolerance. Understanding the molecular mechanism that regulates T(reg) differentiation will facilitate the development of effective therapeutic strategies against autoimmune diseases. We report here that the SUMO E3 ligase PIAS1 restricts the differentiation of natural T(reg) cells by maintaining a repressive chromatin state of the Foxp3 promoter. PIAS1 acts by binding to the Foxp3 promoter to recruit DNA methyltransferases and heterochromatin protein 1 for epigenetic modifications. Pias1 deletion caused promoter demethylation, reduced histone H3 methylation at Lys(9), and enhanced promoter accessibility. Consistently, Pias1(-/-) mice displayed an increased natural T(reg) cell population and were resistant to the development of experimental autoimmune encephalomyelitis. Our studies have identified an epigenetic mechanism that negatively regulates the differentiation of natural T(reg) cells.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3043201/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3043201/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Liu, Bin -- Tahk, Samuel -- Yee, Kathleen M -- Fan, Guoping -- Shuai, Ke -- K01 AR52717-01/AR/NIAMS NIH HHS/ -- R01 AI063286/AI/NIAID NIH HHS/ -- R01 AI063286-05/AI/NIAID NIH HHS/ -- R01 GM085797/GM/NIGMS NIH HHS/ -- R01 GM085797-03/GM/NIGMS NIH HHS/ -- R01AI063286/AI/NIAID NIH HHS/ -- R01GM085797/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2010 Oct 22;330(6003):521-5. doi: 10.1126/science.1193787.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Hematology-Oncology, Department of Medicine, 11-934 Factor Building, 10833 Le Conte Avenue, University of California, Los Angeles, Los Angeles, CA 90095, USA. bliu@ucla.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20966256" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Binding Sites ; CD4-Positive T-Lymphocytes/cytology ; Chromatin/metabolism ; DNA (Cytosine-5-)-Methyltransferase/metabolism ; DNA Methylation ; Encephalomyelitis, Autoimmune, Experimental/immunology ; *Epigenesis, Genetic ; Female ; Forkhead Transcription Factors/genetics ; Histones/metabolism ; Lymphopoiesis/*genetics ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Inbred Strains ; Promoter Regions, Genetic ; Protein Inhibitors of Activated STAT/*physiology ; Repressor Proteins/*physiology ; T-Lymphocytes, Regulatory/*cytology/immunology ; Ubiquitin-Protein Ligases/*physiology
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    Cell biology. The case for RNA (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-11-27
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Liu, Chang C -- Arkin, Adam P -- New York, N.Y. -- Science. 2010 Nov 26;330(6008):1185-6. doi: 10.1126/science.1199495.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Bioengineering, University of California, Berkeley, CA 94720, USA. ccliu@berkeley.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21109657" target="_blank"〉PubMed〈/a〉
    Keywords: Alternative Splicing ; Apoptosis ; Aptamers, Nucleotide/chemistry/genetics/*metabolism ; Artificial Gene Fusion ; Biotechnology ; Ganciclovir/pharmacology ; *Gene Expression Regulation ; *Genetic Engineering ; Humans ; Introns ; NF-kappa B/genetics/metabolism ; Nucleic Acid Conformation ; Protein Biosynthesis ; RNA/chemistry/genetics/*metabolism ; Signal Transduction ; beta Catenin/genetics/metabolism
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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    The control of the metabolic switch in cancers by oncogenes and tumor suppressor genes (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-12-04
    Description: Cells from some tumors use an altered metabolic pattern compared with that of normal differentiated adult cells in the body. Tumor cells take up much more glucose and mainly process it through aerobic glycolysis, producing large quantities of secreted lactate with a lower use of oxidative phosphorylation that would generate more adenosine triphosphate (ATP), water, and carbon dioxide. This is the Warburg effect, which provides substrates for cell growth and division and free energy (ATP) from enhanced glucose use. This metabolic switch places the emphasis on producing intermediates for cell growth and division, and it is regulated by both oncogenes and tumor suppressor genes in a number of key cancer-producing pathways. Blocking these metabolic pathways or restoring these altered pathways could lead to a new approach in cancer treatments.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Levine, Arnold J -- Puzio-Kuter, Anna M -- New York, N.Y. -- Science. 2010 Dec 3;330(6009):1340-4. doi: 10.1126/science.1193494.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Advanced Study, Princeton, NJ 08540, USA. alevine@ias.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21127244" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/metabolism ; Cell Division ; Citric Acid Cycle ; Gene Expression Regulation, Neoplastic ; *Genes, Tumor Suppressor ; Glucose/metabolism ; Glutamine/metabolism ; Glycolysis ; Humans ; NADP/metabolism ; Neoplasms/drug therapy/*genetics/*metabolism/pathology ; *Oncogenes ; Pentose Phosphate Pathway ; Signal Transduction
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    Covering a broad dynamic range: information processing at the erythropoietin receptor (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-05-22
    Description: Cell surface receptors convert extracellular cues into receptor activation, thereby triggering intracellular signaling networks and controlling cellular decisions. A major unresolved issue is the identification of receptor properties that critically determine processing of ligand-encoded information. We show by mathematical modeling of quantitative data and experimental validation that rapid ligand depletion and replenishment of the cell surface receptor are characteristic features of the erythropoietin (Epo) receptor (EpoR). The amount of Epo-EpoR complexes and EpoR activation integrated over time corresponds linearly to ligand input; this process is carried out over a broad range of ligand concentrations. This relation depends solely on EpoR turnover independent of ligand binding, which suggests an essential role of large intracellular receptor pools. These receptor properties enable the system to cope with basal and acute demand in the hematopoietic system.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Becker, Verena -- Schilling, Marcel -- Bachmann, Julie -- Baumann, Ute -- Raue, Andreas -- Maiwald, Thomas -- Timmer, Jens -- Klingmuller, Ursula -- New York, N.Y. -- Science. 2010 Jun 11;328(5984):1404-8. doi: 10.1126/science.1184913. Epub 2010 May 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division Systems Biology of Signal Transduction, DKFZ-ZMBH Alliance, German Cancer Research Center, 69120 Heidelberg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20488988" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; Cell Membrane/*metabolism ; Computer Simulation ; Endocytosis ; Epoetin Alfa ; Erythropoietin/metabolism/pharmacology ; Kinetics ; Ligands ; Mice ; Models, Biological ; Protein Binding ; Receptors, Erythropoietin/*metabolism ; Recombinant Proteins ; Signal Transduction
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    Identification of RACK1 and protein kinase Calpha as integral components of the mammalian circadian clock (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-01-23
    Description: At the core of the mammalian circadian clock is a negative feedback loop in which the dimeric transcription factor CLOCK-BMAL1 drives processes that in turn suppress its transcriptional activity. To gain insight into the mechanisms of circadian feedback, we analyzed mouse protein complexes containing BMAL1. Receptor for activated C kinase-1 (RACK1) and protein kinase C-alpha (PKCalpha) were recruited in a circadian manner into a nuclear BMAL1 complex during the negative feedback phase of the cycle. Overexpression of RACK1 and PKCalpha suppressed CLOCK-BMAL1 transcriptional activity, and RACK1 stimulated phosphorylation of BMAL1 by PKCalpha in vitro. Depletion of endogenous RACK1 or PKCalpha from fibroblasts shortened the circadian period, demonstrating that both molecules function in the clock oscillatory mechanism. Thus, the classical PKC signaling pathway is not limited to relaying external stimuli but is rhythmically activated by internal processes, forming an integral part of the circadian feedback loop.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Robles, Maria S -- Boyault, Cyril -- Knutti, Darko -- Padmanabhan, Kiran -- Weitz, Charles J -- New York, N.Y. -- Science. 2010 Jan 22;327(5964):463-6. doi: 10.1126/science.1180067.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20093473" target="_blank"〉PubMed〈/a〉
    Keywords: ARNTL Transcription Factors/metabolism ; Animals ; CLOCK Proteins/metabolism ; Cell Nucleus/metabolism ; Circadian Rhythm/*physiology ; Feedback, Physiological ; Fibroblasts/metabolism/physiology ; Mice ; Mice, Inbred C57BL ; Neuropeptides/genetics/*metabolism ; Phosphorylation ; Protein Binding ; Protein Kinase C-alpha/*metabolism ; RNA Interference ; Signal Transduction ; Transcription, Genetic
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    Rewiring of genetic networks in response to DNA damage (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-12-04
    Description: Although cellular behaviors are dynamic, the networks that govern these behaviors have been mapped primarily as static snapshots. Using an approach called differential epistasis mapping, we have discovered widespread changes in genetic interaction among yeast kinases, phosphatases, and transcription factors as the cell responds to DNA damage. Differential interactions uncover many gene functions that go undetected in static conditions. They are very effective at identifying DNA repair pathways, highlighting new damage-dependent roles for the Slt2 kinase, Pph3 phosphatase, and histone variant Htz1. The data also reveal that protein complexes are generally stable in response to perturbation, but the functional relations between these complexes are substantially reorganized. Differential networks chart a new type of genetic landscape that is invaluable for mapping cellular responses to stimuli.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3006187/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3006187/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bandyopadhyay, Sourav -- Mehta, Monika -- Kuo, Dwight -- Sung, Min-Kyung -- Chuang, Ryan -- Jaehnig, Eric J -- Bodenmiller, Bernd -- Licon, Katherine -- Copeland, Wilbert -- Shales, Michael -- Fiedler, Dorothea -- Dutkowski, Janusz -- Guenole, Aude -- van Attikum, Haico -- Shokat, Kevan M -- Kolodner, Richard D -- Huh, Won-Ki -- Aebersold, Ruedi -- Keogh, Michael-Christopher -- Krogan, Nevan J -- Ideker, Trey -- P30CA013330/CA/NCI NIH HHS/ -- P50 GM081879/GM/NIGMS NIH HHS/ -- R01 ES014811/ES/NIEHS NIH HHS/ -- R01 ES014811-01A1/ES/NIEHS NIH HHS/ -- R01 ES014811-02/ES/NIEHS NIH HHS/ -- R01 ES014811-02S1/ES/NIEHS NIH HHS/ -- R01 ES014811-03/ES/NIEHS NIH HHS/ -- R01 ES014811-04/ES/NIEHS NIH HHS/ -- R01 ES014811-05/ES/NIEHS NIH HHS/ -- R01 ES014811-05S1/ES/NIEHS NIH HHS/ -- R01 ES014811-06/ES/NIEHS NIH HHS/ -- R01 GM026017/GM/NIGMS NIH HHS/ -- R01 GM084279/GM/NIGMS NIH HHS/ -- R01 GM084279-01A1/GM/NIGMS NIH HHS/ -- R01 GM084279-02/GM/NIGMS NIH HHS/ -- R01 GM084279-02S1/GM/NIGMS NIH HHS/ -- R01 GM084279-03/GM/NIGMS NIH HHS/ -- R01 GM084279-04/GM/NIGMS NIH HHS/ -- R01 GM084448/GM/NIGMS NIH HHS/ -- R01-ES14811/ES/NIEHS NIH HHS/ -- R01-GM084279/GM/NIGMS NIH HHS/ -- R37 GM026017/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2010 Dec 3;330(6009):1385-9. doi: 10.1126/science.1195618.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21127252" target="_blank"〉PubMed〈/a〉
    Keywords: Chromatin/metabolism ; *DNA Damage ; DNA Repair/*genetics ; DNA, Fungal/genetics ; *Epistasis, Genetic ; *Gene Regulatory Networks ; Genes, Fungal ; Histones/genetics/metabolism ; Methyl Methanesulfonate/pharmacology ; Mitogen-Activated Protein Kinases/genetics/metabolism ; Mutagens/pharmacology ; Mutation ; Phosphoprotein Phosphatases/genetics/metabolism ; Protein Interaction Mapping ; Protein-Serine-Threonine Kinases/genetics/metabolism ; Saccharomyces cerevisiae/*genetics/*metabolism ; Saccharomyces cerevisiae Proteins/genetics/*metabolism ; Signal Transduction ; Transcription Factors/genetics/metabolism
    Print ISSN: 0036-8075
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    Cell signaling. Signaling through cooperation (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-05-22
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Levy, Emmanuel D -- Landry, Christian R -- Michnick, Stephen W -- New York, N.Y. -- Science. 2010 May 21;328(5981):983-4. doi: 10.1126/science.1190993.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Departement de Biochimie, Universite de Montreal, Montreal, Quebec, Canada H3T 1J4.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20489011" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; Mass Spectrometry ; Metabolic Networks and Pathways ; Models, Biological ; Phosphoprotein Phosphatases/*metabolism ; Phosphorylation ; Protein Interaction Mapping ; Protein Kinases/*metabolism ; Saccharomyces cerevisiae/enzymology/*metabolism ; Saccharomyces cerevisiae Proteins/*metabolism ; *Signal Transduction
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    Cell biology. Septins at the nexus (2010)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2010-09-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Barral, Yves -- New York, N.Y. -- Science. 2010 Sep 10;329(5997):1289-90. doi: 10.1126/science.1195445.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Biochemistry, ETH Zurich, 8093 Zurich, Switzerland. yves.barral@bc.biol.ethz.ch〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20829470" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Membrane/metabolism/ultrastructure ; *Cell Polarity ; Centrioles/metabolism ; Cilia/*metabolism/ultrastructure ; Cytoskeletal Proteins/chemistry/*metabolism ; Diffusion ; GTP-Binding Proteins/chemistry/*metabolism ; Glycoproteins/genetics/metabolism ; Hedgehog Proteins/metabolism ; Humans ; Mutant Proteins/metabolism ; Mutation ; Receptors, Cell Surface/metabolism ; Signal Transduction ; Xenopus Proteins/metabolism
    Print ISSN: 0036-8075
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    Restriction of receptor movement alters cellular response: physical force sensing by EphA2 (2010)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2010-03-13
    Description: Activation of the EphA2 receptor tyrosine kinase by ephrin-A1 ligands presented on apposed cell surfaces plays important roles in development and exhibits poorly understood functional alterations in cancer. We reconstituted this intermembrane signaling geometry between live EphA2-expressing human breast cancer cells and supported membranes displaying laterally mobile ephrin-A1. Receptor-ligand binding, clustering, and subsequent lateral transport within this junction were observed. EphA2 transport can be blocked by physical barriers nanofabricated onto the underlying substrate. This physical reorganization of EphA2 alters the cellular response to ephrin-A1, as observed by changes in cytoskeleton morphology and recruitment of a disintegrin and metalloprotease 10. Quantitative analysis of receptor-ligand spatial organization across a library of 26 mammary epithelial cell lines reveals characteristic differences that strongly correlate with invasion potential. These observations reveal a mechanism for spatio-mechanical regulation of EphA2 signaling pathways.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2895569/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2895569/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Salaita, Khalid -- Nair, Pradeep M -- Petit, Rebecca S -- Neve, Richard M -- Das, Debopriya -- Gray, Joe W -- Groves, Jay T -- P50 CA 58207/CA/NCI NIH HHS/ -- P50 CA058207/CA/NCI NIH HHS/ -- P50 CA058207-060002/CA/NCI NIH HHS/ -- P50 CA058207-08/CA/NCI NIH HHS/ -- P50 CA058207-09/CA/NCI NIH HHS/ -- U54 CA 112970/CA/NCI NIH HHS/ -- U54 CA112970/CA/NCI NIH HHS/ -- U54 CA112970-01/CA/NCI NIH HHS/ -- U54 CA143836/CA/NCI NIH HHS/ -- U54 CA143836-01/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2010 Mar 12;327(5971):1380-5. doi: 10.1126/science.1181729.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Department of Chemistry, University of California, Berkeley, CA 94720, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20223987" target="_blank"〉PubMed〈/a〉
    Keywords: ADAM Proteins/metabolism ; Actomyosin/physiology ; Amyloid Precursor Protein Secretases/metabolism ; Antigens, CD44/metabolism ; Breast Neoplasms/*metabolism/pathology ; Cell Line, Tumor ; Cell Membrane/metabolism ; Cell Shape ; Cytoskeleton/physiology/ultrastructure ; Ephrin-A1/*chemistry/*metabolism ; Female ; Humans ; Ligands ; Lipid Bilayers ; *Mechanotransduction, Cellular ; Membrane Proteins/metabolism ; Neoplasm Invasiveness ; Protein Binding ; Protein Multimerization ; Protein Transport ; Receptor, EphA2/*chemistry/*metabolism ; Signal Transduction
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    Structural basis for activation of class Ib ribonucleotide reductase (2010)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2010-08-07
    Description: The class Ib ribonucleotide reductase of Escherichia coli can initiate reduction of nucleotides to deoxynucleotides with either a Mn(III)2-tyrosyl radical (Y*) or a Fe(III)2-Y* cofactor in the NrdF subunit. Whereas Fe(III)2-Y* can self-assemble from Fe(II)2-NrdF and O2, activation of Mn(II)2-NrdF requires a reduced flavoprotein, NrdI, proposed to form the oxidant for cofactor assembly by reduction of O2. The crystal structures reported here of E. coli Mn(II)2-NrdF and Fe(II)2-NrdF reveal different coordination environments, suggesting distinct initial binding sites for the oxidants during cofactor activation. In the structures of Mn(II)2-NrdF in complex with reduced and oxidized NrdI, a continuous channel connects the NrdI flavin cofactor to the NrdF Mn(II)2 active site. Crystallographic detection of a putative peroxide in this channel supports the proposed mechanism of Mn(III)2-Y* cofactor assembly.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3020666/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3020666/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Boal, Amie K -- Cotruvo, Joseph A Jr -- Stubbe, JoAnne -- Rosenzweig, Amy C -- GM58518/GM/NIGMS NIH HHS/ -- GM81393/GM/NIGMS NIH HHS/ -- R01 GM058518/GM/NIGMS NIH HHS/ -- R01 GM058518-13/GM/NIGMS NIH HHS/ -- Y1-CO-1020/CO/NCI NIH HHS/ -- Y1-GM-1104/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2010 Sep 17;329(5998):1526-30. doi: 10.1126/science.1190187. Epub 2010 Aug 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, Evanston, IL 60208, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20688982" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; Catalytic Domain ; Coenzymes/chemistry/metabolism ; Crystallography, X-Ray ; Enzyme Activation ; Escherichia coli/*enzymology ; Escherichia coli Proteins/*chemistry/*metabolism ; Ferrous Compounds/chemistry/metabolism ; Flavin Mononucleotide/chemistry/metabolism ; Flavodoxin/*chemistry/metabolism ; Hydrogen Bonding ; Ligands ; Manganese/*chemistry/metabolism ; Models, Molecular ; Oxidants/chemistry/metabolism ; Oxidation-Reduction ; Oxygen/chemistry/metabolism ; Peroxides/chemistry/metabolism ; Protein Folding ; Protein Multimerization ; Protein Subunits/chemistry/metabolism ; Ribonucleotide Reductases/*chemistry/*metabolism
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    Activation of beta-catenin in dendritic cells regulates immunity versus tolerance in the intestine (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-08-14
    Description: Dendritic cells (DCs) play a vital role in initiating robust immunity against pathogens as well as maintaining immunological tolerance to self antigens. However, the intracellular signaling networks that program DCs to become tolerogenic remain unknown. We report here that the Wnt-beta-catenin signaling in intestinal dendritic cells regulates the balance between inflammatory versus regulatory responses in the gut. beta-catenin in intestinal dendritic cells was required for the expression of anti-inflammatory mediators such as retinoic acid-metabolizing enzymes, interleukin-10, and transforming growth factor-beta, and the stimulation of regulatory T cell induction while suppressing inflammatory effector T cells. Furthermore, ablation of beta-catenin expression in DCs enhanced inflammatory responses and disease in a mouse model of inflammatory bowel disease. Thus, beta-catenin signaling programs DCs to a tolerogenic state, limiting the inflammatory response.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3732486/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3732486/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Manicassamy, Santhakumar -- Reizis, Boris -- Ravindran, Rajesh -- Nakaya, Helder -- Salazar-Gonzalez, Rosa Maria -- Wang, Yi-Chong -- Pulendran, Bali -- HHSN266 200700006C/PHS HHS/ -- N01 AI50019/AI/NIAID NIH HHS/ -- N01 AI50025/AI/NIAID NIH HHS/ -- R01 AI048638/AI/NIAID NIH HHS/ -- R01 AI056499/AI/NIAID NIH HHS/ -- R01 DK057665/DK/NIDDK NIH HHS/ -- R01DK057665,/DK/NIDDK NIH HHS/ -- R37 AI048638/AI/NIAID NIH HHS/ -- R37 DK057665/DK/NIDDK NIH HHS/ -- R37AI48638,/AI/NIAID NIH HHS/ -- U19 AI057266/AI/NIAID NIH HHS/ -- U19AI057266,/AI/NIAID NIH HHS/ -- U54 AI057157/AI/NIAID NIH HHS/ -- U54AI057157/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2010 Aug 13;329(5993):849-53. doi: 10.1126/science.1188510.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Emory Vaccine Center, and Yerkes National Primate Research Center, 954 Gatewood Road, Atlanta, GA 30329, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20705860" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cytokines/metabolism ; Dendritic Cells/*immunology/metabolism ; Gene Expression Profiling ; *Inflammation ; Inflammatory Bowel Diseases/*immunology ; Intestinal Mucosa/cytology/*immunology/metabolism ; Macrophages/immunology/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Oligonucleotide Array Sequence Analysis ; *Self Tolerance ; Signal Transduction ; T-Lymphocytes, Helper-Inducer/cytology/*immunology ; T-Lymphocytes, Regulatory/*immunology ; Tretinoin/metabolism ; Wnt Proteins/metabolism ; beta Catenin/*metabolism
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    Noise can induce bimodality in positive transcriptional feedback loops without bistability (2010)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2010-02-27
    Description: Transcriptional positive-feedback loops are widely associated with bistability, characterized by two stable expression states that allow cells to respond to analog signals in a digital manner. Using a synthetic system in budding yeast, we show that positive feedback involving a promoter with multiple transcription factor (TF) binding sites can induce a steady-state bimodal response without cooperative binding of the TF. Deterministic models of this system do not predict bistability. Rather, the bimodal response requires a short-lived TF and stochastic fluctuations in the TF's expression. Multiple binding sites provide these fluctuations. Because many promoters possess multiple binding sites and many TFs are unstable, positive-feedback loops in gene regulatory networks may exhibit bimodal responses, but not necessarily because of deterministic bistability, as is commonly thought.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉To, Tsz-Leung -- Maheshri, Narendra -- New York, N.Y. -- Science. 2010 Feb 26;327(5969):1142-5. doi: 10.1126/science.1178962.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20185727" target="_blank"〉PubMed〈/a〉
    Keywords: Active Transport, Cell Nucleus ; Binding Sites ; Cell Nucleus/metabolism ; Doxycycline/metabolism ; Feedback, Physiological ; *Gene Expression Regulation, Fungal ; *Gene Regulatory Networks ; Models, Genetic ; Models, Statistical ; Promoter Regions, Genetic ; Protein Stability ; Recombinant Fusion Proteins/metabolism ; Saccharomyces cerevisiae/*genetics/metabolism ; Saccharomyces cerevisiae Proteins/chemistry/genetics/metabolism ; Stochastic Processes ; Transcription Factors/chemistry/genetics/*metabolism ; *Transcription, Genetic
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    Variation in transcription factor binding among humans (2010)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2010-03-20
    Description: Differences in gene expression may play a major role in speciation and phenotypic diversity. We examined genome-wide differences in transcription factor (TF) binding in several humans and a single chimpanzee by using chromatin immunoprecipitation followed by sequencing. The binding sites of RNA polymerase II (PolII) and a key regulator of immune responses, nuclear factor kappaB (p65), were mapped in 10 lymphoblastoid cell lines, and 25 and 7.5% of the respective binding regions were found to differ between individuals. Binding differences were frequently associated with single-nucleotide polymorphisms and genomic structural variants, and these differences were often correlated with differences in gene expression, suggesting functional consequences of binding variation. Furthermore, comparing PolII binding between humans and chimpanzee suggests extensive divergence in TF binding. Our results indicate that many differences in individuals and species occur at the level of TF binding, and they provide insight into the genetic events responsible for these differences.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2938768/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2938768/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kasowski, Maya -- Grubert, Fabian -- Heffelfinger, Christopher -- Hariharan, Manoj -- Asabere, Akwasi -- Waszak, Sebastian M -- Habegger, Lukas -- Rozowsky, Joel -- Shi, Minyi -- Urban, Alexander E -- Hong, Mi-Young -- Karczewski, Konrad J -- Huber, Wolfgang -- Weissman, Sherman M -- Gerstein, Mark B -- Korbel, Jan O -- Snyder, Michael -- R01 CA077808/CA/NCI NIH HHS/ -- R01 CA077808-09/CA/NCI NIH HHS/ -- T32 GM007205/GM/NIGMS NIH HHS/ -- T32 GM007205-34/GM/NIGMS NIH HHS/ -- T32GM07205/GM/NIGMS NIH HHS/ -- U54 HG004558/HG/NHGRI NIH HHS/ -- U54 HG004558-04/HG/NHGRI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2010 Apr 9;328(5975):232-5. doi: 10.1126/science.1183621. Epub 2010 Mar 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06520, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20299548" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Binding Sites ; Cell Line ; Chromatin Immunoprecipitation ; DNA Copy Number Variations ; DNA, Intergenic ; Female ; *Gene Expression Regulation ; Humans ; Male ; Pan troglodytes/genetics ; *Polymorphism, Single Nucleotide ; Protein Binding ; RNA Polymerase II/genetics/*metabolism ; Sequence Analysis, DNA ; Species Specificity ; Transcription Factor RelA/genetics/*metabolism ; Transcription Initiation Site
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    Cyclooxygenase-2 controls energy homeostasis in mice by de novo recruitment of brown adipocytes (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-05-08
    Description: Obesity results from chronic energy surplus and excess lipid storage in white adipose tissue (WAT). In contrast, brown adipose tissue (BAT) efficiently burns lipids through adaptive thermogenesis. Studying mouse models, we show that cyclooxygenase (COX)-2, a rate-limiting enzyme in prostaglandin (PG) synthesis, is a downstream effector of beta-adrenergic signaling in WAT and is required for the induction of BAT in WAT depots. PG shifted the differentiation of defined mesenchymal progenitors toward a brown adipocyte phenotype. Overexpression of COX-2 in WAT induced de novo BAT recruitment in WAT, increased systemic energy expenditure, and protected mice against high-fat diet-induced obesity. Thus, COX-2 appears integral to de novo BAT recruitment, which suggests that the PG pathway regulates systemic energy homeostasis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vegiopoulos, Alexandros -- Muller-Decker, Karin -- Strzoda, Daniela -- Schmitt, Iris -- Chichelnitskiy, Evgeny -- Ostertag, Anke -- Berriel Diaz, Mauricio -- Rozman, Jan -- Hrabe de Angelis, Martin -- Nusing, Rolf M -- Meyer, Carola W -- Wahli, Walter -- Klingenspor, Martin -- Herzig, Stephan -- New York, N.Y. -- Science. 2010 May 28;328(5982):1158-61. doi: 10.1126/science.1186034. Epub 2010 May 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Emmy Noether and Marie Curie Research Group Molecular Metabolic Control, German Cancer Research Center (DKFZ) Heidelberg, 69120 Heidelberg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20448152" target="_blank"〉PubMed〈/a〉
    Keywords: Adipocytes, Brown/cytology/*physiology ; Adipogenesis ; Adipose Tissue ; Adipose Tissue, Brown/cytology/*physiology ; Adipose Tissue, White/enzymology/*physiology ; Adrenergic beta-3 Receptor Agonists ; Adrenergic beta-Agonists/pharmacology ; Animals ; Body Weight ; Cyclooxygenase 2/*genetics/*metabolism ; Dietary Fats/administration & dosage ; Dioxoles/pharmacology ; *Energy Metabolism ; Female ; Gene Expression Regulation, Enzymologic ; Homeostasis ; Male ; Mesenchymal Stromal Cells/cytology ; Mice ; Mice, Inbred C57BL ; Mice, Obese ; Mice, Transgenic ; Norepinephrine/metabolism ; Obesity/etiology/prevention & control ; Oxygen Consumption ; Prostaglandins/*metabolism ; Receptors, Adrenergic, beta-3/metabolism ; Signal Transduction ; *Thermogenesis
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    G protein subunit Galpha13 binds to integrin alphaIIbbeta3 and mediates integrin "outside-in" signaling (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-01-16
    Description: Integrins mediate cell adhesion to the extracellular matrix and transmit signals within the cell that stimulate cell spreading, retraction, migration, and proliferation. The mechanism of integrin outside-in signaling has been unclear. We found that the heterotrimeric guanine nucleotide-binding protein (G protein) Galpha13 directly bound to the integrin beta3 cytoplasmic domain and that Galpha13-integrin interaction was promoted by ligand binding to the integrin alphaIIbbeta3 and by guanosine triphosphate (GTP) loading of Galpha13. Interference of Galpha13 expression or a myristoylated fragment of Galpha13 that inhibited interaction of alphaIIbbeta3 with Galpha13 diminished activation of protein kinase c-Src and stimulated the small guanosine triphosphatase RhoA, consequently inhibiting cell spreading and accelerating cell retraction. We conclude that integrins are noncanonical Galpha13-coupled receptors that provide a mechanism for dynamic regulation of RhoA.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2842917/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2842917/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gong, Haixia -- Shen, Bo -- Flevaris, Panagiotis -- Chow, Christina -- Lam, Stephen C-T -- Voyno-Yasenetskaya, Tatyana A -- Kozasa, Tohru -- Du, Xiaoping -- GM061454/GM/NIGMS NIH HHS/ -- GM074001/GM/NIGMS NIH HHS/ -- HL062350/HL/NHLBI NIH HHS/ -- HL068819/HL/NHLBI NIH HHS/ -- HL080264/HL/NHLBI NIH HHS/ -- R01 GM061454/GM/NIGMS NIH HHS/ -- R01 GM061454-09/GM/NIGMS NIH HHS/ -- R01 GM074001/GM/NIGMS NIH HHS/ -- R01 GM074001-02/GM/NIGMS NIH HHS/ -- R01 HL062350/HL/NHLBI NIH HHS/ -- R01 HL062350-09/HL/NHLBI NIH HHS/ -- R01 HL068819/HL/NHLBI NIH HHS/ -- R01 HL068819-08/HL/NHLBI NIH HHS/ -- R01 HL080264/HL/NHLBI NIH HHS/ -- R01 HL080264-04/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2010 Jan 15;327(5963):340-3. doi: 10.1126/science.1174779.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, University of Illinois at Chicago, 835 South Wolcott Avenue, Room E403, Chicago, IL 60612, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20075254" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Binding Sites ; Blood Platelets/*physiology ; Clot Retraction ; Fibrinogen/metabolism ; GTP-Binding Protein alpha Subunits, G12-G13/genetics/*metabolism ; Humans ; Integrin beta3/*metabolism ; Ligands ; Mice ; Mice, Inbred C57BL ; Phosphorylation ; Platelet Adhesiveness ; Platelet Glycoprotein GPIIb-IIIa Complex/*metabolism ; Protein Binding ; Protein Structure, Tertiary ; Proto-Oncogene Proteins pp60(c-src)/metabolism ; RNA, Small Interfering ; Recombinant Fusion Proteins/metabolism ; *Signal Transduction ; rhoA GTP-Binding Protein/antagonists & inhibitors/metabolism
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    Cell biology. Burn out or fade away? (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-03-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Topisirovic, Ivan -- Sonenberg, Nahum -- New York, N.Y. -- Science. 2010 Mar 5;327(5970):1210-1. doi: 10.1126/science.1187497.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, McGill University, Montreal, Quebec, H3A 1A3, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20203039" target="_blank"〉PubMed〈/a〉
    Keywords: AMP-Activated Protein Kinases/metabolism ; *Aging ; Animals ; Autophagy ; Caloric Restriction ; Drosophila Proteins/*genetics/metabolism/*physiology ; Drosophila melanogaster/genetics/metabolism/*physiology ; Feedback, Physiological ; Heat-Shock Proteins/*genetics/*physiology ; Metabolic Networks and Pathways ; Mitochondria/metabolism ; Models, Animal ; Oxidation-Reduction ; Oxidative Stress ; Protein Biosynthesis ; Protein Kinases/*metabolism ; Reactive Oxygen Species/metabolism ; Signal Transduction ; TOR Serine-Threonine Kinases
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    Changing face of microglia (2010)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2010-11-06
    Description: Microglia are resident brain cells that sense pathological tissue alterations. They can develop into brain macrophages and perform immunological functions. However, expression of immune proteins by microglia is not synonymous with inflammation, because these molecules can have central nervous system (CNS)-specific roles. Through their involvement in pain mechanisms, microglia also respond to external threats. Experimental studies support the idea that microglia have a role in the maintenance of synaptic integrity. Analogous to electricians, they are capable of removing defunct axon terminals, thereby helping neuronal connections to stay intact. Microglia in healthy CNS tissue do not qualify as macrophages, and their specific functions are beginning to be explored.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Graeber, Manuel B -- New York, N.Y. -- Science. 2010 Nov 5;330(6005):783-8. doi: 10.1126/science.1190929.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Brain and Mind Research Institute, University of Sydney, Camperdown, NSW 2050, Australia. manuel@graeber.net〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21051630" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Behavior ; Behavior, Animal ; Bone Marrow Transplantation ; Brain/*cytology/pathology/physiology ; Brain Diseases/pathology/physiopathology/therapy ; Humans ; Macrophages/cytology/physiology ; Mental Disorders/physiopathology ; Microglia/immunology/*physiology ; Mutation ; Neuralgia/physiopathology ; Neurodegenerative Diseases/pathology/physiopathology/therapy ; Signal Transduction ; Spinal Cord/*cytology/pathology/physiology ; Synapses/physiology
    Print ISSN: 0036-8075
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    The onset of collective behavior in social amoebae (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-04-24
    Description: In the social amoebae Dictyostelium discoideum, periodic synthesis and release of extracellular cyclic adenosine 3',5'-monophosphate (cAMP) guide cell aggregation and commitment to form fruiting bodies. It is unclear whether these oscillations are an intrinsic property of individual cells or if they exist only as a population-level phenomenon. Here, we showed by live-cell imaging of intact cell populations that pulses originate from a discrete location despite constant exchange of cells to and from the region. In a perfusion chamber, both isolated single cells and cell populations switched from quiescence to rhythmic activity depending on the concentration of extracellular cAMP. A quantitative analysis showed that stochastic pulsing of individual cells below the threshold concentration of extracellular cAMP plays a critical role in the onset of collective behavior.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3120019/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3120019/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gregor, Thomas -- Fujimoto, Koichi -- Masaki, Noritaka -- Sawai, Satoshi -- P50 GM071508/GM/NIGMS NIH HHS/ -- P50 GM071508-08/GM/NIGMS NIH HHS/ -- R01 GM098407/GM/NIGMS NIH HHS/ -- R01 GM098407-01A1/GM/NIGMS NIH HHS/ -- R01 GM098407-02/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2010 May 21;328(5981):1021-5. doi: 10.1126/science.1183415. Epub 2010 Apr 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Graduate School of Arts and Sciences, University of Tokyo, Tokyo 153-8902, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20413456" target="_blank"〉PubMed〈/a〉
    Keywords: 3',5'-Cyclic-AMP Phosphodiesterases/metabolism ; Adenylyl Cyclases/metabolism ; Cell Aggregation ; Cell Count ; Cyclic AMP/*metabolism/pharmacology ; Cyclic AMP-Dependent Protein Kinases/genetics/metabolism ; Cytosol/metabolism ; Dictyostelium/cytology/genetics/growth & development/*physiology ; Fluorescence Resonance Energy Transfer ; Models, Biological ; Periodicity ; Protozoan Proteins/genetics/metabolism ; Quorum Sensing ; Signal Transduction ; Stochastic Processes
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    An oxidative enzyme boosting the enzymatic conversion of recalcitrant polysaccharides (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-10-12
    Description: Efficient enzymatic conversion of crystalline polysaccharides is crucial for an economically and environmentally sustainable bioeconomy but remains unfavorably inefficient. We describe an enzyme that acts on the surface of crystalline chitin, where it introduces chain breaks and generates oxidized chain ends, thus promoting further degradation by chitinases. This enzymatic activity was discovered and further characterized by using mass spectrometry and chromatographic separation methods to detect oxidized products generated in the absence or presence of H(2)(18)O or (18)O(2). There are strong indications that similar enzymes exist that work on cellulose. Our findings not only demonstrate the existence of a hitherto unknown enzyme activity but also provide new avenues toward more efficient enzymatic conversion of biomass.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vaaje-Kolstad, Gustav -- Westereng, Bjorge -- Horn, Svein J -- Liu, Zhanliang -- Zhai, Hong -- Sorlie, Morten -- Eijsink, Vincent G H -- New York, N.Y. -- Science. 2010 Oct 8;330(6001):219-22. doi: 10.1126/science.1192231.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, Post Office Box 5003, 1432 As, Norway.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20929773" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Proteins/antagonists & inhibitors/chemistry/genetics/*metabolism ; Binding Sites ; Biocatalysis ; Biomass ; Carrier Proteins/antagonists & inhibitors/chemistry/genetics/*metabolism ; Cations, Divalent/metabolism/pharmacology ; Chitin/*metabolism ; Chitinase/*metabolism ; Chromatography, High Pressure Liquid ; Edetic Acid/pharmacology ; Enzyme Inhibitors/pharmacology ; Hydrolysis ; Isotope Labeling ; Oligosaccharides/metabolism ; Oxidation-Reduction ; Oxygen Isotopes/metabolism ; Serratia marcescens/*enzymology ; Solubility ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
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    Secreted peptide signals required for maintenance of root stem cell niche in Arabidopsis (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-08-28
    Description: Stem cells are maintained in the niche by intercellular interactions and signaling networks. In this work, we study extracellular signals required for maintenance of the root stem cell niche in higher plants. We identify a family of functionally redundant homologous peptides that are secreted, tyrosine-sulfated, and expressed mainly in the stem cell area and the innermost layer of central columella cells. We name these peptides root meristem growth factors (RGFs). RGFs are required for maintenance of the root stem cell niche and transit amplifying cell proliferation in Arabidopsis. RGF1 defines expression levels and patterns of the stem cell transcription factor PLETHORA, mainly at the posttranscriptional level. The RGFs function independently of the auxin pathway. These peptide signals play a crucial role in postembryonic root development.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Matsuzaki, Yo -- Ogawa-Ohnishi, Mari -- Mori, Ayaka -- Matsubayashi, Yoshikatsu -- New York, N.Y. -- Science. 2010 Aug 27;329(5995):1065-7. doi: 10.1126/science.1191132.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Graduate School of Bio-Agricultural Sciences, Nagoya University, Chikusa, Nagoya 464-8601, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20798316" target="_blank"〉PubMed〈/a〉
    Keywords: Arabidopsis/cytology/genetics/growth & development/*physiology ; Arabidopsis Proteins/genetics/*metabolism/secretion ; Cell Proliferation ; Gene Expression Regulation, Plant ; Genes, Plant ; Indoleacetic Acids/metabolism ; Meristem/cytology/growth & development/physiology ; Peptides/genetics/*metabolism/secretion ; Phenotype ; Plant Growth Regulators/genetics/*metabolism ; Plant Roots/*cytology/growth & development/physiology ; Plants, Genetically Modified ; Recombinant Fusion Proteins/metabolism ; Signal Transduction ; Stem Cell Niche/*physiology ; Stem Cells/cytology/*physiology ; Sulfotransferases/genetics/metabolism ; Transcription Factors/genetics/metabolism ; Up-Regulation
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    A transient niche regulates the specification of Drosophila intestinal stem cells (2010)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2010-01-09
    Description: Stem cell niches are locations where stem cells reside and self-renew. Although studies have shown how niches maintain stem cell fate during tissue homeostasis, less is known about their roles in establishing stem cells. The adult Drosophila midgut is maintained by intestinal stem cells (ISCs); however, how they are established is unknown. Here, we show that an ISC progenitor generates a niche cell via Notch signaling. This niche uses the bone morphogenetic protein 2/4 homolog, decapentaplegic, to allow progenitors to divide in an undifferentiated state and subsequently breaks down and dies, resulting in the specification of ISCs in the adult midgut. Our results demonstrate a paradigm for stem cell-niche biology, where progenitors generate transient niches that determine stem cell fate and may give insights into stem cell specification in other tissues.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2857772/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2857772/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mathur, Divya -- Bost, Alyssa -- Driver, Ian -- Ohlstein, Benjamin -- R01 DK082456/DK/NIDDK NIH HHS/ -- R01 DK082456-01/DK/NIDDK NIH HHS/ -- T32 GM007088/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2010 Jan 8;327(5962):210-3. doi: 10.1126/science.1181958.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics and Development, Columbia University Medical Center, New York, NY 10032, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20056890" target="_blank"〉PubMed〈/a〉
    Keywords: Adult Stem Cells/*cytology/physiology ; Animals ; Cell Differentiation ; Cell Lineage ; Cell Proliferation ; Drosophila/*cytology/growth & development/metabolism ; Drosophila Proteins/genetics/metabolism ; Enterocytes/cytology ; Epithelial Cells/*cytology ; Intestines/cytology/growth & development ; Larva/cytology/growth & development/metabolism ; Metamorphosis, Biological ; Organogenesis ; Receptors, Notch/metabolism ; Signal Transduction ; Stem Cell Niche/*physiology
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    Loss of Rap1 induces telomere recombination in the absence of NHEJ or a DNA damage signal (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-03-27
    Description: Shelterin is an essential telomeric protein complex that prevents DNA damage signaling and DNA repair at mammalian chromosome ends. Here we report on the role of the TRF2-interacting factor Rap1, a conserved shelterin subunit of unknown function. We removed Rap1 from mouse telomeres either through gene deletion or by replacing TRF2 with a mutant that does not bind Rap1. Rap1 was dispensable for the essential functions of TRF2--repression of ATM kinase signaling and nonhomologous end joining (NHEJ)--and mice lacking telomeric Rap1 were viable and fertile. However, Rap1 was critical for the repression of homology-directed repair (HDR), which can alter telomere length. The data reveal that HDR at telomeres can take place in the absence of DNA damage foci and underscore the functional compartmentalization within shelterin.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2864730/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2864730/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sfeir, Agnel -- Kabir, Shaheen -- van Overbeek, Megan -- Celli, Giulia B -- de Lange, Titia -- AG016642/AG/NIA NIH HHS/ -- GM049046/GM/NIGMS NIH HHS/ -- R01 AG016642/AG/NIA NIH HHS/ -- R01 AG016642-01/AG/NIA NIH HHS/ -- R01 AG016642-02/AG/NIA NIH HHS/ -- R01 AG016642-03/AG/NIA NIH HHS/ -- R01 AG016642-04/AG/NIA NIH HHS/ -- R01 AG016642-05/AG/NIA NIH HHS/ -- R01 AG016642-06/AG/NIA NIH HHS/ -- R01 AG016642-07/AG/NIA NIH HHS/ -- R01 AG016642-08/AG/NIA NIH HHS/ -- R01 AG016642-09/AG/NIA NIH HHS/ -- R01 AG016642-10/AG/NIA NIH HHS/ -- R01 AG016642-11/AG/NIA NIH HHS/ -- R01 GM049046/GM/NIGMS NIH HHS/ -- R01 GM049046-07/GM/NIGMS NIH HHS/ -- R01 GM049046-08/GM/NIGMS NIH HHS/ -- R01 GM049046-09/GM/NIGMS NIH HHS/ -- R01 GM049046-10/GM/NIGMS NIH HHS/ -- R01 GM049046-11/GM/NIGMS NIH HHS/ -- R01 GM049046-12/GM/NIGMS NIH HHS/ -- R37 GM049046/GM/NIGMS NIH HHS/ -- R37 GM049046-13/GM/NIGMS NIH HHS/ -- R37 GM049046-14/GM/NIGMS NIH HHS/ -- R37 GM049046-15/GM/NIGMS NIH HHS/ -- R37 GM049046-16/GM/NIGMS NIH HHS/ -- R37 GM049046-17/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2010 Mar 26;327(5973):1657-61. doi: 10.1126/science.1185100.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20339076" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Ataxia Telangiectasia Mutated Proteins ; Cell Cycle Proteins/metabolism ; Cell Proliferation ; Cells, Cultured ; Checkpoint Kinase 2 ; *DNA Damage ; *DNA Repair ; DNA-Binding Proteins/metabolism ; Gene Deletion ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Molecular Sequence Data ; Protein-Serine-Threonine Kinases/metabolism ; Recombination, Genetic ; Signal Transduction ; Sister Chromatid Exchange ; Telomere/*genetics/metabolism ; Telomere-Binding Proteins/chemistry/*genetics/*metabolism ; Telomeric Repeat Binding Protein 2/genetics/metabolism ; Tumor Suppressor Proteins/metabolism
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    Sfrp5 is an anti-inflammatory adipokine that modulates metabolic dysfunction in obesity (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-06-19
    Description: Adipose tissue secretes proteins referred to as adipokines, many of which promote inflammation and disrupt glucose homeostasis. Here we show that secreted frizzled-related protein 5 (Sfrp5), a protein previously linked to the Wnt signaling pathway, is an anti-inflammatory adipokine whose expression is perturbed in models of obesity and type 2 diabetes. Sfrp5-deficient mice fed a high-calorie diet developed severe glucose intolerance and hepatic steatosis, and their adipose tissue showed an accumulation of activated macrophages that was associated with activation of the c-Jun N-terminal kinase signaling pathway. Adenovirus-mediated delivery of Sfrp5 to mouse models of obesity ameliorated glucose intolerance and hepatic steatosis. Thus, in the setting of obesity, Sfrp5 secretion by adipocytes exerts salutary effects on metabolic dysfunction by controlling inflammatory cells within adipose tissue.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3132938/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3132938/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ouchi, Noriyuki -- Higuchi, Akiko -- Ohashi, Koji -- Oshima, Yuichi -- Gokce, Noyan -- Shibata, Rei -- Akasaki, Yuichi -- Shimono, Akihiko -- Walsh, Kenneth -- AG15052/AG/NIA NIH HHS/ -- AG34972/AG/NIA NIH HHS/ -- HL81587/HL/NHLBI NIH HHS/ -- HL86785/HL/NHLBI NIH HHS/ -- P01 HL081587/HL/NHLBI NIH HHS/ -- P01 HL081587-05/HL/NHLBI NIH HHS/ -- R01 AG015052/AG/NIA NIH HHS/ -- R01 AG015052-06/AG/NIA NIH HHS/ -- R01 AG034972/AG/NIA NIH HHS/ -- R01 AG034972-03/AG/NIA NIH HHS/ -- R01 HL086785/HL/NHLBI NIH HHS/ -- R01 HL086785-19/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2010 Jul 23;329(5990):454-7. doi: 10.1126/science.1188280. Epub 2010 Jun 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Cardiology and Whitaker Cardiovascular Institute, Boston University School of Medicine, 715 Albany Street, W611, Boston, MA 02118, USA. nouchi@bu.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20558665" target="_blank"〉PubMed〈/a〉
    Keywords: 3T3-L1 Cells ; Adipocytes/*metabolism/pathology ; Adipokines/genetics/*metabolism ; Adipose Tissue/*metabolism/pathology ; Animals ; Dietary Fats/administration & dosage ; Dietary Sucrose/administration & dosage ; Fatty Liver/pathology/therapy ; Genetic Vectors ; Glucose/metabolism ; Humans ; Inflammation ; Insulin/metabolism ; Insulin Resistance ; Intercellular Signaling Peptides and Proteins/genetics/*metabolism ; Macrophages/*metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Obese ; Mitogen-Activated Protein Kinase 8/genetics/metabolism ; Obesity/*metabolism/pathology ; Phosphorylation ; Rats ; Rats, Zucker ; Signal Transduction ; Wnt Proteins/metabolism
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    Parasympathetic innervation maintains epithelial progenitor cells during salivary organogenesis (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-10-12
    Description: The maintenance of a progenitor cell population as a reservoir of undifferentiated cells is required for organ development and regeneration. However, the mechanisms by which epithelial progenitor cells are maintained during organogenesis are poorly understood. We report that removal of the parasympathetic ganglion in mouse explant organ culture decreased the number and morphogenesis of keratin 5-positive epithelial progenitor cells. These effects were rescued with an acetylcholine analog. We demonstrate that acetylcholine signaling, via the muscarinic M1 receptor and epidermal growth factor receptor, increased epithelial morphogenesis and proliferation of the keratin 5-positive progenitor cells. Parasympathetic innervation maintained the epithelial progenitor cell population in an undifferentiated state, which was required for organogenesis. This mechanism for epithelial progenitor cell maintenance may be targeted for organ repair or regeneration.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3376907/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3376907/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Knox, S M -- Lombaert, I M A -- Reed, X -- Vitale-Cross, L -- Gutkind, J S -- Hoffman, M P -- Z99 DE999999/Intramural NIH HHS/ -- ZIA DE000707-08/Intramural NIH HHS/ -- ZIA DE000722-04/Intramural NIH HHS/ -- New York, N.Y. -- Science. 2010 Sep 24;329(5999):1645-7. doi: 10.1126/science.1192046.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Matrix and Morphogenesis Unit, Laboratory of Cell and Developmental Biology, National Institute of Dental and Craniofacial Research, NIH, 30 Convent Drive, Bethesda, MD 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20929848" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylcholine/metabolism ; Animals ; Carbachol/metabolism/pharmacology ; Cell Differentiation ; Epithelial Cells/cytology/*physiology ; Epithelium/embryology/innervation ; Ganglia, Parasympathetic/cytology/embryology/*physiology ; Heparin-binding EGF-like Growth Factor ; Intercellular Signaling Peptides and Proteins/metabolism/pharmacology ; Keratin-5/analysis/genetics ; Male ; Mice ; Morphogenesis/drug effects ; Neurons/cytology/*physiology ; Organ Culture Techniques ; *Organogenesis ; Prostate/cytology/embryology/innervation ; Quinazolines/pharmacology ; Receptor, Epidermal Growth Factor/metabolism ; Receptor, Muscarinic M1/metabolism ; Regeneration ; Signal Transduction ; Stem Cells/cytology/*physiology ; Submandibular Gland/cytology/*embryology/*innervation
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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    Immunology. CAR'ing for the skin (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-09-04
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shaw, Andrey S -- Huang, Yina -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2010 Sep 3;329(5996):1154-5. doi: 10.1126/science.1195337.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology and Immunology and Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, MO 63110, USA. shaw@pathology.wustl.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20813941" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Adhesion Molecules/chemistry/*metabolism ; Coxsackie and Adenovirus Receptor-Like Membrane Protein ; Crystallization ; Epidermis/*immunology/metabolism/ultrastructure ; Hydrogen Bonding ; Ligands ; Lymphocyte Activation ; Mice ; Phosphatidylinositol 3-Kinases/metabolism ; Protein Binding ; Protein Interaction Domains and Motifs ; Protein Multimerization ; Receptors, Antigen, T-Cell, gamma-delta/*immunology/metabolism ; Receptors, Virus/chemistry/*metabolism ; Signal Transduction ; T-Lymphocyte Subsets/*immunology/*metabolism ; Tight Junctions/metabolism
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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    Maize tumors caused by Ustilago maydis require organ-specific genes in host and pathogen (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-04-03
    Description: Infection of maize by corn smut (Ustilago maydis) provides an agronomically important model of biotrophic host-pathogen interactions. After penetration of the maize epidermis, fungal colonization of host tissue induces tumor formation on all aerial maize organs. We hypothesized that transformation of different primordia into plant tumors would require organ-specific gene expression by both host and pathogen and documented these differences by transcriptome profiling. Phenotypic screening of U. maydis mutants deleted for genes encoding secreted proteins and maize mutants with organ-specific defects confirmed organ-restricted tumorigenesis. This is the foundation for exploring how individual pathogen effectors, deployed in an organ-specific pattern, interact with host factors to reprogram normal ontogeny into a tumor pathway.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Skibbe, David S -- Doehlemann, Gunther -- Fernandes, John -- Walbot, Virginia -- New York, N.Y. -- Science. 2010 Apr 2;328(5974):89-92. doi: 10.1126/science.1185775.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, Stanford University, Stanford, CA 94305-5020, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20360107" target="_blank"〉PubMed〈/a〉
    Keywords: Flowers/genetics/microbiology ; Gene Expression ; Gene Expression Profiling ; Gene Expression Regulation, Fungal ; Gene Expression Regulation, Plant ; Genes, Fungal ; Genes, Plant ; Gibberellins/metabolism ; Host-Pathogen Interactions ; Oligonucleotide Array Sequence Analysis ; Phenotype ; Plant Leaves/genetics/microbiology ; Plant Tumors/*genetics/*microbiology ; Seedlings/genetics/microbiology ; Signal Transduction ; Up-Regulation ; Ustilago/*genetics/*physiology ; Zea mays/*genetics/*microbiology
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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    Intravascular danger signals guide neutrophils to sites of sterile inflammation (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-10-16
    Description: Neutrophils are recruited from the blood to sites of sterile inflammation, where they contribute to wound healing but may also cause tissue damage. By using spinning disk confocal intravital microscopy, we examined the kinetics and molecular mechanisms of neutrophil recruitment to sites of focal hepatic necrosis in vivo. Adenosine triphosphate released from necrotic cells activated the Nlrp3 inflammasome to generate an inflammatory microenvironment that alerted circulating neutrophils to adhere within liver sinusoids. Subsequently, generation of an intravascular chemokine gradient directed neutrophil migration through healthy tissue toward foci of damage. Lastly, formyl-peptide signals released from necrotic cells guided neutrophils through nonperfused sinusoids into the injury. Thus, dynamic in vivo imaging revealed a multistep hierarchy of directional cues that guide neutrophil localization to sites of sterile inflammation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McDonald, Braedon -- Pittman, Keir -- Menezes, Gustavo B -- Hirota, Simon A -- Slaba, Ingrid -- Waterhouse, Christopher C M -- Beck, Paul L -- Muruve, Daniel A -- Kubes, Paul -- Canadian Institutes of Health Research/Canada -- New York, N.Y. -- Science. 2010 Oct 15;330(6002):362-6. doi: 10.1126/science.1195491.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Immunology Research Group, University of Calgary, Alberta T2N 4N1, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20947763" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/metabolism ; Animals ; Carrier Proteins/metabolism ; Cell Adhesion ; Chemokine CXCL2/metabolism ; Chemokines/metabolism ; Chemotaxis, Leukocyte ; Cues ; Endothelium, Vascular/physiology ; Inflammation/*immunology/metabolism/*pathology ; Kinetics ; Liver/blood supply/*immunology/metabolism/*pathology ; Liver Diseases/*immunology/metabolism/*pathology ; Macrophage-1 Antigen/physiology ; Mice ; Microscopy/methods ; Microscopy, Confocal ; Microvessels/physiology ; Necrosis ; *Neutrophil Infiltration ; Neutrophils/physiology ; Peptides/metabolism ; Receptors, Formyl Peptide/metabolism ; Receptors, Interleukin-8B/metabolism ; Receptors, Purinergic P2/metabolism ; Receptors, Purinergic P2X7 ; Signal Transduction
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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    Vibrio cholerae VpsT regulates matrix production and motility by directly sensing cyclic di-GMP (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-02-13
    Description: Microorganisms can switch from a planktonic, free-swimming life-style to a sessile, colonial state, called a biofilm, which confers resistance to environmental stress. Conversion between the motile and biofilm life-styles has been attributed to increased levels of the prokaryotic second messenger cyclic di-guanosine monophosphate (c-di-GMP), yet the signaling mechanisms mediating such a global switch are poorly understood. Here we show that the transcriptional regulator VpsT from Vibrio cholerae directly senses c-di-GMP to inversely control extracellular matrix production and motility, which identifies VpsT as a master regulator for biofilm formation. Rather than being regulated by phosphorylation, VpsT undergoes a change in oligomerization on c-di-GMP binding.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2828054/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2828054/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Krasteva, Petya V -- Fong, Jiunn C N -- Shikuma, Nicholas J -- Beyhan, Sinem -- Navarro, Marcos V A S -- Yildiz, Fitnat H -- Sondermann, Holger -- 1R01GM081373/GM/NIGMS NIH HHS/ -- P30 EB009998/EB/NIBIB NIH HHS/ -- R01 AI055987/AI/NIAID NIH HHS/ -- R01 AI055987-06A1/AI/NIAID NIH HHS/ -- R01 GM081373/GM/NIGMS NIH HHS/ -- R01 GM081373-03/GM/NIGMS NIH HHS/ -- R01AI055987/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2010 Feb 12;327(5967):866-8. doi: 10.1126/science.1181185.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Medicine, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20150502" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Bacterial Proteins/chemistry/genetics/*metabolism ; Binding Sites ; Biofilms/*growth & development ; Crystallography, X-Ray ; Cyclic GMP/*analogs & derivatives/metabolism ; DNA, Bacterial/metabolism ; Dimerization ; Extracellular Matrix/*metabolism ; Gene Expression Profiling ; Gene Expression Regulation, Bacterial ; Models, Molecular ; Movement ; Point Mutation ; Polysaccharides, Bacterial/genetics/metabolism ; Protein Folding ; Protein Multimerization ; Protein Structure, Tertiary ; Signal Transduction ; Transcription Factors/chemistry/genetics/*metabolism ; Transcription, Genetic ; Vibrio cholerae O1/cytology/genetics/*physiology
    Print ISSN: 0036-8075
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    Medicine. Refugee receptors switch sides (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-03-27
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dorn, Gerald W 2nd -- R01 HL087871/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2010 Mar 26;327(5973):1586-7. doi: 10.1126/science.1188538.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA. gdorn@wustl.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20339055" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Compartmentation ; Cell Membrane/*metabolism/ultrastructure ; Cyclic AMP/*metabolism ; Heart Failure/*metabolism/pathology/physiopathology ; Humans ; Membrane Microdomains/metabolism ; Mice ; Myocardial Contraction ; Myocytes, Cardiac/*metabolism/ultrastructure ; Rats ; Receptors, Adrenergic, beta-1/*metabolism ; Receptors, Adrenergic, beta-2/*metabolism ; Sarcolemma/metabolism/ultrastructure ; Signal Transduction
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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    Induction of lymphoidlike stroma and immune escape by tumors that express the chemokine CCL21 (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-03-27
    Description: Tumor manipulation of host immunity is important for tumor survival and invasion. Many cancers secrete CCL21, a chemoattractant for various leukocytes and lymphoid tissue inducer cells, which drive lymphoid neogenesis. CCL21 expression by melanoma tumors in mice was associated with an immunotolerant microenvironment, which included the induction of lymphoid-like reticular stromal networks, an altered cytokine milieu, and the recruitment of regulatory leukocyte populations. In contrast, CCL21-deficient tumors induced antigen-specific immunity. CCL21-mediated immune tolerance was dependent on host rather than tumor expression of the CCL21 receptor, CCR7, and could protect distant, coimplanted CCL21-deficient tumors and even nonsyngeneic allografts from rejection. We suggest that by altering the tumor microenvironment, CCL21-secreting tumors shift the host immune response from immunogenic to tolerogenic, which facilitates tumor progression.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shields, Jacqueline D -- Kourtis, Iraklis C -- Tomei, Alice A -- Roberts, Joanna M -- Swartz, Melody A -- New York, N.Y. -- Science. 2010 May 7;328(5979):749-52. doi: 10.1126/science.1185837. Epub 2010 Mar 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Bioengineering, Ecole Polytechnique Federale de Lausanne, 1015 Lausanne, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20339029" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigen-Presenting Cells/immunology ; CD8-Positive T-Lymphocytes/immunology ; Cell Line, Tumor ; Chemokine CCL21/*metabolism ; Cytokines/metabolism ; Disease Progression ; Female ; Immune Tolerance ; Lymph Nodes/immunology ; Lymphoid Tissue/*immunology/pathology ; Melanoma, Experimental/*immunology/*pathology ; Mice ; Mice, Inbred C57BL ; Neoplasm Transplantation ; RNA Interference ; Receptors, CCR7/metabolism ; Signal Transduction ; Stromal Cells/*immunology/pathology ; T-Lymphocytes/immunology ; T-Lymphocytes, Regulatory/immunology ; *Tumor Escape
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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    Molecular basis of alternating access membrane transport by the sodium-hydantoin transporter Mhp1 (2010)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2010-04-24
    Description: The structure of the sodium-benzylhydantoin transport protein Mhp1 from Microbacterium liquefaciens comprises a five-helix inverted repeat, which is widespread among secondary transporters. Here, we report the crystal structure of an inward-facing conformation of Mhp1 at 3.8 angstroms resolution, complementing its previously described structures in outward-facing and occluded states. From analyses of the three structures and molecular dynamics simulations, we propose a mechanism for the transport cycle in Mhp1. Switching from the outward- to the inward-facing state, to effect the inward release of sodium and benzylhydantoin, is primarily achieved by a rigid body movement of transmembrane helices 3, 4, 8, and 9 relative to the rest of the protein. This forms the basis of an alternating access mechanism applicable to many transporters of this emerging superfamily.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2885435/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2885435/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shimamura, Tatsuro -- Weyand, Simone -- Beckstein, Oliver -- Rutherford, Nicholas G -- Hadden, Jonathan M -- Sharples, David -- Sansom, Mark S P -- Iwata, So -- Henderson, Peter J F -- Cameron, Alexander D -- 062164/Z/00/Z/Wellcome Trust/United Kingdom -- 079209/Wellcome Trust/United Kingdom -- BB/C51725/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/G020043/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/G023425/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BBS/B/14418/Biotechnology and Biological Sciences Research Council/United Kingdom -- New York, N.Y. -- Science. 2010 Apr 23;328(5977):470-3. doi: 10.1126/science.1186303.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Molecular Biosciences, Membrane Protein Crystallography Group, Imperial College, London SW7 2AZ, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20413494" target="_blank"〉PubMed〈/a〉
    Keywords: Actinomycetales/*chemistry/metabolism ; Amino Acid Motifs ; Bacterial Proteins/chemistry/metabolism ; Binding Sites ; Biological Transport ; Crystallography, X-Ray ; Hydantoins/chemistry/*metabolism ; Ion Transport ; Membrane Transport Proteins/*chemistry/*metabolism ; Models, Molecular ; Molecular Dynamics Simulation ; Protein Conformation ; Protein Folding ; Protein Structure, Secondary ; Sodium/*metabolism
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    Structural sources of robustness in biochemical reaction networks (2010)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2010-03-13
    Description: In vivo variations in the concentrations of biomolecular species are inevitable. These variations in turn propagate along networks of chemical reactions and modify the concentrations of still other species, which influence biological activity. Because excessive variations in the amounts of certain active species might hamper cell function, regulation systems have evolved that act to maintain concentrations within tight bounds. We identify simple yet subtle structural attributes that impart concentration robustness to any mass-action network possessing them. We thereby describe a large class of robustness-inducing networks that already embraces two quite different biochemical modules for which concentration robustness has been observed experimentally: the Escherichia coli osmoregulation system EnvZ-OmpR and the glyoxylate bypass control system isocitrate dehydrogenase kinase-phosphatase-isocitrate dehydrogenase. The structural attributes identified here might confer robustness far more broadly.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shinar, Guy -- Feinberg, Martin -- 1R01GM086881-01/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2010 Mar 12;327(5971):1389-91. doi: 10.1126/science.1183372.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20223989" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Outer Membrane Proteins/*metabolism ; Bacterial Proteins/*metabolism ; Escherichia coli/*metabolism ; Escherichia coli Proteins/*metabolism ; Glyoxylates/metabolism ; Isocitrate Dehydrogenase/*metabolism ; *Metabolic Networks and Pathways ; Models, Biological ; Models, Chemical ; Multienzyme Complexes/*metabolism ; Osmolar Concentration ; Phosphorylation ; Signal Transduction ; Trans-Activators/*metabolism
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    Neuroscience. Lynx for braking plasticity (2010)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2010-11-27
    Description: 〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3244692/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3244692/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Higley, Michael J -- Strittmatter, Stephen M -- R37 NS033020/NS/NINDS NIH HHS/ -- R37 NS033020-19/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2010 Nov 26;330(6008):1189-90. doi: 10.1126/science.1198983.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cellular Neuroscience, Neurodegeneration and Repair Program, Department of Neurology, Yale University School of Medicine, New Haven, CT 06536, USA. michael.higley@yale.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21109660" target="_blank"〉PubMed〈/a〉
    Keywords: Aging ; Amblyopia/physiopathology/therapy ; Animals ; Chondroitin Sulfate Proteoglycans/physiology ; *Dominance, Ocular ; Membrane Glycoproteins/*genetics/*physiology ; Mice ; Mice, Knockout ; *Neuronal Plasticity ; Neuropeptides/*genetics/*physiology ; Nicotinic Antagonists ; Receptors, Immunologic/physiology ; Receptors, Nicotinic/metabolism ; Sensory Deprivation ; Signal Transduction ; *Vision, Ocular ; Visual Cortex/*physiology ; Visual Pathways/physiology
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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    mTORC1-mediated cell proliferation, but not cell growth, controlled by the 4E-BPs (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-05-29
    Description: The mammalian target of rapamycin complex 1 (mTORC1) integrates mitogen and nutrient signals to control cell proliferation and cell size. Hence, mTORC1 is implicated in a large number of human diseases--including diabetes, obesity, heart disease, and cancer--that are characterized by aberrant cell growth and proliferation. Although eukaryotic translation initiation factor 4E-binding proteins (4E-BPs) are critical mediators of mTORC1 function, their precise contribution to mTORC1 signaling and the mechanisms by which they mediate mTORC1 function have remained unclear. We inhibited the mTORC1 pathway in cells lacking 4E-BPs and analyzed the effects on cell size, cell proliferation, and cell cycle progression. Although the 4E-BPs had no effect on cell size, they inhibited cell proliferation by selectively inhibiting the translation of messenger RNAs that encode proliferation-promoting proteins and proteins involved in cell cycle progression. Thus, control of cell size and cell cycle progression appear to be independent in mammalian cells, whereas in lower eukaryotes, 4E-BPs influence both cell growth and proliferation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2893390/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2893390/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dowling, Ryan J O -- Topisirovic, Ivan -- Alain, Tommy -- Bidinosti, Michael -- Fonseca, Bruno D -- Petroulakis, Emmanuel -- Wang, Xiaoshan -- Larsson, Ola -- Selvaraj, Anand -- Liu, Yi -- Kozma, Sara C -- Thomas, George -- Sonenberg, Nahum -- P50 NS057531/NS/NINDS NIH HHS/ -- P50 NS057531-01A2/NS/NINDS NIH HHS/ -- R01 DK078019/DK/NIDDK NIH HHS/ -- R01 DK73802/DK/NIDDK NIH HHS/ -- U01 CA84292-06/CA/NCI NIH HHS/ -- Canadian Institutes of Health Research/Canada -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2010 May 28;328(5982):1172-6. doi: 10.1126/science.1187532.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Goodman Cancer Research Centre, McGill University, Montreal, Quebec H3A 1A3, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20508131" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Carrier Proteins/genetics/*metabolism ; Cell Cycle ; *Cell Enlargement ; Cell Line ; *Cell Proliferation ; Cell Size ; Cell Survival ; Eukaryotic Initiation Factors/genetics/*metabolism ; Humans ; Mice ; Mice, Knockout ; Multiprotein Complexes ; Phosphoproteins/genetics/*metabolism ; Phosphorylation ; Protein Biosynthesis ; Proteins ; RNA, Messenger/genetics/metabolism ; Ribosomal Protein S6 Kinases/metabolism ; Signal Transduction ; Sirolimus/pharmacology ; TOR Serine-Threonine Kinases ; Transcription Factors/*metabolism
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    Dopaminergic network differences in human impulsivity (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-07-31
    Description: Dopamine (DA) has long been implicated in impulsivity, but the precise mechanisms linking human variability in DA signaling to differences in impulsive traits remain largely unknown. By using a dual-scan positron emission tomography approach in healthy human volunteers with amphetamine and the D2/D3 ligand [18F]fallypride, we found that higher levels of trait impulsivity were predicted by diminished midbrain D2/D3 autoreceptor binding and greater amphetamine-induced DA release in the striatum, which was in turn associated with stimulant craving. Path analysis confirmed that the impact of decreased midbrain D2/D3 autoreceptor availability on trait impulsivity is mediated in part through its effect on stimulated striatal DA release.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3161413/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3161413/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Buckholtz, Joshua W -- Treadway, Michael T -- Cowan, Ronald L -- Woodward, Neil D -- Li, Rui -- Ansari, M Sib -- Baldwin, Ronald M -- Schwartzman, Ashley N -- Shelby, Evan S -- Smith, Clarence E -- Kessler, Robert M -- Zald, David H -- R01 DA019670/DA/NIDA NIH HHS/ -- R01 DA019670-04/DA/NIDA NIH HHS/ -- R01DA019670-04/DA/NIDA NIH HHS/ -- T32 MH018921/MH/NIMH NIH HHS/ -- T32 MH018921-22/MH/NIMH NIH HHS/ -- New York, N.Y. -- Science. 2010 Jul 30;329(5991):532. doi: 10.1126/science.1185778.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Psychology, Vanderbilt University, Nashville, TN 37240, USA. joshua.buckholtz@vanderbilt.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20671181" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; Adult ; Amphetamine-Related Disorders/etiology/metabolism ; Autoreceptors/metabolism ; Benzamides/metabolism ; Corpus Striatum/*metabolism ; Dextroamphetamine/*administration & dosage ; Dopamine/*metabolism ; Female ; Humans ; Impulsive Behavior/*metabolism ; Ligands ; Male ; Positron-Emission Tomography ; Pyrrolidines/metabolism ; Receptors, Dopamine D2/metabolism ; Receptors, Dopamine D3/*metabolism ; Signal Transduction ; Substantia Nigra/metabolism ; Tegmentum Mesencephali/*metabolism ; Ventral Tegmental Area/metabolism ; Young Adult
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    Temperature as a universal resetting cue for mammalian circadian oscillators (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-10-16
    Description: Environmental temperature cycles are a universal entraining cue for all circadian systems at the organismal level with the exception of homeothermic vertebrates. We report here that resistance to temperature entrainment is a property of the suprachiasmatic nucleus (SCN) network and is not a cell-autonomous property of mammalian clocks. This differential sensitivity to temperature allows the SCN to drive circadian rhythms in body temperature, which can then act as a universal cue for the entrainment of cell-autonomous oscillators throughout the body. Pharmacological experiments show that network interactions in the SCN are required for temperature resistance and that the heat shock pathway is integral to temperature resetting and temperature compensation in mammalian cells. These results suggest that the evolutionarily ancient temperature resetting response can be used in homeothermic animals to enhance internal circadian synchronization.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3625727/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3625727/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Buhr, Ethan D -- Yoo, Seung-Hee -- Takahashi, Joseph S -- P50 MH074924/MH/NIMH NIH HHS/ -- P50 MH074924-01/MH/NIMH NIH HHS/ -- P50 MH074924-02/MH/NIMH NIH HHS/ -- P50 MH074924-03/MH/NIMH NIH HHS/ -- P50 MH074924-04/MH/NIMH NIH HHS/ -- P50 MH074924-05/MH/NIMH NIH HHS/ -- T32 AG 20418/AG/NIA NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2010 Oct 15;330(6002):379-85. doi: 10.1126/science.1195262.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurobiology and Physiology, Northwestern University, Evanston, IL 60208-3520, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20947768" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arginine Vasopressin/metabolism ; Benzhydryl Compounds/pharmacology ; Biological Clocks/*physiology ; *Body Temperature ; Body Temperature Regulation ; Calcium Channels, L-Type/physiology ; Cell Communication ; Circadian Rhythm/*physiology ; Cues ; DNA-Binding Proteins/metabolism ; Heat-Shock Response ; Lung/physiology ; Mice ; Pituitary Gland/physiology ; Pyrrolidinones/pharmacology ; Signal Transduction ; Suprachiasmatic Nucleus/cytology/*physiology ; Temperature ; Tissue Culture Techniques ; Transcription Factors/metabolism ; Transcription, Genetic/drug effects ; Vasoactive Intestinal Peptide/metabolism
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    Genetic evidence for high-altitude adaptation in Tibet (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-05-15
    Description: Tibetans have lived at very high altitudes for thousands of years, and they have a distinctive suite of physiological traits that enable them to tolerate environmental hypoxia. These phenotypes are clearly the result of adaptation to this environment, but their genetic basis remains unknown. We report genome-wide scans that reveal positive selection in several regions that contain genes whose products are likely involved in high-altitude adaptation. Positively selected haplotypes of EGLN1 and PPARA were significantly associated with the decreased hemoglobin phenotype that is unique to this highland population. Identification of these genes provides support for previously hypothesized mechanisms of high-altitude adaptation and illuminates the complexity of hypoxia-response pathways in humans.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Simonson, Tatum S -- Yang, Yingzhong -- Huff, Chad D -- Yun, Haixia -- Qin, Ga -- Witherspoon, David J -- Bai, Zhenzhong -- Lorenzo, Felipe R -- Xing, Jinchuan -- Jorde, Lynn B -- Prchal, Josef T -- Ge, RiLi -- 1P01CA108671-01A2/CA/NCI NIH HHS/ -- DK069513/DK/NIDDK NIH HHS/ -- GM059290/GM/NIGMS NIH HHS/ -- HL50077/HL/NHLBI NIH HHS/ -- R00 HG005846/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2010 Jul 2;329(5987):72-5. doi: 10.1126/science.1189406. Epub 2010 May 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Eccles Institute of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20466884" target="_blank"〉PubMed〈/a〉
    Keywords: *Acclimatization ; *Altitude ; Asian Continental Ancestry Group/genetics ; Ethnic Groups/genetics ; Female ; Genetic Association Studies ; Genetic Variation ; Genome, Human ; Haplotypes ; Hemoglobins/*analysis ; Humans ; Hypoxia-Inducible Factor 1/metabolism ; Hypoxia-Inducible Factor-Proline Dioxygenases ; Linear Models ; Male ; *Oxygen ; PPAR alpha/*genetics ; Phenotype ; Polymorphism, Single Nucleotide ; Procollagen-Proline Dioxygenase/*genetics ; *Selection, Genetic ; Signal Transduction ; Tibet
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    Signaling kinase AMPK activates stress-promoted transcription via histone H2B phosphorylation (2010)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2010-07-22
    Description: The mammalian adenosine monophosphate-activated protein kinase (AMPK) is a serine-threonine kinase protein complex that is a central regulator of cellular energy homeostasis. However, the mechanisms by which AMPK mediates cellular responses to metabolic stress remain unclear. We found that AMPK activates transcription through direct association with chromatin and phosphorylation of histone H2B at serine 36. AMPK recruitment and H2B Ser36 phosphorylation colocalized within genes activated by AMPK-dependent pathways, both in promoters and in transcribed regions. Ectopic expression of H2B in which Ser36 was substituted by alanine reduced transcription and RNA polymerase II association to AMPK-dependent genes, and lowered cell survival in response to stress. Our results place AMPK-dependent H2B Ser36 phosphorylation in a direct transcriptional and chromatin regulatory pathway leading to cellular adaptation to stress.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3922052/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3922052/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bungard, David -- Fuerth, Benjamin J -- Zeng, Ping-Yao -- Faubert, Brandon -- Maas, Nancy L -- Viollet, Benoit -- Carling, David -- Thompson, Craig B -- Jones, Russell G -- Berger, Shelley L -- CA078831/CA/NCI NIH HHS/ -- CA09171/CA/NCI NIH HHS/ -- CA105463/CA/NCI NIH HHS/ -- MC_U120027537/Medical Research Council/United Kingdom -- MOP-93799/Canadian Institutes of Health Research/Canada -- P01 AG031862/AG/NIA NIH HHS/ -- P01 CA104838/CA/NCI NIH HHS/ -- R01 CA078831/CA/NCI NIH HHS/ -- R01 CA105463/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2010 Sep 3;329(5996):1201-5. doi: 10.1126/science.1191241. Epub 2010 Jul 15.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cellular and Developmental Biology, University of Pennsylvania Medical School, Philadelphia, PA 19104, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20647423" target="_blank"〉PubMed〈/a〉
    Keywords: AMP-Activated Protein Kinases/chemistry/*metabolism ; Adaptation, Physiological ; Amino Acid Motifs ; Amino Acid Substitution ; Animals ; Cell Line ; Cell Line, Tumor ; Cell Survival ; Cells, Cultured ; Chromatin/*metabolism ; Chromatin Immunoprecipitation ; Enzyme Activation ; Gene Expression Regulation ; Histones/chemistry/*metabolism ; Humans ; Mice ; Phosphorylation ; Promoter Regions, Genetic ; Protein-Serine-Threonine Kinases/genetics/metabolism ; Serine/metabolism ; Signal Transduction ; *Stress, Physiological ; *Transcription, Genetic ; Tumor Suppressor Protein p53/metabolism
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    Photorhabdus luminescens toxins ADP-ribosylate actin and RhoA to force actin clustering (2010)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2010-02-27
    Description: The bacterium Photorhabdus luminescens is mutualistically associated with entomopathogenetic nematodes. These nematodes invade insect larvae and release the bacteria from their intestine, which kills the insects through the action of toxin complexes. We elucidated the mode of action of two of these insecticidal toxins from P. luminescens. We identified the biologically active components TccC3 and TccC5 as adenosine diphosphate (ADP)-ribosyltransferases, which modify unusual amino acids. TccC3 ADP-ribosylated threonine-148 of actin, resulting in actin polymerization. TccC5 ADP-ribosylated Rho guanosine triphosphatase proteins at glutamine-61 and glutamine-63, inducing their activation. The concerted action of both toxins inhibited phagocytosis of target insect cells and induced extensive intracellular polymerization and clustering of actin. Several human pathogenic bacteria produce related toxins.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lang, Alexander E -- Schmidt, Gudula -- Schlosser, Andreas -- Hey, Timothy D -- Larrinua, Ignacio M -- Sheets, Joel J -- Mannherz, Hans G -- Aktories, Klaus -- New York, N.Y. -- Science. 2010 Feb 26;327(5969):1139-42. doi: 10.1126/science.1184557.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut fur Experimentelle und Klinische Pharmakologie und Toxikologie, Albert-Ludwigs-Universitat Freiburg, 79104 Freiburg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20185726" target="_blank"〉PubMed〈/a〉
    Keywords: ADP Ribose Transferases/chemistry/*metabolism ; Actins/chemistry/*metabolism ; Adenosine Diphosphate Ribose/*metabolism ; Animals ; Bacterial Toxins/chemistry/*metabolism/pharmacology ; Cell Line ; Glutamine/metabolism ; HeLa Cells ; Hemocytes/immunology ; Humans ; Moths ; Phagocytosis/drug effects ; *Photorhabdus ; Signal Transduction ; Stress Fibers/metabolism ; Threonine/metabolism ; Thymosin/metabolism/pharmacology ; rhoA GTP-Binding Protein/*metabolism
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    Down-regulation of a host microRNA by a Herpesvirus saimiri noncoding RNA (2010)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2010-06-19
    Description: T cells transformed by Herpesvirus saimiri express seven viral U-rich noncoding RNAs of unknown function called HSURs. We noted that conserved sequences in HSURs 1 and 2 constitute potential binding sites for three host-cell microRNAs (miRNAs). Coimmunoprecipitation experiments confirmed that HSURs 1 and 2 interact with the predicted miRNAs in virally transformed T cells. The abundance of one of these miRNAs, miR-27, is dramatically lowered in transformed cells, with consequent effects on the expression of miR-27 target genes. Transient knockdown and ectopic expression of HSUR 1 demonstrate that it directs degradation of mature miR-27 in a sequence-specific and binding-dependent manner. This viral strategy illustrates use of a ncRNA to manipulate host-cell gene expression via the miRNA pathway.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3075239/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3075239/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cazalla, Demian -- Yario, Therese -- Steitz, Joan A -- CA16038/CA/NCI NIH HHS/ -- P01 CA016038/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2010 Jun 18;328(5985):1563-6. doi: 10.1126/science.1187197.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Yale University School of Medicine, Boyer Center for Molecular Medicine, 295 Congress Avenue, New Haven, CT 06536, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20558719" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Pairing ; Binding Sites ; Callithrix ; Cell Line, Transformed ; Cell Transformation, Viral ; Conserved Sequence ; *Down-Regulation ; Herpesvirus 2, Saimiriine/*genetics/metabolism ; Humans ; Jurkat Cells ; MicroRNAs/chemistry/genetics/*metabolism ; *RNA Stability ; RNA, Untranslated/chemistry/*metabolism ; RNA, Viral/chemistry/*metabolism ; T-Lymphocytes
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    Immunology. A guardian of T cell fate (2010)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2010-07-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Di Santo, James P -- R01 AR060723/AR/NIAMS NIH HHS/ -- New York, N.Y. -- Science. 2010 Jul 2;329(5987):44-5. doi: 10.1126/science.1191664.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Innate Immunity Unit, Institut Pasteur, Paris F-75724, France. james.di-santo@pasteur.fr〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20595605" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Lineage ; Cells, Cultured ; Cytokines/metabolism ; Gene Deletion ; Gene Expression Regulation ; Interleukin-7/physiology ; Killer Cells, Natural/cytology/immunology/*physiology ; *Lymphopoiesis/genetics ; Mice ; Models, Biological ; Precursor Cells, T-Lymphoid/cytology/physiology ; Repressor Proteins/*genetics/*metabolism ; Signal Transduction ; T-Lymphocytes/cytology/immunology/*physiology ; Tumor Suppressor Proteins/*genetics/*metabolism
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    Functional modules and structural basis of conformational coupling in mitochondrial complex I (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-07-03
    Description: Proton-pumping respiratory complex I is one of the largest and most complicated membrane protein complexes. Its function is critical for efficient energy supply in aerobic cells, and malfunctions are implicated in many neurodegenerative disorders. Here, we report an x-ray crystallographic analysis of mitochondrial complex I. The positions of all iron-sulfur clusters relative to the membrane arm were determined in the complete enzyme complex. The ubiquinone reduction site resides close to 30 angstroms above the membrane domain. The arrangement of functional modules suggests conformational coupling of redox chemistry with proton pumping and essentially excludes direct mechanisms. We suggest that a approximately 60-angstrom-long helical transmission element is critical for transducing conformational energy to proton-pumping elements in the distal module of the membrane arm.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hunte, Carola -- Zickermann, Volker -- Brandt, Ulrich -- New York, N.Y. -- Science. 2010 Jul 23;329(5990):448-51. doi: 10.1126/science.1191046. Epub 2010 Jul 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Biochemistry and Molecular Biology, Centre for Biological Signalling Studies (BIOSS), University of Freiburg, D-79104 Freiburg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20595580" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Binding Sites ; Crystallography, X-Ray ; Electron Transport Complex I/*chemistry/*metabolism ; Fungal Proteins/chemistry/metabolism ; Iron/chemistry ; Mitochondria/enzymology ; Mitochondrial Proteins/*chemistry/*metabolism ; Models, Molecular ; Molecular Sequence Data ; Oxidation-Reduction ; Protein Conformation ; Protein Structure, Quaternary ; Protein Structure, Tertiary ; Protein Subunits/chemistry/metabolism ; Protons ; Sulfur/chemistry ; Ubiquinone/chemistry/metabolism ; Yarrowia/*enzymology
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    Autophagy and metabolism (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-12-04
    Description: Autophagy is a process of self-cannibalization. Cells capture their own cytoplasm and organelles and consume them in lysosomes. The resulting breakdown products are inputs to cellular metabolism, through which they are used to generate energy and to build new proteins and membranes. Autophagy preserves the health of cells and tissues by replacing outdated and damaged cellular components with fresh ones. In starvation, it provides an internal source of nutrients for energy generation and, thus, survival. A powerful promoter of metabolic homeostasis at both the cellular and whole-animal level, autophagy prevents degenerative diseases. It does have a downside, however--cancer cells exploit it to survive in nutrient-poor tumors.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3010857/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3010857/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rabinowitz, Joshua D -- White, Eileen -- R01 CA130893/CA/NCI NIH HHS/ -- R01 CA130893-03/CA/NCI NIH HHS/ -- R37 CA053370/CA/NCI NIH HHS/ -- R37 CA053370-19/CA/NCI NIH HHS/ -- RC1 CA147961/CA/NCI NIH HHS/ -- RC1 CA147961-02/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2010 Dec 3;330(6009):1344-8. doi: 10.1126/science.1193497.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry and Lewis-Sigler Institute for Integrative Genomics, 241 Carl Icahn Laboratory, Washington Road, Princeton University, Princeton, NJ 08544, USA. joshr@genomics.princeton.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21127245" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Autophagy ; Cell Survival ; Disease ; Energy Metabolism ; Homeostasis ; Humans ; *Metabolism ; Neoplasms/metabolism/pathology ; Phagosomes/metabolism ; Proteins/metabolism ; Signal Transduction ; Starvation ; TOR Serine-Threonine Kinases/metabolism
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    Regulation of oligodendrocyte differentiation and myelination (2010)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2010-11-06
    Description: Despite the importance of myelin for the rapid conduction of action potentials, the molecular bases of oligodendrocyte differentiation and central nervous system (CNS) myelination are still incompletely understood. Recent results have greatly advanced this understanding, identifying new transcriptional regulators of myelin gene expression, elucidating vital roles for microRNAs in controlling myelination, and clarifying the extracellular signaling mechanisms that orchestrate the development of myelin. Studies have also demonstrated an unexpected level of plasticity of myelin in the adult CNS. These recent advances provide new insight into how remyelination may be stimulated in demyelinating disorders such as multiple sclerosis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Emery, Ben -- New York, N.Y. -- Science. 2010 Nov 5;330(6005):779-82. doi: 10.1126/science.1190927.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre for Neuroscience and Florey Neuroscience Institutes, Level 2, Alan Gilbert Building, The University of Melbourne, 161 Barry Street, Carlton South, Victoria 3053, Australia. emeryb@unimelb.edu.au〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21051629" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Axons/physiology ; Cell Differentiation ; Central Nervous System/cytology/*physiology ; Chromatin Assembly and Disassembly ; Demyelinating Diseases/physiopathology/therapy ; Gene Expression Regulation ; Humans ; MicroRNAs/metabolism ; Myelin Sheath/*physiology ; Oligodendroglia/*cytology/*physiology ; Signal Transduction ; Transcription, Genetic
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    Dnmt3a-dependent nonpromoter DNA methylation facilitates transcription of neurogenic genes (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-07-24
    Description: DNA methylation at proximal promoters facilitates lineage restriction by silencing cell type-specific genes. However, euchromatic DNA methylation frequently occurs in regions outside promoters. The functions of such nonproximal promoter DNA methylation are unclear. Here we show that the de novo DNA methyltransferase Dnmt3a is expressed in postnatal neural stem cells (NSCs) and is required for neurogenesis. Genome-wide analysis of postnatal NSCs indicates that Dnmt3a occupies and methylates intergenic regions and gene bodies flanking proximal promoters of a large cohort of transcriptionally permissive genes, many of which encode regulators of neurogenesis. Surprisingly, Dnmt3a-dependent nonproximal promoter methylation promotes expression of these neurogenic genes by functionally antagonizing Polycomb repression. Thus, nonpromoter DNA methylation by Dnmt3a may be used for maintaining active chromatin states of genes critical for development.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3539760/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3539760/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wu, Hao -- Coskun, Volkan -- Tao, Jifang -- Xie, Wei -- Ge, Weihong -- Yoshikawa, Kazuaki -- Li, En -- Zhang, Yi -- Sun, Yi Eve -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2010 Jul 23;329(5990):444-8. doi: 10.1126/science.1190485.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Medical Pharmacology, University of California Los Angeles (UCLA), Los Angeles, CA 90095, USA. haowu7@gmail.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20651149" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Binding Sites ; Brain/cytology/growth & development/*metabolism ; Chromatin Immunoprecipitation ; DNA (Cytosine-5-)-Methyltransferase/*metabolism ; *DNA Methylation ; DNA, Intergenic ; Gene Expression Profiling ; *Gene Expression Regulation, Developmental ; Genome ; Histones/genetics/metabolism ; Mice ; Mice, Knockout ; Nervous System/growth & development ; Neurogenesis/*genetics ; Neuroglia/cytology ; Neurons/*cytology/metabolism ; Polycomb-Group Proteins ; Promoter Regions, Genetic ; Repressor Proteins/metabolism ; Stem Cells/*metabolism ; *Transcription, Genetic
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    Siah regulation of Pard3A controls neuronal cell adhesion during germinal zone exit (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-11-27
    Description: The brain's circuitry is established by directed migration and synaptogenesis of neurons during development. Although neurons mature and migrate in specific patterns, little is known about how neurons exit their germinal zone niche. We found that cerebellar granule neuron germinal zone exit is regulated by proteasomal degradation of Pard3A by the Seven in Absentia homolog (Siah) E3 ubiquitin ligase. Pard3A gain of function and Siah loss of function induce precocious radial migration. Time-lapse imaging using a probe to measure neuronal cell contact reveals that Pard3A promotes adhesive interactions needed for germinal zone exit by recruiting the epithelial tight junction adhesion molecule C to the neuronal cell surface. Our findings define a Siah-Pard3A signaling pathway that controls adhesion-dependent exit of neuronal progenitors or immature neurons from a germinal zone niche.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3065828/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3065828/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Famulski, Jakub K -- Trivedi, Niraj -- Howell, Danielle -- Yang, Yuan -- Tong, Yiai -- Gilbertson, Richard -- Solecki, David J -- P01 CA096832/CA/NCI NIH HHS/ -- P01 CA096832-07/CA/NCI NIH HHS/ -- P30 CA021765/CA/NCI NIH HHS/ -- P30 CA021765-33/CA/NCI NIH HHS/ -- R01 CA129541/CA/NCI NIH HHS/ -- R01 CA129541-04/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2010 Dec 24;330(6012):1834-8. doi: 10.1126/science.1198480. Epub 2010 Nov 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Developmental Neurobiology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21109632" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Cell Adhesion ; Cell Adhesion Molecules/chemistry/*metabolism ; Cell Line ; *Cell Movement ; Cell Polarity ; Cerebellum/*cytology/embryology/*metabolism ; Dogs ; Humans ; Immunoglobulins/chemistry/metabolism ; Mice ; Morphogenesis ; Neurons/cytology/*physiology ; Protein Binding ; Protein Interaction Domains and Motifs ; Protein Structure, Tertiary ; RNA Interference ; Signal Transduction ; Stem Cells/physiology ; Transfection ; Ubiquitin-Protein Ligases/genetics/*metabolism ; Ubiquitination
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    Self-assembly of filopodia-like structures on supported lipid bilayers (2010)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2010-09-11
    Description: Filopodia are finger-like protrusive structures, containing actin bundles. By incubating frog egg extracts with supported lipid bilayers containing phosphatidylinositol 4,5 bisphosphate, we have reconstituted the assembly of filopodia-like structures (FLSs). The actin assembles into parallel bundles, and known filopodial components localize to the tip and shaft. The filopodia tip complexes self-organize--they are not templated by preexisting membrane microdomains. The F-BAR domain protein toca-1 recruits N-WASP, followed by the Arp2/3 complex and actin. Elongation proteins, Diaphanous-related formin, VASP, and fascin are recruited subsequently. Although the Arp2/3 complex is required for FLS initiation, it is not essential for elongation, which involves formins. We propose that filopodia form via clustering of Arp2/3 complex activators, self-assembly of filopodial tip complexes on the membrane, and outgrowth of actin bundles.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2982780/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2982780/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, Kwonmoo -- Gallop, Jennifer L -- Rambani, Komal -- Kirschner, Marc W -- GM26875/GM/NIGMS NIH HHS/ -- R01 GM026875/GM/NIGMS NIH HHS/ -- R01 GM026875-34/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2010 Sep 10;329(5997):1341-5. doi: 10.1126/science.1191710.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20829485" target="_blank"〉PubMed〈/a〉
    Keywords: Actin Cytoskeleton/ultrastructure ; Actin-Related Protein 2-3 Complex/metabolism ; Actins/*metabolism ; Animals ; Carrier Proteins/metabolism ; Cell Adhesion Molecules/metabolism ; Cell Membrane/metabolism ; Humans ; Kinetics ; *Lipid Bilayers ; Membrane Microdomains ; Mice ; Microfilament Proteins/metabolism ; Microtubule-Associated Proteins/metabolism ; NADPH Dehydrogenase/metabolism ; Phosphatidylinositol Phosphates/metabolism ; Phosphoproteins/metabolism ; Pseudopodia/*metabolism/*ultrastructure ; Recombinant Fusion Proteins/metabolism ; Signal Transduction ; Wiskott-Aldrich Syndrome Protein, Neuronal/metabolism ; Xenopus ; Xenopus Proteins/metabolism
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    Shaping development of autophagy inhibitors with the structure of the lipid kinase Vps34 (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-03-27
    Description: Phosphoinositide 3-kinases (PI3Ks) are lipid kinases with diverse roles in health and disease. The primordial PI3K, Vps34, is present in all eukaryotes and has essential roles in autophagy, membrane trafficking, and cell signaling. We solved the crystal structure of Vps34 at 2.9 angstrom resolution, which revealed a constricted adenine-binding pocket, suggesting the reason that specific inhibitors of this class of PI3K have proven elusive. Both the phosphoinositide-binding loop and the carboxyl-terminal helix of Vps34 mediate catalysis on membranes and suppress futile adenosine triphosphatase cycles. Vps34 appears to alternate between a closed cytosolic form and an open form on the membrane. Structures of Vps34 complexes with a series of inhibitors reveal the reason that an autophagy inhibitor preferentially inhibits Vps34 and underpin the development of new potent and specific Vps34 inhibitors.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2860105/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2860105/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Miller, Simon -- Tavshanjian, Brandon -- Oleksy, Arkadiusz -- Perisic, Olga -- Houseman, Benjamin T -- Shokat, Kevan M -- Williams, Roger L -- MC_U105184308/Medical Research Council/United Kingdom -- U.1051.03.014(78824)/Medical Research Council/United Kingdom -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2010 Mar 26;327(5973):1638-42. doi: 10.1126/science.1184429.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20339072" target="_blank"〉PubMed〈/a〉
    Keywords: Adenine/*analogs & derivatives/metabolism/pharmacology ; Adenosine Triphosphatases/metabolism ; Animals ; Autophagy/*drug effects ; Binding Sites ; Catalysis ; Catalytic Domain ; Cell Membrane/metabolism ; Crystallography, X-Ray ; Drosophila Proteins/*antagonists & inhibitors/*chemistry/genetics/metabolism ; Drosophila melanogaster ; Enzyme Inhibitors/chemical synthesis/chemistry/*metabolism/pharmacology ; Furans/chemistry/metabolism/pharmacology ; Humans ; Hydrophobic and Hydrophilic Interactions ; Models, Molecular ; Phosphatidylinositol 3-Kinases/*antagonists & ; inhibitors/*chemistry/genetics/metabolism ; Phosphatidylinositols/metabolism ; Point Mutation ; Protein Conformation ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Pyridines/chemistry/metabolism/pharmacology ; Pyrimidines/chemistry/metabolism/pharmacology
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    Structural biology. The Tao of chloride transporter structure (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-10-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mindell, Joseph A -- New York, N.Y. -- Science. 2010 Oct 29;330(6004):601-2. doi: 10.1126/science.1198306.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Membrane Transport Biophysics Section, Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. mindellj@ninds.nih.gov〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21030639" target="_blank"〉PubMed〈/a〉
    Keywords: Algal Proteins/*chemistry/metabolism ; Antiporters/*chemistry/metabolism ; Binding Sites ; Chloride Channels/*chemistry/metabolism ; Chlorides/*metabolism ; Crystallization ; Crystallography, X-Ray ; Cytoplasm/chemistry ; Eukaryota/*chemistry ; Glutamic Acid/metabolism ; Ion Channel Gating ; Ion Transport ; Models, Molecular ; Protein Structure, Tertiary ; Protons
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    Phosphatidic acid is a pH biosensor that links membrane biogenesis to metabolism (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-08-28
    Description: Recognition of lipids by proteins is important for their targeting and activation in many signaling pathways, but the mechanisms that regulate such interactions are largely unknown. Here, we found that binding of proteins to the ubiquitous signaling lipid phosphatidic acid (PA) depended on intracellular pH and the protonation state of its phosphate headgroup. In yeast, a rapid decrease in intracellular pH in response to glucose starvation regulated binding of PA to a transcription factor, Opi1, that coordinately repressed phospholipid metabolic genes. This enabled coupling of membrane biogenesis to nutrient availability.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Young, Barry P -- Shin, John J H -- Orij, Rick -- Chao, Jesse T -- Li, Shu Chen -- Guan, Xue Li -- Khong, Anthony -- Jan, Eric -- Wenk, Markus R -- Prinz, William A -- Smits, Gertien J -- Loewen, Christopher J R -- Canadian Institutes of Health Research/Canada -- Intramural NIH HHS/ -- New York, N.Y. -- Science. 2010 Aug 27;329(5995):1085-8. doi: 10.1126/science.1191026.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, British Columbia, V6T 1Z3, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20798321" target="_blank"〉PubMed〈/a〉
    Keywords: Active Transport, Cell Nucleus ; Cation Transport Proteins/genetics/metabolism ; Cell Membrane/*metabolism ; Cell Nucleus/metabolism ; Endoplasmic Reticulum/metabolism ; Gene Expression Regulation, Fungal ; Genes, Fungal ; Glucose/metabolism ; Hydrogen-Ion Concentration ; Inositol/genetics/metabolism ; Liposomes/metabolism ; Mutation ; Phosphatidic Acids/*metabolism ; Protein Binding ; Protein Phosphatase 1/genetics/metabolism ; Proton-Translocating ATPases/genetics/metabolism ; Recombinant Fusion Proteins/metabolism ; Repressor Proteins/genetics/*metabolism ; Saccharomyces cerevisiae/genetics/growth & development/*metabolism ; Saccharomyces cerevisiae Proteins/genetics/*metabolism ; Signal Transduction ; Transcription, Genetic ; Vacuolar Proton-Translocating ATPases/genetics/metabolism
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    Oscillating gene expression determines competence for periodic Arabidopsis root branching (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-09-11
    Description: Plants and animals produce modular developmental units in a periodic fashion. In plants, lateral roots form as repeating units along the root primary axis; however, the developmental mechanism regulating this process is unknown. We found that cyclic expression pulses of a reporter gene mark the position of future lateral roots by establishing prebranch sites and that prebranch site production and root bending are periodic. Microarray and promoter-luciferase studies revealed two sets of genes oscillating in opposite phases at the root tip. Genetic studies show that some oscillating transcriptional regulators are required for periodicity in one or both developmental processes. This molecular mechanism has characteristics that resemble molecular clock-driven activities in animal species.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2976612/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2976612/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Moreno-Risueno, Miguel A -- Van Norman, Jaimie M -- Moreno, Antonio -- Zhang, Jingyuan -- Ahnert, Sebastian E -- Benfey, Philip N -- R01 GM043778/GM/NIGMS NIH HHS/ -- R01 GM043778-19/GM/NIGMS NIH HHS/ -- R01 GM043778-20/GM/NIGMS NIH HHS/ -- R01 GM043778-21/GM/NIGMS NIH HHS/ -- R01-GM043778/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2010 Sep 10;329(5997):1306-11. doi: 10.1126/science.1191937.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology and Institute for Genome Sciences and Policy Center for Systems Biology, Duke University, Durham, NC 27708, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20829477" target="_blank"〉PubMed〈/a〉
    Keywords: Arabidopsis/cytology/*genetics/*growth & development/metabolism ; Arabidopsis Proteins/genetics/metabolism ; Gene Expression Profiling ; *Gene Expression Regulation, Plant ; Gene Regulatory Networks ; Genes, Plant ; Genes, Reporter ; Gravitation ; Indoleacetic Acids/metabolism/pharmacology ; Meristem/*genetics/*growth & development/metabolism ; Oligonucleotide Array Sequence Analysis ; Phthalimides/pharmacology ; Plant Roots/cytology/genetics/*growth & development ; Promoter Regions, Genetic ; Signal Transduction ; Temperature ; Time Factors ; Transcription Factors/genetics/metabolism ; Transcription, Genetic
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    Regulation of adaptive immunity by the innate immune system (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-01-16
    Description: Twenty years after the proposal that pattern recognition receptors detect invasion by microbial pathogens, the field of immunology has witnessed several discoveries that have elucidated receptors and signaling pathways of microbial recognition systems and how they control the generation of T and B lymphocyte-mediated immune responses. However, there are still many fundamental questions that remain poorly understood, even though sometimes the answers are assumed to be known. Here, we discuss some of these questions, including the mechanisms by which pathogen-specific innate immune recognition activates antigen-specific adaptive immune responses and the roles of different types of innate immune recognition in host defense from infection and injury.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3645875/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3645875/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Iwasaki, Akiko -- Medzhitov, Ruslan -- R01 AI054359/AI/NIAID NIH HHS/ -- R01 AI055502/AI/NIAID NIH HHS/ -- R01 AI062428/AI/NIAID NIH HHS/ -- R01 AI064705/AI/NIAID NIH HHS/ -- R01 AI081884/AI/NIAID NIH HHS/ -- R01AI054359/AI/NIAID NIH HHS/ -- R01AI055502/AI/NIAID NIH HHS/ -- R01AI064705/AI/NIAID NIH HHS/ -- R01DK071754/DK/NIDDK NIH HHS/ -- R21AI083242/AI/NIAID NIH HHS/ -- R37AI046688/AI/NIAID NIH HHS/ -- U54 AI057160/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2010 Jan 15;327(5963):291-5. doi: 10.1126/science.1183021.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunobiology, School of Medicine, Yale University, New Haven, CT 06520, USA. akiko.iwasaki@yale.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20075244" target="_blank"〉PubMed〈/a〉
    Keywords: *Adaptive Immunity ; Animals ; Antigen-Presenting Cells/immunology ; Bacterial Infections/*immunology ; Humans ; *Immunity, Innate ; Ligands ; Receptors, Pattern Recognition/immunology/*metabolism ; Signal Transduction ; Toll-Like Receptors/immunology/metabolism ; Virus Diseases/*immunology
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    Conformational spread as a mechanism for cooperativity in the bacterial flagellar switch (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-02-06
    Description: The bacterial flagellar switch that controls the direction of flagellar rotation during chemotaxis has a highly cooperative response. This has previously been understood in terms of the classic two-state, concerted model of allosteric regulation. Here, we used high-resolution optical microscopy to observe switching of single motors and uncover the stochastic multistate nature of the switch. Our observations are in detailed quantitative agreement with a recent general model of allosteric cooperativity that exhibits conformational spread--the stochastic growth and shrinkage of domains of adjacent subunits sharing a particular conformational state. We expect that conformational spread will be important in explaining cooperativity in other large signaling complexes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bai, Fan -- Branch, Richard W -- Nicolau, Dan V Jr -- Pilizota, Teuta -- Steel, Bradley C -- Maini, Philip K -- Berry, Richard M -- BB/E00458X/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/H01991X/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- New York, N.Y. -- Science. 2010 Feb 5;327(5966):685-9. doi: 10.1126/science.1182105.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Clarendon Laboratory, Department of Physics, University of Oxford, Parks Road, Oxford OX1 3PU, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20133571" target="_blank"〉PubMed〈/a〉
    Keywords: Allosteric Regulation ; Bacterial Proteins/chemistry/metabolism ; Binding Sites ; Escherichia coli/metabolism ; Escherichia coli Proteins/*chemistry/*metabolism ; Flagella/*chemistry ; Membrane Proteins/chemistry/metabolism ; Models, Biological ; Models, Molecular ; Molecular Motor Proteins/*chemistry/*metabolism ; Monte Carlo Method ; Protein Binding ; Protein Conformation ; Protein Subunits/*chemistry/*metabolism ; Signal Transduction ; Thermodynamics
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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    Lynx1, a cholinergic brake, limits plasticity in adult visual cortex (2010)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2010-11-13
    Description: Experience-dependent brain plasticity typically declines after an early critical period during which circuits are established. Loss of plasticity with closure of the critical period limits improvement of function in adulthood, but the mechanisms that change the brain's plasticity remain poorly understood. Here, we identified an increase in expression of Lynx1 protein in mice that prevented plasticity in the primary visual cortex late in life. Removal of this molecular brake enhanced nicotinic acetylcholine receptor signaling. Lynx1 expression thus maintains stability of mature cortical networks in the presence of cholinergic innervation. The results suggest that modulating the balance between excitatory and inhibitory circuits reactivates visual plasticity and may present a therapeutic target.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3387538/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3387538/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Morishita, Hirofumi -- Miwa, Julie M -- Heintz, Nathaniel -- Hensch, Takao K -- 1 DP1 OD003699-01/OD/NIH HHS/ -- DA-17279/DA/NIDA NIH HHS/ -- DP1 OD003699/OD/NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2010 Nov 26;330(6008):1238-40. doi: 10.1126/science.1195320. Epub 2010 Nov 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉FM Kirby Neurobiology Center, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21071629" target="_blank"〉PubMed〈/a〉
    Keywords: Aging ; Amblyopia/metabolism ; Animals ; Cholinesterase Inhibitors/pharmacology ; Dominance, Ocular ; Evoked Potentials, Visual ; Mecamylamine/pharmacology ; Membrane Glycoproteins/*genetics/metabolism/*physiology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Neural Inhibition ; *Neuronal Plasticity ; Neuropeptides/*genetics/metabolism/*physiology ; Nicotinic Antagonists/pharmacology ; Physostigmine/pharmacology ; Receptors, Nicotinic/genetics/*metabolism ; Sensory Deprivation ; Signal Transduction ; *Vision, Ocular ; Visual Cortex/*physiology ; Visual Pathways
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    Structure of the human BK channel Ca2+-activation apparatus at 3.0 A resolution (2010)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2010-05-29
    Description: High-conductance voltage- and Ca2+-activated K+ (BK) channels encode negative feedback regulation of membrane voltage and Ca2+ signaling, playing a central role in numerous physiological processes. We determined the x-ray structure of the human BK Ca2+ gating apparatus at a resolution of 3.0 angstroms and deduced its tetrameric assembly by solving a 6 angstrom resolution structure of a Na+-activated homolog. Two tandem C-terminal regulator of K+ conductance (RCK) domains from each of four channel subunits form a 350-kilodalton gating ring at the intracellular membrane surface. A sequence of aspartic amino acids that is known as the Ca2+ bowl, and is located within the second of the tandem RCK domains, creates four Ca2+ binding sites on the outer perimeter of the gating ring at the "assembly interface" between RCK domains. Functionally important mutations cluster near the Ca2+ bowl, near the "flexible interface" between RCK domains, and on the surface of the gating ring that faces the voltage sensors. The structure suggests that the Ca2+ gating ring, in addition to regulating the pore directly, may also modulate the voltage sensor.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3022345/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3022345/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yuan, Peng -- Leonetti, Manuel D -- Pico, Alexander R -- Hsiung, Yichun -- MacKinnon, Roderick -- P30 EB009998/EB/NIBIB NIH HHS/ -- R01 GM043949/GM/NIGMS NIH HHS/ -- R01 GM043949-20/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2010 Jul 9;329(5988):182-6. doi: 10.1126/science.1190414. Epub 2010 May 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Molecular Neurobiology and Biophysics, Rockefeller University, Howard Hughes Medical Institute, 1230 York Avenue, New York, NY 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20508092" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Binding Sites ; Calcium/*metabolism ; Crystallography, X-Ray ; Humans ; *Ion Channel Gating ; Large-Conductance Calcium-Activated Potassium Channel alpha ; Subunits/*chemistry/genetics/*metabolism ; Ligands ; Models, Molecular ; Molecular Sequence Data ; Mutant Proteins/chemistry/metabolism ; Patch-Clamp Techniques ; Protein Conformation ; Protein Folding ; Protein Structure, Quaternary ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Protein Subunits/chemistry ; Sodium/metabolism
    Print ISSN: 0036-8075
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    Structure of a eukaryotic CLC transporter defines an intermediate state in the transport cycle (2010)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2010-10-12
    Description: CLC proteins transport chloride (Cl(-)) ions across cell membranes to control the electrical potential of muscle cells, transfer electrolytes across epithelia, and control the pH and electrolyte composition of intracellular organelles. Some members of this protein family are Cl(-) ion channels, whereas others are secondary active transporters that exchange Cl(-) ions and protons (H(+)) with a 2:1 stoichiometry. We have determined the structure of a eukaryotic CLC transporter at 3.5 angstrom resolution. Cytoplasmic cystathionine beta-synthase (CBS) domains are strategically positioned to regulate the ion-transport pathway, and many disease-causing mutations in human CLCs reside on the CBS-transmembrane interface. Comparison with prokaryotic CLC shows that a gating glutamate residue changes conformation and suggests a basis for 2:1 Cl(-)/H(+) exchange and a simple mechanistic connection between CLC channels and transporters.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3079386/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3079386/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Feng, Liang -- Campbell, Ernest B -- Hsiung, Yichun -- MacKinnon, Roderick -- P30 EB009998/EB/NIBIB NIH HHS/ -- R01 GM043949/GM/NIGMS NIH HHS/ -- R01 GM043949-20/GM/NIGMS NIH HHS/ -- R01 GM043949-21/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2010 Oct 29;330(6004):635-41. doi: 10.1126/science.1195230. Epub 2010 Sep 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Molecular Neurobiology and Biophysics, Rockefeller University, Howard Hughes Medical Institute, 1230 York Avenue, New York, NY 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20929736" target="_blank"〉PubMed〈/a〉
    Keywords: Algal Proteins/chemistry/metabolism ; Animals ; Antiporters/*chemistry/metabolism ; Binding Sites ; Cell Line ; Cell Membrane/chemistry ; Chloride Channels/*chemistry/metabolism ; Chlorides/*metabolism ; Crystallization ; Crystallography, X-Ray ; Cystathionine beta-Synthase/chemistry ; Cytoplasm/chemistry ; Glutamic Acid/metabolism ; Ion Channel Gating ; Ion Transport ; Models, Biological ; Models, Molecular ; Protein Conformation ; Protein Multimerization ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Protein Subunits/chemistry ; Protons ; Rhodophyta/*chemistry/metabolism
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    The genetic landscape of the childhood cancer medulloblastoma (2010)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2010-12-18
    Description: Medulloblastoma (MB) is the most common malignant brain tumor of children. To identify the genetic alterations in this tumor type, we searched for copy number alterations using high-density microarrays and sequenced all known protein-coding genes and microRNA genes using Sanger sequencing in a set of 22 MBs. We found that, on average, each tumor had 11 gene alterations, fewer by a factor of 5 to 10 than in the adult solid tumors that have been sequenced to date. In addition to alterations in the Hedgehog and Wnt pathways, our analysis led to the discovery of genes not previously known to be altered in MBs. Most notably, inactivating mutations of the histone-lysine N-methyltransferase genes MLL2 or MLL3 were identified in 16% of MB patients. These results demonstrate key differences between the genetic landscapes of adult and childhood cancers, highlight dysregulation of developmental pathways as an important mechanism underlying MBs, and identify a role for a specific type of histone methylation in human tumorigenesis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3110744/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3110744/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Parsons, D Williams -- Li, Meng -- Zhang, Xiaosong -- Jones, Sian -- Leary, Rebecca J -- Lin, Jimmy Cheng-Ho -- Boca, Simina M -- Carter, Hannah -- Samayoa, Josue -- Bettegowda, Chetan -- Gallia, Gary L -- Jallo, George I -- Binder, Zev A -- Nikolsky, Yuri -- Hartigan, James -- Smith, Doug R -- Gerhard, Daniela S -- Fults, Daniel W -- VandenBerg, Scott -- Berger, Mitchel S -- Marie, Suely Kazue Nagahashi -- Shinjo, Sueli Mieko Oba -- Clara, Carlos -- Phillips, Peter C -- Minturn, Jane E -- Biegel, Jaclyn A -- Judkins, Alexander R -- Resnick, Adam C -- Storm, Phillip B -- Curran, Tom -- He, Yiping -- Rasheed, B Ahmed -- Friedman, Henry S -- Keir, Stephen T -- McLendon, Roger -- Northcott, Paul A -- Taylor, Michael D -- Burger, Peter C -- Riggins, Gregory J -- Karchin, Rachel -- Parmigiani, Giovanni -- Bigner, Darell D -- Yan, Hai -- Papadopoulos, Nick -- Vogelstein, Bert -- Kinzler, Kenneth W -- Velculescu, Victor E -- CA057345/CA/NCI NIH HHS/ -- CA096832/CA/NCI NIH HHS/ -- CA118822/CA/NCI NIH HHS/ -- CA121113/CA/NCI NIH HHS/ -- CA135877/CA/NCI NIH HHS/ -- GM074906-01A1/GM/NIGMS NIH HHS/ -- HHSN261200800001E/PHS HHS/ -- P01 CA096832/CA/NCI NIH HHS/ -- P01 CA096832-03/CA/NCI NIH HHS/ -- R01 CA108622/CA/NCI NIH HHS/ -- R01 CA121113/CA/NCI NIH HHS/ -- R01 CA121113-05/CA/NCI NIH HHS/ -- R37 CA057345/CA/NCI NIH HHS/ -- R37 CA057345-20/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2011 Jan 28;331(6016):435-9. doi: 10.1126/science.1198056. Epub 2010 Dec 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Ludwig Center for Cancer Genetics and Therapeutics and Howard Hughes Medical Institute, Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21231, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21163964" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Cerebellar Neoplasms/*genetics/metabolism ; Child ; DNA Copy Number Variations ; DNA-Binding Proteins/genetics/metabolism ; *Genes, Neoplasm ; Genes, Tumor Suppressor ; Histone-Lysine N-Methyltransferase/genetics/metabolism ; Histones/metabolism ; Humans ; Medulloblastoma/*genetics/metabolism ; Methylation ; MicroRNAs/genetics ; *Mutation ; Neoplasm Proteins/genetics/metabolism ; Oligonucleotide Array Sequence Analysis ; Point Mutation ; Sequence Analysis, DNA ; Signal Transduction
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    Pivotal roles of cGAS-cGAMP signaling in antiviral defense and immune adjuvant effects (2013)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2013-08-31
    Description: Invasion of microbial DNA into the cytoplasm of animal cells triggers a cascade of host immune reactions that help clear the infection; however, self DNA in the cytoplasm can cause autoimmune diseases. Biochemical approaches led to the identification of cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) synthase (cGAS) as a cytosolic DNA sensor that triggers innate immune responses. Here, we show that cells from cGAS-deficient (cGas(-/-)) mice, including fibroblasts, macrophages, and dendritic cells, failed to produce type I interferons and other cytokines in response to DNA transfection or DNA virus infection. cGas(-/-) mice were more susceptible to lethal infection with herpes simplex virus 1 (HSV1) than wild-type mice. We also show that cGAMP is an adjuvant that boosts antigen-specific T cell activation and antibody production in mice.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3863637/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3863637/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Li, Xiao-Dong -- Wu, Jiaxi -- Gao, Daxing -- Wang, Hua -- Sun, Lijun -- Chen, Zhijian J -- 5T32AI070116/AI/NIAID NIH HHS/ -- AI-093967/AI/NIAID NIH HHS/ -- R01 AI093967/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2013 Sep 20;341(6152):1390-4. doi: 10.1126/science.1244040. Epub 2013 Aug 29.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23989956" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Viral/biosynthesis ; DNA, Viral/genetics/immunology ; Dendritic Cells/immunology ; Fibroblasts/immunology ; Herpes Simplex/*immunology ; *Herpesvirus 1, Human ; Interferon Regulatory Factor-3/genetics ; Interferon-beta/*biosynthesis/genetics ; Lymphocyte Activation ; Macrophages/immunology ; Mice ; Mice, Knockout ; Nucleotidyltransferases/genetics/*immunology ; Signal Transduction ; T-Lymphocytes/immunology ; Transfection
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    A mechanism for reorientation of cortical microtubule arrays driven by microtubule severing (2013)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2013-11-10
    Description: Environmental and hormonal signals cause reorganization of microtubule arrays in higher plants, but the mechanisms driving these transitions have remained elusive. The organization of these arrays is required to direct morphogenesis. We discovered that microtubule severing by the protein katanin plays a crucial and unexpected role in the reorientation of cortical arrays, as triggered by blue light. Imaging and genetic experiments revealed that phototropin photoreceptors stimulate katanin-mediated severing specifically at microtubule intersections, leading to the generation of new microtubules at these locations. We show how this activity serves as the basis for a mechanism that amplifies microtubules orthogonal to the initial array, thereby driving array reorientation. Our observations show how severing is used constructively to build a new microtubule array.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lindeboom, Jelmer J -- Nakamura, Masayoshi -- Hibbel, Anneke -- Shundyak, Kostya -- Gutierrez, Ryan -- Ketelaar, Tijs -- Emons, Anne Mie C -- Mulder, Bela M -- Kirik, Viktor -- Ehrhardt, David W -- New York, N.Y. -- Science. 2013 Dec 6;342(6163):1245533. doi: 10.1126/science.1245533. Epub 2013 Nov 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Plant Biology, Carnegie Institution for Science, Stanford, CA 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24200811" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphatases/genetics/*metabolism ; Arabidopsis/genetics/growth & development/*metabolism/*ultrastructure ; Arabidopsis Proteins/genetics/*metabolism ; Hypocotyl/metabolism/ultrastructure ; Light ; Microtubules/*metabolism/ultrastructure ; Phosphoproteins/metabolism ; *Phototropism ; Recombinant Fusion Proteins/metabolism ; Signal Transduction
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    Structural basis for the counter-transport mechanism of a H+/Ca2+ exchanger (2013)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2013-05-25
    Description: Ca(2+)/cation antiporters catalyze the exchange of Ca(2+) with various cations across biological membranes to regulate cytosolic calcium levels. The recently reported structure of a prokaryotic Na(+)/Ca(2+) exchanger (NCX_Mj) revealed its overall architecture in an outward-facing state. Here, we report the crystal structure of a H(+)/Ca(2+) exchanger from Archaeoglobus fulgidus (CAX_Af) in the two representatives of the inward-facing conformation at 2.3 A resolution. The structures suggested Ca(2+) or H(+) binds to the cation-binding site mutually exclusively. Structural comparison of CAX_Af with NCX_Mj revealed that the first and sixth transmembrane helices alternately create hydrophilic cavities on the intra- and extracellular sides. The structures and functional analyses provide insight into the mechanism of how the inward- to outward-facing state transition is triggered by the Ca(2+) and H(+) binding.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nishizawa, Tomohiro -- Kita, Satomi -- Maturana, Andres D -- Furuya, Noritaka -- Hirata, Kunio -- Kasuya, Go -- Ogasawara, Satoshi -- Dohmae, Naoshi -- Iwamoto, Takahiro -- Ishitani, Ryuichiro -- Nureki, Osamu -- New York, N.Y. -- Science. 2013 Jul 12;341(6142):168-72. doi: 10.1126/science.1239002. Epub 2013 May 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biophysics and Biochemistry, Graduate School of Science, University of Tokyo, 2-11-16 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23704374" target="_blank"〉PubMed〈/a〉
    Keywords: Antiporters/*chemistry/genetics/metabolism ; Archaeal Proteins/*chemistry/genetics/metabolism ; Archaeoglobus fulgidus/*metabolism ; Binding Sites ; Calcium/chemistry/metabolism ; Cation Transport Proteins/*chemistry/genetics/metabolism ; Crystallography, X-Ray ; Hydrogen/chemistry/metabolism ; Protein Structure, Secondary ; Protein Structure, Tertiary
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    Emergence and diversification of fly pigmentation through evolution of a gene regulatory module (2013)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2013-03-23
    Description: The typical pattern of morphological evolution associated with the radiation of a group of related species is the emergence of a novel trait and its subsequent diversification. Yet the genetic mechanisms associated with these two evolutionary steps are poorly characterized. Here, we show that a spot of dark pigment on fly wings emerged from the assembly of a novel gene regulatory module in which a set of pigmentation genes evolved to respond to a common transcriptional regulator determining their spatial distribution. The primitive wing spot pattern subsequently diversified through changes in the expression pattern of this regulator. These results suggest that the genetic changes underlying the emergence and diversification of wing pigmentation patterns are partitioned within genetic networks.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Arnoult, Laurent -- Su, Kathy F Y -- Manoel, Diogo -- Minervino, Caroline -- Magrina, Justine -- Gompel, Nicolas -- Prud'homme, Benjamin -- New York, N.Y. -- Science. 2013 Mar 22;339(6126):1423-6. doi: 10.1126/science.1233749.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Aix-Marseille Universite, CNRS, UMR 7288, Institut de Biologie du Developpement de Marseille-Luminy, 13288 Marseille cedex 9, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23520110" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Binding Sites ; Biological Evolution ; Drosophila/anatomy & histology/genetics/growth & development ; Drosophila Proteins/genetics/metabolism ; Drosophila melanogaster/anatomy & histology/*genetics/growth & ; development/metabolism ; *Evolution, Molecular ; Gene Expression Profiling ; Gene Expression Regulation, Developmental ; *Gene Regulatory Networks ; *Genes, Insect ; Homeodomain Proteins/genetics/*metabolism ; Phylogeny ; Pigmentation/*genetics ; Pigments, Biological/analysis/metabolism ; Pupa ; RNA Interference ; Transcription Factors/genetics/*metabolism ; Wings, Animal/*anatomy & histology/chemistry
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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    Cryo-EM structure of a fully glycosylated soluble cleaved HIV-1 envelope trimer (2013)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2013-11-02
    Description: The HIV-1 envelope glycoprotein (Env) trimer contains the receptor binding sites and membrane fusion machinery that introduce the viral genome into the host cell. As the only target for broadly neutralizing antibodies (bnAbs), Env is a focus for rational vaccine design. We present a cryo-electron microscopy reconstruction and structural model of a cleaved, soluble Env trimer (termed BG505 SOSIP.664 gp140) in complex with a CD4 binding site (CD4bs) bnAb, PGV04, at 5.8 angstrom resolution. The structure reveals the spatial arrangement of Env components, including the V1/V2, V3, HR1, and HR2 domains, as well as shielding glycans. The structure also provides insights into trimer assembly, gp120-gp41 interactions, and the CD4bs epitope cluster for bnAbs, which covers a more extensive area and defines a more complex site of vulnerability than previously described.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3954647/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3954647/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lyumkis, Dmitry -- Julien, Jean-Philippe -- de Val, Natalia -- Cupo, Albert -- Potter, Clinton S -- Klasse, Per-Johan -- Burton, Dennis R -- Sanders, Rogier W -- Moore, John P -- Carragher, Bridget -- Wilson, Ian A -- Ward, Andrew B -- GM103310/GM/NIGMS NIH HHS/ -- P01 AI082362/AI/NIAID NIH HHS/ -- P01 AI82362/AI/NIAID NIH HHS/ -- P41 GM103310/GM/NIGMS NIH HHS/ -- R01 AI084817/AI/NIAID NIH HHS/ -- R01 AI36082/AI/NIAID NIH HHS/ -- R37 AI036082/AI/NIAID NIH HHS/ -- UM1 AI100663/AI/NIAID NIH HHS/ -- Canadian Institutes of Health Research/Canada -- New York, N.Y. -- Science. 2013 Dec 20;342(6165):1484-90. doi: 10.1126/science.1245627. Epub 2013 Oct 31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉National Resource for Automated Molecular Microscopy, The Scripps Research Institute, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24179160" target="_blank"〉PubMed〈/a〉
    Keywords: AIDS Vaccines/chemistry/immunology ; Antibodies, Neutralizing/chemistry ; Antibodies, Viral/chemistry ; Antigens, CD4/*chemistry/immunology ; Binding Sites ; Cryoelectron Microscopy ; Glycosylation ; Immunodominant Epitopes/chemistry/immunology ; *Models, Molecular ; Polysaccharides/chemistry ; Protein Multimerization ; Protein Structure, Quaternary ; Protein Structure, Tertiary ; env Gene Products, Human Immunodeficiency Virus/*chemistry/immunology
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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    Beyond stem cells: self-renewal of differentiated macrophages (2013)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2013-11-23
    Description: In many mammalian tissues, mature differentiated cells are replaced by self-renewing stem cells, either continuously during homeostasis or in response to challenge and injury. For example, hematopoietic stem cells generate all mature blood cells, including monocytes, which have long been thought to be the major source of tissue macrophages. Recently, however, major macrophage populations were found to be derived from embryonic progenitors and to renew independently of hematopoietic stem cells. This process may not require progenitors, as mature macrophages can proliferate in response to specific stimuli indefinitely and without transformation or loss of functional differentiation. These findings suggest that macrophages are mature differentiated cells that may have a self-renewal potential similar to that of stem cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sieweke, Michael H -- Allen, Judith E -- MR/J001929/1/Medical Research Council/United Kingdom -- MR/K01207X1/Medical Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2013 Nov 22;342(6161):1242974. doi: 10.1126/science.1242974.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre d'Immunologie de Marseille-Luminy (CIML), Aix-Marseille Universite, UM2, Campus de Luminy, Case 906, 13288 Marseille Cedex 09, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24264994" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Cell Differentiation ; Cell Proliferation ; Cytokines/metabolism ; Embryonic Stem Cells/cytology ; Humans ; Macrophages/*cytology ; Mice ; Monocytes/cytology ; Rats ; Signal Transduction ; Stem Cells/*cytology
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    Mitochondrial fusion directs cardiomyocyte differentiation via calcineurin and Notch signaling (2013)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2013-10-05
    Description: Mitochondrial morphology is crucial for tissue homeostasis, but its role in cell differentiation is unclear. We found that mitochondrial fusion was required for proper cardiomyocyte development. Ablation of mitochondrial fusion proteins Mitofusin 1 and 2 in the embryonic mouse heart, or gene-trapping of Mitofusin 2 or Optic atrophy 1 in mouse embryonic stem cells (ESCs), arrested mouse heart development and impaired differentiation of ESCs into cardiomyocytes. Gene expression profiling revealed decreased levels of transcription factors transforming growth factor-beta/bone morphogenetic protein, serum response factor, GATA4, and myocyte enhancer factor 2, linked to increased Ca(2+)-dependent calcineurin activity and Notch1 signaling that impaired ESC differentiation. Orchestration of cardiomyocyte differentiation by mitochondrial morphology reveals how mitochondria, Ca(2+), and calcineurin interact to regulate Notch1 signaling.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kasahara, Atsuko -- Cipolat, Sara -- Chen, Yun -- Dorn, Gerald W 2nd -- Scorrano, Luca -- GPP10005/Telethon/Italy -- R01 HL059888/HL/NHLBI NIH HHS/ -- R01 HL59888/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2013 Nov 8;342(6159):734-7. doi: 10.1126/science.1241359. Epub 2013 Oct 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell Physiology and Metabolism, University of Geneva, 1206 Geneva, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24091702" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Calcineurin/*metabolism ; Calcineurin Inhibitors ; Cell Differentiation/genetics/*physiology ; GTP Phosphohydrolases/genetics/metabolism ; Gene Expression Profiling ; Heart/embryology ; Mice ; Mice, Knockout ; Mitochondrial Dynamics/genetics/*physiology ; Myocytes, Cardiac/*cytology/ultrastructure ; Receptor, Notch1/*metabolism ; Signal Transduction ; Transcription Factors/genetics/metabolism
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    Structural basis for molecular recognition at serotonin receptors (2013)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2013-03-23
    Description: Serotonin or 5-hydroxytryptamine (5-HT) regulates a wide spectrum of human physiology through the 5-HT receptor family. We report the crystal structures of the human 5-HT1B G protein-coupled receptor bound to the agonist antimigraine medications ergotamine and dihydroergotamine. The structures reveal similar binding modes for these ligands, which occupy the orthosteric pocket and an extended binding pocket close to the extracellular loops. The orthosteric pocket is formed by residues conserved in the 5-HT receptor family, clarifying the family-wide agonist activity of 5-HT. Compared with the structure of the 5-HT2B receptor, the 5-HT1B receptor displays a 3 angstrom outward shift at the extracellular end of helix V, resulting in a more open extended pocket that explains subtype selectivity. Together with docking and mutagenesis studies, these structures provide a comprehensive structural basis for understanding receptor-ligand interactions and designing subtype-selective serotonergic drugs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3644373/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3644373/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Chong -- Jiang, Yi -- Ma, Jinming -- Wu, Huixian -- Wacker, Daniel -- Katritch, Vsevolod -- Han, Gye Won -- Liu, Wei -- Huang, Xi-Ping -- Vardy, Eyal -- McCorvy, John D -- Gao, Xiang -- Zhou, X Edward -- Melcher, Karsten -- Zhang, Chenghai -- Bai, Fang -- Yang, Huaiyu -- Yang, Linlin -- Jiang, Hualiang -- Roth, Bryan L -- Cherezov, Vadim -- Stevens, Raymond C -- Xu, H Eric -- P50 GM073197/GM/NIGMS NIH HHS/ -- R01 DA027170/DA/NIDA NIH HHS/ -- R01 DA27170/DA/NIDA NIH HHS/ -- R01 DK071662/DK/NIDDK NIH HHS/ -- R01 MH061887/MH/NIMH NIH HHS/ -- R01 MH61887/MH/NIMH NIH HHS/ -- U19 MH082441/MH/NIMH NIH HHS/ -- U19 MH82441/MH/NIMH NIH HHS/ -- U54 GM094618/GM/NIGMS NIH HHS/ -- Y1-CO-1020/CO/NCI NIH HHS/ -- Y1-GM-1104/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2013 May 3;340(6132):610-4. doi: 10.1126/science.1232807. Epub 2013 Mar 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23519210" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Binding Sites ; Crystallography, X-Ray ; Dihydroergotamine/chemistry/*metabolism ; Ergotamine/chemistry/*metabolism ; Humans ; Hydrogen Bonding ; Hydrophobic and Hydrophilic Interactions ; Ligands ; Lysergic Acid Diethylamide/chemistry/metabolism ; Models, Molecular ; Molecular Docking Simulation ; Molecular Sequence Data ; Mutagenesis ; Norfenfluramine/chemistry/metabolism ; Pindolol/analogs & derivatives/chemistry/metabolism ; Propranolol/chemistry/metabolism ; Protein Conformation ; Protein Folding ; Protein Structure, Secondary ; Receptor, Serotonin, 5-HT1B/*chemistry/genetics/*metabolism ; Serotonin 5-HT1 Receptor Agonists/*chemistry/*metabolism ; Tryptamines/chemistry/metabolism
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    Extensive variation in chromatin states across humans (2013)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2013-10-19
    Description: The majority of disease-associated variants lie outside protein-coding regions, suggesting a link between variation in regulatory regions and disease predisposition. We studied differences in chromatin states using five histone modifications, cohesin, and CTCF in lymphoblastoid lines from 19 individuals of diverse ancestry. We found extensive signal variation in regulatory regions, which often switch between active and repressed states across individuals. Enhancer activity is particularly diverse among individuals, whereas gene expression remains relatively stable. Chromatin variability shows genetic inheritance in trios, correlates with genetic variation and population divergence, and is associated with disruptions of transcription factor binding motifs. Overall, our results provide insights into chromatin variation among humans.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4075767/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4075767/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kasowski, Maya -- Kyriazopoulou-Panagiotopoulou, Sofia -- Grubert, Fabian -- Zaugg, Judith B -- Kundaje, Anshul -- Liu, Yuling -- Boyle, Alan P -- Zhang, Qiangfeng Cliff -- Zakharia, Fouad -- Spacek, Damek V -- Li, Jingjing -- Xie, Dan -- Olarerin-George, Anthony -- Steinmetz, Lars M -- Hogenesch, John B -- Kellis, Manolis -- Batzoglou, Serafim -- Snyder, Michael -- R01 HG004037/HG/NHGRI NIH HHS/ -- T32 GM007205/GM/NIGMS NIH HHS/ -- T32 HG000044/HG/NHGRI NIH HHS/ -- T32GM07205/GM/NIGMS NIH HHS/ -- U01 HL107393/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2013 Nov 8;342(6159):750-2. doi: 10.1126/science.1242510. Epub 2013 Oct 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24136358" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; Cell Cycle Proteins/genetics/metabolism ; Cell Line, Tumor ; Chromatin/*genetics/*metabolism ; Chromosomal Proteins, Non-Histone/genetics/metabolism ; Enhancer Elements, Genetic/genetics ; *Gene Expression Regulation ; Genetic Predisposition to Disease/*genetics ; Genetic Variation ; Histones/genetics/metabolism ; Humans ; Repressor Proteins/genetics/metabolism ; Transcription Factors/genetics/metabolism
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    Probing allostery through DNA (2013)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2013-02-16
    Description: Allostery is well documented for proteins but less recognized for DNA-protein interactions. Here, we report that specific binding of a protein on DNA is substantially stabilized or destabilized by another protein bound nearby. The ternary complex's free energy oscillates as a function of the separation between the two proteins with a periodicity of ~10 base pairs, the helical pitch of B-form DNA, and a decay length of ~15 base pairs. The binding affinity of a protein near a DNA hairpin is similarly dependent on their separation, which-together with molecular dynamics simulations-suggests that deformation of the double-helical structure is the origin of DNA allostery. The physiological relevance of this phenomenon is illustrated by its effect on gene expression in live bacteria and on a transcription factor's affinity near nucleosomes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3586787/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3586787/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kim, Sangjin -- Brostromer, Erik -- Xing, Dong -- Jin, Jianshi -- Chong, Shasha -- Ge, Hao -- Wang, Siyuan -- Gu, Chan -- Yang, Lijiang -- Gao, Yi Qin -- Su, Xiao-dong -- Sun, Yujie -- Xie, X Sunney -- DP1 OD000277/OD/NIH HHS/ -- New York, N.Y. -- Science. 2013 Feb 15;339(6121):816-9. doi: 10.1126/science.1229223.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23413354" target="_blank"〉PubMed〈/a〉
    Keywords: *Allosteric Regulation ; Base Sequence ; Binding Sites ; DNA, B-Form/*chemistry ; DNA-Binding Proteins/*chemistry ; DNA-Directed RNA Polymerases/chemistry ; Escherichia coli/genetics/metabolism ; Gene Expression ; *Gene Expression Regulation, Bacterial ; Lac Repressors/chemistry ; Molecular Dynamics Simulation ; Nucleosomes/chemistry ; Protein Binding ; Protein Structure, Tertiary ; Receptors, Glucocorticoid/chemistry ; Transcription Factors/*chemistry ; Viral Proteins/chemistry
    Print ISSN: 0036-8075
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    A conserved mechanism for centromeric nucleosome recognition by centromere protein CENP-C (2013)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2013-06-01
    Description: Chromosome segregation during mitosis requires assembly of the kinetochore complex at the centromere. Kinetochore assembly depends on specific recognition of the histone variant CENP-A in the centromeric nucleosome by centromere protein C (CENP-C). We have defined the determinants of this recognition mechanism and discovered that CENP-C binds a hydrophobic region in the CENP-A tail and docks onto the acidic patch of histone H2A and H2B. We further found that the more broadly conserved CENP-C motif uses the same mechanism for CENP-A nucleosome recognition. Our findings reveal a conserved mechanism for protein recruitment to centromeres and a histone recognition mode whereby a disordered peptide binds the histone tail through hydrophobic interactions facilitated by nucleosome docking.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3763809/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3763809/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kato, Hidenori -- Jiang, Jiansheng -- Zhou, Bing-Rui -- Rozendaal, Marieke -- Feng, Hanqiao -- Ghirlando, Rodolfo -- Xiao, T Sam -- Straight, Aaron F -- Bai, Yawen -- R01 GM074728/GM/NIGMS NIH HHS/ -- Y1-CO-1020/CO/NCI NIH HHS/ -- Y1-GM-1104/GM/NIGMS NIH HHS/ -- ZIA AI000960-07/Intramural NIH HHS/ -- New York, N.Y. -- Science. 2013 May 31;340(6136):1110-3. doi: 10.1126/science.1235532.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, Bethesda, MD 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23723239" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Amino Acid Sequence ; Animals ; Autoantigens/metabolism ; Binding Sites ; Centromere/*metabolism ; Chromosomal Proteins, Non-Histone/genetics/*metabolism ; Conserved Sequence ; Drosophila ; Histones/*metabolism ; Humans ; Hydrophobic and Hydrophilic Interactions ; Molecular Sequence Data ; Nucleosomes/*metabolism ; Protein Structure, Secondary
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    Preferential recognition of avian-like receptors in human influenza A H7N9 viruses (2013)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2013-12-07
    Description: The 2013 outbreak of avian-origin H7N9 influenza in eastern China has raised concerns about its ability to transmit in the human population. The hemagglutinin glycoprotein of most human H7N9 viruses carries Leu(226), a residue linked to adaptation of H2N2 and H3N2 pandemic viruses to human receptors. However, glycan array analysis of the H7 hemagglutinin reveals negligible binding to humanlike alpha2-6-linked receptors and strong preference for a subset of avian-like alpha2-3-linked glycans recognized by all avian H7 viruses. Crystal structures of H7N9 hemagglutinin and six hemagglutinin-glycan complexes have elucidated the structural basis for preferential recognition of avian-like receptors. These findings suggest that the current human H7N9 viruses are poorly adapted for efficient human-to-human transmission.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3954636/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3954636/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Xu, Rui -- de Vries, Robert P -- Zhu, Xueyong -- Nycholat, Corwin M -- McBride, Ryan -- Yu, Wenli -- Paulson, James C -- Wilson, Ian A -- GM62116/GM/NIGMS NIH HHS/ -- P41GM103393/GM/NIGMS NIH HHS/ -- P41RR001209/RR/NCRR NIH HHS/ -- R56 AI099275/AI/NIAID NIH HHS/ -- Y1-CO-1020/CO/NCI NIH HHS/ -- Y1-GM-1104/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2013 Dec 6;342(6163):1230-5. doi: 10.1126/science.1243761.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24311689" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Binding Sites ; Birds ; Carbohydrate Conformation ; Crystallography, X-Ray ; Hemagglutinin Glycoproteins, Influenza Virus/*chemistry/*metabolism ; Humans ; Influenza A Virus, H7N9 Subtype/*metabolism/*pathogenicity ; Influenza in Birds/transmission/virology ; Influenza, Human/transmission/virology ; Ligands ; Microarray Analysis ; Models, Molecular ; Molecular Sequence Data ; Mutation ; Polysaccharides/chemistry/*metabolism ; Receptors, Virus/chemistry/*metabolism ; Recombinant Proteins/chemistry/metabolism
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    Structure of the repulsive guidance molecule (RGM)-neogenin signaling hub (2013)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2013-06-08
    Description: Repulsive guidance molecule family members (RGMs) control fundamental and diverse cellular processes, including motility and adhesion, immune cell regulation, and systemic iron metabolism. However, it is not known how RGMs initiate signaling through their common cell-surface receptor, neogenin (NEO1). Here, we present crystal structures of the NEO1 RGM-binding region and its complex with human RGMB (also called dragon). The RGMB structure reveals a previously unknown protein fold and a functionally important autocatalytic cleavage mechanism and provides a framework to explain numerous disease-linked mutations in RGMs. In the complex, two RGMB ectodomains conformationally stabilize the juxtamembrane regions of two NEO1 receptors in a pH-dependent manner. We demonstrate that all RGM-NEO1 complexes share this architecture, which therefore represents the core of multiple signaling pathways.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4730555/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4730555/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bell, Christian H -- Healey, Eleanor -- van Erp, Susan -- Bishop, Benjamin -- Tang, Chenxiang -- Gilbert, Robert J C -- Aricescu, A Radu -- Pasterkamp, R Jeroen -- Siebold, Christian -- 082301/Wellcome Trust/United Kingdom -- 083111/Wellcome Trust/United Kingdom -- 090532/Wellcome Trust/United Kingdom -- 097301/Wellcome Trust/United Kingdom -- A14414/Cancer Research UK/United Kingdom -- G0700232/Medical Research Council/United Kingdom -- Medical Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2013 Jul 5;341(6141):77-80. doi: 10.1126/science.1232322. Epub 2013 Jun 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK. christian@strubi.ox.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23744777" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Biophysical Phenomena ; Cell Adhesion Molecules, Neuronal/*chemistry/genetics ; Conserved Sequence ; Crystallography, X-Ray ; Humans ; Membrane Proteins/*chemistry ; Mutation ; Oligopeptides/chemistry ; Protein Structure, Tertiary ; Signal Transduction
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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