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  • American Association for the Advancement of Science  (89,372)
  • Nature Publishing Group  (67,391)
  • Annual Reviews
  • 2010-2014  (25,994)
  • 2000-2004  (46,448)
  • 1990-1994  (42,529)
  • 1980-1984  (36,649)
  • 1950-1954  (24,624)
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  • 1
    Publication Date: 2020-12-21
    Description: BREVIA
    Description: We report on the discovery in southern Egypt of an impact crater 45 m in diameter with a pristine rayed structure. Such pristine structures have been previously observed only on atmosphereless rocky or icy planetary bodies in the Solar System. This feature and the association with an iron meteorite impactor and shock metamorphism provides a unique picture of small-scale hypervelocity impacts on the Earth's crust. Contrary to current geophysical models, ground data indicate that iron meteorites with masses of the order of tens of tons can penetrate the atmosphere without significant fragmentation.
    Description: Published
    Description: 804
    Description: 1.8. Osservazioni di geofisica ambientale
    Description: 3.8. Geofisica per l'ambiente
    Description: JCR Journal
    Description: open
    Keywords: Impact crater ; Egypt ; geophysical exploration ; ataxite ; 04. Solid Earth::04.04. Geology::04.04.03. Geomorphology
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Type: article
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  • 2
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    Nature Publishing Group
    In:  EPIC3Nature Geoscience, Nature Publishing Group, 7(5), pp. 376-381, ISSN: 1752-0894
    Publication Date: 2014-07-14
    Description: During the Middle Miocene climate transition about 14 million years ago, the Antarctic ice sheet expanded to near-modern volume. Surprisingly, this ice sheet growth was accompanied by a warming in the surface waters of the Southern Ocean, whereas a slight deep-water temperature increase was delayed by more than 200 thousand years. Here we use a coupled atmosphere–ocean model to assess the relative effects of changes in atmospheric CO2 concentration and ice sheet growth on regional and global temperatures. In the simulations, changes in the wind field associated with the growth of the ice sheet induce changes in ocean circulation, deep-water formation and sea-ice cover that result in sea surface warming and deep-water cooling in large swaths of the Atlantic and Indian ocean sectors of the Southern Ocean. We interpret these changes as the dominant ocean surface response to a 100-thousand-year phase of massive ice growth in Antarctica. A rise in global annual mean temperatures is also seen in response to increased Antarctic ice surface elevation. In contrast, the longer-term surface and deep-water temperature trends are dominated by changes in atmospheric CO2 concentration. We therefore conclude that the climatic and oceanographic impacts of the Miocene expansion of the Antarctic ice sheet are governed by a complex interplay between wind field, ocean circulation and the sea-ice system.
    Repository Name: EPIC Alfred Wegener Institut
    Type: Article , isiRev
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  • 3
    Publication Date: 2014-07-17
    Description: Thermokarst lakes formed across vast regions of Siberia and Alaska during the last deglaciation and are thought to be a net source of atmospheric methane and carbon dioxide during the Holocene epoch1, 2, 3, 4. However, the same thermokarst lakes can also sequester carbon5, and it remains uncertain whether carbon uptake by thermokarst lakes can offset their greenhouse gas emissions. Here we use field observations of Siberian permafrost exposures, radiocarbon dating and spatial analyses to quantify Holocene carbon stocks and fluxes in lake sediments overlying thawed Pleistocene-aged permafrost. We find that carbon accumulation in deep thermokarst-lake sediments since the last deglaciation is about 1.6 times larger than the mass of Pleistocene-aged permafrost carbon released as greenhouse gases when the lakes first formed. Although methane and carbon dioxide emissions following thaw lead to immediate radiative warming, carbon uptake in peat-rich sediments occurs over millennial timescales. We assess thermokarst-lake carbon feedbacks to climate with an atmospheric perturbation model and find that thermokarst basins switched from a net radiative warming to a net cooling climate effect about 5,000 years ago. High rates of Holocene carbon accumulation in 20 lake sediments (47 ± 10 grams of carbon per square metre per year; mean ± standard error) were driven by thermokarst erosion and deposition of terrestrial organic matter, by nutrient release from thawing permafrost that stimulated lake productivity and by slow decomposition in cold, anoxic lake bottoms. When lakes eventually drained, permafrost formation rapidly sequestered sediment carbon. Our estimate of about 160 petagrams of Holocene organic carbon in deep lake basins of Siberia and Alaska increases the circumpolar peat carbon pool estimate for permafrost regions by over 50 per cent (ref. 6). The carbon in perennially frozen drained lake sediments may become vulnerable to mineralization as permafrost disappears7, 8, 9, potentially negating the climate stabilization provided by thermokarst lakes during the late Holocene.
    Repository Name: EPIC Alfred Wegener Institut
    Type: Article , isiRev , info:eu-repo/semantics/article
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  • 4
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    Nature Publishing Group
    In:  EPIC3Nature, Nature Publishing Group, 512(7514), pp. 290-294, ISSN: 0028-0836
    Publication Date: 2014-09-04
    Description: During glacial periods of the Late Pleistocene, an abundance of proxy data demonstrates the existence of large and repeated millennial-scale warming episodes, known as Dansgaard–Oeschger (DO) events1. This ubiquitous feature of rapid glacial climate change can be extended back as far as 800,000 years before present (BP) in the ice core record2, and has drawn broad attention within the science and policy-making communities alike3. Many studies have been dedicated to investigating the underlying causes of these changes, but no coherent mechanism has yet been identified3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15. Here we show, by using a comprehensive fully coupled model16, that gradual changes in the height of the Northern Hemisphere ice sheets (NHISs) can alter the coupled atmosphere–ocean system and cause rapid glacial climate shifts closely resembling DO events. The simulated global climate responses—including abrupt warming in the North Atlantic, a northward shift of the tropical rainbelts, and Southern Hemisphere cooling related to the bipolar seesaw—are generally consistent with empirical evidence1, 3, 17. As a result of the coexistence of two glacial ocean circulation states at intermediate heights of the ice sheets, minor changes in the height of the NHISs and the amount of atmospheric CO2 can trigger the rapid climate transitions via a local positive atmosphere–ocean–sea-ice feedback in the North Atlantic. Our results, although based on a single model, thus provide a coherent concept for understanding the recorded millennial-scale variability and abrupt climate changes in the coupled atmosphere–ocean system, as well as their linkages to the volume of the intermediate ice sheets during glacials.
    Repository Name: EPIC Alfred Wegener Institut
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  • 5
    Publication Date: 2019-03-08
    Description: Coccolithophores have influenced the global climate for over 200 million years1. These marine phytoplankton can account for 20 per cent of total carbon fixation in some systems2. They form blooms that can occupy hundreds of thousands of square kilometres and are distinguished by their elegantly sculpted calcium carbonate exoskeletons (coccoliths), rendering themvisible fromspace3.Although coccolithophores export carbon in the form of organic matter and calcite to the sea floor, they also release CO2 in the calcification process. Hence, they have a complex influence on the carbon cycle, driving either CO2 production or uptake, sequestration and export to the deep ocean4. Here we report the first haptophyte reference genome, from the coccolithophore Emiliania huxleyi strain CCMP1516, and sequences from 13 additional isolates. Our analyses reveal a pan genome (core genes plus genes distributed variably between strains) probably supported by an atypical complement of repetitive sequence in the genome. Comparisons across strains demonstrate thatE. huxleyi, which has long been considered a single species, harbours extensive genome variability reflected in different metabolic repertoires. Genome variability within this species complex seems to underpin its capacity both to thrive in habitats ranging from the equator to the subarctic and to form large-scale episodic blooms under a wide variety of environmental conditions.
    Repository Name: EPIC Alfred Wegener Institut
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  • 6
    Publication Date: 2017-04-04
    Description: The MW 8.8 mega-thrust earthquake and tsunami that occurred on February 27, 2010, offshore Maule region, Chile, was not unexpected. A clearly identified seismic gap existed in an area where tectonic loading has been accumulating since the great 1835 earthquake experienced and described by Darwin during the voyage of the Beagle. Here we jointly invert tsunami and geodetic data (InSAR, GPS, land-level changes), to derive a robust model for the co-seismic slip distribution and induced co-seismic stress changes, and compare them to past earthquakes and the pre-seismic locking distribution. We aim to assess if the Maule earthquake has filled the Darwin gap, decreasing the probability of a future shock . We find that the main slip patch is located to the north of the gap, overlapping the rupture zone of the MW 8.0 1928 earthquake, and that a secondary concentration of slip occurred to the south; the Darwin gap was only partially filled and a zone of high pre-seismic locking remains unbroken. This observation is not consistent with the assumption that distributions of seismic rupture might be correlated with pre-seismic locking, potentially allowing the anticipation of slip distributions in seismic gaps. Moreover, increased stress on this unbroken patch might have increased the probability of another major to great earthquake there in the near future.
    Description: Published
    Description: 173-177
    Description: 3.1. Fisica dei terremoti
    Description: 4.2. TTC - Modelli per la stima della pericolosità sismica a scala nazionale
    Description: JCR Journal
    Description: restricted
    Keywords: Source process ; Chile ; Tsunami ; Joint Inversion ; Seismic Gap ; 04. Solid Earth::04.06. Seismology::04.06.99. General or miscellaneous ; 04. Solid Earth::04.07. Tectonophysics::04.07.05. Stress ; 04. Solid Earth::04.07. Tectonophysics::04.07.06. Subduction related processes ; 05. General::05.01. Computational geophysics::05.01.03. Inverse methods
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 7
    Publication Date: 2017-04-04
    Description: Studies of past sea-level markers are commonly used to unveil the tectonic history and seismic behavior of subduction zones. We present new evidence on vertical motions of the Hellenic subduction zone as resulting from a suite of Late Pleistocene - Holocene shorelines in western Crete (Greece). Shoreline ages obtained by AMS radiocarbon dating of seashells, together with the reappraisal of shoreline ages from previous works, testify a long-term uplift rate of 2.5-2.7 mm/y. This average value, however, includes periods in which the vertical motions vary significantly: 2.6-3.2 mm/y subsidence rate from 42 ka to 23 ka, followed by ~7.7 mm/y sustained uplift rate from 23 ka to present. The last ~5 ky shows a relatively slower uplift rate of 3.0-3.3 mm/y, yet slightly higher than the long-term average. A preliminary tectonic model attempts at explaining these up and down motions by across-strike partitioning of fault activity in the subduction zone.
    Description: Published
    Description: 5677
    Description: 2T. Tettonica attiva
    Description: JCR Journal
    Description: restricted
    Keywords: coastal geomorphology ; tectonic rates ; paleoshorelines ; subduction ; Crete ; 04. Solid Earth::04.04. Geology::04.04.03. Geomorphology ; 04. Solid Earth::04.07. Tectonophysics::04.07.07. Tectonics
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 8
    Publication Date: 2017-04-04
    Description: The 2011 Tohoku-oki (Mw 9.1) earthquake is so far the best-observed megathrust rupture, which allowed the collection of unprecedented offshore data. The joint inversion of tsunami waveforms (DART buoys, bottom pressure sensors, coastal wave gauges, and GPS-buoys) and static geodetic data (onshore GPS, seafloor displacements obtained by a GPS/acoustic combination technique), allows us to retrieve the slip distribution on a non-planar fault. We show that the inclusion of near-source data is necessary to image the details of slip pattern (maximum slip ,48 m, up to ,35 m close to the Japan trench), which generated the large and shallow seafloor coseismic deformations and the devastating inundation of the Japanese coast. We investigate the relation between the spatial distribution of previously inferred interseismic coupling and coseismic slip and we highlight the importance of seafloor geodetic measurements to constrain the interseismic coupling, which is one of the key-elements for long-term earthquake and tsunami hazard assessment.
    Description: Published
    Description: 385
    Description: 3.1. Fisica dei terremoti
    Description: N/A or not JCR
    Description: restricted
    Keywords: Tohoku ; Subduction ; Tsunami ; Inverse problem ; 04. Solid Earth::04.06. Seismology::04.06.03. Earthquake source and dynamics ; 04. Solid Earth::04.07. Tectonophysics::04.07.06. Subduction related processes
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 9
    Publication Date: 2017-04-04
    Description: Improving lava flow hazard assessment is one of the most important and challenging fields of volcanology, and has an immediate and practical impact on society. Here, we present a methodology for the quantitative assessment of lava flow hazards based on a combination of field data, numerical simulations and probability analyses. With the extensive data available on historic eruptions of Mt. Etna, going back over 2000 years, it has been possible to construct two hazard maps, one for flank and the other for summit eruptions, allowing a quantitative analysis of the most likely future courses of lava flows. The effective use of hazard maps of Etna may help in minimizing the damage from volcanic eruptions through correct land use in densely urbanized area with a population of almost one million people. Although this study was conducted on Mt. Etna, the approach used is designed to be applicable to other volcanic areas.
    Description: This work was developed within the framework of TecnoLab, the Laboratory for Technological Advance in Volcano Geophysics organized by INGV-CT, DIEES-UNICT, and DMI-UNICT.
    Description: Published
    Description: 3493
    Description: 1V. Storia e struttura dei sistemi vulcanici
    Description: 2V. Dinamiche di unrest e scenari pre-eruttivi
    Description: 3V. Dinamiche e scenari eruttivi
    Description: 4V. Vulcani e ambiente
    Description: 6A. Monitoraggio ambientale, sicurezza e territorio
    Description: 3IT. Calcolo scientifico e sistemi informatici
    Description: JCR Journal
    Description: restricted
    Keywords: Lava flow hazard ; Etna ; 04. Solid Earth::04.04. Geology::04.04.99. General or miscellaneous ; 04. Solid Earth::04.08. Volcanology::04.08.99. General or miscellaneous ; 05. General::05.01. Computational geophysics::05.01.99. General or miscellaneous ; 05. General::05.02. Data dissemination::05.02.99. General or miscellaneous ; 05. General::05.08. Risk::05.08.99. General or miscellaneous
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 10
    Publication Date: 2017-04-04
    Description: In recent decades, geophysical investigations have detected wide magma reservoirs beneath quiescent calderas. However, the discovery of partially melted horizons inside the crust is not sufficient to put constraints on capability of reservoirs to supply cataclysmic eruptions, which strictly depends on the chemical-physical properties of magmas (composition, viscosity, gas content etc.), and thus on their differentiation histories. In this study, by using geochemical, isotopic and textural records of rocks erupted from the high-risk Campi Flegrei caldera, we show that the alkaline magmas have evolved toward a critical state of explosive behaviour over a time span shorter than the repose time of most volcanic systems and that these magmas have risen rapidly toward the surface. Moreover, similar results on the depth and timescale of magma storage were previously obtained for the neighbouring Somma-Vesuvius volcano. This consistency suggests that there might be a unique long-lived magma pool beneath the whole Neapolitan area.
    Description: Published
    Description: article 712
    Description: 2.3. TTC - Laboratori di chimica e fisica delle rocce
    Description: 3.5. Geologia e storia dei vulcani ed evoluzione dei magmi
    Description: 3.6. Fisica del vulcanismo
    Description: 4.3. TTC - Scenari di pericolosità vulcanica
    Description: N/A or not JCR
    Description: open
    Keywords: magma ; campi flegrei caldera ; 04. Solid Earth::04.04. Geology::04.04.05. Mineralogy and petrology ; 04. Solid Earth::04.08. Volcanology::04.08.03. Magmas ; 04. Solid Earth::04.08. Volcanology::04.08.05. Volcanic rocks ; 04. Solid Earth::04.08. Volcanology::04.08.08. Volcanic risk
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 11
    Publication Date: 2019-07-17
    Description: The mid-Piacenzian climate represents the most geologically recent interval of long-term average warmth relative to the last million years, and shares similarities with the climate projected for the end of the 21st century. As such, it represents a natural experiment from which we can gain insight into potential climate change impacts, enabling more informed policy decisions for mitigation and adaptation. Here, we present the first systematic comparison of Pliocene sea surface temperature (SST) between an ensemble of eight climate model simulations produced as part of PlioMIP (Pliocene Model Intercomparison Project) with the PRISM (Pliocene Research, Interpretation and Synoptic Mapping) Project mean annual SST field. Our results highlight key regional and dynamic situations where there is discord between the palaeoenvironmental reconstruction and the climate model simulations. These differences have led to improved strategies for both experimental design and temporal refinement of the palaeoenvironmental reconstruction.
    Repository Name: EPIC Alfred Wegener Institut
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  • 12
    Publication Date: 2019-07-17
    Description: Comparing simulations of key warm periods in Earth history with contemporaneous geological proxy data is a useful approach for evaluating the ability of climate models to simulate warm, high-CO2 climates that are unprecedented in the more recent past. Here we use a global data set of confidence-assessed, proxy-based temperature estimates and biome reconstructions to assess the ability of eight models to simulate warm terrestrial climates of the Pliocene epoch. The Late Pliocene, 3.6–2.6 million years ago, is an accessible geological interval to understand climate processes of a warmer world. We show that model-predicted surface air temperatures reveal a substantial cold bias in the Northern Hemisphere. Particularly strong data–model mismatches in mean annual temperatures (up to 18 °C) exist in northern Russia. Our model sensitivity tests identify insufficient temporal constraints hampering the accurate configuration of model boundary conditions as an important factor impacting on data–model discrepancies. We conclude that to allow a more robust evaluation of the ability of present climate models to predict warm climates, future Pliocene data–model comparison studies should focus on orbitally defined time slices.
    Repository Name: EPIC Alfred Wegener Institut
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  • 13
    Publication Date: 2017-10-18
    Description: Efforts to extract a Greenland ice core with a complete record of the Eemian interglacial (130,000 to 115,000 years ago) have until now been unsuccessful. The response of the Greenland ice sheet to the warmer-than-present climate of the Eemian has thus remained unclear. Here we present the new North Greenland Eemian Ice Drilling (‘NEEM’) ice core and show only a modest ice-sheet response to the strong warming in the early Eemian. We reconstructed the Eemian record from folded ice using globally homogeneous parameters known from dated Greenland and Antarctic ice-core records. On the basis of water stable isotopes, NEEM surface temperatures after the onset of the Eemian (126,000 years ago) peaked at 8 ± 4 degrees Celsius above the mean of the past millennium, followed by a gradual cooling that was probably driven by the decreasing summer insolation. Between 128,000 and 122,000 years ago, the thickness of the northwest Greenland ice sheet decreased by 400 ± 250 metres, reaching surface elevations 122,000 years ago of 130 ± 300 metres lower than the present. Extensive surface melt occurred at the NEEM site during the Eemian, a phenomenon witnessed when melt layers formed again at NEEM during the exceptional heat of July 2012. With additional warming, surface melt might become more common in the future.
    Repository Name: EPIC Alfred Wegener Institut
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  • 14
    Publication Date: 2019-07-17
    Description: The public health, tourism, fisheries, and ecosystem impacts from harmful algal blooms (HABs) have all increased over the past few decades. This has led to heightened scientific and regulatory attention, and the development of many new technologies and approaches for research and management. This, in turn, is leading to significant paradigm shifts with regard to, e.g.,our interpretation of the phytoplankton species concept (strain variation), the dogma of their apparent cosmopolitanism, the role of bacteria and zooplankton grazing in HABs, and our approaches to investigating the ecological and genetic basis for the production of toxins and allelochemicals. Increasingly,eutrophication and climate change are viewed andmanaged as multifactorial environmental stressors that will further challenge managers of coastal resources and those responsible for protecting human health. Here we review HABscience with an eye toward new concepts and approaches,emphasizing, where possible, the unexpected yet promising new directions that research has taken in this diverse field.
    Repository Name: EPIC Alfred Wegener Institut
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  • 15
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    Nature Publishing Group
    In:  EPIC3Nature Geoscience, Nature Publishing Group, 7(2), pp. 113-116, ISSN: 1752-0894
    Publication Date: 2018-08-10
    Description: The Antarctic Circumpolar Current is key to the mixing and ventilation of the world’s oceans1, 2, 3, 4, 5. This current flows from west to east between about 45° and 70° S (refs 1, 2, 3) connecting the Atlantic, Pacific and Indian oceans, and is driven by westerly winds and buoyancy forcing. High levels of productivity in the current regulate atmospheric CO2 concentrations6. Reconstructions of the current during the last glacial period suggest that flow speeds were faster7 or similar8 to present, and it is uncertain whether the strength and position of the westerly winds changed9, 10, 11. Here we reconstruct Antarctic Circumpolar Current bottom speeds through the constricting Drake Passage and Scotia Sea during the Last Glacial Maximum and Holocene based on the mean grain size of sortable silt from a suite of sediment cores. We find essentially no change in bottom flow speeds through the region, and, given that the momentum imparted by winds, and modulated by sea-ice cover, is balanced by the interaction of these flows with the seabed, this argues against substantial changes in wind stress. However, glacial flow speeds in the sea-ice zone12 south of 56° S were significantly slower than present, whereas flow in the north was faster, but not significantly so. We suggest that slower flow over the rough topography south of 56° S may have reduced diapycnal mixing in this region during the last glacial period, possibly reducing the diapycnal contribution to the Southern Ocean overturning circulation.
    Repository Name: EPIC Alfred Wegener Institut
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  • 16
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    Nature Publishing Group
    In:  EPIC3Scientific Reports, Nature Publishing Group, 4(4119), ISSN: 2045-2322
    Publication Date: 2019-07-17
    Description: Complex network approaches have recently been applied to continuous spatial dynamical systems, like climate, successfully uncovering the system's interaction structure. However the relationship between the underlying atmospheric or oceanic flow's dynamics and the estimated network measures have remained largely unclear. We bridge this crucial gap in a bottom-up approach and define a continuous analytical analogue of Pearson correlation networks for advection-diffusion dynamics on a background flow. Analysing complex networks of prototypical flows and from time series data of the equatorial Pacific, we find that our analytical model reproduces the most salient features of these networks and thus provides a general foundation of climate networks. The relationships we obtain between velocity field and network measures show that line-like structures of high betweenness mark transition zones in the flow rather than, as previously thought, the propagation of dynamical information.
    Repository Name: EPIC Alfred Wegener Institut
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  • 17
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    American Association for the Advancement of Science
    In:  EPIC3Science, American Association for the Advancement of Science, 345(6202), pp. 1354-1358
    Publication Date: 2019-01-15
    Description: Grounding zones, where ice sheets transition between resting on bedrock to full floatation, help regulate ice flow. Exposure of the sea floor by the 2002 Larsen-B Ice Shelf collapse allowed detailed morphologic mapping and sampling of the embayment sea floor. Marine geophysical data collected in 2006 reveal a large, arcuate, complex grounding zone sediment system at the front of Crane Fjord. Radiocarbon-constrained chronologies from marine sediment cores indicate loss of ice contact with the bed at this site about 12,000 years ago. Previous studies and morphologic mapping of the fjord suggest that the Crane Glacier grounding zone was well within the fjord before 2002 and did not retreat further until after the ice shelf collapse. This implies that the 2002 Larsen-B Ice Shelf collapse likely was a response to surface warming rather than to grounding zone instability, strengthening the idea that surface processes controlled the disintegration of the Larsen Ice Shelf .
    Repository Name: EPIC Alfred Wegener Institut
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  • 18
    Publication Date: 2022-05-25
    Description: © Macmillan Publishers Limited, 2010. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial-No Derivative Works 3.0 Unported License. The definitive version was published in Nature Communications 1 (2010): 49, doi:10.1038/ncomms1045.
    Description: Motor innervation to the tetrapod forelimb and fish pectoral fin is assumed to share a conserved spinal cord origin, despite major structural and functional innovations of the appendage during the vertebrate water-to-land transition. In this paper, we present anatomical and embryological evidence showing that pectoral motoneurons also originate in the hindbrain among ray-finned fish. New and previous data for lobe-finned fish, a group that includes tetrapods, and more basal cartilaginous fish showed pectoral innervation that was consistent with a hindbrain-spinal origin of motoneurons. Together, these findings support a hindbrain–spinal phenotype as the ancestral vertebrate condition that originated as a postural adaptation for pectoral control of head orientation. A phylogenetic analysis indicated that Hox gene modules were shared in fish and tetrapod pectoral systems. We propose that evolutionary shifts in Hox gene expression along the body axis provided a transcriptional mechanism allowing eventual decoupling of pectoral motoneurons from the hindbrain much like their target appendage gained independence from the head.
    Description: Th is work was supported by the National Institutes of Health and National Science Foundation.
    Repository Name: Woods Hole Open Access Server
    Type: Article
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  • 19
    Publication Date: 2022-05-25
    Description: © Macmillan Publishers Limited, 2012. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Nature Communications 3 (2012): 669, doi:10.1038/ncomms1673.
    Description: Na+/K+ pumps move net charge through the cell membrane by mediating unequal exchange of intracellular Na+ and extracellular K+. Most charge moves during transitions that release Na+ to the cell exterior. When pumps are constrained to bind and release only Na+, a membrane voltage-step redistributes pumps among conformations with zero, one, two or three bound Na+, thereby transiently generating current. By applying rapid voltage steps to squid giant axons, we previously identified three components in such transient currents, with distinct relaxation speeds: fast (which nearly parallels the voltage-jump time course), medium speed (τm=0.2–0.5 ms) and slow (τs=1–10 ms). Here we show that these three components are tightly correlated, both in their magnitudes and in the time courses of their changes. The correlations reveal the dynamics of the conformational rearrangements that release three Na+ to the exterior (or sequester them into their binding sites) one at a time, in an obligatorily sequential manner.
    Description: This research was directly supported by the Intramural Research Program of the National Institutes of Health (NIH), NINDS, grants NIH HL36783 to D.C.G., and NIH U54GM087519 and R01GM030376 to F.B.
    Repository Name: Woods Hole Open Access Server
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  • 20
    Publication Date: 2022-05-25
    Description: © The Author(s), 2012. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Scientific Reports 2 (2012): 582, doi:10.1038/srep00582.
    Description: Over the last century humans have altered the export of fluvial materials leading to significant changes in morphology, chemistry, and biology of the coastal ocean. Here we present sedimentary, paleoenvironmental and paleogenetic evidence to show that the Black Sea, a nearly enclosed marine basin, was affected by land use long before the changes of the Industrial Era. Although watershed hydroclimate was spatially and temporally variable over the last ~3000 years, surface salinity dropped systematically in the Black Sea. Sediment loads delivered by Danube River, the main tributary of the Black Sea, significantly increased as land use intensified in the last two millennia, which led to a rapid expansion of its delta. Lastly, proliferation of diatoms and dinoflagellates over the last five to six centuries, when intensive deforestation occurred in Eastern Europe, points to an anthropogenic pulse of river-borne nutrients that radically transformed the food web structure in the Black Sea.
    Description: This study was supported by grants OISE 0637108, EAR 0952146, OCE 0602423 and OCE 0825020 from the National Science Foundation and grants from the Woods Hole Oceanographic Institution.
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  • 21
    Publication Date: 2022-05-25
    Description: © The Author(s), 2013. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Scientific Reports 3 (2013): 2802, doi:10.1038/srep02802.
    Description: It is usually assumed that metabolic constraints restrict deep-sea corals to cold-water habitats, with ‘deep-sea’ and ‘cold-water’ corals often used as synonymous. Here we report on the first measurements of biological characters of deep-sea corals from the central Red Sea, where they occur at temperatures exceeding 20°C in highly oligotrophic and oxygen-limited waters. Low respiration rates, low calcification rates, and minimized tissue cover indicate that a reduced metabolism is one of the key adaptations to prevailing environmental conditions. We investigated four sites and encountered six species of which at least two appear to be undescribed. One species is previously reported from the Red Sea but occurs in deep cold waters outside the Red Sea raising interesting questions about presumed environmental constraints for other deep-sea corals. Our findings suggest that the present understanding of deep-sea coral persistence and resilience needs to be revisited.
    Keywords: Ecosystem ecology ; Biodiversity ; Genetics ; Metabolism
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  • 22
    Publication Date: 2022-05-25
    Description: © Macmillan Publishers Limited, 2011. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Nature Communications 2 (2011): 293, doi:10.1038/ncomms1297.
    Description: The relative importance of north–south migrations of the intertropical convergence zone (ITCZ) versus El Niño-Southern Oscillation and its associated Pacific Walker Circulation (PWC) variability for past hydrological change in the western tropical Pacific is unclear. Here we show that north–south ITCZ migration was not the only mechanism of tropical Pacific hydrologic variability during the last millennium, and that PWC variability profoundly influenced tropical Pacific hydrology. We present hydrological reconstructions from Cattle Pond, Dongdao Island of the South China Sea, where multi-decadal rainfall and downcore grain size variations are correlated to the Southern Oscillation Index during the instrumental era. Our downcore grain size reconstructions indicate that this site received less precipitation during relatively warm periods, AD 1000–1400 and AD 1850–2000, compared with the cool period (AD 1400–1850). Including our new reconstructions in a synthesis of tropical Pacific records results in a spatial pattern of hydrologic variability that implicates the PWC.
    Description: This work was supported by the Natural Science Foundation of China (NSFC) (40730107) and the Major State Basic Research Development Program of China (973 Program) (No.2010CB428902). DWO acknowledges support from the US NSF.
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  • 23
    Publication Date: 2022-05-25
    Description: © Macmillan Publishers Limited, 2012. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Nature Communications 3 (2012): 620, doi:10.1038/ncomms1636.
    Description: The Mid-Cayman spreading centre is an ultraslow-spreading ridge in the Caribbean Sea. Its extreme depth and geographic isolation from other mid-ocean ridges offer insights into the effects of pressure on hydrothermal venting, and the biogeography of vent fauna. Here we report the discovery of two hydrothermal vent fields on the Mid-Cayman spreading centre. The Von Damm Vent Field is located on the upper slopes of an oceanic core complex at a depth of 2,300 m. High-temperature venting in this off-axis setting suggests that the global incidence of vent fields may be underestimated. At a depth of 4,960 m on the Mid-Cayman spreading centre axis, the Beebe Vent Field emits copper-enriched fluids and a buoyant plume that rises 1,100 m, consistent with 〉 400 °C venting from the world’s deepest known hydrothermal system. At both sites, a new morphospecies of alvinocaridid shrimp dominates faunal assemblages, which exhibit similarities to those of Mid-Atlantic vents.
    Description: This work is supported by a UK NERC award (NE/F017774/1 & NE/F017758/1) to J.T.C., D.P.C., B.J.M., K.S. and P.A.T., Royal Society Travel Grant 2009/R3 to R.C.S., A.M. is supported by SENSEnet, a Marie Curie Initial Training Network (ITN) funded by the European Commission Seventh Framework Programme, Contract Number PITN-GA-2009-237868 and a NASA ASTEP Grant NNX09AB75G to C.R.G. and C.L.V.D., which are gratefully acknowledged.
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  • 24
    Publication Date: 2022-05-25
    Description: © The Author(s), 2012. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Nature Genetics 44 (2012): 121-126, doi:10.1038/ng.1054.
    Description: To make full use of research data, the bioscience community needs to adopt technologies and reward mechanisms that support interoperability and promote the growth of an open 'data commoning' culture. Here we describe the prerequisites for data commoning and present an established and growing ecosystem of solutions using the shared 'Investigation-Study-Assay' framework to support that vision.
    Description: The authors also acknowledge the following funding sources in particular: UK Biotechnology and Biological Sciences Research Council (BBSRC) BB/I000771/1 to S.-A.S. and A.T.; UK BBSRC BB/I025840/1 to S.-A.S.; UK BBSRC BB/I000917/1 to D.F.; EU CarcinoGENOMICS (PL037712) to J.K.; US National Institutes of Health (NIH) 1RC2CA148222-01 to W.H. and the HSCI; US MIRADA LTERS DEB-0717390 and Alfred P. Sloan Foundation (ICoMM) to L.A.-Z.; Swiss Federal Government through the Federal Office of Education and Science (FOES) to L.B. and I.X.; EU Innovative Medicines Initiative (IMI) Open PHACTS 115191 to C.T.E.; US Department of Energy (DOE) DE-AC02- 06CH11357 and Arthur P. Sloan Foundation (2011- 6-05) to J.G.; UK BBSRC SysMO-DB2 BB/I004637/1 and BBG0102181 to C.G.; UK BBSRC BB/I000933/1 to C.S. and J.L.G.; UK MRC UD99999906 to J.L.G.; US NIH R21 MH087336 (National Institute of Mental Health) and R00 GM079953 (National Institute of General Medical Science) to A.L.; NIH U54 HG006097 to J.C. and C.E.S.; Australian government through the National Collaborative Research Infrastructure Strategy (NCRIS); BIRN U24-RR025736 and BioScholar RO1-GM083871 to G.B. and the 2009 Super Science initiative to C.A.S.
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  • 25
    Publication Date: 2022-05-25
    Description: © The Author(s), 2012. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Nature Communications 3 (2012): 803, doi:10.1038/ncomms1811.
    Description: Ventilation and mixing of oceanic gyres is important to ocean-atmosphere heat and gas transfer, and to mid-latitude nutrient supply. The rates of mode water formation are believed to impact climate and carbon exchange between the surface and mid-depth water over decadal periods. Here, a record of 14C/12C (1780–1940), which is a proxy for vertical ocean mixing, from an annually banded coral from Bermuda, shows limited inter-annual variability and a substantial Suess Effect (the decrease in 14C/12C since 1900). The Sargasso Sea mixing rates between the surface and thermocline varied minimally over the past two centuries, despite changes to mean-hemispheric climate, including the Little Ice Age and variability in the North Atlantic Oscillation. This result indicates that regional formation rates of sub-tropical mode water are stable over decades, and that anthropogenic carbon absorbed by the ocean does not return to the surface at a variable rate.
    Description: Funding provided by NSF’s Chemical Oceanography Program OCE - 0526463 and 0961980 and the Stephen Hui Trust Fund.
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  • 26
    Publication Date: 2022-05-25
    Description: © The Author(s), 2012. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Scientific Reports 2 (2012): 553, doi:10.1038/srep00553.
    Description: Sea surface temperature imagery, satellite altimetry, and a surface drifter track reveal an unusual tilt in the Gulf Stream path that brought the Gulf Stream to 39.9°N near the Middle Atlantic Bight shelfbreak—200 km north of its mean position—in October 2011, while a large meander brought Gulf Stream water within 12 km of the shelfbreak in December 2011. Near-bottom temperature measurements from lobster traps on the outer continental shelf south of New England show distinct warming events (temperature increases exceeding 6°C) in November and December 2011. Moored profiler measurements over the continental slope show high salinities and temperatures, suggesting that the warm water on the continental shelf originated in the Gulf Stream. The combination of unusual water properties over the shelf and slope in late fall and the subsequent mild winter may affect seasonal stratification and habitat selection for marine life over the continental shelf in 2012.
    Description: Profiler data were made available by the Ocean Observatory Initiative (OOI) during the construction phase of the project. The OOI is funded by the National Science Foundation and managed by the Consortium for Ocean Leadership. Drifter data were provided by Tim Shaw and David Calhoun at Cape Fear Community College.GGGwas supported by NSFGrant OCE-1129125. RET was supported by the Postdoctoral Scholar Program at the Woods Hole Oceanographic Institution, with funding provided by the Cooperative Institute for the North Atlantic Region. MA was supported by the Penzance Endowed Fund in Support of Assistant Scientists.
    Keywords: Ecology ; Climate change ; Atmospheric science ; Oceanography
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  • 27
    Publication Date: 2022-05-25
    Description: © The Author(s), 2013. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Nature 496 (2013): 311-316, doi:10.1038/nature12027.
    Description: The discovery of a living coelacanth specimen in 1938 was remarkable, as this lineage of lobe-finned fish was thought to have become extinct 70 million years ago. The modern coelacanth looks remarkably similar to many of its ancient relatives, and its evolutionary proximity to our own fish ancestors provides a glimpse of the fish that first walked on land. Here we report the genome sequence of the African coelacanth, Latimeria chalumnae. Through a phylogenomic analysis, we conclude that the lungfish, and not the coelacanth, is the closest living relative of tetrapods. Coelacanth protein-coding genes are significantly more slowly evolving than those of tetrapods, unlike other genomic features. Analyses of changes in genes and regulatory elements during the vertebrate adaptation to land highlight genes involved in immunity, nitrogen excretion and the development of fins, tail, ear, eye, brain and olfaction. Functional assays of enhancers involved in the fin-to-limb transition and in the emergence of extra-embryonic tissues show the importance of the coelacanth genome as a blueprint for understanding tetrapod evolution.
    Description: cquisition and storage of Latimeria chalumnae samples was supported by grants from the African Coelacanth Ecosystem Programme of the South African National Department of Science and Technology. Generation of the Latimeria chalumnae and Protopterus annectens sequences by the Broad Institute of the Massachusetts Institute of Technology (MIT) and Harvard University was supported by grants from the National Human Genome Research Institute (NHGRI). K.L.T. is the recipient of a EURYI award from the European Science Foundation.
    Keywords: Genome evolution ; Comparative genomics
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  • 28
    Publication Date: 2022-05-25
    Description: © The Author(s), 2013. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Nature 499 (2013): 209–213, doi:10.1038/nature12221.
    Description: Coccolithophores have influenced the global climate for over 200 million years1. These marine phytoplankton can account for 20 per cent of total carbon fixation in some systems2. They form blooms that can occupy hundreds of thousands of square kilometres and are distinguished by their elegantly sculpted calcium carbonate exoskeletons (coccoliths), rendering them visible from space3. Although coccolithophores export carbon in the form of organic matter and calcite to the sea floor, they also release CO2 in the calcification process. Hence, they have a complex influence on the carbon cycle, driving either CO2 production or uptake, sequestration and export to the deep ocean4. Here we report the first haptophyte reference genome, from the coccolithophore Emiliania huxleyi strain CCMP1516, and sequences from 13 additional isolates. Our analyses reveal a pan genome (core genes plus genes distributed variably between strains) probably supported by an atypical complement of repetitive sequence in the genome. Comparisons across strains demonstrate that E. huxleyi, which has long been considered a single species, harbours extensive genome variability reflected in different metabolic repertoires. Genome variability within this species complex seems to underpin its capacity both to thrive in habitats ranging from the equator to the subarctic and to form large-scale episodic blooms under a wide variety of environmental conditions.
    Description: Joint Genome Institute (JGI) contributions were supported by the Office of Science of the US Department of Energy (DOE) under contract no. 7DE-AC02-05CH11231.
    Keywords: Genetic variation
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  • 29
    Publication Date: 2022-05-25
    Description: © The Author(s), 2013. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Nature 499 (2013): 431–437, doi:10.1038/nature12352.
    Description: Genome sequencing enhances our understanding of the biological world by providing blueprints for the evolutionary and functional diversity that shapes the biosphere. However, microbial genomes that are currently available are of limited phylogenetic breadth, owing to our historical inability to cultivate most microorganisms in the laboratory. We apply single-cell genomics to target and sequence 201 uncultivated archaeal and bacterial cells from nine diverse habitats belonging to 29 major mostly uncharted branches of the tree of life, so-called ‘microbial dark matter’. With this additional genomic information, we are able to resolve many intra- and inter-phylum-level relationships and to propose two new superphyla. We uncover unexpected metabolic features that extend our understanding of biology and challenge established boundaries between the three domains of life. These include a novel amino acid use for the opal stop codon, an archaeal-type purine synthesis in Bacteria and complete sigma factors in Archaea similar to those in Bacteria. The single-cell genomes also served to phylogenetically anchor up to 20% of metagenomic reads in some habitats, facilitating organism-level interpretation of ecosystem function. This study greatly expands the genomic representation of the tree of life and provides a systematic step towards a better understanding of biological evolution on our planet.
    Description: The work conducted by the US Department of Energy Joint Genome Institute is supported by the Office of Science of the US Department of Energy under Contract No. DE-AC02-05CH11231. We also thank the CeBiTec Bioinformatics Resource Facility, which is supported byBMBF grant 031A190. B.P.H. and J.A.D. were supported by the NASA Exobiology grant EXO-NNX11AR78GandNSFOISE 096842and B.P.H. by a generous contribution from G. Fullmer through the UNLV Foundation. S.M.S was supported by NSF grants OCE-0452333 and OCE-1136727, and the WHOI’s Andrew W. Mellon Fund for Innovative Research; and S.J.H. by the Canadian Foundation for Innovation, the British Columbia Knowledge Development Fund, the National Sciences and Engineering Research Council (NSERC) of Canada and the TULA foundation funded Centre for Microbial Diversity and Evolution (CMDE), and the Canadian Institute for Advanced Research (CIFAR). R.S. was supported by NSF grants DEB-841933, EF-826924, OCE-1232982, OCE-821374 and OCE-1136488, and the Deep Life I grant by the Alfred P. Sloan Foundation. P.H.was supported by a Discovery Outstanding Researcher Award (DORA) from the Australian Research Council, grant DP120103498.
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  • 30
    Publication Date: 2022-05-25
    Description: © The Author(s), 2014]. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Scientific Reports 4 (2014): 6648, doi:10.1038/srep06648.
    Description: Sediments from Tibetan lakes in NW China are potentially sensitive recorders of climate change and its impact on ecosystem function. However, the important plankton members in many Tibetan Lakes do not make and leave microscopically diagnostic features in the sedimentary record. Here we established a taxon-specific molecular approach to specifically identify and quantify sedimentary ancient DNA (sedaDNA) of non-fossilized planktonic organisms preserved in a 5-m sediment core from Kusai Lake spanning the last 3100 years. The reliability of the approach was validated with multiple independent genetic markers. Parallel analyses of the geochemistry of the core and paleo-climate proxies revealed that Monsoon strength-driven changes in nutrient availability, temperature, and salinity as well as orbitally-driven changes in light intensity were all responsible for the observed temporal changes in the abundance of two dominant phytoplankton groups in the lake, Synechococcus (cyanobacteria) and Isochrysis (haptophyte algae). Collectively our data show that global and regional climatic events exhibited a strong influence on the paleoecology of phototrophic plankton in Kusai Lake.
    Description: This research was supported by grants from the National Natural Science Foundation of China (Grant Nos. 41030211 and 41302022), the National Basic Research Program of China (Grant No. 2011CB808800), and State Key Laboratory of Biogeology and Environmental Geology, China University of Geosciences (Nos GBL11410 and GBL11201).
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  • 31
    Publication Date: 2022-05-25
    Description: © International Society for Microbial Ecology, 2011. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in The ISME Journal 5 (2011): 1748–1758, doi:10.1038/ismej.2011.48.
    Description: A novel hydrothermal field has been discovered at the base of Lōihi Seamount, Hawaii, at 5000 mbsl. Geochemical analyses demonstrate that ‘FeMO Deep’, while only 0.2 °C above ambient seawater temperature, derives from a distal, ultra-diffuse hydrothermal source. FeMO Deep is expressed as regional seafloor seepage of gelatinous iron- and silica-rich deposits, pooling between and over basalt pillows, in places over a meter thick. The system is capped by mm to cm thick hydrothermally derived iron-oxyhydroxide- and manganese-oxide-layered crusts. We use molecular analyses (16S rDNA-based) of extant communities combined with fluorescent in situ hybridizations to demonstrate that FeMO Deep deposits contain living iron-oxidizing Zetaproteobacteria related to the recently isolated strain Mariprofundus ferroxydans. Bioenergetic calculations, based on in-situ electrochemical measurements and cell counts, indicate that reactions between iron and oxygen are important in supporting chemosynthesis in the mats, which we infer forms a trophic base of the mat ecosystem. We suggest that the biogenic FeMO Deep hydrothermal deposit represents a modern analog for one class of geological iron deposits known as ‘umbers’ (for example, Troodos ophilolites, Cyprus) because of striking similarities in size, setting and internal structures.
    Description: Funding has been provided by the NSF Microbial Observatories Program (KJE, DE, BT, HS and CM), by the Gordon and Betty Moore Foundation (KJE), the College of Letters, Arts, and Sciences at the University of Southern California (KJE) and by the NASA Astrobiology Institute (KJE, DE).
    Keywords: Geomicrobiology ; Deep biosphere ; Hydrothermal ; Iron bacteria ; Iron oxidation
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  • 32
    Publication Date: 2022-05-25
    Description: Author Posting. © The Authors, 2012. This article is posted here by permission of Nature Publishing Group. The definitive version was published in Nature 486 (2012): 207-214, doi:10.1038/nature11234.
    Description: Studies of the human microbiome have revealed that even healthy individuals differ remarkably in the microbes that occupy habitats such as the gut, skin and vagina. Much of this diversity remains unexplained, although diet, environment, host genetics and early microbial exposure have all been implicated. Accordingly, to characterize the ecology of human-associated microbial communities, the Human Microbiome Project has analysed the largest cohort and set of distinct, clinically relevant body habitats so far. We found the diversity and abundance of each habitat’s signature microbes to vary widely even among healthy subjects, with strong niche specialization both within and among individuals. The project encountered an estimated 81–99% of the genera, enzyme families and community configurations occupied by the healthy Western microbiome. Metagenomic carriage of metabolic pathways was stable among individuals despite variation in community structure, and ethnic/racial background proved to be one of the strongest associations of both pathways and microbes with clinical metadata. These results thus delineate the range of structural and functional configurations normal in the microbial communities of a healthy population, enabling future characterization of the epidemiology, ecology and translational applications of the human microbiome.
    Description: This research was supported in part by National Institutes of Health grants U54HG004969 to B.W.B.; U54HG003273 to R.A.G.; U54HG004973 to R.A.G., S.K.H. and J.F.P.; U54HG003067 to E.S.Lander; U54AI084844 to K.E.N.; N01AI30071 to R.L.Strausberg; U54HG004968 to G.M.W.; U01HG004866 to O.R.W.; U54HG003079 to R.K.W.; R01HG005969 to C.H.; R01HG004872 to R.K.; R01HG004885 to M.P.; R01HG005975 to P.D.S.; R01HG004908 to Y.Y.; R01HG004900 to M.K.Cho and P. Sankar; R01HG005171 to D.E.H.; R01HG004853 to A.L.M.; R01HG004856 to R.R.; R01HG004877 to R.R.S. and R.F.; R01HG005172 to P. Spicer.; R01HG004857 to M.P.; R01HG004906 to T.M.S.; R21HG005811 to E.A.V.; M.J.B. was supported by UH2AR057506; G.A.B. was supported by UH2AI083263 and UH3AI083263 (G.A.B., C. N. Cornelissen, L. K. Eaves and J. F. Strauss); S.M.H. was supported by UH3DK083993 (V. B. Young, E. B. Chang, F. Meyer, T. M. S., M. L. Sogin, J. M. Tiedje); K.P.R. was supported by UH2DK083990 (J. V.); J.A.S. and H.H.K. were supported by UH2AR057504 and UH3AR057504 (J.A.S.); DP2OD001500 to K.M.A.; N01HG62088 to the Coriell Institute for Medical Research; U01DE016937 to F.E.D.; S.K.H. was supported by RC1DE0202098 and R01DE021574 (S.K.H. and H. Li); J.I. was supported by R21CA139193 (J.I. and D. S. Michaud); K.P.L. was supported by P30DE020751 (D. J. Smith); Army Research Office grant W911NF-11-1-0473 to C.H.; National Science Foundation grants NSF DBI-1053486 to C.H. and NSF IIS-0812111 to M.P.; The Office of Science of the US Department of Energy under Contract No. DE-AC02-05CH11231 for P.S. C.; LANL Laboratory-Directed Research and Development grant 20100034DR and the US Defense Threat Reduction Agency grants B104153I and B084531I to P.S.C.; Research Foundation - Flanders (FWO) grant to K.F. and J.Raes; R.K. is an HHMI Early Career Scientist; Gordon&BettyMoore Foundation funding and institutional funding fromthe J. David Gladstone Institutes to K.S.P.; A.M.S. was supported by fellowships provided by the Rackham Graduate School and the NIH Molecular Mechanisms in Microbial Pathogenesis Training Grant T32AI007528; a Crohn’s and Colitis Foundation of Canada Grant in Aid of Research to E.A.V.; 2010 IBM Faculty Award to K.C.W.; analysis of the HMPdata was performed using National Energy Research Scientific Computing resources, the BluBioU Computational Resource at Rice University.
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  • 33
    Publication Date: 2022-05-25
    Description: © International Society for Microbial Ecology, 2011. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in The ISME Journal 5 (2011): 1565–1567, doi:10.1038/ismej.2011.39.
    Description: Interest in sampling of diverse environments, combined with advances in high-throughput sequencing, vastly accelerates the pace at which new genomes and metagenomes are generated. For example, as of January 2011, 12 500 user-generated metagenomes have been submitted to the public MG-RAST Annotation server (http://metagenomics. nmpdr.org; Meyer et al., 2008), 490% of which were produced using high-throughput sequencing methodologies. We have entered into an era of ‘mega-sequencing projects’ that include the Genomic Encyclopaedia of Bacteria and Archaea project (http://www.jgi.doe.gov/programs/GEBA), the Microbial Earth Project (http://genome.jgi-psf. org/programs/bacteria-archaea/MEP/index.jsf), the Human Microbiome Project (http://nihroadmap.nih. gov/hmp), the Metagenomics of the Human Intestinal Tract consortium (http://www.metahit.eu), the Terragenome Initiative (http://www.terragenome. org), the Tara Oceans Expedition (http://oceans. taraexpeditions.org), the National Ecological Observatory Network (NEON-http://www.neoninc.org), the International Census of Marine Microbes (ICoMM-http://icomm.mbl.edu), Microbial Inventory Research Across Diverse Aquatic Long-Term Ecological Research Sites (http://amarallab.mbl. edu/mirada/mirada.html), the Earth Microbiome Project (http://www.earthmicrobiome.org) and other funded and unfunded projects, with many more visionary projects on the horizon.
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  • 34
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    Nature Publishing Group
    In:  EPIC3Nature Communications, Nature Publishing Group, 5, pp. 5520, ISSN: 2041-1723
    Publication Date: 2016-06-13
    Description: One of the most abrupt and yet unexplained past rises in atmospheric CO2 (〉10 p.p.m.v. in two centuries) occurred in quasi-synchrony with abrupt northern hemispheric warming into the Bølling/Allerød, ~14,600 years ago. Here we use a U/Th-dated record of atmospheric Δ14C from Tahiti corals to provide an independent and precise age control for this CO2 rise. We also use model simulations to show that the release of old (nearly 14C-free) carbon can explain these changes in CO2 and Δ14C. The Δ14C record provides an independent constraint on the amount of carbon released (~125 Pg C). We suggest, in line with observations of atmospheric CH4 and terrigenous biomarkers, that thawing permafrost in high northern latitudes could have been the source of carbon, possibly with contribution from flooding of the Siberian continental shelf during meltwater pulse 1A. Our findings highlight the potential of the permafrost carbon reservoir to modulate abrupt climate changes via greenhouse-gas feedbacks.
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  • 35
    Publication Date: 2014-12-17
    Description: Interior Antarctica is among the most remote places on Earth and was thought to be beyond the reach of human impacts when Amundsen and Scott raced to the South Pole in 1911. Here we show detailed measurements from an extensive array of 16 ice cores quantifying substantial toxic heavy metal lead pollution at South Pole and throughout Antarctica by 1889 – beating polar explorers by more than 22 years. Unlike the Arctic where lead pollution peaked in the 1970s, lead pollution in Antarctica was as high in the early 20th century as at any time since industrialization. The similar timing and magnitude of changes in lead deposition across Antarctica, as well as the characteristic isotopic signature of Broken Hill lead found throughout the continent, suggest that this single emission source in southern Australia was responsible for the introduction of lead pollution into Antarctica at the end of the 19th century and remains a significant source today. An estimated 660 t of industrial lead have been deposited over Antarctica during the past 130 years as a result of mid-latitude industrial emissions, with regional-to-global scale circulation likely modulating aerosol concentrations. Despite abatement efforts, significant lead pollution in Antarctica persists into the 21st century.
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  • 36
    Publication Date: 2017-01-04
    Description: Citation only. Published in Science 316: 567-570, doi: 10.1126/science.1137959
    Description: Funding was obtained primarily through the NSF, Ocean Sciences Programs in Chemical and Biological Oceanography, with additional support from the U.S. Department of Energy, Office of Science, Biological and Environmental Research Program, and other national programs, including the Australian Cooperative Research Centre program and Australian Antarctic Division.
    Keywords: Carbon flux ; Carbon sequestration ; Biological pump
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  • 37
    Publication Date: 2022-05-26
    Description: © The Author(s), 2013. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Nature 500 (2013): 453–457, doi:10.1038/nature12326.
    Description: Loss of sexual reproduction is considered an evolutionary dead end for metazoans, but bdelloid rotifers challenge this view as they appear to have persisted asexually for millions of years1. Neither male sex organs nor meiosis have ever been observed in these microscopic animals: oocytes are formed through mitotic divisions, with no reduction of chromosome number and no indication of chromosome pairing2. However, current evidence does not exclude that they may engage in sex on rare, cryptic occasions. Here we report the genome of a bdelloid rotifer, Adineta vaga (Davis, 1873)3, and show that its structure is incompatible with conventional meiosis. At gene scale, the genome of A. vaga is tetraploid and comprises both anciently duplicated segments and less divergent allelic regions. However, in contrast to sexual species, the allelic regions are rearranged and sometimes even found on the same chromosome. Such structure does not allow meiotic pairing; instead, we find abundant evidence of gene conversion, which may limit the accumulation of deleterious mutations in the absence of meiosis. Gene families involved in resistance to oxidation, carbohydrate metabolism and defence against transposons are significantly expanded, which may explain why transposable elements cover only 3% of the assembled sequence. Furthermore, 8% of the genes are likely to be of non-metazoan origin and were probably acquired horizontally. This apparent convergence between bdelloids and prokaryotes sheds new light on the evolutionary significance of sex.
    Description: This work was supported by Genoscope-CES (where most of the sequencing was performed), by US National Science Foundation grants MCB-0821956 and MCB-1121334 to I.A., by German Research Foundation grant HA 5163/2-1 to O.H., by grant 11.G34.31.0008 fromthe Ministry of Education and Science of the Russian Federation to A.S.K., by grant NSF CAREER number 0644282 to M.K., by US National Science Foundation grant MCB-0923676 to D.B.M.W., by FRFC grant 2.4.655.09.F from the Belgian Fonds National de la Recherche Scientifique (FNRS) and a start-up grant from the University of Namur to K.V.D.; J.F.F. and K.V.D. thank also J.-P. Descy (University of Namur) for funding support.
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  • 38
    Publication Date: 2022-05-26
    Description: © The Author(s), 2014. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Nature Communications 5 (2014): 4342, doi:10.1038/ncomms5342.
    Description: Three-dimensional (3D) bioimaging, visualization and data analysis are in strong need of powerful 3D exploration techniques. We develop virtual finger (VF) to generate 3D curves, points and regions-of-interest in the 3D space of a volumetric image with a single finger operation, such as a computer mouse stroke, or click or zoom from the 2D-projection plane of an image as visualized with a computer. VF provides efficient methods for acquisition, visualization and analysis of 3D images for roundworm, fruitfly, dragonfly, mouse, rat and human. Specifically, VF enables instant 3D optical zoom-in imaging, 3D free-form optical microsurgery, and 3D visualization and annotation of terabytes of whole-brain image volumes. VF also leads to orders of magnitude better efficiency of automated 3D reconstruction of neurons and similar biostructures over our previous systems. We use VF to generate from images of 1,107 Drosophila GAL4 lines a projectome of a Drosophila brain.
    Description: This work was mainly supported by Howard Hughes Medical Institute. H.P. is currently supported by the Allen Institute for Brain Science. R.W.T. and A.M. were supported by a grant MH071739 (MERIT).
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  • 39
    Publication Date: 2022-05-26
    Description: © The Author(s), 2014. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Nature Communications 5 (2014): 5385, doi:10.1038/ncomms6385.
    Description: Submarine mud volcanoes are important sources of methane to the water column. However, the temporal variability of their mud and methane emissions is unknown. Methane emissions were previously proposed to result from a dynamic equilibrium between upward migration and consumption at the seabed by methane-consuming microbes. Here we show non-steady-state situations of vigorous mud movement that are revealed through variations in fluid flow, seabed temperature and seafloor bathymetry. Time series data for pressure, temperature, pH and seafloor photography were collected over 431 days using a benthic observatory at the active Håkon Mosby Mud Volcano. We documented 25 pulses of hot subsurface fluids, accompanied by eruptions that changed the landscape of the mud volcano. Four major events triggered rapid sediment uplift of more than a metre in height, substantial lateral flow of muds at average velocities of 0.4 m per day, and significant emissions of methane and CO2 from the seafloor.
    Description: Participation of the Sentry AUV and TETHYS team from WHOI was funded by the Arctic Research Initiative of WHOI’s Ocean and Climate Change Institute and the NASA ASTEP grant NNX09AB76G. Additional funds were made available by the AWI, the Max Planck Society and the DFG METEOR/MERIAN programme, as well as the Leibniz programme to A.B.
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  • 40
    Publication Date: 2022-05-26
    Description: © The Author(s), 2014. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Nature Communications 5 (2014): 4102, doi:10.1038/ncomms5102.
    Description: Tropical south-western Pacific temperatures are of vital importance to the Great Barrier Reef (GBR), but the role of sea surface temperatures (SSTs) in the growth of the GBR since the Last Glacial Maximum remains largely unknown. Here we present records of Sr/Ca and δ18O for Last Glacial Maximum and deglacial corals that show a considerably steeper meridional SST gradient than the present day in the central GBR. We find a 1–2 °C larger temperature decrease between 17° and 20°S about 20,000 to 13,000 years ago. The result is best explained by the northward expansion of cooler subtropical waters due to a weakening of the South Pacific gyre and East Australian Current. Our findings indicate that the GBR experienced substantial meridional temperature change during the last deglaciation, and serve to explain anomalous deglacial drying of northeastern Australia. Overall, the GBR developed through significant SST change and may be more resilient than previously thought.
    Description: Funding was provided by Deutsche Forschungsgemeinschaft (FE 615/4-1), Australian Research Council (Discovery grant DP1094001), Australia and New Zealand IODP Consortium, Australian Institute of Nuclear Science and Engineering, Natural Environmental Research Council (NE/H014136/1, NE/H014268/1), the Cooperative Research Program of the Center for Advanced Marine Core Research (10B039, 11A013, 11B041), Ministry of Earth Sciences, Govt. of India (with partial support from DST & ISRO-GBP) and Japan Society for the Promotion of Science (JSPS NEXT-GR031).
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  • 41
    Publication Date: 2022-05-26
    Description: © The Author(s), 2012. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in The ISME Journal 6 (2012): 1901-1915, doi:10.1038/ismej.2012.31.
    Description: Antarctic surface oceans are well-studied during summer when irradiance levels are high, sea ice is melting and primary productivity is at a maximum. Coincident with this timing, the bacterioplankton respond with significant increases in secondary productivity. Little is known about bacterioplankton in winter when darkness and sea-ice cover inhibit photoautotrophic primary production. We report here an environmental genomic and small subunit ribosomal RNA (SSU rRNA) analysis of winter and summer Antarctic Peninsula coastal seawater bacterioplankton. Intense inter-seasonal differences were reflected through shifts in community composition and functional capacities encoded in winter and summer environmental genomes with significantly higher phylogenetic and functional diversity in winter. In general, inferred metabolisms of summer bacterioplankton were characterized by chemoheterotrophy, photoheterotrophy and aerobic anoxygenic photosynthesis while the winter community included the capacity for bacterial and archaeal chemolithoautotrophy. Chemolithoautotrophic pathways were dominant in winter and were similar to those recently reported in global ‘dark ocean’ mesopelagic waters. If chemolithoautotrophy is widespread in the Southern Ocean in winter, this process may be a previously unaccounted carbon sink and may help account for the unexplained anomalies in surface inorganic nitrogen content.
    Description: CSR was supported by an NSF Postdoctoral Fellowship in Biological Informatics (DBI-0532893). The research was supported by National Science Foundation awards: ANT 0632389 (to AEM and JJG), and ANT 0632278 and 0217282 (to HWD), all from the Antarctic Organisms and Ecosystems Program.
    Keywords: Antarctic bacterioplankton ; Metagenomics ; Chemolithoautotrophy
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  • 42
    Publication Date: 2022-05-26
    Description: © Macmillan Publishers, 2013. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Oncogene 32 (2013): 1135–1143, doi:10.1038/onc.2012.135.
    Description: Neurofibromatosis type 2 patients develop schwannomas, meningiomas and ependymomas resulting from mutations in the tumor suppressor gene, NF2, encoding a membrane-cytoskeleton adapter protein called merlin. Merlin regulates contact inhibition of growth and controls the availability of growth factor receptors at the cell surface. We tested if microtubule-based vesicular trafficking might be a mechanism by which merlin acts. We found that schwannoma cells, containing merlin mutations and constitutive activation of the Rho/Rac family of GTPases, had decreased intracellular vesicular trafficking relative to normal human Schwann cells. In Nf2−/− mouse Schwann (SC4) cells, re-expression of merlin as well as inhibition of Rac or its effector kinases, MLK and p38SAPK, each increased the velocity of Rab6 positive exocytic vesicles. Conversely, an activated Rac mutant decreased Rab6 vesicle velocity. Vesicle motility assays in isolated squid axoplasm further demonstrated that both mutant merlin and active Rac specifically reduce anterograde microtubule-based transport of vesicles dependent upon the activity of p38SAPK kinase. Taken together, our data suggest loss of merlin results in the Rac-dependent decrease of anterograde trafficking of exocytic vesicles, representing a possible mechanism controlling the concentration of growth factor receptors at the cell surface.
    Description: This work was supported by NIH R01 CA118032 (to NR), and MBL research fellowships (to NR and GM), NIH R01 NS23868 (to STB).
    Keywords: Merlin ; NF2 ; Rac ; Trafficking ; Exocytosis
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  • 43
    Publication Date: 2022-05-26
    Description: © The Author(s), 2014. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Scientific Reports 4 (2014): 4170, doi:10.1038/srep04170.
    Description: Estimating abundance of Antarctic minke whales is central to the International Whaling Commission's conservation and management work and understanding impacts of climate change on polar marine ecosystems. Detecting abundance trends is problematic, in part because minke whales are frequently sighted within Antarctic sea ice where navigational safety concerns prevent ships from surveying. Using icebreaker-supported helicopters, we conducted aerial surveys across a gradient of ice conditions to estimate minke whale density in the Weddell Sea. The surveys revealed substantial numbers of whales inside the sea ice. The Antarctic summer sea ice is undergoing rapid regional change in annual extent, distribution, and length of ice-covered season. These trends, along with substantial interannual variability in ice conditions, affect the proportion of whales available to be counted by traditional shipboard surveys. The strong association between whales and the dynamic, changing sea ice requires reexamination of the power to detect trends in whale abundance or predict ecosystem responses to climate change.
    Description: This work received funding from the following institutions: Alfred Wegener Institute for Polar and Marine Research (AWI); Dutch Ministry of Agriculture, Nature and Food Quality (EL & I); German Federal Ministry of Food, Agriculture and Consumer Protection (BMELV); German Federal Ministry for the Environment, Nature Conservation and Nuclear Safety (BMU); the Institute for Marine Resources and Ecosystem Studies (Wageningen IMARES); Johann Heinrich von Thu¨nen Institute (Federal Research Institute for Rural Areas, Forestry and Fisheries); the Netherlands Polar Programme (NPP) of the Netherlands Organisation for Scientific Research (NOW); Research and Technology Centre Westcoast (FTZ) of the University Kiel. RW was funded by a Marie Curie International Incoming Fellowship within the 7th European Community Framework Programme (proposal Nu 253407 (call reference: FP7- PEOPLE-2009-IIF).
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  • 44
    Publication Date: 2022-05-26
    Description: © The Author(s), 2013. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in ISME Journal 8 (2014): 1-3, doi:10.1038/ismej.2013.176.
    Description: The need for metadata standards for microbe sampling in the built environment.
    Description: We would like to thank the Alfred P Sloan Foundation grant FP047325-01-PR for support for this project.
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  • 45
    Publication Date: 2022-05-26
    Description: © The Author(s), 2014. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Scientific Reports 4 (2014): 5024, doi:10.1038/srep05024.
    Description: Climate change is a major threat to global biodiversity. Antarctic ecosystems are no exception. Investigating past species responses to climatic events can distinguish natural from anthropogenic impacts. Climate change produces ‘winners’, species that benefit from these events and ‘losers’, species that decline or become extinct. Using molecular techniques, we assess the demographic history and population structure of Pygoscelis penguins in the Scotia Arc related to climate warming after the Last Glacial Maximum (LGM). All three pygoscelid penguins responded positively to post-LGM warming by expanding from glacial refugia, with those breeding at higher latitudes expanding most. Northern (Pygoscelis papua papua) and Southern (Pygoscelis papua ellsworthii) gentoo sub-species likely diverged during the LGM. Comparing historical responses with the literature on current trends, we see Southern gentoo penguins are responding to current warming as they did during post-LGM warming, expanding their range southwards. Conversely, Adélie and chinstrap penguins are experiencing a ‘reversal of fortunes’ as they are now declining in the Antarctic Peninsula, the opposite of their response to post-LGM warming. This suggests current climate warming has decoupled historic population responses in the Antarctic Peninsula, favoring generalist gentoo penguins as climate change ‘winners’, while Adélie and chinstrap penguins have become climate change ‘losers’.
    Description: We thank the Zoological Society of London, Quark Expeditions, Exodus Travels ltd., Oceanites, the Holly Hill Charitable Trust, the Charities Advisory Trust and an U.S. National Science Foundation (NSF) Office of Polar Programs grant (ANT-0739575) for funding.
    Keywords: Climate-change ecology ; Molecular ecology ; Molecular evolution ; Population genetics
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  • 46
    Publication Date: 2022-05-26
    Description: © The Author(s), 2014. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Scientific Reports 4 (2014): 5316, doi:10.1038/srep05316.
    Description: During the propagation of coherent mesoscale eddies, they directly or indirectly induce many effects and interactions at different scales, implying eddies are actually serving as a kind of energy carrier or energy source for these eddy-related dynamic processes. To quantify this dynamically significant energy flow, the multi-year averaged horizontal eddy energy fluxes (EEFs) were estimated by using satellite altimetry data and a two-layer model based on hydrographic climatology. There is a strong net westward transport of eddy energy estimated at the mean value of ~13.3 GW north of 5°N and ~14.6 GW at the band 5°S ~ 44°S in the Southern Hemisphere. However, poleward of 44°S east-propagating eddies carry their energy eastward with an averaged net flux of ~3.2 GW. If confirmed, it would signify that geostrophic eddies not only contain the most of oceanic kinetic energy (KE), but also carry and spread a significant amount of energy with them.
    Description: This study is supported by Grants XDA11010202, 2011CB403505, 2013CB430303; Projects 41306016, U1033002, 40976021 of NNSFC and LTOZZ1304.
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  • 47
    facet.materialart.
    Unknown
    Nature Publishing Group
    Publication Date: 2022-05-26
    Description: Author Posting. © The Author(s), 2014. This is the author's version of the work. It is posted here by permission of Nature Publishing Group for personal use, not for redistribution. The definitive version was published in Nature Climate Change 4 (2014): 862-863, doi:10.1038/nclimate2386.
    Description: Low oxygen levels in tropical oceans shape marine ecosystems and biogeochemistry with climate change expected to expand these regions. Now, a study indicates that regional dynamics control tropical oxygen trends, bucking projected global reductions in ocean oxygen.
    Description: 2015-03-25
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  • 48
    Publication Date: 2022-05-26
    Description: © The Author(s), 2014. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Nature Communications 5 (2014): 4274, doi:10.1038/ncomms5274.
    Description: Ecological connections between surface waters and the deep ocean remain poorly studied despite the high biomass of fishes and squids residing at depths beyond the euphotic zone. These animals likely support pelagic food webs containing a suite of predators that include commercially important fishes and marine mammals. Here we deploy pop-up satellite archival transmitting tags on 15 Chilean devil rays (Mobula tarapacana) in the central North Atlantic Ocean, which provide movement patterns of individuals for up to 9 months. Devil rays were considered surface dwellers but our data reveal individuals descending at speeds up to 6.0 m s−1 to depths of almost 2,000 m and water temperatures 〈4 °C. The shape of the dive profiles suggests that the rays are foraging at these depths in deep scattering layers. Our results provide evidence of an important link between predators in the surface ocean and forage species occupying pelagic habitats below the euphotic zone in ocean ecosystems.
    Description: This research was partially supported by the Portuguese Foundation for Science and Technology/Ministry of Education and Science (FCT/MCTES-MEC) through individual support to P.A. (Cieˆncia 2008/POPH/QREN) and J.F. (SFRH/BPD/66532/2009) and the LARSyS Strategic Project (PEst/OE/EEI/LA00009/2011). This study was support by the US National Science Foundation (OCE 0825148 to S.R.T. and G.B.S.), The Harrison Foundation, Rodney and Elizabeth Berens, the King Abdullah University of Science and Technology (baseline research funds to M.L.B.) and the Woods Hole Oceanographic Institution.
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  • 49
    Publication Date: 2022-05-26
    Description: © The Author(s), 2014. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Scientific Reports 4 (2014): 5848, doi:10.1038/srep05848.
    Description: Interior Antarctica is among the most remote places on Earth and was thought to be beyond the reach of human impacts when Amundsen and Scott raced to the South Pole in 1911. Here we show detailed measurements from an extensive array of 16 ice cores quantifying substantial toxic heavy metal lead pollution at South Pole and throughout Antarctica by 1889 – beating polar explorers by more than 22 years. Unlike the Arctic where lead pollution peaked in the 1970s, lead pollution in Antarctica was as high in the early 20th century as at any time since industrialization. The similar timing and magnitude of changes in lead deposition across Antarctica, as well as the characteristic isotopic signature of Broken Hill lead found throughout the continent, suggest that this single emission source in southern Australia was responsible for the introduction of lead pollution into Antarctica at the end of the 19th century and remains a significant source today. An estimated 660 t of industrial lead have been deposited over Antarctica during the past 130 years as a result of mid-latitude industrial emissions, with regional-to-global scale circulation likely modulating aerosol concentrations. Despite abatement efforts, significant lead pollution in Antarctica persists into the 21st century.
    Description: This work primarily was supported by the U.S. National Science Foundation Division of Polar Programs (research grants 9903744, 0538427, 0538416, 0968391, 1142166, 0632031; instrument grants 0216552, 0421412).
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  • 50
    Publication Date: 2022-05-26
    Description: © The Author(s), 2014. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Scientific Reports 4 (2014): 7366, doi:10.1038/srep07366.
    Description: The magnitude of flooding in New York City by Hurricane Sandy is commonly believed to be extremely rare, with estimated return periods near or greater than 1000 years. However, the brevity of tide gauge records result in significant uncertainties when estimating the uniqueness of such an event. Here we compare resultant deposition by Hurricane Sandy to earlier storm-induced flood layers in order to extend records of flooding to the city beyond the instrumental dataset. Inversely modeled storm conditions from grain size trends show that a more compact yet more intense hurricane in 1821 CE probably resulted in a similar storm tide and a significantly larger storm surge. Our results indicate the occurrence of additional flood events like Hurricane Sandy in recent centuries, and highlight the inadequacies of the instrumental record in estimating current flood risk by such extreme events.
    Description: Funding for this work was provided by the Hudson River Foundation Expedited Grant #004/12E, the Hudson River Foundation Graduate Fellowship 02–13, the National Science Foundation (RAPID grant #1313859 and instrument and facility support via grant IF-0949313), and the Dalio Explore Fund.
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  • 51
    Electronic Resource
    Electronic Resource
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 18 (2000), S. 1-17 
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract The discovery that genes in the major histocompatibility complex (MHC) play an important role in the immune response depended on the chance interaction of several unrelated events. The first, and most important, was the decision by Michael Sela to synthesize a series of branched, multichain, synthetic polypeptides based on a backbone of poly-l-lysine. The prototype compound, (T,G)-A-L, was tipped with short random sequences of tyrosine and glutamic acid. This resulted in a restricted range of antigenic determinants composed of only two or three amino acids with a variable length-ideal for binding to the peptide binding groove of MHC class II molecules. The second was the decision by John Humphrey to immunize various strains of rabbits with this synthetic polypeptide. Two of these rabbit strains showed very large quantitative differences in antibody response to (T,G)-A-L. In transferring this system to inbred mouse strains, the third bit of good fortune was the availability at the National Institute of Medical Research, in Mill Hill (London), of the CBA (H2k) and C57 (H2b) strains. The H2b haplotype is the only one mediating a uniform high antibody response to (T,G)-A-L. The fourth critical ingredient was the availability of numerous congenic and H2 recombinant inbred strains of mice produced earlier by Snell, Stimpfling, Shreffler, and Klein. A search for congenic pairs of mice expressing the responder and nonresponder H2 haplotypes on the same background revealed that these strains responded as a function of their H2 haplotype, not of their inbred background. Extensive studies in a variety of inbred strains carrying recombinant H2 haplotypes, as well as a four-point linkage cross, mapped immune response to (T,G)A-L within the murine MHC, between the K and Ss loci. The demonstration that stimulation in the mixed lymphocyte reaction (MLR) mapped to the same region quickly led to attempts to produce antisera in congenic H2 recombinant strain combinations. These antisera identified I-region associated (Ia) antigens. Immunoprecipitation and blocking studies showed that the gene products controlling specific immune responses, the mixed lymphocyte reaction, and the structure of Ia antigens were one and the same-now designated as the I-A MHC class II molecules. These antisera and inbred strains enabled Unanue to demonstrate the peptide binding function of class II MHC molecules.
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  • 52
    Electronic Resource
    Electronic Resource
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 18 (2000), S. 165-184 
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract Ligation of the T cell antigen receptor (TCR) stimulates protein tyrosine kinases (PTKs), which regulate intracellular calcium and control the activity of protein kinase C (PKC) isozymes. PTKs activated by antigen receptors and costimulatory molecules also couple to phosphatidylinositol-3 kinase (PI3K) and control the activity of Ras- and Rho-family GTPases. T cell signal transduction is triggered physiologically by antigen in the context of antigen presenting cells (APC). The formation of stable and prolonged contacts between T cells and APCs is not neccessary to initiate T cell signaling but is required for effective T cell proliferation and differentiation. The stabilization of the T cell/ APC conjugate is regulated by intracellular signals induced by antigen receptors and costimulators. These coordinate the regulation of the actin and microtubule cytoskeleton and organize a specialized signaling zone that allows sustained TCR signaling.
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  • 53
    Electronic Resource
    Electronic Resource
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 18 (2000), S. 245-273 
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract The potential to harness the potency and specificity of the immune system underlies the growing interest in cancer immunotherapy. One such approach uses bone marrow-derived dendritic cells, phenotypically distinct and extremely potent antigen-presenting cells, to present tumor-associated antigens and thereby generate tumor-specific immunity. Support for this strategy comes from animal studies that have demonstrated that dendritic cells, when loaded ex vivo with tumor antigens and administered to tumor-bearing hosts, can elicit T cell-mediated tumor destruction. These observations have led to clinical trials designed to investigate the immunologic and clinical effects of antigen-loaded dendritic cells administered as a therapeutic vaccine to patients with cancer. In the design and conduct of such trials, important considerations include antigen selection, methods for introducing the antigen into MHC class I and II processing pathways, methods for isolating and activating dendritic cells, and route of administration. Although current dendritic cell-based vaccination methods are cumbersome, promising results from clinical trials in patients with malignant lymphoma, melanoma, and prostate cancer suggest that immunotherapeutic strategies that take advantage of the antigen presenting properties of dendritic cells may ultimately prove both efficacious and widely applicable to human tumors.
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  • 54
    Electronic Resource
    Electronic Resource
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 18 (2000), S. 347-366 
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract Allergic diseases affect approximately one third of the general population. This class of disease, characterized by elevated serum IgE levels and hypersensitivity to normally innocuous antigen, can manifest in practically any mucosal tissue or as a systemic response. A few examples of serious allergic diseases include asthma, dermatitis, bee sting allergy, food allergy, conjunctivitis, and severe systemic anaphylaxis. Taken together, allergic diseases constitute one of the major problems of modern day medicine. A considerable portion of the healthcare budget is expended in the treatment of allergic disease, and morbidity rates of inner city asthmatics are rising steadily. Due to the enormity of the problem, there has been a worldwide effort to identify factors that contribute to the etiology of allergic diseases. Epidemiologic studies of multigeneration families and large numbers of twins clearly indicate a strong genetic component to atopic diseases. At least two independently segregating diseasesusceptibility genes are thought to come together with environmental factors to result in allergic inflammation in a particular tissue. On the basis of the strong genetic studies, multiple groups have attempted to identify disease-susceptibility genes via either a candidate gene approach or by genome-wide scans. Both of these approaches have implicated multiple regions in the human and mouse genomes, which are currently being evaluated as harboring putative atopy genes.
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  • 55
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract The human thymus is a complex chimeric organ comprised of central (thymic epithelial space) and peripheral (perivascular space) components that functions well into adult life to produce naive T lymphocytes. Recent advances in identifying thymic emigrants and development of safe methods to study thymic function in vivo in adults have provided new opportunities to understand the role that the human thymus plays in immune reconstitution in aging, in bone marrow transplantation, and in HIV-1 infection. The emerging concept is that there are age-dependent contributions of thymic emigrants and proliferation of postthymic T cells to maintain the peripheral T cell pool and to contribute to T cell regeneration, with the thymus contributing more at younger ages and peripheral T cell expansion contributing more in older subjects. New studies have revealed a dynamic interplay between postnatal thymus output and peripheral T cell pool proliferation, which play important roles in determining the nature of immune reconstitution in congenital immunodeficiency diseases, in bone marrow transplantation, and in HIV-1 infection. In this paper, we review recent data on human postnatal thymus function that, taken together, support the notion that the human thymus is functional well into the sixth decade and plays a role throughout life to optimize human immune system function.
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  • 56
    Electronic Resource
    Electronic Resource
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 18 (2000), S. 709-737 
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract Antibodies can completely suppress or enhance the antibody response to their specific antigen by several hundredfold. Immunoglobulin M (IgM) enhances antibody responses via the complement system, and complement activation by IgM probably starts the chain of events leading to antibody responses to suboptimal antigen doses. IgG can enhance primary antibody responses in the absence of the complement system and seems to be dependent on Fc receptors for IgG (FcgammaRs). IgE enhances antibody responses via the low-affinity receptor for IgE (FcepsilonRII/CD23). The precise effector mechanisms that cause enhancement are not known, but direct B-cell signaling, antigen presentation, and increased follicular localization are all possibilities. IgG, IgE, and IgM may also suppress antibody responses when used in certain immunization regimes, and it seems reasonable that an important mechanism behind suppression is the masking of antigenic epitopes by antibodies. In addition, FcgammaRIIB, which contains a cytoplasmic inhibitory motif, acts as a negative regulator of antibody responses. This receptor, however, may prevent the antibody responses from exceeding a certain level rather than causing complete suppression.
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    Annual Review of Immunology 18 (2000), S. 767-811 
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Abstract Dendritic cells (DCs) are antigen-presenting cells with a unique ability to induce primary immune responses. DCs capture and transfer information from the outside world to the cells of the adaptive immune system. DCs are not only critical for the induction of primary immune responses, but may also be important for the induction of immunological tolerance, as well as for the regulation of the type of T cell-mediated immune response. Although our understanding of DC biology is still in its infancy, we are now beginning to use DC-based immunotherapy protocols to elicit immunity against cancer and infectious diseases.
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    Annual Review of Immunology 18 (2000), S. 927-974 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Abstract The development and widespread use of vaccines against infectious agents have been a great triumph of medical science. One reason for the success of currently available vaccines is that they are capable of inducing long-lived antibody responses, which are the principal agents of immune protection against most viruses and bacteria. Despite these successes, vaccination against intracellular organisms that require cell-mediated immunity, such as the agents of tuberculosis, malaria, leishmaniasis, and human immunodeficiency virus infection, are either not available or not uniformly effective. Owing to the substantial morbidity and mortality associated with these diseases worldwide, an understanding of the mechanisms involved in generating long-lived cellular immune responses has tremendous practical importance. For these reasons, a new form of vaccination, using DNA that contains the gene for the antigen of interest, is under intensive investigation, because it can engender both humoral and cellular immune responses. This review focuses on the mechanisms by which DNA vaccines elicit immune responses. In addition, a list of potential applications in a variety of preclinical models is provided.
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    Notes: Abstract Physical detection of antigen-specific CD4 T cells has revealed features of the in vivo immune response that were not appreciated from in vitro studies. In vivo, antigen is initially presented to naive CD4 T cells exclusively by dendritic cells within the T cell areas of secondary lymphoid tissues. Anatomic constraints make it likely that these dendritic cells acquire the antigen at the site where it enters the body. Inflammation enhances in vivo T cell activation by stimulating dendritic cells to migrate to the T cell areas and display stable peptide-MHC complexes and costimulatory ligands. Once stimulated by a dendritic cell, antigen-specific CD4 T cells produce IL-2 but proliferate in an IL-2-independent fashion. Inflammatory signals induce chemokine receptors on activated T cells that direct their migration into the B cell areas to interact with antigen-specific B cells. Most of the activated T cells then die within the lymphoid tissues. However, in the presence of inflammation, a population of memory T cells survives. This population is composed of two functional classes. One recirculates through nonlymphoid tissues and is capable of immediate effector lymphokine production. The other recirculates through lymph nodes and quickly acquires the capacity to produce effector lymphokines if stimulated. Therefore, antigenic stimulation in the presence of inflammation produces an increased number of specific T cells capable of producing effector lymphokines throughout the body.
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    Annual Review of Immunology 19 (2001), S. 163-196 
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract Rheumatoid arthritis (RA), a systemic disease, is characterized by a chronic inflammatory reaction in the synovium of joints and is associated with degeneration of cartilage and erosion of juxta-articular bone. Many pro-inflammatory cytokines including TNFalpha, chemokines, and growth factors are expressed in diseased joints. The rationale that TNFalpha played a central role in regulating these molecules, and their pathophysiological potential, was initially provided by the demonstration that anti-TNFalpha antibodies added to in vitro cultures of a representative population of cells derived from diseased joints inhibited the spontaneous production of IL-1 and other pro-inflammatory cytokines. Systemic administration of anti-TNFalpha antibody or sTNFR fusion protein to mouse models of RA was shown to be anti-inflammatory and joint protective. Clinical investigations in which the activcity of TNFalpha in RA patients was blocked with intravenously administered infliximab, a chimeric anti-TNFalpha monoclonal antibody (mAB), has provided evidence that TNF regulates IL-6, IL-8, MCP-1, and VEGF production, recruitment of immune and inflammatory cells into joints, angiogenesis, and reduction of blood levels of matrix metalloproteinases-1 and -3. Randomized, placebo-controlled, multi-center clinical trials of human TNFalpha inhibitors have demonstrated their consistent and remarkable efficacy in controlling signs and symptoms, with a favorable safety profile, in approximately two thirds of patients for up to 2 years, and their ability to retard joint damage. Infliximab (a mAB), and etanercept (a sTNF-R-Fc fusion protein) have been approved by regulatory authorities in the United States and Europe for treating RA, and they represent a significant new addition to available therapeutic options.
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    Notes: Abstract Natural killer cells can discriminate between normal cells and cells that do not express adequate amounts of major histocompatibility complex (MHC) class I molecules. The discovery, both in mouse and in human, of MHC-specific inhibitory receptors clarified the molecular basis of this important NK cell function. However, the triggering receptors responsible for positive NK cell stimulation remained elusive until recently. Some of these receptors have now been identified in humans, thus shedding some light on the molecular mechanisms involved in NK cell activation during the process of natural cytotoxicity. Three novel, NK-specific, triggering surface molecules (NKp46, NKp30, and NKp44) have been identified. They represent the first members of a novel emerging group of receptors collectively termed natural cytotoxicity receptors (NCR). Monoclonal antibodies (mAbs) to NCR block to differing extents the NK-mediated lysis of various tumors. Moreover, lysis of certain tumors can be virtually abrogated by the simultaneous masking of the three NCRs. There is a coordinated surface expression of the three NCRs, their surface density varying in different individuals and also in the NK cells isolated from a given individual. A direct correlation exists between the surface density of NCR and the ability of NK cells to kill various tumors. NKp46 is the only NCR involved in human NK-mediated killing of murine target cells. Accordingly, a homologue of NKp46 has been detected in mouse. Molecular cloning of NCR revealed novel members of the Ig superfamily displaying a low degree of similarity to each other and to known human molecules. NCRs are coupled to different signal transducing adaptor proteins, including CD3zeta, FcRIgamma, and KARAP/DAP12. Another triggering NK receptor is NKG2D. It appears to play either a complementary or a synergistic role with NCRs. Thus, the triggering of NK cells in the process of tumor cell lysis may often depend on the concerted action of NCR and NKG2D. In some instances, however, it may uniquely depend upon the activity of NCR or NKG2D only. Strict NKG2D-dependency can be appreciated using clones that, in spite of their NCRdull phenotype, efficiently lyse certain epithelial tumors or leukemic cell lines. Other triggering surface molecules including 2B4 and the novel NKp80 appear to function as coreceptors rather than as true receptors. Indeed, they can induce natural cytotoxicity only when co-engaged with a triggering receptor. While an altered expression or function of NCR or NKG2D is being explored as a possible cause of immunological disorders, 2B4 dysfunction has already been associated with a severe form of immunodeficiency. Indeed, in patients with the X-linked lymphoproliferative disease, the inability to control Epstein-Barr virus infections may be consequent to a major dysfunction of 2B4 that exerts inhibitory instead of activating functions.
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    Annual Review of Immunology 19 (2001), S. 497-521 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract Elevation of intracellular free Ca2+ is one of the key triggering signals for T-cell activation by antigen. A remarkable variety of Ca2+ signals in T cells, ranging from infrequent spikes to sustained oscillations and plateaus, derives from the interactions of multiple Ca2+ sources and sinks in the cell. Following engagement of the T cell receptor, intracellular channels (IP3 and ryanodine receptors) release Ca2+ from intracellular stores, and by depleting the stores trigger prolonged Ca2+ influx through store-operated Ca2+ (CRAC) channels in the plasma membrane. The amplitude and dynamics of the Ca2+ signal are shaped by several mechanisms, including K+ channels and membrane potential, slow modulation of the plasma membrane Ca2+-ATPase, and mitochondria that buffer Ca2+ and prevent the inactivation of CRAC channels. Ca2+ signals have a number of downstream targets occurring on multiple time scales. At short times, Ca2+ signals help to stabilize contacts between T cells and antigen-presenting cells through changes in motility and cytoskeletal reorganization. Over periods of minutes to hours, the amplitude, duration, and kinetic signature of Ca2+ signals increase the efficiency and specificity of gene activation events. The complexity of Ca2+ signals contains a wealth of information that may help to instruct lymphocytes to choose between alternate fates in response to antigenic stimulation.
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    Annual Review of Immunology 19 (2001), S. 595-621 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Abstract B cell development is a highly regulated process whereby functional peripheral subsets are produced from hematopoietic stem cells, in the fetal liver before birth and in the bone marrow afterward. Here we review progress in understanding some aspects of this process in the mouse bone marrow, focusing on delineation of the earliest stages of commitment, on pre-B cell receptor selection, and B cell tolerance during the immature-to-mature B cell transition. Then we note some of the distinctions in hematopoiesis and pre-B selection between fetal liver and adult bone marrow, drawing a connection from fetal development to B-1/CD5+ B cells. Finally, focusing on CD5+ cells, we consider the forces that influence the generation and maintenance of this distinctive peripheral B cell population, enriched for natural autoreactive specificities that are encoded by particular germline VH-VL combinations.
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    Annual Review of Immunology 1 (1983), S. 87-115 
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    Annual Review of Immunology 1 (1983), S. 143-173 
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    Annual Review of Immunology 1 (1983), S. 335-359 
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    Annual Review of Immunology 1 (1983), S. 307-327 
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    Annual Review of Immunology 1 (1983), S. 439-461 
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    Annual Review of Immunology 1 (1983), S. 529-568 
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    Annual Review of Immunology 20 (2002), S. 1-28 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: In this essay, I make four points about the operation of the immune system. First, thanks to the innate immune system's regulation of the main costimulatory molecules CD80 and CD86, the immune system rarely mistakes a pathogen for a self-antigen. Second, the adaptive immune system consisting of T lymphocytes and B lymphocytes can mistake self for non-self because adaptive immunity is selected in single somatic cells. Third, the adaptive immune system of T lymphocytes and B lymphocytes is always referential to self, as it is selected on self-ligands; it persists in the periphery on self-ligands; and at least for T cells, it is dependent on self-ligands to be able to mount a response. Fourth, it is becoming clear that regulatory or suppressor T cells are our main defense against autoimmunity, as my first boss, Richard Gershon, had predicted. These cells recognize antigen as do all T cells, but they secrete the immunoregulatory cytokines IL-10 and TGFbeta.
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    Annual Review of Immunology 20 (2002), S. 125-163 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Abstract A reciprocal regulation exists between the central nervous and immune systems through which the CNS signals the immune system via hormonal and neuronal pathways and the immune system signals the CNS through cytokines. The primary hormonal pathway by which the CNS regulates the immune system is the hypothalamic-pituitary-adrenal axis, through the hormones of the neuroendocrine stress response. The sympathetic nervous system regulates the function of the immune system primarily via adrenergic neurotransmitters released through neuronal routes. Neuroendocrine regulation of immune function is essential for survival during stress or infection and to modulate immune responses in inflammatory disease. Glucocorticoids are the main effector end point of this neuroendocrine system and, through the glucocorticoid receptor, have multiple effects on immune cells and molecules. This review focuses on the regulation of the immune response via the neuroendocrine system. Particular details are presented on the effects of interruptions of this regulatory loop at multiple levels in predisposition and expression of immune diseases and on mechanisms of glucocorticoid effects on immune cells and molecules.
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    Annual Review of Immunology 20 (2002), S. 217-251 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Abstract KIR genes have evolved in primates to generate a diverse family of receptors with unique structures that enable them to recognize MHC-class I molecules with locus and allele-specificity. Their combinatorial expression creates a repertoire of NK cells that surveys the expression of almost every MHC molecule independently, thus antagonizing the spread of pathogens and tumors that subvert innate and adaptive defense by selectively downregulating certain MHC class I molecules. The genes encoding KIR that recognize classical MHC molecules have diversified rapidly in human and primates; this contrasts with conservation of immunoglobulin- and lectin-like receptors for nonclassical MHC molecules. As a result of the variable KIR-gene content in the genome and the polymorphism of the HLA system, dissimilar numbers and qualities of KIR:HLA pairs function in different humans. This diversity likely contributes variability to the function of NK cells and T-lymphocytes by modulating innate and adaptive immune responses to specific challenges.
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    Annual Review of Immunology 20 (2002), S. 371-394 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Abstract Engagement of the T cell antigen receptor (TCR) leads to a complex series of molecular changes at the plasma membrane, in the cytoplasm, and at the nucleus that lead ultimately to T cell effector function. Activation at the TCR of a set of protein tyrosine kinases (PTKs) is an early event in this process. This chapter reviews some of the critical substrates of these PTKs, the adapter proteins that, following phosphorylation on tyrosine residues, serve as binding sites for many of the critical effector enzymes and other adapter proteins required for T cell activation. The role of these adapters in binding various proteins, the interaction of adapters with plasma membrane microdomains, and the function of adapter proteins in control of the cytoskeleton are discussed.
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    Annual Review of Immunology 20 (2002), S. 551-579 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Abstract Typical immune responses lead to prominent clonal expansion of antigen-specific T and B cells followed by differentiation into effector cells. Most effector cells die at the end of the immune response but some of these cells survive and form long-lived memory cells. The factors controlling the formation and survival of memory T cells are reviewed.
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    Annual Review of Immunology 20 (2002), S. 709-760 
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    Notes: Abstract Unmethylated CpG motifs are prevalent in bacterial but not vertebrate genomic DNAs. Oligodeoxynucleotides (ODN) containing CpG motifs activate host defense mechanisms leading to innate and acquired immune responses. The recognition of CpG motifs requires Toll-like receptor (TLR) 9, which triggers alterations in cellular redox balance and the induction of cell signaling pathways including the mitogen activated protein kinases (MAPKs) and NFkappaB. Cells that express TLR-9, which include plasmacytoid dendritic cells (PDCs) and B cells, produce Th1-like proinflammatory cytokines, interferons, and chemokines. Certain CpG motifs (CpG-A) are especially potent at activating NK cells and inducing IFN-alpha production by PDCs, while other motifs (CpG-B) are especially potent B cell activators. CpG-induced activation of innate immunity protects against lethal challenge with a wide variety of pathogens, and has therapeutic activity in murine models of cancer and allergy. CpG ODN also enhance the development of acquired immune responses for prophylactic and therapeutic vaccination.
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    Annual Review of Immunology 21 (2003), S. 29-70 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Abstract CD8 T cells respond to viral infections but also participate in defense against bacterial and protozoal infections. In the last few years, as new methods to accurately quantify and characterize pathogen-specific CD8 T cells have become available, our understanding of in vivo T cell responses has increased dramatically. Pathogen-specific T cells, once thought to be quite rare following infection, are now known to be present at very high frequencies, particularly in peripheral, nonlymphoid tissues. With the ability to visualize in vivo CD8 T cell responses has come the recognition that T cell expansion is programmed and, to a great extent, independent of antigen concentrations. Comparison of CD8 T cell responses to different pathogens also highlights the intricate relationship between microbially induced innate inflammatory responses and the kinetics, magnitude, and character of long-term T cell responses. This review describes recent progress in some of the major murine models of CD8 T cell-mediated immunity to viral, bacterial, and protozoal infection.
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    Annual Review of Immunology 21 (2003), S. 139-176 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Abstract A functional immune system requires the selection of T lymphocytes expressing receptors that are major histocompatibility complex restricted but tolerant to self-antigens. This selection occurs predominantly in the thymus, where lymphocyte precursors first assemble a surface receptor. In this review we summarize the current state of the field regarding the natural ligands and molecular factors required for positive and negative selection and discuss a model for how these disparate outcomes can be signaled via the same receptor. We also discuss emerging data on the selection of regulatory T cells. Such cells require a high-affinity interaction with self-antigens, yet differentiate into regulatory cells instead of being eliminated.
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    Annual Review of Immunology 21 (2003), S. 265-304 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Abstract In the absence of antiretroviral treatment, HIV-1 establishes a chronic, progressive infection of the human immune system that invariably, over the course of years, leads to its destruction and fatal immunodeficiency. Paradoxically, while viral replication is extensive throughout the course of infection, deterioration of conventional measures of immunity is slow, including the characteristic loss of CD4+ T cells that is thought to play a key role in the development of immunodeficiency. This conundrum suggests that CD4+ T cell-directed viral cytopathicity alone cannot explain the course of disease. Indeed, recent advances now indicate that HIV-1 pathogenesis is likely to result from a complex interplay between the virus and the immune system, particularly the mechanisms responsible for T cell homeostasis and regeneration. We review these data and present a model of HIV-1 pathogenesis in which the protracted loss of CD4+ T cells results from early viral destruction of selected memory T cell populations, followed by a combination of profound increases in overall memory T cell turnover, damage to the thymus and other lymphoid tissues, and physiological limitations in peripheral CD4+ T cell renewal.
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    Annual Review of Immunology 21 (2003), S. 425-456 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Abstract IL-13 was first recognized for its effects on B cells and monocytes, where it upregulated class II expression, promoted IgE class switching and inhibited inflammatory cytokine production. It was also thought to be functionally redundant with IL-4. However, studies conducted with knockout mice, neutralizing antibodies, and novel antagonists demonstrate that IL-13 possesses several unique effector functions that distinguish it from IL-4. Resistance to most gastrointestinal nematodes is mediated by type-2 cytokine responses, in which IL-13 plays a dominant role. By regulating cell-mediated immunity, IL-13 modulates resistance to intracellular organisms including Leishmania major, Leishmania mexicana, and Listeria monocytogenes. In the lung, IL-13 is the central mediator of allergic asthma, where it regulates eosinophilic inflammation, mucus secretion, and airway hyperresponsiveness. Manipulation of IL-13 effector function may also prove useful in the treatment of some cancers like B-cell chronic lymphocytic leukemia and Hodgkin's disease, where IL-13 modulates apoptosis or tumor cell growth. IL-13 can also inhibit tumor immunosurveillance. As such, inhibitors of IL-13 might be effective as cancer immunotherapeutics by boosting type-1-associated anti-tumor defenses. Finally, IL-13 was revealed as a potent mediator of tissue fibrosis in both schistosomiasis and asthma, which indicates that it is a key regulator of the extracellular matrix. The mechanisms that regulate IL-13 production and/or function have also been investigated, and IL-4, IL-12, IL-18, IFN-gamma, IL-10, TGF-beta, TNF-alpha, and the IL-4/IL-13 receptor complex play important roles. This review highlights the effector functions of IL-13 and describes multiple pathways for modulating its activity in vivo.
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    Annual Review of Immunology 21 (2003), S. 547-578 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Abstract Collectins and ficolins, present in plasma and on mucosal surfaces, are humoral molecules of the innate immune systems, which recognize pathogen-associated molecular patterns. The human collectins, mannan-binding lectin (MBL) and surfactant protein A and D (SP-A and SP-D), are oligomeric proteins composed of carbohydrate-recognition domains (CRDs) attached to collagenous regions and are thus structurally similar to the ficolins, L-ficolin, M-ficolin, and H-ficolin. However, they make use of different CRD structures: C-type lectin domains for the collectins and fibrinogen-like domains for the ficolins. Upon recognition of the infectious agent, MBL and the ficolins initiate the lectin pathway of complement activation through attached serine proteases (MASPs), whereas SP-A and SP-D rely on other effector mechanisms: direct opsonization, neutralization, and agglutination. This limits the infection and concurrently orchestrates the subsequent adaptive immune response. Deficiencies of the proteins may predispose to infections or other complications, e.g., reperfusion injuries or autoimmune diseases. Structure, function, clinical implications, and phylogeny are reviewed.
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    Annual Review of Immunology 21 (2003), S. 713-758 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Abstract The T helper lymphocyte is responsible for orchestrating the appropriate immune response to a wide variety of pathogens. The recognition of the polarized T helper cell subsets Th1 and Th2 has led to an understanding of the role of these cells in coordinating a variety of immune responses, both in responses to pathogens and in autoimmune and allergic disease. Here, we discuss the mechanisms that control lineage commitment to the Th1 phenotype. What has recently emerged is a rich understanding of the cytokines, receptors, signal transduction pathways, and transcription factors involved in Th1 differentiation. Although the picture is still incomplete, the basic pathways leading to Th1 differentiation can now be understood in in vitro and a number of infection and disease models.
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    Annual Review of Immunology 21 (2003), S. 685-711 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Abstract Dendritic cells (DCs) have several functions in innate and adaptive immunity. In addition, there is increasing evidence that DCs in situ induce antigen-specific unresponsiveness or tolerance in central lymphoid organs and in the periphery. In the thymus DCs generate tolerance by deleting self-reactive T cells. In peripheral lymphoid organs DCs also induce tolerance to antigens captured by receptors that mediate efficient uptake of proteins and dying cells. Uptake by these receptors leads to the constitutive presentation of antigens on major histocompatibility complex (MHC) class I and II products. In the steady state the targeting of DC antigen capture receptors with low doses of antigens leads to deletion of the corresponding T cells and unresponsiveness to antigenic rechallenge with strong adjuvants. In contrast, if a stimulus for DC maturation is coadministered with the antigen, the mice develop immunity, including interferon-gamma-secreting effector T cells and memory T cells. There is also new evidence that DCs can contribute to the expansion and differentiation of T cells that regulate or suppress other immune T cells. One possibility is that distinct developmental stages and subsets of DCs and T cells can account for the different pathways to peripheral tolerance, such as deletion or suppression. We suggest that several clinical situations, including autoimmunity and certain infectious diseases, can be influenced by the antigen-specific tolerogenic role of DCs.
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    Annual Review of Immunology 21 (2003), S. 841-894 
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    Notes: Abstract B cell chronic lymphocytic leukemia (B-CLL) is an accumulative disease of slowly proliferating CD5+ B lymphocytes that develops in the aging population. Whereas some patients with B-CLL have an indolent course and die after many years from unrelated causes, others progress very rapidly and succumb within a few years from this currently incurable leukemia. Over the past decade studies of the structure and function of the B cell antigen receptor (BCR) used by these leukemic cells have helped redefine the nature of this disease. In this review we summarize and reinterpret several aspects of these BCR-related studies and how they might relate to the disease. In particular, we address the ability of antigens to select out and drive B cell clones from the normal state to overt leukemic cells by binding to BCRs that are relatively unique and characteristic of B-CLL cells. The differential capacity of some B-CLL cases to continue to transduce signals through the BCR during the leukemic phase and the consequences for the in vivo biology of the leukemic clone is also considered. Finally, we discuss current and emerging views of the cellular origin of B-CLL cells and the differentiation pathways down which we believe these cells progress.
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 22 (2004), S. 817-890 
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: This review summarizes the major features of CD1 genes and proteins, the patterns of intracellular trafficking of CD1 molecules, and how they sample different intracellular compartments for self- and foreign lipids. We describe how lipid antigens bind to CD1 molecules with their alkyl chains buried in hydrophobic pockets and expose their polar lipid headgroup whose fine structure is recognized by the TCR of CD1-restricted T cells. CD1-restricted T cells carry out effector, helper, and adjuvant-like functions and interact with other cell types including macrophages, dendritic cells, NK cells, T cells, and B cells, thereby contributing to both innate and adaptive immune responses. Insights gained from mice and humans now delineate the extensive range of diseases in which CD1-restricted T cells play important roles and reveal differences in the role of CD1a, CD1b, and CD1c in contrast to CD1d. Invariant TCRalpha chains, self-lipid reactivity, and rapid effector responses empower a subset of CD1d-restricted T cells (NKT cells) to have unique effector functions without counterpart among MHC-restricted T cells. This review describes the function of CD1-restricted T cells in antimicrobial responses, antitumor immunity, and in regulating the balance between tolerance and autoimmunity.
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    Annual Review of Immunology 22 (2004), S. 329-360 
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: After a century of controversy, the notion that the immune system regulates cancer development is experiencing a new resurgence. An overwhelming amount of data from animal models-together with compelling data from human patients-indicate that a functional cancer immunosurveillance process indeed exists that acts as an extrinsic tumor suppressor. However, it has also become clear that the immune system can facilitate tumor progression, at least in part, by sculpting the immunogenic phenotype of tumors as they develop. The recognition that immunity plays a dual role in the complex interactions between tumors and the host prompted a refinement of the cancer immunosurveillance hypothesis into one termed "cancer immunoediting." In this review, we summarize the history of the cancer immunosurveillance controversy and discuss its resolution and evolution into the three Es of cancer immunoediting-elimination, equilibrium, and escape.
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    Annual Review of Immunology 22 (2004), S. 307-328 
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Development of the acquired immune response is dependent on the signaling of CD40 by its ligand, CD154. These molecules govern both the magnitude and quality of humoral- and cell-mediated immunity. A litany of studies have conclusively documented that blockade of this ligand-receptor pair can prevent, and also intervene in, the progression of antibody- and cell-mediated autoimmune diseases, and can instill long-lived allogeneic and xenogeneic graft tolerance. Many effector mechanisms of inflammation are abolished as a result of CD154 blockade, but we are now beginning to understand that CD154 blockade may, in some instances, engender long-lived, antigen-specific tolerance. In the context of transplantation tolerance, we present a hypothesis that alphaCD154 blockade is most effective at inducing long-lived allospecific tolerance if anergy and regulation can be elicited prior to the onslaught of inflammation that is induced by grafting (preemptive tolerance). This facet of alphaCD154-induced tolerance appears to co-opt the normal processes of peripheral tolerance induced by immature DCs and can be exploited to induce long-lived antigen-specific tolerance. The underlying science and the prospects for inducing long-lived antigen-specific tolerance in a model of allograft tolerance through CD154 blockade are presented and discussed.
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    Annual Review of Immunology 22 (2004), S. 129-156 
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Understanding the molecular basis of lymphocyte homing to lymphoid organs was originally a problem of concern only to immunologists. With the discovery of l-selectin and its ligands, interested scientists have expanded to include glycobiologists, immunopathologists, cancer biologists, and developmental biologists. Going beyond its first discovered role in homing to lymph nodes, the l-selectin system is implicated in such diverse processes as inflammatory leukocyte trafficking in both acute and chronic settings, hematogenous metastasis of carcinoma cells, effector mechanisms for inflammatory demyelination of axons, and implantation of the early mammalian embryo. This review focuses on the ligands for l-selectin that are found on vascular endothelium, leukocytes, carcinoma cells, and at various extravascular sites. The discovery of selectins and their ligands has validated the long-predicted hypothesis that carbohydrate-directed cell adhesion is relevant in eukaryotic systems. Emphasis will be given to the carbohydrate and sulfation modifications of the ligands, which enable recognition by l-selectin. The rapid "homing" of labeled cells into the lymph nodes presumably had its basis in the special affinity of small lymphocytes for the endothelium of the postcapillary venules. Gowans & Knight (1)
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    Annual Review of Immunology 22 (2004), S. 929-979 
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: The Class 2 alpha-helical cytokines consist of interleukin-10 (IL-10), IL-19, IL-20, IL-22, IL-24 (Mda-7), and IL-26, interferons (IFN-alpha, -beta, -e, -kappa, -omega, -delta, -tau, and -gamma) and interferon-like molecules (limitin, IL-28A, IL-28B, and IL-29). The interaction of these cytokines with their specific receptor molecules initiates a broad and varied array of signals that induce cellular antiviral states, modulate inflammatory responses, inhibit or stimulate cell growth, produce or inhibit apoptosis, and affect many immune mechanisms. The information derived from crystal structures and molecular evolution has led to progress in the analysis of the molecular mechanisms initiating their biological activities. These cytokines have significant roles in a variety of pathophysiological processes as well as in regulation of the immune system. Further investigation of these critical intercellular signaling molecules will provide important information to enable these proteins to be used more extensively in therapy for a variety of diseases.
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    Annual Review of Immunology 22 (2004), S. 457-483 
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Because of the evolutionary conservation of innate mechanisms of host defense, Drosophila has emerged as an ideal animal in which to study the genetic control of immune recognition and responses. The discovery that the Toll pathway is required for defense against fungal infection in Drosophila was pivotal in studies of both mammalian and Drosophila immunity. Subsequent genetic screens in Drosophila to isolate additional mutants unable to induce humoral responses to infection have identified and ordered the function of components of two signaling cascades, the Toll and Imd pathways, that activate responses to infection. Drosophila blood cells also contribute to host defense through phagocytosis and signaling, and may carry out a form of self-nonself recognition that is independent of microbial pattern recognition. Recent work suggests that Drosophila will be a useful model for dissecting virulence mechanisms of several medically important pathogens.
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  • 90
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Immune cell-mediated destruction of pathogens may result in excessive collateral damage to normal tissues, and the failure to control activated immune cells may cause immunopathologies. The search for physiological mechanisms that downregulate activated immune cells has revealed a critical role for extracellular adenosine and for immunosuppressive A2A adenosine receptors in protecting tissue from inflammatory damage. Tissue damage-associated deep hypoxia, hypoxia-inducible factors, and hypoxia-induced accumulation of adenosine may represent one of the most fundamental and immediate tissue-protecting mechanisms, with adenosine A2A receptors triggering "OFF" signals in activated immune cells. In these regulatory mechanisms, oxygen deprivation and extracellular adenosine accumulation serve as "reporters," while A2A adenosine receptors serve as "sensors" of excessive tissue damage. The A2A receptor-triggered generation of intracellular cAMP then inhibits activated immune cells in a delayed negative feedback manner to prevent additional tissue damage. Targeting A2A adenosine receptors may have important clinical applications.
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  • 91
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    Annual Review of Immunology 22 (2004), S. 361-403 
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: The present review focuses on the concept that cellular and humoral immunity to the phylogenetically highly conserved antigen heat shock protein 60 (HSP60) is the initiating mechanism in the earliest stages of atherosclerosis. Subjecting arterial endothelial cells to classical atherosclerosis risk factors leads to the expression of HSP60 that then may serve as a target for pre-existent cross-reactive antimicrobial HSP60 immunity or bona fide autoimmune reactions induced by biochemically altered autologous HSP60. Endothelial cells can also bind microbial or autologous HSP60 via Toll-like receptors, providing another possibility for targetting adaptive or innate immunological effector mechanisms.
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    Annual Review of Pharmacology 40 (2000), S. 133-157 
    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Notes: Abstract The application of rapid methods currently used for screening discovery drug candidates for metabolism and pharmacokinetic characteristics is discussed. General considerations are given for screening in this context, including the criteria for good screens, the use of counterscreens, the proper sequencing of screens, ambiguity in the interpretation of results, strategies for false positives and negatives, and the special difficulties encountered in drug metabolism and pharmacokinetic screening. Detailed descriptions of the present status of screening are provided for absorption potential, blood-brain barrier penetration, inhibition and induction of cytochrome P450, pharmacokinetics, biotransformation, and computer modeling. Although none of the systems currently employed for drug metabolism and pharmacokinetic screening can be considered truly high-throughput, several of them are rapid enough to be a practical part of the screening paradigm for modern, fast-moving discovery programs.
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    Annual Review of Immunology 19 (2001), S. 131-161 
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract Tolerance to beta cell autoantigens represents a fragile equilibrium. Autoreactive T cells specific to these autoantigens are present in most normal individuals but are kept under control by a number of peripheral tolerance mechanisms, among which CD4+ CD25+ CD62L+ T cell-mediated regulation probably plays a central role. The equilibrium may be disrupted by inappropriate activation of autoantigen-specific T cells, notably following to local inflammation that enhances the expression of the various molecules contributing to antigen recognition by T cells. Even when T cell activation finally overrides regulation, stimulation of regulatory cells by CD3 antibodies may reset the control of autoimmunity. Other procedures may also lead to disease prevention. These procedures are essentially focused on Th2 cytokines, whether used systemically or produced by Th2 cells after specific stimulation by autoantigens. Protection can also be obtained by NK T cell stimulation. Administration of beta cell antigens or CD3 antibodies is now being tested in clinical trials in prediabetics and/or recently diagnosed diabetes.
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    Annual Review of Immunology 19 (2001), S. 275-290 
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract Since the description of the first mouse knockout for an IgG Fc receptor seven years ago, considerable progress has been made in defining the in vivo functions of these receptors in diverse biological systems. The role of activating FcgammaRs in providing a critical link between ligands and effector cells in type II and type III inflammation is now well established and has led to a fundamental revision of the significance of these receptors in initiating cellular responses in host defense, in determining the efficacy of therapeutic antibodies, and in pathological autoimmune conditions. Considerable progress has been made in the last two years on the in vivo regulation of these responses, through the appreciation of the importance of balancing activation responses with inhibitory signaling. The inhibitory FcR functions in the maintenance of peripheral tolerance, in regulating the threshold of activation responses, and ultimately in terminating IgG mediated effector stimulation. The consequences of deleting the inhibitory arm of this system are thus manifested in both the afferent and efferent immune responses. The hyperresponsive state that results leads to greatly magnified effector responses by cytotoxic antibodies and immune complexes and can culminate in autoimmunity and autoimmune disease when modified by environmental or genetic factors. FcgammaRs offer a paradigm for the biological significance of balancing activation and inhibitory signaling in the expanding family of activation/inhibitory receptor pairs found in the immune system.
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    Notes: Abstract The adaptive immune response is initiated by the interaction of T cell antigen receptors with major histocompatibility complex molecule-peptide complexes in the nanometer scale gap between a T cell and an antigen-presenting cell, referred to as an immunological synapse. In this review we focus on the concept of immunological synapse formation as it relates to membrane structure, T cell polarity, signaling pathways, and the antigen-presenting cell. Membrane domains provide an organizational principle for compartmentalization within the immunological synapse. T cell polarization by chemokines increases T cell sensitivity to antigen. The current model is that signaling and formation of the immunological synapse are tightly interwoven in mature T cells. We also extend this model to natural killer cell activation, where the inhibitory NK synapse provides a striking example in which inhibition of signaling leaves the synapse in its nascent, inverted state. The APC may also play an active role in immunological synapse formation, particularly for activation of naive T cells.
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    Annual Review of Immunology 19 (2001), S. 397-421 
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract A broad array of biological responses, including cell polarization, movement, immune and inflammatory responses, and prevention of HIV-1 infection, are triggered by the chemokines, a family of structurally related chemoattractant proteins that bind to specific seven-transmembrane receptors linked to G proteins. Here we discuss one of the early signaling pathways activated by chemokines, the JAK/STAT pathway. Through this pathway, and possibly in conjunction with other signaling pathways, the chemokines promote changes in cellular morphology, collectively known as polarization, required for chemotactic responses. The polarized cell expresses the chemokine receptors at the leading cell edge, to which they are conveyed by rafts, a cholesterol-enriched membrane fraction fundamental to the lateral organization of the plasma membrane. Finally, the mechanisms through which the chemokines promote their effect are discussed in the context of the prevention of HIV-1 infection.
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    Annual Review of Immunology 19 (2001), S. 565-594 
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract The T cell compartment of adaptive immunity provides vertebrates with the potential to survey for and respond specifically to an incredible diversity of antigens. The T cell repertoire must be carefully regulated to prevent unwanted responses to self. In the periphery, one important level of regulation is the action of costimulatory signals in concert with T cell antigen-receptor (TCR) signals to promote full T cell activation. The past few years have revealed that costimulation is quite complex, involving an integration of activating signals and inhibitory signals from CD28 and CTLA-4 molecules, respectively, with TCR signals to determine the outcome of a T cell's encounter with antigen. Newly emerging data suggest that inhibitory signals mediated by CTLA-4 not only can determine whether T cells become activated, but also can play a role in regulating the clonal representation in a polyclonal response. This review primarily focuses on the cellular and molecular mechanisms of regulation by CTLA-4 and its manipulation as a strategy for tumor immunotherapy.
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    Annual Review of Immunology 19 (2001), S. 683-765 
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract Interleukin-10 (IL-10), first recognized for its ability to inhibit activation and effector function of T cells, monocytes, and macrophages, is a multifunctional cytokine with diverse effects on most hemopoietic cell types. The principal routine function of IL-10 appears to be to limit and ultimately terminate inflammatory responses. In addition to these activities, IL-10 regulates growth and/or differentiation of B cells, NK cells, cytotoxic and helper T cells, mast cells, granulocytes, dendritic cells, keratinocytes, and endothelial cells. IL-10 plays a key role in differentiation and function of a newly appreciated type of T cell, the T regulatory cell, which may figure prominently in control of immune responses and tolerance in vivo. Uniquely among hemopoietic cytokines, IL-10 has closely related homologs in several virus genomes, which testify to its crucial role in regulating immune and inflammatory responses. This review highlights findings that have advanced our understanding of IL-10 and its receptor, as well as its in vivo function in health and disease.
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    Annual Review of Immunology 1 (1983), S. 119-142 
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    Annual Review of Immunology 1 (1983), S. 211-241 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
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