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  • American Institute of Physics  (79.595)
  • BioMed Central  (14.038)
  • Copernicus
  • Annual Reviews
  • 2005-2009  (109.575)
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  • 1
    Publikationsdatum: 2020-12-14
    Beschreibung: In this study we present an intercomparison of measurements of very low water vapor column content obtained with a Ground-Based Millimeter-wave Spectrometer (GBMS), Vaisala RS92k radiosondes, a Raman Lidar, and an IR Fourier Transform Spectrometer. These sets of measurements were carried out during the primary field campaign of the ECOWAR (Earth COoling by WAter vapor Radiation) project which took place on the Western Italian Alps from 3 to 16 March, 2007.
    Beschreibung: Published
    Beschreibung: 135-138
    Beschreibung: 1.8. Osservazioni di geofisica ambientale
    Beschreibung: N/A or not JCR
    Beschreibung: open
    Schlagwort(e): Precipitable Water Vapor ; ECOWAR ; IR and Millimeter-Wave Spectroscopy ; 01. Atmosphere::01.01. Atmosphere::01.01.01. Composition and Structure ; 01. Atmosphere::01.01. Atmosphere::01.01.02. Climate
    Repository-Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Materialart: article
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  • 2
    Publikationsdatum: 2017-04-04
    Beschreibung: COST (Co-operation in the field of Scientific and Technical Research) is an important instrument supporting co-operation among scientists and researchers across Europe now joining 35 member countries. Scientific projects in the COST framework are called COST Actions and have the objectives embodied in their respective Memorandum of Understanding (MoU). The main objectives of the COST Actions within the European ionospheric and radio propagation community have been: to study the influence of upper atmospheric conditions on terrestrial and Earthspace communications, to develop methods and techniques to improve existing and generate new ionospheric and propagation models over Europe for telecommunication and navigation applications and to transfer the results to the appropriate national and international organizations, institutions and industry dealing with the modern communication systems. This paper summarises in brief the background and historical context of four ionospheric COST Actions and outlines their main objectives and results. In addition, the paper discusses the dissemination of the results and the collaboration among the participating institutions and researchers.
    Beschreibung: DRS Codem Systems Ball Aerospace Corporation University of Massachusetts Lowell
    Beschreibung: Published
    Beschreibung: Lowell, Massachusetts, U.S.A., April 29, 2007
    Beschreibung: 3.9. Fisica della magnetosfera, ionosfera e meteorologia spaziale
    Beschreibung: open
    Schlagwort(e): Physics of the Ionosphere ; 01. Atmosphere::01.02. Ionosphere::01.02.99. General or miscellaneous ; 05. General::05.07. Space and Planetary sciences::05.07.02. Space weather
    Repository-Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Materialart: Conference paper
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  • 3
    Publikationsdatum: 2017-04-04
    Beschreibung: Volcanoes represent an important natural source of several trace elements to the atmosphere. For some species (e.g., As, Cd, Pb and Se) they may be the main natural source and thereby strongly influencing geochemical cycles from the local to the global scale. Mount Etna is one of the most actively degassing volcanoes in the world, and it is considered to be, on the long-term average, the major atmospheric point source of many environmental harmful compounds. Their emission occurs either through continuous passive degassing from open-conduit activity or through sporadic paroxysmal eruptive activity, in the form of gases, aerosols or particulate. To estimate the environmental impact of magma-derived trace metals and their depositions processes, rainwater and snow samples were collected at Mount Etna area. Five bulk collectors have been deployed at various altitudes on the upper flanks around the summit craters of the volcano; samples were collected every two week for a period of one year and analyzed for the main chemical-physical parameters (electric conductivity and pH) and for major and trace elements concentrations. Chemical analysis of rainwater clearly shows that the volcanic contribution is always prevailing in the sampling site closest to the summit crater (about 1.5 km). In the distal sites (5.5-10 km from the summit) and downwind of the summit craters, the volcanic contribution is also detectable but often overwhelmed by anthropogenic or other natural (seawater spray, geogenic dust) contributions. Volcanic contribution may derive from both dry and wet deposition of gases and aerosols from the volcanic plume, but sometimes also from leaching of freshly emitted volcanic ashes. In fact, in our background site (7.5 km in the upwind direction) volcanic contribution has been detected only following an ash deposition event. About 30 samples of fresh snow were collected in the upper part of the volcano, during the winters 2006 and 2007 to estimate deposition processes at high altitude during cold periods. Some of the samples were collected immediately after a major explosive event from the summit craters to understand the interaction between snow and fresh erupted ash. Sulphur, Chlorine and Fluorine, are the major elements that prevailingly characterize the volcanic contribution in atmospheric precipitation on Mount Etna, but high concentrations of many trace elements are also detected in the studied samples. In particular, bulk deposition samples display high concentration of Al, Fe, Ti, Cu, As, Rb, Pb, Tl, Cd, Cr, U and Ag, in the site most exposed to the volcanic emissions: median concentration values are about two orders of magnitude higher than those measured in our background site. Also in the snow samples the volcanic signature is clearly detectable and decreases with distance from the summit craters. Some of the analysed elements display very high enrichment values with respect to the average crust and, in the closest site to the summit craters, also deposition values higher than those measured in polluted urban or industrial sites.
    Beschreibung: Published
    Beschreibung: Vienna, Austria
    Beschreibung: 4.5. Degassamento naturale
    Beschreibung: open
    Schlagwort(e): Mt. Etna ; trace elements ; rainwater ; 01. Atmosphere::01.01. Atmosphere::01.01.07. Volcanic effects ; 03. Hydrosphere::03.03. Physical::03.03.01. Air/water/earth interactions ; 03. Hydrosphere::03.04. Chemical and biological::03.04.03. Chemistry of waters
    Repository-Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Materialart: Oral presentation
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  • 4
    Publikationsdatum: 2017-04-04
    Beschreibung: Improving the constraints on the atmospheric fate and depletion rates of acidic compounds persistently emitted by non-erupting (quiescent) volcanoes is important for quantitatively predicting the environmental impact of volcanic gas plumes. Here, we present new experimental data coupled with modelling studies to investigate the chemical processing of acidic volcanogenic species during tropospheric dispersion. Diffusive tube samplers were deployed at Mount Etna, a very active open-conduit basaltic volcano in eastern Sicily, and Vulcano Island, a closed-conduit quiescent volcano in the Aeolian Islands (northern Sicily). Sulphur dioxide (SO2), hydrogen sulphide (H2S), hydrogen chloride (HCl) and hydrogen fluoride (HF) concentrations in the volcanic plumes (typically several minutes to a few hours old) were repeatedly determined at distances from the summit vents ranging from 0.1 to ~10 km, and under different environmental conditions. At both volcanoes, acidic gas concentrations were found to decrease exponentially with distance from the summit vents (e.g., SO2 decreases from ~10,000 μg/m3 at 0.1 km from Etna’s vents down to ~7 _μg/m3 at ~10km distance), reflecting the atmospheric dilution of the plume within the acid gas-free background troposphere. Conversely, SO2/HCl, SO2/HF, and SO2/H2S ratios in the plume showed no systematic changes with plume aging, and fit source compositions within analytical error. Assuming that SO2 losses by reaction are small during short-range atmospheric transport within quiescent (ash-free) volcanic plumes, our observations suggest that, for these short transport distances, atmospheric reactions for H2S and halogens are also negligible. The one-dimensional model MISTRA was used to simulate quantitatively the evolution of halogen and sulphur compounds in the plume of Mt. Etna. Model predictions support the hypothesis of minor HCl chemical processing during plume transport, at least in cloud-free conditions. Larger variations in the modelled SO2/HCl ratios were predicted under cloudy conditions, due to heterogeneous chlorine cycling in the aerosol phase. The modelled evolution of the SO2/H2S ratios is found to be substantially dependent on whether or not the interactions of H2S with halogens are included in the model. In the former case, H2S is assumed to be oxidized in the atmosphere mainly by OH, which results in minor chemical loss for H2S during plume aging and produces a fair match between modelled and measured SO2/H2S ratios. In the latter case, fast oxidation of H2S by Cl leads to H2S chemical lifetimes in the early plume of a few seconds, and thus SO2 to H2S ratios that increase sharply during plume transport. This disagreement between modelled and observed plume compositions suggests that more in-detail kinetic investigations are required for a proper evaluation of H2S chemical processing in volcanic plumes.
    Beschreibung: Published
    Beschreibung: 1441-1450
    Beschreibung: 1.2. TTC - Sorveglianza geochimica delle aree vulcaniche attive
    Beschreibung: 4.5. Degassamento naturale
    Beschreibung: JCR Journal
    Beschreibung: open
    Schlagwort(e): Mt. Etna ; volcanic gas plumes ; tropospheric processing ; 01. Atmosphere::01.01. Atmosphere::01.01.07. Volcanic effects
    Repository-Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Materialart: article
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  • 5
    Publikationsdatum: 2017-04-04
    Beschreibung: After some short test surveys, during the 2004–2005 summer expedition in Antarctica, a geomagnetic French-Italian observatory was installed on the plateau (geographic coordinates: 75.1 S, 123.4 E; corrected geomagnetic coordinates: 88.9 S, 54.3 E; UT=LT−8) very close to the geomagnetic pole. In this paper we present some peculiarities of the daily variation as observed at this polar cap observatory during the years 2005 and 2006, taking into account the different Loyd seasons and different interplanetary magnetic field conditions. Some interesting results emerge from the analysis, confirming the dependence of the daily variation (and of the associated polar current systems) on the IMF Bz and By components. In particular the analysis showed that different Bz conditions correspond to different contribution to daily variation of ionospheric and field aligned currents, while particular By conditions lead to a time shift of the diurnal variation, indicating an asymmetry with respect to the noon meridian.
    Beschreibung: Published
    Beschreibung: 2045–2051
    Beschreibung: 3.9. Fisica della magnetosfera, ionosfera e meteorologia spaziale
    Beschreibung: 1.6. Osservazioni di geomagnetismo
    Beschreibung: JCR Journal
    Beschreibung: reserved
    Schlagwort(e): Geomagnetism and paleomagnetism (Time variations, diurnal to secular) ; Magnetospheric physics (Polar cap phenomena; Solar wind-magnetosphere interactions) ; 01. Atmosphere::01.03. Magnetosphere::01.03.99. General or miscellaneous
    Repository-Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Materialart: article
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  • 6
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    American Institute of Physics
    Publikationsdatum: 2020-02-24
    Beschreibung: A high-resolution Fabry–Perot interferometer was inserted in a feedback loop which, by monitoring elements of the fringe pattern, keeps the position of the transmitting window fixed with respect to a given line, taking into account the instability of the radiation source which would produce a wander of the line itself and the noise affecting the tuning of the receiving interferometer. The system, in this preliminary form, is able to lock itself and maintain its position indefinitely for slow and moderately fast varying disturbances.
    Beschreibung: Published
    Beschreibung: 2940-2944
    Beschreibung: 1.7. Osservazioni di alta e media atmosfera
    Beschreibung: JCR Journal
    Beschreibung: reserved
    Schlagwort(e): FABRY-PEROT ; INTERFEROMETER ; SERVOMECHANISMS ; FEEDBACK ; 01. Atmosphere::01.01. Atmosphere::01.01.08. Instruments and techniques
    Repository-Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 7
    Publikationsdatum: 2022-05-25
    Beschreibung: © 2008 Hutt et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License 2.0, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The definitive version was published in BMC Developmental Biology 8 (2008): 1, doi:10.1186/1471-213X-8-1.
    Beschreibung: Environmental toxicants, whose actions are often mediated through the aryl hydrocarbon receptor (AhR) pathway, pose risks to the health and well-being of exposed species, including humans. Of particular concern are exposures during the earliest stages of development that while failing to abrogate embryogenesis, may have long term effects on newborns or adults. The purpose of this study was to evaluate the effect of maternal exposure to the AhR-specific ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the development of rat pre-implantation embryos with respect to nuclear and cytoskeletal architecture and cell lineage allocation. We performed a systematic 3 dimensional (3D) confocal microscopy analysis of rat pre-implantation embryos following maternal exposure to environmentally relevant doses of TCDD. Both chronic (50 ng/kg/wk for 3 months) and acute (50 ng/kg and 1 μg/kg at proestrus) maternal TCDD exposure disrupted morphogenesis at the compaction stage (8–16 cell), with defects including monopolar spindle formation, f-actin capping and fragmentation due to aberrant cytokinesis. Additionally, the size, shape and position of nuclei were modified in compaction stage pre-implantation embryos collected from treated animals. Notably, maternal TCDD exposure did not compromise survival to blastocyst, which with the exception of nuclear shape, were morphologically similar to control blastocysts. We have identified the compaction stage of pre-implantation embryogenesis as critically sensitive to the effects of TCDD, while survival to the blastocyst stage is not compromised. To the best of our knowledge this is the first in vivo study to demonstrate a critical window of pre-implantation mammalian development that is vulnerable to disruption by an AhR ligand at environmentally relevant doses.
    Beschreibung: This research was supported by NIH/NIEHS-012916 (BKP), ESHE Fund (DFA), Hall Family Foundation (DFA and KJH) and Biomedical Research Training Grant KUMC (KJH).
    Repository-Name: Woods Hole Open Access Server
    Materialart: Article
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  • 8
    Publikationsdatum: 2022-05-25
    Beschreibung: © 2007 Ioannidis et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The definitive version was published in BMC Genomics 8 (2007): 182, doi:10.1186/1471-2164-8-182.
    Beschreibung: Background: The annotated genomes of two closely related strains of the intracellular bacterium Wolbachia pipientis have been reported without the identifications of the putative origin of replication (ori). Identifying the ori of these bacteria and related alpha-Proteobacteria as well as their patterns of sequence evolution will aid studies of cell replication and cell density, as well as the potential genetic manipulation of these widespread intracellular bacteria. Results: Using features that have been previously experimentally verified in the alpha-Proteobacterium Caulobacter crescentus, the origin of DNA replication (ori) regions were identified in silico for Wolbachia strains and eleven other related bacteria belonging to Ehrlichia, Anaplasma, and Rickettsia genera. These features include DnaA-, CtrA- and IHF-binding sites as well as the flanking genes in C. crescentus. The Wolbachia ori boundary genes were found to be hemE and COG1253 protein (CBS domain protein). Comparisons of the putative ori region among related Wolbachia strains showed higher conservation of bases within binding sites. Conclusion: The sequences of the ori regions described here are only similar among closely related bacteria while fundamental characteristics like presence of DnaA and IHF binding sites as well as the boundary genes are more widely conserved. The relative paucity of CtrA binding sites in the ori regions, as well as the absence of key enzymes associated with DNA replication in the respective genomes, suggest that several of these obligate intracellular bacteria may have altered replication mechanisms. Based on these analyses, criteria are set forth for identifying the ori region in genome sequencing projects.
    Beschreibung: PI, PS, SS, GT and KB acknowledge support of their work from intramural funding from the University of Ioannina. SB, JDH, LB and JW acknowledge support of their work from the U.S. National Science Foundation grant EF-0328363. SB also acknowledges the support from the NASA Astrobiology Institute (NNA04CC04A)
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  • 9
    Publikationsdatum: 2022-05-25
    Beschreibung: © 2007 Huse et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The definitive version was published in Genome Biology 8 (2007): R143, doi:10.1186/gb-2007-8-7-r143.
    Beschreibung: Additional data file 1 is a fasta file of the 43 known sequences used. Additional data file 2 is a gzip-compressed fasta file of the sequences output by the GS20. These sequences correspond to those included in Additional data files 3, 4, 5 but include only the final sequence information. Additional data files 3, 4, 5 are three compressed text files representing the text translations of the original GS20 binary output (sff) files for all of the sequencing used in the analysis, including sequence, flowgram and other run information. GS20 data are reported by region of the PicoTiterPlate™; we sequenced three plate regions.
    Beschreibung: Massively parallel pyrosequencing systems have increased the efficiency of DNA sequencing, although the published per-base accuracy of a Roche GS20 is only 96%. In genome projects, highly redundant consensus assemblies can compensate for sequencing errors. In contrast, studies of microbial diversity that catalogue differences between PCR amplicons of ribosomal RNA genes (rDNA) or other conserved gene families cannot take advantage of consensus assemblies to detect and minimize incorrect base calls. We performed an empirical study of the per-base error rate for the Roche GS20 system using sequences of the V6 hypervariable region from cloned microbial ribosomal DNA (tag sequencing). We calculated a 99.5% accuracy rate in unassembled sequences, and identified several factors that can be used to remove a small percentage of low-quality reads, improving the accuracy to 99.75% or better. By using objective criteria to eliminate low quality data, the quality of individual GS20 sequence reads in molecular ecological applications can surpass the accuracy of traditional capillary methods.
    Beschreibung: This work was supported by National Aeronautics and Space Administration Astrobiology Institute Cooperative Agreement NNA04CC04A (to MLS), subcontracts from the Woods Hole Center for Oceans and Human Health from the National Institutes of Health and National Science Foundation (NIH/NIEHS 1 P50 ES012742-01 and NSF/OCE 0430724-J Stegeman PI to HGM and MLS), grants from the WM Keck Foundation and the G Unger Vetlesen Foundation (to MLS), and a National Research Council Research Associateship Award (to JAH).
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  • 10
    Publikationsdatum: 2022-05-25
    Beschreibung: © 2008 Salvador-Recatalà et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License. The definitive version was published in BMC Physiology 8 (2008): 6, doi:10.1186/1472-6793-8-6.
    Beschreibung: The function of voltage-gated calcium (Cav) channels greatly depends on coupling to cytoplasmic accessory β subunits, which not only promote surface expression, but also modulate gating and kinetic properties of the α1 subunit. Schistosomes, parasitic platyhelminths that cause schistosomiasis, express two β subunit subtypes: a structurally conventional β subunit and a variant β subunit with unusual functional properties. We have previously characterized the functional properties of the variant Cavβ subunit. Here, we focus on the modulatory phenotype of the conventional Cavβ subunit (SmCavβ) using the human Cav2.3 channel as the substrate for SmCavβ and the whole-cell patch-clamp technique. The conventional Schistosoma mansoni Cavβ subunit markedly increases Cav2.3 currents, slows macroscopic inactivation and shifts steady state inactivation in the hyperpolarizing direction. However, currents produced by Cav2.3 in the presence of SmCavβ run-down to approximately 75% of their initial amplitudes within two minutes of establishing the whole-cell configuration. This suppressive effect was independent of Ca2+, but dependent on intracellular Mg2+-ATP. Additional experiments revealed that SmCavβ lends the Cav2.3/SmCavβ complex sensitivity to Na+ ions. A mutant version of the Cavβ subunit lacking the first forty-six amino acids, including a string of twenty-two acidic residues, no longer conferred sensitivity to intracellular Mg2+-ATP and Na+ ions, while continuing to show wild type modulation of current amplitude and inactivation of Cav2.3. The data presented in this article provide insights into novel mechanisms employed by platyhelminth Cavβ subunits to modulate voltage-gated Ca2+ currents that indicate interactions between the Ca2+ channel complex and chelated forms of ATP as well as Na+ ions. These results have potentially important implications for understanding previously unknown mechanisms by which platyhelminths and perhaps other organisms modulate Ca2+ currents in excitable cells.
    Beschreibung: This work was supported by NIH grant #s R01 AI-40522 and R01 AI-73660 to RMG and by NIH-NCRR grant # P41 RR001395 to the Biocurrents Research Center (BRC) at MBL.
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  • 11
    Publikationsdatum: 2022-05-25
    Beschreibung: © 2008 Riley et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The definitive version was published in BMC Genomics 9 (2008): 210, doi:10.1186/1471-2164-9-210.
    Beschreibung: The genome sequence of the sea-ice bacterium Psychromonas ingrahamii 37, which grows exponentially at -12C, may reveal features that help to explain how this extreme psychrophile is able to grow at such low temperatures. Determination of the whole genome sequence allows comparison with genes of other psychrophiles and mesophiles. Correspondence analysis of the composition of all P. ingrahamii proteins showed that (1) there are 6 classes of proteins, at least one more than other bacteria, (2) integral inner membrane proteins are not sharply separated from bulk proteins suggesting that, overall, they may have a lower hydrophobic character, and (3) there is strong opposition between asparagine and the oxygen-sensitive amino acids methionine, arginine, cysteine and histidine and (4) one of the previously unseen clusters of proteins has a high proportion of "orphan" hypothetical proteins, raising the possibility these are cold-specific proteins. Based on annotation of proteins by sequence similarity, (1) P. ingrahamii has a large number (61) of regulators of cyclic GDP, suggesting that this bacterium produces an extracellular polysaccharide that may help sequester water or lower the freezing point in the vicinity of the cell. (2) P. ingrahamii has genes for production of the osmolyte, betaine choline, which may balance the osmotic pressure as sea ice freezes. (3) P. ingrahamii has a large number (11) of three-subunit TRAP systems that may play an important role in the transport of nutrients into the cell at low temperatures. (4) Chaperones and stress proteins may play a critical role in transforming nascent polypeptides into 3-dimensional configurations that permit low temperature growth. (5) Metabolic properties of P. ingrahamii were deduced. Finally, a few small sets of proteins of unknown function which may play a role in psychrophily have been singled out as worthy of future study. The results of this genomic analysis provide a springboard for further investigations into mechanisms of psychrophily. Focus on the role of asparagine excess in proteins, targeted phenotypic characterizations and gene expression investigations are needed to ascertain if and how the organism regulates various proteins in response to growth at lower temperatures.
    Beschreibung: MR acknowledges support from DE-FG02-04ER63940. JTS acknowledges the support from the University of Washington NASA NAI program and the NSF Astrobiology IGERT program. TZW acknowledges support from a grant from the Fondation Fourmentin-Guilbert and AD acknowledges support from the European Union BioSapiens Network of Excellence, Grant LSHG CT-2003-503265
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  • 12
    Publikationsdatum: 2022-05-25
    Beschreibung: © 2009 The Authors. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in BMC Genomics 10 (2009): 11, doi:10.1186/1471-2164-10-11.
    Beschreibung: Cold adapted or psychrophilic organisms grow at low temperatures, where most of other organisms cannot grow. This adaptation requires a vast array of sequence, structural and physiological adjustments. To understand the molecular basis of cold adaptation of proteins, we analyzed proteomes of psychrophilic and mesophilic bacterial species and compared the differences in amino acid composition and substitution patterns to investigate their likely association with growth temperatures. In psychrophilic bacteria, serine, aspartic acid, threonine and alanine are overrepresented in the coil regions of secondary structures, whilst glutamic acid and leucine are underrepresented in the helical regions. Compared to mesophiles, psychrophiles comprise a significantly higher proportion of amino acids that contribute to higher protein flexibility in the coil regions of proteins, such as those with tiny/small or neutral side chains. Amino acids with aliphatic, basic, aromatic and hydrophilic side chains are underrepresented in the helical regions of proteins of psychrophiles. The patterns of amino acid substitutions between the orthologous proteins of psychrophiles versus mesophiles are significantly different for several amino acids when compared to their substitutions in orthologous proteins of within the mesophiles or psychrophiles. Current results provide quantitative substitution preferences (or avoidance) of amino acids that lead to the adaptation of proteins to cold temperatures. These finding would help future efforts in selecting mutations for rational design of proteins with enhanced psychrophilic properties.
    Beschreibung: This work was supported by a grant from Howard Hughes Medical Institute to Queens College, CUNY, and Queens College Research Enhancement Grant.
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  • 13
    Publikationsdatum: 2022-05-25
    Beschreibung: © 2009 Sarkar et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License. The definitive version was published in BMC Research Notes 2 (2009): 101, doi:10.1186/1756-0500-2-101.
    Beschreibung: GenBank(R) is a public repository of all publicly available molecular sequence data from a range of sources. In addition to relevant metadata (e.g., sequence description, source organism and taxonomy), publication information is recorded in the GenBank data file. The identification of literature associated with a given molecular sequence may be an essential first step in developing research hypotheses. Although many of the publications associated with GenBank records may not be linked into or part of complementary literature databases (e.g., PubMed), GenBank records associated with literature indexed in Medline are identifiable as they contain PubMed identifiers (PMIDs). Here we show that an analysis of 87,116,501 GenBank sequence files reveals that 42% are associated with a publication or patent. Of these, 71% are associated with PMIDs, and can therefore be linked to a citation record in the PubMed database. The remaining (29%) of publication-associated GenBank entries either do not have PMIDs or cite a publication that is not currently indexed by PubMed. We also identify the journal titles that are linked through citations in the GenBank files to the largest number of sequences. Our analysis suggests that GenBank contains molecular sequences from a range of disciplines beyond biomedicine, the initial scope of PubMed. The findings thus suggest opportunities to develop mechanisms for integrating biological knowledge beyond the biomedical field.
    Beschreibung: INS and HM are funded in part by a research grant from the Ellison Medical Foundation and National Library of Medicine award R01LM009725 to INS.
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  • 14
    Publikationsdatum: 2022-05-25
    Beschreibung: © 2009 Reitzel and Tarrant. This is an open-access article distributed under the terms of the Creative Commons Attribution License. The definitive version was published in BMC Evolutionary Biology 9 (2009): 230, doi:10.1186/1471-2148-9-230.
    Beschreibung: Nuclear receptors are a superfamily of metazoan transcription factors that regulate diverse developmental and physiological processes. Sequenced genomes from an increasing number of bilaterians have provided a more complete picture of duplication and loss of nuclear receptors in protostomes and deuterostomes but have left open the question of which nuclear receptors were present in the cnidarian-bilaterian ancestor. In addition, nuclear receptor expression and function are largely uncharacterized within cnidarians, preventing determination of conserved and novel nuclear receptor functions in the context of animal evolution. Here we report the first complete set of nuclear receptors from a cnidarian, the starlet sea anemone Nematostella vectensis. Genomic searches using conserved DNA- and ligand-binding domains revealed seventeen nuclear receptors in N. vectensis. Phylogenetic analyses support N. vectensis orthologs of bilaterian nuclear receptors in four nuclear receptor subfamilies within nuclear receptor family 2 (COUP-TF, TLL, HNF4, TR2/4) and one putative ortholog of GCNF (nuclear receptor family 6). Other N. vectensis genes grouped well with nuclear receptor family 2 but represented lineage-specific duplications somewhere within the cnidarian lineage and were not clear orthologs of bilaterian genes. Three nuclear receptors were not well-supported within any particular nuclear receptor family. The seventeen nuclear receptors exhibited distinct developmental expression patterns, with expression of several nuclear receptors limited to a subset of developmental stages. N. vectensis contains a diverse complement of nuclear receptors including orthologs of several bilaterian nuclear receptors. Novel nuclear receptors in N. vectensis may be ancient genes lost from triploblastic lineages or may represent cnidarian-specific radiations. Nuclear receptors exhibited distinct developmental expression patterns, which are consistent with diverse regulatory roles for these genes. Understanding the evolutionary relationships and developmental expression of the N. vectensis nuclear receptor complement provides insight into the evolution of the nuclear receptor superfamily and a foundation for mechanistic characterization of cnidarian nuclear receptor function.
    Beschreibung: We are grateful for financial support from the Woods Hole Oceanographic Institution (WHOI) through the Tropical Research Initiative, the Ocean Life Institute (AMT), the Academic Programs Office, and to the Beacon Institute for Rivers and Estuaries (AMR).
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  • 15
    Publikationsdatum: 2022-05-25
    Beschreibung: Author Posting. © Annual Reviews, 2003. This article is posted here by permission of Annual Reviews for personal use, not for redistribution. The definitive version was published in Annual Review of Environment and Resources 28 (2003): 521-558, doi:10.1146/annurev.energy.28.011503.163443.
    Beschreibung: Agriculture and industrial development have led to inadvertent changes in the natural carbon cycle. As a consequence, concentrations of carbon dioxide and other greenhouse gases have increased in the atmosphere and may lead to changes in climate. The current challenge facing society is to develop options for future management of the carbon cycle. A variety of approaches has been suggested: direct reduction of emissions, deliberate manipulation of the natural carbon cycle to enhance sequestration, and capture and isolation of carbon from fossil fuel use. Policy development to date has laid out some of the general principles to which carbon management should adhere. These are summarized as: how much carbon is stored, by what means, and for how long. To successfully manage carbon for climate purposes requires increased understanding of carbon cycle dynamics and improvement in the scientific capabilities available for measurement as well as for policy needs. The specific needs for scientific information to underpin carbon cycle management decisions are not yet broadly known. A stronger dialogue between decision makers and scientists must be developed to foster improved application of scientific knowledge to decisions. This review focuses on the current knowledge of the carbon cycle, carbon measurement capabilities (with an emphasis on the continental scale) and the relevance of carbon cycle science to carbon sequestration goals.
    Beschreibung: The National Center for Atmospheric Research is supported by the National Science Foundation.
    Schlagwort(e): Carbon sequestration ; Measurement techniques ; Climate ; Kyoto protocol
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  • 16
    Publikationsdatum: 2022-05-25
    Beschreibung: Author Posting. © 2001 Serres et al. The definitive version was published in Genome Biology 2 (2001): research0035.1–0035.7, doi:10.1186/gb-2001-2-9-research0035.
    Beschreibung: Background: Since the genome of Escherichia coli K-12 was initially annotated in 1997, additional functional information based on biological characterization and functions of sequence-similar proteins has become available. On the basis of this new information, an updated version of the annotated chromosome has been generated. Results: The E. coli K-12 chromosome is currently represented by 4,401 genes encoding 116 RNAs and 4,285 proteins. The boundaries of the genes identified in the GenBank Accession U00096 were used. Some protein-coding sequences are compound and encode multimodular proteins. The coding sequences (CDSs) are represented by modules (protein elements of at least 100 amino acids with biological activity and independent evolutionary history). There are 4,616 identified modules in the 4,285 proteins. Of these, 48.9% have been characterized, 29.5% have an imputed function, 2.1% have a phenotype and 19.5% have no function assignment. Only 7% of the modules appear unique to E. coli, and this number is expected to be reduced as more genome data becomes available. The imputed functions were assigned on the basis of manual evaluation of functions predicted by BLAST and DARWIN analyses and by the MAGPIE genome annotation system. Conclusions: Much knowledge has been gained about functions encoded by the E. coli K-12 genome since the 1997 annotation was published. The data presented here should be useful for analysis of E. coli gene products as well as gene products encoded by other genomes.
    Beschreibung: This work was supported by NIH grant RO1 RR07861, the NASA Astrobiology Institute grant NCC2-1054, grants from the Edward Mallinckrodt, Jr Foundation and the Sinsheimer Foundation, and NSF grants NSF DBI - 9984882 and NSF IIS - 9996304.
    Schlagwort(e): Escherichia coli K-12
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  • 17
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    Annual Reviews
    Publikationsdatum: 2022-05-25
    Beschreibung: Author Posting. © Annual Reviews, 2006. This article is posted here by permission of Annual Reviews for personal use, not for redistribution. The definitive version was published in Annual Review of Fluid Mechanics 38 (2006): 395-425, doi:10.1146/annurev.fluid.38.050304.092129.
    Beschreibung: Over the past four decades, the combination of in situ and remote sensing observations has demonstrated that long nonlinear internal solitary-like waves are ubiquitous features of coastal oceans. The following provides an overview of the properties of steady internal solitary waves and the transient processes of wave generation and evolution, primarily from the point of view of weakly nonlinear theory, of which the Korteweg-de Vries equation is the most frequently used example. However, the oceanographically important processes of wave instability and breaking, generally inaccessible with these models, are also discussed. Furthermore, observations often show strongly nonlinear waves whose properties can only be explained with fully nonlinear models.
    Beschreibung: KRH acknowledges support from NSF and ONR and an Independent Study Award from the Woods Hole Oceanographic Institution. WKM acknowledges support from NSF and ONR, which has made his work in this area possible, in close collaboration with former graduate students at Scripps Institution of Oceanography and MIT.
    Schlagwort(e): Solitary waves ; Nonlinear waves ; Stratified flow ; Physical Oceanography
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  • 18
    Publikationsdatum: 2022-05-25
    Beschreibung: From The Third Annual Conference of the MidSouth Computational Biology and Bioinformatics Society Baton Rouge, Louisiana. 2–4 March, 2006.
    Beschreibung: © 2006 Nahum et al; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
    Beschreibung: EGenBio is a system for manipulation and filtering of large numbers of sequences, integrating curated sequence alignments and phylogenetic trees, managing evolutionary analyses, and visualizing their output. EGenBio is organized into three conceptual divisions, Evolution, Genomics, and Biodiversity. The Genomics division includes tools for selecting pre-aligned sequences from different genes and species, and for modifying and filtering these alignments for further analysis. Species searches are handled through queries that can be modified based on a tree-based navigation system and saved. The Biodiversity division contains tools for analyzing individual sequences or sequence alignments, whereas the Evolution division contains tools involving phylogenetic trees. Alignments are annotated with analytical results and modification history using our PRAED format. A miscellaneous Tools section and Help framework are also available. EGenBio was developed around our comparative genomic research and a prototype database of mtDNA genomes. It utilizes MySQL-relational databases and dynamic page generation, and calls numerous custom programs.
    Beschreibung: This work was partly funded by the National Institutes of Health (R22/R33 Innovation and Development grant to David Pollock), the National Science Foundation (CBM2/EPSCOR), and the State of Louisiana (Biological Computation and Visualization Center, Governor's iotechnology Initiative, and startup funds to David Pollock).
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  • 19
    Publikationsdatum: 2022-05-25
    Beschreibung: © 2006 Erdner and Anderson. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The definitive version was published in BMC Genomics 7 (2006): 88, doi:10.1186/1471-2164-7-88.
    Beschreibung: Dinoflagellates are one of the most important classes of marine and freshwater algae, notable both for their functional diversity and ecological significance. They occur naturally as free-living cells, as endosymbionts of marine invertebrates and are well known for their involvement in "red tides". Dinoflagellates are also notable for their unusual genome content and structure, which suggests that the organization and regulation of dinoflagellate genes may be very different from that of most eukaryotes. To investigate the content and regulation of the dinoflagellate genome, we performed a global analysis of the transcriptome of the toxic dinoflagellate Alexandrium fundyense under nitrate- and phosphate-limited conditions using Massively Parallel Signature Sequencing (MPSS).
    Beschreibung: This work was funded by National Science Foundation OCE-0136861 and OCE-0430724, National Institute of Environmental Health Sciences 1 P50 ES012742-01, and a grant from the Woods Hole Oceanographic Institution Ocean Life Institute.
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  • 20
    Publikationsdatum: 2022-05-25
    Beschreibung: © 2003 BioMed Central. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The definitive version was published in Genome Biology 4 (2003): 235, doi:10.1186/gb-2003-4-11-235.
    Beschreibung: One of the challenges for ‘post-genomic’ biology is the integration of data from many different sources. Two recent studies independently take steps towards this goal for Escherichia coli, using mathematical modeling and a combination of gene expression and protein levels to predict new gene functions and metabolic behaviors.
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  • 21
    Publikationsdatum: 2022-05-25
    Beschreibung: © 2006 Hutt and Albertini. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The definitive version was published in Journal of Experimental & Clinical Assisted Reproduction 3 (2006): 6, doi:10.1186/1743-1050-3-6.
    Beschreibung: The publication of a report in Nature in 2004 by the Tilly group suggesting that mouse ovaries are capable of generating oocytes de novo post-natally, has sparked interest in a problem long thought to have been resolved from classical studies in a variety of mammalian species. Within a nearly two year time period, laboratories around the world have taken up the challenge to dogma raised by this initial report, either to test this concept in an experimental basic science setting or give direction to clinical applications that could result, were the original premises of this work in the mouse valid for extrapolation to humans. This review provides a status report for this promising area of research, (1) to summarize recent findings in the literature with respect to the validity of the original hypothesis proffered by the Tilly group, and, (2) to gauge the potential utility of ovarian stem cells as a treatment for certain forms of human infertility.
    Beschreibung: Support and the funding provided from the Hall Family Foundation.
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  • 22
    Publikationsdatum: 2022-05-25
    Beschreibung: © 2008 Author et al. This is an open access article distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Environmental Health 7 (2008): S3, doi:10.1186/1476-069X-7-S2-S3.
    Beschreibung: Innovative research relating oceans and human health is advancing our understanding of disease-causing organisms in coastal ecosystems. Novel techniques are elucidating the loading, transport and fate of pathogens in coastal ecosystems, and identifying sources of contamination. This research is facilitating improved risk assessments for seafood consumers and those who use the oceans for recreation. A number of challenges still remain and define future directions of research and public policy. Sample processing and molecular detection techniques need to be advanced to allow rapid and specific identification of microbes of public health concern from complex environmental samples. Water quality standards need to be updated to more accurately reflect health risks and to provide managers with improved tools for decision-making. Greater discrimination of virulent versus harmless microbes is needed to identify environmental reservoirs of pathogens and factors leading to human infections. Investigations must include examination of microbial community dynamics that may be important from a human health perspective. Further research is needed to evaluate the ecology of non-enteric water-transmitted diseases. Sentinels should also be established and monitored, providing early warning of dangers to ecosystem health. Taken together, this effort will provide more reliable information about public health risks associated with beaches and seafood consumption, and how human activities can affect their exposure to disease-causing organisms from the oceans.
    Beschreibung: The Oceans and Human Health Initiative research described within this paper is supported by the National Science Foundation, The National Institute for Environmental Health Sciences and the National Oceanic and Atmospheric Administration. Grant numbers are: NIEHS P50 ES012742 and NSF OCE- 043072 (RJG, LAA-Z, MFP), NSF OCE04-32479 and NIEHS P50 ES012740 (RSF), NSF OCE-0432368 and NIEHS P50 ES12736 (HMS-G), NIEHS P50 ES012762 and NSF OCE-0434087 (JSM).
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  • 23
    Publikationsdatum: 2022-05-25
    Beschreibung: © 2008 Author et al. This is an open access article distributed under the terms of the Creative Commons Attribution License The definitive version was published in Environmental Health 7 (2008): S6, doi:10.1186/1476-069X-7-S2-S6.
    Beschreibung: We review the major linkages between the oceans and public health, focusing on exposures and potential health effects due to anthropogenic and natural factors including: harmful algal blooms, microbes, and chemical pollutants in the oceans; consumption of seafood; and flooding events. We summarize briefly the current state of knowledge about public health effects and their economic consequences; and we discuss priorities for future research. We find that: • There are numerous connections between the oceans, human activities, and human health that result in both positive and negative exposures and health effects (risks and benefits); and the study of these connections comprises a new interdisciplinary area, "oceans and human health." • The state of present knowledge about the linkages between oceans and public health varies. Some risks, such as the acute health effects caused by toxins associated with shellfish poisoning and red tide, are relatively well understood. Other risks, such as those posed by chronic exposure to many anthropogenic chemicals, pathogens, and naturally occurring toxins in coastal waters, are less well quantified. Even where there is a good understanding of the mechanism for health effects, good epidemiological data are often lacking. Solid data on economic and social consequences of these linkages are also lacking in most cases. • The design of management measures to address these risks must take into account the complexities of human response to warnings and other guidance, and the economic tradeoffs among different risks and benefits. Future research in oceans and human health to address public health risks associated with marine pathogens and toxins, and with marine dimensions of global change, should include epidemiological, behavioral, and economic components to ensure that resulting management measures incorporate effective economic and risk/benefit tradeoffs.
    Beschreibung: Funding was provided in part by the NSF-NIEHS Oceans Centers at Woods Hole, University of Hawaii, University of Miami, and University of Washington, and the NOAA Oceans and Human Health Initiative Centers of Excellent in Charleston, Seattle and Milwaukee, the National Center for Environmental Health (NCEH) of the Centers for Disease Control and Prevention (CDC), and the WHOI Marine Policy Center. Grant numbers are: NIEHS P50 ES012742 and NSF OCE-043072 (HLKP, RJG, PH); NSF OCE 0432368 and NIEHS P50 ES12736 (LEF); NIEHS P50 ES012762 and NSF OCE-0434087 (EMF, AT, LRY); NSF OCE04-32479 and NIEHS P50 ES012740 (BAW)
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  • 24
    Publikationsdatum: 2022-05-25
    Beschreibung: © 2007 Dietz et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 2.0, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The definitive version was published in BMC Ecology 7 (2007): 14, doi:10.1186/1472-6785-7-14.
    Beschreibung: Free-ranging narwhals (Monodon monoceros) were instrumented in Admiralty Inlet, Canada with both satellite tags to study migration and stock separation and short-term, high-resolution digital archival tags to explore diving and feeding behaviour. Three narwhals were equipped with an underwater camera pod (Crittercam), another individual was equipped with a digital archival tag (DTAG), and a fifth with both units during August 2003 and 2004. Crittercam footage indicated that of the combined 286 minutes of recordings, 12% of the time was spent along the bottom. When the bottom was visible in the camera footage, the narwhals were oriented upside-down 80% of the time (range: 61 100%). The DTAG data (14.6 hours of recordings) revealed that during time spent below the surface, the two tagged narwhals were supine an average of 13% (range: 9–18%) of the time. Roughly 70% of this time spent in a supine posture occurred during the descent. Possible reasons for this upside-down swimming behaviour are discussed. No preference for a clockwise or counter-clockwise direction of roll was observed, discounting the possibility that rolling movements contribute to the asymmetric left-handed helical turns of the tusk.
    Beschreibung: This study was funded by the National Environmental Research Institute, the Greenland Institute of Natural Resources (organized by Mads Peter Heide-Jørgensen), the Department of Fisheries and Oceans, the Nunavut Wildlife Research Trust Fund and the Danish Cooperation for the Environment in the Arctic (DANCEA). Ari D. Shapiro received financial support from the WHOI Academic Programs Office, the National Science Foundation Research Fellowship and the National Defense Science & Engineering Graduate Fellowship.
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  • 25
    Publikationsdatum: 2022-05-25
    Beschreibung: © 2008 Author et al. This is an open access article distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Environmental Health 7 (2008): S1, doi:10.1186/1476-069X-7-S2-S1.
    Beschreibung: The oceans are the dominant feature of the planet and are fundamentally linked to human history and to human health. Concerns about the impact of the oceans on human health can be traced to ancient times. Jewish law prohibited the consumption of shellfish, probably reflecting the fact that filter-feeding bivalves can accumulate pathogens and toxins. The Portuguese explorer Pedro Fernandes de Queirós described symptoms associated with ciguatera fish poisoning after eating Caribbean sea bream in 1606, and several of British explorer James Cook's crew experienced similar symptoms after eating fish off the coast of Vanuatu in 1774 [1]. Roughly 1,200 people died from the consumption of fish and shellfish contaminated with methyl mercury in Minamata (Japan) during the 20th century; an even larger number were affected by chronic long-term neurotoxicological impacts [2]. A tsunami caused by an undersea earthquake on December 26, 2004 killed more than 225,000 people in eleven countries bordering the Indian Ocean; and more than 1,400 people died within a single day when the storm surge generated by Hurricane Katrina overwhelmed the New Orleans levee system on August 29, 2005 [3]. Looking ahead, the International Panel on Climate Change has projected a sea level rise of as much as 88 cm during the 21st century as a result of global warming [4], with major implications for the welfare and sustainability of coastal communities.
    Beschreibung: The support of the National Science Foundation (US) and the National Institute of Environmental Health Sciences (US) is gratefully acknowledged: Grant numbers NSF OCE04- 32479 and NIEHS P50 ES012740 (EAL), NSF OCE-0432368 and NIEHS P50 ES12736 (LEB), and NIEHS P50 ES012742 and NSF OCE-043072 (JJS).
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  • 26
    Publikationsdatum: 2022-05-25
    Beschreibung: © 2008 Author et al. This is an open access article distributed under the terms of the Creative Commons Attribution License The definitive version was published in Environmental Health 7 (2008): S2, doi:10.1186/1476-069X-7-S2-S2.
    Beschreibung: Harmful algal blooms (HABs) are one focus of the national research initiatives on Oceans and Human Health (OHH) at NIEHS, NOAA and NSF. All of the OHH Centers, from the east coast to Hawaii, include one or more research projects devoted to studying HAB problems and their relationship to human health. The research shares common goals for understanding, monitoring and predicting HAB events to protect and improve human health: understanding the basic biology of the organisms; identifying how chemistry, hydrography and genetic diversity influence blooms; developing analytical methods and sensors for cells and toxins; understanding health effects of toxin exposure; and developing conceptual, empirical and numerical models of bloom dynamics. In the past several years, there has been significant progress toward all of the common goals. Several studies have elucidated the effects of environmental conditions and genetic heterogeneity on bloom dynamics. New methods have been developed or implemented for the detection of HAB cells and toxins, including genetic assays for Pseudo-nitzschia and Microcystis, and a biosensor for domoic acid. There have been advances in predictive models of blooms, most notably for the toxic dinoflagellates Alexandrium and Karenia. Other work is focused on the future, studying the ways in which climate change may affect HAB incidence, and assessing the threat from emerging HABs and toxins, such as the cyanobacterial neurotoxin β-N-methylamino-L-alanine. Along the way, many challenges have been encountered that are common to the OHH Centers and also echo those of the wider HAB community. Long-term field data and basic biological information are needed to develop accurate models. Sensor development is hindered by the lack of simple and rapid assays for algal cells and especially toxins. It is also critical to adequately understand the human health effects of HAB toxins. Currently, we understand best the effects of acute toxicity, but almost nothing is known about the effects of chronic, subacute toxin exposure. The OHH initiatives have brought scientists together to work collectively on HAB issues, within and across regions. The successes that have been achieved highlight the value of collaboration and cooperation across disciplines, if we are to continue to advance our understanding of HABs and their relationship to human health.
    Beschreibung: This work was funded through grants from the NSF/NIEHS Centers for Oceans and Human Health, NIEHS P50 ES012742 and NSF OCE-043072 (DLE and DMA), NSF OCE04-32479 and NIEHS P50 ES012740 (PB and RRB), NSF OCE-0432368 and NIEHS P50 ES12736 (LEB), NIEHS P50 ES012762 and NSF OCE-0434087 (RCS, KAL, MSP, MLW, and KAH). Additional support was provided by the ECOHAB Grant program NSF Grant OCE-9808173 and NOAA Grant NA96OP0099 (DMA), NOAA OHHI NA04OAR4600206 (RRB) and Washington State Sea Grant NA16RG1044 (RCS). KAL and VLT were supported in part by the West Coast Center for Oceans and Human Health (WCCOHH) as part of the NOAA Oceans and Human Health Initiative.
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  • 27
    Publikationsdatum: 2022-05-25
    Beschreibung: © 2008 Author et al. This is an open access article distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Environmental Health 7 (2008): S5, doi:10.1186/1476-069X-7-S2-S5.
    Beschreibung: Coupled physical-biological models are capable of linking the complex interactions between environmental factors and physical hydrodynamics to simulate the growth, toxicity and transport of infectious pathogens and harmful algal blooms (HABs). Such simulations can be used to assess and predict the impact of pathogens and HABs on human health. Given the widespread and increasing reliance of coastal communities on aquatic systems for drinking water, seafood and recreation, such predictions are critical for making informed resource management decisions. Here we identify three challenges to making this connection between pathogens/HABs and human health: predicting concentrations and toxicity; identifying the spatial and temporal scales of population and ecosystem interactions; and applying the understanding of population dynamics of pathogens/HABs to management strategies. We elaborate on the need to meet each of these challenges, describe how modeling approaches can be used and discuss strategies for moving forward in addressing these challenges.
    Beschreibung: The authors acknowledge the financial support for the NSF/NIEHS and NOAA Centers for Oceans and Human Health
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  • 28
    Publikationsdatum: 2022-05-25
    Beschreibung: © 2009 The Authors. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Biology Direct 4 (2009): 46, doi:10.1186/1745-6150-4-46.
    Beschreibung: Sequence related families of genes and proteins are common in bacterial genomes. In Escherichia coli they constitute over half of the genome. The presence of families and superfamilies of proteins suggest a history of gene duplication and divergence during evolution. Genome encoded protein families, their size and functional composition, reflect metabolic potentials of the organisms they are found in. Comparing protein families of different organisms give insight into functional differences and similarities. Equivalent enzyme families with metabolic functions were selected from the genomes of four experimentally characterized bacteria belonging to separate genera. Both similarities and differences were detected in the protein family memberships, with more similarities being detected among the more closely related organisms. Protein family memberships reflected known metabolic characteristics of the organisms. Differences in divergence of functionally characterized enzyme family members accounted for characteristics of taxa known to differ in those biochemical properties and capabilities. While some members of the gene families will have been acquired by lateral exchange and other former family members will have been lost over time, duplication and divergence of genes and functions appear to have been a significant contributor to the functional diversity of today’s microbes. Protein families seem likely to have arisen during evolution by gene duplication and divergence where the gene copies that have been retained are the variants that have led to distinct bacterial physiologies and taxa. Thus divergence of the duplicate enzymes has been a major process in the generation of different kinds of bacteria.
    Beschreibung: This research was supported by the Office of Science (BER), U.S. Department of Energy, Grant No. DE-FG02-08ER64511.
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  • 29
    Publikationsdatum: 2022-05-25
    Beschreibung: © 2005 Serres and Riley. This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The definitive version was published in BMC Genomics 6 (2005): 33, doi:10.1186/1471-2164-6-33.
    Beschreibung: Background: Escherichia coli a model organism provides information for annotation of other genomes. Our analysis of its genome has shown that proteins encoded by fused genes need special attention. Such composite (multimodular) proteins consist of two or more components (modules) encoding distinct functions. Multimodular proteins have been found to complicate both annotation and generation of sequence similar groups. Previous work overstated the number of multimodular proteins in E. coli. This work corrects the identification of modules by including sequence information from proteins in 50 sequenced microbial genomes. Results: Multimodular E. coli K-12 proteins were identified from sequence similarities between their component modules and non-fused proteins in 50 genomes and from the literature. We found 109 multimodular proteins in E. coli containing either two or three modules. Most modules had standalone sequence relatives in other genomes. The separated modules together with all the single (un-fused) proteins constitute the sum of all unimodular proteins of E. coli. Pairwise sequence relationships among all E. coli unimodular proteins generated 490 sequence similar, paralogous groups. Groups ranged in size from 92 to 2 members and had varying degrees of relatedness among their members. Some E. coli enzyme groups were compared to homologs in other bacterial genomes. Conclusion: The deleterious effects of multimodular proteins on annotation and on the formation of groups of paralogs are emphasized. To improve annotation results, all multimodular proteins in an organism should be detected and when known each function should be connected with its location in the sequence of the protein. When transferring functions by sequence similarity, alignment locations must be noted, particularly when alignments cover only part of the sequences, in order to enable transfer of the correct function. Separating multimodular proteins into module units makes it possible to generate protein groups related by both sequence and function, avoiding mixing of unrelated sequences. Organisms differ in sizes of groups of sequence-related proteins. A sample comparison of orthologs to selected E. coli paralogous groups correlates with known physiological and taxonomic relationships between the organisms.
    Beschreibung: The research was supported by the Office of Science (BER), U.S. Department of Energy, Grant No. DE-FG02-01ER63202 and by National Aeronautics and Space Administration Astrobiology grant NCC2-1054.
    Schlagwort(e): Escherichia coli ; Multimodular proteins
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  • 30
    Publikationsdatum: 2022-05-25
    Beschreibung: First published online as a Review in Advance on October 24, 2005. (Some corrections may occur before final publication online and in print)
    Beschreibung: Author Posting. © Annual Reviews, 2005. This article is posted here by permission of Annual Reviews for personal use, not for redistribution. The definitive version was published in Annual Review of Physiology 68 (2006): 22.1-22.29, doi:10.1146/annurev.physiol.68.040104.105418.
    Beschreibung: Superfast muscles of vertebrates power sound production. The fastest, the swimbladder muscle of toadfish, generates mechanical power at frequencies in excess of 200 Hz. To operate at these frequencies, the speed of relaxation has had to increase approximately 50-fold. This increase is accomplished by modifications of three kinetic traits: (a) a fast calcium transient due to extremely high concentration of sarcoplasmic reticulum (SR)-Ca2+ pumps and parvalbumin, (b) fast off-rate of Ca2+ from troponin C due to an alteration in troponin, and (c) fast cross-bridge detachment rate constant (g, 50 times faster than that in rabbit fast-twitch muscle) due to an alteration in myosin. Although these three modifications permit swimbladder muscle to generate mechanical work at high frequencies (where locomotor muscles cannot), it comes with a cost: The high g causes a large reduction in attached force-generating cross-bridges, making the swimbladder incapable of powering low-frequency locomotory movements. Hence the locomotory and sound-producing muscles have mutually exclusive designs.
    Beschreibung: This work was made possible by support from NIH grants AR38404 and AR46125 as well as the University of Pennsylvania Research Foundation.
    Schlagwort(e): Parvalbumin ; Ca2+ release ; Ca2+ uptake ; Cross-bridges ; Adaptation ; Sound production ; Whitman Center
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  • 31
    Publikationsdatum: 2022-05-25
    Beschreibung: © 2007 Huang and Gogarten. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The definitive version was published in Genome Biology 8 (2007): R99, doi:10.1186/gb-2007-8-6-r99.
    Beschreibung: Ancient endosymbioses are responsible for the origins of mitochondria and plastids, and they contribute to the divergence of several major eukaryotic groups. Although chlamydiae, a group of obligate intracellular bacteria, are not found in plants, an unexpected number of chlamydial genes are most similar to plant homologs, which, interestingly, often contain a plastid-targeting signal. This observation has prompted several hypotheses, including gene transfer between chlamydiae and plant-related groups and an ancestral relationship between chlamydiae and cyanobacteria. We conducted phylogenomic analyses of the red alga Cyanidioschyzon merolae to identify genes specifically related to chlamydial homologs. We show that at least 21 genes were transferred between chlamydiae and primary photosynthetic eukaryotes, with the donor most similar to the environmental Protochlamydia. Such an unusually high number of transferred genes suggests an ancient chlamydial endosymbiosis with the ancestral primary photosynthetic eukaryote. We hypothesize that three organisms were involved in establishing the primary photosynthetic lineage: the eukaryotic host cell, the cyanobacterial endosymbiont that provided photosynthetic capability, and a chlamydial endosymbiont or parasite that facilitated the establishment of the cyanobacterial endosymbiont. Our findings provide a glimpse into the complex interactions that were necessary to establish the primary endosymbiotic relationship between plastid and host cytoplasms, and thereby explain the rarity with which long-term successful endosymbiotic relationships between heterotrophs and photoautotrophs were established. Our data also provide strong and independent support for a common origin of all primary photosynthetic eukaryotes and of the plastids they harbor.
    Beschreibung: This work was performed while JH held a National Research Council Associateship Award at the NASA Astrobiology Institute at the Marine Biological Laboratory in Woods Hole, Massachusetts (NCC2-1054). Additional support was provided through NSF (MCB-0237197) and NASA AISR (NNG04GP90G) grants to JPG.
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  • 32
    Publikationsdatum: 2022-05-26
    Beschreibung: This is an Open Access article distributed under the terms of the Creative Commons Attribution License 2.0 which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The definitive version was published in BMC Evolutionary Biology 8 (2008): 14, doi:10.1186/1471-2148-8-14.
    Beschreibung: Our understanding of the eukaryotic tree of life and the tremendous diversity of microbial eukaryotes is in flux as additional genes and diverse taxa are sampled for molecular analyses. Despite instability in many analyses, there is an increasing trend to classify eukaryotic diversity into six major supergroups: the 'Amoebozoa', 'Chromalveolata', 'Excavata', 'Opisthokonta', 'Plantae', and 'Rhizaria'. Previous molecular analyses have often suffered from either a broad taxon sampling using only single-gene data or have used multigene data with a limited sample of taxa. This study has two major aims: (1) to place taxa represented by 72 sequences, 61 of which have not been characterized previously, onto a well-sampled multigene genealogy, and (2) to evaluate the support for the six putative supergroups using two taxon-rich data sets and a variety of phylogenetic approaches.
    Beschreibung: This project was made possible by a collaborative grant from the National Science Foundation Assembling the Tree of Life program (EF 04-31117) that was awarded to L.A.K., D.B., J.L., D.J.P., and to the ATCC
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  • 33
    Publikationsdatum: 2022-05-26
    Beschreibung: © 2009 The Authors. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in BMC Biology 7 (2009): 72, doi:10.1186/1741-7007-7-72.
    Beschreibung: Recent advances in sequencing strategies make possible unprecedented depth and scale of sampling for molecular detection of microbial diversity. Two major paradigm-shifting discoveries include the detection of bacterial diversity that is one to two orders of magnitude greater than previous estimates, and the discovery of an exciting 'rare biosphere' of molecular signatures ('species') of poorly understood ecological significance. We applied a high-throughput parallel tag sequencing (454 sequencing) protocol adopted for eukaryotes to investigate protistan community complexity in two contrasting anoxic marine ecosystems (Framvaren Fjord, Norway; Cariaco deep-sea basin, Venezuela). Both sampling sites have previously been scrutinized for protistan diversity by traditional clone library construction and Sanger sequencing. By comparing these clone library data with 454 amplicon library data, we assess the efficiency of high-throughput tag sequencing strategies. We here present a novel, highly conservative bioinformatic analysis pipeline for the processing of large tag sequence data sets.The analyses of ca. 250,000 sequence reads revealed that the number of detected Operational Taxonomic Units (OTUs) far exceeded previous richness estimates from the same sites based on clone libraries and Sanger sequencing. More than 90% of this diversity was represented by OTUs with less than 10 sequence tags. We detected a substantial number of taxonomic groups like Apusozoa, Chrysomerophytes, Centroheliozoa, Eustigmatophytes, hyphochytriomycetes, Ichthyosporea, Oikomonads, Phaeothamniophytes, and rhodophytes which remained undetected by previous clone library-based diversity surveys of the sampling sites. The most important innovations in our newly developed bioinformatics pipeline employ (i) BLASTN with query parameters adjusted for highly variable domains and a complete database of public ribosomal RNA (rRNA) gene sequences for taxonomic assignments of tags; (ii) a clustering of tags at k differences (Levenshtein distance) with a newly developed algorithm enabling very fast OTU clustering for large tag sequence data sets; and (iii) a novel parsing procedure to combine the data from individual analyses. Our data highlight the magnitude of the under-sampled 'protistan gap' in the eukaryotic tree of life. This study illustrates that our current understanding of the ecological complexity of protist communities, and of the global species richness and genome diversity of protists, is severely limited. Even though 454 pyrosequencing is not a panacea, it allows for more comprehensive insights into the diversity of protistan communities, and combined with appropriate statistical tools, enables improved ecological interpretations of the data and projections of global diversity.
    Beschreibung: The International Census of Marine Microbes and the W.M. Keck Foundation award to the Marine Biological Laboratory at Woods Hole (MA) supported the pyrosequencing part of this study. Further financial support came from a grant from the Deutsche Forschungsgemeinschaft to TS (STO414/3-1). Support for the unpublished work on Cariaco Basin protists came from NSF MCB-0348407 to VE (collaborative project with S Epstein at Northeastern University, Boston, MA, USA). Financial support to AC was provided by NSF MCB-0348045. Financial support to RC was provided by the ANR-Biodiversité project Aquaparadox.
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  • 34
    Publikationsdatum: 2022-05-26
    Beschreibung: © 2009 The Authors. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in BMC Microbiology 9 (2009): 16, doi:10.1186/1471-2180-9-16.
    Beschreibung: The Euglenozoa is a large group of eukaryotic flagellates with diverse modes of nutrition. The group consists of three main subclades – euglenids, kinetoplastids and diplonemids – that have been confirmed with both molecular phylogenetic analyses and a combination of shared ultrastructural characteristics. Several poorly understood lineages of putative euglenozoans live in anoxic environments, such as Calkinsia aureus, and have yet to be characterized at the molecular and ultrastructural levels. Improved understanding of these lineages is expected to shed considerable light onto the ultrastructure of prokaryote-eukaryote symbioses and the associated cellular innovations found within the Euglenozoa and beyond. We collected Calkinsia aureus from core samples taken from the low-oxygen seafloor of the Santa Barbara Basin (580 – 592 m depth), California. These biflagellates were distinctively orange in color and covered with a dense array of elongated epibiotic bacteria. Serial TEM sections through individually prepared cells demonstrated that C. aureus shares derived ultrastructural features with other members of the Euglenozoa (e.g. the same paraxonemal rods, microtubular root system and extrusomes). However, C. aureus also possessed several novel ultrastructural systems, such as modified mitochondria (i.e. hydrogenosome-like), an "extrusomal pocket", a highly organized extracellular matrix beneath epibiotic bacteria and a complex flagellar transition zone. Molecular phylogenies inferred from SSU rDNA sequences demonstrated that C. aureus grouped strongly within the Euglenozoa and with several environmental sequences taken from low-oxygen sediments in various locations around the world. Calkinsia aureus possesses all of the synapomorphies for the Euglenozoa, but lacks traits that are specific to any of the three previously recognized euglenozoan subgroups. Molecular phylogenetic analyses of C. aureus demonstrate that this lineage is a member of a novel euglenozoan subclade consisting of uncharacterized cells living in low-oxygen environments. Our ultrastructural description of C. aureus establishes the cellular identity of a fourth group of euglenozoans, referred to as the "Symbiontida".
    Beschreibung: This work was supported by grants to BSL from the Tula Foundation (Centre for Microbial Diversity and Evolution), the National Science and Engineering Research Council of Canada (NSERC 283091-04) and the Canadian Institute for Advanced Research, Program in Integrated Microbial Biodiversity. Funding for the collection of sediments and participation of VPE and JMB in this research was provided by the US National Science Foundation grant MCB-060484.
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  • 35
    Publikationsdatum: 2022-05-26
    Beschreibung: © 2001 Samuel et al; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL. The definitive version was published in BMC Microbiology 1 (2001): 4, doi:10.1186/1471-2180-1-4.
    Beschreibung: Many bacteria swim by rotating helical flagellar filaments. Waterbury et al. discovered an exception, strains of the cyanobacterium Synechococcus that swim without flagella or visible changes in shape. Other species of cyanobacteria glide on surfaces. The hypothesis that Synechococcus might swim using traveling surface waves prompted this investigation. Results Using quick-freeze electron microscopy, we have identified a crystalline surface layer that encloses the outer membrane of the motile strain Synechococcus sp. WH8113, the components of which are arranged in a rhomboid lattice. Spicules emerge in profusion from the layer and extend up to 150 nm into the surrounding fluid. These spicules also send extensions inwards to the inner cell membrane where motility is powered by an ion-motive force. Conclusion The envelope structure of Synechococcus sp. WH8113 provides new constraints on its motile mechanism. The spicules are well positioned to transduce energy at the cell membrane into mechanical work at the cell surface. One model is that an unidentified motor embedded in the cell membrane utilizes the spicules as oars to generate a traveling wave external to the surface layer in the manner of ciliated eukaryotes.
    Beschreibung: ADTS was supported by the Rowland Institute for Science and is an Amgen Fellow of the Life Sciences Research Foundation.
    Schlagwort(e): Synechococcus sp. ; Motile mechanism
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  • 36
    Publikationsdatum: 2022-05-26
    Beschreibung: © 2008 Sarkar et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License. The definitive version was published in BMC Evolutionary Biology 8 (2008): 144, doi:10.1186/1471-2148-8-144.
    Beschreibung: Authority and year information have been attached to taxonomic names since Linnaean times. The systematic structure of taxonomic nomenclature facilitates the ability to develop tools that can be used to explore historical trends that may be associated with taxonomy. From the over 10.7 million taxonomic names that are part of the uBio system, approximately 3 million names were identified to have taxonomic authority information from the years 1750 to 2004. A pipe-delimited file was then generated, organized according to a Linnaean hierarchy and by years from 1750 to 2004, and imported into an Excel workbook. A series of macros were developed to create an Excel-based tool and a complementary Web site to explore the taxonomic data. A cursory and speculative analysis of the data reveals observable trends that may be attributable to significant events that are of both taxonomic (e.g., publishing of key monographs) and societal importance (e.g., world wars). The findings also help quantify the number of taxonomic descriptions that may be made available through digitization initiatives. Temporal organization of taxonomic data can be used to identify interesting biological epochs relative to historically significant events and ongoing efforts. We have developed an Excel workbook and complementary Web site that enables one to explore taxonomic trends for Linnaean taxonomic groupings, from Kingdoms to Families.
    Beschreibung: The work presented here was funded in part by the MBLWHOI Library and the DAB Lindberg Research Fellowship from the Medical Library Association to INS.
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  • 37
    Publikationsdatum: 2022-05-26
    Beschreibung: © 2008 Sarkar et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License 2.0, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The definitive version was published in BMC Bioinformatics 9 (2008): 103, doi:10.1186/1471-2105-9-103.
    Beschreibung: The availability of sequences from whole genomes to reconstruct the tree of life has the potential to enable the development of phylogenomic hypotheses in ways that have not been before possible. A significant bottleneck in the analysis of genomic-scale views of the tree of life is the time required for manual curation of genomic data into multi-gene phylogenetic matrices. To keep pace with the exponentially growing volume of molecular data in the genomic era, we have developed an automated technique, ASAP (Automated Simultaneous Analysis Phylogenetics), to assemble these multigene/multi species matrices and to evaluate the significance of individual genes within the context of a given phylogenetic hypothesis. Applications of ASAP may enable scientists to re-evaluate species relationships and to develop new phylogenomic hypotheses based on genome-scale data.
    Beschreibung: This work is funded in part by NSF DBI-0421604 to GC and RD. INS is supported in part by the Ellison Medical Foundation.
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  • 38
    facet.materialart.
    Unbekannt
    American Institute of Physics
    Publikationsdatum: 2022-05-26
    Beschreibung: Author Posting. © American Institute of Physics, 2009. This article is posted here by permission of American Institute of Physics for personal use, not for redistribution. The definitive version was published in Physics Today 62 n.11 (2009): 39-44.
    Beschreibung: Most species of large whales are endangered because for centuries whaling fleets have decimated their populations. In the late 1960s, marine-mammal biologists discovered that fishermen setting nets for tuna in the Pacific Ocean were killing more than 100,000 dolphins a year. The cause of marine-mammal conservation became so popular at the dawn of the environmental movement that one of the first environmental accomplishments of the US Congress was to enact the Marine Mammal Protection Act of 1972, which prohibits the killing or injuring of marine mammals. Today, small remnant populations of whales, such as the North Atlantic right whale, are threatened by entanglement in fishing gear and collisions by ships. Indeed, marine biologists have estimated that hundreds of thousands of marine mammals are killed each year in fishing gear. Inadvertent effects of human activities can pose a serious risk to coastal populations, as evidenced by the recent extinction of the Chinese river dolphin due to fishing, pollution, and overdevelopment of the Yangtze River. A few decades ago, conservation efforts focused on reducing the intentional hunting of marine mammals. Nowadays, when hunts for marine mammals are better controlled, the slow degradation of habitat from a combination of sources may have a bigger impact. For example, biologists have documented cases in which the effects of coastal development—including noise, pollution, and dredging—have caused marine mammals to abandon critical breeding habitat. Noise in particular is at issue in legal actions that have been brought against the US Navy for sonar exercises that may have caused whales to strand and die.
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  • 39
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 23 (2005), S. 161-196 
    ISSN: 0732-0582
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Our views regarding the origins and functions of splenic marginal zone B cells have changed considerably over the past few years. Perspectives regarding the development and function of these cells vary considerably between investigators studying human and rodent immunology. Marginal zone B cells are now recognized to constitute a distinct naive B lymphoid lineage. Considerable progress has been made regarding the mechanisms involved in marginal zone B cell development in the mouse. Many of the molecular events that participate in the retention of this lineage of B cells in the marginal zone have been identified. Here, we discuss the functions of these cells in both innate and adaptive immunity. We also attempt to reconcile differing viewpoints regarding the generation and function of marginal zone B cells in rodents and primates.
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  • 40
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 23 (2005), S. 487-513 
    ISSN: 0732-0582
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Helper T (Th) cellĐ??regulated B cell immunity progresses in an ordered cascade of cellular development that culminates in the production of antigen-specific memory B cells. The recognition of peptide MHC class II complexes on activated antigen-presenting cells is critical for effective Th cell selection, clonal expansion, and effector Th cell function development (Phase I). Cognate effector Th cellĐ??B cell interactions then promote the development of either short-lived plasma cells (PCs) or germinal centers (GCs) (Phase II). These GCs expand, diversify, and select high-affinity variants of antigen-specific B cells for entry into the long-lived memory B cell compartment (Phase III). Upon antigen rechallenge, memory B cells rapidly expand and differentiate into PCs under the cognate control of memory Th cells (Phase IV). We review the cellular and molecular regulators of this dynamic process with emphasis on the multiple memory B cell fates that develop in vivo.
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  • 41
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 23 (2005), S. 415-445 
    ISSN: 0732-0582
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: The proliferation and differentiation of lymphocytes are regulated by receptors localized on the cell surface. Engagement of these receptors induces the activation of intracellular signaling proteins that transmit the receptor signals to distinct targets and control the cellular responses. The first signaling proteins to be discovered in higher organisms were the products of oncogenes. For example, the kinases Src and Abelson (Abl) were originally identified as oncogenes and were later characterized as important proteins for signal transduction in various cell types, including lymphocytes. Now, as many cellular signaling molecules have been discovered and ordered into certain pathways, we can better understand why particular signaling proteins are associated with tumorigenesis. In this review, we discuss recent progress in unraveling the molecular mechanisms of signaling pathways that control the proliferation and differentiation of early B cells. We point out the concepts of auto-inhibition and subcellular localization as crucial aspects in the regulation of B cell signaling.
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  • 42
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 23 (2005), S. 683-747 
    ISSN: 0732-0582
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Multiple sclerosis (MS) develops in young adults with a complex predisposing genetic trait and probably requires an inciting environmental insult such as a viral infection to trigger the disease. The activation of CD4+ autoreactive T cells and their differentiation into a Th1 phenotype are a crucial events in the initial steps, and these cells are probably also important players in the long-term evolution of the disease. Damage of the target tissue, the central nervous system, is, however, most likely mediated by other components of the immune system, such as antibodies, complement, CD8+ T cells, and factors produced by innate immune cells. Perturbations in immunomodulatory networks that include Th2 cells, regulatory CD4+ T cells, NK cells, and others may in part be responsible for the relapsing-remitting or chronic progressive nature of the disease. However, an important paradigmatic shift in the study of MS has occurred in the past decade. It is now clear that MS is not just a disease of the immune system, but that factors contributed by the central nervous system are equally important and must be considered in the future.
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  • 43
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 23 (2005), S. 651-682 
    ISSN: 0732-0582
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: CD8+ T cells play a critical role in antiviral immunity by exerting direct antiviral activity against infected cells. Because of their ability to recognize all types of viral proteins, they offer the promise of providing broad immunity to viruses that evade humoral immunity by varying their surface proteins. Consequently, there is considerable interest in developing vaccines that elicit effective antiviral TCD8+ responses. Generating optimal vaccines ultimately requires rational design based on detailed knowledge of how TCD8+ are activated in vivo under natural circumstances. Here we review recent progress obtained largely by in vivo studies in mice to understand the mechanistic basis for activation of naive TCD8+ in virus infections. These studies point the way to detailed understanding and provide some key information for vaccine development, although much remains to be learned to enable truly rational vaccine design.
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  • 44
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 23 (2005), S. 945-974 
    ISSN: 0732-0582
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: The Notch pathway is gaining increasing recognition as a key regulator of developmental choices, differentiation, and function throughout the hematolymphoid system. Notch controls the generation of hematopoietic stem cells during embryonic development and may affect their subsequent homeostasis. Commitment to the T??cell lineage and subsequent stages of early thymopoiesis is critically regulated by Notch. Recent data indicate that Notch can also direct the differentiation and activity of peripheral T and B cells. Thus, the full spectrum of Notch effects is just beginning to be understood. In this review, we discuss this explosion of knowledge as well as current controversies and challenges in the field.
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  • 45
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 23 (2005), S. 975-1028 
    ISSN: 0732-0582
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: The conversion of exogenous and endogenous proteins into immunogenic peptides recognized by T lymphocytes involves a series of proteolytic and other enzymatic events culminating in the formation of peptides bound to MHC class I or class II molecules. Although the biochemistry of these events has been studied in detail, only in the past few years has similar information begun to emerge describing the cellular context in which these events take place. This review thus concentrates on the properties of antigen-presenting cells, especially those aspects of their overall organization, regulation, and intracellular transport that both facilitate and modulate the processing of protein antigens. Emphasis is placed on dendritic cells and the specializations that help account for their marked efficiency at antigen processing and presentation both in vitro and, importantly, in vivo. How dendritic cells handle antigens is likely to be as important a determinant of immunogenicity and tolerance as is the nature of the antigens themselves.
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  • 46
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 23 (2005), S. 515-548 
    ISSN: 0732-0582
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: The discovery of new functions for the original B7 family members, together with the identification of additional B7 and CD28 family members, have revealed new ways in which the B7:CD28 family regulates T cell activation and tolerance. B7-1/B7-2:CD28 interactions not only promote initial T cell activation but also regulate self-tolerance by supporting CD4+CD25+ T regulatory cell homeostasis. CTLA-4 can exert its inhibitory effects in both B7-1/B7-2 dependent and independent fashions. B7-1 and B7-2 can signal bidirectionally by engaging CD28 and CTLA-4 on T cells and by delivering signals into B7-expressing cells. The five new B7 family members, ICOS ligand, PD-L1 (B7-H1), PD-L2 (B7-DC), B7-H3, and B7-H4 (B7x/B7-S1) are expressed on professional antigen-presenting cells as well as on cells within nonlymphoid organs, providing new means for regulating T cell activation and tolerance in peripheral tissues. The new CD28 families members, ICOS, PD-1, and BTLA, are inducibly expressed on T cells, and they have important roles in regulating previously activated T cells. PD-1 and BTLA also are expressed on B cells and may have broader immunoregulatory functions. The ICOS:ICOSL pathway appears to be particularly important for stimulating effector T cell responses and T cellĐ??dependent B cell responses, but it also has an important role in regulating T cell tolerance. In addition, the PD-1:PD-L1/PD-L2 pathway plays a critical role in regulating T cell activation and tolerance. In this review, we revisit the roles of the B7:CD28 family members in regulating immune responses, and we discuss their therapeutic potential.
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  • 47
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 26 (2005), S. 877-900 
    ISSN: 0732-0582
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Natural killer T (NKT) cells constitute a conserved T cell sublineage with unique properties, including reactivity for a synthetic glycolipid presented by CD1d, expression of an invariant T cell antigen receptor (TCR) ʼ̛ chain, and unusual requirements for thymic selection. They rapidly produce many cytokines after stimulation and thus influence diverse immune responses and pathogenic processes. Because of intensive research effort, we have learned much about factors promoting the development and survival of NKT cells, regulation of their cytokine production, and the means by which they influence dendritic cells and other cell types. Despite this progress, knowledge of the natural antigen(s) they recognize and their physiologic role remain incomplete. The activation of NKT cells paradoxically can lead either to suppression or stimulation of immune responses, and we cannot predict which will occur. Despite this uncertainty, many investigators are hopeful that immune therapies can be developed based on NKT cell stimulation.
    Materialart: Digitale Medien
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  • 48
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 23 (2005), S. 549-600 
    ISSN: 0732-0582
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: The Tec family tyrosine kinases are now recognized as important mediators of antigen receptor signaling in lymphocytes. Three members of this family, Itk, Rlk, and Tec, are expressed in T cells and activated in response to T cell receptor (TCR) engagement. Although initial studies demonstrated a role for these proteins in TCR-mediated activation of phospholipase C-??, recent data indicate that Tec family kinases also regulate actin cytoskeletal reorganization and cellular adhesion following TCR stimulation. In addition, Tec family kinases are activated downstream of G proteinĐ??coupled chemokine receptors, where they play parallel roles in the regulation of Rho GTPases, cell polarization, adhesion, and migration. In all these systems, however, Tec family kinases are not essential signaling components, but instead function to modulate or amplify signaling pathways. Although they quantitatively reduce proximal signaling, mutations that eliminate Tec family kinases in T cells nonetheless qualitatively alter T cell development and differentiation.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 49
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 23 (2005), S. 69-99 
    ISSN: 0732-0582
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: The immune response to the malaria parasite is complex and poorly understood. Although antibodies and T cells can control parasite growth in model systems, natural immunity to malaria in regions of high endemicity takes several years to develop. Variation and polymorphism of antibody target antigens are known to impede immune responses, but these factors alone cannot account for the slow acquisition of immunity. In human and animal model systems, cell-mediated responses can control parasite growth effectively, but such responses are regulated by parasite load via direct effects on dendritic cells and possibly on T and B cells as well. Furthermore, high parasite load is associated with pathology, and cell-mediated responses may also harm the host. Inflammatory cytokines have been implicated in the pathogenesis of cerebral malaria, anemia, weight loss, and respiratory distress in malaria. Immunity without pathology requires rapid parasite clearance, effective regulation of the inflammatory antiparasite effects of cellular responses, and the eventual development of a repertoire of antibodies effective against multiple strains. Data suggest that this may be hastened by exposure to malaria antigens in low dose, leading to augmented cellular immunity and rapid parasite clearance.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 50
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 23 (2005), S. 23-68 
    ISSN: 0732-0582
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Several members of the tumor necrosis factor receptor (TNFR) family function after initial T cell activation to sustain T cell responses. This review focuses on CD27, 4-1BB (CD137), OX40 (CD134), HVEM, CD30, and GITR, all of which can have costimulatory effects on T cells. The effects of these costimulatory TNFR family members can often be functionally, temporally, or spatially segregated from those of CD28 and from each other. The sequential and transient regulation of T cell activation/survival signals by different costimulators may function to allow longevity of the response while maintaining tight control of T cell survival. Depending on the disease condition, stimulation via costimulatory TNF family members can exacerbate or ameliorate disease. Despite these complexities, stimulation or blockade of TNFR family costimulators shows promise for several therapeutic applications, including cancer, infectious disease, transplantation, and autoimmunity.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 51
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 23 (2005), S. 447-485 
    ISSN: 0732-0582
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Autoimmunity is a complex process that likely results from the summation of multiple defective tolerance mechanisms. The NOD mouse strain is an excellent model of autoimmune disease and an important tool for dissecting tolerance mechanisms. The strength of this mouse strain is that it develops spontaneous autoimmune diabetes, which shares many similarities to autoimmune or type 1a diabetes (T1D) in human subjects, including the presence of pancreas-specific autoantibodies, autoreactive CD4+ and CD8+ T cells, and genetic linkage to disease syntenic to that found in humans. During the past ten years, investigators have used a wide variety of tools to study these mice, including immunological reagents and transgenic and knockout strains; these tools have tremendously enhanced the study of the fundamental disease mechanisms. In addition, investigators have recently developed a number of therapeutic interventions in this animal model that have now been translated into human therapies. In this review, we summarize many of the important features of disease development and progression in the NOD strain, emphasizing the role of central and peripheral tolerance mechanisms that affect diabetes in these mice. The information gained from this highly relevant model of human disease will lead to potential therapies that may alter the development of the disease and its progression in patients with T1D.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 52
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 23 (2005), S. 101-125 
    ISSN: 0732-0582
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Recent studies have demonstrated that cell membranes provide a unique environment for protein-protein and protein-lipid interactions that are critical for the assembly and function of the T cell receptor (TCR)-CD3 complex. Highly specific polar interactions among transmembrane (TM) domains that are uniquely favorable in the lipid environment organize the association of the three signaling dimers with the TCR. Each of these three assembly steps depends on the formation of a three-helix interface between one basic and two acidic residues in the membrane environment. The same polar TM residues that drive assembly also play a central role in quality control and export by directing the retention and degradation of free subunits and partial complexes, while membrane proximal cytoplasmic signals control recycling and degradation of surface receptors. Recent studies also suggest that interactions between the membrane and the cytoplasmic domains of CD3 proteins may be important for receptor triggering.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 53
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 45 (2005), S. 1-25 
    ISSN: 0362-1642
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Chemie und Pharmazie
    Notizen: The author describes studies that led to the resolution and reconstitution of the cytochrome P450 enzyme system in microsomal membranes. The review indicates how purification and characterization of the cytochromes led to rigorous evidence for multiple isoforms of the oxygenases with distinct chemical and physical properties and different but somewhat overlapping substrate specificities. Present knowledge of the individual steps in the P450 and reductase reaction cycles is summarized, including evidence for the generation of multiple functional oxidants that may contribute to the exceptional diversity of the reactions catalyzed.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 54
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 45 (2005), S. 51-88 
    ISSN: 0362-1642
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Chemie und Pharmazie
    Notizen: This review describes the three mammalian glutathione transferase (GST) families, namely cytosolic, mitochondrial, and microsomal GST, the latter now designated MAPEG. Besides detoxifying electrophilic xenobiotics, such as chemical carcinogens, environmental pollutants, and antitumor agents, these transferases inactivate endogenous ʼ̛,?‚-unsaturated aldehydes, quinones, epoxides, and hydroperoxides formed as secondary metabolites during oxidative stress. These enzymes are also intimately involved in the biosynthesis of leukotrienes, prostaglandins, testosterone, and progesterone, as well as the degradation of tyrosine. Among their substrates, GSTs conjugate the signaling molecules 15-deoxy-??12,14-prostaglandin J2 (15d-PGJ2) and 4-hydroxynonenal with glutathione, and consequently they antagonize expression of genes trans-activated by the peroxisome proliferator-activated receptor ?? (PPAR??) and nuclear factor-erythroid 2 p45-related factor 2 (Nrf2). Through metabolism of 15d-PGJ2, GST may enhance gene expression driven by nuclear factor-?”B (NF-?”B). Cytosolic human GST exhibit genetic polymorphisms and this variation can increase susceptibility to carcinogenesis and inflammatory disease. Polymorphisms in human MAPEG are associated with alterations in lung function and increased risk of myocardial infarction and stroke. Targeted disruption of murine genes has demonstrated that cytosolic GST isoenzymes are broadly cytoprotective, whereas MAPEG proteins have proinflammatory activities. Furthermore, knockout of mouse GSTA4 and GSTZ1 leads to overexpression of transferases in the Alpha, Mu, and Pi classes, an observation suggesting they are part of an adaptive mechanism that responds to endogenous chemical cues such as 4-hydroxynonenal and tyrosine degradation products. Consistent with this hypothesis, the promoters of cytosolic GST and MAPEG genes contain antioxidant response elements through which they are transcriptionally activated during exposure to Michael reaction acceptors and oxidative stress.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 55
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 45 (2005), S. 177-202 
    ISSN: 0362-1642
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Chemie und Pharmazie
    Notizen: The importance of reactive metabolites in the pathogenesis of drug-induced toxicity has been a focus of research interest since pioneering investigations in the 1950s revealed the link between toxic metabolites and chemical carcinogenesis. There is now a great deal of evidence that shows that reactive metabolites are formed from drugs known to cause hepatotoxicity, but how these toxic species initiate and propagate tissue damage is still poorly understood. This review summarizes the evidence for reactive metabolite formation from hepatotoxic drugs, such as acetaminophen, tamoxifen, diclofenac, and troglitazone, and the current hypotheses of how this leads to liver injury. Several hepatic proteins can be modified by reactive metabolites, but this in general equates poorly with the extent of toxicity. Much more important may be the identification of the critical proteins modified by these toxic species and how this alters their function. It is also important to note that the toxicity of reactive metabolites may be mediated by noncovalent binding mechanisms, which may also have profound effects on normal liver physiology. Technological developments in the wake of the genomic revolution now provide unprecedented power to characterize and quantify covalent modification of individual target proteins and their functional consequences; such information should dramatically improve our understanding of drug-induced hepatotoxic reactions.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 56
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 45 (2005), S. 291-310 
    ISSN: 0362-1642
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Chemie und Pharmazie
    Notizen: The cytochrome P450 monooxygenases (CYPs) are the dominant enzyme system responsible for xenobiotic detoxification and drug metabolism. Several CYP isoforms exhibit non-Michaelis-Menten, or "atypical," steady state kinetic patterns. The allosteric kinetics confound prediction of drug metabolism and drug-drug interactions, and they challenge the theoretical paradigms of allosterism. Both homotropic and heterotropic ligand effects are now widely documented. It is becoming apparent that multiple ligands can simultaneously bind within the active sites of individual CYPs, and the kinetic parameters change with ligand occupancy. In fact, the functional effect of any specific ligand as an activator or inhibitor can be substrate dependent. Divergent approaches, including kinetic modeling and X-ray crystallography, are providing new information about how multiple ligand binding yields complex CYP kinetics.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 57
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 45 (2005), S. 335-355 
    ISSN: 0362-1642
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Chemie und Pharmazie
    Notizen: Recent discoveries of novel and potentially important biological activity have spurred interest in the chemistry and biochemistry of nitroxyl (HNO). It has become clear that, among all the nitrogen oxides, HNO is unique in its chemistry and biology. Currently, the intimate chemical details of the biological actions of HNO are not well understood. Moreover, many of the previously accepted chemical properties of HNO have been recently revised, thus requiring reevaluation of possible mechanisms of biological action. Herein, we review these developments in HNO chemistry and biology.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 58
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 45 (2005), S. 385-412 
    ISSN: 0362-1642
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Chemie und Pharmazie
    Notizen: Adenosine and its receptors have been the topic of many recent reviews ( 1Đ??26 ). These reviews provide a good summary of much of the relevant literatureĐ??including the older literature. We have, therefore, chosen to focus the present review on the insights gained from recent studies on genetically modified mice, particularly with respect to the function of adenosine receptors and their potential as therapeutic targets. The information gained from studies of drug effects is discussed in this context, and discrepancies between genetic and pharmacological results are highlighted.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 59
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 45 (2005), S. 657-687 
    ISSN: 0362-1642
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Chemie und Pharmazie
    Notizen: Cardiac fibroblasts play a central role in the maintenance of extracellular matrix in the normal heart and as mediators of inflammatory and fibrotic myocardial remodeling in the injured and failing heart. In this review, we evaluate the cardiac fibroblast as a therapeutic target in heart disease. Unique features of cardiac fibroblast cell biology are discussed in relation to normal and pathophysiological cardiac function. The contribution of cardiac fibrosis as an independent risk factor in the outcome of heart failure is considered. Candidate drug therapies that derive benefit from actions on cardiac fibroblasts are summarized, including inhibitors of angiotensin-aldosterone systems, endothelin receptor antagonists, statins, anticytokine therapies, matrix metalloproteinase inhibitors, and novel antifibrotic/anti-inflammatory agents. These findings point the way to future challenges in cardiac fibroblast biology and pharmacotherapy.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 60
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 46 (2006), S. 65-100 
    ISSN: 0362-1642
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Chemie und Pharmazie
    Notizen: This review summarizes recent information concerning the pharmacological and toxicological significance of the human flavin-containing monooxygenase (FMO, EC 1.14.13.8). The human FMO oxygenates nucleophilic heteroatom-containing chemicals and drugs and generally converts them into harmless, polar, readily excreted metabolites. Sometimes, however, FMO bioactivates chemicals into reactive materials that can cause toxicity. Most of the interindividual differences of FMO are due to genetic variability and allelic variation, and splicing variants may contribute to interindividual and interethnic variability observed for FMO-mediated metabolism. In contrast to cytochrome P450 (CYP), FMO is not easily induced nor readily inhibited, and potential adverse drug-drug interactions are minimized for drugs prominently metabolized by FMO. These properties may provide advantages in drug design and discovery, and by incorporating FMO detoxication pathways into drug candidates, more drug-like materials may be forthcoming. Although exhaustive examples are not available, physiological factors can influence FMO function, and this may have implications for the clinical significance of FMO and a role in human disease.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 61
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 23 (2005), S. 367-386 
    ISSN: 0732-0582
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: In vertebrates, serum antibodies are an essential component of innate and adaptive immunity and immunological memory. They also can contribute significantly to immunopathology. Their composition is the result of tightly regulated differentiation of B lymphocytes into antibody-secreting plasma blasts and plasma cells. The survival of antibody-secreting cells determines their contribution to the immune response in which they were generated and to long-lasting immunity, as provided by stable serum antibody levels. Short-lived plasma blasts and/or plasma cells secrete antibodies for a reactive immune response. Short-lived plasma blasts can become long-lived plasma cells, probably by competition with preexisting plasma cells for occupation of a limited number of survival niches in the body, in a process not yet fully understood. Limitation of the number of long-lived plasma cells allows the immune system to maintain a stable humoral immunological memory over long periods, to react to new pathogenic challenges, and to adapt the humoral memory in response to these antigens.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 62
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 23 (2005), S. 337-366 
    ISSN: 0732-0582
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: C reactive protein, the first innate immunity receptor identified, and serum amyloid P component are classic short pentraxins produced in the liver. Long pentraxins, including the prototype PTX3, are expressed in a variety of tissues. Some long pentraxins are expressed in the brain and some are involved in neuronal plasticity and degeneration. PTX3 is produced by a variety of cells and tissues, most notably dendritic cells and macrophages, in response to Toll-like receptor (TLR) engagement and inflammatory cytokines. PTX3 acts as a functional ancestor of antibodies, recognizing microbes, activating complement, and facilitating pathogen recognition by phagocytes, hence playing a nonredundant role in resistance against selected pathogens. In addition, PTX3 is essential in female fertility because it acts as a nodal point for the assembly of the cumulus oophorus hyaluronan-rich extracellular matrix. Thus, the prototypic long pentraxin PTX3 is a multifunctional soluble pattern recognition receptor at the crossroads between innate immunity, inflammation, matrix deposition, and female fertility.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 63
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 23 (2005), S. 225-274 
    ISSN: 0732-0582
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: The integrated processing of signals transduced by activating and inhibitory cell surface receptors regulates NK cell effector functions. Here, I review the structure, function, and ligand specificity of the receptors responsible for NK cell recognition.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 64
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 23 (2005), S. 787-819 
    ISSN: 0732-0582
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Lymphotoxins (LT) provide essential communication links between lymphocytes and the surrounding stromal and parenchymal cells and together with the two related cytokines, tumor necrosis factor (TNF) and LIGHT (LT-related inducible ligand that competes for glycoprotein D binding to herpesvirus entry mediator on T cells), form an integrated signaling network necessary for efficient innate and adaptive immune responses. Recent studies have identified signaling pathways that regulate several genes, including chemokines and interferons, which participate in the development and function of microenvironments in lymphoid tissue and host defense. Disruption of the LT/TNF/LIGHT network alleviates inflammation in certain autoimmune disease models, but decreases resistance to selected pathogens. Pharmacological disruption of this network in human autoimmune diseases such as rheumatoid arthritis alleviates inflammation in a significant number of patients, but not in other diseases, a finding that challenges our molecular paradigms of autoimmunity and perhaps will reveal novel roles for this network in pathogenesis.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 65
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 23 (2005), S. 387-414 
    ISSN: 0732-0582
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: The newly discovered CATERPILLER (CLR) gene family encodes proteins with a variable but limited number of N-terminal domains, followed by a nucleotide-binding domain (NBD) and leucine-rich repeats (LRR). The N-terminal domain consists of transactivation, CARD, Pyrin, or BIR domains, with a minority containing undefined domains. These proteins are remarkably similar in structure to the TIR-NBD-LRR and CC-NBD-LRR disease resistance (R) proteins that mediate immune responses in plants. The NBD-LRR architecture is conserved in plants and vertebrates, but only remnants are found in worms and flies. The CLRs regulate inflammatory and apoptotic responses, and some act as sensors that detect pathogen products. Several CLR genes have been genetically linked to susceptibility to immunologic disorders. We describe prominent family members, including CIITA, CARD4/NOD1, NOD2/CARD15, CIAS1, CARD7/NALP1, and NAIP, in more detail. We also discuss implied roles of these proteins in diversifying immune detection and in providing a check-and-balance during inflammation.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 66
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 23 (2005), S. 901-944 
    ISSN: 0732-0582
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Macrophages express a broad range of plasma membrane receptors that mediate their interactions with natural and altered-self components of the host as well as a range of microorganisms. Recognition is followed by surface changes, uptake, signaling, and altered gene expression, contributing to homeostasis, host defense, innate effector mechanisms, and the induction of acquired immunity. This review covers recent studies of selected families of structurally defined molecules, studies that have improved understanding of ligand discrimination in the absence of opsonins and differential responses by macrophages and related myeloid cells.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 67
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 23 (2005), S. 601-649 
    ISSN: 0732-0582
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: T cell development is guided by a complex set of transcription factors that act recursively, in different combinations, at each of the developmental choice points from T-lineage specification to peripheral T cell specialization. This review describes the modes of action of the major T-lineage-defining transcription factors and the signal pathways that activate them during intrathymic differentiation from pluripotent precursors. Roles of Notch and its effector RBPSuh (CSL), GATA-3, E2A/HEB and Id proteins, c-Myb, TCF-1, and members of the Runx, Ets, and Ikaros families are critical. Less known transcription factors that are newly recognized as being required for T cell development at particular checkpoints are also described. The transcriptional regulation of T cell development is contrasted with that of B cell development, in terms of their different degrees of overlap with the stem-cell program and the different roles of key transcription factors in gene regulatory networks leading to lineage commitment.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 68
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 23 (2005), S. 307-335 
    ISSN: 0732-0582
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: The significance of type I interferons (IFN-ʼ̛/?‚) in biology and medicine renders research on their activities continuously relevant to our understanding of normal and abnormal (auto) immune responses. This relevance is bolstered by discoveries that unambiguously establish IFN-ʼ̛/?‚, among the multitude of cytokines, as dominant in defining qualitative and quantitative characteristics of innate and adaptive immune processes. Recent advances elucidating the biology of these key cytokines include better definition of their complex signaling pathways, determination of their importance in modifying the effects of other cytokines, the role of Toll-like receptors in their induction, their major cellular producers, and their broad and diverse impact on both cellular and humoral immune responses. Consequently, the role of IFN-ʼ̛/?‚ in the pathogenesis of autoimmunity remains at the forefront of scientific inquiry and has begun to illuminate the mechanisms by which these molecules promote or inhibit systemic and organ-specific autoimmune diseases.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 69
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 23 (2005), S. 127-159 
    ISSN: 0732-0582
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Secondary lymphoid organs serve as hubs for the adaptive immune system, bringing together antigen, antigen-presenting cells, and lymphocytes. Two families of G proteinĐ??coupled receptors play essential roles in lymphocyte migration through these organs: chemokine receptors and sphingosine-1-phosphate (S1P) receptors. Chemokines expressed by lymphoid stromal cells guide lymphocyte and dendritic cell movements during antigen surveillance and the initiation of adaptive immune responses. S1P receptor-1 is required for lymphocyte egress from thymus and secondary lymphoid organs and is downregulated by the immunosuppressive drug FTY720. Here, we review the steps associated with the initiation of adaptive immune responses in secondary lymphoid organs, highlighting the roles of chemokines and S1P.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 70
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 23 (2005), S. 749-786 
    ISSN: 0732-0582
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: This review focuses on recent progress in our understanding of how mast cells can contribute to the initiation, development, expression, and regulation of acquired immune responses, both those associated with IgE and those that are apparently expressed independently of this class of Ig. We emphasize findings derived from in vivo studies in mice, particularly those employing genetic approaches to influence mast cell numbers and/or to alter or delete components of pathways that can regulate mast cell development, signaling, or function. We advance the hypothesis that mast cells not only can function as proinflammatory effector cells and drivers of tissue remodeling in established acquired immune responses, but also may contribute to the initiation and regulation of such responses. That is, we propose that mast cells can also function as immunoregulatory cells. Finally, we show that the notion that mast cells have primarily two functional configurations, off (or resting) or on (or activated for extensive mediator release), markedly oversimplifies reality. Instead, we propose that mast cells are "tunable," by both genetic and environmental factors, such that, depending on the circumstances, the cell can be positioned phenotypically to express a wide spectrum of variation in the types, kinetics, and/or magnitude of its secretory functions.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 71
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 23 (2005), S. 1-21 
    ISSN: 0732-0582
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: This essay summarizes my 40 years of research in immunology. As a young physician, I encountered a patient with Waldenstro?m's macroglobulinemia, and this inspired me to study the structure of IgM. I began to ask how antibody responses are regulated. In the late 1960s, the essential role of T cells in antibody production had been reported. In search of molecules mediating T cell helper function, I discovered activities in the culture supernatant of T cells that induced proliferation and differentiation of B cells. This led to my life's work: studying one of those factors, interleukin-6 (IL-6). To my surprise, IL-6 turned out to play additional roles, including myeloma growth factor and hepatocyte-stimulating factor activities. More importantly, it was involved in a number of diseases, such as rheumatoid arthritis and Castleman's disease. I feel exceptionally fortunate that my work not only revealed the framework of cytokine signaling, including identification of the IL-6 receptor, gp130, NF-IL6, STAT3, and SOCS-1, but also led to the development of a new therapy for chronic inflammatory diseases.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 72
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 23 (2005), S. 853-875 
    ISSN: 0732-0582
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Most mammalian cells have nuclei that contain DNA, which replicates during cell proliferation. DNA is destroyed by various developmental processes in mammals. It is degraded during programmed cell death that accompanies mammalian development. The nuclei of erythrocytes and eye lens fiber cells are also removed during their differentiation into mature cells. If DNA is not properly degraded in these processes, it can cause various diseases, including tissue atrophy, anemia, cataract, and autoimmune diseases, which indicates that DNA can be a pathogenic molecule. Here, I present how DNA is degraded during programmed cell death, erythroid cell differentiation, and lens cell differentiation. I discuss what might be or will be learned from understanding the molecular mechanisms of DNA degradation that occurs during mammalian development.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 73
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 45 (2005), S. 465-476 
    ISSN: 0362-1642
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Chemie und Pharmazie
    Notizen: Normal cellular functioning requires processing of proteins regulating cell cycle, growth, and apoptosis. The ubiquitin-proteasome pathway (UBP) modulates intracellular protein degradation. Specifically, the 26S proteasome is a multienzyme protease that degrades misfolded or redundant proteins; conversely, blockade of the proteasomal degradation pathways results in accumulation of unwanted proteins and cell death. Because cancer cells are more highly proliferative than normal cells, their rate of protein translation and degradation is also higher. This notion led to the development of proteasome inhibitors as therapeutics in cancer. The FDA recently approved the first proteasome inhibitor bortezomib (VelcadeĐ?„), formerly known as PS-341, for the treatment of newly diagnosed and relapsed/refractory multiple myeloma (MM). Ongoing studies are examining other novel proteasome inhibitors, in addition to bortezomib, for the treatment of MM and other cancers.
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  • 74
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 45 (2005), S. 565-585 
    ISSN: 0362-1642
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Chemie und Pharmazie
    Notizen: The enormous public health problem posed by malaria has been substantially worsened in recent years by the emergence and worldwide spread of drug-resistant parasites. The utility of two major therapies, chloroquine and the synergistic combination of pyrimethamine/sulfadoxine, is now seriously compromised. Although several genetic mechanisms have been described, the major source of drug resistance appears to be point mutations in protein target genes. Clinically significant resistance to these agents requires the accumulation of multiple mutations, which genetic studies of parasite populations suggest arise focally and sweep through the population. Efforts to circumvent resistance range from the use of combination therapy with existing agents to laboratory studies directed toward discovering novel targets and therapies. The prevention and management of drug resistance are among the most important practical problems of tropical medicine and public health. Leonard J. Bruce-Chwatt, 1972
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  • 75
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 46 (2006), S. 1-39 
    ISSN: 0362-1642
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Chemie und Pharmazie
    Notizen: Peroxisome proliferator-activated receptors (PPARs) alpha (ʼ̛), beta/delta (?‚/??), and gamma (??) are members of the nuclear receptor superfamily, which also includes the estrogen, androgen, and glucocorticoid receptors. Recent evidence suggests that PPARs regulate genes involved in lipid metabolism, glucose homeostasis, and inflammation in various tissues; however, the mechanisms involved are not completely understood. Anti-diabetic drugs, called glitazones, can selectively activate PPAR??, and hypolipidemic drugs, called fibrates, can weakly activate PPARʼ̛. Both classes of drugs can decrease insulin resistance and dyslipidemias, which also makes them attractive for treating the metabolic syndrome. The metabolic syndrome exhibits a constellation of risk factors for atherosclerosis that include obesity, insulin resistance, dyslipidemias, and hypertension. Interestingly, all three PPARs are present in macrophages and can therefore have a profound effect on several disease processes, including atherosclerosis. Macrophages are key players in atherosclerotic lesion development. Currently, the first line of defense in reducing the risk of atherosclerosis is aimed at lowering low-density lipoproteins (LDL) and raising high-density lipoproteins (HDL), but a large percentage of patients on statins still succumb to coronary artery disease. However, with the development of drugs selectively activating PPARs, a new arsenal of drugs specifically targeting to the macrophage/foam cell may potentially have a profound impact on how we treat cardiovascular disease.
    Materialart: Digitale Medien
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  • 76
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 46 (2006), S. 235-276 
    ISSN: 0362-1642
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Chemie und Pharmazie
    Notizen: Nitric oxide (NO) is a small, diffusible, lipophilic free radical gas that mediates significant and diverse signaling functions in nearly every organ system in the body. The endothelial isoform of nitric oxide synthase (eNOS) is a key source of NO found in the cardiovascular system. This review summarizes the pharmacology of NO and the cellular regulation of endothelial NOS (eNOS). The molecular intricacies of the chemistry of NO and the enzymology of NOSs are discussed, followed by a review of the biological activities of NO. This information is then used to develop a more global picture of the pharmacological control of NO synthesis by NOSs in both physiologic conditions and pathophysiologic states.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 77
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 46 (2006), S. 41-64 
    ISSN: 0362-1642
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Medizin , Chemie und Pharmazie
    Notizen: Most xenobiotics that enter the body are subjected to metabolism that functions primarily to facilitate their elimination. Metabolism of certain xenobiotics can also result in the production of electrophilic derivatives that can cause cell toxicity and transformation. Many xenobiotics can also activate receptors that in turn induce the expression of genes encoding xenobiotic-metabolizing enzymes and xenobiotic transporters. However, there are marked species differences in the way mammals respond to xenobiotics, which are due in large part to molecular differences in receptors and xenobiotic-metabolizing enzymes. This presents a problem in extrapolating data obtained with rodent model systems to humans. There are also polymorphisms in xenobiotic-metabolizing enzymes that can impact drug therapy and cancer susceptibility. In an effort to generate more reliable in vivo systems to study and predict human response to xenobiotics, humanized mice are under development.
    Materialart: Digitale Medien
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  • 78
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 23 (2005), S. 197-223 
    ISSN: 0732-0582
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Neutrophils provide the first line of defense of the innate immune system by phagocytosing, killing, and digesting bacteria and fungi. Killing was previously believed to be accomplished by oxygen free radicals and other reactive oxygen species generated by the NADPH oxidase, and by oxidized halides produced by myeloperoxidase. We now know this is incorrect. The oxidase pumps electrons into the phagocytic vacuole, thereby inducing a charge across the membrane that must be compensated. The movement of compensating ions produces conditions in the vacuole conducive to microbial killing and digestion by enzymes released into the vacuole from the cytoplasmic granules.
    Materialart: Digitale Medien
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  • 79
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 23 (2005), S. 821-852 
    ISSN: 0732-0582
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: The complement system not only represents an effective innate immune mechanism of host defense to eradicate microbial pathogens, but it is also widely involved in many forms of acute and chronic inflammatory diseases including sepsis, acute lung injury, ischemia-reperfusion injury, and asthma, to give just a few examples. The complement-activated product, C5a, displays powerful biological activities that lead to inflammatory sequelae. C5a is a strong chemoattractant and is involved in the recruitment of inflammatory cells such as neutrophils, eosinophils, monocytes, and T lymphocytes, in activation of phagocytic cells and release of granule-based enzymes and generation of oxidants, all of which may contribute to innate immune functions or tissue damage. Accumulating data suggest that C5a provides a vital bridge between innate and adaptive immune functions, extending the roles of C5a in inflammation. Herein, we review human and animal data describing the cellular and molecular mechanisms of C5a in the development of inflammatory disorders, sepsis, acute lung injury, ischemia-reperfusion injury, and asthma.
    Materialart: Digitale Medien
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  • 80
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 23 (2005), S. 275-306 
    ISSN: 0732-0582
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Type 1 interferon-(ʼ̛, ?‚, ?)-producing cells (IPCs), also known as plasmacytoid dendritic cell precursors (pDCs), represent 0.2%Đ??0.8% of peripheral blood mononuclear cells in both humans and mice. IPCs display plasma cell morphology, selectively express Toll-like receptor (TLR)-7 and TLR9, and are specialized in rapidly secreting massive amounts of type 1 interferon following viral stimulation. IPCs can promote the function of natural killer cells, B cells, T cells, and myeloid DCs through type 1 interferons during an antiviral immune response. At a later stage of viral infection, IPCs differentiate into a unique type of mature dendritic cell, which directly regulates the function of T cells and thus links innate and adaptive immune responses. After more than two decades of effort by researchers, IPCs finally claim their place in the hematopoietic chart as the most important cell type in antiviral innate immunity. Understanding IPC biology holds future promise for developing cures for infectious diseases, cancer, and autoimmune diseases.
    Materialart: Digitale Medien
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  • 81
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 34 (2005), S. 267-294 
    ISSN: 1056-8700
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Physik
    Notizen: With genome sequencing nearing completion for the model organisms used in biomedical research, there is a rapidly growing appreciation that proteomics, the study of covalent modification to proteins, and transcriptional regulation will likely dominate the research headlines in the next decade. Protein methylation plays a central role in both of these fields, as several different residues (Arg, Lys, Gln) are methylated in cells and methylation plays a central role in the "histone code" that regulates chromatin structure and impacts transcription. In some cases, a single lysine can be mono-, di-, or trimethylated, with different functional consequences for each of the three forms. This review describes structural aspects of methylation of histone lysine residues by two enzyme families with entirely different structural scaffolding (the SET proteins and Dot1p) and methylation of protein arginine residues by PRMTs.
    Materialart: Digitale Medien
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  • 82
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 34 (2005), S. 153-171 
    ISSN: 1056-8700
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Physik
    Notizen: Potassium (K+) channels are tetrameric membrane-spanning proteins that provide a selective pore for the conductance of K+ across the cell membranes. These channels are most remarkable in their ability to discriminate K+ from Na+ by more than a thousandfold and conduct at a throughput rate near diffusion limit. The recent progress in the structural characterization of K+ channel provides us with a unique opportunity to understand their function at the atomic level. With their ability to go beyond static structures, molecular dynamics simulations based on atomic models can play an important role in shaping our view of how ion channels carry out their function. The purpose of this review is to summarize the most important findings from experiments and computations and to highlight a number of fundamental mechanistic questions about ion conduction and selectivity that will require further work.
    Materialart: Digitale Medien
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  • 83
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 34 (2005), S. 91-118 
    ISSN: 1056-8700
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Physik
    Notizen: Proteins have become accessible targets for chemical synthesis. The basic strategy is to use native chemical ligation, Staudinger ligation, or other orthogonal chemical reactions to couple synthetic peptides. The ligation reactions are compatible with a variety of solvents and proceed in solution or on a solid support. Chemical synthesis enables a level of control on protein composition that greatly exceeds that attainable with ribosome-mediated biosynthesis. Accordingly, the chemical synthesis of proteins is providing previously unattainable insight into the structure and function of proteins.
    Materialart: Digitale Medien
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  • 84
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 34 (2005), S. 71-90 
    ISSN: 1056-8700
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Physik
    Notizen: Despite the central importance of peripheral membrane proteins to cellular signaling and metabolic pathways, the structures of protein-membrane interfaces remain largely inaccessible to high-resolution structural methods. In recent years a number of laboratories have contributed to the development of an electron paramagnetic resonance (EPR) power saturation approach that utilizes site-directed spin labeling to determine the key geometric parameters of membrane-docked proteins, including their penetration depths and angular orientations relative to the membrane surface. Representative applications to Ca2+-activated, membrane-docking C2 domains are described.
    Materialart: Digitale Medien
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  • 85
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 34 (2005), S. 119-151 
    ISSN: 1056-8700
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Physik
    Notizen: Research in the past decade has revealed that many cytosolic proteins are recruited to different cellular membranes to form protein-protein and lipid-protein interactions during cell signaling and membrane trafficking. Membrane recruitment of these peripheral proteins is mediated by a growing number of modular membrane-targeting domains, including C1, C2, PH, FYVE, PX, ENTH, ANTH, BAR, FERM, and tubby domains, that recognize specific lipid molecules in the membranes. Structural studies of these membrane-targeting domains demonstrate how they specifically recognize their cognate lipid ligands. However, the mechanisms by which these domains and their host proteins are recruited to and interact with various cell membranes are only beginning to unravel with recent computational studies, in vitro membrane binding studies using model membranes, and cellular translocation studies using fluorescent protein-tagged proteins. This review summarizes the recent progress in our understanding of how the kinetics and energetics of membrane-protein interactions are regulated during the cellular membrane targeting and activation of peripheral proteins.
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  • 86
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 34 (2005), S. 173-199 
    ISSN: 1056-8700
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Physik
    Notizen: Water plays a central role in the structures and properties of biomoleculesĐ??proteins, nucleic acids, and membranesĐ??and in their interactions with ligands and drugs. Over the past half century, our understanding of water has been advanced significantly owing to theoretical and computational modeling. However, like the blind men and the elephant, different models describe different aspects of water's behavior. The trend in water modeling has been toward finer-scale properties and increasing structural detail, at increasing computational expense. Recently, our labs and others have moved in the opposite direction, toward simpler physical models, focusing on more global propertiesĐ??water's thermodynamics, phase diagram, and solvation properties, for exampleĐ??and toward less computational expense. Simplified models can guide a better understanding of water in ways that complement what we learn from more complex models. One ultimate goal is more tractable models for computer simulations of biomolecules. This review gives a perspective from simple models on how the physical properties of waterĐ??as a pure liquid and as a solventĐ??derive from the geometric and hydrogen bonding properties of water.
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  • 87
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 34 (2005), S. 379-398 
    ISSN: 1056-8700
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Physik
    Notizen: Structural data on protein-DNA complexes provide clues for understanding the mechanism of protein-DNA recognition. Although the structures of a large number of protein-DNA complexes are known, the mechanisms underlying their specific binding are still only poorly understood. Analysis of these structures has shown that there is no simple one-to-one correspondence between bases and amino acids within protein-DNA complexes; nevertheless, the observed patterns of interaction carry important information on the mechanisms of protein-DNA recognition. In this review, we show how the patterns of interaction, either observed in known structures or derived from computer simulations, confer recognition specificity, and how they can be used to examine the relationship between structure and specificity and to predict target DNA sequences used by regulatory proteins.
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  • 88
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 34 (2005), S. 319-349 
    ISSN: 1056-8700
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Physik
    Notizen: Progress in experimental and theoretical biology is likely to provide us with the opportunity to assemble detailed predictive models of mammalian cells. Using a functional format to describe the organization of mammalian cells, we describe current approaches for developing qualitative and quantitative models using data from a variety of experimental sources. Recent developments and applications of graph theory to biological networks are reviewed. The use of these qualitative models to identify the topology of regulatory motifs and functional modules is discussed. Cellular homeostasis and plasticity are interpreted within the framework of balance between regulatory motifs and interactions between modules. From this analysis we identify the need for detailed quantitative models on the basis of the representation of the chemistry underlying the cellular process. The use of deterministic, stochastic, and hybrid models to represent cellular processes is reviewed, and an initial integrated approach for the development of large-scale predictive models of a mammalian cell is presented.
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  • 89
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 21 (2005), S. 319-346 
    ISSN: 1081-0706
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Bacteria communicate with one another using chemical signal molecules. As in higher organisms, the information supplied by these molecules is critical for synchronizing the activities of large groups of cells. In bacteria, chemical communication involves producing, releasing, detecting, and responding to small hormone-like molecules termed autoinducers . This process, termed quorum sensing, allows bacteria to monitor the environment for other bacteria and to alter behavior on a population-wide scale in response to changes in the number and/or species present in a community. Most quorum-sensing-controlled processes are unproductive when undertaken by an individual bacterium acting alone but become beneficial when carried out simultaneously by a large number of cells. Thus, quorum sensing confuses the distinction between prokaryotes and eukaryotes because it enables bacteria to act as multicellular organisms. This review focuses on the architectures of bacterial chemical communication networks; how chemical information is integrated, processed, and transduced to control gene expression; how intra- and interspecies cell-cell communication is accomplished; and the intriguing possibility of prokaryote-eukaryote cross-communication.
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  • 90
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 21 (2005), S. 177-201 
    ISSN: 1081-0706
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Brassinosteroids (BRs), the polyhydroxylated steroid hormones of plants, regulate the growth and differentiation of plants throughout their life cycle. Over the past several years, genetic and biochemical approaches have yielded great progress in understanding BR signaling. Unlike their animal counterparts, BRs are perceived at the plasma membrane by direct binding to the extracellular domain of the BRI1 receptor S/T kinase. BR perception initiates a signaling cascade, acting through a GSK3 kinase, BIN2, and the BSU1 phosphatase, which in turn modulates the phosphorylation state and stability of the nuclear transcription factors BES1 and BZR1. Microarray technology has been used extensively to provide a global view of BR genomic effects, as well as a specific set of target genes for BES1 and BZR1. These gene products thus provide a framework for how BRs regulate the growth of plants.
    Materialart: Digitale Medien
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  • 91
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 21 (2005), S. 381-410 
    ISSN: 1081-0706
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: ʼ̛?‚ heterodimeric integrins mediate dynamic adhesive cell-cell and cell-extracellular matrix (ECM) interactions in metazoa that are critical in growth and development, hemostasis, and host defense. A central feature of these receptors is their capacity to change rapidly and reversibly their adhesive functions by modulating their ligand-binding affinity. This is normally achieved through interactions of the short cytoplasmic integrin tails with intracellular proteins, which trigger restructuring of the ligand-binding site through long-range conformational changes in the ectodomain. Ligand binding in turn elicits conformational changes that are transmitted back to the cell to regulate diverse responses. The publication of the integrin ʼ̛V?‚3 crystal structure has provided the context for interpreting decades-old biochemical studies. Newer NMR, crystallographic, and EM data, reviewed here, are providing a better picture of the dynamic integrin structure and the allosteric changes that guide its diverse functions.
    Materialart: Digitale Medien
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  • 92
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 21 (2005), S. 105-131 
    ISSN: 1081-0706
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: This review surveys what is known about the structure and function of the subnuclear domains called Cajal bodies (CBs). The major focus is on CBs in mammalian cells but we provide an overview of homologous CB structures in other organisms. We discuss the protein and RNA components of CBs, including factors recently found to associate in a cell cycle-dependent fashion or under specific metabolic or stress conditions. We also consider the dynamic properties of both CBs and their molecular components, based largely on recent data obtained thanks to the advent of improved in vivo detection and imaging methods. We discuss how these data contribute to an understanding of CB functions and highlight major questions that remain to be answered. Finally, we consider the interesting links that have emerged between CBs and alterations in nuclear structure apparent in a range of human pathologies, including cancer and inherited neurodegenerative diseases. We speculate on the relationship between CB function and molecular disease.
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  • 93
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 21 (2005), S. 581-603 
    ISSN: 1081-0706
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Over the past decades, intravital microscopy (IVM), the imaging of cells in living organisms, has become a valuable tool for studying the molecular determinants of lymphocyte trafficking. Recent advances in microscopy now make it possible to image cell migration and cell-cell interactions in vivo deep within intact tissues. Here, we summarize the principal techniques that are currently used in IVM, discuss options and tools for fluorescence-based visualization of lymphocytes in microvessels and tissues, and describe IVM models used to explore lymphoid and non-lymphoid organs. The latter will be introduced according to the physiologic itinerary of developing and differentiating T and B lymphocytes as they traffic through the body, beginning with their development in bone marrow and thymus and continuing with their migration to secondary lymphoid organs and peripheral tissues.
    Materialart: Digitale Medien
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  • 94
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 21 (2005), S. 223-245 
    ISSN: 1081-0706
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: In eukaryotes, the entwined pathways of RNA transport and local translational regulation are key determinants in the spatio-temporal articulation of gene expression. One of the main advantages of this mechanism over transcriptional control in the nucleus lies in the fact that it endows local sites with independent decision-making authority, a consideration that is of particular relevance in cells with complex cellular architecture such as neurons. Localized RNAs typically contain codes, expressed within cis-acting elements, that specify subcellular targeting. Such codes are recognized by trans-acting factors, adaptors that mediate translocation along cytoskeletal elements by molecular motors. Most transported mRNAs are assumed translationally dormant while en route. In some cell types, especially in neurons, it is considered crucial that translation remains repressed after arrival at the destination site (e.g., a postsynaptic microdomain) until an appropriate activation signal is received. Several candidate mechanisms have been suggested to participate in the local implementation of translational repression and activation, and such mechanisms may target translation at the level of initiation and/or elongation. Recent data indicate that untranslated RNAs may play important roles in the local control of translation.
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  • 95
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 21 (2005), S. 297-318 
    ISSN: 1081-0706
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: RNA silencing refers to a broad range of phenomena sharing the common feature that large, double-stranded RNAs or stem-loop precursors are processed to ca. 21Đ??26 nucleotide small RNAs, which then guide the cleavage of cognate RNAs, block productive translation of these RNAs, or induce methylation of specific target DNAs. Although the core mechanisms are evolutionarily conserved, epigenetic maintenance of silencing by amplification of small RNAs and the elaboration of mobile, RNA-based silencing signals occur predominantly in plants. Plant RNA silencing systems are organized into a network with shared components and overlapping functions. MicroRNAs, and probably trans-acting small RNAs, help regulate development at the posttranscriptional level. Small interfering RNAs associated with transgene- and virus-induced silencing function primarily in defending against foreign nucleic acids. Another system, which is concerned with RNA-directed methylation of DNA repeats, seems to have roles in epigenetic silencing of certain transposable elements and genes under their control.
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  • 96
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Materials Research 35 (2005), S. 315-350 
    ISSN: 1531-7331
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Maschinenbau
    Notizen: There is a pressing need for cleaner fuels (free or aromatics and of minimal sulfur content) or ones that convert chemical energy directly to electricity, silently and without production of noxious oxides and particulates; chemical, petrochemical and pharmaceutical processes that may be conducted in a one-step, solvent-free manner and that use air as the preferred oxidant; and industrial processes that minimize consumption of energy, production of waste, or the use of corrosive, explosive, volatile, and nonbiodegradable materials. All these needs and other desiderata, such as the in situ production and containment of aggressive and hazardous reagents, and the avoidance of use of ecologically harmful elements, may be achieved by designing the appropriate heterogeneous inorganic catalyst, which ideally should be cheap, readily preparable and fully characterizable, preferably under in situ reaction conditions. A range of nanoporous and nanoparticle catalysts that meet most of the stringent demands of sustainable development and responsible (clean) technology is described. Specific examples that are highlighted include the production of adipic acid (precursor of polyamides and urethanes) without the use of concentrated nitric acid nor the production of greenhouse gases such as nitrous oxide; the production of caprolactam (precursor of nylon) without the use of oleum and hydroxylamine sulfate; and the terminal oxyfunctionalization of linear alkanes in air. The topic of biocatalysis and sustainable development is also briefly discussed for the epoxidation of terpenes and fatty acid methyl esters; for the generation of polymers, polylactides, and polyesters; and for the production of 1,3-propanediol from corn.
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  • 97
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Materials Research 35 (2005), S. 571-615 
    ISSN: 1531-7331
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Maschinenbau
    Notizen: The review highlights the state-of-the-art research regarding the application of modern in situ spectroscopic, microscopic, and electrochemical techniques to improve the understanding of the interaction of organic molecules with metal surfaces. We also consider the chemical and electrochemical processes that lead to a de-adhesion of polymers from metal surfaces. Spectroscopic techniques such as surface-enhanced infrared or Raman spectroscopy provide molecular understanding of organic molecules and water at buried metal surfaces. This information is complementary to adhesion studies by means of atomic force microscopy and de-adhesion studies of polymer layers from metals by means of a scanning Kelvin probe. Adhesion and de-adhesion mechanisms are discussed, especially those involving humid and corrosive environments, which are the predominant and most important for metal/polymer composites in engineering applications.
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  • 98
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Materials Research 35 (2005), S. 239-314 
    ISSN: 1531-7331
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Maschinenbau
    Notizen: Chemical analysis at high spatial resolution is the domain of analytical transmission electron microscopy. Owing to rapid instrumental developments during the past decade, electron energy-loss spectroscopy offers now a spatial resolution close to 0.1 nm and an energy resolution close to 0.1 eV. This development has been accompanied by the introduction of numerous new techniques and methods for data acquisition and analysis, which are outlined in the present article. Recent results for a wide range of material systems are addressed. These comprise first-principles calculations, which have contributed to enormous progress in the calculation of near-edge fine structures, and fingerprinting methods, which are still important for the interpretation of experimental data.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 99
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Ecology, Evolution, and Systematics 36 (2005), S. 169-189 
    ISSN: 1543-592X
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie
    Notizen: Plant secondary metabolites (PSMs) significantly impact the nutritional ecology of terrestrial vertebrate herbivores. Herbivores have a wide range of mechanisms (herbivore offenses) to mitigate the negative effects of PSMs. We discuss several behavioral and physiological offenses used by terrestrial vertebrates. Several newly recognized herbivore offenses such as regulated absorption and regulation of toxin intake are presented. We give a detailed description of the biotransformation system with respect to PSMs. We also summarize recent findings of plantĐ??animal interactions for lizards, birds, and mammals. Finally, we discuss some new tools that can be applied to long-standing questions of plantĐ??vertebrate interactions.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 100
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Fluid Mechanics 37 (2005), S. 357-392 
    ISSN: 0066-4189
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Maschinenbau , Physik
    Notizen: The objective of this review is to critically assess the different approaches developed in recent years to understand the dynamics of open flows such as mixing layers, jets, wakes, separation bubbles, boundary layers, and so on. These complex flows develop in extended domains in which fluid particles are continuously advected downstream. They behave either as noise amplifiers or as oscillators, both of which exhibit strong nonlinearities ( Huerre & Monkewitz 1990 ). The local approach is inherently weakly nonparallel and it assumes that the basic flow varies on a long length scale compared to the wavelength of the instability waves. The dynamics of the flow is then considered as a superposition of linear or nonlinear instability waves that, at leading order, behave at each streamwise station as if the flow were homogeneous in the streamwise direction. In the fully global context, the basic flow and the instabilities do not have to be characterized by widely separated length scales, and the dynamics is then viewed as the result of the interactions between Global modes living in the entire physical domain with the streamwise direction as an eigendirection. This second approach is more and more resorted to as a result of increased computational capability. The earlier review of Huerre & Monkewitz (1990) emphasized how local linear theory can account for the noise amplifier behavior as well as for the onset of a Global mode. The present survey first adopts the opposite point of view by demonstrating how fully global theory accounts for the noise amplifier behavior of open flows. From such a perspective, there is strong emphasis on the very peculiar nonorthogonality of linear Global modes, which in turn allows a novel interpretation of recent numerical simulations and experimental observations. The nonorthogonality of linear Global modes also imposes severe constraints on the extension of linear global theory to the fully nonlinear re??gime. When the flow is weakly nonparallel, this limitation is so severe that the linear Global mode theory is of little help. It is then much more appropriate to develop a fully nonlinear formulation involving the presence of a front separating the base state region from the bifurcated state region.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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