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  • 1
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2014
    In:  Translational Psychiatry Vol. 4, No. 12 ( 2014-12-16), p. e489-e489
    In: Translational Psychiatry, Springer Science and Business Media LLC, Vol. 4, No. 12 ( 2014-12-16), p. e489-e489
    Abstract: Alzheimer’s disease (AD) is a progressive neurodegenerative brain disorder and the most frequent cause of dementia. To date, there are only a few approved drugs for AD, which show little or no effect on disease progression. Impaired intracellular calcium homeostasis is believed to occur early in the cascade of events leading to AD. Here, we examined the possibility of normalizing the disrupted calcium homeostasis in the endoplasmic reticulum (ER) store as an innovative approach for AD drug discovery. High-throughput screening of a small-molecule compound library led to the identification of tetrahydrocarbazoles, a novel multifactorial class of compounds that can normalize the impaired ER calcium homeostasis. We found that the tetrahydrocarbazole lead structure, first, dampens the enhanced calcium release from ER in HEK293 cells expressing familial Alzheimer’s disease (FAD)-linked presenilin 1 mutations. Second, the lead structure also improves mitochondrial function, measured by increased mitochondrial membrane potential. Third, the same lead structure also attenuates the production of amyloid-beta (Aβ) peptides by decreasing the cleavage of amyloid precursor protein (APP) by β-secretase, without notably affecting α- and γ-secretase cleavage activities. Considering the beneficial effects of tetrahydrocarbazoles addressing three key pathological aspects of AD, these compounds hold promise for the development of potentially effective AD drug candidates.
    Type of Medium: Online Resource
    ISSN: 2158-3188
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2014
    detail.hit.zdb_id: 2609311-X
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  • 2
    In: Atmospheric Chemistry and Physics, Copernicus GmbH, Vol. 13, No. 11 ( 2013-06-14), p. 5791-5811
    Abstract: Abstract. Water vapour (H2O) is one of the operationally retrieved key species of the Michelson Interferometer for Passive Atmospheric Sounding (MIPAS) instrument aboard the Environmental Satellite (ENVISAT) which was launched into its sun-synchronous orbit on 1 March 2002 and operated until April 2012. Within the MIPAS validation activities, independent observations from balloons, aircraft, satellites, and ground-based stations have been compared to European Space Agency (ESA) version 4.61 operational H2O data comprising the time period from July 2002 until March 2004 where MIPAS measured with full spectral resolution. No significant bias in the MIPAS H2O data is seen in the lower stratosphere (above the hygropause) between about 15 and 30 km. Differences of H2O quantities observed by MIPAS and the validation instruments are mostly well within the combined total errors in this altitude region. In the upper stratosphere (above about 30 km), a tendency towards a small positive bias (up to about 10%) is present in the MIPAS data when compared to its balloon-borne counterpart MIPAS-B, to the satellite instruments HALOE (Halogen Occultation Experiment) and ACE-FTS (Atmospheric Chemistry Experiment, Fourier Transform Spectrometer), and to the millimeter-wave airborne sensor AMSOS (Airborne Microwave Stratospheric Observing System). In the mesosphere the situation is unclear due to the occurrence of different biases when comparing HALOE and ACE-FTS data. Pronounced deviations between MIPAS and the correlative instruments occur in the lowermost stratosphere and upper troposphere, a region where retrievals of H2O are most challenging. Altogether it can be concluded that MIPAS H2O profiles yield valuable information on the vertical distribution of H2O in the stratosphere with an overall accuracy of about 10 to 30% and a precision of typically 5 to 15% – well within the predicted error budget, showing that these global and continuous data are very valuable for scientific studies. However, in the region around the tropopause retrieved MIPAS H2O profiles are less reliable, suffering from a number of obstacles such as retrieval boundary and cloud effects, sharp vertical discontinuities, and frequent horizontal gradients in both temperature and H2O volume mixing ratio (VMR). Some profiles are characterized by retrieval instabilities.
    Type of Medium: Online Resource
    ISSN: 1680-7324
    Language: English
    Publisher: Copernicus GmbH
    Publication Date: 2013
    detail.hit.zdb_id: 2092549-9
    detail.hit.zdb_id: 2069847-1
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  • 3
    In: Equine Veterinary Journal, Wiley, Vol. 25, No. S15 ( 2010-06-10), p. 75-78
    Type of Medium: Online Resource
    ISSN: 0425-1644 , 2042-3306
    Language: English
    Publisher: Wiley
    Publication Date: 2010
    detail.hit.zdb_id: 2205089-9
    SSG: 12
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  • 4
    In: Neuroscience, Elsevier BV, Vol. 167, No. 1 ( 2010-4), p. 143-153
    Type of Medium: Online Resource
    ISSN: 0306-4522
    RVK:
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2010
    detail.hit.zdb_id: 1498423-4
    SSG: 12
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  • 5
    Online Resource
    Online Resource
    Copernicus GmbH ; 2014
    In:  Biogeosciences Vol. 11, No. 18 ( 2014-09-19), p. 5073-5085
    In: Biogeosciences, Copernicus GmbH, Vol. 11, No. 18 ( 2014-09-19), p. 5073-5085
    Abstract: Abstract. Degradation of plant material by animals is an important transformation pathway in the nitrogen (N) cycle. During the involved processes, volatile reduced alkaline nitrogen compounds, mainly ammonia (NH3) and aliphatic amines such as trimethylamine (TMA), are formed. Today, animal husbandry is estimated to constitute a main source of aliphatic amines in the atmosphere with TMA being the main emitted compound. Here, we show how the interaction between faeces and urine in animal production systems provides the primary source for agricultural TMA emissions. Excreted urine contains large quantities of urea and TMA-N-oxide, which are transformed into NH3 and TMA, respectively, via enzymatic processes provided by microbes present in faeces. TMA emissions from areas polluted with urine–faeces mixtures are on average of the order of 10 to 50 nmol m−2s−1. Released amines promote secondary aerosol particle formation in the agricultural emission plume. The atmospheric lifetime of TMA, which was estimated to be of the order of 30 to 1000 s, is determined by the condensation onto aerosol particles.
    Type of Medium: Online Resource
    ISSN: 1726-4189
    Language: English
    Publisher: Copernicus GmbH
    Publication Date: 2014
    detail.hit.zdb_id: 2158181-2
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  • 6
    In: Journal of Marine Systems, Elsevier BV, Vol. 132 ( 2014-04), p. 196-207
    Type of Medium: Online Resource
    ISSN: 0924-7963
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2014
    detail.hit.zdb_id: 1483106-5
    detail.hit.zdb_id: 1041191-4
    SSG: 14
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  • 7
    Online Resource
    Online Resource
    British Institute of Radiology ; 2013
    In:  Dentomaxillofacial Radiology Vol. 42, No. 6 ( 2013-06), p. 20120321-
    In: Dentomaxillofacial Radiology, British Institute of Radiology, Vol. 42, No. 6 ( 2013-06), p. 20120321-
    Type of Medium: Online Resource
    ISSN: 0250-832X , 1476-542X
    Language: English
    Publisher: British Institute of Radiology
    Publication Date: 2013
    detail.hit.zdb_id: 2004893-2
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  • 8
    In: Biogeosciences, Copernicus GmbH, Vol. 10, No. 5 ( 2013-05-16), p. 3297-3311
    Abstract: Abstract. Here we present results of the first comprehensive study of sulphur compounds and methane in the oligotrophic tropical western Pacific Ocean. The concentrations of dimethylsuphide (DMS), dimethylsulphoniopropionate (DMSP), dimethylsulphoxide (DMSO), and methane (CH4), as well as various phytoplankton marker pigments in the surface ocean were measured along a north–south transit from Japan to Australia in October 2009. DMS (0.9 nmol L−1), dissolved DMSP (DMSPd, 1.6 nmol L−1) and particulate DMSP (DMSPp, 2 nmol L−1) concentrations were generally low, while dissolved DMSO (DMSOd, 4.4 nmol L−1) and particulate DMSO (DMSOp, 11.5 nmol L−1) concentrations were comparably enhanced. Positive correlations were found between DMSO and DMSP as well as DMSP and DMSO with chlorophyll a, which suggests a similar source for both compounds. Similar phytoplankton groups were identified as being important for the DMSO and DMSP pool, thus, the same algae taxa might produce both DMSP and DMSO. In contrast, phytoplankton seemed to play only a minor role for the DMS distribution in the western Pacific Ocean. The observed DMSPp : DMSOp ratios were very low and seem to be characteristic of oligotrophic tropical waters representing the extreme endpoint of the global DMSPp : DMSOp ratio vs SST relationship. It is most likely that nutrient limitation and oxidative stress in the tropical western Pacific Ocean triggered enhanced DMSO production leading to an accumulation of DMSO in the sea surface. Positive correlations between DMSPd and CH4, as well as between DMSO (particulate and total) and CH4, were found along the transit. We conclude that DMSP and DMSO and/or their degradation products might serve as potential substrates for CH4 production in the oxic surface layer of the western Pacific Ocean.
    Type of Medium: Online Resource
    ISSN: 1726-4189
    Language: English
    Publisher: Copernicus GmbH
    Publication Date: 2013
    detail.hit.zdb_id: 2158181-2
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  • 9
    In: Biogeosciences, Copernicus GmbH, Vol. 9, No. 6 ( 2012-06-14), p. 2127-2143
    Abstract: Abstract. In this study temporal variations of coccolithophore blooms are investigated using satellite data. Eight years (from 2003 to 2010) of data of SCIAMACHY, a hyper-spectral satellite sensor on-board ENVISAT, were processed by the PhytoDOAS method to monitor the biomass of coccolithophores in three selected regions. These regions are characterized by frequent occurrence of large coccolithophore blooms. The retrieval results, shown as monthly mean time series, were compared to related satellite products, including the total surface phytoplankton, i.e. total chlorophyll a (from GlobColour merged data) and the particulate inorganic carbon (from MODIS-Aqua). The inter-annual variations of the phytoplankton bloom cycles and their maximum monthly mean values have been compared in the three selected regions to the variations of the geophysical parameters: sea-surface temperature (SST), mixed-layer depth (MLD) and surface wind-speed, which are known to affect phytoplankton dynamics. For each region, the anomalies and linear trends of the monitored parameters over the period of this study have been computed. The patterns of total phytoplankton biomass and specific dynamics of coccolithophore chlorophyll a in the selected regions are discussed in relation to other studies. The PhytoDOAS results are consistent with the two other ocean color products and support the reported dependencies of coccolithophore biomass dynamics on the compared geophysical variables. This suggests that PhytoDOAS is a valid method for retrieving coccolithophore biomass and for monitoring its bloom developments in the global oceans. Future applications of time series studies using the PhytoDOAS data set are proposed, also using the new upcoming generations of hyper-spectral satellite sensors with improved spatial resolution.
    Type of Medium: Online Resource
    ISSN: 1726-4189
    Language: English
    Publisher: Copernicus GmbH
    Publication Date: 2012
    detail.hit.zdb_id: 2158181-2
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  • 10
    In: Rapid Communications in Mass Spectrometry, Wiley, Vol. 28, No. 13 ( 2014-07-15), p. 1507-1514
    Abstract: Fatty acids and sterol lipids play crucial roles in several biological processes and several biological facts underline the interconnection between these lipid classes. Therefore, it is of interest to develop a comprehensive method analysing both classes in the form of their most favourable derivatives suitable for quantification and isotopologue analysis. METHODS Lipids were derivatised by a sequential one‐pot procedure using N‐tert ‐butyldimethylsilyl‐ N ‐methyltrifluoroacetamide (M t BSTFA) and N,O ‐bis(trimethylsilyl)trifluoroacetamide (BSTFA). No clean‐up or concentration steps were necessary. The prepared samples were directly available for gas chromatography–electron ionisation mass spectrometric (GC–EI‐MS) analysis on a standard column. For quantification, the SIM mode was used and for isotopologue analysis scheduled scan mode was applied. RESULTS Development of a sequential one‐pot derivatisation for GC–EI‐MS allowing comprehensive analysis of fatty acids and sterols as their most favourable derivatives. Validation carried out using human plasma, comparison with certified NIST plasma. LLOQ of usually 3.3 ng/mL achieved. Isotopologue analysis of 2‐[ 13 C]‐acetate incorporation in HL‐60 cells proving feasibility of method. CONCLUSIONS The presented method successfully combines two consecutive silylation reactions in one pot, enabling the analysis of both fatty acids and sterols in a comprehensive analytical method. The method has great potential for the quantification of lipids as well as the comprehensive study of both biochemical pathways, using [ 13 C]‐flux analysis. Copyright © 2014 John Wiley & Sons, Ltd.
    Type of Medium: Online Resource
    ISSN: 0951-4198 , 1097-0231
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2014
    detail.hit.zdb_id: 2002158-6
    detail.hit.zdb_id: 58731-X
    SSG: 11
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