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  • 1
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    Neutralizing Polyclonal IgG Present during Acute Infection Prevents Rapid Disease Onset in Simian-Human Immunodeficiency Virus SHIVSF162P3-Infected Infant Rhesus Macaques [Pathogenesis and Immunity] (2013)
    The American Society for Microbiology (ASM)
    Details
    Publication Date: 2013-09-07
    Description: Simian-human immunodeficiency virus (SHIV) models for human immunodeficiency virus (HIV) infection have been widely used in passive studies with HIV neutralizing antibodies (NAbs) to test for protection against infection. However, because SHIV-infected adult macaques often rapidly control plasma viremia and any resulting pathogenesis is minor, the model has been unsuitable for studying the impact of antibodies on pathogenesis in infected animals. We found that SHIV SF162P3 infection in 1-month-old rhesus macaques not only results in high persistent plasma viremia but also leads to very rapid disease progression within 12 to 16 weeks. In this model, passive transfer of high doses of neutralizing IgG (SHIVIG) prevents infection. Here, we show that at lower doses, SHIVIG reduces both plasma and peripheral blood mononuclear cell (PBMC)-associated viremia and mitigates pathogenesis in infected animals. Moreover, production of endogenous NAbs correlated with lower set-point viremia and 100% survival of infected animals. New SHIV models are needed to investigate whether passively transferred antibodies or antibodies elicited by vaccination that fall short of providing sterilizing immunity impact disease progression or influence immune responses. The 1-month-old rhesus macaque SHIV model of infection provides a new tool to investigate the effects of antibodies on viral replication and clearance, mechanisms of B cell maintenance, and the induction of adaptive immunity in disease progression.
    Print ISSN: 0022-538X
    Electronic ISSN: 1098-5514
    Topics: Medicine
    Published by The American Society for Microbiology (ASM)
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  • 2
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    Excitability governs neural development in a hippocampal region-specific manner [RESEARCH ARTICLES] (2015)
    The Company of Biologists
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    Publication Date: 2015-11-18
    Description: Erin M. Johnson-Venkatesh, Mudassar N. Khan, Geoffrey G. Murphy, Michael A. Sutton, and Hisashi Umemori Neuronal activity, including intrinsic neuronal excitability and synaptic transmission, is an essential regulator of brain development. However, how the intrinsic neuronal excitability of distinct neurons affects their integration into developing circuits remains poorly understood. To investigate this problem, we created several transgenic mouse lines in which intrinsic excitability is suppressed, and the neurons are effectively silenced, in different excitatory neuronal populations of the hippocampus. Here we show that CA1, CA3 and dentate gyrus neurons each have unique responses to suppressed intrinsic excitability during circuit development. Silenced CA1 pyramidal neurons show altered spine development and synaptic transmission after postnatal day 15. By contrast, silenced CA3 pyramidal neurons seem to develop normally. Silenced dentate granule cells develop with input-specific decreases in spine density starting at postnatal day 11; however, a compensatory enhancement of neurotransmitter release onto these neurons maintains normal levels of synaptic activity. The synaptic changes in CA1 and dentate granule neurons are not observed when synaptic transmission, rather than intrinsic excitability, is blocked in these neurons. Thus, our results demonstrate a crucial role for intrinsic neuronal excitability in establishing hippocampal connectivity and reveal that neuronal development in each hippocampal region is distinctly regulated by excitability.
    Print ISSN: 0950-1991
    Electronic ISSN: 1477-9129
    Topics: Biology
    Published by The Company of Biologists
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  • 3
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    Diagnosing the accretion flow in ultraluminous X-ray sources using soft X-ray atomic features (2015)
    Oxford University Press
    Details
    Publication Date: 2015-10-19
    Description: The lack of unambiguous detections of atomic features in the X-ray spectra of ultraluminous X-ray sources (ULXs) has proven a hindrance in diagnosing the nature of the accretion flow. The possible association of spectral residuals at soft energies with atomic features seen in absorption and/or emission and potentially broadened by velocity dispersion could therefore hold the key to understanding much about these enigmatic sources. Here we show for the first time that such residuals are seen in several sources and appear extremely similar in shape, implying a common origin. Via simple arguments we assert that emission from extreme colliding winds, absorption in a shell of material associated with the ULX nebula and thermal plasma emission associated with star formation are all highly unlikely to provide an origin. Whilst CCD spectra lack the energy resolution necessary to directly determine the nature of the features (i.e. formed of a complex of narrow lines or intrinsically broad lines), studying the evolution of the residuals with underlying spectral shape allows for an important, indirect test for their origin. The ULX NGC 1313 X-1 provides the best opportunity to perform such a test due to the dynamic range in spectral hardness provided by archival observations. We show through highly simplified spectral modelling that the strength of the features (in either absorption or emission) appears to anticorrelate with spectral hardness, which would rule out an origin via reflection of a primary continuum and instead supports a picture of atomic transitions in a wind or nearby material associated with such an outflow.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
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  • 4
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    Voluntary wheel running attenuates lipopolysaccharide-induced liver inflammation in mice (2016)
    The American Physiological Society (APS)
    Details
    Publication Date: 2016-05-17
    Description: Sepsis induces an acute inflammatory response in the liver, which can lead to organ failure and death. Given the anti-inflammatory effects of exercise, we hypothesized that habitual physical activity could protect against acute sepsis-induced liver inflammation via mechanisms, including heat shock protein (HSP) 70/72. Male C57BL/6J mice ( n = 80, ~8 wk of age) engaged in physical activity via voluntary wheel running (VWR) or cage control (SED) for 10 wk. To induce sepsis, we injected (2 mg/kg ip) LPS or sterile saline (SAL), and liver was harvested 6 or 12 h later. VWR attenuated increases in body and epididymal adipose tissue mass, improved glucose tolerance, and increased liver protein content of PEPCK ( P 〈 0.05). VWR attenuated increases in LPS-induced IL-6 signaling and mRNA expression of other inflammatory markers (TNF-α, chemokine C-C motif ligand 2, inducible nitric oxide synthase, IL-10, IL-1β) in the liver; however, this was not reflected at the whole body level, as systemic markers of inflammation were similar between SED and VWR. Insulin tolerance was greater in VWR compared with SED at 6 but not 12 h after LPS. The protective effect of VWR occurred in parallel with increases in the liver protein content of HSP70/72, a molecular chaperone that can protect against inflammatory challenges. This study provides novel evidence that physical activity protects against the inflammatory cascade induced by LPS in the liver and that these effects may be mediated via HSP70/72.
    Print ISSN: 0363-6119
    Electronic ISSN: 1522-1490
    Topics: Medicine
    Published by The American Physiological Society (APS)
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  • 5
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    The bonobo genome compared with the chimpanzee and human genomes (2012)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2012-06-23
    Description: Two African apes are the closest living relatives of humans: the chimpanzee (Pan troglodytes) and the bonobo (Pan paniscus). Although they are similar in many respects, bonobos and chimpanzees differ strikingly in key social and sexual behaviours, and for some of these traits they show more similarity with humans than with each other. Here we report the sequencing and assembly of the bonobo genome to study its evolutionary relationship with the chimpanzee and human genomes. We find that more than three per cent of the human genome is more closely related to either the bonobo or the chimpanzee genome than these are to each other. These regions allow various aspects of the ancestry of the two ape species to be reconstructed. In addition, many of the regions that overlap genes may eventually help us understand the genetic basis of phenotypes that humans share with one of the two apes to the exclusion of the other.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3498939/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3498939/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Prufer, Kay -- Munch, Kasper -- Hellmann, Ines -- Akagi, Keiko -- Miller, Jason R -- Walenz, Brian -- Koren, Sergey -- Sutton, Granger -- Kodira, Chinnappa -- Winer, Roger -- Knight, James R -- Mullikin, James C -- Meader, Stephen J -- Ponting, Chris P -- Lunter, Gerton -- Higashino, Saneyuki -- Hobolth, Asger -- Dutheil, Julien -- Karakoc, Emre -- Alkan, Can -- Sajjadian, Saba -- Catacchio, Claudia Rita -- Ventura, Mario -- Marques-Bonet, Tomas -- Eichler, Evan E -- Andre, Claudine -- Atencia, Rebeca -- Mugisha, Lawrence -- Junhold, Jorg -- Patterson, Nick -- Siebauer, Michael -- Good, Jeffrey M -- Fischer, Anne -- Ptak, Susan E -- Lachmann, Michael -- Symer, David E -- Mailund, Thomas -- Schierup, Mikkel H -- Andres, Aida M -- Kelso, Janet -- Paabo, Svante -- 090532/Wellcome Trust/United Kingdom -- 090532/Z/09/Z/Wellcome Trust/United Kingdom -- 2R01GM077117-04A1/GM/NIGMS NIH HHS/ -- HG002385/HG/NHGRI NIH HHS/ -- MC_U137761446/Medical Research Council/United Kingdom -- R01 GM077117/GM/NIGMS NIH HHS/ -- R01 HG002385/HG/NHGRI NIH HHS/ -- Howard Hughes Medical Institute/ -- Intramural NIH HHS/ -- England -- Nature. 2012 Jun 28;486(7404):527-31. doi: 10.1038/nature11128.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Max Planck Institute for Evolutionary Anthropology, D-04103 Leipzig, Germany. pruefer@eva.mpg.de〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22722832" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; DNA Transposable Elements/genetics ; *Evolution, Molecular ; Gene Duplication/genetics ; Genetic Variation/*genetics ; Genome/*genetics ; Genome, Human/*genetics ; Genotype ; Humans ; Molecular Sequence Data ; Pan paniscus/*genetics ; Pan troglodytes/*genetics ; Phenotype ; Phylogeny ; Species Specificity
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 6
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    The adenosine triphosphate test in the diagnosis of unexplained syncope: a test looking for a home (2014)
    Oxford University Press
    In: Europace
    Details
    Publication Date: 2014-11-24
    Print ISSN: 1099-5129
    Electronic ISSN: 1532-2092
    Topics: Medicine
    Published by Oxford University Press
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  • 7
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    A micro-patterned silicon chip as sample holder for macromolecular crystallography experiments with minimal background scattering (2015)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2015-05-30
    Description: At low emittance synchrotron sources it has become possible to perform structure determinations from the measurement of multiple microcrystals which were previously considered too small for diffraction experiments. Conventional mounting techniques do not fulfill the requirements of these new experiments. They significantly contribute to background scattering and it is difficult to locate the crystals, making them incompatible with automated serial crystallography. We have developed a micro-fabricated sample holder from single crystalline silicon with micropores, which carries up to thousands of crystals and significantly reduces the background scattering level. For loading, the suspended microcrystals are pipetted onto the chip and excess mother liquor is subsequently soaked off through the micropores. Crystals larger than the pore size are retained and arrange themselves according to the micropore pattern. Using our chip we were able to collect 1.5 Å high resolution diffraction data from protein microcrystals with sizes of 4 micrometers and smaller. Scientific Reports 5 doi: 10.1038/srep10451
    Electronic ISSN: 2045-2322
    Topics: Natural Sciences in General
    Published by Nature Publishing Group (NPG)
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  • 8
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    Monitoring of childhood ALL using BCR-ABL1 genomic breakpoints identifies a subgroup with CML-like biology (2017)
    American Society of Hematology (ASH)
    In: Blood
    Details
    Publication Date: 2017-05-19
    Description: We used the genomic breakpoint between BCR and ABL1 genes for the DNA-based monitoring of minimal residual disease (MRD) in 48 patients with childhood acute lymphoblastic leukemia (ALL). Comparing the results with standard MRD monitoring based on immunoglobulin/T-cell receptor (Ig/TCR) gene rearrangements and with quantification of IKZF1 deletion, we observed very good correlation for the methods in a majority of patients; however, 〉20% of children (25% [8/32] with minor and 12.5% [1/8] with major- BCR-ABL1 variants in the consecutive cohorts) had significantly (〉1 log) higher levels of BCR-ABL1 fusion than Ig/TCR rearrangements and/or IKZF1 deletion. We performed cell sorting of the diagnostic material and assessed the frequency of BCR-ABL1 -positive cells in various hematopoietic subpopulations; 12% to 83% of non–ALL B lymphocytes, T cells, and/or myeloid cells harbored the BCR-ABL1 fusion in patients with discrepant MRD results. The multilineage involvement of the BCR-ABL1 -positive clone demonstrates that in some patients diagnosed with BCR-ABL1 -positive ALL, a multipotent hematopoietic progenitor is affected by the BCR-ABL1 fusion. These patients have BCR-ABL1 -positive clonal hematopoiesis resembling a chronic myeloid leukemia (CML)–like disease manifesting in "lymphoid blast crisis." The biological heterogeneity of BCR-ABL1 -positive ALL may impact the patient outcomes and optimal treatment (early stem cell transplantation vs long-term administration of tyrosine-kinase inhibitors) as well as on MRD testing. Therefore, we recommend further investigations on CML-like BCR-ABL1 -positive ALL.
    Keywords: Pediatric Hematology, Lymphoid Neoplasia, Clinical Trials and Observations
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
    Published by American Society of Hematology (ASH)
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  • 9
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    Detection and learning of floral electric fields by bumblebees (2013)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2013-02-23
    Description: Insects use several senses to forage, detecting floral cues such as color, shape, pattern, and volatiles. We report a formerly unappreciated sensory modality in bumblebees (Bombus terrestris), detection of floral electric fields. These fields act as floral cues, which are affected by the visit of naturally charged bees. Like visual cues, floral electric fields exhibit variations in pattern and structure, which can be discriminated by bumblebees. We also show that such electric field information contributes to the complex array of floral cues that together improve a pollinator's memory of floral rewards. Because floral electric fields can change within seconds, this sensory modality may facilitate rapid and dynamic communication between flowers and their pollinators.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Clarke, Dominic -- Whitney, Heather -- Sutton, Gregory -- Robert, Daniel -- New York, N.Y. -- Science. 2013 Apr 5;340(6128):66-9. doi: 10.1126/science.1230883. Epub 2013 Feb 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of Biological Sciences, University of Bristol, Woodland Road, Bristol BS8 1UG, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23429701" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bees/*physiology ; *Cues ; *Electromagnetic Fields ; Flowers/anatomy & histology/*physiology ; *Pollination
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 10
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    Interacting gears synchronize propulsive leg movements in a jumping insect (2013)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2013-09-14
    Description: Gears are found rarely in animals and have never been reported to intermesh and rotate functionally like mechanical gears. We now demonstrate functional gears in the ballistic jumping movements of the flightless planthopper insect Issus. The nymphs, but not adults, have a row of cuticular gear (cog) teeth around the curved medial surfaces of their two hindleg trochantera. The gear teeth on one trochanter engaged with and sequentially moved past those on the other trochanter during the preparatory cocking and the propulsive phases of jumping. Close registration between the gears ensured that both hindlegs moved at the same angular velocities to propel the body without yaw rotation. At the final molt to adulthood, this synchronization mechanism is jettisoned.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Burrows, Malcolm -- Sutton, Gregory -- New York, N.Y. -- Science. 2013 Sep 13;341(6151):1254-6. doi: 10.1126/science.1240284.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Zoology, University of Cambridge, Cambridge, UK. mb135@hermes.cam.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24031019" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Extremities/anatomy & histology/*physiology ; Hemiptera/anatomy & histology/*physiology ; *Locomotion
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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