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  • 1
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    Identification and analysis of atmospheric states and associated cloud properties for Darwin, Australia (2012)
    Wiley
    Details
    Publication Date: 2012-03-21
    Description: An iterative automated classification technique that combines European Centre for Medium-Range Weather Forecasts analysis data and vertically pointing millimeter wavelength cloud radar observations is used to identify commonly occurring atmospheric patterns or states around Darwin, Australia. The technique defines the atmospheric states by large-scale, synoptic variables such that, once defined, these states will be suitable to composite climate model output. Radar observations of clouds are used to test the statistical significance of each state and prompt the automated refinement of the states until each state produces a statistically stable and unique hydrometeor occurrence profile. The technique identifies eight atmospheric states: two monsoon states, two transition season states, and four dry season states. The two monsoon states can be identified as the active monsoon and the break monsoon. Among the dry season states, periods of isolated and suppressed convection can be identified. We use these states as the basis for compositing hydrometeor occurrence, precipitation rate, outgoing longwave radiation, and Madden-Julian Oscillation phase to further understand the meteorology of each state.
    Print ISSN: 0148-0227
    Topics: Geosciences , Physics
    Published by Wiley on behalf of American Geophysical Union (AGU).
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  • 2
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    Coordination of heart and lung co-development by a multipotent cardiopulmonary progenitor (2013)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2013-07-23
    Description: Co-development of the cardiovascular and pulmonary systems is a recent evolutionary adaption to terrestrial life that couples cardiac output with the gas exchange function of the lung. Here we show that the murine pulmonary vasculature develops even in the absence of lung development. We have identified a population of multipotent cardiopulmonary mesoderm progenitors (CPPs) within the posterior pole of the heart that are marked by the expression of Wnt2, Gli1 and Isl1. We show that CPPs arise from cardiac progenitors before lung development. Lineage tracing and clonal analysis demonstrates that CPPs generate the mesoderm lineages within the cardiac inflow tract and lung including cardiomyocytes, pulmonary vascular and airway smooth muscle, proximal vascular endothelium, and pericyte-like cells. CPPs are regulated by hedgehog expression from the foregut endoderm, which is required for connection of the pulmonary vasculature to the heart. Together, these studies identify a novel population of multipotent cardiopulmonary progenitors that coordinates heart and lung co-development that is required for adaptation to terrestrial existence.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3758448/" 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/PMC3758448/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Peng, Tien -- Tian, Ying -- Boogerd, Cornelis J -- Lu, Min Min -- Kadzik, Rachel S -- Stewart, Kathleen M -- Evans, Sylvia M -- Morrisey, Edward E -- HL087825/HL/NHLBI NIH HHS/ -- HL100405/HL/NHLBI NIH HHS/ -- HL110942/HL/NHLBI NIH HHS/ -- HL117649/HL/NHLBI NIH HHS/ -- P30 NS047101/NS/NINDS NIH HHS/ -- R01 HL074066/HL/NHLBI NIH HHS/ -- R01 HL087825/HL/NHLBI NIH HHS/ -- T32 HL07586-23/HL/NHLBI NIH HHS/ -- U01 HL107442/HL/NHLBI NIH HHS/ -- England -- Nature. 2013 Aug 29;500(7464):589-92. doi: 10.1038/nature12358. Epub 2013 Jul 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23873040" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cardiac Output ; Cell Lineage ; Endoderm/metabolism ; Heart/anatomy & histology/*embryology ; Hedgehog Proteins/metabolism ; Kruppel-Like Transcription Factors/metabolism ; LIM-Homeodomain Proteins/metabolism ; Lung/blood supply/*cytology/*embryology ; Mesoderm/cytology ; Mice ; Models, Animal ; Multipotent Stem Cells/*cytology ; Myoblasts, Cardiac/*cytology ; *Organogenesis ; Pericytes/cytology ; Pulmonary Gas Exchange ; Transcription Factors/metabolism ; Wnt Proteins/metabolism
    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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  • 3
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    Islet-1 specifies striatonigral neurons [Neuroscience] (2014)
    National Academy of Sciences
    Details
    Publication Date: 2014-01-08
    Description: Striatal projection neurons comprise two populations of striatonigral and striatopallidal neurons. These two neuronal populations play distinct roles in controlling movement-related functions in the basal ganglia circuits. An important issue is how striatal progenitors are developmentally specified into these two distinct neuronal populations. In the present study, we characterized the...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 4
    Electronic Resource
    Electronic Resource
    Potential antitumor agents. Synthesis, reactivity, and cytotoxicity of .alpha.-methylene carbonyl compounds (1978)
    s.l. : American Chemical Society
    Journal of medicinal chemistry 21 (1978), S. 815-819 
    Details
    ISSN: 1520-4804
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1021/jm00206a020
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    Paper (German National Licenses)
    Fulltext
  • 5
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    Dual role for Islet-1 in promoting striatonigral and repressing striatopallidal genetic programs to specify striatonigral cell identity (2013)
    National Academy of Sciences
    Details
    Publication Date: 2013-12-18
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 6
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    Myofibroblasts revert to an inactive phenotype during regression of liver fibrosis (2012)
    National Academy of Sciences
    Details
    Publication Date: 2012-05-07
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 7
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    Inactivation of myofibroblasts [Cell Biology] (2012)
    National Academy of Sciences
    Details
    Publication Date: 2012-06-13
    Description: Myofibroblasts produce the fibrous scar in hepatic fibrosis. In the carbon tetrachloride (CCl4) model of liver fibrosis, quiescent hepatic stellate cells (HSC) are activated to become myofibroblasts. When the underlying etiological agent is removed, clinical and experimental fibrosis undergoes a remarkable regression with complete disappearance of these myofibroblasts. Although some myofibroblasts apoptose, it is unknown whether other myofibroblasts may revert to an inactive phenotype during regression of fibrosis. We elucidated the fate of HSCs/myofibroblasts during recovery from CCl4- and alcohol-induced liver fibrosis using Cre-LoxP–based genetic labeling of myofibroblasts. Here we demonstrate that half of the myofibroblasts escape apoptosis during regression of liver fibrosis, down-regulate fibrogenic genes, and acquire a phenotype similar to, but distinct from, quiescent HSCs in their ability to more rapidly reactivate into myofibroblasts in response to fibrogenic stimuli and strongly contribute to liver fibrosis. Inactivation of HSCs was associated with up-regulation of the anti-apoptotic genes Hspa1a/b, which participate in the survival of HSCs in culture and in vivo.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 8
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    Dual transcriptional activator and repressor roles of TBX20 regulate adult cardiac structure and function (2012)
    Oxford University Press
    Details
    Publication Date: 2012-04-25
    Description: The ongoing requirement in adult heart for transcription factors with key roles in cardiac development is not well understood. We recently demonstrated that TBX20, a transcriptional regulator required for cardiac development, has key roles in the maintenance of functional and structural phenotypes in adult mouse heart. Conditional ablation of Tbx20 in adult cardiomyocytes leads to a rapid onset and progression of heart failure, with prominent conduction and contractility phenotypes that lead to death. Here we describe a more comprehensive molecular characterization of the functions of TBX20 in adult mouse heart. Coupling genome-wide chromatin immunoprecipitation and transcriptome analyses (RNA-Seq), we identified a subset of genes that change expression in Tbx20 adult cardiomyocyte-specific knockout hearts which are direct downstream targets of TBX20. This analysis revealed a dual role for TBX20 as both a transcriptional activator and a repressor, and that each of these functions regulates genes with very specialized and distinct molecular roles. We also show how TBX20 binds to its targets genome-wide in a context-dependent manner, using various cohorts of co-factors to either promote or repress distinct genetic programs within adult heart. Our integrative approach has uncovered several novel aspects of TBX20 and T-box protein function within adult heart. Sequencing data accession number ( http://www.ncbi.nlm.nih.gov/geo ): GSE30943.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 9
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    Peatland restoration: controls on sediment production and reductions in carbon and pollutant export (2014)
    Wiley
    Details
    Publication Date: 2014-08-27
    Description: ABSTRACT Peatlands are an important store of soil carbon, and play a vital role in global carbon cycling, and when located in close proximity to urban and industrial areas, can also act as sinks of atmospherically deposited heavy metals. Large areas of the UK's blanket peat are significantly degraded and actively eroding which negatively impacts carbon and pollutant storage. The restoration of eroding UK peatlands is a major conservation concern, and over the last decade measures have been taken to try to control erosion and restore large areas of degraded peat. This study utilises a sediment source fingerprinting approach to assess the effect of restoration practices on sediment production, and carbon and pollutant export in the Peak District National Park, southern Pennines (UK). Suspended sediment was collected using time integrated mass flux samplers (TIMS), deployed across three field areas which represent the surface conditions exhibited through an erosion-restoration cycle: (i) intact (ii) actively eroding, and (iii) recently re-vegetated. Anthropogenic pollutants stored near the peat's surface have allowed material mobilised by sheet erosion to be distinguished from sediment eroded from gully walls. Re-vegetation of eroding gully systems is most effective at stabilising interfluve surfaces, switching the locus of sediment production from contaminated surface peat to relatively ‘clean’ gully walls. The stabilisation of eroding surfaces reduces particulate organic carbon (POC) and lead (Pb) fluxes by two orders of magnitude, to levels comparable with those of an intact peatland, thus maintaining this important carbon and pollutant store. The re-vegetation of gully floors also plays a key role in decoupling eroding surfaces from the fluvial system, and further reducing the flux of material. These findings indicate that the restoration practices have been effective over a relatively short timescale, and will help target and refine future restoration initiatives. This article is protected by copyright. All rights reserved.
    Print ISSN: 0197-9337
    Electronic ISSN: 1096-9837
    Topics: Geography , Geosciences
    Published by Wiley
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  • 10
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    Connexin defects underlie arrhythmogenic right ventricular cardiomyopathy in a novel mouse model (2014)
    Oxford University Press
    Details
    Publication Date: 2014-02-08
    Description: Arrhythmogenic right ventricular cardiomyopathy (ARVC) termed a ‘disease of the desmosome’ is an inherited cardiomyopathy that recently underwent reclassification owing to the identification of left-dominant and biventricular disease forms. Homozygous loss-of-function mutations in the desmosomal component, desmoplakin, are found in patients exhibiting a biventricular form of ARVC; however, no models recapitulate the postnatal hallmarks of the disease as seen in these patients. To gain insights into the homozygous loss-of-function effects of desmoplakin in the heart, we generated cardiomyocyte-specific desmoplakin-deficient mice (DSP-cKO) using ventricular myosin light chain-2-Cre mice. Homozygous DSP-cKO mice are viable but display early ultrastructural defects in desmosomal integrity leading to a cardiomyopathy reminiscent of a biventricular form of ARVC, which includes cell death and fibro-fatty replacement within the ventricle leading to biventricular dysfunction, failure and premature death. DSP-cKO mice also exhibited ventricular arrhythmias that are exacerbated with exercise and catecholamine stimulation. Furthermore, DSP-cKO hearts exhibited right ventricular conduction defects associated with loss of connexin 40 expression and electrical wavefront propagation defects associated with loss of connexin 43 expression. Dose-dependent assessment of the effects of loss of desmoplakin in neonatal ventricular cardiomyocytes revealed primary loss of connexin 43 levels, phosphorylation and function independent of the molecular dissociation of the mechanical junction complex and fibro-fatty manifestation associated with ARVC, suggesting a role for desmoplakin as a primary stabilizer of connexin integrity. In summary, we provide evidence for a novel mouse model, which is reminiscent of the postnatal onset of ARVC while highlighting mechanisms underlying a biventricular form of human ARVC.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
    Published by Oxford University Press
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