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  • 1
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    Auditory cortex controls sound-driven innate defense behaviour through corticofugal projections to inferior colliculus (2015)
    Springer Nature
    Details
    Publication Date: 2015-06-13
    Description: Article Defense against environmental threats is essential for survival, yet the neural circuits mediating innate defensive behaviours are not completely understood. Here the authors demonstrate that descending projections from the auditory cortex to the midbrain mediate innate, sound-evoked flight behaviour. Nature Communications doi: 10.1038/ncomms8224 Authors: Xiaorui R. Xiong, Feixue Liang, Brian Zingg, Xu-ying Ji, Leena A. Ibrahim, Huizhong W. Tao, Li I. Zhang
    Electronic ISSN: 2041-1723
    Topics: Biology , Chemistry and Pharmacology , Natural Sciences in General , Physics
    Published by Springer Nature
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  • 2
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    AIBP-mediated cholesterol efflux instructs hematopoietic stem and progenitor cell fate (2019)
    American Association for the Advancement of Science (AAAS)
    In: Science
    Details
    Publication Date: 2019
    Description: 〈p〉Hypercholesterolemia, the driving force of atherosclerosis, accelerates the expansion and mobilization of hematopoietic stem and progenitor cells (HSPCs). The molecular determinants connecting hypercholesterolemia with hematopoiesis are unclear. Here, we report that a somite-derived prohematopoietic cue, AIBP, orchestrates HSPC emergence from the hemogenic endothelium, a type of specialized endothelium manifesting hematopoietic potential. Mechanistically, AIBP-mediated cholesterol efflux activates endothelial Srebp2, the master transcription factor for cholesterol biosynthesis, which in turn transactivates Notch and promotes HSPC emergence. Srebp2 inhibition impairs hypercholesterolemia-induced HSPC expansion. Srebp2 activation and Notch up-regulation are associated with HSPC expansion in hypercholesterolemic human subjects. Genome-wide chromatin immunoprecipitation followed by sequencing (ChIP-seq), RNA sequencing (RNA-seq), and assay for transposase-accessible chromatin using sequencing (ATAC-seq) indicate that Srebp2 transregulates Notch pathway genes required for hematopoiesis. Our studies outline an AIBP-regulated Srebp2-dependent paradigm for HSPC emergence in development and HPSC expansion in atherosclerotic cardiovascular disease.〈/p〉
    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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  • 3
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    Kinematic rupture process of the 2014 Chile Mw 8.1 earthquake constrained by strong-motion, GPS static offsets and teleseismic data (2015)
    Oxford University Press
    Details
    Publication Date: 2015-06-28
    Description: On 2014 April 1, a magnitude M w  8.1 interplate thrust earthquake ruptured a densely instrumented region of Iquique seismic gap in northern Chile. The abundant data sets near and around the rupture zone provide a unique opportunity to study the detailed source process of this megathrust earthquake. We retrieved the spatial and temporal distributions of slip during the main shock and one strong aftershock through a joint inversion of teleseismic records, GPS offsets and strong motion data. The main shock rupture initiated at a focal depth of about 25 km and propagated around the hypocentre. The peak slip amplitude in the model is ~6.5 m, located in the southeast of the hypocentre. The major slip patch is located around the hypocentre, spanning ~150 km along dip and ~160 km along strike. The associated static stress drop is ~3 MPa. Most of the seismic moment was released within 150 s. The total seismic moment of our preferred model is 1.72 x 10 21 N m, equivalent to M w  8.1. For the strong aftershock on 2014 April 3, the slip mainly occurred in a relatively compact area, and the major slip area surrounded the hypocentre with the peak amplitude of ~2.5 m. There is a secondary slip patch located downdip from the hypocentre with the peak slip of ~2.1 m. The total seismic moment is about 3.9 x 10 20 N m, equivalent to M w  7.7. Between the rupture areas of the main shock and the 2007 November 14 M w  7.7 Antofagasta, Chile earthquake, there is an earthquake vacant zone with a total length of about 150 km. Historically, if there is no big earthquake or obvious aseismic creep occurring in this area, it has a great potential of generating strong earthquakes with magnitude larger than M w 7.0 in the future.
    Keywords: Seismology
    Print ISSN: 0956-540X
    Electronic ISSN: 1365-246X
    Topics: Geosciences
    Published by Oxford University Press on behalf of The Deutsche Geophysikalische Gesellschaft (DGG) and the Royal Astronomical Society (RAS).
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  • 4
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    Nonsense RNA decay protects cells from ER stress [Biochemistry] (2012)
    National Academy of Sciences
    Details
    Publication Date: 2012-05-23
    Description: The unfolded protein response (UPR) is an intracellular stress-signaling pathway that counteracts the accumulation of misfolded proteins in the endoplasmic reticulum (ER). Because defects in ER protein folding are associated with many pathological states, including metabolic, neurologic, genetic, and inflammatory diseases, it is important to understand how the UPR maintains ER protein-folding homeostasis. All metazoans have conserved the fundamental UPR transducers IRE1, ATF6, and PERK. In Caenorhabditis elegans, the UPR is required to prevent larval lethality and intestinal degeneration. Although ire-1-null worms are viable, they are particularly sensitive to ER stress. To identify genes that are required for development of ire-1-null worms, we performed a comprehensive RNA interference screen to find 10 genes that exhibit synthetic growth and intestinal defects with the ire-1(v33) mutant but not with atf-6(tm1153) or pek-1(ok275) mutants. The expression of two of these genes, exos-3 and F48E8.6, was induced by ER stress, and their knockdown in a wild-type strain caused ER stress. Because these genes encode subunits of the exosome complex that functions in mRNA surveillance, we analyzed other gene products required for nonsense-mediated mRNA decay (NMD). Our results demonstrate that defects in smg-1, smg-4, and smg-6 in C. elegans and SMG6 in mammalian cells cause ER stress and sensitize to the lethal effects of ER stress. Although ER stress did not activate mRNA surveillance complex assembly, ER stress did induce SMG6 expression, and NMD regulators were constitutively localized to the ER. Importantly, the findings demonstrate a unique and fundamental interaction where NMD-mediated mRNA quality control is required to prevent ER stress.
    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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  • 5
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    A comparative evaluation on prediction methods of nucleosome positioning (2014)
    Oxford University Press
    Details
    Publication Date: 2014-11-20
    Description: Nucleosome positioning plays an essential role in cellular processes by modulating accessibility of DNA to proteins. Many computational models have been developed to predict genome-wide nucleosome positions from DNA sequences. Comparative analysis of predicted and experimental nucleosome positioning maps facilitates understanding the regulatory mechanisms of transcription and DNA replication. Therefore, a comprehensive evaluation of existing computational methods is important and useful for biologists to choose appropriate ones in their research. In this article, we carried out a performance comparison among eight widely used computational methods on four species including yeast, fruitfly, mouse and human. In particular, we compared these methods on different regions of each species such as gene sequences, promoters and 5'UTR exons. The experimental results show that the performances of the two latest versions of the thermodynamic model are relatively steadier than the other four methods. Moreover, these methods are workable on four species, but their performances decrease gradually from yeast to human, indicating that the fundamental mechanism of nucleosome positioning is conserved through the evolution process, but more and more factors participate in the determination of nucleosome positions, which leads to sophisticated regulation mechanisms.
    Print ISSN: 1467-5463
    Electronic ISSN: 1477-4054
    Topics: Biology , Computer Science
    Published by Oxford University Press
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  • 6
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    AIBP-mediated cholesterol efflux instructs hematopoietic stem and progenitor cell fate (2019)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2019
    Description: 〈p〉Hypercholesterolemia, the driving force of atherosclerosis, accelerates the expansion and mobilization of hematopoietic stem and progenitor cells (HSPCs). The molecular determinants connecting hypercholesterolemia with hematopoiesis are unclear. Here we report that a somite-derived pro-hematopoietic cue, AIBP, orchestrates HSPC emergence from the hemogenic endothelium, a type of specialized endothelium manifesting hematopoietic potential. Mechanistically, AIBP-mediated cholesterol efflux activates endothelial Srebp2, the master transcription factor for cholesterol biosynthesis, which in turn transactivates Notch and promotes HSPC emergence. Srebp2 inhibition impairs hypercholesterolemia-induced HSPC expansion. Srebp2 activation and Notch upregulation are associated with HSPC expansion in hypercholesterolemic human subjects. Genome-wide ChIP-seq, RNA-seq, and ATAC-seq indicate that Srebp2 trans-regulates Notch pathway genes required for hematopoiesis. Our studies outline an AIBP-regulated Srebp2-dependent paradigm for HSPC emergence in development and HPSC expansion in atherosclerotic cardiovascular disease.〈/p〉
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Natural Sciences in General
    Published by American Association for the Advancement of Science (AAAS)
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  • 7
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    Telomere dysfunction induces metabolic and mitochondrial compromise (2011)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2011-02-11
    Description: Telomere dysfunction activates p53-mediated cellular growth arrest, senescence and apoptosis to drive progressive atrophy and functional decline in high-turnover tissues. The broader adverse impact of telomere dysfunction across many tissues including more quiescent systems prompted transcriptomic network analyses to identify common mechanisms operative in haematopoietic stem cells, heart and liver. These unbiased studies revealed profound repression of peroxisome proliferator-activated receptor gamma, coactivator 1 alpha and beta (PGC-1alpha and PGC-1beta, also known as Ppargc1a and Ppargc1b, respectively) and the downstream network in mice null for either telomerase reverse transcriptase (Tert) or telomerase RNA component (Terc) genes. Consistent with PGCs as master regulators of mitochondrial physiology and metabolism, telomere dysfunction is associated with impaired mitochondrial biogenesis and function, decreased gluconeogenesis, cardiomyopathy, and increased reactive oxygen species. In the setting of telomere dysfunction, enforced Tert or PGC-1alpha expression or germline deletion of p53 (also known as Trp53) substantially restores PGC network expression, mitochondrial respiration, cardiac function and gluconeogenesis. We demonstrate that telomere dysfunction activates p53 which in turn binds and represses PGC-1alpha and PGC-1beta promoters, thereby forging a direct link between telomere and mitochondrial biology. We propose that this telomere-p53-PGC axis contributes to organ and metabolic failure and to diminishing organismal fitness in the setting of telomere dysfunction.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3741661/" 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/PMC3741661/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sahin, Ergun -- Colla, Simona -- Liesa, Marc -- Moslehi, Javid -- Muller, Florian L -- Guo, Mira -- Cooper, Marcus -- Kotton, Darrell -- Fabian, Attila J -- Walkey, Carl -- Maser, Richard S -- Tonon, Giovanni -- Foerster, Friedrich -- Xiong, Robert -- Wang, Y Alan -- Shukla, Sachet A -- Jaskelioff, Mariela -- Martin, Eric S -- Heffernan, Timothy P -- Protopopov, Alexei -- Ivanova, Elena -- Mahoney, John E -- Kost-Alimova, Maria -- Perry, Samuel R -- Bronson, Roderick -- Liao, Ronglih -- Mulligan, Richard -- Shirihai, Orian S -- Chin, Lynda -- DePinho, Ronald A -- P30 DK046200/DK/NIDDK NIH HHS/ -- P30DK079638/DK/NIDDK NIH HHS/ -- R01 CA084628/CA/NCI NIH HHS/ -- R01 DK035914/DK/NIDDK NIH HHS/ -- R01 DK056690/DK/NIDDK NIH HHS/ -- R01 DK063356/DK/NIDDK NIH HHS/ -- R01 DK089185/DK/NIDDK NIH HHS/ -- U24 DK-59635/DK/NIDDK NIH HHS/ -- England -- Nature. 2011 Feb 17;470(7334):359-65. doi: 10.1038/nature09787. Epub 2011 Feb 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Belfer Institute for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21307849" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/biosynthesis ; Aging/metabolism/pathology ; Animals ; Cardiomyopathies/chemically induced/metabolism/pathology/physiopathology ; Cell Proliferation ; DNA, Mitochondrial/analysis ; Doxorubicin/toxicity ; Gluconeogenesis ; Hematopoietic Stem Cells/metabolism/pathology ; Liver/cytology/metabolism ; Mice ; Mitochondria/*metabolism/*pathology ; Myocardium/cytology/metabolism ; RNA/genetics ; Reactive Oxygen Species/metabolism ; Telomerase/deficiency/genetics ; Telomere/enzymology/genetics/*metabolism/*pathology ; Transcription Factors/antagonists & inhibitors/metabolism ; Tumor Suppressor Protein p53/deficiency/genetics/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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  • 8
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    CDKL5-PSD-95 interaction in spine development [Neuroscience] (2013)
    National Academy of Sciences
    Details
    Publication Date: 2013-05-29
    Description: The X-linked gene cyclin-dependent kinase-like 5 (CDKL5) is mutated in severe neurodevelopmental disorders, including some forms of atypical Rett syndrome, but the function and regulation of CDKL5 protein in neurons remain to be elucidated. Here, we show that CDKL5 binds to the scaffolding protein postsynaptic density (PSD)-95, and that this...
    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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  • 9
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    Endogenous FAAH inhibitor and insulin resistance [Biochemistry] (2013)
    National Academy of Sciences
    Details
    Publication Date: 2013-11-20
    Description: High-fat diet (HFD)–induced obesity and insulin resistance are associated with increased activity of the endocannabinoid/CB1 receptor (CB1R) system that promotes the hepatic expression of lipogenic genes, including stearoyl-CoA desaturase-1 (SCD1). Mice deficient in CB1R or SCD1 remain lean and insulin-sensitive on an HFD, suggesting a functional link between the two...
    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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  • 10
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    Moho fabrics of North Qinling Belt, Weihe Graben and Ordos Block in China constrained from large dynamite shots (2017)
    Oxford University Press
    Details
    Publication Date: 2017-04-19
    Description: 〈span class="paragraphSection"〉〈div class="boxTitle"〉Abstract〈/div〉The Qinling Orogen Belt (QOB), Weihe Graben (WG) and the southern margin of the Ordos Block (SOB), lying on the central portion of China, had been involved into the amalgamation of China (Asian continent) through subduction, collision to exhumation processes. The Moho fabrics beneath this region, recorded part of the evolution. Therefore, its thickness and internal structure may provide significant knowledge and contribute to the understanding the intracontinental deformation of central China. In this paper, in order to place constrain on the nature beneath the study area, nine large dynamite shots (the charge ≥500 kg) used to infer the internal structure and characteristics of the crustal boundary. We analyse the specific characteristics of the Moho reflection, the amplitude decay curves in near vertical zone and generate a single-fold profile; in addition, it also address the internal structure and discuss its implication. The Moho is approximately at the depth of 39 km beneath the North Qinling Orogen (NQB) and the WG, and at the depth of 42 km beneath the SOB. The Moho shows a subtle uplift and the crust is thin under the NQB. The north-dipping reflectors between the lower crust and the uppermost mantle extend to the middle of the WG, and the south-dipping reflectors in the lower crust of the NQB are truncated by the Moho, therefore both of features and structures exhibit a ‘Crocodile’ like structure and are most probably the remnants of the amalgamation of the NQB and the NCB. The transparent reflection Moho beneath the southern part of the WG may indicate the existence of a magma channel. The Weihe Fault is interpreted as a shallow, near-surface feature resulted from the upwelling magma; SOB represents a relatively weak region and could accommodate the crustal shortening during the formation of the China continent in Triassic.〈/span〉
    Print ISSN: 0956-540X
    Electronic ISSN: 1365-246X
    Topics: Geosciences
    Published by Oxford University Press on behalf of The Deutsche Geophysikalische Gesellschaft (DGG) and the Royal Astronomical Society (RAS).
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