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  • 1
    Publication Date: 2016-09-20
    Description: The Ku protein, a heterodimer of Ku70 and Ku80, binds to chromosomal replication origins maximally at G1-phase and plays an essential role in assembly of origin recognition complex. However, the mechanism regulating such a critical periodic activity of Ku remained unknown. Here, we establish human Ku70 as a novel target of cyclin B1-Cdk1, which phosphorylates it in a Cy-motif dependent manner. Interestingly, cyclin E1- and A2-Cdk2 also phosphorylate Ku70, and as a result, the protein remains in a phosphorylated state during S-M phases of cell cycle. Intriguingly, the phosphorylation of Ku70 by cyclin-Cdks abolishes the interaction of Ku protein with replication origin due to disruption of the dimer. Furthermore, Ku70 is dephosphorylated in G1-phase, when Ku interacts with replication origin maximally. Strikingly, the over-expression of Ku70 with non-phosphorylable Cdk targets enhances the episomal replication of Ors8 origin and induces rereplication in HeLa cells, substantiating a preventive role of Ku phosphorylation in premature and untimely licensing of replication origin. Therefore, periodic phosphorylation of Ku70 by cyclin-Cdks prevents the interaction of Ku with replication origin after initiation events in S-phase and the dephosphorylation at the end of mitosis facilitates its participation in pre-replication complex formation.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 2
    Publication Date: 2013-12-23
    Description: We develop a novel statistical strong-lensing approach to probe the cosmological parameters by exploiting multiple redshift image systems behind galaxies or galaxy clusters. The method relies on free-form mass inversion of strong lenses and does not need any additional information other than gravitational lensing. Since in free-form lensing the solution space is a high-dimensional convex polytope, we consider Bayesian model comparison analysis to infer the cosmological parameters. The volume of the solution space is taken as a tracer of the probability of the underlying cosmological assumption. In contrast to parametric mass inversions, our method accounts for the mass-sheet degeneracy, which implies a degeneracy between the steepness of the profile and the cosmological parameters. Parametric models typically break this degeneracy, introducing hidden priors to the analysis that contaminate the inference of the parameters. We test our method with synthetic lenses, showing that it is able to infer the assumed cosmological parameters. Applied to the Cluster Lensing And Supernova survey with Hubble (CLASH) clusters, the method might be competitive with other probes.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
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  • 3
    Publication Date: 2012-05-09
    Description: In the preimplantation mouse embryo, TEAD4 is critical to establishing the trophectoderm (TE)-specific transcriptional program and segregating TE from the inner cell mass (ICM). However, TEAD4 is expressed in the TE and the ICM. Thus, differential function of TEAD4 rather than expression itself regulates specification of the first two cell lineages. We used ChIP sequencing to define genomewide TEAD4 target genes and asked how transcription of TEAD4 target genes is specifically maintained in the TE. Our analyses revealed an evolutionarily conserved mechanism, in which lack of nuclear localization of TEAD4 impairs the TE-specific transcriptional program in inner blastomeres, thereby allowing their maturation toward the ICM lineage. Restoration of TEAD4 nuclear localization maintains the TE-specific transcriptional program in the inner blastomeres and prevents segregation of the TE and ICM lineages and blastocyst formation. We propose that altered subcellular localization of TEAD4 in blastomeres dictates first mammalian cell fate specification.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 4
    Publication Date: 2014-08-29
    Description: Magmas functions as a ROS regulator and provides cytoprotection against oxidative stress-mediated damages Cell Death and Disease 5, e1394 (August 2014). doi:10.1038/cddis.2014.355 Authors: S Srivastava, D Sinha, P P Saha, H Marthala & P D'Silva
    Electronic ISSN: 2041-4889
    Topics: Biology , Medicine
    Published by Springer Nature
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  • 5
    Publication Date: 2008-11-29
    Description: Hepatic glucose production is critical for basal brain function and survival when dietary glucose is unavailable. Glucose-6-phosphatase (G6Pase) is an essential, rate-limiting enzyme that serves as a terminal gatekeeper for hepatic glucose release into the plasma. Mutations in G6Pase result in Von Gierke's disease (glycogen storage disease-1a), a potentially fatal genetic disorder. We have identified the transcriptional coactivator SRC-2 as a regulator of fasting hepatic glucose release, a function that SRC-2 performs by controlling the expression of hepatic G6Pase. SRC-2 modulates G6Pase expression directly by acting as a coactivator with the orphan nuclear receptor RORalpha. In addition, SRC-2 ablation, in both a whole-body and liver-specific manner, resulted in a Von Gierke's disease phenotype in mice. Our results position SRC-2 as a critical regulator of mammalian glucose production.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2668604/" 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/PMC2668604/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chopra, Atul R -- Louet, Jean-Francois -- Saha, Pradip -- An, Jie -- Demayo, Franco -- Xu, Jianming -- York, Brian -- Karpen, Saul -- Finegold, Milton -- Moore, David -- Chan, Lawrence -- Newgard, Christopher B -- O'Malley, Bert W -- DK58242/DK/NIDDK NIH HHS/ -- HL51586/HL/NHLBI NIH HHS/ -- P01 DK059820/DK/NIDDK NIH HHS/ -- P01 DK059820-08/DK/NIDDK NIH HHS/ -- P01 DK58398/DK/NIDDK NIH HHS/ -- P01 DK59820/DK/NIDDK NIH HHS/ -- R01 DK056239/DK/NIDDK NIH HHS/ -- R01 DK056239-08/DK/NIDDK NIH HHS/ -- U19 DK062434/DK/NIDDK NIH HHS/ -- U19 DK062434-07/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 2008 Nov 28;322(5906):1395-9. doi: 10.1126/science.1164847.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cellular Biology, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19039140" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cells, Cultured ; Fasting ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Enzymologic ; Glucose/*metabolism ; Glucose-6-Phosphatase/*genetics/metabolism ; Glycogen Storage Disease Type I/*genetics/metabolism ; Hepatocytes/metabolism ; Kidney/metabolism ; Liver/*metabolism ; Liver Glycogen/metabolism ; Male ; Mice ; Mice, Knockout ; Nuclear Receptor Coactivator 2/genetics/*metabolism ; RNA Interference ; Receptors, Retinoic Acid/metabolism ; Response Elements ; Transcription, Genetic ; Triglycerides/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 6
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1996-11-22
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Saha, D P -- New York, N.Y. -- Science. 1996 Nov 22;274(5291):1287.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8966592" target="_blank"〉PubMed〈/a〉
    Keywords: *Arsenic Poisoning ; Humans ; India ; Keratosis/chemically induced ; Skin Diseases/*chemically induced
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 7
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1996-11-22
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Saha, D P -- New York, N.Y. -- Science. 1996 Nov 22;274(5291):1287a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17772036" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 8
    Publication Date: 2013-04-13
    Description: Author(s): Hari P. Saha Very recently we were successful in extending the multiconfiguration Hartree-Fock (MCHF) method for electron-impact ionization of atoms to allow double photoionization of atoms. We report, as a test case, the results of our calculation of the triple differential cross section (TDCS) for double photo... [Phys. Rev. A 87, 042703] Published Fri Apr 12, 2013
    Keywords: Atomic and molecular collisions and interactions
    Print ISSN: 1050-2947
    Electronic ISSN: 1094-1622
    Topics: Physics
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  • 9
    Publication Date: 2017-06-28
    Description: Author(s): Hari P. Saha We extended the multiconfiguration Hartree-Fock (MCHF) + effective charge (EFC) method for double photoionization of atoms and investigated the effect of valence-electron correlation in the double K -shell photoionization of atomic beryllium. We used the MCHF method, which accounts for electron corre... [Phys. Rev. A 95, 063423] Published Tue Jun 27, 2017
    Keywords: Atomic and molecular processes in external fields, including interactions with strong fields and short pulses
    Print ISSN: 1050-2947
    Electronic ISSN: 1094-1622
    Topics: Physics
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  • 10
    Publication Date: 2006-03-28
    Print ISSN: 0022-2461
    Electronic ISSN: 1573-4803
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Published by Springer
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