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  • 1
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    A novel role for CARM1 in promoting nonsense-mediated mRNA decay: potential implications for spinal muscular atrophy (2016)
    Oxford University Press
    Details
    Publication Date: 2016-04-08
    Description: Loss of ‘Survival of Motor Neurons’ (SMN) leads to spinal muscular atrophy (SMA), a disease characterized by degeneration of spinal cord alpha motor neurons, resulting in muscle weakness, paralysis and death during early childhood. SMN is required for assembly of the core splicing machinery, and splicing defects were documented in SMA. We previously uncovered that Coactivator-Associated Methyltransferase-1 (CARM1) is abnormally up-regulated in SMA, leading to mis-regulation of a number of transcriptional and alternative splicing events. We report here that CARM1 can promote decay of a premature terminating codon (PTC)-containing mRNA reporter, suggesting it can act as a mediator of nonsense-mediated mRNA decay (NMD). Interestingly, this pathway, while originally perceived as solely a surveillance mechanism preventing expression of potentially detrimental proteins, is now emerging as a highly regulated RNA decay pathway also acting on a subset of normal mRNAs. We further show that CARM1 associates with major NMD factor UPF1 and promotes its occupancy on PTC-containing transcripts. Finally, we identify a specific subset of NMD targets that are dependent on CARM1 for degradation and that are also misregulated in SMA, potentially adding exacerbated targeting of PTC-containing mRNAs to the already complex array of molecular defects associated with this disease.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 2
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    DOCK1 regulates breast cancer progression [Medical Sciences] (2013)
    National Academy of Sciences
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    Publication Date: 2013-05-01
    Description: Progression of solid tumors to the metastatic stage is accountable for the majority of cancer-related deaths. Further understanding of the molecular mechanisms governing metastasis is essential for the development of antimetastatic regimens. Here, we aimed to identify Rac activators that could promote metastasis downstream of human epithelial growth factor receptor...
    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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  • 3
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    The globular cluster system of NGC 6822 (2015)
    Oxford University Press
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    Publication Date: 2015-07-04
    Description: We present a comprehensive analysis of the globular cluster (GC) system of the Local Group dwarf irregular galaxy NGC 6822. Our study is based on homogeneous optical and near-IR photometry, as well as long-slit spectroscopic observations which are used to determine new radial velocities for six GCs, two of which had no previous spectroscopic information. We construct optical-near-IR colour–colour diagrams and through comparison to simple stellar population models infer that the GCs have old ages consistent with being 9 Gyr or older, while their metallicities are in the range between –1.6  [Fe/H]  –0.4. We conduct a kinematic analysis of the GC population and find tentative evidence for weak net rotation of the GC system, in the same sense as that exhibited by the underlying spheroid. The most likely amplitude of rotation is 10 km s –1 , approximately half the magnitude of the observed velocity dispersion. Finally, we use the GCs to estimate the dynamical mass of NGC 6822 within ~11 kpc and we formally find it to be in the range between (3 and 4)  x  10 9 M . This implies an overall mass-to-light ratio in the range of ~30–40 and indicates that NGC 6822 is highly dark-matter-dominated. The mass and the corresponding mass-to-light ratio estimates are affected by various additional systematic effects due to limitations of the data and the model that are not necessary reflected in the formal uncertainties.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
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  • 4
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    Two Dimensional Soft Material: New Faces of Graphene Oxide (2012)
    American Chemical Society (ACS)
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    Publication Date: 2012-06-05
    Description: Accounts of Chemical Research DOI: 10.1021/ar300047s
    Print ISSN: 0001-4842
    Electronic ISSN: 1520-4898
    Topics: Chemistry and Pharmacology
    Published by American Chemical Society (ACS)
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  • 5
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    In situ post-weld heat treatment on martensitic stainless steel turbine runners using a robotic induction heating process to control temperature distribution (2014)
    Institute of Physics (IOP)
    Details
    Publication Date: 2014-12-11
    Description: A new robotic heat treatment process is developed. Using this solution it is now possible to perform local heat treatment on large steel components. Crack, cavitation and erosion repairs on turbine blades and Pelton buckets are among the applications of this technique. The proof of concept is made on a 13Cr-4Ni stainless steel designated "CA6NM". This alloy is widely used in the power industry for modern system components. Given the very tight temperature tolerance (600 to 630 °C) for post-weld heat treatment on this alloy, 13Cr-4Ni stainless steel is very well suited for demonstrating the possibilities of this process. To achieve heat treatment requirements, an induction heating system is mounted on a compact manipulator named "Scompi". This robot moves a pancake coil in order to control the temperature distribution. A simulator using thermal finite element analysis is first used for path planning. A feedback loop adjusts parameters in function of environmental conditions.
    Print ISSN: 1755-1307
    Electronic ISSN: 1755-1315
    Topics: Geography , Geosciences , Physics
    Published by Institute of Physics (IOP)
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  • 6
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    Persistent site-specific remodeling of a nucleosome array by transient action of the SWI/SNF complex (1996)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1996-07-26
    Description: The SWI/SNF complex participates in the restructuring of chromatin for transcription. The function of the yeast SWI/SNF complex in the remodeling of a nucleosome array has now been analyzed in vitro. Binding of the purified SWI/SNF complex to a nucleosome array disrupted multiple nucleosomes in an adenosine triphosphate-dependent reaction. However, removal of SWI/SNF left a deoxyribonuclease I-hypersensitive site specifically at a nucleosome that was bound by derivatives of the transcription factor Gal4p. Analysis of individual nucleosomes revealed that the SWI/SNF complex catalyzed eviction of histones from the Gal4-bound nucleosomes. Thus, the transient action of the SWI/SNF complex facilitated irreversible disruption of transcription factor-bound nucleosomes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Owen-Hughes, T -- Utley, R T -- Cote, J -- Peterson, C L -- Workman, J L -- GM47867/GM/NIGMS NIH HHS/ -- R01 GM049650/GM/NIGMS NIH HHS/ -- R37 GM049650/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1996 Jul 26;273(5274):513-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biology and Center for Gene Regulation, Pennsylvania State University, University Park, PA 16802-4500, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8662543" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphatases ; Adenosine Triphosphate/metabolism ; Base Sequence ; Binding Sites ; DNA, Fungal/metabolism ; DNA-Binding Proteins/*metabolism ; Deoxyribonuclease I/metabolism ; Fungal Proteins/*metabolism ; Histones/metabolism ; Molecular Sequence Data ; *Nuclear Proteins ; Nucleosomes/*metabolism/ultrastructure ; Saccharomyces cerevisiae ; *Saccharomyces cerevisiae Proteins ; Transcription Factors/*metabolism
    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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  • 7
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    Single-cell differences in matrix gene expression do not predict matrix deposition (2016)
    Springer Nature
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    Publication Date: 2016-03-05
    Description: Article Regenerative tissue engineering with mesenchymal stem cells is hampered by bulk methods of assessing differentiation status and a general assumption that expression of individual markers of stem cell differentiation correlate with functional capacity. Here the authors debunk this assumption by applying single-cell techniques to disassociate aggrecan mRNA abundance and matrix deposition. Nature Communications doi: 10.1038/ncomms10865 Authors: Allison J. Cote, Claire M. McLeod, Megan J. Farrell, Patrick D. McClanahan, Margaret C. Dunagin, Arjun Raj, Robert L. Mauck
    Electronic ISSN: 2041-1723
    Topics: Biology , Chemistry and Pharmacology , Natural Sciences in General , Physics
    Published by Springer Nature
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  • 8
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    Primers for mitochondrial DNA replication generated by endonuclease G (1993)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1993-08-06
    Description: Endonuclease G (Endo G) is widely distributed among animals and cleaves DNA at double-stranded (dG)n.(dC)n and at single-stranded (dC)n tracts. Endo G is synthesized as a propeptide with an amino-terminal presequence that targets the nuclease to mitochondria. Endo G can also be detected in extranucleolar chromatin. In addition to deoxyribonuclease activities, Endo G also has ribonuclease (RNase) and RNase H activities and specifically cleaves mouse mitochondrial RNA and DNA-RNA substrates containing the origin of heavy-strand DNA replication (OH). The cleavage sites match those found in vivo, indicating that Endo G is capable of generating the RNA primers required by DNA polymerase gamma to initiate replication of mitochondrial DNA.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cote, J -- Ruiz-Carrillo, A -- New York, N.Y. -- Science. 1993 Aug 6;261(5122):765-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cancer Research Center, Medical School of Laval University, L'Hotel-Dieu de Quebec, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7688144" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Base Sequence ; Cell Line ; Cell Nucleus/enzymology ; DNA/genetics ; *DNA Replication ; DNA, Mitochondrial/*metabolism ; Endodeoxyribonucleases/chemistry/genetics/*metabolism ; Genetic Vectors ; Mitochondria/enzymology ; Molecular Sequence Data ; RNA/*metabolism ; Ribonuclease H/metabolism ; Ribonucleases/metabolism ; Transfection
    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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  • 9
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    Mutations in the sulfonylurea receptor gene in familial persistent hyperinsulinemic hypoglycemia of infancy (1995)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1995-04-21
    Description: Familial persistent hyperinsulinemic hypoglycemia of infancy (PHHI), an autosomal recessive disorder characterized by unregulated insulin secretion, is linked to chromosome 11p14-15.1. The newly cloned high-affinity sulfonylurea receptor (SUR) gene, a regulator of insulin secretion, was mapped to 11p15.1 by means of fluorescence in situ hybridization. Two separate SUR gene splice site mutations, which segregated with disease phenotype, were identified in affected individuals from nine different families. Both mutations resulted in aberrant processing of the RNA sequence and disruption of the putative second nucleotide binding domain of the SUR protein. Abnormal insulin secretion in PHHI appears to be caused by mutations in the SUR gene.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Thomas, P M -- Cote, G J -- Wohllk, N -- Haddad, B -- Mathew, P M -- Rabl, W -- Aguilar-Bryan, L -- Gagel, R F -- Bryan, J -- DK38146/DK/NIDDK NIH HHS/ -- DK44311/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 1995 Apr 21;268(5209):426-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medical Specialties, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7716548" target="_blank"〉PubMed〈/a〉
    Keywords: *ATP-Binding Cassette Transporters ; Amino Acid Sequence ; Base Sequence ; Chromosome Mapping ; Chromosomes, Human, Pair 11 ; DNA Mutational Analysis ; DNA, Complementary/genetics ; Genotype ; Humans ; Hyperinsulinism/*genetics ; Hypoglycemia/*genetics ; Infant ; Insulin/secretion ; Molecular Sequence Data ; Mutation ; Pancreatic Diseases/*genetics ; Phenotype ; Point Mutation ; Potassium Channels/chemistry/*genetics ; *Potassium Channels, Inwardly Rectifying ; RNA Splicing ; Receptors, Drug/chemistry/*genetics ; Sulfonylurea Compounds/metabolism ; Sulfonylurea Receptors
    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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    Stimulation of GAL4 derivative binding to nucleosomal DNA by the yeast SWI/SNF complex (1994)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1994-07-01
    Description: The SWI/SNF protein complex is required for the enhancement of transcription by many transcriptional activators in yeast. Here it is shown that the purified SWI/SNF complex is composed of 10 subunits and includes the SWI1, SWI2/SNF2, SWI3, SNF5, and SNF6 gene products. The complex exhibited DNA-stimulated adenosine triphosphatase (ATPase) activity, but lacked helicase activity. The SWI/SNF complex caused a 10- to 30-fold stimulation in the binding of GAL4 derivatives to nucleosomal DNA in a reaction that required adenosine triphosphate (ATP) hydrolysis but was activation domain-independent. Stimulation of GAL4 binding by the complex was abolished by a mutant SWI2 subunit, and was increased by the presence of a histone-binding protein, nucleoplasmin. A direct ATP-dependent interaction between the SWI/SNF complex and nucleosomal DNA was detected. These observations suggest that a primary role of the SWI/SNF complex is to promote activator binding to nucleosomal DNA.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cote, J -- Quinn, J -- Workman, J L -- Peterson, C L -- GM47867-02/GM/NIGMS NIH HHS/ -- GM49650-01/GM/NIGMS NIH HHS/ -- R01 GM049650/GM/NIGMS NIH HHS/ -- R37 GM049650/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1994 Jul 1;265(5168):53-60.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park 16802.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8016655" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphatases/metabolism ; Adenosine Triphosphate/metabolism ; Base Sequence ; DNA Helicases/metabolism ; DNA Probes ; DNA, Fungal/*metabolism ; DNA-Binding Proteins/genetics/metabolism ; Deoxyribonuclease I/metabolism ; Fungal Proteins/*metabolism ; Gene Expression Regulation, Fungal ; Molecular Sequence Data ; Nuclear Proteins/metabolism/pharmacology ; Nucleoplasmins ; Nucleosomes/*metabolism ; *Phosphoproteins ; Saccharomyces cerevisiae/genetics/metabolism ; *Saccharomyces cerevisiae Proteins ; Transcription Factors/genetics/isolation & purification/*metabolism ; Transcription, Genetic
    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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