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  • 1
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    A highly conserved G-rich consensus sequence in hepatitis C virus core gene represents a new anti-hepatitis C target (2016)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2016-04-03
    Description: G-quadruplex (G4) is one of the most important secondary structures in nucleic acids. Until recently, G4 RNAs have not been reported in any ribovirus, such as the hepatitis C virus. Our bioinformatics analysis reveals highly conserved guanine-rich consensus sequences within the core gene of hepatitis C despite the high genetic variability of this ribovirus; we further show using various methods that such consensus sequences can fold into unimolecular G4 RNA structures, both in vitro and under physiological conditions. Furthermore, we provide direct evidences that small molecules specifically targeting G4 can stabilize this structure to reduce RNA replication and inhibit protein translation of intracellular hepatitis C. Ultimately, the stabilization of G4 RNA in the genome of hepatitis C represents a promising new strategy for anti–hepatitis C drug development.
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
    Published by American Association for the Advancement of Science (AAAS)
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  • 2
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    TGF-beta-induced Foxp3 inhibits T(H)17 cell differentiation by antagonizing RORgammat function (2008)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2008-03-28
    Description: T helper cells that produce IL-17 (T(H)17 cells) promote autoimmunity in mice and have been implicated in the pathogenesis of human inflammatory diseases. At mucosal surfaces, T(H)17 cells are thought to protect the host from infection, whereas regulatory T (T(reg)) cells control immune responses and inflammation triggered by the resident microflora. Differentiation of both cell types requires transforming growth factor-beta (TGF-beta), but depends on distinct transcription factors: RORgammat (encoded by Rorc(gammat)) for T(H)17 cells and Foxp3 for T(reg) cells. How TGF-beta regulates the differentiation of T cells with opposing activities has been perplexing. Here we demonstrate that, together with pro-inflammatory cytokines, TGF-beta orchestrates T(H)17 cell differentiation in a concentration-dependent manner. At low concentrations, TGF-beta synergizes with interleukin (IL)-6 and IL-21 (refs 9-11) to promote IL-23 receptor (Il23r) expression, favouring T(H)17 cell differentiation. High concentrations of TGF-beta repress IL23r expression and favour Foxp3+ T(reg) cells. RORgammat and Foxp3 are co-expressed in naive CD4+ T cells exposed to TGF-beta and in a subset of T cells in the small intestinal lamina propria of the mouse. In vitro, TGF-beta-induced Foxp3 inhibits RORgammat function, at least in part through their interaction. Accordingly, lamina propria T cells that co-express both transcription factors produce less IL-17 (also known as IL-17a) than those that express RORgammat alone. IL-6, IL-21 and IL-23 relieve Foxp3-mediated inhibition of RORgammat, thereby promoting T(H)17 cell differentiation. Therefore, the decision of antigen-stimulated cells to differentiate into either T(H)17 or T(reg) cells depends on the cytokine-regulated balance of RORgammat and Foxp3.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2597437/" 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/PMC2597437/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhou, Liang -- Lopes, Jared E -- Chong, Mark M W -- Ivanov, Ivaylo I -- Min, Roy -- Victora, Gabriel D -- Shen, Yuelei -- Du, Jianguang -- Rubtsov, Yuri P -- Rudensky, Alexander Y -- Ziegler, Steven F -- Littman, Dan R -- AI48779/AI/NIAID NIH HHS/ -- R01 AI048779/AI/NIAID NIH HHS/ -- R01 AI048779-05/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2008 May 8;453(7192):236-40. doi: 10.1038/nature06878. Epub 2008 Mar 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, New York 10016, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18368049" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Differentiation/drug effects ; Cell Line ; Cells, Cultured ; Forkhead Transcription Factors/genetics/*metabolism ; Gene Expression Regulation/drug effects ; Humans ; Interleukin-17/biosynthesis/genetics/*metabolism ; Mice ; Mice, Inbred C57BL ; Nuclear Receptor Subfamily 1, Group F, Member 3 ; Receptors, Interleukin/genetics/metabolism ; Receptors, Retinoic Acid/*antagonists & inhibitors/genetics/metabolism ; Receptors, Thyroid Hormone/*antagonists & inhibitors/genetics/metabolism ; T-Lymphocytes, Helper-Inducer/*cytology/*drug effects/metabolism ; Transforming Growth Factor beta/*pharmacology
    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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    Architecture of the human regulatory network derived from ENCODE data (2012)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2012-09-08
    Description: Transcription factors bind in a combinatorial fashion to specify the on-and-off states of genes; the ensemble of these binding events forms a regulatory network, constituting the wiring diagram for a cell. To examine the principles of the human transcriptional regulatory network, we determined the genomic binding information of 119 transcription-related factors in over 450 distinct experiments. We found the combinatorial, co-association of transcription factors to be highly context specific: distinct combinations of factors bind at specific genomic locations. In particular, there are significant differences in the binding proximal and distal to genes. We organized all the transcription factor binding into a hierarchy and integrated it with other genomic information (for example, microRNA regulation), forming a dense meta-network. Factors at different levels have different properties; for instance, top-level transcription factors more strongly influence expression and middle-level ones co-regulate targets to mitigate information-flow bottlenecks. Moreover, these co-regulations give rise to many enriched network motifs (for example, noise-buffering feed-forward loops). Finally, more connected network components are under stronger selection and exhibit a greater degree of allele-specific activity (that is, differential binding to the two parental alleles). The regulatory information obtained in this study will be crucial for interpreting personal genome sequences and understanding basic principles of human biology and disease.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4154057/" 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/PMC4154057/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gerstein, Mark B -- Kundaje, Anshul -- Hariharan, Manoj -- Landt, Stephen G -- Yan, Koon-Kiu -- Cheng, Chao -- Mu, Xinmeng Jasmine -- Khurana, Ekta -- Rozowsky, Joel -- Alexander, Roger -- Min, Renqiang -- Alves, Pedro -- Abyzov, Alexej -- Addleman, Nick -- Bhardwaj, Nitin -- Boyle, Alan P -- Cayting, Philip -- Charos, Alexandra -- Chen, David Z -- Cheng, Yong -- Clarke, Declan -- Eastman, Catharine -- Euskirchen, Ghia -- Frietze, Seth -- Fu, Yao -- Gertz, Jason -- Grubert, Fabian -- Harmanci, Arif -- Jain, Preti -- Kasowski, Maya -- Lacroute, Phil -- Leng, Jing -- Lian, Jin -- Monahan, Hannah -- O'Geen, Henriette -- Ouyang, Zhengqing -- Partridge, E Christopher -- Patacsil, Dorrelyn -- Pauli, Florencia -- Raha, Debasish -- Ramirez, Lucia -- Reddy, Timothy E -- Reed, Brian -- Shi, Minyi -- Slifer, Teri -- Wang, Jing -- Wu, Linfeng -- Yang, Xinqiong -- Yip, Kevin Y -- Zilberman-Schapira, Gili -- Batzoglou, Serafim -- Sidow, Arend -- Farnham, Peggy J -- Myers, Richard M -- Weissman, Sherman M -- Snyder, Michael -- T32 GM007205/GM/NIGMS NIH HHS/ -- T32GM008283-24/GM/NIGMS NIH HHS/ -- U01 HG004695/HG/NHGRI NIH HHS/ -- U54 HG004558/HG/NHGRI NIH HHS/ -- England -- Nature. 2012 Sep 6;489(7414):91-100. doi: 10.1038/nature11245.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Program in Computational Biology and Bioinformatics, Yale University, New Haven, Connecticut 06520, USA. mark.gerstein@yale.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22955619" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Cell Line ; DNA/*genetics ; *Encyclopedias as Topic ; GATA1 Transcription Factor/metabolism ; Gene Expression Profiling ; Gene Regulatory Networks/*genetics ; Genome, Human/*genetics ; Genomics ; Humans ; K562 Cells ; *Molecular Sequence Annotation ; Organ Specificity ; Phosphorylation/genetics ; Polymorphism, Single Nucleotide/genetics ; Protein Interaction Maps ; RNA, Untranslated/genetics/metabolism ; Regulatory Sequences, Nucleic Acid/*genetics ; Selection, Genetic/genetics ; Transcription Factors/*metabolism ; Transcription Initiation Site
    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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  • 4
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    Gastrointestinal Bacterial and Methanogenic Archaea Diversity Dynamics Associated with Condensed Tannin-Containing Pine Bark Diet in Goats Using 16S rDNA Amplicon Pyrosequencing (2014)
    Hindawi
    Details
    Publication Date: 2014-01-03
    Description: Eighteen Kiko-cross meat goats () were used to collect gastrointestinal (GI) bacteria and methanogenic archaea for diversity measures when fed condensed tannin-containing pine bark (PB). Three dietary treatments were tested: control diet (0% PB and 30% wheat straw (WS); 0.17% condensed tannins (CT) dry matter (DM)); 15% PB and 15% WS (1.6% CT DM), and 30% PB and 0% WS (3.2% CT DM). A 16S rDNA bacterial tag-encoded FLX amplicon pyrosequencing technique was used to characterize and elucidate changes in GI bacteria and methanogenic archaea diversity among the diets. Proteobacteria was the most dominant phylum in goats with mean relative abundance values ranging from 39.7 (30% PB) to 46.5% (control) and 47.1% (15% PB). Other phyla individually accounted for fewer than 25% of the relative abundance observed. Predominant methanogens were Methanobrevibacter (75, 72, and 49%), Methanosphaera (3.3, 2.3, and 3.4%), and Methanobacteriaceae (1.2, 0.6, and 0.7%) population in control, 15, and 30% PB, respectively. Among methanogens, Methanobrevibacter was linearly decreased () with increasing PB supplementation. These results indicate that feeding PB selectively altered bacteria and methanogenic archaeal populations in the GI tract of goats.
    Print ISSN: 1687-918X
    Electronic ISSN: 1687-9198
    Topics: Biology , Medicine
    Published by Hindawi
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  • 5
    Electronic Resource
    Electronic Resource
    On-line monitoring of penicillin V during penicillin fermentations: a comparison of two different methods based on flow-injection analysis
    Amsterdam : Elsevier
    Analytica Chimica Acta 279 (1993), S. 51-58 
    Details
    ISSN: 0003-2670
    Keywords: Biosensors ; Flow injection: Fermentation ; On-line measurements ; Penicillin
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://linkinghub.elsevier.com/retrieve/pii/0003-2670(93)85065-R
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  • 6
    Electronic Resource
    Electronic Resource
    Ethoxycarboxylation of methylpyridines (1976)
    Springer
    Chemistry of heterocyclic compounds 12 (1976), S. 194-195 
    Details
    ISSN: 1573-8353
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The ethyl esters of pyridine carboxylic acids were obtained by reaction of the ethoxycarbonyl radical with methyl-substituted pyridines. A mechanism is proposed for the carboxylation reaction.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00523968
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  • 7
    Electronic Resource
    Electronic Resource
    Homolytic ethoxycarbonylation of aminopyridines (1988)
    Springer
    Chemistry of heterocyclic compounds 24 (1988), S. 885-886 
    Details
    ISSN: 1573-8353
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Pyridinecarboxylic acid ethyl esters are formed in the reaction of ethoxycarbonyl radicals with aminopyridines.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00479343
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  • 8
    Electronic Resource
    Electronic Resource
    Homolytic oxoalkylation of furan, α-methylfuran, and thiophene (1981)
    Springer
    Russian chemical bulletin 30 (1981), S. 1902-1907 
    Details
    ISSN: 1573-9171
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Conclusions 1. Homolytic substitution in the heteroaromatic ring of furan,α-methylfuran, and thiophene by CH3COCH2 and CH3 COCHCOCH3 radicals generated from acetone and acetylacetone using Mn(III) acetate (a one-electron oxidizing agent) proceeds regiospecifically at theα-carbon atom of the ring and leads to 2-furyl- and 2-thienyl ketones. 2. Acetoxylation and C-C or C-O dehydrodimerization occurs in the oxidation of 2-furyl- and 2-thienyl ketones by Mn(III) acetate. The reaction pathway depends on the concentration of Mn(OAc)3.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00963420
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  • 9
    Electronic Resource
    Electronic Resource
    Kinetics of the oxidative addition of acetone to aromatic compounds under the action of Mn(III) acetate (1982)
    Springer
    Russian chemical bulletin 31 (1982), S. 1760-1765 
    Details
    ISSN: 1573-9171
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Conclusions Kinetic data indicate that the principal path followed in the oxidative addition of acetone to aromatic compounds (ArH) under the action of Mn(III) acetate in AcOH solution to be the formation of a [CH2=C(CH3)-OMnIII·ArH] complex, which breaks down with rupture of the MnIII-O bond and subsequent addition of the acetonyl radical to the coordinated ArH (limiting step); this is, in turn, followed by rapid one-electron oxidation of the intermediate adduct radical by the Mn(III) ion, and formation of the final product.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00952371
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  • 10
    Electronic Resource
    Electronic Resource
    The homolytic oxoalkylation of methylpyridines by the action of Mn(III) acetate (1985)
    Springer
    Russian chemical bulletin 34 (1985), S. 646-648 
    Details
    ISSN: 1573-9171
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Conclusions A method was developed for the introduction of a 4-oxoalkyl substituent into the pyridine ring by the reaction of protonated methylpyridines with acetone and 1-alkenes by the action of Mn(III) acetate.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00947745
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