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  • 1
    Publikationsdatum: 2013-02-13
    Beschreibung: Capsid-like particles consisting of a hepatitis B core (HBc) protein have been studied for their potential as carriers for drug delivery systems (DDS). The hollow HBc particle, which is formed by the self-assembly of core proteins comprising 183 aa residues, has the ability to bind to various cells non-specifically via the action of an arginine-rich domain. In this study, we developed an engineered HBc particle that specifically recognizes and targets human epidermal growth factor receptor-related 2 (HER2)-expressing breast cancer cells. To despoil the non-specific binding property of an HBc particle, we genetically deleted the C-terminal 150–183 aa part of the core protein that encodes the arginine-rich domain (HBc). Then, we genetically inserted a Z HER2 affibody molecule into the 78–81 aa position of the core protein to confer the ability of target-cell-specific recognition. The constructed Z HER2 -displaying HBc (Z HER2 -HBc) particle specifically recognized HER2-expressing SKBR3 and MCF-7 breast cancer cells. In addition, the Z HER2 -HBc particle exhibited different binding amounts in accordance with the HER2 expression levels of cancer cells. These results show that the display of other types of affibody molecules on HBc particles would be an expandable strategy for targeting several kinds of cancer cells that would help enable a pinpoint DDS.
    Print ISSN: 0021-924X
    Digitale ISSN: 1756-2651
    Thema: Biologie , Chemie und Pharmazie
    Standort Signatur Erwartet Verfügbarkeit
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  • 2
    Publikationsdatum: 2012-09-08
    Beschreibung: Motivation: Unexpected drug activities derived from off-targets are usually undesired and harmful; however, they can occasionally be beneficial for different therapeutic indications. There are many uncharacterized drugs whose target proteins (including the primary target and off-targets) remain unknown. The identification of all potential drug targets has become an important issue in drug repositioning to reuse known drugs for new therapeutic indications. Results: We defined pharmacological similarity for all possible drugs using the US Food and Drug Administration's (FDA's) adverse event reporting system (AERS) and developed a new method to predict unknown drug–target interactions on a large scale from the integration of pharmacological similarity of drugs and genomic sequence similarity of target proteins in the framework of a pharmacogenomic approach. The proposed method was applicable to a large number of drugs and it was useful especially for predicting unknown drug–target interactions that could not be expected from drug chemical structures. We made a comprehensive prediction for potential off-targets of 1874 drugs with known targets and potential target profiles of 2519 drugs without known targets, which suggests many potential drug–target interactions that were not predicted by previous chemogenomic or pharmacogenomic approaches. Availability: Softwares are available upon request. Contact: yamanishi@bioreg.kyushu-u.ac.jp Supplementary Information: Datasets and all results are available at http://cbio.ensmp.fr/~yyamanishi/aers/ .
    Print ISSN: 1367-4803
    Digitale ISSN: 1460-2059
    Thema: Biologie , Informatik , Medizin
    Publiziert von Oxford University Press
    Standort Signatur Erwartet Verfügbarkeit
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  • 3
    Publikationsdatum: 2012-06-06
    Beschreibung: Sperm chromatin remodeling after oocyte entry is the essential step that initiates embryogenesis. This reaction involves the removal of sperm-specific basic proteins and chromatin assembly with histones. In mammals, three nucleoplasmin/nucleophosmin (NPM) family proteins–NPM1, NPM2 and NPM3–expressed in oocytes are presumed to cooperatively regulate sperm chromatin remodeling. We characterized the sperm chromatin decondensation and nucleosome assembly activities of three human NPM proteins. NPM1 and NPM2 mediated nucleosome assembly independently of other NPM proteins, whereas the function of NPM3 was largely dependent on formation of a complex with NPM1. Maximal sperm chromatin remodeling activity of NPM2 required the inhibition of its non-specific nucleic acid-binding activity by phosphorylation. Furthermore, the oligomer formation with NPM1 elicited NPM3 nucleosome assembly and sperm chromatin decondensation activity. NPM3 also suppressed the RNA-binding activity of NPM1, which enhanced the nucleoplasm–nucleolus shuttling of NPM1 in somatic cell nuclei. Our results proposed a novel mechanism whereby three NPM proteins cooperatively regulate chromatin disassembly and assembly in the early embryo and in somatic cells.
    Print ISSN: 0305-1048
    Digitale ISSN: 1362-4962
    Thema: Biologie
    Publiziert von Oxford University Press
    Standort Signatur Erwartet Verfügbarkeit
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  • 4
    Publikationsdatum: 2011-12-01
    Beschreibung: Author(s): M. Sato, S. Imai, N. Fujita, S. Nishimura, Y. Takao, Y. Sada, B. E. Hubbard, B. Ilic, and A. J. Sievers [Phys. Rev. Lett. 107, 234101] Published Wed Nov 30, 2011
    Schlagwort(e): Nonlinear Dynamics, Fluid Dynamics, Classical Optics, etc.
    Print ISSN: 0031-9007
    Digitale ISSN: 1079-7114
    Thema: Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 5
    Publikationsdatum: 2013-10-12
    Beschreibung: Sigma factor is a subunit of plastid-encoded RNA polymerase that regulates the transcription of plastid-encoded genes by recognizing a set of promoters. Sigma factors have increased in copy number and have diversified during the evolution of land plants, but details of this process remain unknown. Liverworts represent the basal group of embryophytes and are expected to retain the ancestral features of land plants. In liverwort ( Marchantia polymorpha L.), we isolated and characterized a T-DNA-tagged mutant ( Mpsig1 ) of sigma factor 1 ( MpSIG1 ). The mutant did not show any visible phenotypes, implying that MpSIG1 function is redundant with that of other sigma factors. However, quantitative reverse-transcription polymerase chain reaction and RNA gel blot analysis revealed that genes related to photosynthesis were downregulated, resulting in the minor reduction of some protein complexes. The transcript levels of genes clustered in the petL , psaA , psbB , psbK , and psbE operons of liverwort were lower than those in the wild type, a result similar to that in the SIG1 defective mutant in rice ( Oryza sativa ). Overexpression analysis revealed primitive functional divergence between the SIG1 and SIG2 proteins in bryophytes, whereas these proteins still retain functional redundancy. We also discovered that the predominant sigma factor for ndhF mRNA expression has been diversified in liverwort, Arabidopsis ( Arabidopsis thaliana ), and rice. Our study shows the ancestral function of SIG1 and the process of functional partitioning (subfunctionalization) of sigma factors during the evolution of land plants.
    Digitale ISSN: 1759-6653
    Thema: Biologie
    Publiziert von Oxford University Press
    Standort Signatur Erwartet Verfügbarkeit
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  • 6
    Publikationsdatum: 2014-02-11
    Beschreibung: Telomeric DNAs consist of tandem repeats of G-clusters such as TTAGGG and TG 1-3 , which are the human and yeast repeat sequences, respectively. In the yeast Saccharomyces cerevisiae , the telomeric repeats are non-nucleosomal, whereas in humans, they are organized in tightly packaged nucleosomes. However, previous in vitro studies revealed that the binding affinities of human and yeast telomeric repeat sequences to histone octamers in vitro were similar, which is apparently inconsistent with the differences in the human and yeast telomeric chromatin structures. To further investigate the relationship between telomeric sequences and chromatin structure, we examined the effect of telomeric repeats on the formation of positioned nucleosomes in vivo by indirect end-label mapping, primer extension mapping and nucleosome repeat analyses, using a defined minichromosome in yeast cells. We found that the human and yeast telomeric repeat sequences both disfavour nucleosome assembly and alter nucleosome positioning in the yeast minichromosome. We further demonstrated that the G-clusters in the telomeric repeats are required for the nucleosome-disfavouring properties. Thus, our results suggest that this inherent structural feature of the telomeric repeat sequences is involved in the functional dynamics of the telomeric chromatin structure.
    Print ISSN: 0305-1048
    Digitale ISSN: 1362-4962
    Thema: Biologie
    Publiziert von Oxford University Press
    Standort Signatur Erwartet Verfügbarkeit
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  • 7
    Publikationsdatum: 2014-03-23
    Beschreibung: Chlorophylls (Chls) play pivotal roles in energy absorption and transduction and also in charge separation in reaction centers in all photosynthetic organisms. In Chl biosynthesis steps, only a step for the enzymatic reduction of protochlorophyllide (Pchlide) to chlorophyllide (Chlide) is mediated by both nuclear- and chloroplast-encoded genes in land plants. Many plants encode the genes for light-dependent Pchlide reductase (LPOR) and light-independent Pchlide reductase (DPOR) in the nucleus and chloroplast genome, respectively. During the diversification of land plants, the reduction step of Pchlide to Chlide has become solely dependent on LPOR, and the genes for DPOR have been lost from chloroplast genome. It remains unclear why DPOR persists in some land plants, how they were eliminated from chloroplast genomes during the diversification of land plants, and under what environmental conditions DPOR was required. We demonstrate that DPOR is functional in liverwort ( Marchantia polymorpha L.) and plays an important role in Chl biosynthesis. Having established a plastid transformation system in liverwort, we disrupted chl B, which encodes a subunit of DPOR in the M . polymorpha chloroplast genome. Morphological and Chl content analysis of a chl B mutant grown under different photoperiods revealed that DPOR is particularly required for Chl biosynthesis under short-day conditions. Our findings suggest that an environmental condition in the form of photoperiod is an important factor that determines the loss or retention of chloroplast-encoded genes mediating Pchlide reduction to Chlide.
    Digitale ISSN: 1759-6653
    Thema: Biologie
    Publiziert von Oxford University Press
    Standort Signatur Erwartet Verfügbarkeit
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  • 8
    Publikationsdatum: 2011-09-23
    Beschreibung: Author(s): S. Haravifard, K. Fritsch, T. Asano, J. P. Clancy, Z. Yamani, G. Ehlers, T. Nishimura, Y. Inagaki, T. Kawae, I. Swainson, and B. D. Gaulin CuMoO 4 is a triclinic quantum magnet based on S =1/2 moments at the Cu 2+ site. It has recently attracted interest due to the remarkable changes in its chromic and volumetric properties at high temperatures and in its magnetic properties at low temperatures. This material exhibits a first-order struct... [Phys. Rev. B 84, 094436] Published Thu Sep 22, 2011
    Schlagwort(e): Magnetism
    Print ISSN: 1098-0121
    Digitale ISSN: 1095-3795
    Thema: Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 9
    Publikationsdatum: 2014-11-12
    Beschreibung: Heterochromatin protein 1 (HP1) is an evolutionarily conserved chromosomal protein that binds to lysine 9-methylated histone H3 (H3K9me), a hallmark of heterochromatin. Although HP1 phosphorylation has been described in several organisms, the biological implications of this modification remain largely elusive. Here we show that HP1's phosphorylation has a critical effect on its nucleosome binding properties. By in vitro phosphorylation assays and conventional chromatography, we demonstrated that casein kinase II (CK2) is the kinase primarily responsible for phosphorylating the N-terminus of human HP1α. Pull-down assays using in vitro -reconstituted nucleosomes showed that unmodified HP1α bound H3K9-methylated and H3K9-unmethylated nucleosomes with comparable affinity, whereas CK2-phosphorylated HP1α showed a high specificity for H3K9me3-modified nucleosomes. Electrophoretic mobility shift assays showed that CK2-mediated phosphorylation diminished HP1α's intrinsic DNA binding, which contributed to its H3K9me-independent nucleosome binding. CK2-mediated phosphorylation had a similar effect on the nucleosome-binding specificity of fly HP1a and S. pombe Swi6. These results suggested that HP1 phosphorylation has an evolutionarily conserved role in HP1's recognition of H3K9me-marked nucleosomes.
    Schlagwort(e): Protein-protein interaction, Recombinant DNA expression, Chromatin and Epigenetics
    Print ISSN: 0305-1048
    Digitale ISSN: 1362-4962
    Thema: Biologie
    Publiziert von Oxford University Press
    Standort Signatur Erwartet Verfügbarkeit
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  • 10
    Publikationsdatum: 2014-10-18
    Beschreibung: The primitive red alga Cyanidioschyzon merolae inhabits acidic hot springs and shows robust resistance to heat shock treatments up to 63 °C. Microarray analysis was performed to identify the key genes underlying the high temperature tolerance of this organism. Among the upregulated genes that were identified, we focused on two small heat shock proteins (sHSPs) that belong to a unique class of HSP families. These two genes are located side by side in an inverted repeat orientation on the same chromosome and share a promoter. These two genes were simultaneously and rapidly upregulated in response to heat shock treatment (〉1,000-fold more than the control). Interestingly, upregulation appeared to be triggered not by a difference in temperatures, but rather by the absolute temperature. Similar sHSP structural genes have been reported in the green alga Chlamydomonas reinhardtii , but the threshold temperature for the expression of these sHSP-encoding genes in Ch. reinhardtii was different from the threshold temperature for the expression of the sHSP genes from Cy. merolae . These results indicate the possible importance of an absolute temperature sensing system in the evolution and tolerance of high-temperature conditions among unicellular microalgae.
    Digitale ISSN: 1759-6653
    Thema: Biologie
    Publiziert von Oxford University Press
    Standort Signatur Erwartet Verfügbarkeit
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