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  • 1
    Publication Date: 2008-09-27
    Description: Variable lymphocyte receptors (VLRs) rather than antibodies play the primary role in recognition of antigens in the adaptive immune system of jawless vertebrates. Combinatorial assembly of leucine-rich repeat (LRR) gene segments achieves the required repertoire for antigen recognition. We have determined a crystal structure for a VLR-antigen complex, VLR RBC36 in complex with the H-antigen trisaccharide from human blood type O erythrocytes, at 1.67 angstrom resolution. RBC36 binds the H-trisaccharide on the concave surface of the LRR modules of the solenoid structure where three key hydrophilic residues, multiple van der Waals interactions, and the highly variable insert of the carboxyl-terminal LRR module determine antigen recognition and specificity. The concave surface assembled from the most highly variable regions of the LRRs, along with diversity in the sequence and length of the highly variable insert, can account for the recognition of diverse antigens by VLRs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2581502/" 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/PMC2581502/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Han, Byung Woo -- Herrin, Brantley R -- Cooper, Max D -- Wilson, Ian A -- AI072435/AI/NIAID NIH HHS/ -- AI42266/AI/NIAID NIH HHS/ -- R37 AI042266/AI/NIAID NIH HHS/ -- R37 AI042266-11/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2008 Sep 26;321(5897):1834-7. doi: 10.1126/science.1162484.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, Scripps Research Institute, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18818359" target="_blank"〉PubMed〈/a〉
    Keywords: ABO Blood-Group System/chemistry/*immunology/metabolism ; Amino Acid Motifs ; Amino Acid Sequence ; Animals ; Binding Sites ; Crystallography, X-Ray ; Humans ; Hydrogen Bonding ; Hydrophobic and Hydrophilic Interactions ; Lampreys/*immunology ; Lymphocytes/*immunology ; Models, Molecular ; Molecular Sequence Data ; Protein Conformation ; Protein Structure, Secondary ; Receptors, Antigen/*chemistry/*immunology/metabolism ; Trisaccharides/chemistry/*immunology/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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  • 2
    Publication Date: 2015-05-16
    Description: PIWI-interacting RNAs (piRNAs) protect the animal germ line by silencing transposons. Primary piRNAs, generated from transcripts of genomic transposon "junkyards" (piRNA clusters), are amplified by the "ping-pong" pathway, yielding secondary piRNAs. We report that secondary piRNAs, bound to the PIWI protein Ago3, can initiate primary piRNA production from cleaved transposon RNAs. The first ~26 nucleotides (nt) of each cleaved RNA becomes a secondary piRNA, but the subsequent ~26 nt become the first in a series of phased primary piRNAs that bind Piwi, allowing piRNAs to spread beyond the site of RNA cleavage. The ping-pong pathway increases only the abundance of piRNAs, whereas production of phased primary piRNAs from cleaved transposon RNAs adds sequence diversity to the piRNA pool, allowing adaptation to changes in transposon sequence.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4545291/" 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/PMC4545291/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Han, Bo W -- Wang, Wei -- Li, Chengjian -- Weng, Zhiping -- Zamore, Phillip D -- GM62862/GM/NIGMS NIH HHS/ -- GM65236/GM/NIGMS NIH HHS/ -- HG007000/HG/NHGRI NIH HHS/ -- R01 GM065236/GM/NIGMS NIH HHS/ -- R37 GM062862/GM/NIGMS NIH HHS/ -- U41 HG007000/HG/NHGRI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 May 15;348(6236):817-21. doi: 10.1126/science.aaa1264.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉RNA Therapeutics Institute, Howard Hughes Medical Institute, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA 01605, USA. Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA 01605, USA. ; RNA Therapeutics Institute, Howard Hughes Medical Institute, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA 01605, USA. Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA 01605, USA. Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA 01605, USA. ; Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA 01605, USA. Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA 01605, USA. zhiping.weng@umassmed.edu phillip.zamore@umassmed.edu. ; RNA Therapeutics Institute, Howard Hughes Medical Institute, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA 01605, USA. Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA 01605, USA. zhiping.weng@umassmed.edu phillip.zamore@umassmed.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25977554" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Argonaute Proteins/genetics/*metabolism ; Drosophila Proteins/genetics/*metabolism ; Drosophila melanogaster/genetics/*metabolism ; Endoribonucleases/genetics/*metabolism ; Female ; Germ Cells/metabolism ; Male ; Metabolic Networks and Pathways ; Mice ; Ovary/metabolism ; Peptide Initiation Factors/genetics/*metabolism ; *RNA Cleavage ; RNA, Guide/*metabolism ; RNA, Small Interfering/biosynthesis/*metabolism ; *Retroelements ; Testis/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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  • 3
    Publication Date: 2018-08-31
    Description: This research evaluates the nutrient management system of Nutrient Expert (NE) in winter wheat grain yield production and greenhouse gas (GHG) emission in the Hebei Plain. Field experiments were conducted to check the yield effects, nutrient use efficiency (NUE) and GHG under NE (nutrient management based on Nutrient Expert recommendation) and FP (nutrient management based on farmers’ practices). The results showed that NE significantly reduced N fertilizer input while maintain higher yield and nutrient use efficiency than FP. The total N 2 O emission and GHG emissions for NE were about 0.69 kg N ha −1 and 1686 kg CO 2 eq ha −1 respectively, significantly lower than for FP (p 〈 0.05), which was about 1.85 kg N ha −1 and 3329 kg CO 2 eq ha −1 , respectively. The NE system showed great potential to be easily used in smallholder farmers in the Hebei Plain.
    Print ISSN: 1755-1307
    Electronic ISSN: 1755-1315
    Topics: Geography , Geosciences , Physics
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  • 4
    Publication Date: 2015-09-30
    Description: Small silencing RNAs, including microRNAs, endogenous small interfering RNAs (endo-siRNAs) and Piwi-interacting RNAs (piRNAs), have been shown to play important roles in fine-tuning gene expression, defending virus and controlling transposons. Loss of small silencing RNAs or components in their pathways often leads to severe developmental defects, including lethality and sterility. Recently, non-templated addition of nucleotides to the 3' end, namely tailing, was found to associate with the processing and stability of small silencing RNAs. Next Generation Sequencing has made it possible to detect such modifications at nucleotide resolution in an unprecedented throughput. Unfortunately, detecting such events from millions of short reads confounded by sequencing errors and RNA editing is still a tricky problem. Here, we developed a computational framework, Tailor, driven by an efficient and accurate aligner specifically designed for capturing the tailing events directly from the alignments without extensive post-processing. The performance of Tailor was fully tested and compared favorably with other general-purpose aligners using both simulated and real datasets for tailing analysis. Moreover, to show the broad utility of Tailor, we used Tailor to reanalyze published datasets and revealed novel findings worth further experimental validation. The source code and the executable binaries are freely available at https://github.com/jhhung/Tailor .
    Keywords: RNA characterisation and manipulation, Computational Methods, Massively Parallel (Deep) Sequencing
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 5
    Publication Date: 2015-02-13
    Description: Motivation: PIWI-interacting RNAs (piRNAs), 23–36 nt small silencing RNAs, repress transposon expression in the metazoan germ line, thereby protecting the genome. Although high-throughput sequencing has made it possible to examine the genome and transcriptome at unprecedented resolution, extracting useful information from gigabytes of sequencing data still requires substantial computational skills. Additionally, researchers may analyze and interpret the same data differently, generating results that are difficult to reconcile. To address these issues, we developed a coordinated set of pipelines, ‘piPipes’, to analyze piRNA and transposon-derived RNAs from a variety of high-throughput sequencing libraries, including small RNA, RNA, degradome or 7-methyl guanosine cap analysis of gene expression (CAGE), chromatin immunoprecipitation (ChIP) and genomic DNA-seq. piPipes can also produce figures and tables suitable for publication. By facilitating data analysis, piPipes provides an opportunity to standardize computational methods in the piRNA field. Supplementary information: Supplementary information, including flowcharts and example figures for each pipeline, are available at Bioinformatics online. Availability and implementation: piPipes is implemented in Bash, C++, Python, Perl and R. piPipes is free, open-source software distributed under the GPLv3 license and is available at http://bowhan.github.io/piPipes/ . Contact : Phillip.Zamore@umassmed.edu or Zhiping.Weng@umassmed.edu Supplementary information: Supplementary data are available at Bioinformatics online.
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
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  • 6
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    Smedley, D., Haider, S., Durinck, S., Pandini, L., Provero, P., Allen, J., Arnaiz, O., Awedh, M. H., Baldock, R., Barbiera, G., Bardou, P., Beck, T., Blake, A., Bonierbale, M., Brookes, A. J., Bucci, G., Buetti, I., Burge, S., Cabau, C., Carlson, J. W., Chelala, C., Chrysostomou, C., Cittaro, D., Collin, O., Cordova, R., Cutts, R. J., Dassi, E., Genova, A. D., Djari, A., Esposito, A., Estrella, H., Eyras, E., Fernandez-Banet, J., Forbes, S., Free, R. C., Fujisawa, T., Gadaleta, E., Garcia-Manteiga, J. M., Goodstein, D., Gray, K., Guerra-Assuncao, J. A., Haggarty, B., Han, D.-J., Han, B. W., Harris, T., Harshbarger, J., Hastings, R. K., Hayes, R. D., Hoede, C., Hu, S., Hu, Z.-L., Hutchins, L., Kan, Z., Kawaji, H., Keliet, A., Kerhornou, A., Kim, S., Kinsella, R., Klopp, C., Kong, L., Lawson, D., Lazarevic, D., Lee, J.-H., Letellier, T., Li, C.-Y., Lio, P., Liu, C.-J., Luo, J., Maass, A., Mariette, J., Maurel, T., Merella, S., Mohamed, A. M., Moreews, F., Nabihoudine, I., Ndegwa, N., Noirot, C., Perez-Llamas, C., Primig, M., Quattrone, A., Quesneville, H., Rambaldi, D., Reecy, J., Riba, M., Rosanoff, S., Saddiq, A. A., Salas, E., Sallou, O., Shepherd, R., Simon, R., Sperling, L., Spooner, W., Staines, D. M., Steinbach, D., Stone, K., Stupka, E., Teague, J. W., Dayem Ullah, A. Z., Wang, J., Ware, D., Wong-Erasmus, M., Youens-Clark, K., Zadissa, A., Zhang, S.-J., Kasprzyk, A.
    Oxford University Press
    Publication Date: 2015-07-02
    Description: The BioMart Community Portal ( www.biomart.org ) is a community-driven effort to provide a unified interface to biomedical databases that are distributed worldwide. The portal provides access to numerous database projects supported by 30 scientific organizations. It includes over 800 different biological datasets spanning genomics, proteomics, model organisms, cancer data, ontology information and more. All resources available through the portal are independently administered and funded by their host organizations. The BioMart data federation technology provides a unified interface to all the available data. The latest version of the portal comes with many new databases that have been created by our ever-growing community. It also comes with better support and extensibility for data analysis and visualization tools. A new addition to our toolbox, the enrichment analysis tool is now accessible through graphical and web service interface. The BioMart community portal averages over one million requests per day. Building on this level of service and the wealth of information that has become available, the BioMart Community Portal has introduced a new, more scalable and cheaper alternative to the large data stores maintained by specialized organizations.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 7
    Publication Date: 2014-11-21
    Description: Previous reports have described several associations of PR, QRS, QT and heart rate with genomic variations by genome-wide association studies (GWASs). In the present study, we examined the association of ~2.5 million SNPs from 2994 Japanese healthy volunteers obtained from the JPDSC database with electrocardiographic parameters. We confirmed associations of PR interval, QRS duration and QT interval in individuals of Japanese ancestry with 11 of the 45 SNPs (6 of 20 for QT, 5 of 19 for PR and 0 of 6 for QRS) observed among individuals of European, African and Asian (Indian and Korean) ancestries. Those results indicate that many of the electrocardiographic associations with genes are shared by different ethnic groups including Japanese. Possible novel associations found in this study were validated by Korean data. As a result, we identified a novel association of SNP rs4952632[G] (maps near SLC8A1 , sodium–calcium exchanger) ( P = 7.595 x 10 –6 ) with PR interval in Japanese individuals, and replication testing among Koreans confirmed the association of the same SNP with prolonged PR interval. Meta-analysis of the Japanese and Korean datasets demonstrated highly significant associations of SNP rs4952632[G] with a 2.325-ms (95% CI, 1.693–2.957 ms) longer PR interval per minor allele copy ( P = 5.598 x 10 –13 ). Cell-type-specific SLC8A1 knockout mice have demonstrated a regulatory role of sodium–calcium exchanger in automaticity and conduction in sinoatrial node, atrium and atrioventricular node. Our findings support a functional role of sodium–calcium exchanger in human atrial and atrioventricular nodal conduction as suggested by genetically modified mouse models.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
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  • 8
    Publication Date: 2014-05-23
    Description: Long non-coding RNAs (lncRNAs) have been recently found to be pervasively transcribed in human genome and link to diverse human diseases. However, the expression patterns and regulatory roles of lncRNAs in hematopoietic malignancies have not been reported. Here, we carried out a genome-wide lncRNA expression study in MLL -rearranged acute lymphoblastic leukemia ( MLL -r ALL) and established lncRNA/messenger RNA coexpression networks to gain insight into the biological roles of these dysregulated lncRNAs. We detected a number of lncRNAs that were differentially expressed in MLL -r ALL samples compared with MLL -r wild-type and identified unique lncRNA expression patterns between MLL -r subtypes with different translocations as well as between infant MLL -r ALL with other MLL -r ALL patients, suggesting that they might be served as novel biomarkers for the disease. Importantly, several lncRNAs that correspond with membrane protein genes, including a lysosome-associated membrane protein, were identified. No such link between the membrane proteins and MLL -r leukemia has been reported previously. Impressively, the functional analysis showed that several lncRNAs corresponded to the expression of MLL-fusion protein target genes, including HOXA9 , MEIS1 , etc., while some other associated with histone-related functions or membrane proteins. Further experiments characterize the effect of some lncRNAs on MLL -r leukemia apoptosis and proliferation as the function of the coexpressed HOXA gene cluster. Finally, a set of lncRNAs epigenetically regulated by H3K79 methylation were also discovered. These findings may provide novel insights into the mechanisms of lncRNAs involved in the initiation of MLL -r leukemia. This is the first study linking lncRNAs to leukemogenesis.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
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  • 9
    Publication Date: 2013-12-22
    Description: As to the impeller blood pump, the high speed of the impeller, the local high shear force of the flow field and the flow dead region are the main reasons for blood damage. The screw centrifugal pump can effectively alleviate the problems of the high speed and the high shear stress for the impeller. The softness and non-destructiveness during the transfer process can effectively reduce the extent of the damage. By using CFD software, the characteristics of internal flow are analyzed in the screw centrifugal pump by exploring the distribution rules of the velocity, pressure and shear deformation rate of the blood when it flows through the impeller and the destructive effects of spiral blades on blood. The results show that: the design of magnetic levitation solves the sealing problems; the design of regurgitation holes solves the problem of the flow dead zone; the magnetic levitated microcirculation screw centrifugal pump can effectively avoid the vortex, turbulence and high shear...
    Print ISSN: 1757-8981
    Electronic ISSN: 1757-899X
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
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  • 10
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