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  • Articles  (29)
  • 2015-2019  (29)
  • Chemistry and Pharmacology  (29)
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  • 1
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    Cardioprotective effects and pharmacokinetic properties of a controlled release formulation of a novel hydrogen sulfide donor in rats with acute myocardial infarction (2015)
    Portland Press
    Details
    Publication Date: 2015-05-01
    Description: Objective : We previously reported that S-propargyl-cysteine (SPRC) exerts cardioprotective effects by elevating H 2 S levels via the CSE/H 2 S pathway. In this study, we investigated the cardioprotective effects and pharmacokinetic properties of a controlled release formulation of S-propargyl-cysteine (CR-SPRC) in an in vivo ratmodel of myocardial infarction (MI). Methods: Rats were randomly assigned to seven groups that were pre-treated with CR-SPRC daily for 7 days prior to ligation of the left anterior descending coronary artery to induce MI. Cardiac function and infarct size were determined after MI, and we examined the activity of antioxidant enzymes, expression of anti-inflammation proteins, and hydrogen sulfide levels. Mixed-mode, reversed-phase and cation-exchange HPLC–MS/MS were used to compare the pharmacokinetic properties of CR-SPRC and SPRC. Results :CR-SPRC significantly reduced infarct size and CK and LDH leakage, and it preserved cardiac function during MI. CR-SPRC displayed antioxidant properties, preserving GSH, CAT and SOD levels while reducing MDA levels. Moreover, CR-SPRC significantly reduced the protein levels of inflammatory biomarkers (phospho-NF-κB p65/NF-κB p65, TNF-α) and increased cystathionine-γ-lyase (CSE) and Iκ-Bα protein levels. CR-SPRC had better pharmacokinetic properties than SPRC, with a reduced concentration peak (C max ), prolonged time to reach peak concentration (T max ), prolonged mean residence time (MRT inf ) and increased AUC 0- t . Conclusions : CR-SPRC showed protective effects against MI via the CSE/H 2 S pathway and demonstrated better cardioprotective effects than SPRC by prolonging the release of endogenous H 2 S.
    Print ISSN: 0144-8463
    Electronic ISSN: 1573-4935
    Topics: Biology , Chemistry and Pharmacology
    Published by Portland Press
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  • 2
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    Mobile genes in the human microbiome are structured from global to individual scales (2016)
    Springer Nature
    In: Nature
    Details
    Publication Date: 2016-07-21
    Description: Mobile genes in the human microbiome are structured from global to individual scales Nature 535, 7612 (2016). doi:10.1038/nature18927 Authors: I. L. Brito, S. Yilmaz, K. Huang, L. Xu, S. D. Jupiter, A. P. Jenkins, W. Naisilisili, M. Tamminen, C. S. Smillie, J. R. Wortman, B. W. Birren, R. J. Xavier, P. C. Blainey, A. K. Singh, D. Gevers & E. J. Alm Recent work has underscored the importance of the microbiome in human health, and has largely attributed differences in phenotype to differences in the species present among individuals. However, mobile genes can confer profoundly different phenotypes on different strains of the same species. Little is known about the function and distribution of mobile genes in the human microbiome, and in particular whether the gene pool is globally homogenous or constrained by human population structure. Here, we investigate this question by comparing the mobile genes found in the microbiomes of 81 metropolitan North Americans with those of 172 agrarian Fiji islanders using a combination of single-cell genomics and metagenomics. We find large differences in mobile gene content between the Fijian and North American microbiomes, with functional variation that mirrors known dietary differences such as the excess of plant-based starch degradation genes found in Fijian individuals. Notably, we also observed differences between the mobile gene pools of neighbouring Fijian villages, even though microbiome composition across villages is similar. Finally, we observe high rates of recombination leading to individual-specific mobile elements, suggesting that the abundance of some genes may reflect environmental selection rather than dispersal limitation. Together, these data support the hypothesis that human activities and behaviours provide selective pressures that shape mobile gene pools, and that acquisition of mobile genes is important for colonizing specific human populations.
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Springer Nature
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  • 3
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    Diagnostic model of saliva peptide finger print analysis of oral squamous cell carcinoma patients using weak cation exchange magnetic beads (2015)
    Portland Press
    Details
    Publication Date: 2015-05-13
    Description: Saliva diagnostics utilizing nanotechnology and molecular technologies to detect oral squamous cell carcinoma (OSCC) has become an attractive field of study. However, no specific methods have been established. To refine the diagnostic power of saliva peptide fingerprints for the early detection of OSCC, we screened the expression spectrum of salivary peptides in 40 T1 stage OSCC patients (and healthy controls) using mass spectrometry matrix-assisted laser-desorption ionization time-of-flight MS (MALDI-TOF-MS) combined with magnetic beads. Fifty proteins showed significantly different expression levels in the OSCC samples (P 〈 0.05). Potential biomarkers were also predicted. The novel diagnostic proteomic model with m/z peaks of 1285.6 Da and 1432.2 Da is of certain value for early diagnosis of OSCC.
    Print ISSN: 0144-8463
    Electronic ISSN: 1573-4935
    Topics: Biology , Chemistry and Pharmacology
    Published by Portland Press
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  • 4
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    Teosinte ligule allele narrows plant architecture and enhances high-density maize yields (2019)
    American Association for the Advancement of Science (AAAS)
    In: Science
    Details
    Publication Date: 2019
    Description: 〈p〉Increased planting densities have boosted maize yields. Upright plant architecture facilitates dense planting. Here, we cloned 〈i〉UPA1〈/i〉 (〈i〉Upright Plant Architecture1〈/i〉) and 〈i〉UPA2〈/i〉, two quantitative trait loci conferring upright plant architecture. 〈i〉UPA2〈/i〉 is controlled by a two-base sequence polymorphism regulating the expression of a B3-domain transcription factor (〈i〉ZmRAVL1〈/i〉) located 9.5 kilobases downstream. 〈i〉UPA2〈/i〉 exhibits differential binding by DRL1 (DROOPING LEAF1), and DRL1 physically interacts with LG1 (LIGULELESS1) and represses LG1 activation of 〈i〉ZmRAVL1〈/i〉. 〈i〉ZmRAVL1〈/i〉 regulates 〈i〉brd1〈/i〉 (〈i〉brassinosteroid C-6 oxidase1〈/i〉), which underlies 〈i〉UPA1〈/i〉, altering endogenous brassinosteroid content and leaf angle. The 〈i〉UPA2〈/i〉 allele that reduces leaf angle originated from teosinte, the wild ancestor of maize, and has been lost during maize domestication. Introgressing the wild 〈i〉UPA2〈/i〉 allele into modern hybrids and editing 〈i〉ZmRAVL1〈/i〉 enhance high-density maize yields.〈/p〉
    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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  • 5
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    Giant piezoelectricity of Sm-doped Pb(Mg1/3Nb2/3)O3-PbTiO3 single crystals (2019)
    American Association for the Advancement of Science (AAAS)
    In: Science
    Details
    Publication Date: 2019
    Description: 〈p〉High-performance piezoelectrics benefit transducers and sensors in a variety of electromechanical applications. The materials with the highest piezoelectric charge coefficients (〈i〉d〈/i〉〈sub〉33〈/sub〉) are relaxor-PbTiO〈sub〉3〈/sub〉 crystals, which were discovered two decades ago. We successfully grew Sm-doped Pb(Mg〈sub〉1/3〈/sub〉Nb〈sub〉2/3〈/sub〉)O〈sub〉3〈/sub〉-PbTiO〈sub〉3〈/sub〉 (Sm-PMN-PT) single crystals with even higher 〈i〉d〈/i〉〈sub〉33〈/sub〉 values ranging from 3400 to 4100 picocoulombs per newton, with variation below 20% over the as-grown crystal boule, exhibiting good property uniformity. We characterized the Sm-PMN-PT on the atomic scale with scanning transmission electron microscopy and made first-principles calculations to determine that the giant piezoelectric properties arise from the enhanced local structural heterogeneity introduced by Sm〈sup〉3+〈/sup〉 dopants. Rare-earth doping is thus identified as a general strategy for introducing local structural heterogeneity in order to enhance the piezoelectricity of relaxor ferroelectric crystals.〈/p〉
    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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  • 6
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    A Eu3+-Eu2+ ion redox shuttle imparts operational durability to Pb-I perovskite solar cells (2019)
    American Association for the Advancement of Science (AAAS)
    In: Science
    Details
    Publication Date: 2019
    Description: 〈p〉The components with soft nature in the metal halide perovskite absorber usually generate lead (Pb)〈sup〉0〈/sup〉 and iodine (I)〈sup〉0〈/sup〉 defects during device fabrication and operation. These defects serve as not only recombination centers to deteriorate device efficiency but also degradation initiators to hamper device lifetimes. We show that the europium ion pair Eu〈sup〉3+〈/sup〉-Eu〈sup〉2+〈/sup〉 acts as the "redox shuttle" that selectively oxidized Pb〈sup〉0〈/sup〉 and reduced I〈sup〉0〈/sup〉 defects simultaneously in a cyclical transition. The resultant device achieves a power conversion efficiency (PCE) of 21.52% (certified 20.52%) with substantially improved long-term durability. The devices retained 92% and 89% of the peak PCE under 1-sun continuous illumination or heating at 85°C for 1500 hours and 91% of the original stable PCE after maximum power point tracking for 500 hours, respectively.〈/p〉
    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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    Pulmonary neuroendocrine cells amplify allergic asthma responses (2018)
    American Association for the Advancement of Science (AAAS)
    In: Science
    Details
    Publication Date: 2018-06-08
    Description: Pulmonary neuroendocrine cells (PNECs) are rare airway epithelial cells whose function is poorly understood. Here we show that Ascl1 -mutant mice that have no PNECs exhibit severely blunted mucosal type 2 response in models of allergic asthma. PNECs reside in close proximity to group 2 innate lymphoid cells (ILC2s) near airway branch points. PNECs act through calcitonin gene-related peptide (CGRP) to stimulate ILC2s and elicit downstream immune responses. In addition, PNECs act through the neurotransmitter -aminobutyric acid (GABA) to induce goblet cell hyperplasia. The instillation of a mixture of CGRP and GABA in Ascl1 -mutant airways restores both immune and goblet cell responses. In accordance, lungs from human asthmatics show increased PNECs. These findings demonstrate that the PNEC-ILC2 neuroimmunological modules function at airway branch points to amplify allergic asthma responses.
    Keywords: Immunology, Medicine, Diseases, Online Only
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 8
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    Imaging the halogen bond in self-assembled halogenbenzenes on silver (2017)
    American Association for the Advancement of Science (AAAS)
    In: Science
    Details
    Publication Date: 2017-10-13
    Description: Halogens are among the most electronegative elements, and the variations in size and polarizability of halogens require different descriptions of the intermolecular bonds they form. Here we use the inelastic tunneling probe (itProbe) to acquire real-space imaging of intermolecular-bonding structures in the two-dimensional self-assembly of halogenbenzene molecules on a metal surface. Direct visualization is obtained for the intermolecular attraction and the "windmill" pattern of bonding among the fully halogenated molecules. Our results provide a hitherto missing understanding of the nature of the halogen bond.
    Keywords: Chemistry
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , 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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    Molecular basis for 5-carboxycytosine recognition by RNA polymerase II elongation complex (2015)
    Nature Publishing Group (NPG)
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    Publication Date: 2015-07-01
    Description: DNA methylation at selective cytosine residues (5-methylcytosine (5mC)) and their removal by TET-mediated DNA demethylation are critical for setting up pluripotent states in early embryonic development. TET enzymes successively convert 5mC to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC), with 5fC and 5caC subject to removal by thymine DNA glycosylase (TDG) in conjunction with base excision repair. Early reports indicate that 5fC and 5caC could be stably detected on enhancers, promoters and gene bodies, with distinct effects on gene expression, but the mechanisms have remained elusive. Here we determined the X-ray crystal structure of yeast elongating RNA polymerase II (Pol II) in complex with a DNA template containing oxidized 5mCs, revealing specific hydrogen bonds between the 5-carboxyl group of 5caC and the conserved epi-DNA recognition loop in the polymerase. This causes a positional shift for incoming nucleoside 5'-triphosphate (NTP), thus compromising nucleotide addition. To test the implication of this structural insight in vivo, we determined the global effect of increased 5fC/5caC levels on transcription, finding that such DNA modifications indeed retarded Pol II elongation on gene bodies. These results demonstrate the functional impact of oxidized 5mCs on gene expression and suggest a novel role for Pol II as a specific and direct epigenetic sensor during transcription elongation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4521995/" 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/PMC4521995/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Lanfeng -- Zhou, Yu -- Xu, Liang -- Xiao, Rui -- Lu, Xingyu -- Chen, Liang -- Chong, Jenny -- Li, Hairi -- He, Chuan -- Fu, Xiang-Dong -- Wang, Dong -- GM052872/GM/NIGMS NIH HHS/ -- GM102362/GM/NIGMS NIH HHS/ -- HG004659/HG/NHGRI NIH HHS/ -- HG006827/HG/NHGRI NIH HHS/ -- R01 GM052872/GM/NIGMS NIH HHS/ -- R01 GM102362/GM/NIGMS NIH HHS/ -- R01 HG004659/HG/NHGRI NIH HHS/ -- R01 HG006827/HG/NHGRI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2015 Jul 30;523(7562):621-5. doi: 10.1038/nature14482. Epub 2015 Jun 29.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Skaggs School of Pharmacy and Pharmaceutical Sciences, The University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA. ; Department of Cellular and Molecular Medicine, School of Medicine, The University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA. ; Department of Chemistry, Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, Howard Hughes Medical Institute, The University of Chicago, Chicago, Illinois 60637, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26123024" target="_blank"〉PubMed〈/a〉
    Keywords: Crystallography, X-Ray ; Cytosine/*analogs & derivatives/chemistry/metabolism ; DNA Methylation ; DNA Repair ; Epigenesis, Genetic ; Hydrogen Bonding ; Kinetics ; RNA Polymerase II/*chemistry/*metabolism ; Saccharomyces cerevisiae/*enzymology/genetics/metabolism ; Substrate Specificity ; Templates, Genetic ; Thymine DNA Glycosylase/metabolism ; *Transcription Elongation, Genetic
    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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  • 10
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    Corrigendum: NLRP10 is a NOD-like receptor essential to initiate adaptive immunity by dendritic cells (2015)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2015-11-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Eisenbarth, Stephanie C -- Williams, Adam -- Colegio, Oscar R -- Meng, Hailong -- Strowig, Till -- Rongvaux, Anthony -- Henao-Mejia, Jorge -- Thaiss, Christoph A -- Joly, Sophie -- Gonzalez, David G -- Xu, Lan -- Zenewicz, Lauren A -- Haberman, Ann M -- Elinav, Eran -- Kleinstein, Steven H -- Sutterwala, Fayyaz S -- Flavell, Richard A -- England -- Nature. 2016 Feb 25;530(7591):504. doi: 10.1038/nature16074. Epub 2015 Nov 25.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26605525" target="_blank"〉PubMed〈/a〉
    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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