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  • 1
    Publication Date: 2015-02-18
    Description: Recently, it was reported that knockdown of DICER reduced the ATM-dependent DNA damage response and homologous recombination repair (HRR) via decreasing DICER-generated small RNAs at the damage sites. However, we found that knockdown of DICER dramatically increased cell resistance to camptothecin that induced damage required ATM to facilitate HRR. This phenotype is due to a prolonged G1/S transition via decreasing DICER-dependent biogenesis of miRNA let-7 , which increased the p21 Waf1/Cip1 /p27 Kip1 levels and resulted in decreasing the HRR efficiency. These results uncover a novel function of DICER in regulating the cell cycle through miRNA biogenesis, thus affecting cell response to DNA damage.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 2
    Publication Date: 2015-12-13
    Description: Because of the lack of long-term pulsed emission in quiescence and the strong timing noise, it is impossible to directly measure the braking index n of a magnetar. Based on the estimated ages of their potentially associated supernova remnants (SNRs), we estimate the values of the mean braking indices of eight magnetars with SNRs, and find that they cluster in the range of 1–42. Five magnetars have smaller mean braking indices of 1 〈  n  〈 3, and we interpret them within a combination of magneto-dipole radiation and wind-aided braking. The larger mean braking indices of n  〉 3 for the other three magnetars are attributed to the decay of external braking torque, which might be caused by magnetic field decay. We estimate the possible wind luminosities for the magnetars with 1 〈  n  〈 3, and the dipolar magnetic field decay rates for the magnetars with n  〉 3, within the updated magneto-thermal evolution models. Although the constrained range of the magnetars’ braking indices is tentative, as a result of the uncertainties in the SNR ages due to distance uncertainties and the unknown conditions of the expanding shells, our method provides an effective way to constrain the magnetars’ braking indices if the measurements of the SNR ages are reliable, which can be improved by future observations.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
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  • 3
    Publication Date: 2016-12-01
    Description: Meiotic recombination is essential for fertility in most sexually reproducing species, but the molecular mechanisms underlying this process remain poorly understood in mammals. Here, we show that RNF20-mediated H2B ubiquitination is required for meiotic recombination. A germ cell-specific knockout of the H2B ubiquitination E3 ligase RNF20 results in complete male infertility. The Stra8-Rnf20 –/– spermatocytes arrest at the pachytene stage because of impaired programmed double-strand break (DSB) repair. Further investigations reveal that the depletion of RNF20 in the germ cells affects chromatin relaxation, thus preventing programmed DSB repair factors from being recruited to proper positions on the chromatin. The gametogenetic defects of the H2B ubiquitination deficient cells could be partially rescued by forced chromatin relaxation. Taken together, our results demonstrate that RNF20/Bre1p-mediated H2B ubiquitination regulates meiotic recombination by promoting chromatin relaxation, and suggest an old drug may provide a new way to treat some oligo- or azoospermia patients with chromatin relaxation disorders.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 4
    Publication Date: 2015-09-15
    Description: This paper investigates the problem of D-stability performance of an L 2 point formation control system with parametric uncertainties. A Quasi linear parameter varying (QLPV) model is introduced for the L 2 point formation flying, based on which a nonlinear control strategy is developed via the polynomial eigenstructure assignment (PEA) approach. The designed controller can guarantee the closed-loop system with invariant performance over a wide range of conditions due to its special structure with varying parameters. The robust D-stability of the multiple input and multiple output (MIMO) system is also addressed. It is shown that the D-stability performance of the L 2 point formation control system with parametric uncertainties can be ensured by using PEA controller. Finally, a simulation of formation flying is performed to illustrate the effectiveness of the proposed control approach.
    Print ISSN: 0265-0754
    Electronic ISSN: 1471-6887
    Topics: Mathematics
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  • 5
    Publication Date: 2015-11-26
    Description: Ferritins and other cage proteins have been utilized as models to understand the fundamentals of protein folding and self-assembly. The bacterioferritin (BFR) from Escherichia coli, a maxi-ferritin made up of 24 subunits, was chosen as the basis for a mutagenesis study to investigate the role of electrostatic intermolecular interactions mediated through charged amino acids. Through structural and computational analyses, three charged amino acids R30, D56 and E60 which involved in an electrostatic interaction network were mutated to the opposite charge. Four mutants, R30D, D56R, E60H and D56R-E60H, were expressed, purified and characterized. All of the mutants fold into α-helical structures. Consistent with the computational prediction, they all show a lowered thermostability; double mutant D56R-E60H was found to be 16°C less stable than the wild type. Except for the mutant E60H, all the other mutations completely shut down the formation of protein cages to favour the dimer state in solution. The mutants, however, retain their ability to form cage-like nanostructures in the dried, surface immobilized conditions of transmission electron microscopy. Our findings confirm that even a single charge-inversion mutation at the 2-fold interface of BFR can affect the quaternary structure of its dimers and their ability to self-assemble into cage structures.
    Print ISSN: 0021-924X
    Electronic ISSN: 1756-2651
    Topics: Biology , Chemistry and Pharmacology
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  • 6
    Publication Date: 2016-07-24
    Description: With the largest spectroscopic galaxy survey volume drawn from the SDSS-III Baryon Oscillation Spectroscopic Survey (BOSS), we can extract cosmological constraints from the measurements of redshift and geometric distortions at quasi-linear scales (e.g. above 50 h –1  Mpc). We analyse the broad-range shape of the monopole and quadrupole correlation functions of the BOSS Data Release 12 (DR12) CMASS galaxy sample, at the effective redshift z = 0.59, to obtain constraints on the Hubble expansion rate H ( z ), the angular- diameter distance D A ( z ), the normalized growth rate f ( z ) 8 ( z ), and the physical matter density m h 2 . We obtain robust measurements by including a polynomial as the model for the systematic errors, and find it works very well against the systematic effects, e.g. ones induced by stars and seeing. We provide accurate measurements { D A (0.59) r s ,fid / r s , H (0.59) r s / r s ,fid , f (0.59) 8 (0.59), m h 2 } = {1427 ± 26 Mpc, 97.3 ± 3.3 km s –1 Mpc –1 , 0.488 ± 0.060, 0.135 ± 0.016}, where r s is the comoving sound horizon at the drag epoch and r s ,fid = 147.66 Mpc is the sound scale of the fiducial cosmology used in this study. The parameters which are not well constrained by our galaxy clustering analysis are marginalized over with wide flat priors. Since no priors from other data sets, e.g. cosmic microwave background (CMB), are adopted and no dark energy models are assumed, our results from BOSS CMASS galaxy clustering alone may be combined with other data sets, i.e. CMB, SNe, lensing or other galaxy clustering data to constrain the parameters of a given cosmological model. The uncertainty on the dark energy equation of state parameter, w , from CMB+CMASS is about 8 per cent. The uncertainty on the curvature fraction, k , is 0.3 per cent. We do not find deviation from flat CDM.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
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  • 7
    Publication Date: 2016-08-03
    Description: The Herschel Extragalactic Legacy Project (HELP) brings together a vast range of data from many astronomical observatories. Its main focus is on the Herschel data, which maps dust-obscured star formation over 1300 deg 2 . With this unprecedented combination of data sets, it is possible to investigate how the star formation versus stellar mass relation (main sequence) of star-forming galaxies depends on environment. In this pilot study, we explore this question within 0.1 〈 z 〈 3.2 using data in the COSMOS field. We estimate the local environment from a smoothed galaxy density field using the full photometric redshift probability distribution. We estimate star formation rates by stacking the SPIRE data from the Herschel Multi-tiered Extragalactic Survey. Our analysis rules out the hypothesis that the main sequence for star-forming systems is independent of environment at 1.5 〈 z 〈 2, while a simple model in which the mean specific star formation rate declines with increasing environmental density gives a better description. However, we cannot exclude a simple hypothesis in which the main sequence for star-forming systems is independent of environment at z 〈 1.5 and z 〉 2. We also estimate the evolution of the star formation rate density in the COSMOS field, and our results are consistent with previous measurements at z 〈 1.5 and z 〉 2 but we find a $1.4^{+0.3}_{-0.2}$ times higher peak value of the star formation rate density at z ~ 1.9.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
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  • 8
    Publication Date: 2013-06-07
    Description: Mutations in Parkin or PINK1 are the most common cause of recessively inherited parkinsonism. Parkin and PINK1 function in a conserved mitochondrial quality control pathway, in which PINK1, a putative mitochondrial kinase, directs Parkin, a cytosolic E3 ubiquitin ligase, selectively to dysfunctional mitochondria to promote their isolation, immobilization and degradation by macroautophagy (hereafter, mitophagy). As Parkin recruitment to mitochondria is robustly induced by PINK1 expression on the outer mitochondrial membrane, Parkin recruitment to mitochondria was used as an assay for PINK1 function. Unexpectedly, mutation of serine residues within the activation segment of PINK1 uncovered a temperature-sensitive variant of PINK1 (tsPINK1). tsPINK1 allowed for the first time the disassociation of PINK1 activity from its expression and localization. Additionally, extensive mutagenesis identified three disease-associated variants in the activation segment and one in an α-helix N-terminal to kinase domain (Q126P) that are similarly thermally labile, suggesting that their activity could be restored post-translationally (e.g. by reducing the temperature or by a chemical or pharmacologic chaperone). Together, these findings suggest that tsPINK1 may represent a valuable tool for the analysis of the PINK1/Parkin pathway in human cells; additionally, as the serine residue promoting thermal lability is conserved among Mus musculus , Danio rerio , Drosophila melanogaster and Caenorhabditis elegans , it may serve as the basis for developing other temperature-sensitive models for the study of recessive parkinsonism and mitophagy. Finally, these results suggest that PINK1 kinase function could be restored for a subset of patients with PINK1 mutations, and perhaps alter the course of their disease.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
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  • 9
    Publication Date: 2016-01-07
    Description: Translational control is crucial in the regulation of gene expression and deregulation of translation is associated with a wide range of cancers and human diseases. Ribosome profiling is a technique that provides genome wide information of mRNA in translation based on deep sequencing of ribosome protected mRNA fragments (RPF). RPFdb is a comprehensive resource for hosting, analyzing and visualizing RPF data, available at www.rpfdb.org or http://sysbio.sysu.edu.cn/rpfdb/index.html . The current version of database contains 777 samples from 82 studies in 8 species, processed and reanalyzed by a unified pipeline. There are two ways to query the database: by keywords of studies or by genes. The outputs are presented in three levels. (i) Study level: including meta information of studies and reprocessed data for gene expression of translated mRNAs; (ii) Sample level: including global perspective of translated mRNA and a list of the most translated mRNA of each sample from a study; (iii) Gene level: including normalized sequence counts of translated mRNA on different genomic location of a gene from multiple samples and studies. To explore rich information provided by RPF, RPFdb also provides a genome browser to query and visualize context-specific translated mRNA. Overall our database provides a simple way to search, analyze, compare, visualize and download RPF data sets.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 10
    Publication Date: 2016-06-26
    Description: We present proper motions for 15 pulsars which are observed regularly by the Nanshan 25-m radio telescope. Two methods, the frequentist method and the Bayesian method, are used and the results are compared. We demonstrate that the two methods can be applied to young pulsar data sets that exhibit large amounts of timing noise with steep spectral exponents and give consistent results. The measured positions also agree with very long baseline interferometric positions. Proper motions for four pulsars are obtained for the first time, and improved values are obtained for five pulsars.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
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