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Global Analyses of the Effect of Different Cellular Contexts on MicroRNA Targeting
Nam, J.W.,Rissland, Olivia S.,Koppstein, D.,Abreu-Goodger, C.,Jan, Calvin H.,Agarwal, V.,Yildirim, Muhammed A.,Rodriguez, A.,Bartel, David P. Cell Press 2014 Molecular cell Vol.53 No.6
MicroRNA (miRNA) regulation clearly impacts animal development, but the extent to which development-with its resulting diversity of cellular contexts-impacts miRNA regulation is unclear. Here, we compared cohorts of genes repressed by the same miRNAs in different cell lines and tissues and found that target repertoires were largely unaffected, with secondary effects explaining most of the differential responses detected. Outliers resulting from differential direct targeting were often attributable to alternative 3' UTR isoform usage that modulated the presence of miRNA sites. More inclusive examination of alternative 3' UTR isoforms revealed that they influence ~10% of predicted targets when comparing any two cell types. Indeed, considering alternative 3' UTR isoform usage improved prediction of targeting efficacy significantly beyond the improvements observed when considering constitutive isoform usage. Thus, although miRNA targeting is remarkably consistent in different cell types, considering the 3' UTR landscape helps predict targeting efficacy and explain differential regulation that is observed.
Lepton-Flavor-Dependent Angular Analysis of B→K*ℓ+ℓ−
Wehle, S.,Niebuhr, C.,Yashchenko, S.,Adachi, I.,Aihara, H.,Al Said, S.,Asner, D. M.,Aulchenko, V.,Aushev, T.,Ayad, R.,Aziz, T.,Babu, V.,Bakich, A. M.,Bansal, V.,Barberio, E.,Bartel, W.,Behera, P.,Bhuy American Physical Society 2017 Physical Review Letters Vol.118 No.11
<P>We present a measurement of angular observables and a test of lepton flavor universality in the B -> K(+)l(+)l(-) decay, where l is either e or mu. The analysis is performed on a data sample corresponding to an integrated luminosity of 711 fb(-1) containing 772 x 10(6) B (B) over bar pairs, collected at the Upsilon(4S) resonance with the Belle detector at the asymmetric-energy e(+)e(-) collider KEKB. The result is consistent with standard model (SM) expectations, where the largest discrepancy from a SM prediction is observed in the muon modes with a local significance of 2.6 sigma.</P>
Eichhorn, Stephen W.,Guo, H.,McGeary, Sean E.,Rodriguez-Mias, Ricard A.,Shin, C.,Baek, D.,Hsu, S.h.,Ghoshal, K.,Villen, J.,Bartel, David P. Cell Press 2014 Molecular cell Vol.56 No.1
MicroRNAs (miRNAs) regulate target mRNAs through a combination of translational repression and mRNA destabilization, with mRNA destabilization dominating at steady state in the few contexts examined globally. Here, we extend the global steady-state measurements to additional mammalian contexts and find that regardless of the miRNA, cell type, growth condition, or translational state, mRNA destabilization explains most (66%→90%) miRNA-mediated repression. We also determine the relative dynamics of translational repression and mRNA destabilization for endogenous mRNAs as a miRNA is induced. Although translational repression occurs rapidly, its effect is relatively weak, such that by the time consequential repression ensues, the effect of mRNA destabilization dominates. These results imply that consequential miRNA-mediated repression is largely irreversible and provide other insights into the nature of miRNA-mediated regulation. They also simplify future studies, dramatically extending the known contexts and time points for which monitoring mRNA changes captures most of the direct miRNA effects.
Yokoyama, Yoshie,Jelenkovic, Aline,Sund, Reijo,Sung, Joohon,Hopper, John L.,Ooki, Syuichi,Heikkilä,, Kauko,Aaltonen, Sari,Tarnoki, Adam D.,Tarnoki, David L.,Willemsen, Gonneke,Bartels, Meike,van B Cambridge University Press 2016 TWIN RESEARCH AND HUMAN GENETICS - Vol.19 No.2
<P>We analyzed birth order differences in means and variances of height and body mass index (BMI) in monozygotic (MZ) and dizygotic (DZ) twins from infancy to old age. The data were derived from the international CODATwins database. The total number of height and BMI measures from 0.5 to 79.5 years of age was 397,466. As expected, first-born twins had greater birth weight than second-born twins. With respect to height, first-born twins were slightly taller than second-born twins in childhood. After adjusting the results for birth weight, the birth order differences decreased and were no longer statistically significant. First-born twins had greater BMI than the second-born twins over childhood and adolescence. After adjusting the results for birth weight, birth order was still associated with BMI until 12 years of age. No interaction effect between birth order and zygosity was found. Only limited evidence was found that birth order influenced variances of height or BMI. The results were similar among boys and girls and also in MZ and DZ twins. Overall, the differences in height and BMI between first- and second-born twins were modest even in early childhood, while adjustment for birth weight reduced the birth order differences but did not remove them for BMI.</P>