Retrotransposition creates sloping shores: a graded influence of hypomethylated CpG islands on flanking CpG sites

Long interspersed elements (LINEs), through both self-mobilization and trans-mobilization of short interspersed elements and processed pseudogenes, have made an indelible impact on the structure and function of the human genome. One consequence is the creation of new CpG islands (CGIs). In fact, more than half of all CGIs in the genome are associated with repetitive DNA, three-quarters of which are derived from retrotransposons. However, little is known about the epigenetic impact of newly inserted CGIs. We utilized a transgenic LINE-1 mouse model and tracked DNA methylation dynamics of individual germline insertions during mouse development. The retrotransposed GFP marker sequence, a strong CGI, is hypomethylated in male germ cells but hypermethylated in somatic tissues, regardless of genomic location. The GFP marker is similarly methylated when delivered into the genome via the Sleeping Beauty DNA transposon, suggesting that the observed methylation pattern may be independent of the mode of insertion. Comparative analyses between insertion- and non-insertion-containing alleles further reveal a graded influence of the retrotransposed CGI on flanking CpG sites, a phenomenon that we described as "sloping shores." Computational analyses of human and mouse methylomic data at single-base resolution confirm that sloping shores are universal for hypomethylated CGIs in sperm and somatic tissues. Additionally, the slope of a hypomethylated CGI can be affected by closely positioned CGI neighbors. Finally, by tracing sloping shore dynamics through embryonic and germ cell reprogramming, we found evidence of bookmarking, a mechanism that likely determines which CGIs will be eventually hyper- or hypomethylated

Striped antiferromagnetic order and electronic properties of stoichiometric LiFeAs from first-principles calculations

We investigate the structural, electronic, and magnetic properties of stoichiometric LiFeAs by using state-of-the-arts first-principles method. We find the magnetic ground-state by comparing the total energies among all the possible magnetic orders. Our calculated internal positions of Li and As are in good agreement with experiment. Our results show that stoichiometric LiFeAs has almost the same striped antiferromagnetic spin order as other FeAs-based parent compounds and tetragonal FeSe do, and the experimental fact that no magnetic phase transition has been observed at finite temperature is attributed to the tiny inter-layer spin coupling

IL-17+ CD8+ T cell suppression by dimethyl fumarate associates with clinical response in multiple sclerosis

IL-17-producing CD8+ (Tc17) cells are enriched in active lesions of patients with multiple sclerosis (MS), suggesting a role in the pathogenesis of autoimmunity. Here we show that amelioration of MS by dimethyl fumarate (DMF), a mechanistically elusive drug, associates with suppression of Tc17 cells. DMF treatment results in reduced frequency of Tc17, contrary to Th17 cells, and in a decreased ratio of the regulators RORC-to-TBX21, along with a shift towards cytotoxic T lymphocyte gene expression signature in CD8+ T cells from MS patients. Mechanistically, DMF potentiates the PI3K-AKT-FOXO1-T-BET pathway, thereby limiting IL-17 and RORγt expression as well as STAT5-signaling in a glutathione-dependent manner. This results in chromatin remodeling at the Il17 locus. Consequently, T-BET-deficiency in mice or inhibition of PI3K-AKT, STAT5 or reactive oxygen species prevents DMF-mediated Tc17 suppression. Overall, our data disclose a DMF-AKT-T-BET driven immune modulation and suggest putative therapy targets in MS and beyond

Strengthening mechanisms in thermomechanically processed NbTi-microalloyed steel

The effect of deformation temperature on microstructure and mechanical properties was investigated for thermomechanically processed NbTi-microalloyed steel with ferrite-pearlite microstructure. With a decrease in the finish deformation temperature at 1348 K to 1098 K (1075 °C to 825 °C) temperature range, the ambient temperature yield stress did not vary significantly, work hardening rate decreased, ultimate tensile strength decreased, and elongation to failure increased. These variations in mechanical properties were correlated to the variations in microstructural parameters (such as ferrite grain size, solid solution concentrations, precipitate number density and dislocation density). Calculations based on the measured microstructural parameters suggested the grain refinement, solid solution strengthening, precipitation strengthening, and work hardening contributed up to 32 pct, up to 48 pct, up to 25 pct, and less than 3 pct to the yield stress, respectively. With a decrease in the finish deformation temperature, both the grain size strengthening and solid solution strengthening increased, the precipitation strengthening decreased, and the work hardening contribution did not vary significantly

Strategies for Controlled Placement of Nanoscale Building Blocks

The capability of placing individual nanoscale building blocks on exact substrate locations in a controlled manner is one of the key requirements to realize future electronic, optical, and magnetic devices and sensors that are composed of such blocks. This article reviews some important advances in the strategies for controlled placement of nanoscale building blocks. In particular, we will overview template assisted placement that utilizes physical, molecular, or electrostatic templates, DNA-programmed assembly, placement using dielectrophoresis, approaches for non-close-packed assembly of spherical particles, and recent development of focused placement schemes including electrostatic funneling, focused placement via molecular gradient patterns, electrodynamic focusing of charged aerosols, and others

Galaxy Clusters Associated with Short GRBs. II. Predictions for the Rate of Short GRBs in Field and Cluster Early-Type Galaxies

We determine the relative rates of short GRBs in cluster and field early-type galaxies as a function of the age probability distribution of their progenitors, P(\tau) \propto \tau^n. This analysis takes advantage of the difference in the growth of stellar mass in clusters and in the field, which arises from the combined effects of the galaxy stellar mass function, the early-type fraction, and the dependence of star formation history on mass and environment. This approach complements the use of the early- to late-type host galaxy ratio, with the added benefit that the star formation histories of early-type galaxies are simpler than those of late-type galaxies, and any systematic differences between progenitors in early- and late-type galaxies are removed. We find that the ratio varies from R(cluster)/R(field) ~ 0.5 for n = -2 to ~ 3 for n = 2. Current observations indicate a ratio of about 2, corresponding to n ~ 0 - 1. This is similar to the value inferred from the ratio of short GRBs in early- and late-type hosts, but it differs from the value of n ~ -1 for NS binaries in the Milky Way. We stress that this general approach can be easily modified with improved knowledge of the effects of environment and mass on the build-up of stellar mass, as well as the effect of globular clusters on the short GRB rate. It can also be used to assess the age distribution of Type Ia supernova progenitors.Comment: ApJ accepted versio

Measurement of Z0 decays to hadrons, and a precise determination of the number of neutrino species

We have made a precise measurement of the cross section for e+e--->Z0-->hadrons with the L3 detector at LEP, covering the range from 88.28 to 95.04 GeV. From a fit to the Z0 mass, total width, and the hadronic cross section to be MZ0=91.160 +/- 0.024 (experiment) +/-0.030(LEP) GeV, [Gamma]Z0=2.539+/-0.054 GeV, and [sigma]h(MZ0)=29.5+/-0.7 nb. We also used the fit to the Z0 peak cross section and the width todetermine [Gamma]invisible=0.548+/-0.029 GeV, which corresponds to 3.29+/-0.17 species of light neutrinos. The possibility of four or more neutrino flavors is thus ruled out at the 4[sigma] confidence level.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28683/3/0000500.pd

A measurement of the Z0 leptonic partial widths and the vector and axial vector coupling constants

We have measured the partial widths of the Z0 into lepton pairs, and the forward-backward charge asymmetry for the process e+e--->[mu]+[mu]- using the L3 detector at LEP. We obtain an average [Gamma]ll of 83.0+/-2.1+/-1.1 MeV.From this result and the asymmetry measurement, we extract the values of the vector and axial vector couplings of the Z0 to leptons: grmv=-0.066-0.027+0.046 and grmA= -0.495-0.007+0.007.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28666/3/0000483.pd