Activation of pluripotency genes in human fibroblast cells by a novel mRNA based approach

Background: Several methods have been used to induce somatic cells to re-enter the pluripotent state. Viral transduction of reprogramming genes yields higher efficiency but involves random insertions of viral sequences into the human genome. Although induced pluripotent stem (iPS) cells can be obtained with the removable PiggyBac transposon system or an episomal system, both approaches still use DNA constructs so that resulting cell lines need to be thoroughly analyzed to confirm they are free of harmful genetic modification. Thus a method to change cell fate without using DNA will be very useful in regenerative medicine. Methodology/Principal Findings: In this study, we synthesized mRNAs encoding OCT4, SOX2, cMYC, KLF4 and SV40 large T (LT) and electroporated them into human fibroblast cells. Upon transfection, fibroblasts expressed these factors at levels comparable to, or higher than those in human embryonic stem (ES) cells. Ectopically expressed OCT4 localized to the cell nucleus within 4 hours after mRNA introduction. Transfecting fibroblasts with a mixture of mRNAs encoding all five factors significantly increased the expression of endogenous OCT4, NANOG, DNMT3 beta, REX1 and SALL4. When such transfected fibroblasts were also exposed to several small molecules (valproic acid, BIX01294 and 5'-aza-2'-deoxycytidine) and cultured in human embryonic stem cell (ES) medium they formed small aggregates positive for alkaline phosphatase activity and OCT4 protein within 30 days. Conclusion/Significance: Our results demonstrate that mRNA transfection can be a useful approach to precisely control the protein expression level and short-term expression of reprogramming factors is sufficient to activate pluripotency genes in differentiated cells

Slip in the 2010–2011 Canterbury earthquakes, New Zealand

The 3rd September 2010 Mw 7.1 Darfield and 21st February 2011 Mw 6.3 Christchurch (New Zealand) earthquakes occurred on previously unknown faults. We use InSAR ground displacements, SAR amplitude offsets, field mapping, aerial photographs, satellite optical imagery, a LiDAR DEM and teleseismic body-wave modeling to constrain the pattern of faulting in these earthquakes. The InSAR measurements reveal slip on multiple strike-slip segments and secondary reverse faults associated with the Darfield main shock. Fault orientations are consistent with those expected from the GPS-derived strain field. The InSAR line-of-sight displacement field indicates the main fault rupture is about 45 km long, and is confined largely to the upper 10 km of the crust. Slip on the individual fault segments of up to 8 m at 4 km depth indicate stress drops of 6–10 MPa. In each event, rupture initiated on a reverse fault segment, before continuing onto a strike-slip segment. The non-double couple seismological moment tensors for each event are matched well by the sum of double couple equivalent moment tensors for fault slip determined by InSAR. The slip distributions derived from InSAR observations of both the Darfield and Christchurch events show a 15-km-long gap in fault slip south-west of Christchurch, which may present a continuing seismic hazard if a further unknown fault structure of significant size should exist there

Electroweak Supersymmetry around the Electroweak Scale

Inspired by the phenomenological constraints, LHC supersymmetry and Higgs searches, dark matter search as well as string model building, we propose the electroweak supersymmetry around the electroweak scale: the squarks and/or gluinos are around a few TeV while the sleptons, sneutrinos, bino and winos are within one TeV. The Higgsinos can be either heavy or light. We consider bino as the dominant component of dark matter candidate, and the observed dark matter relic density is achieved via the neutralino-stau coannihilations. Considering the Generalized Minimal Supergravity (GmSUGRA), we show explicitly that the electroweak supersymmetry can be realized, and the gauge coupling unification can be preserved. With two Scenarios, we study the viable parameter spaces that satisfy all the current phenomenological constraints, and we present the concrete benchmark points. Furthermore, we comment on the fine-tuning problem and LHC searches.Comment: RevTex4, 28 pages, 8 figures, 8 tables, version to appear in EPJ

Background Dependent Lorentz Violation: Natural Solutions to the Theoretical Challenges of the OPERA Experiment

To explain both the OPERA experiment and all the known phenomenological constraints/observations on Lorentz violation, the Background Dependent Lorentz Violation (BDLV) has been proposed. We study the BDLV in a model independent way, and conjecture that there may exist a "Dream Special Relativity Theory", where all the Standard Model (SM) particles can be subluminal due to the background effects. Assuming that the Lorentz violation on the Earth is much larger than those on the interstellar scale, we automatically escape all the astrophysical constraints on Lorentz violation. For the BDLV from the effective field theory, we present a simple model and discuss the possible solutions to the theoretical challenges of the OPERA experiment such as the Bremsstrahlung effects for muon neutrinos and the pion decays. Also, we address the Lorentz violation constraints from the LEP and KamLAMD experiments. For the BDLV from the Type IIB string theory with D3-branes and D7-branes, we point out that the D3-branes are flavour blind, and all the SM particles are the conventional particles as in the traditional SM when they do not interact with the D3-branes. Thus, we not only can naturally avoid all the known phenomenological constraints on Lorentz violation, but also can naturally explain all the theoretical challenges. Interestingly, the energy dependent photon velocities may be tested at the experiments.Comment: RevTex4, 14 pages, minor corrections, references adde

Understanding wavelength scaling in 19-cell core hollow-core photonic bandgap fibers

First experimental wavelength scaling in 19-cell core HC-PBGF indicates that the minimum loss waveband occurs at longer wavelengths than previously predicted. Record low loss (2.5dB/km) fibers operating around 2µm and gas-purging experiments are also reported

Antiflow of kaons in relativistic heavy ion collisions

We compare relativistic transport model calculations to recent data on the sideward flow of neutral strange K^0_s mesons for Au+Au collisions at 6 AGeV. A soft nuclear equation of state is found to describe very well the positive proton flow data measured in the same experiment. In the absence of kaon potential, the K^0 flow pattern is similar to that of protons. The kaon flow becomes negative if a repulsive kaon potential determined from the impulse approximation is introduced. However, this potential underestimates the data which exhibits larger antiflow. An excellent agreement with the data is obtained when a relativistic scalar-vector kaon potential, that has stronger density dependence, is used. We further find that the transverse momentum dependence of directed and elliptic flow is quite sensitive to the kaon potential in dense matter.Comment: 5 pages, Revtex, 4 figure

Study of Doubly Heavy Baryon Spectrum via QCD Sum Rules

In this work, we calculate the mass spectrum of doubly heavy baryons with the diquark model in terms of the QCD sum rules. The interpolating currents are composed of a heavy diquark field and a light quark field. Contributions of the operators up to dimension six are taken into account in the operator product expansion. Within a reasonable error tolerance, our numerical results are compatible with other theoretical predictions. This indicates that the diquark picture reflects the reality and is applicable to the study of doubly heavy baryons.Comment: 23 pages, 9 figures, minor corrections in expression

Effects of dilute Zn impurities on the uniform magnetic susceptibility of YBa2Cu3O{7-delta}

The effects of dilute Zn impurities on the uniform magnetic susceptibility are calculated in the normal metallic state for a model of the spin fluctuations of the layered cuprates. It is shown that scatterings from extended impurity potentials can lead to a coupling of the q~(pi,pi) and the q~0 components of the magnetic susceptibility chi(q). Within the presence of antiferromagnetic correlations, this coupling can enhance the uniform susceptibility. The implications of this result for the experimental data on Zn substituted YBa2Cu3O{7-delta} are discussed.Comment: 4 pages, 4 figure

Artery tertiary lymphoid organs control multi-layered territorialized atherosclerosis B cell responses in aged ApoE-/- mice

Objective: Explore aorta B cell immunity in aged ApoE-/- mice. Approach and Results: Transcript maps, FACS, immunofluorescence analyses, cell transfers, and Ig-ELISPOT assays showed multi-layered atherosclerosis B cell responses in artery tertiary lymphoid organs (ATLOs). Aging-associated aorta B cell-related transcriptomes were identified and transcript atlases revealed highly territorialized B cell responses in ATLOs versus atherosclerotic lesions: ATLOs showed upregulation of bona fide B cell genes including Cd19, Ms4a1 (Cd20), Cd79a/b, and Ighm though intima plaques preferentially expressed molecules involved in non-B effector responses towards B cell-derived mediators, i.e. Fcgr3 (Cd16), Fcer1g (Cd23), and the C1q family. ATLOs promoted B cell recruitment. ATLO B-2 B cells included naïve, transitional, follicular, germinal center, switched IgG1+, IgA+, and IgE+ memory cells, plasmablasts, and long-lived plasma cells (PCs). ATLOs recruited large numbers of B-1 cells whose subtypes were skewed towards IL-10+ B-1b cells versus IL-10- B-1a cells. ATLO B-1 cells and PCs constitutively produced IgM and IgG and a fraction of PCs expressed IL-10. Moreover, ApoE-/- mice showed increased germinal center B cells in renal lymph nodes, IgM-producing PCs in the bone marrow, and higher IgM and anti-MDA-LDL IgG serum titers. Conclusions: ATLOs orchestrate dichotomic, territorialized, and multi-layered B cell responses in the diseased aorta; germinal center reactions indicate generation of autoimmune B cells within the diseased arterial wall during aging