Cell stemness is maintained upon concurrent expression of RB and the mitochondrial ribosomal protein S18-2

Stemness encompasses the capability of a cell for self-renewal and differentiation. The stem cell maintains a balance between proliferation, quiescence, and regeneration via interactions with the microenvironment. Previously, we showed that ectopic expression of the mitochondrial ribosomal protein S18-2 (MRPS18-2) led to immortalization of primary fibroblasts, accompanied by induction of an embryonic stem cell (ESC) phenotype. Moreover, we demonstrated interaction between S18-2 and the retinoblastoma-associated protein (RB) and hypothesized that the simultaneous expression of RB and S18-2 is essential for maintaining cell stemness. Here, we experimentally investigated the role of S18-2 in cell stemness and differentiation. Concurrent expression of RB and S18-2 resulted in immortalization of Rb1−/− primary mouse embryonic fibroblasts and in aggressive tumor growth in severe combined immunodeficiency mice. These cells, which express both RB and S18-2 at high levels, exhibited the potential to differentiate into various lineages in vitro, including osteogenic, chondrogenic, and adipogenic lineages. Mechanistically, S18-2 formed a multimeric protein complex with prohibitin and the ring finger protein 2 (RNF2). This molecular complex increased the monoubiquitination of histone H2ALys119, a characteristic trait of ESCs, by enhanced E3-ligase activity of RNF2. Furthermore, we found enrichment of KLF4 at the S18-2 promoter region and that the S18-2 expression is positively correlated with KLF4 levels. Importantly, knockdown of S18-2 in zebrafish larvae led to embryonic lethality. Collectively, our findings suggest an important role for S18-2 in cell stemness and differentiation and potentially also in cancerogenesis

Long Wavelength Anomalous Diffusion Mode in the 2D XY Dipole Magnet

In 2D XY ferromagnet the dipole force induces a strong interaction between spin-waves in the long-wavelength limit. The major effect of this interaction is the transformation of a propagating spin-wave into a diffusion mode. We study the anomalous dynamics of such diffusion modes. We find that the Janssen-De Dominics functional, which governs this dynamics, approaches the non-Gaussian fixed-point. A spin-wave propagates by an anomalous anisotropic diffusion with the dispersion relation: $i\omega{\sim}k_{y}^{\Delta_y}$ and $i\omega{\sim}k_{x}^{\Delta_x}$, where ${\Delta_y}=47/27$ and ${\Delta_x}=47/36$. The low-frequency response to the external magnetic field is found.Comment: 34 pages, RevTeX, 2 .ps figures, the third figure is available upon reques

Antiretroviral Pharmacology in Mucosal Tissues

Strategies to prevent HIV infection using pre-exposure prophylaxis (PrEP) are required to curtail the HIV pandemic. The mucosal tissues of the genital and rectal tracts play a critical role in HIV acquisition, but antiretroviral (ARV) disposition and correlates of efficacy within these tissues are not well understood. Pre-clinical and clinical strategies to describe ARV pharmacokinetic-pharmacodynamic relationships (PK/PD) within mucosal tissues are currently being investigated. In this review, we summarize the physiochemical and biologic factors influencing ARV tissue exposure. Further, we discuss the necessary steps to generate relevant PK/PD data and the challenges associated with this process. Finally, we suggest how pre-clinical and clinical data might be practically translated into optimal PrEP dosing strategies for clinical trials testing using mathematical modeling and simulation

Striped periodic minimizers of a two-dimensional model for martensitic phase transitions

In this paper we consider a simplified two-dimensional scalar model for the formation of mesoscopic domain patterns in martensitic shape-memory alloys at the interface between a region occupied by the parent (austenite) phase and a region occupied by the product (martensite) phase, which can occur in two variants (twins). The model, first proposed by Kohn and Mueller, is defined by the following functional: $${\cal E}(u)=\beta||u(0,\cdot)||^2_{H^{1/2}([0,h])}+ \int_{0}^{L} dx \int_0^h dy \big(|u_x|^2 + \epsilon |u_{yy}| \big)$$ where $u:[0,L]\times[0,h]\to R$ is periodic in $y$ and $u_y=\pm 1$ almost everywhere. Conti proved that if $\beta\gtrsim\epsilon L/h^2$ then the minimal specific energy scales like $\sim \min\{(\epsilon\beta/L)^{1/2}, (\epsilon/L)^{2/3}\}$, as $(\epsilon/L)\to 0$. In the regime $(\epsilon\beta/L)^{1/2}\ll (\epsilon/L)^{2/3}$, we improve Conti's results, by computing exactly the minimal energy and by proving that minimizers are periodic one-dimensional sawtooth functions.Comment: 29 pages, 3 figure

Giant Magnetoresistance Oscillations Induced by Microwave Radiation and a Zero-Resistance State in a 2D Electron System with a Moderate Mobility

The effect of a microwave field in the frequency range from 54 to 140 $\mathrm{GHz}$ on the magnetotransport in a GaAs quantum well with AlAs/GaAs superlattice barriers and with an electron mobility no higher than $10^6$ $\mathrm{cm^2/Vs}$ is investigated. In the given two-dimensional system under the effect of microwave radiation, giant resistance oscillations are observed with their positions in magnetic field being determined by the ratio of the radiation frequency to the cyclotron frequency. Earlier, such oscillations had only been observed in GaAs/AlGaAs heterostructures with much higher mobilities. When the samples under study are irradiated with a 140-$\mathrm{GHz}$ microwave field, the resistance corresponding to the main oscillation minimum, which occurs near the cyclotron resonance, appears to be close to zero. The results of the study suggest that a mobility value lower than $10^6$ $\mathrm{cm^2/Vs}$ does not prevent the formation of zero-resistance states in magnetic field in a two-dimensional system under the effect of microwave radiation.Comment: 4 pages, 2 figur

Awareness and willingness to use HIV pre-exposure prophylaxis amongst gay and bisexual men in Scotland: implications for biomedical HIV prevention

Objectives:<p></p> To investigate the awareness of, and willingness to use, HIV Pre-Exposure Prophylaxis (PrEP), and willingness to take part in a PrEP study among gay and bisexual men in Scotland.<p></p> Methods:<p></p> Cross-sectional survey of 17 gay commercial venues in Glasgow and Edinburgh in May 2011 (N = 1515, 65.2% response rate); 1393 are included in the analyses.<p></p> Results:<p></p> Just under one-third of participants had heard of PrEP (n = 434; 31.2%), with awareness associated with being aged older than 35 years, talking to UAI partners about HIV, and with having had an HIV or STI test in the previous 12 months. Around half were willing to take part in a PrEP study (n = 695; 49.9%) or to take PrEP on a daily basis (n = 756; 54.3%). In multivariate analysis, willingness to take PrEP was associated with lower levels of education, regular gay scene attendance, ‘high-risk’ unprotected anal intercourse (UAI) and testing for HIV or STI in the previous 12 months. Reasons for not wanting to participate in a PrEP study or take PrEP included perceptions of low personal risk of HIV and concerns with using medication as an HIV prevention method.<p></p> Conclusions:<p></p> There is a willingness to engage in new forms of HIV prevention and research amongst a significant number of gay and bisexual men in Scotland. Future biomedical HIV interventions need to consider the links between sexual risk behaviour, testing, and potential PrEP use

Expression profile of nuclear receptors upon epstein — barr virus induced b cell transformation

Background: Infection of human B cells with Epstein—Barr virus (EBV) induces metabolic activation, morphological transformation, cell proliferation and eventual immortalization. Aim: To identify the nuclear receptors, which are the cellular interaction partners of EBNAs, that will help to elucidate the mechanism of B cell transformation. Methods: We have compared the nuclear receptor profile in the naïve and EBV-transformed B-lymphocytes, using TaqMan LDA microfluidic card technology. Results: Out of 48 nuclear receptor, 17 showed differential expression at the mRNA level. The expression of 5 genes was elevated in EBV-transformed cells, whereas 12 genes were downregulated in lymphoblastoid cells (LCLs). 7 genes were studied at the protein level; 2 genes were up regulated (Nr2F2 and RARA) and 4 genes were down regulated (ERB, NUR77, PPARG, and VDR) in LCLs. Conclusion: The nuclear receptor profiling on EBV infected B cells showed alterations of nuclear receptors expression at both mRNA and protein levels compared with non infected peripheral blood cells. Further analysis on a possible role of each nuclear receptor in EBV induced cell transformation should be performed

Superconducting Transition Temperature in Heterogeneous Ferromagnet-Superconductor Systems

We study the shift of the the superconducting transition temperature $T_c$ in ferromagnetic-superconducting bi-layers and in a superconducting film supplied a square array of ferromagnetic dots. We find that the transition temperature in these two cases change presumably in opposite direction and that its change is not too small. We extend these results to multilayer structures. We predict that rather small external magnetic field $\sim 10$ Oe can change the transition temperature of the bilayer by 10% .Comment: 9 pages, 2 figure