Overexpression of molecular chaperons GRP78 and GRP94 in CD44hi/CD24lo breast cancer stem cells

Introduction: Breast cancer stem cell with CD44hi/CD24lo phonotype is described having stem cell properties and represented as the main driving factor in breast cancer initiation, growth, metastasis and low response to anti-cancer agents. Glucoseregulated proteins (GRPs) are heat shock protein family chaperons that are charged with regulation of protein machinery and modulation of endoplasmic reticulum homeostasis whose important roles in stem cell development and invasion of various cancers have been demonstrated. Here, we investigated the expression levels of GRP78 and GRP94 in CD44hi/CD24lo phenotype breast cancer stem cells (BCSCs). Methods: MCF7, T-47D and MDA-MB-231 breast cancer cell lines were used. CD44hi/CD24lo phenotype cell population were analyzed and sorted by fluorescence-activated cell sorting (FACS). Transcriptional and translational expression of GRP78 and GRP94 were investigated by western blotting and quantitative real time PCR. Results: Results showed different proportion of CD44hi/CD24lo phenotype cell population in their original bulk cells. The ranking of the cell lines in terms of CD44hi/CD24lo phenotype cell population was as MCF7<T-47D<MDA-MB-231. Our results also indicated that CD44hi/CD24lo phenotype cells exhibited higher mRNA and protein expression level of GRP78 and GRP94 compared to their original bulk cells. Conclusion: Our results show a relationship between overexpression of GRP78 and GRP94 and exhibiting CD44hi/CD24lo phenotype in breast cancer cells. We conclude that upregulation of GRPs may be an important factor in the emergence of CD44hi/CD24lo phenotype BCSCs features. � 2016 The Author(s)

ALMA Observations of the IRDC Clump G34.43+00.24 MM3: DNC/HNC Ratio

We have observed the clump G34.43+00.24 MM3 associated with an infrared dark cloud in DNC $J$=3--2, HN$^{13}$C $J$=3--2, and N$_2$H$^+$ $J$=3--2 with the Atacama Large Millimeter/submillimeter Array (ALMA). The N$_2$H$^+$ emission is found to be relatively weak near the hot core and the outflows, and its distribution is clearly anti-correlated with the CS emission. This result indicates that a young outflow is interacting with cold ambient gas. The HN$^{13}$C emission is compact and mostly emanates from the hot core, whereas the DNC emission is extended around the hot core. Thus, the DNC and HN$^{13}$C emission traces warm regions near the protostar differently. The DNC emission is stronger than the HN$^{13}$C emission toward most parts of this clump. The DNC/HNC abundance ratio averaged within a $15^{\prime\prime} \times 15^{\prime\prime}$ area around the phase center is higher than 0.06. This ratio is much higher than the value obtained by the previous single-dish observations of DNC and HN$^{13}$C $J$=1--0 ($\sim$0.003). It seems likely that the DNC and HNC emission observed with the single-dish telescope traces lower density envelopes, while that observed with ALMA traces higher density and highly deuterated regions. We have compared the observational results with chemical-model results in order to investigate the behavior of DNC and HNC in the dense cores. Taking these results into account, we suggest that the low DNC/HNC ratio in the high-mass sources obtained by the single-dish observations are at least partly due to the low filling factor of the high density regions.Comment: accepted to Ap

Quasinormal modes of a massless charged scalar field on a small Reissner-Nordstr\"om-anti-de Sitter black hole

We investigate quasinormal modes of a massless charged scalar field on a small Reissner-Nordstr\"om-anti-de Sitter (RN-AdS) black hole both with analytical and numerical approaches. In the analytical approach, by using the small black hole approximation (r_+ << L), we obtain the quasinormal mode frequencies in the limit of r_+/L -> 0, where r_+ and L stand for the black hole event horizon radius and the AdS scale, respectively. We then show that the small RN-AdS black hole is unstable if its quasinormal modes satisfy the superradiance condition and that the instability condition of the RN-AdS black hole in the limit of r_+/L -> 0 is given by Q>(3/eL)Q_c, where Q, Q_c, and e are the charge of the black hole, the critical (maximum) charge of the black hole, and the charge of the scalar field, respectively. In the numerical approach, we calculate the quasinormal modes for the small RN-AdS black holes with r_+ << L and confirm that the RN-AdS black hole is unstable if its quasinormal modes satisfy the superradiance condition. Our numerical results show that the RN-AdS black holes with r_+ =0.2L, 0.1L, and 0.01L become unstable against scalar perturbations with eL=4 when the charge of the black hole satisfies Q > 0.8Q_c, 0.78Q_c, and 0.76Q_c, respectively.Comment: 13 pages, 11 figure

Screening Corrections to the Electron Capture Rates in Dense Stars by the Relativistically Degenerate Electron Liquid

We calculate the screening corrections to the electron capture rates in dense stars by the relativistically degenerate electron liquid. In order to calculate the screening corrections we adopt the linear response theory which is widely used in the field of solid state physics and liquid metal physics. In particular, we use the longitudinal dielectric function for the relativistically degenerate electron liquid derived by Jancovici. We calculate the screening potential at the position of the nucleus. By using this screening potential one can calculate the screening corrections to the electron capture rates. We will present accurate analytic fitting formulae which summarize our numerical results. These fitting formulae will facilitate the application of the present results. The screening corrections to the electron capture rates are typically a few percent.Comment: uses AAS LaTeX macro package (Ver. 5.0), 8 pages, 2 tables, 4 figures, 2 subroutines, published in ApJ 579, 380-385 (2002

Influence of the magnetic sublattices in the double perovskite LaCaNiReO6

The magnetism of double perovskites is a complex phenomenon, determined from intra- or interatomic magnetic moment interactions, and strongly influenced by geometry. We take advantage of the complementary length and timescales of the muon spin rotation, relaxation, and resonance (μ+SR) microscopic technique and bulk ac/dc magnetic susceptibility measurements to study the magnetic phases of the LaCaNiReO6 double perovskite. As a result, we are able to discern and report ferrimagnetic ordering below TC=102K and the formation of different magnetic domains above TC. Between TC&lt;T&lt;270K, the following two magnetic environments appear, a dense spin region and a static-dilute spin region. The paramagnetic state is obtained only above T&gt;270K. An evolution of the interaction between Ni and Re magnetic sublattices, in this geometrically frustrated fcc perovskite structure, is revealed as a function of temperature through the critical behavior and thermal evolution of microscopic and macroscopic physical quantities

Human stem cell-derived monocytes and microglia-like cells reveal impaired amyloid plaque clearance upon heterozygous or homozygous loss of TREM2

INTRODUCTION: Murine microglia expressing the Alzheimer's disease-linked TREM2R47H mutation display variable decrease in phagocytosis, while impaired phagocytosis is reported following loss of TREM2. However, no data exist on TREM2+/R47H human microglia. Therefore, we created human pluripotent stem cell (hPSC) monocytes and transdifferentiated microglia-like cells (tMGs) to examine the effect of the TREM2+/R47H mutation and loss of TREM2 on phagocytosis. METHODS: We generated isogenic TREM2+/R47H, TREM2+/-, and TREM2-/- hPSCs using CRISPR/Cas9. Following differentiation to monocytes and tMGs, we studied the uptake of Escherichia coli fragments and analyzed amyloid plaque clearance from cryosections of APP/PS1+/- mouse brains. RESULTS: We demonstrated that tMGs resemble cultured human microglia. TREM2+/- and TREM2-/- hPSC monocytes and tMGs phagocytosed significantly less E. coli fragments and cleared less amyloid plaques than wild-type hPSC progeny, with no difference for TREM2+/R47H progeny. DISCUSSION: In vitro phagocytosis of hPSC monocytes and tMGs was not affected by the TREM2+/R47H mutation but was significantly impaired in TREM2+/- and TREM2-/- progeny