The G1 cyclin, cyclin D1, has been implicated in the development of human and mouse tumors. Here we describe immunohistochemical analyses of cyclin D1 for a large panel of mouse B cell tumors. In ...addition, we characterize cyclin D1 expression in a series of cultured cell lines that represent transformed B cells at different stages of development. Immunohistochemical analysis showed that for low-grade lymphomas, cyclin D1 was expressed by 83% of centroblastic–centrocytic (CBCC) and 14% of small lymphocytic lymphomas (SLL). For high-grade tumors, 28% of B lymphoblastic and 23% of centroblastic tumors expressed cyclin D1, while all immunoblastic lymphomas were negative. Studies of RNA and protein prepared from cultured B lineage tumors showed that cyclin D1 was expressed by all pre-B and most B cell tumors but not by cell lines representative of late B cell differentiation or by plasma cells. Expression of cyclin D1 in the lymphomas was not associated with alterations in the genomic structure of the
Fis-1 (
Bcl-1) common proviral integration site or cyclin D1 itself or with cell growth activity as assessed by expression of proliferating cell nuclear antigen (PCNA).
The results of this study demonstrate that murine cytomegalovirus (MCMV) induces polyclonal B cell activation in mice during the acute phase of primary infection. First, flow cytometric analysis ...revealed that surface expression of CD45R, IgM, and Igκ by splenocytes from MCMV-infected mice was significantly reduced with a concomitant increase in the frequency of surface IgG-expressing cells. Second, ELIspot assays demonstrated that the changes revealed by flow cytometry were paralleled by increases in the numbers of IgG-producing cells, especially those secreting IgG2a. Third, the IgG antibodies from MCMV-infected animals reacted against a variety of self and foreign antigens. MCMV-induced B cell activation was independent of CD4+T-cell-mediated help and CD40, since activation was observed in two models of mice deficient for this T cell subset and in mice deficient for CD40. Reverse transcription–polymerase chain reaction analysis showed that mRNA transcripts for the cytokines IL-6, IL-10, and IFN-γ were rapidly induced following infection with MCMV, but only IL-6 and IFN-γ proteins were detectable by ELISA. In addition, the numbers of cells producing IL-6 and IFN-γ were significantly increased in the spleen. The magnitude of the polyclonal B cell activation response was diminished by 50% in IL-6-deficient mice but not in mice lacking IFN-γ. In the absence of IFN-γ, surface expression and serum levels of IgG2awere reduced while IgG1expression was increased.
LY315920 is a potent, selective inhibitor of recombinant human, group IIA, nonpancreatic secretory PLA2 (sPLA2). In a chromogenic isolated enzyme assay, LY315920 inhibited sPLA2 activity with an IC50 ...of 9 +/- 1 nM or 7.3 x 10(-6) mole fraction, which approached the stiochiometric limit of this assay. The true potency of LY315920 was defined using a deoxycholate/phosphatidylcholine assay with a mole fraction of 1.5 x 10(-6). LY315920 was 40-fold less active against human, group IB, pancreatic sPLA2 and was inactive against cytosolic PLA2 and the constitutive and inducible forms of cyclooxygenase. Human sPLA2-induced release of thromboxane A2 (TXA2) from isolated guinea pig lung bronchoalveolar lavage cells was inhibited by LY315920 with an IC50 of 0.79 microM. The release of TXA2 from these cells by N-formyl-methionyl-leucyl-phenylalanine or arachidonic acid was not inhibited. The i.v. administration of LY315920, 5 min before harvesting the bronchoalveolar lavage cells, resulted in the inhibition of sPLA2-induced production of TXA2 with an ED50 of 16.1 mg/kg. Challenge of guinea pig lung pleural strips with sPLA2 produced contractile responses that were suppressed in a concentration-dependent manner by LY315920 with an apparent KB of 83 +/- 14 nM. Contractile responses induced by arachidonic acid were not altered. Intravenous or oral administration of LY315920 to transgenic mice expressing the human sPLA2 protein inhibited serum sPLA2 activity in a dose-related manner over a 4-h time course. LY315920 is a potent and selective sPLA2 inhibitor and represents a new class of anti-inflammatory agent designated SPI. This agent is currently undergoing clinical evaluation and should help to define the role of sPLA2 in various inflammatory disease states.
The population of Milky Way (MW) satellites contains the faintest known galaxies and thus provides essential insight into galaxy formation and dark matter microphysics. Here we combine a model of the ...galaxy--halo connection with newly derived observational selection functions based on searches for satellites in photometric surveys over nearly the entire high Galactic latitude sky. In particular, we use cosmological zoom-in simulations of MW-like halos that include realistic Large Magellanic Cloud (LMC) analogs to fit the position-dependent MW satellite luminosity function. We report decisive evidence for the statistical impact of the LMC on the MW satellite population due to an estimated \(6\pm 2\) observed LMC-associated satellites, consistent with the number of LMC satellites inferred from Gaia proper-motion measurements, confirming the predictions of cold dark matter models for the existence of satellites within satellite halos. Moreover, we infer that the LMC fell into the MW within the last \(2\ \rm{Gyr}\) at high confidence. Based on our detailed full-sky modeling, we find that the faintest observed satellites inhabit halos with peak virial masses below \(3.2\times 10^{8}\ M_{\rm{\odot}}\) at \(95\%\) confidence, and we place the first robust constraints on the fraction of halos that host galaxies in this regime. We predict that the faintest detectable satellites occupy halos with peak virial masses above \(10^{6}\ M_{\rm{\odot}}\), highlighting the potential for powerful galaxy formation and dark matter constraints from future dwarf galaxy searches.
Mice infected with LP-BM5 murine leukemia virus (MuLV) develop a syndrome denoted as murine AIDS. Macrophages harvested from the peritoneal cavities of these mice at 4 or 9 wk postinoculation with ...LP-BM5 MuLV were analyzed by Northern hybridization for the presence of the defective LP-BM5 virus and their ability to synthesize various cytokines upon induction with Newcastle disease virus (NDV) or (LPS). Neither IFN-alpha or IFN-beta was found to be constitutively expressed in LP-BM5-infected macrophages and in NDV induction studies, and the levels of biologically active IFN-alpha and its mRNA were found to be lower in LP-BM5 MuLV-infected macrophages than in the macrophages from uninfected controls. Similarly, after NDV or LPS induction, the levels of TNF mRNA and TNF protein were significantly lower in LP-BM5-infected macrophages than in macrophages from uninfected mice. The LP-BM5 MuLV-infected macrophages constitutively expressed low levels of IL-1 beta, and when induced with LPS, the relative levels of IL-1 beta were significantly higher in infected than in uninfected macrophages. Although no constitutive expression of IL-6 was detected, the levels of IL-6 mRNA induced with NDV were higher in LP-BM5 MuLV-infected macrophages than in controls. Thus, we found alterations in the expression of selected cytokines in macrophages from mice inoculated with LP-BM5 MuLV rather than a general deregulation of all cytokine expression. These results show that macrophages infected with the defective LP-BM5 virus respond differently to NDV- or LPS-stimulation and suggest that aberrant expression of certain cytokine genes may play a role in the immunopathologic condition in mice with murine AIDS.
Here we present photometric redshift estimates for galaxies used in the weak lensing analysis of the Dark Energy Survey Science Verification (DES SV) data. Four model- or machine learning-based ...photometric redshift methods—annz2, bpz calibrated against BCC-Ufig simulations, skynet, and tpz—are analyzed. For training, calibration, and testing of these methods, we construct a catalogue of spectroscopically confirmed galaxies matched against DES SV data. The performance of the methods is evaluated against the matched spectroscopic catalogue, focusing on metrics relevant for weak lensing analyses, with additional validation against COSMOS photo-z’s. From the galaxies in the DES SV shear catalogue, which have mean redshift 0.72±0.01 over the range 0.3<z<1.3, we construct three tomographic bins with means of z={0.45,0.67,1.00}. These bins each have systematic uncertainties δz≲0.05 in the mean of the fiducial skynet photo-z n(z). We propagate the errors in the redshift distributions through to their impact on cosmological parameters estimated with cosmic shear, and find that they cause shifts in the value of σ8 of approximately 3%. This shift is within the one sigma statistical errors on σ8 for the DES SV shear catalogue. We further study the potential impact of systematic differences on the critical surface density, Σcrit, finding levels of bias safely less than the statistical power of DES SV data. In conclusion, we recommend a final Gaussian prior for the photo-z bias in the mean of n(z) of width 0.05 for each of the three tomographic bins, and show that this is a sufficient bias model for the corresponding cosmology analysis.
We derive the stellar mass fraction in the galaxy cluster RXC J2248.7-4431 observed with the Dark Energy Survey (DES) during the Science Verification period. We compare the stellar mass results from ...DES (five filters) with those from the Hubble Space Telescope Cluster Lensing And Supernova Survey (CLASH; 17 filters). When the cluster spectroscopic redshift is assumed, we show that stellar masses from DES can be estimated within 25 per cent of CLASH values. We compute the stellar mass contribution coming from red and blue galaxies, and study the relation between stellar mass and the underlying dark matter using weak lensing studies with DES and CLASH. An analysis of the radial profiles of the DES total and stellar mass yields a stellar-to-total fraction of f(star) = (6.8 +/- 1.7) x 10(-3) within a radius of r(200c) similar or equal to 2 Mpc. Our analysis also includes a comparison of photometric redshifts and star/galaxy separation efficiency for both data sets. We conclude that space-based small field imaging can be used to calibrate the galaxy properties in DES for the much wider field of view. The technique developed to derive the stellar mass fraction in galaxy clusters can be applied to the similar to 100 000 clusters that will be observed within this survey and yield important information about galaxy evolution.
PDF
