Heat-induced and spontaneous expression of Hsp70.1Luciferase transgene copies localized on Xp22 in female bovine cells

<p>Abstract</p> <p>Background</p> <p>Expression of several copies of the heat-inducible <it>Hsp70.1Luciferase </it>(<it>LUC</it>) transgene inserted at a single X chromosome locus of a bull (<it>Bos taurus</it>) was assessed in females after X-chromosome inactivation (XCI). Furthermore, impact of the chromosomal environment on the spontaneous expression of these transgene copies before XCI was studied during early development in embryos obtained after in vitro fertilization (IVF), when the locus was carried by the X chromosome inherited from the bull, and after somatic cell nuclear transfer (SCNT) cloning, when the locus could be carried by the inactive Xi or the active Xa chromosome in a female donor cell, or by the (active) X in a male donor cell.</p> <p>Findings</p> <p>Transgene copies were mapped to bovine Xp22. In XX^{<it>LUC </it>}female fibroblasts, i.e. after random XCI, the proportions of late-replicating inactive and early-replicating active X^{<it>LUC </it>}chromosomes were not biased and the proportion of cells displaying an increase in the level of immunostained luciferase protein after heat-shock induction was similar to that in male fibroblasts. Spontaneous transgene expression occurred at the 8-16-cell stage both in transgenic (female) embryos obtained after IVF and in male and female embryos obtained after SCNT.</p> <p>Conclusions</p> <p>The X^{<it>LUC </it>}chromosome is normally inactivated but at least part of the inactivated X-linked <it>Hsp70.1Luciferase </it>transgene copies remains heat-inducible after random XCI in somatic cells. Before XCI, the profile of the transgenes' spontaneous expression is independent of the epigenetic origin of the X^{<it>LUC </it>}chromosome since it is similar in IVF female, SCNT male and SCNT female embryos.</p

The Elusive Optical Jets

Paper freely available at http://cdsads.u-strasbg.fr/cgi-bin/nph-iarticle_query?1991AJ....101...88F&data_type=PDF_HIGH&type=PRINTERImaging observations in the U band of eight radio galaxies are presented. We find no optical counterpart to the radio jets. For the three radio galaxies 3C 147, 3C 279 and 3C 433, we show that the radio to optical spectral index of the jet is significantly higher than the typical values found in the three best known optical jets (M87, 3C 273 and 3C 66B). We conclude that the cut-off frequencies are lower than $10^{14}$Hz in these cases. For the 3C 31 jet, our data are consistent with the radio to optical spectral index being comparable to the typical values. This result is in contradiction with the detection of the optical jet in the B band by Butcher et al (1980). Finally, the lower limit on the radio to optical spectral index we obtain for the four other radio jets of our sample is still consistent with the typical values

In Utero Exposure to Maternal Diabetes Impairs Vascular Expression of Prostacyclin Receptor in Rat Offspring

International audienc

OA04-01. Safety and immunogenicity of LIPO-5, a HIV-1 lipopeptide vaccine: results of ANRS VAC18, a phase 2, randomized, double-blind, placebo-controlled trial

International audiencen.

Interleukin 7 Increases Human Immunodeficiency Virus Type 1 LAI-Mediated Fas-Induced T-Cell Death

Fas-mediated T-cell death is known to occur during human immunodeficiency virus (HIV) infection. In this study, we found that HIV type 1 LAI (HIV-1(LAI)) primes CD8(+) T cells from healthy donors for apoptosis, which occurs after Fas ligation. This effect is counteracted by a broad caspase inhibitor (zVAD-fmk). Fas-mediated cell death does not depend on CD8(+) T-cell infection, because it occurred in the presence of reverse transcriptase inhibitors. However, purified CD8(+) T cells are sensitive to Fas only in the presence of soluble CD4. Finally, we found that interleukin 7 (IL-7) increases Fas-mediated CD4(+) and CD8(+) T-cell death induced by HIV-1(LAI). Since high levels of IL-7 are a marker of poor prognosis during HIV infection, our data suggest that enhancement of Fas-mediated T-cell death by HIV-1(LAI) and IL-7 is one of the mechanisms involved in progression to AIDS

The density of coreceptors at the surface of CD4+ T cells contributes to the extent of human immunodeficiency virus type 1 viral replication-mediated T cell death

Chemokine receptors serve as coreceptors for HIV-1 entry into CD4(+) T cells. Several reports have mentioned that density of CCR5 expression modulates in vitro viral replication and in vivo the course of the disease. Our goal was to investigate the impact of coreceptor density at the surface of a CD4(+) cell line on HIV-1 entry, replication, spreading, and programmed cell death. We engineered a CEM cell line that expresses constitutively CD4 and CXCR4 and CCR5 after transfection. This model allows us to compare the effect of the X4 and R5 strains to induce T cell death in the same T cell host. We show here that the extent of T cell death correlates with the rate of virus replication. X4 induces faster T cell death than R5 that depends at least in part on the higher density of CXCR4 compared to CCR5. Furthermore, sorting CEM populations expressing low, intermediate, and high densities of CCR5 molecules but constant amount of CD4, we found that the capacity to induce T cell death depends at least in part on the level of CCR5 when low amount of virus was used to infect the CEM cells. Moreover, viral transcription, assessed by cell-associated HIV-1 RNA/DNA ratio, was increased in CCR5high as compared to CCR5low cells, while inhibition of replication by zidovudine was more effective in CCR5low cells. Our data indicate that the density of chemokine receptors expressed on CD4(+) T cells may be a critical parameters for the cytopathic effect of HIV strains and may have major impact on CD4 T cell depletion during HAART

Negative modulation of suppressive HIV-specific regulatory T cells by IL-2 adjuvanted therapeutic vaccine.

The potential benefit in using IL-2 in immunotherapy for cancer and autoimmunity has been linked to the modulation of immune responses, which partly relies on a direct effect on Tregs populations. Here, we revisited the role of IL-2 in HIV infection and investigated whether its use as an adjuvant with therapeutic vaccination, impacts on HIV-specific responses. Antiretroviral therapy treated-patients were randomized to receive 4 boosts of vaccination (ALVACHIV/Lipo-6T, weeks 0/4/8/12) followed by 3 cycles of IL-2 (weeks 16/24/32) before treatment interruption (TI) at week40. IL-2 administration increased significantly HIV-specific CD4+CD25+CD134+ T-cell responses, which inversely correlated with viral load after TI (r = -0.7, p <0.007) in the vaccine/IL-2 group. IL-2 increased global CD25+CD127lowFoxP3+Tregs (p <0.05) while it decreased HIV- but not CMV- specific CD39+FoxP3+CD25+CD134+Tregs (p <0.05). HIV-specific Tregs were inversely correlated with IFN-γ producing specific-effectors (p = 0.03) and positively correlated with viral load (r = 0.7, p = 0.01), revealing their undesired presence during chronic infection. Global Tregs, but not HIV-specific Tregs, inversely correlated with a decrease in exhausted PD1+CD95+ T-cells (p = 0.001). Altogether, our results underline the negative impact of HIV-specific Tregs on HIV-specific effectors and reveal the beneficial use of IL-2 as an adjuvant as its administration increases global Tregs that impact on T-cell exhaustion and decreases HIV-specific CD39+Tregs by shifting the balance towards effectors