194 research outputs found
Immunity to HIV-1 Is Influenced by Continued Natural Exposure to Exogenous Virus
Unprotected sexual intercourse between individuals who are both infected with HIV-1 can lead to exposure to their partner's virus, and potentially to super-infection. However, the immunological consequences of continued exposure to HIV-1 by individuals already infected, has to our knowledge never been reported. We measured T cell responses in 49 HIV-1 infected individuals who were on antiretroviral therapy with suppressed viral loads. All the individuals were in a long-term sexual partnership with another HIV-1 infected individual, who was either also on HAART and suppressing their viral loads, or viremic (>9000 copies/ml). T cell responses to HIV-1 epitopes were measured directly ex-vivo by the IFN-γ enzyme linked immuno-spot assay and by cytokine flow cytometry. Sexual exposure data was generated from questionnaires given to both individuals within each partnership. Individuals who continued to have regular sexual contact with a HIV-1 infected viremic partner had significantly higher frequencies of HIV-1-specific T cell responses, compared to individuals with aviremic partners. Strikingly, the magnitude of the HIV-1-specific T cell response correlated strongly with the level and route of exposure. Responses consisted of both CD4+ and CD8+ T cell subsets. Longitudinally, decreases in exposure were mirrored by a lower T cell response. However, no evidence for systemic super-infection was found in any of the individuals. Continued sexual exposure to exogenous HIV-1 was associated with increased HIV-1-specific T cell responses, in the absence of systemic super-infection, and correlated with the level and type of exposure
Akt1 Is Essential for Postnatal Mammary Gland Development, Function, and the Expression of Btn1a1
Akt1, a serine-threonine protein kinase member of the PKB/Akt gene family, plays critical roles in the regulation of multiple cellular processes, and has previously been implicated in lactation and breast cancer development. In this study, we utilized Akt1+/+ and Akt1−/− C57/Bl6 female mice to assess the role that Akt1 plays in normal mammary gland postnatal development and function. We examined postnatal morphology at multiple time points, and analyzed gene and protein expression changes that persist into adulthood. Akt1 deficiency resulted in several mammary gland developmental defects, including ductal outgrowth and defective terminal end bud formation. Adult Akt1−/− mammary gland composition remained altered, exhibiting fewer alveolar buds coupled with increased epithelial cell apoptosis. Microarray analysis revealed that Akt1 deficiency altered expression of genes involved in numerous biological processes in the mammary gland, including organismal development, cell death, and tissue morphology. Of particular importance, a significant decrease in expression of Btn1a1, a gene involved in milk lipid secretion, was observed in Akt1−/− mammary glands. Additionally, pseudopregnant Akt1−/− females failed to induce Btn1a1 expression in response to hormonal stimulation compared to their wild-type counterparts. Retroviral-mediated shRNA knockdown of Akt1 and Btn1a1 in MCF-7 human breast epithelial further illustrated the importance of Akt1 in mammary epithelial cell proliferation, as well as in the regulation of Btn1a1 and subsequent expression of ß-casein, a gene that encodes for milk protein. Overall these findings provide mechanistic insight into the role of Akt1 in mammary morphogenesis and function
Akt-Induced Phosphorylation of N-CoR at Serine 1450 Contributes to Its Misfolded Conformational Dependent Loss (MCDL) in Acute Myeloid Leukemia of the M5 Subtype
10.1371/journal.pone.0070891PLoS ONE88-POLN
Magnitude and Complexity of Rectal Mucosa HIV-1-Specific CD8+ T-Cell Responses during Chronic Infection Reflect Clinical Status
The intestinal mucosa displays robust virus replication and pronounced CD4+ T-cell loss during acute human immunodeficiency virus type 1 (HIV-1) infection. The ability of HIV-specific CD8+ T-cells to modulate disease course has prompted intensive study, yet the significance of virus-specific CD8+ T-cells in mucosal sites remains unclear.We evaluated five distinct effector functions of HIVgag-specific CD8+ T-cells in rectal mucosa and blood, individually and in combination, in relationship to clinical status and antiretroviral therapy (ART). In subjects not on ART, the percentage of rectal Gag-specific CD8+ T-cells capable of 3, 4 or 5 simultaneous effector functions was significantly related to blood CD4 count and inversely related to plasma viral load (PVL) (p<0.05). Polyfunctional rectal CD8+ T-cells expressed higher levels of MIP-1beta and CD107a on a per cell basis than mono- or bifunctional cells. The production of TNFalpha, IFN-gamma, and CD107a by Gag-specific rectal CD8+ T-cells each correlated inversely (p<0.05) with PVL, and MIP-1beta expression revealed a similar trend. CD107a and IFN-gamma production were positively related to blood CD4 count (p<0.05), with MIP-1beta showing a similar trend. IL-2 production by rectal CD8+ T-cells was highly variable and generally low, and showed no relationship to viral load or blood CD4 count.The polyfunctionality of rectal Gag-specific CD8+ T-cells appears to be related to blood CD4 count and inversely related to PVL. The extent to which these associations reflect causality remains to be determined; nevertheless, our data suggest a potentially important role for mucosal T-cells in limiting virus replication during chronic infection
Improved Measurement of the Pseudoscalar Decay Constant
We present a new determination of the Ds decay constant, f_{Ds} using 5
million continuum charm events obtained with the CLEO II detector. Our value is
derived from our new measured ratio of widths for Ds -> mu nu/Ds -> phi pi of
0.173+/- 0.021 +/- 0.031. Taking the branching ratio for Ds -> phi pi as (3.6
+/- 0.9)% from the PDG, we extract f_{Ds} = (280 +/- 17 +/- 25 +/- 34){MeV}. We
compare this result with various model calculations.Comment: 23 page postscript file, postscript file also available through
http://w4.lns.cornell.edu/public/CLN
First Observation of and Decays
We have observed new channels for decays with an in the final
state. We study 3-prong tau decays, using the and
\eta\to 3\piz decay modes and 1-prong decays with two \piz's using the
channel. The measured branching fractions are
\B(\tau^{-}\to \pi^{-}\pi^{-}\pi^{+}\eta\nu_{\tau})
=(3.4^{+0.6}_{-0.5}\pm0.6)\times10^{-4} and \B(\tau^{-}\to
\pi^{-}2\piz\eta\nu_{\tau}
=(1.4\pm0.6\pm0.3)\times10^{-4}. We observe clear evidence for
substructure and measure \B(\tau^{-}\to
f_1\pi^{-}\nu_{\tau})=(5.8^{+1.4}_{-1.3}\pm1.8)\times10^{-4}. We have also
searched for production and obtain 90% CL upper limits
\B(\tau^{-}\to \pi^{-}\eta'\nu_\tau)<7.4\times10^{-5} and \B(\tau^{-}\to
\pi^{-}\piz\eta'\nu_\tau)<8.0\times10^{-5}.Comment: 11 page postscript file, postscript file also available through
http://w4.lns.cornell.edu/public/CLN
Search for the Decays B^0 -> D^{(*)+} D^{(*)-}
Using the CLEO-II data set we have searched for the Cabibbo-suppressed decays
B^0 -> D^{(*)+} D^{(*)-}. For the decay B^0 -> D^{*+} D^{*-}, we observe one
candidate signal event, with an expected background of 0.022 +/- 0.011 events.
This yield corresponds to a branching fraction of Br(B^0 -> D^{*+} D^{*-}) =
(5.3^{+7.1}_{-3.7}(stat) +/- 1.0(syst)) x 10^{-4} and an upper limit of Br(B^0
-> D^{*+} D^{*-}) D^{*\pm} D^\mp and
B^0 -> D^+ D^-, no significant excess of signal above the expected background
level is seen, and we calculate the 90% CL upper limits on the branching
fractions to be Br(B^0 -> D^{*\pm} D^\mp) D^+
D^-) < 1.2 x 10^{-3}.Comment: 12 page postscript file also available through
http://w4.lns.cornell.edu/public/CLNS, submitted to Physical Review Letter
Production in Two-Photon Interactions at CLEO
Using the CLEO detector at the Cornell storage ring, CESR, we study
the two-photon production of , making the first
observation of . We present the
cross-section for as a function of
the center of mass energy and compare it to that predicted by
the quark-diquark model.Comment: 10 pages, postscript file also available through
http://w4.lns.cornell.edu/public/CLN
Observation of the Decay
Using e+e- annihilation data collected by the CLEO~II detector at CESR, we
have observed the decay Ds+ to omega pi+. This final state may be produced
through the annihilation decay of the Ds+, or through final state interactions.
We find a branching ratio of [Gamma(Ds+ to omega pi+)/Gamma(Ds+ to eta
pi+)]=0.16+-0.04+-0.03, where the first error is statistical and the second is
systematic.Comment: 9 pages, postscript file also available through
http://w4.lns.cornell.edu/public/CLN
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