Systematic Definition of Protein Constituents along the Major Polarization Axis Reveals an Adaptive Reuse of the Polarization Machinery in Pheromone-Treated Budding Yeast

Polarizing cells extensively restructure cellular components in a spatially and temporally coupledmanner along the major axis of cellular extension. Budding yeast are a useful model of polarized growth, helping to define many molecular components of this conserved process. Besides budding, yeast cells also differentiate upon treatment with pheromone from the opposite mating type, forming a mating projection (the ‘shmoo’) by directional restructuring of the cytoskeleton, localized vesicular transport and overall reorganization of the cytosol. To characterize the proteomic localization changes ac-companying polarized growth, we developed and implemented a novel cell microarray-based imaging assay for measuring the spatial redistribution of a large fraction of the yeast proteome, and applied this assay to identify proteins localized along the mating projection following pheromone treatment. We further trained a machine learning algorithm to refine the cell imaging screen, identifying additional shmoo-localized proteins. In all, we identified 74 proteins that specifically localize to the mating projection, including previously uncharacterized proteins (Ycr043c, Ydr348c, Yer071c, Ymr295c, and Yor304c-a) and known polarization complexes such as the exocyst. Functional analysis of these proteins, coupled with quantitative analysis of individual organelle movements during shmoo formation, suggests a model in which the basic machinery for cell polarization is generally conserved between processe

Defining forgiveness: Christian clergy and general population perspectives.

The lack of any consensual definition of forgiveness is a serious weakness in the research literature (McCullough, Pargament &amp; Thoresen, 2000). As forgiveness is at the core of Christianity, this study returns to the Christian source of the concept to explore the meaning of forgiveness for practicing Christian clergy. Comparisons are made with a general population sample and social science definitions of forgiveness to ensure that a shared meaning of forgiveness is articulated. Anglican and Roman Catholic clergy (N = 209) and a general population sample (N = 159) completed a postal questionnaire about forgiveness. There is agreement on the existence of individual differences in forgiveness. Clergy and the general population perceive reconciliation as necessary for forgiveness while there is no consensus within psychology. The clergy suggests that forgiveness is limitless and that repentance is unnecessary while the general population suggests that there are limits and that repentance is necessary. Psychological definitions do not conceptualize repentance as necessary for forgiveness and the question of limits has not been addressed although within therapy the implicit assumption is that forgiveness is limitless.</p

CD4 Depletion in SIV-Infected Macaques Results in Macrophage and Microglia Infection with Rapid Turnover of Infected Cells

In rhesus macaques (RMs), experimental depletion of CD4+ T-cells prior to SIV infection results in higher viremia and emergence of CD4-independent SIV-envelopes. In this study we used the rhesus recombinant anti-CD4 antibody CD4R1 to deplete RM CD4+ T-cells prior to SIVmac251 infection and investigate the sources of the increased viral burden and the lifespan of productively infected cells. CD4-depleted animals showed (i) set-point viral load two-logs higher than controls; (ii) macrophages constituting 80% of all SIV vRNA+ cells in lymph node and mucosal tissues; (iii) substantial expansion of pro-inflammatory monocytes; (iv) aberrant activation and infection of microglial cells; and (v) lifespan of productively infected cells significantly longer in comparison to controls, but markedly shorter than previously estimated for macrophages. The net effect of CD4+ T-cell depletion is an inability to control SIV replication and a shift in the tropism of infected cells to macrophages, microglia, and, potentially, other CD4-low cells which all appear to have a shortened in vivo lifespan. We believe these findings have important implications for HIV eradication studies

Measurement of inclusive charged current interactions on carbon in a few-GeV neutrino beam

The SciBooNE Collaboration reports a measurement of inclusive charged current interactions of muon neutrinos on carbon with an average energy of 0.8 GeV using the Fermilab Booster Neutrino Beam. We compare our measurement with two neutrino interaction simulations: NEUT and NUANCE. The charged current interaction rates (product of flux and cross section) are extracted by fitting the muon kinematics, with a precision of 6-15% for the energy dependent and 3% for the energy integrated analyses. We also extract CC inclusive interaction cross sections from the observed rates, with a precision of 10-30% for the energy dependent and 8% for the energy integrated analyses. This is the first measurement of the CC inclusive cross section on carbon around 1 GeV. These results can be used to convert previous SciBooNE cross section ratio measurements to absolute cross section values.Comment: 21 pages, 16 figures. Accepted by Phys. Rev. D. Minor revisions to match the accepted versio

The Akt inhibitor KP372-1 suppresses Akt activity and cell proliferation and induces apoptosis in thyroid cancer cells

The phosphatidylinositol 3′ kinase (PI3K)/phosphatase and tensin homologue deleted on chromosome ten/Akt pathway, which is a critical regulator of cell proliferation and survival, is mutated or activated in a wide variety of cancers. Akt appears to be a key central node in this pathway and thus is an attractive target for targeted molecular therapy. We demonstrated that Akt is highly phosphorylated in thyroid cancer cell lines and human thyroid cancer specimens, and hypothesised that KP372-1, an Akt inhibitor, would block signalling through the PI3K pathway and inhibit cell proliferation while inducing apoptosis of thyroid cancer cells. KP372-1 blocked signalling downstream of Akt in thyroid tumour cells, leading to inhibition of cell proliferation and increased apoptosis. As thyroid cancer consistently expresses phosphorylated Akt and KP372-1 effectively blocks Akt signalling, further preclinical evaluation of this compound for treatment of thyroid cancer is warranted

Measurement of inclusive charged current interactions on carbon in a few-GeV neutrino beam

We report a measurement of inclusive charged current interactions of muon neutrinos on carbon with an average energy of 0.8 GeV using the Fermilab Booster Neutrino Beam. We compare our measurement with two neutrino interaction simulations: NEUT and NUANCE. The charged current interaction rates (product of flux and cross section) are extracted by fitting the muon kinematics, with a precision of 6%-15% for the energy dependent and 3% for the energy integrated analyses. We also extract charged current inclusive interaction cross sections from the observed rates, with a precision of 10%-30% for the energy dependent and 8% for the energy integrated analyses. This is the first measurement of the charged current inclusive cross section on carbon around 1 GeV. These results can be used to convert previous SciBooNE cross-section ratio measurements to absolute cross-section values. © 2011 American Physical Society

Measurement of K\u3csup\u3e+\u3c/sup\u3e production cross section by 8 GeV protons using high-energy neutrino interactions in the SciBooNE detector

The SciBooNE Collaboration reports K+ production cross section and rate measurements using high-energy daughter muon neutrino scattering data off the SciBar polystyrene (C8H8) target in the SciBooNE detector. The K+ mesons are produced by 8 GeV protons striking a beryllium target in Fermilab Booster Neutrino Beam line (BNB). Using observed neutrino and antineutrino events in SciBooNE, we measure d2σdpdΩ=(5. 34±0.76)mb/(GeV/c×sr) for p+Be→K++X at mean K + energy of 3.9 GeV and angle (with respect to the proton beam direction) of 3.7 degrees, corresponding to the selected K+ sample. Compared to Monte Carlo predictions using previous higher energy K+ production measurements, this measurement, which uses the NUANCE neutrino interaction generator, is consistent with a normalization factor of 0.85±0.12. This agreement is evidence that the extrapolation of the higher energy K+ measurements to an 8 GeV beam energy using Feynman scaling is valid. This measurement reduces the error on the K+ production cross section from 40% to 14%. © 2011 American Physical Society

Improved measurement of neutral current coherent π0 production on carbon in a few-GeV neutrino beam

The SciBooNE Collaboration reports a measurement of neutral current coherent π0 production on carbon by a muon neutrino beam with average energy 0.8 GeV. The separation of coherent from inclusive π0 production has been improved by detecting recoil protons from resonant π0 production. We measure the ratio of the neutral current coherent π0 production to total charged current cross sections to be (1.16±0.24)×10-2. The ratio of charged current coherent π+ to neutral current coherent π0 production is calculated to be 0.14-0.28+0.30, using our published charged current coherent pion measurement. © 2010 The American Physical Society

Measurement of inclusive neutral current π0 production on carbon in a few-GeV neutrino beam

The SciBooNE Collaboration reports inclusive neutral current neutral pion production by a muon neutrino beam on a polystyrene target (C8H8). We obtain (7.7±0.5(stat)±0.5(sys))×10-2 as the ratio of the neutral current neutral pion production to total charged current cross section; the mean energy of neutrinos producing detected neutral pions is 1.11/2 GeV. The result agrees with the Rein-Sehgal model implemented in our neutrino interaction simulation program with nuclear effects. The spectrum shape of the π0 momentum and angle agree with the model. We also measure the ratio of the neutral current coherent pion production to total charged current cross section to be (0.7±0.4)×10-2. © 2010 The American Physical Society

Measurement of the \nu_\mu charged current \pi^+ to quasi-elastic cross section ratio on mineral oil in a 0.8 GeV neutrino beam

Using high statistics samples of charged current $\nu_\mu$ interactions, MiniBooNE reports a measurement of the single charged pion production to quasi-elastic cross section ratio on mineral oil (CH$_2$), both with and without corrections for hadron re-interactions in the target nucleus. The result is provided as a function of neutrino energy in the range 0.4 GeV $< E_\nu <$ 2.4 GeV with 11% precision in the region of highest statistics. The results are consistent with previous measurements and the prediction from historical neutrino calculations.Comment: 4 pages, 2 figure