A36-dependent actin filament nucleation promotes release of vaccinia virus

Cell-to-cell transmission of vaccinia virus can be mediated by enveloped virions that remain attached to the outer surface of the cell or those released into the medium. During egress, the outer membrane of the double-enveloped virus fuses with the plasma membrane leaving extracellular virus attached to the cell surface via viral envelope proteins. Here we report that F-actin nucleation by the viral protein A36 promotes the disengagement of virus attachment and release of enveloped virus. Cells infected with the A36YdF virus, which has mutations at two critical tyrosine residues abrogating localised actin nucleation, displayed a 10-fold reduction in virus release. We examined A36YdF infected cells by transmission electron microscopy and observed that during release, virus appeared trapped in small invaginations at the plasma membrane. To further characterise the mechanism by which actin nucleation drives the dissociation of enveloped virus from the cell surface, we examined recombinant viruses by super-resolution microscopy. Fluorescently-tagged A36 was visualised at sub-viral resolution to image cell-virus attachment in mutant and parental backgrounds. We confirmed that A36YdF extracellular virus remained closely associated to the plasma membrane in small membrane pits. Virus-induced actin nucleation reduced the extent of association, thereby promoting the untethering of virus from the cell surface. Virus release can be enhanced via a point mutation in the luminal region of B5 (P189S), another virus envelope protein. We found that the B5P189S mutation led to reduced contact between extracellular virus and the host membrane during release, even in the absence of virus-induced actin nucleation. Our results posit that during release virus is tightly tethered to the host cell through interactions mediated by viral envelope proteins. Untethering of virus into the surrounding extracellular space requires these interactions be relieved, either through the force of actin nucleation or by mutations in luminal proteins that weaken these interactions. © 2013 Horsington et al

Myosin 1c and myosin IIB serve opposing roles in lamellipodial dynamics of the neuronal growth cone

The myosin family of motor proteins is implicated in mediating actin-based growth cone motility, but the roles of many myosins remain unclear. We previously implicated myosin 1c (M1c; formerly myosin Iβ) in the retention of lamellipodia (Wang et al., 1996). Here we address the role of myosin II (MII) in chick dorsal root ganglion neuronal growth cone motility and the contribution of M1c and MII to retrograde F-actin flow using chromophore-assisted laser inactivation (CALI). CALI of MII reduced neurite outgrowth and growth cone area by 25%, suggesting a role for MII in lamellipodial expansion. Micro-CALI of MII caused a rapid reduction in local lamellipodial protrusion in growth cones with no effects on filopodial dynamics. This is opposite to micro-CALI of M1c, which caused an increase in lamellipodial protrusion. We used fiduciary beads (Forscher et al., 1992) to observe retrograde F-actin flow during the acute loss of M1c or MII. Micro-CALI of M1c reduced retrograde bead flow by 76%, whereas micro-CALI of MII or the MIIB isoform did not. Thus, M1c and MIIB serve opposite and nonredundant roles in regulating lamellipodial dynamics, and M1c activity is specifically required for retrograde F-actin flow

Computerized cognitive training in prostate cancer patients on androgen deprivation therapy: a pilot study

© 2017, Springer-Verlag GmbH Germany, part of Springer Nature. Purpose: Prostate cancer patients who have undergone androgen deprivation therapy (ADT) may experience cognitive impairment, yet there is an unmet need for nonpharmacological interventions to address cognitive impairment in this population. This study examines the feasibility, acceptability, and preliminary efficacy of a home-based computerized cognitive training (CCT) program to treat cancer-related cognitive impairment. Methods: Sixty men who had received ≥ 3 months of ADT were screened for at least mild cognitive or neurobehavioral impairment and randomized to 8 weeks of CCT or usual care. Follow-up assessments occurred immediately post-intervention or equivalent (T2) and 8 weeks later (T3). The acceptability of CCT was also assessed. Results: Feasibility:A priori feasibility thresholds were partially met (i.e., randomization rate \u3e 50%, retention rate \u3e 70% excluding CCT drop-outs, but \u3c 70% for intent-to-treat). Acceptability: Participants were mostly satisfied with CCT and found it somewhat enjoyable, though barriers to uptake existed. Preliminary efficacy: Linear mixed models indicated significant time by group effects favorable to CCT in reaction time (p =.01), but unfavorable to CCT in verbal and visual memory (ps \u3c .05). Memory was temporarily suppressed in the CCT group at T2, but normalized by T3. There was no effect of CCT on self-reported cognitive functioning, neurobehavioral functioning, nor quality of life. Conclusions: This study provides tentative support for the feasibility and acceptability of CCT to treat mild cognitive impairment in ADT patients. CCT had a beneficial effect on reaction time, but temporarily suppressed memory. CCT’s benefits may be limited to a narrow area of functioning. Larger-scale studies are needed

Measurement of the Transverse Beam Spin Asymmetry in Elastic Electron Proton Scattering and the Inelastic Contribution to the Imaginary Part of the Two-Photon Exchange Amplitude

We report on a measurement of the asymmetry in the scattering of transversely polarized electrons off unpolarized protons, A$_\perp$, at two Q$^2$ values of \qsquaredaveragedlow (GeV/c)$^2$ and \qsquaredaveragedhighII (GeV/c)$^2$ and a scattering angle of $30^\circ < \theta_e < 40^\circ$. The measured transverse asymmetries are A$_{\perp}$(Q$^2$ = \qsquaredaveragedlow (GeV/c)$^2$) = (\experimentalasymmetry alulowcorr $\pm$ \statisticalerrorlow$_{\rm stat}$ $\pm$ \combinedsyspolerrorlowalucor$_{\rm sys}$) $\times$ 10$^{-6}$ and A$_{\perp}$(Q$^2$ = \qsquaredaveragedhighII (GeV/c)$^2$) = (\experimentalasymme tryaluhighcorr $\pm$ \statisticalerrorhigh$_{\rm stat}$ $\pm$ \combinedsyspolerrorhighalucor$_{\rm sys}$) $\times$ 10$^{-6}$. The first errors denotes the statistical error and the second the systematic uncertainties. A$_\perp$ arises from the imaginary part of the two-photon exchange amplitude and is zero in the one-photon exchange approximation. From comparison with theoretical estimates of A$_\perp$ we conclude that $\pi$N-intermediate states give a substantial contribution to the imaginary part of the two-photon amplitude. The contribution from the ground state proton to the imaginary part of the two-photon exchange can be neglected. There is no obvious reason why this should be different for the real part of the two-photon amplitude, which enters into the radiative corrections for the Rosenbluth separation measurements of the electric form factor of the proton.Comment: 4 figures, submitted to PRL on Oct.

A luminosity monitor for the A4 parity violation experiment at MAMI

A water Cherenkov luminosity monitor system with associated electronics has been developed for the A4 parity violation experiment at MAMI. The detector system measures the luminosity of the hydrogen target hit by the MAMI electron beam and monitors the stability of the liquid hydrogen target. Both is required for the precise study of the count rate asymmetries in the scattering of longitudinally polarized electrons on unpolarized protons. Any helicity correlated fluctuation of the target density leads to false asymmetries. The performance of the luminosity monitor, investigated in about 2000 hours with electron beam, and the results of its application in the A4 experiment are presented.Comment: 22 pages, 12 figures, submitted to NIM

Evidence for Strange Quark Contributions to the Nucleon's Form Factors at Q2Q^2 = 0.108 (GeV/c)2^2

We report on a measurement of the parity violating asymmetry in the elastic scattering of polarized electrons off unpolarized protons with the A4 apparatus at MAMI in Mainz at a four momentum transfer value of $Q^2$ = \Qsquare (GeV/c)$^2$ and at a forward electron scattering angle of 30$^\circ < \theta_e < 40^\circ$. The measured asymmetry is $A_{LR}(\vec{e}p)$ = (\Aphys $\pm$ \Deltastat$_{stat}$ $\pm$ \Deltasyst$_{syst}$) $\times$ 10$^{-6}$. The expectation from the Standard Model assuming no strangeness contribution to the vector current is A$_0$ = (\Azero $\pm$ \DeltaAzero) $\times$ 10$^{-6}$. We have improved the statistical accuracy by a factor of 3 as compared to our previous measurements at a higher $Q^2$. We have extracted the strangeness contribution to the electromagnetic form factors from our data to be $G_E^s$ + \FakGMs $G_M^s$ = \GEsGMs $\pm$ \DeltaGEsGMs at $Q^2$ = \Qsquare (GeV/c)$^2$. As in our previous measurement at higher momentum transfer for $G_E^s$ + 0.230 $G_M^s$, we again find the value for $G_E^s$ + \FakGMs $G_M^s$ to be positive, this time at an improved significance level of 2 $\sigma$.Comment: 4 pages, 3 figure

Structural and Electronic Properties of Small Neutral (MgO)n Clusters

Ab initio Perturbed Ion (PI) calculations are reported for neutral stoichiometric (MgO)n clusters (n<14). An extensive number of isomer structures was identified and studied. For the isomers of (MgO)n (n<8) clusters, a full geometrical relaxation was considered. Correlation corrections were included for all cluster sizes using the Coulomb-Hartree-Fock (CHF) model proposed by Clementi. The results obtained compare favorably to the experimental data and other previous theoretical studies. Inclusion of correlaiotn is crucial in order to achieve a good description of these systems. We find an important number of new isomers which allows us to interpret the experimental magic numbers without the assumption of structures based on (MgO)3 subunits. Finally, as an electronic property, the variations in the cluster ionization potential with the cluster size were studied and related to the structural isomer properties.Comment: 24 pages, LaTeX, 7 figures in GIF format. Accepted for publication in Phys. Rev.