1,278 research outputs found
SUMOylation inhibits FOXM1 activity and delays mitotic transition
The forkhead box transcription factor FOXM1 is an essential effector of G2/M-phase transition, mitosis and the DNA damage response. As such, it is frequently deregulated during tumorigenesis. Here we report that FOXM1 is dynamically modified by SUMO1 but not by SUMO2/3 at multiple sites. We show that FOXM1 SUMOylation is enhanced in MCF-7 breast cancer cells in response to treatment with epirubicin and mitotic inhibitors. Mutation of five consensus conjugation motifs yielded a SUMOylation-deficient mutant FOXM1. Conversely, fusion of the E2 ligase Ubc9 to FOXM1 generated an auto-SUMOylating mutant (FOXM1-Ubc9). Analysis of wild-type FOXM1 and mutants revealed that SUMOylation inhibits FOXM1 activity, promotes translocation to the cytoplasm and enhances APC/Cdh1-mediated ubiquitination and degradation. Further, expression of the SUMOylation-deficient mutant enhanced cell proliferation compared with wild-type FOXM1, whereas the FOXM1-Ubc9 fusion protein resulted in persistent cyclin B1 expression and slowed the time from mitotic entry to exit. In summary, our findings suggest that SUMOylation attenuates FOXM1 activity and causes mitotic delay in cytotoxic drug response
Evaluation of applying IHC4 as a prognostic model in the translational study of Intergroup Exemestane Study (IES): PathIES
Background: Intergroup Exemestane Study (IES) was a randomised study that showed a survival benefit of switching adjuvant endocrine therapy after 2–3 years from tamoxifen to exemestane. This PathIES aimed to assess the role of immunohistochemical (IHC)4 score in determining the relative sensitivity to either tamoxifen or sequential treatment with tamoxifen and exemestane. Patients and methods: Primary tumour samples were available for 1274 patients (27% of IES population). Only patients for whom the IHC4 score could be calculated (based on oestrogen receptor, progesterone receptor, HER2 and Ki67) were included in this analysis (N = 430 patients). The clinical score (C) was based on age, grade, tumour size and nodal status. The association of clinicopathological parameters, IHC4(+C) scores and treatment effect with time to distant recurrence-free survival (TTDR) was assessed in univariable and multivariable Cox regression analyses. A modified clinical score (PathIEscore) (N = 350) was also estimated. Results: Our results confirm the prognostic importance of the original IHC4, alone and in conjunction with clinical scores, but no significant difference with treatment effects was observed. The combined IHC4 + Clinical PathIES score was prognostic for TTDR (P < 0.001) with a hazard ratio (HR) of 5.54 (95% CI 1.29–23.70) for a change from 1st quartile (Q1) to Q1–Q3 and HR of 15.54 (95% CI 3.70–65.24) for a change from Q1 to Q4. Conclusion: In the PathIES population, the IHC4 score is useful in predicting long-term relapse in patients who remain disease-free after 2–3 years. This is a first trial to suggest the extending use of IHC4+C score for prognostic indication for patients who have switched endocrine therapies at 2–3 years and who remain disease-free after 2–3 years
Thermodynamics of the bilinear-biquadratic spin one Heisenberg chain
The magnetic susceptibility and specific heat of the one-dimensional S=1
bilinear-biquadratic Heisenberg model are calculated using the transfer matrix
renormalization group. By comparing the results with the experimental data of
measured by Millet et al. (Phys. Rev. Lett. {\bf 83}, 4176
(1999)), we find that the susceptibility data of this material, after
subtracting the impurity contribution, can be quantitatively explained with
this model. The biquadratic exchange interaction in this material is found to
be ferromagnetic, i.e. with a positive coupling constant.Comment: 4 pages, 4 postscript figure
Parity Violation in Proton-Proton Scattering at 221 MeV
The parity-violating longitudinal analyzing power, Az, has been measured in
pp elastic scattering at an incident proton energy of 221 MeV. The result
obtained is Az =(0.84 +/- 0.29 (stat.) +/- 0.17 (syst.)) x 10^{-7}. This
experiment is unique in that it selects a single parity violating transition
amplitude, 3P2-1D2, and consequently directly constrains the weak meson-nucleon
coupling constant h^pp_rho When this result is taken together with the existing
pp parity violation data, the weak meson-nucleon coupling constants h^pp_rho
and h^pp_omega can, for the first time, both be determined.Comment: 8 pages RevTeX4, 3 PostScript figures. Conclusion revised. New
information about weak coupling constants adde
Spike-Train Responses of a Pair of Hodgkin-Huxley Neurons with Time-Delayed Couplings
Model calculations have been performed on the spike-train response of a pair
of Hodgkin-Huxley (HH) neurons coupled by recurrent excitatory-excitatory
couplings with time delay. The coupled, excitable HH neurons are assumed to
receive the two kinds of spike-train inputs: the transient input consisting of
impulses for the finite duration (: integer) and the sequential input
with the constant interspike interval (ISI). The distribution of the output ISI
shows a rich of variety depending on the coupling strength and the
time delay. The comparison is made between the dependence of the output ISI for
the transient inputs and that for the sequential inputs.Comment: 19 pages, 4 figure
A density matrix renormalisation group algorithm for quantum lattice systems with a large number of states per site
A variant of White's density matrix renormalisation group scheme which is
designed to compute low-lying energies of one-dimensional quantum lattice
models with a large number of degrees of freedom per site is described. The
method is tested on two exactly solvable models---the spin-1/2
antiferromagnetic Heisenberg chain and a dimerised XY spin chain. To illustrate
the potential of the method, it is applied to a model of spins interacting with
quantum phonons. It is shown that the method accurately resolves a number of
energy gaps on periodic rings which are sufficiently large to afford an
accurate investigation of critical properties via the use of finite-size
scaling theory.Comment: RevTeX, 8 pages, 2 figure
Why I tense up when you watch me: inferior parietal cortex mediates an audience’s influence on motor performance
The presence of an evaluative audience can alter skilled motor performance through changes in force output. To investigate how this is mediated within the brain, we emulated real-time social monitoring of participants’ performance of a fine grip task during functional magnetic resonance neuroimaging. We observed an increase in force output during social evaluation that was accompanied by focal reductions in activity within bilateral inferior parietal cortex. Moreover, deactivation of the left inferior parietal cortex predicted both inter- and intra-individual differences in socially-induced change in grip force. Social evaluation also enhanced activation within the posterior superior temporal sulcus, which conveys visual information about others’ actions to the inferior parietal cortex. Interestingly, functional connectivity between these two regions was attenuated by social evaluation. Our data suggest that social evaluation can vary force output through the altered engagement of inferior parietal cortex; a region implicated in sensorimotor integration necessary for object manipulation, and a component of the action-observation network which integrates and facilitates performance of observed actions. Social-evaluative situations may induce high-level representational incoherence between one’s own intentioned action and the perceived intention of others which, by uncoupling the dynamics of sensorimotor facilitation, could ultimately perturbe motor output
Parity Violation in Proton-Proton Scattering at 221 MeV
TRIUMF experiment 497 has measured the parity violating longitudinal
analyzing power, A_z, in pp elastic scattering at 221.3 MeV incident proton
energy. This paper includes details of the corrections, some of magnitude
comparable to A_z itself, required to arrive at the final result. The largest
correction was for the effects of first moments of transverse polarization. The
addition of the result, A_z=(0.84 \pm 0.29 (stat.) \pm 0.17 (syst.)) \times
10^{-7}, to the pp parity violation experimental data base greatly improves the
experimental constraints on the weak meson-nucleon coupling constants
h^{pp}_\rho and h^{pp}_\omega, and has implications for the interpretation of
electron parity violation experiments.Comment: 17 pages RevTeX, 14 PostScript figures. Revised version with
additions suggested by Phys. Rev.
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