Prime movers : mechanochemistry of mitotic kinesins

Mitotic spindles are self-organizing protein machines that harness teams of multiple force generators to drive chromosome segregation. Kinesins are key members of these force-generating teams. Different kinesins walk directionally along dynamic microtubules, anchor, crosslink, align and sort microtubules into polarized bundles, and influence microtubule dynamics by interacting with microtubule tips. The mechanochemical mechanisms of these kinesins are specialized to enable each type to make a specific contribution to spindle self-organization and chromosome segregation

Survival of patients with metastatic breast cancer: twenty-year data from two SEER registries

BACKGROUND: Many researchers are interested to know if there are any improvements in recent treatment results for metastatic breast cancer in the community, especially for 10- or 15-year survival. METHODS: Between 1981 and 1985, 782 and 580 female patients with metastatic breast cancer were extracted respectively from the Connecticut and San Francisco-Oakland registries of the Surveillance, Epidemiology, and End Results (SEER) database. The lognormal statistical method to estimate survival was retrospectively validated since the 15-year cause-specific survival rates could be calculated using the standard life-table actuarial method. Estimated rates were compared to the actuarial data available in 2000. Between 1991 and 1995, further 752 and 632 female patients with metastatic breast cancer were extracted respectively from the Connecticut and San Francisco-Oakland registries. The data were analyzed to estimate the 15-year cause-specific survival rates before the year 2005. RESULTS: The 5-year period (1981–1985) was chosen, and patients were followed as a cohort for an additional 3 years. The estimated 15-year cause-specific survival rates were 7.1% (95% confidence interval, CI, 1.8–12.4) and 9.1% (95% CI, 3.8–14.4) by the lognormal model for the two registries of Connecticut and San Francisco-Oakland respectively. Since the SEER database provides follow-up information to the end of the year 2000, actuarial calculation can be performed to confirm (validate) the estimation. The Kaplan-Meier calculation for the 15-year cause-specific survival rates were 8.3% (95% CI, 5.8–10.8) and 7.0% (95% CI, 4.3–9.7) respectively. Using the 1991–1995 5-year period cohort and followed for an additional 3 years, the 15-year cause-specific survival rates were estimated to be 9.1% (95% CI, 3.8–14.4) and 14.7% (95% CI, 9.8–19.6) for the two registries of Connecticut and San Francisco-Oakland respectively. CONCLUSIONS: For the period 1981–1985, the 15-year cause-specific survival for the Connecticut and the San Francisco-Oakland registries were comparable. For the period 1991–1995, there was not much change in survival for the Connecticut registry patients, but there was an improvement in survival for the San Francisco-Oakland registry patients

Polo-Like Kinase-1 Controls Aurora A Destruction by Activating APC/C-Cdh1

Polo-like kinase-1 (Plk1) is activated before mitosis by Aurora A and its cofactor Bora. In mitosis, Bora is degraded in a manner dependent on Plk1 kinase activity and the E3 ubiquitin ligase SCF-βTrCP. Here, we show that Plk1 is also required for the timely destruction of its activator Aurora A in late anaphase. It has been shown that Aurora A destruction is controlled by the auxiliary subunit Cdh1 of the Anaphase-Promoting Complex/Cyclosome (APC/C). Remarkably, we found that Plk1-depletion prevented the efficient dephosphorylation of Cdh1 during mitotic exit. Plk1 mediated its effect on Cdh1, at least in part, through direct phosphorylation of the human phosphatase Cdc14A, controlling the phosphorylation state of Cdh1. We conclude that Plk1 facilitates efficient Aurora A degradation through APC/C-Cdh1 activation after mitosis, with a potential role for hCdc14A

Essential genes for astroglial development and axon pathfinding during zebrafish embryogenesis

The formation of the central nervous system depends on the coordinated development of neural and glial cell types that arise from a common precursor. Using an existing group of zebrafish mutants generated by viral insertion, we performed a “shelf-screen” to identify genes necessary for astroglial development and axon scaffold formation. We screened 274 of 315 viral insertion lines using antibodies that label axons (anti-Acetylated Tubulin) and astroglia (anti-Gfap) and identified 25 mutants with defects in gliogenesis, glial patterning, neurogenesis, and axon guidance. We also identified a novel class of mutants affecting radial glial cell numbers. Defects in astroglial patterning were always associated with axon defects, supporting an important role for axon-glial interactions during axon scaffold development. The genes disrupted in these viral lines have all been identified, providing a powerful new resource for the study of axon guidance, glio- and neurogenesis, and neuron-glial interactions during development of the vertebrate CNS.National Institutes of Health (U.S.) (Grant T32MH020051)National Institutes of Health (U.S.) (Grant F32NS043872

Search of Dark Matter Annihilation in the Galactic Centre using the ANTARES Neutrino Telescope

A search for high-energy neutrinos coming from the direction of the GalacticCentre is performed using the data recorded by the ANTARES neutrino telescopefrom 2007 to 2012. The event selection criteria are chosen to maximise thesensitivity to possible signals produced by the self-annihilation of weaklyinteracting massive particles accumulated around the centre of the Milky Waywith respect to the atmospheric background. After data unblinding, the numberof neutrinos observed in the line of sight of the Galactic Centre is found tobe compatible with background expectations. The 90% C.L. upper limits in termsof the neutrino+anti-neutrino flux, $\rm \Phi_{\nu_{\mu}+\bar{\nu}_\mu}$, andthe velocity averaged annihilation cross-section, $\rm$, arederived for the WIMP self-annihilation channels into \rmb\bar{b},W^{+}W^{-},\tau^{+}\tau^{-},\mu^{+}\mu^{-},\nu\bar{\nu}. The ANTARESlimits for $\rm$ are shown to be the most stringent for aneutrino telescope over the WIMP masses $\rm 25\,GeV < M_{WIMP} < 10\,TeV$

Observation of charmless hadronic B decays

Four candidates for charmless hadronic B decay are observed in a data sample of four million hadronic Z decays recorded by the ALEPH detector at LEP. The probability that these events come from background sources is estimated to be less than 10(-6). The average branching of weakly decaying B hadrons (a mixture of B-d(0), B-s(0) and Lambda(b) weighted by their production The average branching ratio of weakly decaying B hadrons (a mixture of B-d(0) cross sections and lifetimes, here denoted B) into two long-lived charged hadrons (pions, kaons or protons) is measured to be Br(B-->h(+)h(-))=(1.7(-0.7)(+1.0)+/-0.2)x10(-5). The relative branching fraction Br(B-d(s)(0)-->pi(+)pi(-)(K-))/Br(B-d(s)(0)-->h(+)h(-)) is measured to be 1.0(-0.3-0.1)(+0.0+0.0). In addition, branching ratio upper limits are obtained for a variety of exclusive charmless hadronic two-body decays of B hadrons

Four-fermion production in e+e−e^+e^- collisions at centre-of-mass energies of 130 and 136 GeV

Four-fermion events have been selected in a data sample of 5.8 pb−1 collected with the aleph detector at centre-of-mass energies of 130 and 136 GeV. The final states , ℓ+ℓ−ℓ+ℓ−, , and have been examined. Five events are observed in the data, in agreement with the Standard Model predictions of 6.67±0.38 events from four-fermion processes and 0.14−0.05+0.19 from background processes

Supernova Neutrino Burst Detection with the Deep Underground Neutrino Experiment

The Deep Underground Neutrino Experiment (DUNE), a 40-kton underground liquid argon time projection chamber experiment, will be sensitive to the electron-neutrino flavor component of the burst of neutrinos expected from the next Galactic core-collapse supernova. Such an observation will bring unique insight into the astrophysics of core collapse as well as into the properties of neutrinos. The general capabilities of DUNE for neutrino detection in the relevant few- to few-tens-of-MeV neutrino energy range will be described. As an example, DUNE's ability to constrain the ν_e spectral parameters of the neutrino burst will be considered

Supernova neutrino burst detection with the Deep Underground Neutrino Experiment

The Deep Underground Neutrino Experiment (DUNE), a 40-kton underground liquid argon time projection chamber experiment, will be sensitive to the electron-neutrino flavor component of the burst of neutrinos expected from the next Galactic core-collapse supernova. Such an observation will bring unique insight into the astrophysics of core collapse as well as into the properties of neutrinos. The general capabilities of DUNE for neutrino detection in the relevant few- to few-tens-of-MeV neutrino energy range will be described. As an example, DUNE's ability to constrain the νe spectral parameters of the neutrino burst will be considered