353 research outputs found

    DDA3 recruits microtubule depolymerase Kif2a to spindle poles and controls spindle dynamics and mitotic chromosome movement

    Get PDF
    Dynamic turnover of the spindle is a driving force for chromosome congression and segregation in mitosis. Through a functional genomic analysis, we identify DDA3 as a previously unknown regulator of spindle dynamics that is essential for mitotic progression. DDA3 depletion results in a high frequency of unaligned chromosomes, a substantial reduction in tension across sister kinetochores at metaphase, and a decrease in the velocity of chromosome segregation at anaphase. DDA3 associates with the mitotic spindle and controls microtubule (MT) dynamics. Mechanistically, DDA3 interacts with the MT depolymerase Kif2a in an MT-dependent manner and recruits Kif2a to the mitotic spindle and spindle poles. Depletion of DDA3 increases the steady-state levels of spindle MTs by reducing the turnover rate of the mitotic spindle and by increasing the rate of MT polymerization, which phenocopies the effects of partial knockdown of Kif2a. Thus, DDA3 represents a new class of MT-destabilizing protein that controls spindle dynamics and mitotic progression by regulating MT depolymerases

    Plk1- and β-TrCP–dependent degradation of Bora controls mitotic progression

    Get PDF
    Through a convergence of functional genomic and proteomic studies, we identify Bora as a previously unknown cell cycle protein that interacts with the Plk1 kinase and the SCF–β-TrCP ubiquitin ligase. We show that the Bora protein peaks in G2 and is degraded by proteasomes in mitosis. Proteolysis of Bora requires the Plk1 kinase activity and is mediated by SCF–β-TrCP. Plk1 phosphorylates a conserved DSGxxT degron in Bora and promotes its interaction with β-TrCP. Mutations in this degron stabilize Bora. Expression of a nondegradable Bora variant prolongs the metaphase and delays anaphase onset, indicating a physiological requirement of Bora degradation. Interestingly, the activity of Bora is also required for normal mitotic progression, as knockdown of Bora activates the spindle checkpoint and delays sister chromatid segregation. Mechanistically, Bora regulates spindle stability and microtubule polymerization and promotes tension across sister kinetochores during mitosis. We conclude that tight regulation of the Bora protein by its synthesis and degradation is critical for cell cycle progression

    A comparison of consumer sensory acceptance and value of domestic beef steaks and steaks from a branded, Argentine beef program

    Get PDF
    To determine consumer sensory acceptance and value of branded, Argentine (grass-finished, aged 30+ d) and domestic (U.S. grain-finished beef, aged 9 d) strip loins were paired based on similar Warner-Bratzler shear force values (P = 0.34) and similar marbling levels (P = 0.82). Consumers in Chicago, IL, and San Francisco, CA (n = 124 per city), evaluated one pair of Argentine and domestic steaks, and had the opportunity to participate in a silent, sealed-bid auction to purchase steaks matching the taste panel samples. Consumers were categorized into three groups based on overall acceptability ratings: 1) those who found Argentine steaks more acceptable, 2) those who found domestic steaks more acceptable, and 3) those who were indifferent. Consumers rated domestic steaks higher (P < 0.05) in juiciness, tenderness, flavor, and overall acceptability. Consumers in both Chicago and San Francisco were willing to pay more (P < 0.05) for domestic steaks (0.86and0.86 and 0.52 per 0.45 kg, respectively). In both cities, consumers who found Argentine samples more acceptable were willing to pay more (P < 0.05) for Argentine steaks (0.74per0.45kginChicagoand0.74 per 0.45 kg in Chicago and 1.82 per 0.45 kg in San Francisco), and consumers who found domestic samples more acceptable were willing to pay more (P < 0.05) for domestic steaks (1.66per0.45kginChicagoand1.66 per 0.45 kg in Chicago and 1.34 per 0.45 kg in San Francisco). Consumers who were indifferent were willing to pay similar (P = 0.99) amounts for Argentine and domestic steaks. Although some consumers found Argentine beef more acceptable than domestic beef (19.7 and 16.5% in Chicago and San Francisco, respectively) and were willing to pay more for it, most consumers found domestic beef to be more acceptable (59.0% in Chicago and 61.5% in San Francisco) and were willing to pay more to obtain a more acceptable product

    Quantum Relaxation of Magnetisation in Magnetic Particles

    Full text link
    At temperatures below the magnetic anisotropy energy, monodomain magnetic systems (small particles, nanomagnetic devices, etc.) must relax quantum mechanically. This quantum relaxation must be mediated by the coupling to both nuclear spins and phonons (and electrons if either particle or substrate is conducting. We analyze the effect of each of these couplings, and then combine them. Conducting systems can be modelled by a "giant Kondo" Hamiltonian, with nuclear spins added in as well. At low temperatures, even microscopic particles on a conducting substrate (containing only 10−5010-50 spins) will have their magnetisation frozen over millenia by a combination of electronic dissipation and the "degeneracy blocking" caused by nuclear spins. Raising the temperature leads to a sudden unblocking of the spin dynamics at a well defined temperature. Insulating systems are quite different. The relaxation is strongly enhanced by the coupling to nuclear spins. At short times the magnetisation of an ensemble of particles relaxes logarithmically in time, after an initial very fast decay; this relaxation proceeds entirely via the nuclear spins. At longer times phonons take over, but the decay rate is still governed by the temperature-dependent nuclear bias field acting on the particles - decay may be exponential or power-law depending on the temperature. The most surprising feature of the results is the pivotal role played by the nuclear spins. The results are relevant to any experiments on magnetic particles in which interparticle dipolar interactions are unimportant. They are also relevant to future magnetic device technology.Comment: 30 pages, RevTex, e:mail , Submitted to J.Low Temp.Phys. on 1 Nov. 199

    Noise Probe of the Dynamic Phase Separation in La2/3Ca1/3MnO3

    Full text link
    Giant Random Telegraph Noise (RTN) in the resistance fluctuation of a macroscopic film of perovskite-type manganese oxide La2/3Ca1/3MnO3 has been observed at various temperatures ranging from 4K to 170K, well below the Curie temperature (TC = 210K). The amplitudes of the two-level-fluctuations (TLF) vary from 0.01% to 0.2%. We use a statistical analysis of the life-times of the TLF to gain insight into the microscopic electronic and magnetic state of this manganite. At low temperature (below 30K) The TLF is well described by a thermally activated two-level model. An estimate of the energy difference between the two states is inferred. At higher temperature (between 60K and 170K) we observed critical effects of the temperature on the life-times of the TLF. We discuss this peculiar temperature dependence in terms of a sharp change in the free energy functional of the fluctuators. We attribute the origin of the RTN to be a dynamic mixed-phase percolative conduction process, where manganese clusters switch back and forth between two phases that differ in their conductivity and magnetization.Comment: 15 pages, PDF only, Phys. Rev. Lett. (in press

    Expanding the clinical phenotype of the 3q29 microdeletion syndrome and characterization of the reciprocal microduplication

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>Interstitial deletions of 3q29 have been recently described as a microdeletion syndrome mediated by nonallelic homologous recombination between low-copy repeats resulting in an ~1.6 Mb common-sized deletion. Given the molecular mechanism causing the deletion, the reciprocal duplication is anticipated to occur with equal frequency, although only one family with this duplication has been reported.</p> <p>Results</p> <p>In this study we describe 14 individuals with microdeletions of 3q29, including one family with a mildly affected mother and two affected children, identified among 14,698 individuals with idiopathic mental retardation who were analyzed by array CGH. Eleven individuals had typical 1.6-Mb deletions. Three individuals had deletions that flank, span, or partially overlap the commonly deleted region. Although the clinical presentations of individuals with typical-sized deletions varied, several features were present in multiple individuals, including mental retardation and microcephaly. We also identified 19 individuals with duplications of 3q29, five of which appear to be the reciprocal duplication product of the 3q29 microdeletion and 14 of which flank, span, or partially overlap the common deletion region. The clinical features of individuals with microduplications of 3q29 also varied with few common features. <it>De novo </it>and inherited abnormalities were found in both the microdeletion and microduplication cohorts illustrating the need for parental samples to fully characterize these abnormalities.</p> <p>Conclusion</p> <p>Our report demonstrates that array CGH is especially suited to identify chromosome abnormalities with unclear or variable presentations.</p
    • …
    corecore