Inactivation of Effector Caspases through Nondegradative Polyubiquitylation

Ubiquitin-mediated inactivation of caspases has long been postulated to contribute to the regulation of apoptosis. However, detailed mechanisms and functional consequences of caspase ubiquitylation have not been demonstrated. Here we show that the Drosophila Inhibitor of Apoptosis 1, DIAP1, blocks effector caspases by targeting them for polyubiquitylation and nonproteasomal inactivation. We demonstrate that the conjugation of ubiquitin to drICE suppresses its catalytic potential in cleaving caspase substrates. Our data suggest that ubiquitin conjugation sterically interferes with substrate entry and reduces the caspase’s proteolytic velocity. Disruption of drICE ubiquitylation, either by mutation of DIAP1’s E3 activity or drICE’s ubiquitin-acceptor lysines, abrogates DIAP1’s ability to neutralize drICE and suppress apoptosis in vivo. We also show that DIAP1 rests in an “inactive” conformation that requires caspase-mediated cleavage to subsequently ubiquitylate caspases. Taken together, our findings demonstrate that effector caspases regulate their own inhibition through a negative feedback mechanism involving DIAP1 “activation” and nondegradative polyubiquitylation

Long-range Angular Correlations On The Near And Away Side In P-pb Collisions At √snn=5.02 Tev

7191/Mar294

First measurement of Ωc0 production in pp collisions at s=13 TeV

The inclusive production of the charm–strange baryon 0 c is measured for the first time via its hadronic √ decay into −π+ at midrapidity (|y| <0.5) in proton–proton (pp) collisions at the centre-of-mass energy s =13 TeV with the ALICE detector at the LHC. The transverse momentum (pT) differential cross section multiplied by the branching ratio is presented in the interval 2 < pT < 12 GeV/c. The pT dependence of the 0 c-baryon production relative to the prompt D0-meson and to the prompt 0 c-baryon production is compared to various models that take different hadronisation mechanisms into consideration. In the measured pT interval, the ratio of the pT-integrated cross sections of 0 c and prompt + c baryons multiplied by the −π+ branching ratio is found to be larger by a factor of about 20 with a significance of about 4σ when compared to e+e− collisions

Elliptic flow of charged particles at midrapidity relative to the spectator plane in Pb–Pb and Xe–Xe collisions

Measurements of the elliptic flow coefficient relative to the collision plane defined by the spectator neutrons v2{ SP} in collisions of Pb ions at center-of-mass energy per nucleon–nucleon pair √ 2.76 TeV and Xe ions at √ sNN = sNN =5.44 TeV are reported. The results are presented for charged particles produced at midrapidity as a function of centrality and transverse momentum for the 5–70% and 0.2–6 GeV/c ranges, respectively. The ratio between v2{ SP} and the elliptic flow coefficient relative to the participant plane v2{4}, estimated using four-particle correlations, deviates by up to 20% from unity depending on centrality. This observation differs strongly from the magnitude of the corresponding eccentricity ratios predicted by the TRENTo and the elliptic power models of initial state fluctuations that are tuned to describe the participant plane anisotropies. The differences can be interpreted as a decorrelation of the neutron spectator plane and the reaction plane because of fragmentation of the remnants from the colliding nuclei, which points to an incompleteness of current models describing the initial state fluctuations. A significant transverse momentum dependence of the ratio v2{ SP}/v2{4} is observed in all but the most central collisions, which may help to understand whether momentum anisotropies at low and intermediate transverse momentum have a common origin in initial state f luctuations. The ratios of v2{ SP} and v2{4} to the corresponding initial state eccentricities for Xe–Xe and Pb–Pb collisions at similar initial entropy density show a difference of (7.0 ±0.9)%with an additional variation of +1.8% when including RHIC data in the TRENTo parameter extraction. These observations provide new experimental constraints for viscous effects in the hydrodynamic modeling of the expanding quark–gluon plasma produced in heavy-ion collisions at the LHC

Three-dimensional analysis of mandibular condyle position in patients with deviated mandibular prognathism

Item does not contain fulltextThe purpose of this study was to evaluate the bilateral difference in condyle position in patients with deviated mandibular prognathism. Patients with asymmetrical (n=28) and symmetrical mandibular prognathism (n=23) were compared using the three-dimensional (3D) reformatted image from cone beam computed tomography. Significant positional differences in the condyle and subcondyle region (sigmoid notch) were found between the deviated and contralateral sides in the group with asymmetrical mandibular prognathism, but not in the control group. The lateral condyle was more laterally and inferiorly positioned on the contralateral side than on the deviated side (P<0.05). The sigmoid notch was more laterally, superiorly, and posteriorly positioned on the deviated side (P<0.01). Interestingly, condyle width and height on the deviated side was narrower and shorter than on the contralateral side and in the control group. Menton deviation was closely correlated with the bilateral difference in condyle height and 3D position of the sigmoid notch (P<0.01). The degree of asymmetry was more highly correlated with condyle height than with the spatial orientation of the condyle head. The results demonstrated that mandibular prognathism with asymmetry is associated with bilateral differences in 3D morphology and orientation of the condyle. Therefore, clinicians should consider these variations during surgical planning

Chaotic mixing using periodic and aperiodic sequences of mixing protocols in a micromixer

We conducted a numerical study on mixing in a barrier embedded micromixer with an emphasis on the effect of periodic and aperiodic sequences of mixing protocols on mixing performance. A mapping method was employed to investigate mixing in various sequences, enabling us to qualitatively observe the progress of mixing and also to quantify both the rate and the final state of mixing. First, we introduce the design concept of the four mixing protocols and the route to achieve chaotic mixing of the mixer. Then, several periodic sequences consisting of the four mixing protocols are used to investigate the mixing performance depending on the sequence. Chaotic mixing was observed, but with different mixing rates and different final mixing states significantly influenced by the specific sequence of mixing protocols and inertia. As for the effect of inertia, the higher the Reynolds number the larger the rotational motion of the fluid leading to faster mixing. We found that a sequence showing the best mixing performance at a certain Reynolds number is not always superior to other sequences in a different Reynolds number regime. A properly chosen aperiodic sequence results in faster and more uniform mixing than periodic sequence