Identification of a WNT5A-Responsive Degradation Domain in the Kinesin Superfamily Protein KIF26B.

Noncanonical WNT pathways function independently of the β-catenin transcriptional co-activator to regulate diverse morphogenetic and pathogenic processes. Recent studies showed that noncanonical WNTs, such as WNT5A, can signal the degradation of several downstream effectors, thereby modulating these effectors' cellular activities. The protein domain(s) that mediates the WNT5A-dependent degradation response, however, has not been identified. By coupling protein mutagenesis experiments with a flow cytometry-based degradation reporter assay, we have defined a protein domain in the kinesin superfamily protein KIF26B that is essential for WNT5A-dependent degradation. We found that a human disease-causing KIF26B mutation located at a conserved amino acid within this domain compromises the ability of WNT5A to induce KIF26B degradation. Using pharmacological perturbation, we further uncovered a role of glycogen synthase kinase 3 (GSK3) in WNT5A regulation of KIF26B degradation. Lastly, based on the identification of the WNT5A-responsive domain, we developed a new reporter system that allows for efficient profiling of WNT5A-KIF26B signaling activity in both somatic and stem cells. In conclusion, our study identifies a new protein domain that mediates WNT5A-dependent degradation of KIF26B and provides a new tool for functional characterization of noncanonical WNT5A signaling in cells

Management and outcomes of traumatic hemothorax in children

Background: Adult guidelines for the management of traumatic hemothorax are well established; however, there have been no similar studies conducted in the pediatric population. The purpose of our study was to assess the management and outcomes of children with traumatic hemothorax. Materials and Methods: Following Institutional Review Board approval, we conducted a retrospective cross-sectional study of all trauma patients diagnosed with a hemothorax at a Level-1 pediatric trauma center from 2007 to 2012. Results: Forty-six children with hemothorax were identified, 23 from blunt mechanism and 23 from penetrating mechanism. The majority of children injured by penetrating mechanisms were treated with tube thoracostomy while the majority of blunt injury patients were observed (91.3% vs. 30.4% tube thoracostomy, penetrating vs. blunt, P = 0.00002). Among patients suffering from blunt mechanism, children who were managed with chest tubes had a greater volume of hemothorax than those who were observed. All children who were observed underwent serial chest radiographs demonstrating no progression and required no delayed procedures. Children with a hemothorax identified only by computed tomography, after negative plain radiograph, did not require intervention. No child developed a delayed empyema or fibrothorax. Conclusion: The data suggest that a small-volume hemothorax resulting from blunt mechanism may be safely observed without mandatory tube thoracostomy and with overall low complication rates

Quantum Markov Channels for Qubits

We examine stochastic maps in the context of quantum optics. Making use of the master equation, the damping basis, and the Bloch picture we calculate a non-unital, completely positive, trace-preserving map with unequal damping eigenvalues. This results in what we call the squeezed vacuum channel. A geometrical picture of the effect of stochastic noise on the set of pure state qubit density operators is provided. Finally, we study the capacity of the squeezed vacuum channel to transmit quantum information and to distribute EPR states.Comment: 18 pages, 4 figure

Proteins Found in a CikA Interaction Assay Link the Circadian Clock, Metabolism, and Cell Division in Synechococcus elongatus

Diverse organisms time their cellular activities to occur at distinct phases of Earth's solar day, not through the direct regulation of these processes by light and darkness but rather through the use of an internal biological (circadian) clock that is synchronized with the external cycle. Input pathways serve as mechanisms to transduce external cues to a circadian oscillator to maintain synchrony between this internal oscillation and the environment. The circadian input pathway in the cyanobacterium Synechococcus elongatus PCC 7942 requires the kinase CikA. A cikA null mutant exhibits a short circadian period, the inability to reset its clock in response to pulses of darkness, and a defect in cell division. Although CikA is copurified with the Kai proteins that constitute the circadian central oscillator, no direct interaction between CikA and either KaiA, KaiB, or KaiC has been demonstrated. Here, we identify four proteins that may help connect CikA with the oscillator. Phenotypic analyses of null and overexpression alleles demonstrate that these proteins are involved in at least one of the functions—circadian period regulation, phase resetting, and cell division—attributed to CikA. Predictions based on sequence similarity suggest that these proteins function through protein phosphorylation, iron-sulfur cluster biosynthesis, and redox regulation. Collectively, these results suggest a model for circadian input that incorporates proteins that link the circadian clock, metabolism, and cell division

IFNAR1-Signalling Obstructs ICOS-mediated Humoral Immunity during Non-lethal Blood-Stage Plasmodium Infection

Funding: This work was funded by a Career Development Fellowship (1028634) and a project grant (GRNT1028641) awarded to AHa by the Australian National Health & Medical Research Council (NHMRC). IS was supported by The University of Queensland Centennial and IPRS Scholarships. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Development of Ferroelectric Order in Relaxor (1-x)Pb(Mg1/3Nb2/3)O3 - xPbTiO3

The microstructure and phase transition in relaxor ferroelectric Pb(Mg1/3Nb2/3)O3 (PMN) and its solid solution with PbTiO3 (PT), PMN-xPT, remain to be one of the most puzzling issues of solid state science. In the present work we have investigated the evolution of the phase symmetry in PMN-xPT ceramics as a function of temperature (20 K < T < 500 K) and composition (0 <= x <= 0.15) by means of high-resolution synchrotron x-ray diffraction. Structural analysis based on the experimental data reveals that the substitution of Ti^4+ for the complex B-site (Mg1/3Nb2/3)^4+ ions results in the development of a clean rhombohedral phase at a PT-concentration as low as 5%. The results provide some new insight into the development of the ferroelectric order in PMN-PT, which has been discussed in light of the kinetics of polar nanoregions and the physical models of the relaxor ferroelectrics to illustrate the structural evolution from a relaxor to a ferroelectric state.Comment: Revised version with updated references; 9 pages, 4 figures embedde

Web-based monitoring tools for Resistive Plate Chambers in the CMS experiment at CERN

The Resistive Plate Chambers (RPC) are used in the CMS experiment at the trigger level and also in the standard offline muon reconstruction. In order to guarantee the quality of the data collected and to monitor online the detector performance, a set of tools has been developed in CMS which is heavily used in the RPC system. The Web-based monitoring (WBM) is a set of java servlets that allows users to check the performance of the hardware during data taking, providing distributions and history plots of all the parameters. The functionalities of the RPC WBM monitoring tools are presented along with studies of the detector performance as a function of growing luminosity and environmental conditions that are tracked over time

Radiation background with the CMS RPCs at the LHC

The Resistive Plate Chambers (RPCs) are employed in the CMS Experiment at the LHC as dedicated trigger system both in the barrel and in the endcap. This article presents results of the radiation background measurements performed with the 2011 and 2012 proton-proton collision data collected by CMS. Emphasis is given to the measurements of the background distribution inside the RPCs. The expected background rates during the future running of the LHC are estimated both from extrapolated measurements and from simulation

Declines in violence and police arrest among female sex workers in Karnataka state, south India, following a comprehensive HIV prevention programme.

INTRODUCTION: Female sex workers (FSWs) frequently experience violence, harassment and arrest by the police or their clients, but there is little evidence as to the impact that such factors may have on HIV risk or whether community interventions could mitigate this impact. METHODS: As part of the evaluation of the Avahan programme in Karnataka, serial integrated behavioural and biological assessment (IBBA) surveys (four districts) (2005 to 2011) and anonymous polling booth surveys (PBS) (16 districts) (2007 to 2011) were conducted with random samples of FSWs. Logistic regression analysis was used to assess 1) changes in reported violence and arrests over time and 2) associations between violence by non-partners and police arrest and HIV/STI risk and prevalence. Mediation analysis was used to identify mediating factors. RESULTS: 5,792 FSWs participated in the IBBAs and 15,813 participated in the PBS. Over time, there were significant reductions in the percentages of FSWs reporting being raped in the past year (PBS) (30.0% in 2007, 10.0% in 2011, p<0.001), being arrested in the past year [adjusted odds ratio (AOR) 0.57 (0.35, 0.93), p=0.025] and being beaten in the past six months by a non-partner (clients, police, pimps, strangers, rowdies) [AOR 0.69 (0.49, 0.95), p=0.024)] (IBBA). The proportion drinking alcohol (during the past week) also fell significantly (32.5% in 2005, 24.9% in 2008, 16.8% in 2011; p<0.001). Violence by non-partners (being raped in the past year and/or beaten in the past six months) and being arrested in the past year were both strongly associated with HIV infection [AOR 1.59 (1.18, 2.15), p=0.002; AOR 1.91 (1.17, 3.12), p=0.01, respectively]. They were also associated with drinking alcohol (during the past week) [AOR 1.98 (1.54, 2.53), p<0.001; AOR 2.79 (1.93, 4.04), p<0.001, respectively], reduced condom self-efficacy with clients [AOR 0.36 (0.27, 0.47), p<0.001; AOR 0.62 (0.39, 0.98), p=0.039, respectively], symptomatic STI (during the past year) [AOR 2.62 (2.07, 3.30), p<0.001; AOR 2.17 (1.51, 3.13), p<0.001, respectively], gonorrhoea infection [AOR 2.79 (1.51, 5.15), p=0.001; AOR 2.69 (0.96, 7.56), p=0.060, respectively] and syphilis infection [AOR 1.86 (1.04, 3.31), p=0.036; AOR 3.35 (1.78, 6.28), p<0.001, respectively], but not with exposure to peer education, community mobilization or HIV testing uptake. Mediation analysis suggests that alcohol use and STIs may partially mediate the association between violence or arrests and HIV prevalence. DISCUSSION: Violence by non-partners and arrest are both strongly associated with HIV infection among FSWs. Large-scale, comprehensive HIV prevention programming can reduce violence, arrests and HIV/STI infection among FSWs