Bilateral inhibition of HAUSP deubiquitinase by a viral interferon regulatory factor protein

Herpesvirus-associated ubiquitin specific protease (HAUSP) regulates the stability of p53 and MDM2, implicating HAUSP as a therapeutic target for tuning p53-mediated anti-tumor activity. Here, we report the structural analysis of HAUSP with Kaposi’s sarcoma-associated herpesvirus vIRF4 and the discovery of two vIRF4-derived peptides, vif1 and vif2, as potent and selective HAUSP antagonists. This analysis reveals a bilateral belt-type interaction resulting in inhibition of HAUSP. The vif1 peptide binds the HAUSP TRAF domain, competitively blocking substrate binding, while the vif2 peptide binds both the HAUSP TRAF and catalytic domains, robustly suppressing its deubiquitination activity. Consequently, peptide treatments comprehensively blocked HAUSP, leading to p53-dependent cell cycle arrest and apoptosis in culture and tumor regression in xenograft mouse model. Thus, the virus has developed a unique molecular strategy to target the HAUSP-MDM2-p53 pathway, and these virus-derived short peptides represent biologically active HAUSP antagonists

Depicting the tree of life in museums: guiding principles from psychological research

The Tree of Life is revolutionizing our understanding of life on Earth, and, accordingly, evolutionary trees are increasingly important parts of exhibits on biodiversity and evolution. The authors argue that in using these trees to effectively communicate evolutionary principles, museums need to take into account research results from cognitive, developmental, and educational psychology while maintaining a focus on visitor engagement and enjoyment. Six guiding principles for depicting evolutionary trees in museum exhibits distilled from this research literature were used to evaluate five current or recent museum trees. One of the trees was then redesigned in light of the research while preserving the exhibit’s original learning goals. By attending both to traditional factors that influence museum exhibit design and to psychological research on how people understand diagrams in general and Tree of Life graphics in particular, museums can play a key role in fostering 21st century scientific literacy

Supernova remnants: the X-ray perspective

Supernova remnants are beautiful astronomical objects that are also of high scientific interest, because they provide insights into supernova explosion mechanisms, and because they are the likely sources of Galactic cosmic rays. X-ray observations are an important means to study these objects.And in particular the advances made in X-ray imaging spectroscopy over the last two decades has greatly increased our knowledge about supernova remnants. It has made it possible to map the products of fresh nucleosynthesis, and resulted in the identification of regions near shock fronts that emit X-ray synchrotron radiation. In this text all the relevant aspects of X-ray emission from supernova remnants are reviewed and put into the context of supernova explosion properties and the physics and evolution of supernova remnants. The first half of this review has a more tutorial style and discusses the basics of supernova remnant physics and thermal and non-thermal X-ray emission. The second half offers a review of the recent advances.The topics addressed there are core collapse and thermonuclear supernova remnants, SN 1987A, mature supernova remnants, mixed-morphology remnants, including a discussion of the recent finding of overionization in some of them, and finally X-ray synchrotron radiation and its consequences for particle acceleration and magnetic fields.Comment: Published in Astronomy and Astrophysics Reviews. This version has 2 column-layout. 78 pages, 42 figures. This replaced version has some minor language edits and several references have been correcte

Performance of the CMS muon trigger system in proton-proton collisions at root s=13 TeV

The muon trigger system of the CMS experiment uses a combination of hardware and software to identify events containing a muon. During Run 2 (covering 2015–2018) the LHC achieved instantaneous luminosities as high as 2 × 1034 while delivering proton-proton collisions at √(s) = 13. The challenge for the trigger system of the CMS experiment is to reduce the registered event rate from about 40MHz to about 1kHz. Significant improvements important for the success of the CMS physics program have been made to the muon trigger system via improved muon reconstruction and identification algorithms since the end of Run 1 and throughout the Run 2 data-taking period. The new algorithms maintain the acceptance of the muon triggers at the same or even lower rate throughout the data-taking period despite the increasing number of additional proton-proton interactions in each LHC bunch crossing. In this paper, the algorithms used in 2015 and 2016 and their improvements throughout 2017 and 2018 are described. Measurements of the CMS muon trigger performance for this data-taking period are presented, including efficiencies, transverse momentum resolution, trigger rates, and the purity of the selected muon sample. This paper focuses on the single- and double-muon triggers with the lowest sustainable transverse momentum thresholds used by CMS. The efficiency is measured in a transverse momentum range from 8 to several hundred

Measurement of the Higgs boson width and evidence of its off-shell contributions to ZZ production

Since the discovery of the Higgs boson in 2012, detailed studies of its properties have been ongoing. Besides its mass, its width—related to its lifetime—is an important parameter. One way to determine this quantity is to measure its off-shell production, where the Higgs boson mass is far away from its nominal value, and relating it to its on-shell production, where the mass is close to the nominal value. Here we report evidence for such off-shell contributions to the production cross-section of two Z bosons with data from the CMS experiment at the CERN Large Hadron Collider. We constrain the total rate of the off-shell Higgs boson contribution beyond the Z boson pair production threshold, relative to its standard model expectation, to the interval [0.0061, 2.0] at the 95% confidence level. The scenario with no off-shell contribution is excluded at a p-value of 0.0003 (3.6 standard deviations). We measure the width of the Higgs boson as ΓH=3.2+2.4−1.7MeV, in agreement with the standard model expectation of 4.1 MeV. In addition, we set constraints on anomalous Higgs boson couplings to W and Z boson pairs

Exploring the definition of «acute» neck pain: a prospective cohort observational study comparing the outcomes of chiropractic patients with 0-2 weeks, 2-4 weeks and 4-12 weeks of symptoms

Abstract Background Neck pain is a common complaint in chiropractic patients. Amongst other baseline variables, numerous studies identify duration of symptoms as a strong predictor of outcome in neck pain patients. The usual time frame used for ‘acute’ onset of pain is between 0 and 4 weeks. However, the appropriateness of this time frame has been challenged for chiropractic low back pain patients. Therefore, the purpose of this study was to compare outcomes in neck pain patients with 0–2 vs 2–4 and 4–12 weeks of symptoms undergoing chiropractic treatment. Methods This is a prospective cohort observational study with 1 year follow-up including 495 patients whose data was collected between October 2009 and March 2015. Patients were divided into high-acute (0–2 weeks), mid-acute (2–4 weeks) and subacute (4–12 weeks) corresponding to duration of their symptoms at initial treatment. Patients completed the numerical pain rating scale (NRS) and Bournemouth questionnaire for neck pain (BQN) at baseline. At follow-up time points of 1 week, 1 month, 3 months, 6 months and 1 year the NRS and BQN were completed along with the Patient Global Impression of Change (PGIC) scale. The PGIC responses were dichotomized into ‘improved’ and ‘not improved’ patients and compared between the 3 subgroups. The Chi-square test was used to compare improved patients between the 3 subgroups and the unpaired Student’s t-test was used for the NRS and BQN change scores. Results The proportion of patients ‘improved’ was only significantly higher for patients with symptoms of 0–2 weeks compared to 2–4 weeks at the 1 week outcome time point (p = 0.015). The NRS changes scores were significantly greater for patients with 2–4 weeks of symptoms compared to 4–12 weeks of symptoms only at 1 week (p = 0.035). Conclusions The time period of 0–4 weeks of symptoms as the definition of “acute” neck pain should be maintained. Independent of the exact duration of symptoms, medium-term and long-term outcome is favourable for acute as well as subacute neck pain patients. Trial registration Not applicable for prospective cohort studies. Ethics approval prior to study EK 19/2009