The mechano-ubiquitinome of articular cartilage: differential ubiquitination and activation of a group of ER-associated DUBs and ER stress regulators

Understanding how connective tissue cells respond to mechanical stimulation is important to human health and disease processes in musculoskeletal diseases. Injury to articular cartilage is a key risk factor in predisposition to tissue damage and degenerative osteoarthritis. Recently, we have discovered that mechanical injury to connective tissues including murine and porcine articular cartilage causes a significant increase in Lysine 63- polyubiquitination. Here we identified the ubiquitin signature that is unique to injured articular cartilage tissue post mechanical injury (the “mechano-ubiquitinome”). A total of 463 ubiquitinated peptides were identified, with an enrichment of ubiquitinated peptides of proteins involved in protein processing in the endoplasmic reticulum (ER), also known as the ER-associated degradation (ERAD) response, including YOD1, BRCC3, ATXN3 and USP5 as well as the ER stress regulators, RAD23B, VCP/p97 and Ubiquilin 1. Enrichment of these proteins suggested an injury-induced ER stress response and, for instance, ER stress markers DDIT3/CHOP and BIP/GRP78 were upregulated following cartilage injury on the protein and gene expression levels. Similar ER stress induction was also observed in response to tail fin injury in zebrafish larvae, suggesting a generic response to tissue injury. Furthermore, a rapid increase in global DUB activity following injury and significant activity in human osteoarthritic cartilage was observed using DUB specific activity probes. Combined, these results implicate the involvement of ubiquitination events and activation of a set of DUBs and ER stress regulators in cellular responses to cartilage tissue injury and in osteoarthritic cartilage tissues. This link through the ERAD pathway makes this protein set attractive for further investigation in in vivo models of tissue injury and for targeting in osteoarthritis and related musculoskeletal diseases

Accounting for International War: The State of the Discipline

In studies of war it is important to observe that the processes leading to so frequent an event as conflict are not necessarily those that lead to so infrequent an event as war. Also, many models fail to recognize that a phenomenon irregularly distributed in time and space, such as war, cannot be explained on the basis of relatively invariant phenomena. Much research on periodicity in the occurrence of war has yielded little result, suggesting that the direction should now be to focus on such variables as diffusion and contagion. Structural variables, such as bipolarity, show contradictory results with some clear inter-century differences. Bipolarity, some results suggest, might have different effects on different social entities. A considerable number of studies analysing dyadic variables show a clear connection between equal capabilities among contending nations and escalation of conflict into war. Finally, research into national attributes often points to strength and geographical location as important variables. In general, the article concludes, there is room for modest optimism, as research into the question of war is no longer moving in non-cumulative circles. Systematic research is producing results and there is even a discernible tendency of convergence, in spite of a great diversity in theoretical orientations.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/69148/2/10.1177_002234338101800101.pd

Variability of humidity conditions in the Arctic during the first International Polar Year, 1882-83

Of all the early instrumental data for the Arctic, the meteorological data gathered during the first International Polar Year, in 1882–83 (IPY-1), are the best in terms of coverage, quality and resolution. Research carried out during IPY-1 scientific expeditions brought a significant contribution to the development of hygrometry in polar regions at the end of the 19th century. The present paper gives a detailed analysis of a unique series of humidity measurements that were carried out during IPY-1 at hourly resolutions at nine meteorological stations, relatively evenly distributed in the High Arctic. It gives an overall view of the humidity conditions prevalent in the Arctic at that time. The results show that the spatial distribution of atmospheric water vapour pressure (e) and relative humidity (RH) in the Arctic during IPY-1 was similar to the present. In the annual course the highest values of e were noted in July and August, while the lowest occurred in the cold half of the year. In comparison to present-day conditions (1961–1990), the mean values of RH in the IPY-1 period (September 1882 to July 1883) were higher by 2.4–5.6%. Most of the changes observed between historical and modern RH values are not significant. The majority of historical daily RH values lie between a distance of less than two standard deviations from current long-term monthly means

Planck Early Results. VII. The Early Release Compact Source Catalogue

A brief description of the methodology of construction, contents and usage of the Planck Early Release Compact Source Catalogue (ERCSC), including the Early Cold Cores (ECC) and the Early Sunyaev-Zeldovich (ESZ) cluster catalogue is provided. The catalogue is based on data that consist of mapping the entire sky once and 60% of the sky a second time by Planck, thereby comprising the first high sensitivity radio/submillimetre observations of the entire sky. Four source detection algorithms were run as part of the ERCSC pipeline. A Monte-Carlo algorithm based on the injection and extraction of artificial sources into the Planck maps was implemented to select reliable sources among all extracted candidates such that the cumulative reliability of the catalogue is ≥90%. There is no requirement on completeness for the ERCSC. As a result of the Monte-Carlo assessment of reliability of sources from the different techniques, an implementation of the PowellSnakes source extraction technique was used at the five frequencies between 30 and 143 GHz while the SExtractor technique was used between 217 and 857GHz. The 10σ photometric flux density limit of the catalogue at |b| > 30◦ is 0.49, 1.0, 0.67, 0.5, 0.33, 0.28, 0.25, 0.47 and 0.82 Jy at each of the nine frequencies between 30 and 857 GHz. Sources which are up to a factor of ∼2 fainter than this limit, and which are present in “clean” regions of the Galaxy where the sky background due to emission from the interstellar medium is low, are included in the ERCSC if they meet the high reliability criterion. The Planck ERCSC sources have known associations to stars with dust shells, stellar cores, radio galaxies, blazars, infrared luminous galaxies and Galactic interstellar medium features. A significant fraction of unclassified sources are also present in the catalogs. In addition, two early release catalogs that contain 915 cold molecular cloud core candidates and 189 SZ cluster candidates that have been generated using multifrequency algorithms are presented. The entire source list, with more than 15000 unique sources, is ripe for follow-up characterisation with Herschel, ATCA, VLA, SOFIA, ALMA and other ground-based observing facilities

Search for the associated production of the Higgs boson with a top-quark pair

A search for the standard model Higgs boson produced in association with a top-quark pair t t ¯ H (tt¯H) is presented, using data samples corresponding to integrated luminosities of up to 5.1 fb −1 and 19.7 fb −1 collected in pp collisions at center-of-mass energies of 7 TeV and 8 TeV respectively. The search is based on the following signatures of the Higgs boson decay: H → hadrons, H → photons, and H → leptons. The results are characterized by an observed t t ¯ H tt¯H signal strength relative to the standard model cross section, μ = σ/σ SM ,under the assumption that the Higgs boson decays as expected in the standard model. The best fit value is μ = 2.8 ± 1.0 for a Higgs boson mass of 125.6 GeV

Performance of reconstruction and identification of τ leptons decaying to hadrons and vτ in pp collisions at √s=13 TeV

The algorithm developed by the CMS Collaboration to reconstruct and identify τ leptons produced in proton-proton collisions at √s=7 and 8 TeV, via their decays to hadrons and a neutrino, has been significantly improved. The changes include a revised reconstruction of π⁰ candidates, and improvements in multivariate discriminants to separate τ leptons from jets and electrons. The algorithm is extended to reconstruct τ leptons in highly Lorentz-boosted pair production, and in the high-level trigger. The performance of the algorithm is studied using proton-proton collisions recorded during 2016 at √s=13 TeV, corresponding to an integrated luminosity of 35.9 fb¯¹. The performance is evaluated in terms of the efficiency for a genuine τ lepton to pass the identification criteria and of the probabilities for jets, electrons, and muons to be misidentified as τ leptons. The results are found to be very close to those expected from Monte Carlo simulation

Measurement of prompt Jψ\psi pair production in pp collisions at \sqrt s = 7 Tev

Production of prompt J/ ψ meson pairs in proton-proton collisions at s s√ = 7 TeV is measured with the CMS experiment at the LHC in a data sample corresponding to an integrated luminosity of about 4.7 fb −1 . The two J/ ψ mesons are fully reconstructed via their decays into μ + μ − pairs. This observation provides for the first time access to the high-transverse-momentum region of J/ ψ pair production where model predictions are not yet established. The total and differential cross sections are measured in a phase space defined by the individual J/ ψ transverse momentum ( p T J/ ψ ) and rapidity (| y J/ ψ |): | y J/ ψ | 6.5 GeV/ c ; 1.2 4.5 GeV/ c . The total cross section, assuming unpolarized prompt J/ ψ pair production is 1.49 ± 0.07 (stat) ±0.13 (syst) nb. Different assumptions about the J/ ψ polarization imply modifications to the cross section ranging from −31% to +27%