The E3 ubiquitin ligase SCF(Fbxo7) mediates proteasomal degradation of UXT isoform 2 (UXT-V2) to inhibit the NF-κB signaling pathway.

BACKGROUND: Ubiquitously eXpressed Transcript isoform 2 (UXTV2) is a prefoldin-like protein involved in NF-κB signaling, apoptosis, and the androgen and estrogen response. UXT-V2 is a cofactor in the NF-κB transcriptional enhanceosome, and its knockdown inhibits TNF-α -induced NF-κB activation. Fbxo7 is an F-box protein that interacts with SKP1, Cullin1 and RBX1 proteins to form an SCF(Fbxo7) E3 ubiquitin ligase complex. Fbxo7 negatively regulates NF-κB signaling through TRAF2 and cIAP1 ubiquitination. METHODS: We combine co-immunoprecipitation, ubiquitination in vitro and in vivo, cycloheximide chase assay, ubiquitin chain restriction analysis and microscopy to investigate interaction between Fbxo7 and overexpressed UXT-V2-HA. RESULTS: The Ubl domain of Fbxo7 contributes to interaction with UXTV2. This substrate is polyubiquitinated by SCF(Fbxo7) with K48 and K63 ubiquitin chain linkages in vitro and in vivo. This post-translational modification decreases UXT-V2 stability and promotes its proteasomal degradation. We further show that UXTV1, an alternatively spliced isoform of UXT, containing 12 additional amino acids at the N-terminus as compared to UXTV2, also interacts with and is ubiquitinated by Fbxo7. Moreover, FBXO7 knockdown promotes UXT-V2 accumulation, and the overexpression of Fbxo7-ΔF-box protects UXT-V2 from proteasomal degradation and enhances the responsiveness of NF-κB reporter. We find that UXT-V2 colocalizes with Fbxo7 in the cell nucleus. CONCLUSIONS: Together, our study reveals that SCF(Fbxo7) mediates the proteasomal degradation of UXT-V2 causing the inhibition of the NF-κB signaling pathway. GENERAL SIGNIFICANCE: Discovering new substrates of E3 ubiquitin-ligase SCF(Fbxo7) contributes to understand its function in different diseases such as cancer and Parkinson.Biotechnology and Biological Science Research Council [BB/J007846/1]

The Antioxidant Effect of Exercise: A Systematic Review and Meta-Analysis

Physical activity has been associated with reduced oxidative stress (OS) in observational studies and clinical trials. The purpose of this systematic review and meta-analysis of controlled trials was to determine the effect of physical exercise on OS parameters. We conducted a systematic review of the literature up to March 2016 that included the following databases: PubMed, SCOPUS, and Web of Science. A keyword combination referring to exercise training and OS was included as part of a more thorough search process. We also manually searched the reference lists of the articles. From an initial 1573 references, we included 30 controlled trials (1346 participants) in the qualitative analysis, 19 of which were included in the meta-analysis. All trials were conducted in humans and had at least one exercise intervention and a paired control group. Using a standardized protocol, two investigators independently abstracted data on study design, sample size, participant characteristics, intervention, follow-up duration, outcomes, and quantitative data for the meta-analysis. Thus, the investigators independently assigned quality scores with a methodological quality assessment (MQA). The agreement level between the reviewers was 85.3 %. Discrepancies were solved in a consensus meeting. The MQA showed a total score in the quality index between 40 and 90 % and a mean quality of 55 %. Further, in a random-effects model, data from each trial were pooled and weighted by the inverse of the total variance. Physical training was associated with a significant reduction in pro-oxidant parameters (standard mean difference [SMD] -1.08; 95 % confidence interval [CI] -1.57 to -0.58; p < 0.001) and an increase in antioxidant capacity (SMD 1.45; 95 % CI 0.83-2.06; p < 0.001). The pooled analysis revealed that regardless of intensity, volume, type of exercise, and studied population, the antioxidant indicators tended to increase and pro-oxidant indicators tended to decrease after training. Therefore, we conclude that exercise training seems to induce an antioxidant effect. Thus, it is suggested that people practice some kind of exercise to balance the redox state, regardless of their health status, to improve health-related outcomes

Energy Dependence of the Transverse Momentum Distributions of Charged Particles in pp Collisions Measured by ALICE

Differential cross sections of charged particles in inelastic pp collisions as a function of p_T have been measured at $\sqrt{s}$ = 0.9, 2.76 and 7 TeV at the LHC. The $p_T$ spectra are compared to NLO-pQCD calculations. Though the differential cross section for an individual $\sqrt{s}$ cannot be described by NLO-pQCD, the relative increase of cross section with sqrt(s) is in agreement with NLO-pQCD. Based on these measurements and observations, procedures are discussed to construct pp reference spectra at $\sqrt{s}$ = 2.76 and 5.02 TeV up to $p_T$ = 50 GeV/c as required for the calculation of the nuclear modification factor in nucleus-nucleus and proton-nucleus collisions

Multiplicity dependence of the average transverse momentum in pp, p-Pb, and Pb-Pb collisions at the LHC

The average transverse momentum versus the charged-particle multiplicity $N_{ch}$ was measured in p-Pb collisions at a collision energy per nucleon-nucleon pair $\sqrt{s_{NN}}$ = 5.02 TeV and in pp collisions at collision energies of $\sqrt{s}$ = 0.9, 2.76, and 7 Tev in the kinematic range 0.15 with $N_{ch}$ is observed, which is much stronger than that measured in Pb-Pb collisions. For pp collisions, this could be attributed, within a model of hadronizing strings, to multiple-parton interactions and to a final-state color reconnection mechanism. The data in p-Pb and Pb-Pb collisions cannot be described by an incoherent superposition of nucleon-nucleon collisions and pose a challenge to most of the event generators