Role of cellular senescence and NOX4-mediated oxidative stress in systemic sclerosis pathogenesis.

Systemic sclerosis (SSc) is a systemic autoimmune disease characterized by progressive fibrosis of skin and numerous internal organs and a severe fibroproliferative vasculopathy resulting frequently in severe disability and high mortality. Although the etiology of SSc is unknown and the detailed mechanisms responsible for the fibrotic process have not been fully elucidated, one important observation from a large US population study was the demonstration of a late onset of SSc with a peak incidence between 45 and 54 years of age in African-American females and between 65 and 74 years of age in white females. Although it is not appropriate to consider SSc as a disease of aging, the possibility that senescence changes in the cellular elements involved in its pathogenesis may play a role has not been thoroughly examined. The process of cellular senescence is extremely complex, and the mechanisms, molecular events, and signaling pathways involved have not been fully elucidated; however, there is strong evidence to support the concept that oxidative stress caused by the excessive generation of reactive oxygen species may be one important mechanism involved. On the other hand, numerous studies have implicated oxidative stress in SSc pathogenesis, thus, suggesting a plausible mechanism in which excessive oxidative stress induces cellular senescence and that the molecular events associated with this complex process play an important role in the fibrotic and fibroproliferative vasculopathy characteristic of SSc. Here, recent studies examining the role of cellular senescence and of oxidative stress in SSc pathogenesis will be reviewed

The NOX toolbox: validating the role of NADPH oxidases in physiology and disease

Reactive oxygen species (ROS) are cellular signals but also disease triggers; their relative excess (oxidative stress) or shortage (reductive stress) compared to reducing equivalents are potentially deleterious. This may explain why antioxidants fail to combat diseases that correlate with oxidative stress. Instead, targeting of disease-relevant enzymatic ROS sources that leaves physiological ROS signaling unaffected may be more beneficial. NADPH oxidases are the only known enzyme family with the sole function to produce ROS. Of the catalytic NADPH oxidase subunits (NOX), NOX4 is the most widely distributed isoform. We provide here a critical review of the currently available experimental tools to assess the role of NOX and especially NOX4, i.e. knock-out mice, siRNAs, antibodies, and pharmacological inhibitors. We then focus on the characterization of the small molecule NADPH oxidase inhibitor, VAS2870, in vitro and in vivo, its specificity, selectivity, and possible mechanism of action. Finally, we discuss the validation of NOX4 as a potential therapeutic target for indications including stroke, heart failure, and fibrosis

CMS physics technical design report : Addendum on high density QCD with heavy ions

Peer reviewe

Commissioning and performance of the CMS silicon strip tracker with cosmic ray muons

This is the Pre-print version of the Article. The official published version of the Paper can be accessed from the link below - Copyright @ 2010 IOPDuring autumn 2008, the Silicon Strip Tracker was operated with the full CMS experiment in a comprehensive test, in the presence of the 3.8 T magnetic field produced by the CMS superconducting solenoid. Cosmic ray muons were detected in the muon chambers and used to trigger the readout of all CMS sub-detectors. About 15 million events with a muon in the tracker were collected. The efficiency of hit and track reconstruction were measured to be higher than 99% and consistent with expectations from Monte Carlo simulation. This article details the commissioning and performance of the Silicon Strip Tracker with cosmic ray muons.This work is supported by FMSR (Austria); FNRS and FWO (Belgium); CNPq, CAPES, FAPERJ, and FAPESP (Brazil); MES (Bulgaria); CERN; CAS, MoST, and NSFC (China); COLCIENCIAS (Colombia); MSES (Croatia); RPF (Cyprus); Academy of Sciences and NICPB (Estonia); Academy of Finland, ME, and HIP (Finland); CEA and CNRS/IN2P3 (France); BMBF, DFG, and HGF (Germany); GSRT (Greece); OTKA and NKTH (Hungary); DAE and DST (India); IPM (Iran); SFI (Ireland); INFN (Italy); NRF (Korea); LAS (Lithuania); CINVESTAV, CONACYT, SEP, and UASLP-FAI (Mexico); PAEC (Pakistan); SCSR (Poland); FCT (Portugal); JINR (Armenia, Belarus, Georgia, Ukraine, Uzbekistan); MST and MAE (Russia); MSTDS (Serbia); MICINN and CPAN (Spain); Swiss Funding Agencies (Switzerland); NSC (Taipei); TUBITAK and TAEK (Turkey); STFC (United Kingdom); DOE and NSF (USA)

Muscle force development after low-frequency magnetic burst stimulation in dogs.

Introduction: Magnetic stimulation allows for painless and non-invasive extrinsic motor nerve stimulation. Despite several advantages, the limited coupling to the target reduces the application of magnetic pulses in rehabilitation. According to experience with electrical stimulation, magnetic bursts could remove this constraint. Methods: A novel burst stimulator was used to apply single and burst pulses to the femoral nerve in 10 adult dogs. A figure-of-eight coil was connected, and pulses were applied at 7.5 HZ. Contractions of the quadriceps muscle were measured via an angle force transducer. Results: Muscle forces were significantly higher upon burst stimulation than after single pulses. Four consecutive burst pulses proved most effective. Stimulation by more bursts resulted in fatigue. Conclusion: Burst stimulation is superior to standard magnetic single pulses, and 4 consecutive burst pulses proved most effective. Muscle Nerve, 2012 &nbsp