Mitochondrial dysfunction contributes to the senescent phenotype of IPF lung fibroblasts

Increasing evidence highlights that senescence plays an important role in idiopathic pulmonary fibrosis (IPF). This study delineates the specific contribution of mitochondria and the superoxide they form to the senescent phenotype of lung fibroblasts from IPF patients (IPF-LFs). Primary cultures of IPF-LFs exhibited an intensified DNA damage response (DDR) and were more senescent than age-matched fibroblasts from control donors (Ctrl-LFs). Furthermore, IPF-LFs exhibited mitochondrial dysfunction, exemplified by increases in mitochondrial superoxide, DNA, stress and activation of mTORC1. The DNA damaging agent etoposide elicited a DDR and augmented senescence in Ctrl-LFs, which were accompanied by disturbances in mitochondrial homoeostasis including heightened superoxide production. However, etoposide had no effect on IPF-LFs. Mitochondrial perturbation by rotenone involving sharp increases in superoxide production also evoked a DDR and senescence in Ctrl-LFs, but not IPF-LFs. Inhibition of mTORC1, antioxidant treatment and a mitochondrial targeting antioxidant decelerated IPF-LF senescence and/or attenuated pharmacologically induced Ctrl-LF senescence. In conclusion, increased superoxide production by dysfunctional mitochondria reinforces lung fibroblast senescence via prolongation of the DDR. As part of an auto-amplifying loop, mTORC1 is activated, altering mitochondrial homoeostasis and increasing superoxide production. Deeper understanding the mechanisms by which mitochondria contribute to fibroblast senescence in IPF has potentially important therapeutic implications

Carbon dioxide, hydrographic, and chemical data obtained in the South Pacific Ocean (WOCE Sections P16A/P17A, P17E/P19S, and P19C, R/V Knorr, October 1992--April 1993)

This data documentation discusses the procedures and methods used to measure total carbon dioxide concentration (TCO{sub 2}) and partial pressure of CO{sub 2} (pCO{sub 2}) in discrete water samples collected during three expeditions of the Research Vessel (R/V) Knorr in the South Pacific Ocean. Conducted as part of the World Ocean Circulation Experiment (WOCE), the first cruise (WOCE Section P16A/P17A) began in Papeete, Tahiti, French Polynesia, on October 6, 1992, and returned to Papeete on November 25, 1992. The second cruise (WOCE Section P17E/P19S) began in Papeete on December 4, 1992, and finished in Punta Arenas, Chile, on January 22, 1993. The third expedition (WOCE Section P19C) started in Punta Arenas, on February 22 and finished in Panama City, Panama, on April 13, 1993. During the three expeditions, 422 hydrographic stations were occupied. Hydrographic and chemical measurements made along WOCE Sections P16A/P17A, P17E/P19S, and P19C included pressure, temperature, salinity, and oxygen [measured by conductivity, temperature, and depth (CTD) sensor], as well as discrete measurements of salinity, oxygen, phosphate, nitrate, nitrite, silicate, chlorofluorocarbons (CFC-11, CFC-12), TCO{sub 2}, and pCO{sub 2} measured at 4 and 20 C. In addition, potential temperatures were calculated from the measured variables

Resonances in the dynamics of ϕ4\phi^4 kinks perturbed by ac forces

We study the dynamics of $\phi^4$ kinks perturbed by an ac force, both with and without damping. We address this issue by using a collective coordinate theory, which allows us to reduce the problem to the dynamics of the kink center and width. We carry out a careful analysis of the corresponding ordinary differential equations, of Mathieu type in the undamped case, finding and characterizing the resonant frequencies and the regions of existence of resonant solutions. We verify the accuracy of our predictions by numerical simulation of the full partial differential equation, showing that the collective coordinate prediction is very accurate. Numerical simulations for the damped case establish that the strongest resonance is the one at half the frequency of the internal mode of the kink. In the conclusion we discuss on the possible relevance of our results for other systems, especially the sine-Gordon equation. We also obtain additional results regarding the equivalence between different collective coordinate methods applied to this problem.Comment: 23 pages, 7 figures, REVTeX, accepted for publication in Phys. Rev.

Collaborative International Research in Clinical and Longitudinal Experience Study in NMOSD

OBJECTIVE: To develop a resource of systematically collected, longitudinal clinical data and biospecimens for assisting in the investigation into neuromyelitis optica spectrum disorder (NMOSD) epidemiology, pathogenesis, and treatment. METHODS: To illustrate its research-enabling purpose, epidemiologic patterns and disease phenotypes were assessed among enrolled subjects, including age at disease onset, annualized relapse rate (ARR), and time between the first and second attacks. RESULTS: As of December 2017, the Collaborative International Research in Clinical and Longitudinal Experience Study (CIRCLES) had enrolled more than 1,000 participants, of whom 77.5% of the NMOSD cases and 71.7% of the controls continue in active follow-up. Consanguineous relatives of patients with NMOSD represented 43.6% of the control cohort. Of the 599 active cases with complete data, 84% were female, and 76% were anti-AQP4 seropositive. The majority were white/Caucasian (52.6%), whereas blacks/African Americans accounted for 23.5%, Hispanics/Latinos 12.4%, and Asians accounted for 9.0%. The median age at disease onset was 38.4 years, with a median ARR of 0.5. Seropositive cases were older at disease onset, more likely to be black/African American or Hispanic/Latino, and more likely to be female. CONCLUSION: Collectively, the CIRCLES experience to date demonstrates this study to be a useful and readily accessible resource to facilitate accelerating solutions for patients with NMOSD