Ascorbic acid induces an oxidative stress in CCRF cells activating the transcription factors AP-1 and NFRB

We have previously tested the effects of high dose AA supplements on human volunteers in terms of reducing DNA damage, as a possible mechanism of the vitamin’s proposed protective effect against cancer and detected a transient, pro-oxidant effect at high doses (500 mg/day). Herein, we present evidence of a pro-oxidant effect of the vitamin when added to CCRF cells at extracellular concentrations which mimic those present in human serum in vivo (50–150AM). The activation of the transcription factor AP-1 was optimal at 100 AM AA following 3h exposure at 37jC. A minimum dose of 50 AM of AA activated NFnB but there appeared to be no dose-dependent effect. Increases of 2–3 fold were observed for both transcription factors when cells were exposed to 100 AM AA for 3h, comparing well with the pro-oxidant effect of H2O2 at similar concentrations. In parallel experiments the activation of AP-1 (binding to DNA) was potentiated when cells were pre-incubated with AA prior to exposure with H2O2. Cycloheximide pretreatment (10 Ag/ml for 15min) caused a 50% inhibition of AP-1 binding to DNA suggesting that it was due to a combination of increasing the binding of pre-existing Fos and Jun and an increase in their de novo synthesis. Cellular localisation was confirmed by immunocytochemistry using antibodies specific for c-Fos and c-Jun proteins. These results suggest that extracellular AA can elicit an intracellular stress response resulting in the activation of the oxidative stress-responsive transcription factors AP-1 and NFnB. These transcription factors are involved in the induction of genes associated with an oxidative stress response, cell cycle arrest and DNA repair confirmed by our cDNA microarray analysis (Affymetrix). This may explain the abilty for AA to appear to inhibit 8-oxodG, yet simultaneously generate another oxidative stress biomarker, 8-oxo-dA. These results suggest a completely novel DNA repair action for AA. Whether this action is relevant to our in vivo findings will be the subject of our future research.

Nonlinear spectral shaping and optical rogue events in fiber-based systems

We provide an overview of our recent work on the shaping and stability of optical continua in the long pulse regime. Fibers with normal group-velocity dispersion at all-wavelengths are shown to allow for highly coherent continua that can be nonlinearly shaped using appropriate initial conditions. In contrast, supercontinua generated in the anomalous dispersion regime are shown to exhibit large fluctuations in the temporal and spectral domains that can be controlled using a carefully chosen seed. A particular example of this is the first experimental observation of the Peregrine soliton which constitutes a prototype of optical rogue-waves.

From rogue waves to random walks:nonlinear instabilities in supercontinuum generation

The noise properties of supercontinuum generation continue to be a subject of wide interest within both pure and applied physics. Aside from immediate applications in supercontinuum source development, detailed studies of supercontinuum noise mechanisms have attracted interdisciplinary attention because of links with extreme instabilities in other physical systems, especially the infamous and destructive oceanic rogue waves. But the instabilities inherent in supercontinuum generation can also be interpreted in terms of natural links with the general field of random processes, and this raises new possibilities for applications in areas such as random number generation. In this contribution we will describe recent work where we interpret supercontinuum intensity and phase fluctuations in this way.

Nonlinear spectral shaping and optical rogue events in fiber-based systems

We provide an overview of our recent work on the shaping and stability of optical continua in the long pulse regime. Fibers with normal group-velocity dispersion at all-wavelengths are shown to allow for highly coherent continua that can be nonlinearly shaped using appropriate initial conditions. In contrast, supercontinua generated in the anomalous dispersion regime are shown to exhibit large fluctuations in the temporal and spectral domains that can be controlled using a carefully chosen seed. A particular example of this is the first experimental observation of the Peregrine soliton which constitutes a prototype of optical rogue-waves. © 2012 Elsevier Inc. All rights reserved.

Septin6 and Septin7 GTP binding proteins regulate AP-3- and ESCRT-dependent multivesicular body biogenesis

Septins (SEPTs) form a family of GTP-binding proteins implicated in cytoskeleton and membrane organization, cell division and host/pathogen interactions. The precise function of many family members remains elusive. We show that SEPT6 and SEPT7 complexes bound to F-actin regulate protein sorting during multivesicular body (MVB) biogenesis. These complexes bind AP-3, an adapter complex sorting cargos destined to remain in outer membranes of maturing endosomes, modulate AP-3 membrane interactions and the motility of AP-3-positive endosomes. These SEPT-AP interactions also influence the membrane interaction of ESCRT (endosomal-sorting complex required for transport)-I, which selects ubiquitinated cargos for degradation inside MVBs. Whereas our findings demonstrate that SEPT6 and SEPT7 function in the spatial, temporal organization of AP-3- and ESCRT-coated membrane domains, they uncover an unsuspected coordination of these sorting machineries during MVB biogenesis. This requires the E3 ubiquitin ligase LRSAM1, an AP-3 interactor regulating ESCRT-I sorting activity and whose mutations are linked with Charcot-Marie-Tooth neuropathies.

Soliton's eigenvalue based analysis on the generation mechanism of rogue wave phenomenon in optical fibers exhibiting weak third order dispersion

One of the extraordinary aspects of nonlinear wave evolution which has been observed as the spontaneous occurrence of astonishing and statistically extraordinary amplitude wave is called rogue wave. We show that the eigenvalues of the associated equation of nonlinear Schrödinger equation are almost constant in the vicinity of rogue wave and we validate that optical rogue waves are formed by the collision between quasi-solitons in anomalous dispersion fiber exhibiting weak third order dispersion.

Analysis of rogue wave phenomenon in optical fiber based on soliton's eigenvalue

The impact of third-order dispersion (TOD) on optical rogue wave phenomenon is investigated numerically. We validate the TOD coefficient by utilizing the eigenvalue of the associated equation of the nonlinear Schrödinger equation (NLSE). © 2014 OSA.

AP-2 complex-mediated endocytosis of Drosophila Crumbs regulates polarity via antagonizing Stardust

Maintenance of epithelial polarity depends on the correct localization and levels of polarity determinants. The evolutionarily conserved transmembrane protein Crumbs is crucial for the size and identity of the apical membrane, yet little is known about the molecular mechanisms controlling the amount of Crumbs at the surface. Here, we show that Crumbs levels on the apical membrane depend on a well-balanced state of endocytosis and stabilization. The adaptor protein 2 (AP-2) complex binds to a motif in the cytoplasmic tail of Crumbs that overlaps with the binding site of Stardust, a protein known to stabilize Crumbs on the surface. Preventing endocytosis by mutations in AP-2 causes expansion of the Crumbs-positive plasma membrane and polarity defects, which can be partially rescued by removing one copy of crumbs. Strikingly, knocking-down both AP-2 and Stardust retains Crumbs on the membrane. This study provides evidence for a molecular mechanism, based on stabilization and endocytosis, to adjust surface levels of Crumbs, which are essential for maintaining epithelial polarity.

Optical rogue waves in telecommunication data streams

Large broadening of short optical pulses due to fiber dispersion leads to a strong overlap in information data streams resulting in statistical deviations of the local power from its average. We present a theoretical analysis of rare events of high-intensity fluctuations-optical freak waves-that occur in fiber communication links using bit-overlapping transmission. Although the nature of the large fluctuations examined here is completely linear, as compared to commonly studied freak waves generated by nonlinear effects, the considered deviations inherit from rogue waves the key features of practical interest-random appearance of localized high-intensity pulses. We use the term "rogue wave" in an unusual context mostly to attract attention to both the possibility of purely linear statistical generation of huge amplitude waves and to the fact that in optics the occurrence of such pulses might be observable even with the standard Gaussian or even rarer-than-Gaussian statistics, without imposing the condition of an increased probability of extreme value events. © 2011 American Physical Society.

Reply to "comment on 'Optical rogue waves in telecommunication data streams'"

We feel that the main claim made in the abstract of the preceding Comment is wrong. Using results obtained in our paper, we prove that rogue waves with amplitudes much larger than the average level can be observed during a short period of time in purely linear propagation regimes in optical fiber systems. © 2011 American Physical Society.

Dynamics of vector rogue waves in a fiber laser with a ring cavity

A pulse–pulse interaction that leads to rogue wave (RW) generation in lasers was previously attributed either to soliton–soliton or soliton–dispersive-wave interaction. The beating between polarization modes in the absence of a saturable absorber causes similar effects. Accounting for these polarization modes in a laser resonator is the purpose of the distributed vector model of laser resonators. Furthermore, high pump power, high amplitude, and short pulse duration are not necessary conditions to observe pulse attraction, repulsion, and collisions and the resonance exchange of energy between among them. The regimes of interest can be tuned just by changing the birefringence in the cavity with the pump power slightly higher than the laser threshold. This allows the observation of a wide range of RW patterns in the same experiment, as well as to classify them. The dynamics of the interaction between pulses leads us to the conclusion that all of these effects occur due to nonlinearity induced by the inverse population in the active fiber as well as an intrinsic nonlinearity in the passive part of the cavity. Most of the mechanisms of pulse–pulse interaction were found to be mutually exclusive. This means that all the observed RW patterns, namely, the “lonely,” “twins,” “three sisters,” and “cross,” are probably different cases of the same process.

Slow deterministic vector rogue waves

For an erbium-doped fiber laser mode-locked by carbon nanotubes, we demonstrate experimentally and theoretically a new type of the vector rogue waves emerging as a result of the chaotic evolution of the trajectories between two orthogonal states of polarization on the Poincare sphere. In terms of fluctuation induced phenomena, by tuning polarization controller for the pump wave and in-cavity polarization controller, we are able to control the Kramers time, i.e. the residence time of the trajectory in vicinity of each orthogonal state of polarization, and so can cause the rare events satisfying rogue wave criteria and having the form of transitions from the state with the long residence time to the state with a short residence time.