Exploring the Kibble-Zurek mechanism in a secondary bifurcation

We present new experimental results on the quenching dynamics of an extended thermo-convective system (a network array of approximately 100 convective oscillators) going through a secondary subcritical bifurcation. We characterize a dynamical phase transition through the nature of the domain walls (1D-fronts) that connect the basic multicellular pattern with the new oscillating one. Two different mechanisms of the relaxing dynamics at the threshold are characterized depending on the crossing rate $\mu=\left.\frac{d\varepsilon}{dt}\right|_{\varepsilon=0}$ of the quenched transition. From the analysis of fronts, we show that these mechanisms follow different correlation length scales $\xi \sim \mu^{-\sigma}$. Below a critical value $\mu_c$, a slow response dynamics yields a spatiotemporal coherent front with weak coupling between oscillators. Above $\mu_c$, for rapid quenches, defects are trapped at the front with a strong coupling between oscillators, similarly to the Kibble-Zurek mechanism in quenched phase transitions. These defects, pinned to the fronts, yield a strong decay of the correlation length

Frozen dynamics and synchronization through a secondary symmetry-breaking bifurcation

We show evidence of the frozen dynamics (Kibble-Zurek mechanism) at the transition one-dimensional (1D) front of an extended 1D array of convective oscillators that undergo a secondary subcritical bifurcation. Results correspond to a global synchronization process from nonlocal coupling between the oscillating units. The quenched dynamics exhibits defect trapping at the synchronization front according to the Kibble-Zurek mechanism, predicted for condensed matter systems. A stronger subcriticality prevents the fronts from freezing defects during the quenched transitions. A synchronization model of supercritical oscillating units is proposed to explain differentiation mechanisms in morphogenesis above a critical crossing rate when the frequency of the individual oscillators becomes coherent. The phases of such oscillators are spatially coupled through a Kuramoto-Battogtokh term that leads to the experimentally observed subcriticality. As a consequence, we show that the Kibble-Zurek mechanism overcomes non-locality of a geometrical network above a critical crossing rate

Kibble-Zurek mechanism in a pattern forming secondary bifurcation

We present new experimental results on the quenching dynamics of an extended thermo-convective system (a network array of 100 c onvective oscil- lators) through a secondary bifurcation. The topology of th e new coherent struc- tures which are fronts (domain walls), when this secondary bi furcation is crossed upwards from a basic stationary multicellular pattern towar ds a propagative pat- tern, allows us to characterize a freezing dynamics related t o the Kibble-Zurek mechanism (KZM). This mechanism defines a correlation length ξ ∼ σ when the threshold has been crossed at a quench rate = dǫ dt | ǫ =0 sufficiently large to freeze almost instantaneously the phase transition front. This stu dy concerns several sequences of quenches where convective oscillators become d ifferently correlated depending on . Spatio-temporal correlation analysis will allow us to deter mine the behavior of the KZM from the front dynamics. The novelty of these results is that the front dynamics is expected to show the freezing-out dy namics beyond the threshold, and therefore it will provide the healing length of the system depending on the strength of the quench rate. Furthermore, in our system the effect of res- onant nonlinearities pins the front and diminishes its fluctu ations as we increase the quench rate

Supramolecular zippers elicit interbilayer adhesion of membranes producing cell death

11 pags, 6 figsBackground: The fluorescent dye 10-N-nonyl acridine orange (NAO) is widely used as a mitochondrial marker. NAO was reported to have cytotoxic effects in cultured eukaryotic cells when incubated at high concentrations. Although the biochemical response of NAO-induced toxicity has been well identified, the underlying molecular mechanism has not yet been explored in detail. Methods: We use optical techniques, including fluorescence confocal microscopy and lifetime imaging microscopy (FLIM) both in model membranes built up as giant unilamellar vesicles (GUVs) and cultured cells. These experiments are complemented with computational studies to unravel the molecular mechanism that makes NAO cytotoxic. Results: We have obtained direct evidence that NAO promotes strong membrane adhesion of negatively charged vesicles. The attractive forces are derived from van der Waals interactions between anti-parallel H-dimers of NAO molecules from opposing bilayers. Semi-empirical calculations have confirmed the supramolecular scenario by which anti-parallel NAO molecules form a zipper of bonds at the contact region. The membrane remodeling effect of NAO, as well as the formation of H-dimers, was also confirmed in cultured fibroblasts, as shown by the ultrastructure alteration of the mitochondrial cristae. Conclusions: We conclude that membrane adhesion induced by NAO stacking accounts for the supramolecular basis of its cytotoxicity. General significance: Mitochondria are a potential target for cancer and gene therapies. The alteration of the mitochondrial structure by membrane remodeling agents able to form supramolecular assemblies via adhesion properties could be envisaged as a new therapeutic strategy.This work was supported by the ERC Starting Grant “mitochon” (ERC-StG-2013 338133) and the ERC Proof of Concept “mitozippers” (ERC-PoC-2017 780440), FIS2015-70339-C2-1-R from MINECO (I. L-M.and F.M.), FIS2015-70339-C2-2-R (M.P.L. and C.G.) and S2013/MIT-2807 from the Madrid Regional Government (F.M. and A. G-M.)

Supramolecular zippers elicit interbilayer adhesion of membranes producing cell death

Background: The fluorescent dye 10-N-nonyl acridine orange (NAO) is widely used as a mitochondrial marker. NAO was reported to have cytotoxic effects in cultured eukaryotic cells when incubated at high concentrations. Although the biochemical response of NAO-induced toxicity has been well identified, the underlying molecular mechanism has not yet been explored in detail. Methods: We use optical techniques, including fluorescence confocal microscopy and lifetime imaging microscopy (FLIM) both in model membranes built up as giant unilamellar vesicles (GUVs) and cultured cells. These experiments are complemented with computational studies to unravel the molecular mechanism that makes NAO cytotoxic. Results: We have obtained direct evidence that NAO promotes strong membrane adhesion of negatively charged vesicles. The attractive forces are derived from van der Waals interactions between anti-parallel H-dimers of NAO molecules from opposing bilayers. Semi-empirical calculations have confirmed the supramolecular scenario by which anti-parallel NAO molecules form a zipper of bonds at the contact region. The membrane remodeling effect of NAO, as well as the formation of H-dimers, was also confirmed in cultured fibroblasts, as shown by the ultrastructure alteration of the mitochondrial cristae. Conclusions: We conclude that membrane adhesion induced by NAO stacking accounts for the supramolecular basis of its cytotoxicity. General significance: Mitochondria are a potential target for cancer and gene therapies. The alteration of the mitochondrial structure by membrane remodeling agents able to form supramolecular assemblies via adhesion properties could be envisaged as a new therapeutic strategy

Dietary α‐Linolenic Acid, Marine ω‐3 Fatty Acids, and Mortality in a Population With High Fish Consumption: Findings From the PREvención con DIeta MEDiterránea (PREDIMED) Study

Background: Epidemiological evidence suggests a cardioprotective role of α‐linolenic acid (ALA), a plant‐derived ω‐3 fatty acid. It is unclear whether ALA is beneficial in a background of high marine ω‐3 fatty acids (long‐chain n‐3 polyunsaturated fatty acids) intake. In persons at high cardiovascular risk from Spain, a country in which fish consumption is customarily high, we investigated whether meeting the International Society for the Study of Fatty Acids and Lipids recommendation for dietary ALA (0.7% of total energy) at baseline was related to all‐cause and cardiovascular disease mortality. We also examined the effect of meeting the society's recommendation for long‐chain n‐3 polyunsaturated fatty acids (≥500 mg/day). Methods and Results: We longitudinally evaluated 7202 participants in the PREvención con DIeta MEDiterránea (PREDIMED) trial. Multivariable‐adjusted Cox regression models were fitted to estimate hazard ratios. ALA intake correlated to walnut consumption (r=0.94). During a 5.9‐y follow‐up, 431 deaths occurred (104 cardiovascular disease, 55 coronary heart disease, 32 sudden cardiac death, 25 stroke). The hazard ratios for meeting ALA recommendation (n=1615, 22.4%) were 0.72 (95% CI 0.56–0.92) for all‐cause mortality and 0.95 (95% CI 0.58–1.57) for fatal cardiovascular disease. The hazard ratios for meeting the recommendation for long‐chain n‐3 polyunsaturated fatty acids (n=5452, 75.7%) were 0.84 (95% CI 0.67–1.05) for all‐cause mortality, 0.61 (95% CI 0.39–0.96) for fatal cardiovascular disease, 0.54 (95% CI 0.29–0.99) for fatal coronary heart disease, and 0.49 (95% CI 0.22–1.01) for sudden cardiac death. The highest reduction in all‐cause mortality occurred in participants meeting both recommendations (hazard ratio 0.63 [95% CI 0.45–0.87]). Conclusions: In participants without prior cardiovascular disease and high fish consumption, dietary ALA, supplied mainly by walnuts and olive oil, relates inversely to all‐cause mortality, whereas protection from cardiac mortality is limited to fish‐derived long‐chain n‐3 polyunsaturated fatty acids. Clinical Trial Registration URL: http://www.Controlled-trials.com/. Unique identifier: ISRCTN35739639

Kibble-Zurek mechanism in a pattern forming secondary bifurcation

We present new experimental results on the quenching dynamics of an extended thermo-convective system (a network array of 100 c onvective oscil- lators) through a secondary bifurcation. The topology of th e new coherent struc- tures which are fronts (domain walls), when this secondary bi furcation is crossed upwards from a basic stationary multicellular pattern towar ds a propagative pat- tern, allows us to characterize a freezing dynamics related t o the Kibble-Zurek mechanism (KZM). This mechanism defines a correlation length ξ ∼ σ when the threshold has been crossed at a quench rate = dǫ dt | ǫ =0 sufficiently large to freeze almost instantaneously the phase transition front. This stu dy concerns several sequences of quenches where convective oscillators become d ifferently correlated depending on . Spatio-temporal correlation analysis will allow us to deter mine the behavior of the KZM from the front dynamics. The novelty of these results is that the front dynamics is expected to show the freezing-out dy namics beyond the threshold, and therefore it will provide the healing length of the system depending on the strength of the quench rate. Furthermore, in our system the effect of res- onant nonlinearities pins the front and diminishes its fluctu ations as we increase the quench rate

X chromosome inactivation does not necessarily determine the severity of the phenotype in Rett syndrome patients

Rett syndrome (RTT) is a severe neurological disorder usually caused by mutations in the MECP2 gene. Since the MECP2 gene is located on the X chromosome, X chromosome inactivation (XCI) could play a role in the wide range of phenotypic variation of RTT patients; however, classical methylation-based protocols to evaluate XCI could not determine whether the preferentially inactivated X chromosome carried the mutant or the wild-type allele. Therefore, we developed an allele-specific methylation-based assay to evaluate methylation at the loci of several recurrent MECP2 mutations. We analyzed the XCI patterns in the blood of 174 RTT patients, but we did not find a clear correlation between XCI and the clinical presentation. We also compared XCI in blood and brain cortex samples of two patients and found differences between XCI patterns in these tissues. However, RTT mainly being a neurological disease complicates the establishment of a correlation between the XCI in blood and the clinical presentation of the patients. Furthermore, we analyzed MECP2 transcript levels and found differences from the expected levels according to XCI. Many factors other than XCI could affect the RTT phenotype, which in combination could influence the clinical presentation of RTT patients to a greater extent than slight variations in the XCI pattern

Potato consumption does not increase blood pressure or incident hypertension in 2 cohorts of Spanish adults

5 TablasBackground: Potatoes have a high glycemic load but also antioxidants, vitamins, and minerals. It is unclear what mechanisms are involved in relation to their effect on blood pressure (BP) and hypertension. Objectives: This study aimed to assess the association between potato consumption, BP changes, and the risk of hypertension in 2 Spanish populations. Methods: Separate analyses were performed in PREDIMED (PREvención con DIeta MEDiterránea), a multicenter nutrition intervention trial of adults aged 55-80 y, and the SUN (Seguimiento Universidad de Navarra) project, a prospective cohort made up of university graduates and educated adults with ages (means±SDs) of 42.7±13.3 y for men and 35.1± 10.7 y for women. In PREDIMED, generalized estimating equations adjusted for lifestyle and dietary characteristics were used to assess changes in BP across quintiles of total potato consumption during a 4-y follow-up. Controlled BP values (systolic BP < 140 mm Hg and diastolic BP < 90 mm Hg) during follow-up were also assessed. For SUN, multivariateadjusted HRs for incident hypertension during a mean 6.7-y follow-up were calculated. Results: In PREDIMED, the total potato intake was 81.9 ± 40.6 g/d. No overall differences in systolic or diastolic BP changes were detected based on consumption of potatoes. For total potatoes, the mean difference in change between quintile 5 (highest intake) and quintile 1 (lowest intake) in systolic BP after multivariate adjustment was 20.90 mm Hg (95% CI: -2.56, 0.76 mm Hg; P-trend = 0.1) and for diastolic BP was 20.02 mm Hg (95% CI: -0.93, 0.89 mm Hg; P-trend = 0.8). In SUN, the total potato consumption was 52.7 ± 33.6 g/d, and no significant association between potato consumption and hypertension incidence was observed in the fully adjusted HR for total potato consumption (quintile 5 compared with quintile 1: 0.98; 95% CI: 0.80, 1.19; P-trend = 0.8). Conclusions: Potato consumption is not associated with changes over 4 y in blood pressure among older adults in Spain or with the risk of hypertension among Spanish adults.Supported by the official funding agency for biomedical research of the Spanish Government, Instituto de Salud Carlos III through grants provided to research networks specifically developed for the trial (RTIC G03/140, to RE; RTIC RD 06/0045, to MAM-G) and through Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBERobn), and by grants from Centro Nacional de Investigaciones Cardiovasculares (CNIC 06/2007), Fondo de Investigación Sanitaria–Fondo Europeo de Desarrollo Regional [Proyecto de Investigación (PI) 04-2239, PI 05/2584, CP06/00100, PI07/0240, PI07/1138, PI07/0954, PI 07/0473, PI10/01407, PI10/02658, PI11/01647, P11/02505 and PI13/00462], Ministerio de Ciencia e Innovación [Recursos y teconologia agroalimentarias (AGL)-2009-13906-C02 and AGL2010-22319-C03 and AGL2013-49083-C3-1-R], Fundación Mapfre 2010, the Consejería de Salud de la Junta de Andalucía (PI0105/2007), the Public Health Division of the Department of Health of the Autonomous Government of Catalonia, Generalitat Valenciana [Generalitat Valenciana Ayuda Complementaria (GVACOMP) 06109, GVACOMP2010-181, GVACOMP2011-151], Conselleria de Sanitat y AP; Atención Primaria (CS) 2010-AP-111 and CS2011-AP-042, and Regional Government of Navarra (P27/2011)