Antispiral waves are sources in oscillatory reaction-diffusion media

Spiral and antispiral waves are studied numerically in two examples of oscillatory reaction-diffusion media and analytically in the corresponding complex Ginzburg-Landau equation (CGLE). We argue that both these structures are sources of waves in oscillatory media, which are distinguished only by the sign of the phase velocity of the emitted waves. Using known analytical results in the CGLE, we obtain a criterion for the CGLE coefficients that predicts whether antispirals or spirals will occur in the corresponding reaction-diffusion systems. We apply this criterion to the FitzHugh-Nagumo and Brusselator models by deriving the CGLE near the Hopf bifurcations of the respective equations. Numerical simulations of the full reaction-diffusion equations confirm the validity of our simple criterion near the onset of oscillations. They also reveal that antispirals often occur near the onset and turn into spirals further away from it. The transition from antispirals to spirals is characterized by a divergence in the wavelength. A tentative interpretaion of recent experimental observations of antispiral waves in the Belousov-Zhabotinsky reaction in a microemulsion is given.Comment: 10 pages, 8 figures, submitted to J. Phys. Chem. B on Feb. 20, 2004. A short account of the spiral-antispiral criterion has been given in PRL (see http://link.aps.org/abstract/PRL/v92/e089801

Drifting Pattern Domains in a Reaction-Diffusion System with Nonlocal Coupling

Drifting pattern domains (DPDs), moving localized patches of traveling waves embedded in a stationary (Turing) pattern background and vice versa, are observed in simulations of a reaction-diffusion model with nonlocal coupling. Within this model, a region of bistability between Turing patterns and traveling waves arises from a codimension-2 Turing-wave bifurcation (TWB). DPDs are found within that region in a substantial distance from the TWB. We investigated the dynamics of single interfaces between Turing and wave patterns. It is found that DPDs exist due to a locking of the interface velocities, which is imposed by the absence of space-time defects near these interfaces.Comment: 4 pages, 4 figure

Mobility induces global synchronization of oscillators in periodic extended systems

We study synchronization of locally coupled noisy phase oscillators which move diffusively in a one-dimensional ring. Together with the disordered and the globally synchronized states, the system also exhibits several wave-like states which display local order. We use a statistical description valid for a large number of oscillators to show that for any finite system there is a critical spatial diffusion above which all wave-like solutions become unstable. Through Langevin simulations, we show that the transition to global synchronization is mediated by the relative size of attractor basins associated to wave-like states. Spatial diffusion disrupts these states and paves the way for the system to attain global synchronization

Polarization of PAR Proteins by Advective Triggering of a Pattern-Forming System

In the Caenorhabditis elegans zygote, a conserved network of partitioning-defective (PAR) polarity proteins segregates into an anterior and a posterior domain, facilitated by flows of the cortical actomyosin meshwork. The physical mechanisms by which stable asymmetric PAR distributions arise from transient cortical flows remain unclear. We present evidence that PAR polarity arises from coupling of advective transport by the flowing cell cortex to a multistable PAR reaction-diffusion system. By inducing transient PAR segregation, advection serves as a mechanical trigger for the formation of a PAR pattern within an otherwise stably unpolarized system. We suggest that passive advective transport in an active and flowing material may be a general mechanism for mechanochemical pattern formation in developmental systems

Breaking chirality in nonequilibrium systems on the lattice

We study the dynamics of fronts in parametrically forced oscillating lattices. Using as a prototypical example the discrete Ginzburg-Landau equation, we show that much information about front bifurcations can be extracted by projecting onto a cylindrical phase space. Starting from a normal form that describes the nonequilibrium Ising-Bloch bifurcation in the continuum and using symmetry arguments, we derive a simple dynamical system that captures the dynamics of fronts in the lattice. We can expect our approach to be extended to other pattern-forming problems on lattices

Left ventricle remodelling by double-patch sandwich technique

BACKGROUND: The sandwich double-patch technique was adopted as an alternative method for reconstruction of the left ventricle after excision of postinfarction dysfunctional myocardium to solve technical problems due to the thick edges of the ventricular wall. METHODS: Over a 5-year period, 12 of 21 patients with postinfarction antero-apical left ventricular aneurysm had thick wall edges after wall excision. It was due to akinetic muscular thick tissue in 6 cases, while in the other 6 with classic fibrous aneurysm, thick edges remained after the cut of the border zone. The ventricular opening was sandwiched between two patches and this is a technique which is currently used for the treatment of the interventricular septum rupture. In our patients the patches are much smaller than the removed aneurysm and they were sutured simply by a single row of single stitches. However, in contrast to interventricular septum rupture where the patches loosen the tension of the tissues, in our patients the patches pull strongly and restrain the walls by fastening their edges and supporting tight stitches. In this way they could narrow the cavity and close the ventricle. RESULTS: The resected area varied from 5 × 4 to 8 × 8 cm. Excision was extended into the interventricular septum in 5 patients, thus opening the right ventricle. CABG was performed on all patients but two. Left ventricular volumes and the ejection fraction changed significantly: end-systolic volume 93.5 ± 12.4 to 57.8 ± 8.9 ml, p < 0.001; end-diastolic volume 157.2 ± 16.7 to 115.3 ± 14.9 ml, p < 0.001; ejection fraction 40.3 ± 4.2 to 49.5 ± 5.7%, p < 0.001. All patients did well. One patient suffered from bleeding, which was not from the wall suture, and another had a left arm paresis. The post-operative hospital stay was 5 to 30 days with a mean 10.5 ± 7.5 days/patient. At follow-up, 9 to 60 months mean 34, all patients were symptom-free. NYHA class 2.5 ± 0.8 changed to 1.2 ± 0.4, p < 0.001. CONCLUSION: The double-patch sandwich technique (bi-patch closure) offers some advantages and does not result in increased morbidity and mortality. In the case of excising a left ventricular aneurysm, this technique in no way requires eversion of the edges, felt strips, buttressed and multiple sutures, all of which are needed for longitudinal linear closure. Moreover, it does not require purse string sutures, endocardial scar remnant to secure the patch or folding the excluded non-functional tissue, all of which are needed for endoventricular patch repair

Efficacy and safety of reparixin in patients with severe covid-19 Pneumonia. A phase 3, randomized, double-blind placebo-controlled study

Introduction: Polymorphonuclear cell influx into the interstitial and bronchoalveolar spaces is a cardinal feature of severe coronavirus disease 2019 (COVID-19), principally mediated by interleukin-8 (IL-8). We sought to determine whether reparixin, a novel IL-8 pathway inhibitor, could reduce disease progression in patients hospitalized with severe COVID-19 pneumonia. Methods: In this Phase 3, randomized, double-blind, placebo-controlled, multicenter study, hospitalized adult patients with severe COVID-19 pneumonia were randomized 2:1 to receive oral reparixin 1200&nbsp;mg three times daily or placebo for up to 21&nbsp;days or until hospital discharge. The primary endpoint was the proportion of patients alive and free of respiratory failure at Day 28, with key secondary endpoints being the proportion of patients free of respiratory failure at Day 60, incidence of intensive care unit (ICU) admission by Day 28 and time to recovery by Day 28. Results: Of 279 patients randomized, 182 received at least one dose of reparixin and 88 received placebo. The proportion of patients alive and free of respiratory failure at Day 28 was similar in the two groups {83.5% versus 80.7%; odds ratio 1.63 [95% confidence interval (CI) 0.75, 3.51]; p = 0.216}. There were no statistically significant differences in the key secondary endpoints, but a numerically higher proportion of patients in the reparixin group were alive and free of respiratory failure at Day 60 (88.7% versus 84.6%; p = 0.195), fewer required ICU admissions by Day 28 (15.8% versus 21.7%; p = 0.168), and a higher proportion recovered by Day 28 compared with placebo (81.6% versus 74.9%; p = 0.167). Fewer patients experienced adverse events with reparixin than placebo (45.6% versus 54.5%), most mild or moderate intensity and not related to study treatment. Conclusions: This trial did not meet the primary efficacy endpoints, yet reparixin showed a trend toward limiting disease progression as an add-on therapy in COVID-19 severe pneumonia and was well tolerated. Trial registration: ClinicalTrials.gov: NCT04878055, EudraCT: 2020-005919-51

Diffusive coupling can discriminate between similar reaction mechanisms in an allosteric enzyme system

<p>Abstract</p> <p>Background</p> <p>A central question for the understanding of biological reaction networks is how a particular dynamic behavior, such as bistability or oscillations, is realized at the molecular level. So far this question has been mainly addressed in well-mixed reaction systems which are conveniently described by ordinary differential equations. However, much less is known about how molecular details of a reaction mechanism can affect the dynamics in diffusively coupled systems because the resulting partial differential equations are much more difficult to analyze.</p> <p>Results</p> <p>Motivated by recent experiments we compare two closely related mechanisms for the product activation of allosteric enzymes with respect to their ability to induce different types of reaction-diffusion waves and stationary Turing patterns. The analysis is facilitated by mapping each model to an associated complex Ginzburg-Landau equation. We show that a sequential activation mechanism, as implemented in the model of Monod, Wyman and Changeux (MWC), can generate inward rotating spiral waves which were recently observed as glycolytic activity waves in yeast extracts. In contrast, in the limiting case of a simple Hill activation, the formation of inward propagating waves is suppressed by a Turing instability. The occurrence of this unusual wave dynamics is not related to the magnitude of the enzyme cooperativity (as it is true for the occurrence of oscillations), but to the sensitivity with respect to changes of the activator concentration. Also, the MWC mechanism generates wave patterns that are more stable against long wave length perturbations.</p> <p>Conclusions</p> <p>This analysis demonstrates that amplitude equations, which describe the spatio-temporal dynamics near an instability, represent a valuable tool to investigate the molecular effects of reaction mechanisms on pattern formation in spatially extended systems. Using this approach we have shown that the occurrence of inward rotating spiral waves in glycolysis can be explained in terms of an MWC, but not with a Hill mechanism for the activation of the allosteric enzyme phosphofructokinase. Our results also highlight the importance of enzyme oligomerization for a possible experimental generation of Turing patterns in biological systems.</p

Characterization of Yeast Extracellular Vesicles: Evidence for the Participation of Different Pathways of Cellular Traffic in Vesicle Biogenesis

Background: Extracellular vesicles in yeast cells are involved in the molecular traffic across the cell wall. In yeast pathogens, these vesicles have been implicated in the transport of proteins, lipids, polysaccharide and pigments to the extracellular space. Cellular pathways required for the biogenesis of yeast extracellular vesicles are largely unknown. Methodology/Principal Findings: We characterized extracellular vesicle production in wild type (WT) and mutant strains of the model yeast Saccharomyces cerevisiae using transmission electron microscopy in combination with light scattering analysis, lipid extraction and proteomics. WT cells and mutants with defective expression of Sec4p, a secretory vesicleassociated Rab GTPase essential for Golgi-derived exocytosis, or Snf7p, which is involved in multivesicular body (MVB) formation, were analyzed in parallel. Bilayered vesicles with diameters at the 100–300 nm range were found in extracellular fractions from yeast cultures. Proteomic analysis of vesicular fractions from the cells aforementioned and additional mutants with defects in conventional secretion pathways (sec1-1, fusion of Golgi-derived exocytic vesicles with the plasm