Front instabilities in the presence of convection due to thermal and compositional gradients.

Reaction fronts separate fluids of different densities due to thermal and compositional gradients that may lead to convection. The stability of convectionless flat fronts propagating in the vertical direction depends not only on fluid properties but also in the dynamics of a front evolution equation. In this work, we analyze fronts described by the Kuramoto-Sivashinsky (KS) equation coupled to hydrodynamics. Without density gradients, the KS equation has a flat front solution that is unstable to perturbations of long wavelengths. Buoyancy enhances this instability if a fluid of lower density is underneath a denser fluid. In the reverse situation, with the denser fluid underneath, the front can be stabilized with appropriate thermal and compositional gradients. However, in this situation, a different instability develops for large enough thermal gradients. We also solve numerically the nonlinear KS equation coupled to the Navier-Stokes equations to analyze the front propagation in two-dimensional rectangular domains. As convection takes place, the reaction front curves, increasing its velocity.

Molecular basis of ageing in chronic metabolic diseases.

AIM: Over the last decades, the shift in age distribution towards older ages and the progressive ageing which has occurred in most populations have been paralleled by a global epidemic of obesity and its related metabolic disorders, primarily, type 2 diabetes (T2D). Dysfunction of the adipose tissue (AT) is widely recognized as a significant hallmark of the ageing process that, in turn, results in systemic metabolic alterations. These include insulin resistance, accumulation of ectopic lipids and chronic inflammation, which are responsible for an elevated risk of obesity and T2D onset associated to ageing. On the other hand, obesity and T2D, the paradigms of AT dysfunction, share many physiological characteristics with the ageing process, such as an increased burden of senescent cells and epigenetic alterations. Thus, these chronic metabolic disorders may represent a state of accelerated ageing. MATERIALS AND METHODS: A more precise explanation of the fundamental ageing mechanisms that occur in AT and a deeper understanding of their role in the interplay between accelerated ageing and AT dysfunction can be a fundamental leap towards novel therapies that address the causes, not just the symptoms, of obesity and T2D, utilizing strategies that target either senescent cells or DNA methylation. RESULTS: In this review, we summarize the current knowledge of the pathways that lead to AT dysfunction in the chronological ageing process as well as the pathophysiology of obesity and T2D, emphasizing the critical role of cellular senescence and DNA methylation. CONCLUSION: Finally, we highlight the need for further research focused on targeting these mechanisms.

Marangoni flow traveling with reaction fronts: Eikonal approximation.

Chemical reaction fronts traveling in liquids generate gradients of surface tension leading to fluid motion. This surface tension driven flow, known as Marangoni flow, modifies the shape and the speed of the reaction front. We model the front propagation using the Eikonal relation between curvature and normal speed of the front, resulting in a front evolution equation that couples to the fluid velocity. The sharp discontinuity between the reactants and products leads to a surface tension gradient proportional to a delta function. The Stokes equations with the surface tension gradient as part of the boundary conditions provide the corresponding fluid velocity field. Considering stress free boundaries at the bottom of the liquid layer, we find an analytical solution for the fluid vorticity leading to the velocity field. Solving numerically the appropriate no-slip boundary condition, we gain insights into the role of the boundary condition at the bottom layer. We compare our results with results from two other models for front propagation: the deterministic Kardar-Parisi-Zhang equation and a reaction-diffusion equation with cubic autocatalysis, finding good agreement for small differences in surface tension.

Hoxa5 undergoes dynamic DNA methylation and transcriptional repression in the adipose tissue of mice exposed to high-fat diet.

BACKGROUND/OBJECTIVES: The genomic bases of the adipose tissue abnormalities induced by chronic positive calorie excess have been only partially elucidated. We adopted a genome-wide approach to directly test whether long-term high-fat diet (HFD) exposure affects the DNA methylation profile of the mouse adipose tissue and to identify the functional consequences of these changes. SUBJECTS/METHODS: We have used epididymal fat of mice fed either high-fat (HFD) or regular chow (STD) diet for 5 months and performed genome-wide DNA methylation analyses by methylated DNA immunoprecipitation sequencing (MeDIP-seq). Mouse Homeobox (Hox) Gene DNA Methylation PCR, RT-qPCR and bisulphite sequencing analyses were then performed. RESULTS: Mice fed the HFD progressively expanded their adipose mass accompanied by a significant decrease in glucose tolerance (P<0.001) and insulin sensitivity (P<0.05). MeDIP-seq data analysis revealed a uniform distribution of differentially methylated regions (DMR) through the entire adipocyte genome, with a higher number of hypermethylated regions in HFD mice (P<0.005). This different methylation profile was accompanied by increased expression of the Dnmt3a DNA methyltransferase (Dnmt; P<0.05) and the methyl-CpG-binding domain protein Mbd3 (P<0.05) genes in HFD mice. Gene ontology analysis revealed that, in the HFD-treated mice, the Hox family of development genes was highly enriched in differentially methylated genes (P=0.008). To validate this finding, Hoxa5, which is implicated in fat tissue differentiation and remodeling, has been selected and analyzed by bisulphite sequencing, confirming hypermethylation in the adipose tissue from the HFD mice. Hoxa5 hypermethylation was associated with downregulation of Hoxa5 mRNA and protein expression. Feeding animals previously exposed to the HFD with a standard chow diet for two further months improved the metabolic phenotype of the animals, accompanied by return of Hoxa5 methylation and expression levels (P<0.05) to values similar to those of the control mice maintained under standard chow. CONCLUSIONS: HFD induces adipose tissue abnormalities accompanied by epigenetic changes at the Hoxa5 adipose tissue remodeling gene.

Epigenetics: spotlight on type 2 diabetes and obesity.

Type 2 diabetes (T2D) and obesity are the major public health problems. Substantial efforts have been made to define loci and variants contributing to the individual risk of these disorders. However, the overall risk explained by genetic variation is very modest. Epigenetics is one of the fastest growing research areas in biomedicine as changes in the epigenome are involved in many biological processes, impact on the risk for several complex diseases including diabetes and may explain susceptibility. In this review, we focus on the role of DNA methylation in contributing to the risk of T2D and obesity.

Rayleigh-Taylor instability of steady fronts described by the Kuramoto-Sivashinsky equation.

We study steady thin reaction fronts described by the Kuramoto-Sivashinsky equation that separates fluids of different densities. This system may lead to hydrodynamic instabilities as buoyancy forces interact with the propagating fronts in a two-dimensional slab. We use Darcy's law to describe the fluid motion in this geometry. Steady front profiles can be flat, axisymmetric, or nonaxisymmetric, depending on the slab width, the density gradient, and fluid viscosity. Unstable flat fronts can be stabilized having a density gradient with the less dense fluid on top of a denser fluid. We find the steady front solutions from the nonlinear equations executing a linear stability analysis to determine their stability. We show regions of bistability where stable nonaxisymmetric and axisymmetric fronts can coexist. We also consider the stability of steady solutions in large domains, which can be constructed by dividing the domain into smaller parts or cells.

Thermal and compositional driven convection in thin reaction fronts.

Chemical reaction fronts separate regions of reacted and unreacted substances as they propagate in liquids. These fronts may induce density gradients due to different chemical compositions and temperatures across the front. In this paper, we investigate buoyancy-induced convection driven by both types of gradients. We consider a thin front approximation where the normal front velocity depends only on the front curvature. This model applies for small curvature fronts independent of the specific type of chemical reaction. For density changes due only to heat variations near the front, we find that convection can take place for either upward or downward propagating fronts if density gradients are above a threshold. Convection can set in even if the fluid with lower density is above the higher density fluid. Our model consists of Navier-Stokes equations coupled to the front propagation equation. We carry out a linear stability analysis to determine the parameters for the onset of convection. We study the nonlinear front propagation for liquids confined in narrow two-dimensional domains. Convection leads to fronts of steady shape, propagating with constant velocities.

Stability of convective patterns in reaction fronts: a comparison of three models.

Autocatalytic reaction fronts generate density gradients that may lead to convection. Fronts propagating in vertical tubes can be flat, axisymmetric, or nonaxisymmetric, depending on the diameter of the tube. In this paper, we study the transitions to convection as well as the stability of different types of fronts. We analyze the stability of the convective reaction fronts using three different models for front propagation. We use a model based on a reaction-diffusion-advection equation coupled to the Navier-Stokes equations to account for fluid flow. A second model replaces the reaction-diffusion equation with a thin front approximation where the front speed depends on the front curvature. We also introduce a new low-dimensional model based on a finite mode truncation. This model allows a complete analysis of all stable and unstable fronts.

Pattern formation induced by intraspecific interactions in a predator-prey system.

Differential diffusion is a source of instability in population dynamics systems when species diffuse with different rates. Predator-prey systems show this instability only under certain specific conditions, usually requiring one to involve Holling-type functionals. Here we study the effects of intraspecific cooperation and competition on diffusion-driven instability in a predator-prey system with a different structure. We conduct the analysis on a generalized population dynamics that bounds intraspecific and interspecific interactions with Verhulst-type saturation terms instead of Holling-type functionals. We find that instability occurs due to the intraspecific saturation or intraspecific interactions, both cooperative and competitive. We present numerical simulations and show spatial patterns due to diffusion.

Chemical pattern formation induced by a shear flow in a two-layer model.

We study chemical patterns arising from instabilities in reaction-diffusion-advection systems under the influence of shear flow. Turing pattern formation without shear flow can occur in an activator-inhibitor system as long as the diffusivity of the inhibitor is larger than the diffusivity of the activator. In the presence of shear flow, a homogeneous steady state can become unstable even if this condition is not satisfied. Chemical patterns arise as a result of this instability. We study this instability in a simple system consisting of two layers moving relative to each other. We carry out a linear stability analysis showing the onset of the instability as a function of the relative speed between the layers. We solve numerically the nonlinear reaction-diffusion-advection equations to obtain these patterns. We find stationary, oscillatory, and drifting patterns extending along each layer. We also find regions of bistability that allow the formation of localized structures. The instability is analyzed in terms of Taylor dispersion.

Oscillatory instability in a reaction front separating fluids of different densities.

Reaction fronts described by the Kuramoto-Sivashinsky (KS) equation can exhibit complex behavior as they separate reacted from unreacted fluids. If the fluid of higher density is above a fluid of lower density, then the Rayleigh-Taylor instability can lead to fluid motion. In the reverse situation, where the lighter fluid is on top, gravitationally driven forces can stabilize a convectionless flat front inhibiting the complex front propagation described by the KS equation. In these cases, a critical density difference is required to provide stability to the flat front. A linear stability analysis shows that the transition from stable to unstable flat fronts can be oscillatory for viscous fluid motion. Once the transition takes place, the fronts exhibit oscillatory convection resulting in oscillations of the shape and speed of the front.

Convective chemical fronts in a Poiseuille flow.

Autocatalytic reaction fronts propagating in a Poiseuille flow present a change of speed and curvature depending on the strength of the flow and on the direction of front propagation. These chemical fronts separate reacted and unreacted fluids of different densities, consequently convection will always be present due to the horizontal density gradient of the curved front. In this paper, we find the change of speed caused by gravity for fronts propagating in vertical tubes under a Poiseuille flow. For small density differences, we find axisymmetric fronts. Our theory predicts a transition to nonaxisymmetric fronts as the distance between the walls is increased. The transition depends on the average speed of the Poiseuille flow.

Convection induced by thermal gradients on thin reaction fronts.

We present a thin front model for the propagation of chemical reaction fronts in liquids inside a Hele-Shaw cell or porous media. In this model we take into account density gradients due to thermal and compositional changes across a thin interface. The front separating reacted from unreacted fluids evolves following an eikonal relation between the normal speed and the curvature. We carry out a linear stability analysis of convectionless flat fronts confined in a two-dimensional rectangular domain. We find that all fronts are stable to perturbations of short wavelength, but they become unstable for some wavelengths depending on the values of compositional and thermal gradients. If the effects of these gradients oppose each other, we observe a range of wavelengths that make the flat front unstable. Numerical solutions of the nonlinear model show curved fronts of steady shape with convection propagating faster than flat fronts. Exothermic fronts increase the temperature of the fluid as they propagate through the domain. This increment in temperature decreases with increasing speed.

A semi-synthetic repertoire of intrinsically stable antibody fragments derived from a single-framework scaffold.

We report the design, construction and use of an antibody bacteriophage display library built on the scaffold of a single-chain variable fragment (scFv) previously proven to be functionally expressed in the reducing environment of both bacterial and plant cytoplasm and endowed with intrinsic high thermodynamic stability. Four amino acid residues of the third hypervariable loop (CDR3) of both VH and VL were combinatorially mutated, generating a repertoire of approximately 5x10(7) independent scFvs, cloned in a phagemid vector. The ability of the antibody phage library to yield specific binders was tested by biopanning against several antigens. Successful selection of fully active scFvs was obtained, confirming the notion that combinatorial mutagenesis of few amino acid residues centrally located in the antigen-binding site is sufficient to provide binding specificities against virtually any target. High yields of both soluble and phage antibodies were obtained in Escherichia coli. Maintenance of the cognate scFv antibody stability in the newly selected scFv fragments was demonstrated by guanidinium chloride denaturation/renaturation studies and by soluble antibody expression in the bacterial cytoplasm. The antibody library described here allows the isolation of new stable binding specificities, potentially exploitable as immunochemical reagents for intracellular applications.

Polygalacturonase-inhibiting proteins (PGIPs) with different specificities are expressed in Phaseolus vulgaris.

The pgip-1 gene of Phaseolus vulgaris, encoding a polygalacturonase-inhibiting protein (PGIP), PGIP-1 (P. Toubart, A. Desiderio, G. Salvi, F. Cervone, L. Daroda, G. De Lorenzo, C. Bergmann, A. G. Darvill, and P. Albersheim, Plant J. 2:367-373, 1992), was expressed under control of the cauliflower mosaic virus 35S promoter in tomato plants via Agrobacterium tumefaciens-mediated transformation. Transgenic tomato plants with different expression levels of PGIP-1 were used in infection experiments with the pathogenic fungi Fusarium oxysporum f. sp. lycopersici, Botrytis cinerea, and Alternaria solani. No evident enhanced resistance, compared with the resistance of untransformed plants, was observed. The pgip-1 gene was also transiently expressed in Nicotiana benthamiana with potato virus X (PVX) as a vector. PGIP-1 purified from transgenic tomatoes and PGIP-1 in crude protein extracts of PVX-infected N. benthamiana plants were tested with several fungal polygalacturonases (PGs). PGIP-1 from both plant sources exhibited a specificity different from that of PGIP purified from P. vulgaris (bulk bean PGIP). Notably, PGIP-1 was unable to interact with a homogeneous PG from Fusarium moniliforme, as determined by surface plasmon resonance analysis, while the bulk bean PGIP interacted with and inhibited this enzyme. Moreover, PGIP-1 expressed in tomato and N. benthamiana had only a limited capacity to inhibit crude PG preparations from F. oxysporum f. sp. lycopersici, B. cinerea, and A. solani. Differential affinity chromatography was used to separate PGIP proteins present in P. vulgaris extracts. A PGIP-A with specificity similar to that of PGIP-1 was separated from a PGIP-B able to interact with both Aspergillus niger and F. moniliforme PGs. Our data show that PGIPs with different specificities are expressed in P. vulgaris and that the high-level expression of one member (pgip-1) of the PGIP gene family in transgenic plants is not sufficient to confer general, enhanced resistance to fungi.

Comparison of left ventricular function in insulin- and non-insulin-dependent diabetes mellitus.

Diabetes mellitus has been reported to have controversial effects on left ventricular (LV) function in patients with no evidence of coronary artery disease. In this study, LV function at rest was evaluated in 2 groups of diabetic patients, with insulin-dependent (IDD; n = 16) and non-insulin-dependent (NIDD; n = 23) diabetes mellitus, with no evidence of coronary artery disease. All patients underwent an electrocardiographic stress test, and first-pass and equilibrium radionuclide angiography at rest and during supine exercise. Data in each group of diabetic patients were compared with those obtained from age- and sex-matched normal subjects. In both groups of diabetic patients plasma catecholamine levels were significantly greater than in control subjects. Ejection fraction at rest and during exercise did not differ between each group of diabetic patients and their respective control group. In patients with IDD, peak ejection rate (4 +/- 1 end-diastolic count/s) was significantly greater than in control subjects (2.6 +/- 0.1 end-diastolic count/s; p < 0.001); similarly, peak filling rate (4.3 +/- 1.0 end-diastolic count/s) was significantly greater than in controls (3.0 +/- 0.2 end-diastolic count/s; p < 0.001). Cardiac output and systemic vascular resistances did not differ between patients with IDD and control subjects. In contrast, patients with NIDD had significantly reduced cardiac output compared with that of control subjects (5.7 +/- 0.2 vs 5.9 +/- 0.2 liter/min; p < 0.01), and increased systemic vascular resistances (1,422 +/- 137 vs 1,314 +/- 68 dynes.s.cm-5; p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Hemodynamic effects of creatine phosphate in patients with congestive heart failure: a double-blind comparison trial versus placebo.

BACKGROUND: The use of metabolic drugs effective in addition to conventional therapy represents a significant challenge in patients with left ventricular dysfunction. HYPOTHESIS: The aim of this double-blind, placebo-controlled study was to investigate the hemodynamic effects of acute intravenous (i.v.) administration of creatine phosphate (CP) and of short-term treatment in patients with congestive heart failure (CHF) from ischemic heart disease (IHD) or dilated cardiomyopathy in addition to conventional therapy. METHODS: We compared the hemodynamic effects of exogenous creatine phosphate (CP) and placebo in a double-blind, crossover design study in 13 hospitalized patients (12 men, 1 woman, mean age 52 +/- 8 years) with CHF. All patients were in New York Heart Association (NYHA) class II-III and received conventional pharmacologic therapy for CHF; this was not changed during the study period. The study design consisted of two treatment periods (CP or placebo and placebo or CP, respectively) of 4 days each, separated by a 2-day washout interval. The intravenous infusion consisted of 6 g CP or placebo (acute treatment) or 6 g CP or placebo daily for 4 days (short-term treatment) diluted in 50 ml of NaCl 0.9%; infusion duration was about 10 min. Mono-bidimensional echocardiographic examination (Hewlett Packard Sonos 1000, with a 2.5 MHz transducer) was performed at baseline, after acute infusion, and 12 h after the end of short-term treatment. Data were analyzed by ANOVA and Student's t-test for paired data; the results obtained after acute and short-term therapy were compared with the baseline values. RESULTS: After placebo therapy, no significant change was observed. The results after treatment with CP showed a significant reduction of end-systolic diameter [baseline: 4.5 +/- 0.6; acute: 4.2 +/- 0.5, (p < 0.001); short-term 4.3 +/- 0.6 cm, (p < 0.05)] and systemic vascular resistance (baseline: 1064.9 +/- 483.7; acute: 947.5 +/- 390.2 (p < 0.05); short-term: 950.7 +/- 394.3 dyne-s-cm-5 (p < 0.05); moreover, a significant increase of percent ejection fraction [baseline: 48 +/- 12%; acute 53 +/- 12% (p < 0.01); short-term 52 +/- 11% (p < 0.01)], and of percent fractional shortening [baseline: 25 +/- 7; acute 28 +/- 8 (p < 0.05); short-term 28 +/- 7% (p < 0.05)] was observed. CONCLUSION: CP was shown to improve cardiac function, even in the presence of a conventional CHF pharmacologic therapy.

Convection in chemical fronts with quadratic and cubic autocatalysis.

Convection in chemical fronts enhances the speed and determines the curvature of the front. Convection is due to density gradients across the front. Fronts propagating in narrow vertical tubes do not exhibit convection, while convection develops in tubes of larger diameter. The transition to convection is determined not only by the tube diameter, but also by the type of chemical reaction. We determine the transition to convection for chemical fronts with quadratic and cubic autocatalysis. We show that quadratic fronts are more stable to convection than cubic fronts. We compare these results to a thin front approximation based on an eikonal relation. In contrast to the thin front approximation, reaction-diffusion models show a transition to convection that depends on the ratio between the kinematic viscosity and the molecular diffusivity. (c) 2002 American Institute of Physics.

Pattern formation induced by a differential shear flow.

Fluid flow advecting one substance while others are immobilized can generate an instability in a homogeneous steady state of a reaction-diffusion-advection system. This differential-flow instability leads to the formation of steady spatial patterns in a moving reference frame. We study the effects of shear flow on this instability by considering two layers of fluid moving independently from each other, but allowing the substances to diffuse along and across the layers. We find that shear flow can generate instabilities even if the average flow velocity is zero for both substances. These instabilities are strongly dependent on which substance is advected by the shear flow. We explain these effects using the results of Taylor dispersion, where an effective diffusivity is enhanced by shear flow.

Convection in stable and unstable fronts.

Density gradients across a reaction front can lead to convective fluid motion. Stable fronts require a heavier fluid on top of a lighter one to generate convective fluid motion. On the other hand, unstable fronts can be stabilized with an opposing density gradient, where the lighter fluid is on top. In this case, we can have a stable flat front without convection or a steady convective front of a given wavelength near the onset of convection. The fronts are described with the Kuramoto-Sivashinsky equation coupled to hydrodynamics governed by Darcy's law. We obtain a dispersion relation between growth rates and perturbation wave numbers in the presence of a density discontinuity accross the front. We also analyze the effects of this density change in the transition to chaos.