Methylene blue as a suppessor of the genotoxic effect of ultraviolet radiation with a wavelength of 300–400 nm

Ultraviolet radiation with a wavelength of 300–400 nm is characteristic of sunlight at the earth surface and causes DNA damage mediated by energy transfer to O₂ with the transformation of the latter in the singlet state. In connection with this, scavengers of reactive oxygen species (ROSs) are potential protectors against the genotoxic effect of this kind of radiation. It was found that the methylene blue dye at doses differing by several orders of magnitude from those that are toxic for humans is able to suppress completely the SOS response induced by UV with a wavelength of 300–400 nm in Escherichia coli.     

The role of noise in a predator–prey model with Allee effect

The existence and implications of alternative stable states in ecological systems have been investigated extensively within deterministic models. However, it is known that natural systems are undeniably subject to random fluctuations, arising from either environmental variability or internal effects. Thus, in this paper, we study the role of noise on the pattern formation of a spatial predator–prey model with Allee effect. The obtained results show that the spatially extended system exhibits rich dynamic behavior. More specifically, the stationary pattern can be induced to be a stable target wave when the noise intensity is small. As the noise intensity is increased, patchy invasion emerges. These results indicate that the dynamic behavior of predator–prey models may be partly due to stochastic factors instead of deterministic factors, which may also help us to understand the effects arising from the undeniable susceptibility to random fluctuations of real ecosystems.     

Dynamics of the ‘echo’ effect in a phytoplankton system with nitrogen fixation

Consideration of nitrogen fixation adds a positive nonlinear feedback to plankton ecosystem models. We investigate the consequences of this feedback for secondary phytoplankton blooms and the response of phytoplankton dynamics to physical forcing. The dynamics of phytoplankton, Trichodesmium (the nitrogen fixer), and nutrients is modeled with a system of three differential equations. The model includes two types of nonlinear interactions: the competition of phytoplankton and Trichodesmium for light, and the positive feedback resulting from Trichodesmium recycling. A typical simulation of the model in time, with forcing by a varying mixed-layer depth, reveals a clear successional sequence including a secondary or ‘echo’ bloom of the phytoplankton. We explain this sequence of events through the stability analysis of three different steady states of the model. Our analysis shows the existence of a critical biological parameter, the ratio of normalized growth rates, determining the occurrence of ‘echo’ blooms and the specific sequence of events following a physical perturbation. The interplay of positive and negative feedbacks appears essential to the timing and the type of events following such a perturbation.     

Investigating the effect of a single glycine to alanine substitution on interactions of antimicrobial peptide latarcin 2a with a lipid membrane

Latarcins are linear, α-helical antimicrobial peptides purified from the venom of the Central Asian spider Lachesana tarabaevi, with lytic activity against Gram-positive and Gram-negative bacteria, erythrocytes, and yeast at micromolar concentrations. In this work, we investigated the role of the hinge in latarcin 2a (ltc2a, GLFGKLIKKFGRKAISYAVKKARGKH-COOH), which adopts a helix–hinge–helix conformation in membrane-mimicking environments, on peptide–membrane interactions and its potential effect on the selective toxicity of the peptide. A modified latarcin 2a, ltc2aG11A, obtained by replacing the glycine at position 11 with alanine (ltc2aG11A, GLFGKLIKKFARKAISYAVKKARGKH-COOH), adopts a more rigid structure due to the reduced conformational flexibility. Langmuir monolayer measurements combined with atomic force microscopy and X-ray photoemission electron microscopy (X-PEEM) indicate that both peptides bind and insert preferentially into anionic compared with zwitterionic phospholipid monolayers. Modified ltc2aG11A was found to be more disruptive of supported phospholipid bilayer modeling mammalian cell membrane. However, no considerable difference in lytic activity of the two peptides toward bacterial membrane was found. Overall the data indicate that decrease in the flexibility of ltc2a induced by the modification in the hinge region is likely to increase the peptide’s nonspecific interactions with zwitterionic cell membranes and potentially increase its toxicity against eukaryotic cells.     

Interaction of cationic surfactants with DPPC membranes: effect of a novel Nα-benzoylated arginine-based compound

Cationic amino acid-based surfactants are known to interact with the lipid bilayer of microorganism resulting in cell death through a disruption of the membrane topology. To elucidate the interaction of a cationic surfactant synthesized in our lab, investigations involving N^α-benzoyl-arginine decyl amide (Bz-Arg-NHC₁₀), and model membranes composed by 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) were done. Bz-Arg-NHC₁₀was able to penetrate into DPPC monolayers up to a critical pressure of 59.6 mN m⁻¹. Differential scanning calorimetry revealed that as the concentration of Bz-Arg-NHC₁₀ increased, the main transition temperature of DPPC slightly decreased. Atomic force microscopy (AFM) in situ experiments performed on supported DPPC bilayers on mica allowed monitoring the changes induced by Bz-Arg-NHC₁₀. DPPC bilayer patches were partially removed, mainly in borders and bilayer defects for 50 µM Bz-Arg-NHC₁₀ solution. Increasing the concentration to 100 µM resulted in a complete depletion of the supported bilayers. Surface plasmon resonance (SPR) experiments, carried out with fully DPPC bilayers covered chips, showed a net increase of the SPR signal, which can be explained by Bz-Arg-NHC₁₀ adsorption. When patchy DPPC bilayers were formed on the substrate, a SPR signal net decrease was obtained, which is consistent with the phospholipids’ removal observed in the AFM images. The results obtained suggest that the presence of the benzoyl group attached to the polar head of our compound would be the responsible of the increased antimicrobial activity against gram-negative bacteria when compared with other arginine-based surfactants.

     

The effect of phosphorylation on the conformation of oligo-peptides with Ser–Pro motif: a molecular dynamics simulation

Model tetrapeptide system was designed to investigate the cis/trans isomerization of peptidyl-prolyl imide bond of Ser–Pro motif. To establish the side-chain O-phosphorylation effect in regulating the peptides conformations, molecular dynamics (MD) simulations where carried out on the designed tetrapeptides and their corresponding phosphorylated forms by MD Insight II Discovery3 approach. The most stable configurations and the statistic cis/trans concentration distribution demonstrated that the phosphorylation evidently influences the peptidyl-prolyl imide bond isomerization and works as a key effect in regulating the peptide conformations. The charge state and the site provided for the charge of the phosphate moiety might be an important key. The results also demonstrated that phosphorylation changes the cis conformation ratio of the peptide and the maximum cis value is obtained when the phosphate group has no negative charge.     

The complex dynamics of a diffusive prey–predator model with an Allee effect in prey

This paper investigates complex dynamics of a predator–prey interaction model that incorporates: (a) an Allee effect in prey; (b) the Michaelis–Menten type functional response between prey and predator; and (c) diffusion in both prey and predator. We provide rigorous mathematical results of the proposed model including: (1) the stability of non-negative constant steady states; (2) sufficient conditions that lead to Hopf/Turing bifurcations; (3) a prior estimates of positive steady states; (4) the non-existence and existence of non-constant positive steady states when the model is under zero-flux boundary condition. We also perform completed analysis of the corresponding ODE model to obtain a better understanding on effects of diffusion on the stability. Our analytical results show that the small values of the ratio of the prey's diffusion rate to the predator's diffusion rate are more likely to destabilize the system, thus generate Hopf-bifurcation and Turing instability that can lead to different spatial patterns. Through numerical simulations, we observe that our model, with or without Allee effect, can exhibit extremely rich pattern formations that include but not limit to strips, spotted patterns, symmetric patterns. In addition, the strength of Allee effects also plays an important role in generating distinct spatial patterns.     

Atherogenic lipid profile is a feature characteristic of patients with early rheumatoid arthritis: effect of early treatment – a prospective, controlled study

The efficiency of activating latent transforming growth factor (TGF)-β₁ in systemic lupus erythematosus (SLE) may control the balance between inflammation and fibrosis, modulating the disease phenotype. To test this hypothesis we studied the ability to activate TGF-β₁ in SLE patients and control individuals within the context of inflammatory disease activity, cumulative organ damage and early atherosclerosis. An Activation Index (AI) for TGF-β₁ was determined for 32 patients with SLE and 33 age-matched and sex-matched control individuals by quantifying the increase in active TGF-β₁ under controlled standard conditions. Apoptosis in peripheral blood mononuclear cells was determined by fluorescence-activated cell sorting. Carotid artery intima-media thickness was measured using standard Doppler ultrasound. These measures were compared between patients and control individuals. In an analysis conducted in patients, we assessed the associations of these measures with SLE phenotype, including early atherosclerosis. Both intima-media thickness and TGF-β₁ AI for SLE patients were within the normal range. There was a significant inverse association between TGF-β₁ AI and levels of apoptosis in peripheral blood mononuclear cells after 24 hours in culture for both SLE patients and control individuals. Only in SLE patients was there a significant negative correlation between TGF-β₁ AI and low-density lipoprotein cholesterol (r = -0.404; P = 0.022) and between TGF-β₁ AI and carotid artery intima-media thickness (r = -0.587; P = 0.0004). A low AI was associated with irreversible damage (SLICC [Systemic Lupus International Collaborating Clinics] Damage Index ≥1) and was inversely correlated with disease duration. Intima-media thickness was significantly linked to total cholesterol (r = 0.371; P = 0.037). To conclude, in SLE low normal TGF-β₁ activation was linked with increased lymphocyte apoptosis, irreversible organ damage, disease duration, calculated low-density lipoprotein levels and increased carotid IMT, and may contribute to the development of early atherosclerosis.     

Atherogenic lipid profile is a feature characteristic of patients with early rheumatoid arthritis: effect of early treatment – a prospective, controlled study

We investigated lipid profiles and lipoprotein modification after immuno-intervention in patients with early rheumatoid arthritis (ERA). Fifty-eight patients with ERA who met the American College of Rheumatology (ACR) criteria were included in the study. These patients had disease durations of less than one year and had not had prior treatment for it. Smokers or patients suffering from diabetes mellitus, hypothyroidism, liver or kidney disease, Cushing's syndrome, obesity, familiar dyslipidemia and those receiving medications affecting lipid metabolism were excluded from the study. Sixty-three healthy volunteers (controls) were also included. Patients were treated with methotrexate and prednisone. Lipid profiles, disease activity for the 28 joint indices score (DAS-28) as well as ACR 50% response criteria were determined for all patients. The mean DAS-28 at disease onset was 5.8 ± 0.9. After a year of therapy, 53 (91.3%) patients achieved the ACR 20% response criteria, while 45 (77.6%) attained the ACR 50% criteria. In addition, a significant decrease in the DAS-28, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were observed. ERA patients exhibited higher serum levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and triglycerides, whereas their serum high-density lipoprotein cholesterol (HDL-C) levels were significantly lower compared to controls. As a consequence, the atherogenic ratio of TC/HDL-C as well as that of LDL-C/HDL-C was significantly higher in ERA patients compared to controls. After treatment, a significant reduction of the atherogenic ratio of TC/HDL-C as well as that of LDL-C/HDL-C was observed, a phenomenon primarily due to the increase of serum HDL-C levels. These changes were inversely correlated with laboratory changes, especially CRP and ESR. In conclusion, ERA patients are characterized by an atherogenic lipid profile, which improves after therapy. Thus, early immuno-intervention to control disease activity may reduce the risk of the atherosclerotic process and cardiovascular events in ERA patients.     

Therapeutic effect of a peptide inhibitor of TGF-β on pulmonary fibrosis

Pulmonary fibrosis encompasses several respiratory diseases characterized by epithelial cell injury, inflammation and fibrosis. Transforming growth factor (TGF)-β1 is one of the main profibrogenic cytokines involved in the pathogenesis of lung fibrosis. It induces fibroblast differentiation into myofibroblasts, which produce high levels of collagen and concomitantly loss of lung elasticity and reduction of the respiratory function. In the present study, we have investigated the effects of P17 (a TGF-β inhibitor peptide) on IMR-90 lung fibroblast differentiation in vitro, as well as on the inhibition of the development of bleomycin-induced pulmonary fibrosis in mice. It was found that in IMR-90 cells, P17 inhibited TGF-β1-induced expression of connective tissue growth factor and α-smooth muscle actin. In vivo, treatment of mice with P17 2days after bleomycin administration decreased lung fibrosis, areas of myofibroblast-like cells and lymphocyte infiltrate. P17 also reduced mRNA expression of collagen type I, fibronectin and the fibronectin splice isoform EDA in the lung, and increased the expression of IFN-γ mRNA. Finally, therapeutic treatment with P17 in mice with already established fibrosis was able to significantly attenuate the progression of lung fibrosis. These results suggest that P17 may be useful in the treatment of pulmonary fibrosis.     

Contrast enhancement: a physiological effect of striatal dopamine?

Dopamine functions as an important neuromodulator in the dorsal striatum and ventral striatum/nucleus accumbens. Evidence is accumulating for the idea that striatal neurons compete with each other for control over the animals motor resources, and that dopamine plays an important modulatory role that allows a particular subset of neurons, encoding a specific behavior, to predominate in this competition. One means by which dopamine could facilitate selection among competing neurons is to enhance the contrast between stronger and weaker excitations (or to increase the signal to noise ratio among neurons, where the firing of the most excited neurons is assumed to transmit signal and the firing of the least excited to transmit noise). Here, we review the electrophysiological evidence for this hypothesis and discuss potential cellular mechanisms by which dopamine-mediated contrast enhancement could occur.This work was supported by funds provided by the State of California for medical research on alcohol and substance abuse through the University of California, San Francisco, and by NIH grant DA15676 to GOH.     

The physical influence of inositides—a disproportionate effect?

After the initial observation that lipids form a considerable part of biological membranes, the details of the physical role of lipids in biological systems have emerged gradually. There have been few ‘Eureka’ moments in which a class or individual lipid has appeared as a game-changing physical player. However, evidence collected in the last five years suggests that that notion may be about to change. In chemical biology studies, inositides are increasingly showing themselves to be lipids that have a physical influence on membrane systems that is as strong as their biological (signalling) one. Additionally, recent evidence has shown that the concentration of at least one inositide changes during important stages of the cell cycle, and not in a manner consistent with its traditional signalling roles. The balance between these data is explored and a forward-looking view is proposed.     

Is quorum sensing a side effect of diffusion sensing?

Many bacteria appear to communicate by releasing and sensing autoinducer molecules, which are believed to function primarily as sensors of population density. However, this quorum-sensing hypothesis rests on very weak foundations, as neither the need for group action nor the selective conditions required for its evolution have been demonstrated. Here, I argue for a more direct function of autoinducer secretion and response - the ability to determine whether secreted molecules rapidly move away from the cell. This diffusion sensing allows cells to regulate secretion of degradative enzymes and other effectors to minimize losses owing to extracellular diffusion and mixing.     

The effect of change of number of OTU’s in a numerical taxonomic study

The effect of change of number of OTU’s (operational taxonomic units) in a numerical taxonomic study was investigated using 28 taxospecies of the genusSalix in California and 22 sites of sect.Sitchenses of the genus. A coefficient of Euclidean distance was used to estimate relationships among the OTU’s based on 99 morphological characters. Two methods of clustering were employed: 1) Tryon’s key communality cluster analysis, and 2) the unweighted pair group method. The latter results in a phenogram. It was found that the number of OTU’s employed does make a difference. But the difference is not random and is centered around those OTU’s most closely related to the OTU’s being added.     

ψ-esters of depsidones with a lactole ring

The reaction of stictic, norstictic and salazinic acids with methanol, ethanol and tert-butanol has been investigated. 8′-O-Methylstictic acid is identical with methylstictic acid from Lobaria oregana. Ingolfdottir's vesuvianic acid from Stereocaulon vesuvianum and Handong's cetrariastrumin from Cetrariastrum nepalensis have been shown to be 8′-O-ethylstictic acid and 8′,9′-di-O-ethylsalazinic acid, respectively, by reaction of stictic and salazinic acids with ethanol.