Synthetic CpG oligonucleotides induce a genetic profile ameliorating murine myocardial I/R injury

We previously demonstrated that pre‐conditioning with CpG oligonucleotide (ODN) 1668 induces quick up‐regulation of gene expression 3 hours post‐murine myocardial ischaemia/reperfusion (I/R) injury, terminating inflammatory processes that sustain I/R injury. Now, performing comprehensive microarray and biocomputational analyses, we sought to further enlighten the “black box” beyond these first 3 hours. C57BL/6 mice were pretreated with either CpG 1668 or with control ODN 1612, respectively. Sixteen hours later, myocardial ischaemia was induced for 1 hour in a closed‐chest model, followed by reperfusion for 24 hours. RNA was extracted from hearts, and labelled cDNA was hybridized to gene microarrays. Data analysis was performed with BRB ArrayTools and Ingenuity Pathway Analysis. Functional groups mediating restoration of cellular integrity were among the top up‐regulated categories. Genes known to influence cardiomyocyte survival were strongly induced 24 hours post‐I/R. In contrast, proinflammatory pathways were down‐regulated. Interleukin‐10, an upstream regulator, suppressed specifically selected proinflammatory target genes at 24 hours compared to 3 hours post‐I/R. The IL1 complex is supposed to be one regulator of a network increasing cardiovascular angiogenesis. The up‐regulation of numerous protective pathways and the suppression of proinflammatory activity are supposed to be the genetic correlate of the cardioprotective effects of CpG 1668 pre‐conditioning.     

Hepatitis C in Laos: A 7-Year Retrospective Study on 1765 Patients

Hepatitis C virus(HCV) is a global health concern, notably in Southeast Asia, and in Laos the presentation of the HCVinduced liver disease is poorly known. Our objective was thus to describe a comprehensive HCV infection pattern in order to guide national health policies. A study on a group of 1765 patients formerly diagnosed by rapid test in health centres was conducted at the Centre of Infectiology Lao Christophe Merieux in Vientiane. The demographic information of patients,their infection status(viral load: VL), liver function(aminotransferases) and treatments were analysed. Results showed that gender distribution of infected people was balanced; with median ages of 53.8 for men and 51.6 years for women(13–86 years). The majority of patients(72%) were confirmed positive(VL [ 50 IU/mL) and 28% of them had high VL([ 6 log10). About 23% of patients had level of aminotransferases indicative of liver damage([ 40 IU/m L); but less than20% of patients received treatment. Patients rarely received a second sampling or medical imaging. The survey also showed that cycloferon, pegylated interferon and ribavirin were the drugs prescribed preferentially by the medical staff,without following any international recommendations schemes. In conclusion, we recommend that a population screening policy and better management of patients should be urgently implemented in the country, respecting official guidelines.However, the cost of biological analysis and treatment are significant barriers that must be removed. Public health resolutions should be immediately enforced in the perspective of meeting the WHO HCV elimination deadline by 2030.     

Microparticle miRNAs as Biomarkers of Vascular Function and Inflammation Response to Aerobic Exercise in Obesity?

Objective

This study aimed to explore the role of nine microRNAs (miRNAs) in microparticles (MPs) on the efficacy of aerobic exercise in the regulation of inflammation and vascular function in obesity.

Methods

Sedentary women with normal weight (n = 6, BMI < 25 kg/m²) and women with obesity (n = 9, BMI > 30 kg/m²) were recruited at F. Hached Hospital (Sousse, Tunisia) and enrolled in an 8‐week aerobic program. Vascular function was assessed using laser Doppler flowmetry/iontophoresis, circulating MPs by flow cytometry, miRNAs by real‐time polymerase chain reaction, and inflammation by ELISA, before and after exercise.

Results

Women with obesity presented with high prevalence of cardiovascular risk factors and a higher circulating MP level compared with healthy subjects. The MP miRNA profile was significantly different in the two groups. Exercise reduced BMI and inflammation in both groups and significantly improved endothelial‐dependent response (acetylcholine cutaneous vascular conductance) for healthy subjects, with a trend for women with obesity. Circulating MP level was increased after exercise, and miRNA expression was differentially modulated in both populations. Pearson analysis revealed a correlation between MPs miR‐124a and miR150 and adiponectin, TNFα, or IL‐6 levels.

Conclusions

The relation between MPs and miRNA profile, inflammation, vascular function, and exercise is of particular interest for defining “miRNA biomarker signature” in patients with cardiovascular disease who are potentially susceptible to respond to exercise.

     

Friction from Transduction Channels’ Gating Affects Spontaneous Hair-Bundle Oscillations

Hair cells of the inner ear can power spontaneous oscillations of their mechanosensory hair bundle, resulting in amplification of weak inputs near the characteristic frequency of oscillation. Recently, dynamic force measurements have revealed that delayed gating of the mechanosensitive ion channels responsible for mechanoelectrical transduction produces a friction force on the hair bundle. The significance of this intrinsic source of dissipation for the dynamical process underlying active hair-bundle motility has remained elusive. The aim of this work is to determine the role of friction in spontaneous hair-bundle oscillations. To this end, we characterized key oscillation properties over a large ensemble of individual hair cells and measured how viscosity of the endolymph that bathes the hair bundles affects these properties. We found that hair-bundle movements were too slow to be impeded by viscous drag only. Moreover, the oscillation frequency was only marginally affected by increasing endolymph viscosity by up to 30-fold. Stochastic simulations could capture the observed behaviors by adding a contribution to friction that was 3?8-fold larger than viscous drag. The extra friction could be attributed to delayed changes in tip-link tension as the result of the finite activation kinetics of the transduction channels. We exploited our analysis of hair-bundle dynamics to infer the channel activation time, which was ～1 ms. This timescale was two orders-of-magnitude shorter than the oscillation period. However, because the channel activation time was significantly longer than the timescale of mechanical relaxation of the hair bundle, channel kinetics affected hair-bundle dynamics. Our results suggest that friction from channel gating affects the waveform of oscillation and that the channel activation time can tune the characteristic frequency of the hair cell. We conclude that the kinetics of transduction channels’ gating plays a fundamental role in the dynamic process that shapes spontaneous hair-bundle oscillations.     

Functional characterization and FTIR-based 3D modeling of full length and truncated forms of Scorpio maurus venom phospholipase A2

Background

Heterodimeric phospholipase A₂ from venom glands of Tunisian scorpion Scorpio maurus (Sm-PLGV) had been purified. It contains long and short chains linked by a disulfide bridge. Sm-PLGV exhibits hemolytic activity towards human erythrocytes and interacts with phospholipid monolayers at high surface pressure. The investigation of structure-function relationships should provide new clues to understand its activity.

The first world swimming championships of roseobacters—Phylogenomic insights into an exceptional motility phenotype

Many marine Alphaproteobacteria of the Roseobacter group show a characteristic swim-or-stick lifestyle, for which motility is a crucial trait. Three phylogenetically distinct flagellar gene clusters (FGCs) have been identified in Rhodobacteraceae that have been named fla1, fla2 and fla3 according to their relative abundance. In addition to the flagellar-dependent swimming and swarming motility, pilus-dependent twitching mediates bacterial locomotion. Furthermore, filament independent modes of motility, namely gliding and sliding, have been described for various microorganisms. However, no mode of motility other than swimming has so far been described for roseobacters. In the present study, we investigated motility, distribution of flagellar systems and the phylogeny of 120 genome-sequenced Rhodobacteraceae. The phylogenetically broad taxon sampling that included 114 type strains revealed the presence of at least ten distinct clades that were statistically well supported. The investigation of the actual physiological capacity for swimming motility on soft agar plates showed that only about half of the 120 tested strains were motile under the tested conditions. Seven strains developed a conspicuous dendritic motility phenotype that was reminiscent of the swarming motility in Pseudomonas aeruginosa. The observed dendritic motility in two strains (i.e. Sulfitobacter pseudonitzschiae DSM 26842 and Roseovarius pacificus DSM 29589) was particularly surprising because they did not harbor any genes of the FGC. Accordingly, it was concluded that this form of dendritic motility was independent of a flagellum. A comparative genomics approach allowed a remarkable number of pilus-related candidate genes to be identified for this novel type of motility in Rhodobacteraceae.     

Electron requirements for carbon incorporation along a diel light cycle in three marine diatom species

Diatoms account for about 40% of primary production in highly productive ecosystems. The development of a new generation of fluorometers has made it possible to improve estimation of the electron transport rate from photosystem II, which, when coupled with the carbon incorporation rate enables estimation of the electrons required for carbon fixation. The aim of this study was to investigate the daily dynamics of these electron requirements as a function of the diel light cycle in three relevant diatom species and to apprehend if the method of estimating the electron transport rate can lead to different pictures of the dynamics. The results confirmed the species-dependent capacity for photoacclimation under increasing light levels. Despite daily variations in the photosynthetic parameters, the results of this study underline the low daily variability of the electron requirements estimated using functional absorption of the photosystem II compared to an estimation based on a specific absorption cross section of chlorophyll a. The stability of the electron requirements throughout the day would suggest it is potentially possible to estimate high-frequency primary production by using autonomous variable fluorescence measurements from ships-of-opportunity or moorings, without taking potential daily variation in this parameter into consideration, but this result has to be confirmed on natural phytoplankton assemblages. The results obtained in this study confirm the low electron requirements of diatoms to perform photosynthesis, and suggest a potential additional source of energy for carbon fixation, as recently described in the literature for this class.     

Pigment configuration in the light-harvesting protein of the xanthophyte alga <Emphasis Type="Italic">Xanthonema debile</Emphasis>

Proper biogenesis and maintenance of photosynthetic thylakoid membrane complexes are essential for the photosynthetic light reactions. A thylakoid lumenal protein, Psb27, plays a vital role in assembly or/and maintenance of photosystem II (PSII). In cyanobacteria, it is a small lipoprotein docked to the lumenal side of PSII, and functions in the assembly of the Mn₄Ca cluster and in the PSII repair cycle. However, Psb27 from Arabidopsis thaliana is not a lipoprotein, and it is involved in PSII repair and acclimation to fluctuating light stress, suggesting a functional divergence between Arabidopsis Psb27 and cyanobacterial Psb27s. To gain a better understanding of Psb27 from higher plants, we determined the crystal structure of Arabidopsis Psb27 by X-ray crystallography at a resolution of 1.85 Å. The structure of Arabidopsis Psb27 is a four-helix bundle, similar to its orthologues from cyanobacteria. However, there are several structural differences between Arabidopsis Psb27 and cyanobacterial Psb27s concerning the overall molecular shape, the N- and C-terminal structures, and the surface charge. These differences suggest that Psb27 from higher plants and cyanobacteria may function differently.