Stress response factors as hub‐regulators of microRNA biogenesis: implication to the diseased heart

MicroRNAs (miRNAs) are important regulators of heart function and then an intriguing therapeutic target for plenty of diseases. The problem raised is that many data in this area are contradictory, thus limiting the use of miRNA‐based therapy. The goal of this review is to describe the hub‐mechanisms regulating the biogenesis and function of miRNAs, which could help in clarifying some contradictions in the miRNA world. With this scope, we analyse an array of factors, including several known agents of stress response, mediators of epigenetic changes, regulators of alternative splicing, RNA editing, protein synthesis and folding and proteolytic systems. All these factors are important in cardiovascular function and most of them regulate miRNA biogenesis, but their influence on miRNAs was shown for non‐cardiac cells or some specific cardiac pathologies. Finally, we consider that studying the stress response factors, which are upstream regulators of miRNA biogenesis, in the diseased heart could help in (1) explaining some contradictions concerning miRNAs in heart pathology, (2) making the role of miRNAs in pathogenesis of cardiovascular disease more clear, and therefore, (3) getting powerful targets for its molecular therapy. Copyright © 2015 John Wiley & Sons, Ltd.     

Volunteer Bias in Recruitment,Retention, and Blood Sample Donation in a Randomised Controlled Trial Involving Mothers and Their Children at Six Months and Two Years: A Longitudinal Analysis

Background

The vulnerability of clinical trials to volunteer bias is under-reported. Volunteer bias is systematic error due to differences between those who choose to participate in studies and those who do not.

Methods and Results

This paper extends the applications of the concept of volunteer bias by using data from a trial of probiotic supplementation for childhood atopy in healthy dyads to explore 1) differences between a) trial participants and aggregated data from publicly available databases b) participants and non-participants as the trial progressed 2) impact on trial findings of weighting data according to deprivation (Townsend) fifths in the sample and target populations. 1) a) Recruits (n = 454) were less deprived than the target population, matched for area of residence and delivery dates (n = 6,893) (mean [SD] deprivation scores 0.09[4.21] and 0.79[4.08], t = 3.44, df = 511, p<0.001). b) i)As the trial progressed, representation of the most deprived decreased. These participants and smokers were less likely to be retained at 6 months (n = 430[95%]) (OR 0.29,0.13–0.67 and 0.20,0.09–0.46), and 2 years (n = 380[84%]) (aOR 0.68,0.50–0.93 and 0.55,0.28–1.09), and consent to infant blood sample donation (n = 220[48%]) (aOR 0.72,0.57–0.92 and 0.43,0.22–0.83). ii)Mothers interested in probiotics or research or reporting infants’ adverse events or rashes were more likely to attend research clinics and consent to skin-prick testing. Mothers participating to help children were more likely to consent to infant blood sample donation. 2) In one trial outcome, atopic eczema, the intervention had a positive effect only in the over-represented, least deprived group. Here, data weighting attenuated risk reduction from 6.9%(0.9–13.1%) to 4.6%(−1.4–+10.5%), and OR from 0.40(0.18–0.91) to 0.56(0.26–1.21). Other findings were unchanged.

Conclusions

Potential for volunteer bias intensified during the trial, due to non-participation of the most deprived and smokers. However, these were not the only predictors of non-participation. Data weighting quantified volunteer bias and modified one important trial outcome.

Trial Registration

This randomised, double blind, parallel group, placebo controlled trial is registered with the International Standard Randomised Controlled Trials Register, Number (ISRCTN) 26287422. Registered title: Probiotics in the prevention of atopy in infants and children.     

Species traits and shoot-root biomass allocation in 20 dry-grassland species

Aims A plant has a limited amount of resources at any time and it allocates them to different structures. In spite of the large number of previous studies on allocation patterns within single species, knowledge of general patterns in species allocation is still very limited. This is because each study was done in different conditions using different methodology, making generalization difficult. We investigate intraspecific above- versus below-ground biomass allocation among individuals across a spectrum of dry-grassland plant species at two different developmental stages and ask whether allocation is age- and species specific, and whether differences among species can be explained by their life-history traits and phylogeny.Methods We collected data on above- and below-ground biomass of seedlings and adult plants of 20 species from a common garden experiment. We analysed data on shoot–root biomass allocation allometrically and studied the relationship between the allometric exponents (slopes on log–log scale), species life-history traits and phylogenetic distances.Important findings We found isometric as well as allometric patterns of biomass allocation in the studied species. Seedlings and adult individuals of more than half of the species differed in their above- versus below-ground biomass allometric exponents. Seedlings and adult individuals of the remaining species differed in their allometric coefficients (intercepts). Annual species generally allocated proportionally more to above- than below-ground biomass as seedlings than as adults, whereas perennial species showed the opposite pattern. Plant life-history traits, such as plant life span, age of first flowering, month in which the species begin flowering and specific leaf area were much more important in explaining differences in shoot–root allometry among species than were phylogenetic relationships. This suggests that allocation patterns vary greatly among closely related species but can be predicted based on species life-history traits.     

New polymeric thiocyanatoiron(II) complex with N,N′-diethylnicotinamide - Synthesis, structure, magnetic and spectral properties

The iron(II) compound of formula [Fe(NCS)₂(dena)₂]_n (dena = N,N′-diethylnicotinamide) has been prepared by the reaction between iron(III) thiocyanate and dena in ethanol solution. The complex was characterized by elemental analysis, spectral and magnetic measurements. Single-crystal X-ray diffraction methods show that the complex, crystallizing in the triclinic space group, undergoes a phase transition between 220 K and 230 K, connected with the doubling of cell volume. Crystal structures at 230 K (1a; HT phase) and 150 K (1b; LT phase) are described and a transition mechanism is discussed. In both phases the compound has an extended chain structure, in which the neutral molecule of N,N′-diethylnicotinamide acts as a bridging ligand binding through pyridine N atom to one centre and through amide O atom to the neighbouring Fe centre. The Fe²⁺ ion has a slightly distorted trans-octahedral environment with FeO₂N₄ chromophore, and all Fe-O and Fe-N bonds in the typical for high-spin iron(II) compounds range. Variable-temperature magnetic susceptibility data in the temperature range 1.8-300 K show that iron(II) is high-spin S = 2(⁵T_2g) and as a result effects due to zero-field splitting are anticipated at low temperatures. The IR spectrum suggested the coordination of N,N′-diethylnicotinamide to the central atom of iron(II) as a bridging ligand and NCS group as a monodentate ligand.     

Bradykinin Postconditioning Protects Pyramidal CA1 Neurons Against Delayed Neuronal Death in Rat Hippocampus

Aims The present study was undertaken to evaluate possible neuroprotective effect of bradykinin against delayed neuronal death in hippocampal CA1 neurons if applied two days after transient forebrain ischemia in the rat. Methods Transient forebrain ischemia was induced in male Wistar rats by four-vessel occlusion for 8 min. To assess efficacy of bradykinin as a new stressor for delayed postconditioning we used two experimental groups of animals: ischemia 8 min and 3 days of survival, and ischemia 8 min and 3 days of survival with i.p. injection of bradykinin (150 μg/kg) applied 48 h after ischemia. Results We found extensive neuronal degeneration in the CA1 region at day 3 after ischemia/reperfusion. The postischemic neurodegeneration was preceded by increased activity of mitochondrial enzyme MnSOD in cytoplasm, indicating release of MnSOD from mitochondria in the process of delayed neuronal death. Increased cytosolic cytochrome c and subsequently caspase-3 activation are additional signs of neuronal death via the mitochondrial pathway. Bradykinin administration significantly attenuated ischemia-induced neuronal death, and also suppressed the release of MnSOD, and cytochrome c, and prevented caspase-3 activation. Conclusions Bradykinin can be used as an effective stressor able to prevent mitochondrial failure leading to apoptosis-like delayed neuronal death in postischemic rat hippocampus.     

Amidated pectin derivatives with n-propyl-, 3-aminopropyl-, 3-propanol- or 7-aminoheptyl-substituents

Highly methylated (HM) pectin (DM = 90%) was amidated with four amines under anhydrous conditions. The goal was to prepare modified pectins that could be useful components of composites with new properties. The yields and degree of amidation (DA) of the products were, respectively, 67–92% and 67.3–72.0%. Maximal values were obtained for pectin propylamide (1) and minimal for pectin 7-aminoheptylamide (4). While products 1 and pectin 3-propanolamide (2) showed 95 g/100 g solubility in water, pectin 3-aminopropylamide (3) was 46 g/100 g and 4 only 3 g/100 g water-soluble. The TG/DTA data indicate that the thermal properties were not dramatically altered under inert environment and improved as far as thermooxidation resistance. From the overall prospective product 3 seems to be the most valuable component for further composite preparation.     

Health risks associated with wild animal translocation: a case of the European bison and an alien parasite

Introducing an animal into a new location could be hazardous in the form of disease transmission, especially with respect to infections that are often overlooked. Such introduced infectious agents, including parasitic ones, then pose potential danger to the native animal population. Within the conservation program, the European bison was introduced into many European countries. However, this largest European herbivore was recognized as a new host for an invasive parasitic nematode, Ashworthius sidemi, in Poland in 1998. Since then, the prevalence of this non-native parasite in Poland has increased not only in bison but also in other wild ruminants. In 2011 five European bison individuals were transported from Poland to the Czech Republic. In the current study, we examined the gastrointestinal tracts of two European bison and two red deer culled in the ?idlov game reserve. A. sidemi was identified in all investigated animals using both morphological and molecular methods; infection intensity was higher in bison than in deer. Our findings represent the first record of this invasive parasite in European bison at the Czech territory. The results of this study indicate changes in epidemiological patterns of Ashworthius infections in the climatic condition of Central Europe as well as the need to verify the reliability of ashworthiosis intravital diagnostics. One can expect A. sidemi to spread gradually in the Czech Republic and colonize other native ruminant hosts.     

Variation in Trill Characteristics in Tree Pipit Songs: Different Trills for Different Use?

Transmitting information about singer's quality is an important function of song in many bird species, and this information should be useful in territorial interactions. Fast trills, being physically demanding song structures, are particularly suitable candidates for signalling of quality or aggressive motivation. We have evaluated trill characteristics in songs within a population of the Tree Pipit, a common European songbird with no sexual dimorphism, in which song apparently plays a key role in territory defence as well as mate choice. Two types of relatively fast trills (each of them in multiple variants differing in complexity) were commonly observed in repertoires of Tree Pipit males. Trill rates significantly differed among individuals, suggesting that these song structures may carry information about male quality in this species. We tested by playback experiments whether both trill types are used in territorial encounters. Only one of the trill types was sung by males in response to playback, regardless on the trill type played to them. In an immediate response to playback, they increased the frequency of use of this trill, and also significantly increased the trill rate in comparison with spontaneous songs. This confirmed field observations, suggesting that this trill is important in male–male interactions. On the contrary, the use of the fastest, apparently more demanding, trill type actually decreased after the simulated territorial intrusion. We hypothesize that the latter one is more directed towards females, and that while performance of both trill types may reflect male quality, they are primarily used in different contexts.