Semi‐dry grasslands along a climatic gradient across Central Europe: Vegetation classification with validation

Question: What is the variation in species composition of Central European semi‐dry grasslands? Can we apply a training‐and‐test validation approach for identifying phytosociological associations which are floristically well defined in a broad geographic comparison; can we separate them from earlier described associations with only a local validity? Location: A 1200 km long transect running along a gradient of increasing continentality from central Germany via Czech Republic, Slovakia, NE Austria, Hungary to NW Romania. Methods: Relevés with > 25% cover of Brachypodium pin‐natum and/or Bromus erectus were geographically selected from a larger database. They were randomly split into two data sets, TRAINING and TEST, each with 422 relevés. Cluster analysis was performed for each data set on scores from significant principal coordinates. Different partitions of the TRAINING data set were validated on the TEST data set, using a new method based on the comparison of % frequencies of species occurrence in clusters. Clusters were characterized by statistically defined groups of diagnostic species and values of climatic variables. Results: Species composition changed along the NW‐SE gradient and valid clusters were geographically well separated. Optimal partition level was at 11 clusters, six being valid: two clusters Germany and the Czech Republic corresponded to the Bromion erecti; two clusters from the Czech Republic and Hungary to the Cirsio‐Brachypodion, and two clusters were transitional between these two alliances. Conclusion: The training‐and‐test validation method used in this paper proved to be efficient for discriminating between robust clusters, which are appropriate candidates for inclusion in the national or regional syntaxonomic overviews, and weak clusters, which are specific to the particular classification of the given data set.     

Lipoproteins and mitogen-activated protein kinase signaling: a role in atherogenesis?

PURPOSE OF REVIEW: Lipoproteins play a critical role in the development of atherosclerosis, which might result partly from their capacity to induce specific intracellular signaling pathways. The goal of this review is to summarize the signaling properties of lipoproteins, in particular, their capacity to induce activation of mitogen-activated protein kinase pathways and the resulting modulation of cellular responses in blood vessel cells. RECENT FINDINGS: Lipoproteins activate the extracellular signal-regulated kinase and p38 mitogen-activated protein kinase pathways in all blood vessel cell types. This may require lipoprotein docking to scavenger receptor B1, allowing transfer of cholesterol and sphingosine-1-phosphate to plasma membranes. Subsequent propagation of the signals probably requires the stimulation of G protein-coupled receptors, followed by the transactivation of receptor tyrosine kinases. Lipoprotein-induced extracellular signal-regulated kinase activity favors cell proliferation, whereas lipoprotein-induced p38 mitogen-activated protein kinase activity leads to cell hyperplasia and promotes cell migration. Some signaling pathways and cellular effects induced by lipoproteins have been observed in atherosclerotic plaques and therefore represent potential targets for the development of anti-atherosclerotic drugs. SUMMARY: The main blood vessel cell types have the capacity to activate protein kinase pathways in the presence of lipoproteins. This induces cell proliferation, hyperplasia and migration, known to be dysregulated in atherosclerotic lesions.     

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.     

Doxorubicin prodrug on the basis of tert-butyl cephalosporanate sulfones

Doxorubicin-cephalosporin prodrug adapted to the development of elastases for the liberation of parent drug was synthesized on the basis of cephalosporanate sulfone esters.     

Transport Rankings of Non-Steroidal Antiinflammatory Drugs across Blood-Brain Barrier In Vitro Models

The aim of this work was to conduct a comprehensive study about the transport properties of NSAIDs across the blood-brain barrier (BBB) in vitro. Transport studies with celecoxib, diclofenac, ibuprofen, meloxicam, piroxicam and tenoxicam were accomplished across Transwell models based on cell line PBMEC/C1-2, ECV304 or primary rat brain endothelial cells. Single as well as group substance studies were carried out. In group studies substance group compositions, transport medium and serum content were varied, transport inhibitors verapamil and probenecid were added. Resulted permeability coefficients were compared and normalized to internal standards diazepam and carboxyfluorescein. Transport rankings of NSAIDs across each model were obtained. Single substance studies showed similar rankings as corresponding group studies across PBMEC/C1-2 or ECV304 cell layers. Serum content, glioma conditioned medium and inhibitors probenecid and verapamil influenced resulted permeability significantly. Basic differences of transport properties of the investigated NSAIDs were similar comparing all three in vitro BBB models. Different substance combinations in the group studies and addition of probenecid and verapamil suggested that transporter proteins are involved in the transport of every tested NSAID. Results especially underlined the importance of same experimental conditions (transport medium, serum content, species origin, cell line) for proper data comparison.     

Comparative investigation of the pathogenicity of three Mycobacterium tuberculosis mutants defective in the synthesis of p-hydroxybenzoic acid derivatives

p-Hydroxybenzoic acid derivatives (p-HBADs) are glycoconjugates secreted by all Mycobacterium tuberculosis isolates whose contribution to pathogenicity remains to be determined. The pathogenicity of three transposon mutants of M. tuberculosis deficient in the biosynthesis of some or all forms of p-HBADs was studied. Whilst the mutants grew similarly to the wild-type strain in macrophages and C57BL/6 mice, two of the mutants induced a more severe and diffuse inflammation in the lungs. The lack of production of some or all forms of p-HBADs in these two mutants also correlated with an increased secretion of the pro-inflammatory cytokines tumour-necrosis factor alpha, interleukin 6 and interleukin 12 in vivo. We propose that the loss of production of p-HBADs by tubercle bacilli results in their diminished ability to suppress the pro-inflammatory response to infection and that this ultimately provokes extensive pulmonary lesions in the C57BL/6 model of tuberculosis infection.     

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.