d-matrix – database exploration,visualization and analysis

Background  

Motivated by a biomedical database set up by our group, we aimed to develop a generic database front-end with embedded knowledge discovery and analysis features. A major focus was the human-oriented representation of the data and the enabling of a closed circle of data query, exploration, visualization and analysis.     

Quantification of optic disc edema during exposure to high altitude shows no correlation to acute mountain sickness

Background

The study aimed to quantify changes of the optic nerve head (ONH) during exposure to high altitude and to assess a correlation with acute mountain sickness (AMS). This work is related to the Tuebingen High Altitude Ophthalmology (THAO) study.

Methodology/Principal Findings

A confocal scanning laser ophthalmoscope (cSLO, Heidelberg Retina Tomograph, HRT3®) was used to quantify changes at the ONH in 18 healthy participants before, during and after rapid ascent to high altitude (4559 m). Slitlamp biomicroscopy was used for clinical optic disc evaluation; AMS was assessed with Lake Louise (LL) and AMS-cerebral (AMS-c) scores; oxygen saturation (SpO₂) and heart rate (HR) were monitored. These parameters were used to correlate with changes at the ONH. After the first night spent at high altitude, incidence of AMS was 55% and presence of clinical optic disc edema (ODE) 79%. Key stereometric parameters of the HRT3® used to describe ODE (mean retinal nerve fiber layer [RNFL] thickness, RNFL cross sectional area, optic disc rim volume and maximum contour elevation) changed significantly at high altitude compared to baseline (p<0.05) and were consistent with clinically described ODE. All changes were reversible in all participants after descent. There was no significant correlation between parameters of ODE and AMS, SpO₂ or HR.

Conclusions/Significance

Exposure to high altitude leads to reversible ODE in the majority of healthy subjects. However, these changes did not correlate with AMS or basic physiologic parameters such as SpO₂ and HR. For the first time, a quantitative approach has been used to assess these changes during acute, non-acclimatized high altitude exposure. In conclusion, ODE presents a reaction of the body to high altitude exposure unrelated to AMS.     

Contrasting phylogenetic patterns of anther smuts (Pucciniomycotina: Microbotryum) reflect phylogenetic patterns of their caryophyllaceous hosts

Anther smuts in the genus Microbotryum often show very high host specificity toward their caryophyllaceous hosts, but some of the larger host groups such as Dianthus are crucially undersampled for these parasites so that the question of host specificity cannot be answered conclusively. In this study we sequenced the internal transcribed spacer (ITS) region of members of the Microbotryum dianthorum species complex as well as their Dianthus hosts. We compared phylogenetic trees of these parasites including sequences of anther smuts from other Caryophyllaceae, mainly Silene, with phylogenies of Caryophyllaceae that are known to harbor anther smuts. Additionally we tested whether observed patterns in parasites are due to shared ancestry or if geographic separation is a factor that should be taken into consideration in delimitating species. Parasites on Dianthus showed mainly an arbitrary distribution on Dianthus hosts, whereas parasites on other Caryophyllaceae formed well-supported monophyletic clades that corresponded to restricted host groups. The same pattern was observed in the Caryophyllaceae studied: morphologically described Dianthus species did not correspond well with monophyletic clades based on molecular data, whereas other Caryophyllaceae mainly did. We suggest that these different patterns primarily result from different breeding systems and speciation times between different host groups as well as difficulties in species delimitations in the genus Dianthus.     

An amphipathic cyclic tetrapeptide scaffold containing halogenated β2,2‐amino acids with activity against multiresistant bacteria

The present study describes the synthesis and biological studies of a small series of head‐to‐tail cyclic tetrapeptides of the general structure c(Lys‐β^2,2‐Xaa‐Lys) containing one lipophilic β^2,2‐amino acid and Lys, Gly, Ala, or Phe as the Xaa residue in the sequence. The peptides were investigated for antimicrobial activity against gram‐positive and gram‐negative reference strains and 30 multiresistant clinical isolates including strains with extended spectrum β‐lactamase—carbapenemase (ESBL‐CARBA) production. Toxicity was determined against human red blood cells. The most potent peptides showed high activity against the gram‐positive clinical isolates with minimum inhibitory concentrations of 4–8 μg/mL and low haemolytic activity. The combination of high antimicrobial activity and low toxicity shows that these cyclic tetrapeptides containing lipophilic β^2,2‐amino acids form a valuable scaffold for designing novel antimicrobial agents.     

Dependence of the initial adhesion of biofilm forming Pseudomonas putida mt2 on physico-chemical material properties

Bacterial adhesion is strongly dependent on the physico-chemical properties of materials and plays a fundamental role in the development of a growing biofilm. Selected materials were characterized with respect to their physico-chemical surface properties. The different materials, glass and several polymer foils, showed a stepwise range of surface tensions (γ(s)) between 10.3 and 44.7 mN m(-1). Measured zeta potential values were in the range between -74.8 and -28.3 mV. The initial bacterial adhesion parameter q(max) was found to vary between 6.6 × 10(6) and 28.1 × 10(6) cm(-2). By correlation of the initial adhesions kinetic parameters with the surface tension data, the optimal conditions for the immobilization of Pseudomonas putida mt2 were found to be at a surface tension of 24.7 mN m(-1). Both higher and lower surface tensions lead to a smaller number of adherent cells per unit surface area. Higher energy surfaces, commonly termed hydrophilic, could constrain bacterial adhesion because of their more highly ordered water structure (exclusion zone) close to the surface. At low energy surfaces, commonly referred to as hydrophobic, cell adhesion is inhibited due to a thin, less dense zone (depletion layer or clathrate structure) close to the surface. Correlation of q (max) with zeta potential results in a linear relationship. Since P. putida carries weak negative charges, a measurable repulsive effect can be assumed on negative surfaces.     

A single nucleotide polymorphism on chromosome 10 is highly predictive for the polled phenotype in Australian Merino sheep

The aim of this study was to fine map the genomic location of the Horns locus in the Australian Merino sheep population and to identify markers that can be used to predict the horn phenotype. A linkage disequilibrium analysis of horn data from Australian Merino sheep mapped the Horns locus to a small region on chromosome 10. A single nucleotide polymorphism in the region was found to be highly predictive for the polled phenotype in an experimental population of Merino sheep. This was owing to a dominance effect of one of the alleles when inherited maternally. It was suggested that a genetic test would provide a good predictor of the polled phenotype. Finally, an evaluation of industry data showed that the SNP is at very different frequencies in Poll Merino sheep that have been bred for polledness (based on phenotype alone) compared with the Merino sheep breed.     

Substrate Specificity of and Product Formation by Muconate Cycloisomerases: an Analysis of Wild-Type Enzymes and Engineered Variants

Muconate cycloisomerases play a crucial role in the bacterial degradation of aromatic compounds by converting cis,cis-muconate, the product of catechol ring cleavage, to (4S)-muconolactone. Chloromuconate cycloisomerases catalyze both the corresponding reaction and a dehalogenation reaction in the transformation of chloroaromatic compounds. This study reports the first thorough examination of the substrate specificity of the muconate cycloisomerases from Pseudomonas putida PRS2000 and Acinetobacter “calcoaceticus” ADP1. We show that they transform, in addition to cis,cis-muconate, 3-fluoro-, 2-methyl-, and 3-methyl-cis,cis-muconate with high specificity constants but not 2-fluoro-, 2-chloro-, 3-chloro-, or 2,4-dichloro-cis,cis-muconate. Based on known three-dimensional structures, variants of P. putida muconate cycloisomerase were constructed by site-directed mutagenesis to contain amino acids found in equivalent positions in chloromuconate cycloisomerases. Some of the variants had significantly increased specificity constants for 3-chloro- or 2,4-dichloromuconate (e.g., A271S and I54V showed 27- and 22-fold increases, respectively, for the former substrate). These kinetic improvements were not accompanied by a change from protoanemonin to cis,cis-dienelactone as the product of 3-chloro-cis,cis-muconate conversion. The rate of 2-chloro-cis,cis-muconate turnover was not significantly improved, nor was this compound dehalogenated to any significant extent. However, the direction of 2-chloro-cis,cis-muconate cycloisomerization could be influenced by amino acid exchange. While the wild-type enzyme discriminated only slightly between the two possible cycloisomerization directions, some of the enzyme variants showed a strong preference for either (+)-2-chloro- or (+)-5-chloromuconolactone formation. These results show that the different catalytic characteristics of muconate and chloromuconate cycloisomerases are due to a number of features that can be changed independently of each other.