Tranexamic acid suppresses the release of mitochondrial DNA,protects the endothelial monolayer and enhances oxidative phosphorylation

Damage-associated molecular patterns, including mitochondrial DNA (mtDNA) are released during hemorrhage resulting in the development of endotheliopathy. Tranexamic acid (TXA), an antifibrinolytic drug used in hemorrhaging patients, enhances their survival despite the lack of a comprehensive understanding of its cellular mechanisms of action. The present study is aimed to elucidate these mechanisms, with a focus on mitochondria. We found that TXA inhibits the release of endogenous mtDNA from granulocytes and endothelial cells. Furthermore, TXA attenuates the loss of the endothelial monolayer integrity induced by exogenous mtDNA. Using the Seahorse XF technology, it was demonstrated that TXA strongly stimulates mitochondrial respiration. Studies using Mitotracker dye, cells derived from mito-QC mice, and the ActivSignal IPAD assay, indicate that TXA stimulates biogenesis of mitochondria and inhibits mitophagy. These findings open the potential for improvement of the strategies of TXA applications in trauma patients and the development of more efficient TXA derivatives.     

Small-angle neutron and X-ray scattering analysis of the supramolecular organization of rhodopsin in photoreceptor membrane

The supramolecular organization of the visual pigment rhodopsin in the photoreceptor membrane remains contentious. Specifically, whether this G protein-coupled receptor functions as a monomer or dimer remains unknown, as does the presence or absence of ordered packing of rhodopsin molecules in the photoreceptor membrane. Completely opposite opinions have been expressed on both issues. Herein, using small-angle neutron and X-ray scattering approaches, we performed a comparative analysis of the structural characteristics of the photoreceptor membrane samples in buffer, both in the outer segment of photoreceptor cells, and in the free photoreceptor disks. The average distance between the centers of two neighboring rhodopsin molecules was found to be ~5.8 nm in both cases. The results indicate an unusually high packing density of rhodopsin molecules in the photoreceptor membrane, but molecules appear to be randomly distributed in the membrane without any regular ordering.     

Prebiotic Syntheses Under Shock in the Water – Formamide – Potassium Bicarbonate – Sodium Hydroxide System

Origins of Life and Evolution of Biospheres - Syntheses under shock in nitrogen bubbled samples of the water – formamide – bicarbonate – sodium hydroxide system at...     

Phylogenetic and compositional diversity are governed by different rules: a study of fleas parasitic on small mammals in four biogeographic realms

We studied patterns of phylogenetic and compositional diversity of fleas parasitic on small mammals and asked whether these patterns are affected by environmental variation or evolutionary/historical processes. We considered environmental variation via both off‐host (air temperature, precipitation, the amount of green vegetation, latitude) and host‐associated (phylogenetic and species composition) environments. The indicators of evolutionary/historical processes were phylogenetic and compositional uniqueness estimated via phylogenetic or compositional, respectively, β‐diversity of either fleas or hosts. We found that phylogenetic uniqueness of flea assemblages was the main predictor of their phylogenetic diversity in all realms. In addition, host phylogenetic diversity and uniqueness played also some role in the Palearctic, whereas the effect of the off‐host environment was either extremely weak or absent. Compositional diversity of fleas was consistently affected by compositional diversity of hosts in all realms except the Neotropics. The effect of the off‐host environment on compositional flea diversity was substantial in all realms except the Palearctic. No effect of latitude on either metric of flea diversity was found. We conclude that phylogenetic diversity of fleas is driven mainly by evolutionary/historical processes, whereas drivers of their compositional diversity are associated with current ecological conditions.     

Calorimetric study of the order-disorder conformational transition in succinoglycan

Thermally induced order-disorder conformational transition in succinoglycan was studied using the method of high-sensitivity differential scanning microcalorimetry within the range of polysaccharide concentrations from 0.1 to 3.5 mg mL⁻¹ at NaCl concentrations 0, 0.01, and 0.1M. The positions and shapes of the excess heat capacity curves depended substantially on both the NaCl and polysaccharide concentrations. At low polysaccharide concentrations in salt-free solution the experimental curves were closely approximated by the two-state model suggesting the transition mechanism to be of the single helix-coil type. With increasing polysaccharide and/or NaCl concentration, the experimental curves changed significantly in symmetry, which indicated a changing transition mechanism. At high polysaccharide concentrations or in the presence of the salt, the order-disorder transition of succinoglycan was shown to include two stages: the cooperative dissociation of the helix dimer and subsequent two-state melting of the helix monomer. The dependence of thermodynamic parameters for the dissociation and melting of helix structures in succinoglycan on NaCl and polysaccharide concentrations was obtained by fitting the experimental excess heat capacity curves. The cooperativity parameter σ for the single helix-coil transition as well as the average length of the helix segment of succinoglycan were calculated. Some features of succinoglycan ordering in solution are discussed. © 1996 John Wiley & Sons, Inc.     

A Comparison of Brain Gene Expression Levels in Domesticated and Wild Animals

Domestication has led to similar changes in morphology and behavior in several animal species, raising the question whether similarities between different domestication events also exist at the molecular level. We used mRNA sequencing to analyze genome-wide gene expression patterns in brain frontal cortex in three pairs of domesticated and wild species (dogs and wolves, pigs and wild boars, and domesticated and wild rabbits). We compared the expression differences with those between domesticated guinea pigs and a distant wild relative (Cavia aperea) as well as between two lines of rats selected for tameness or aggression towards humans. There were few gene expression differences between domesticated and wild dogs, pigs, and rabbits (30–75 genes (less than 1%) of expressed genes were differentially expressed), while guinea pigs and C. aperea differed more strongly. Almost no overlap was found between the genes with differential expression in the different domestication events. In addition, joint analyses of all domesticated and wild samples provided only suggestive evidence for the existence of a small group of genes that changed their expression in a similar fashion in different domesticated species. The most extreme of these shared expression changes include up-regulation in domesticates of SOX6 and PROM1, two modulators of brain development. There was almost no overlap between gene expression in domesticated animals and the tame and aggressive rats. However, two of the genes with the strongest expression differences between the rats (DLL3 and DHDH) were located in a genomic region associated with tameness and aggression, suggesting a role in influencing tameness. In summary, the majority of brain gene expression changes in domesticated animals are specific to the given domestication event, suggesting that the causative variants of behavioral domestication traits may likewise be different.     

Somatic frameshift mutations in the Bloom syndrome BLM gene are frequent in sporadic gastric carcinomas with microsatellite mutator phenotype

Background  

Genomic instability has been reported at microsatellite tracts in few coding sequences. We have shown that the Bloom syndrome BLM gene may be a target of microsatelliteinstability (MSI) in a short poly-adenine repeat located in its coding region. To further characterize the involvement of BLM in tumorigenesis, we have investigated mutations in nine genes containing coding microsatellites in microsatellite mutator phenotype (MMP) positive and negative gastric carcinomas (GCs).     

Malvone A, a phytoalexin found in Malva sylvestris (family Malvaceae)

The isolation and structure of a phytoalexin, malvone A (2-methyl-3-methoxy-5,6-dihydroxy-1,4-naphthoquinone) is reported. Malvone A formation is induced in Malva sylvestris L. by the plant pathogen Verticillium dahliae. In a turbimetric assay for toxicity to V. dahliae, it had an ED50 value of 24 microg/ml. The structure of malvone A was determined by MS and NMR spectroscopy, and by X-ray crystallographic analysis. The X-ray analysis showed water molecules were located in channels that run along the a-axis.