Monoacylcadaverines in the blood of schizophrenic patients

Concentrations of cadaverine, monoacetylcadaverine and monopropionylcadaverine in the blood of schizophrenic and nonschizophrenic subjects were measured. Two groups, one from the U.S.A. the other from Japan, were tested. Monoacetylcadaverine and monopropionylcadaverine were found elevated in the blood of some schizophrenic patients in comparison with those in controls in each group. Their increase could be caused by a reduced monoamine oxidase activity or by an increased acylation in schizophrenic patients.     

Blocking VLDL secretion causes hepatic steatosis but does not affect peripheral lipid stores or insulin sensitivity in mice

The liver secretes triglyceride-rich VLDLs, and the triglycerides in these particles are taken up by peripheral tissues, mainly heart, skeletal muscle, and adipose tissue. Blocking hepatic VLDL secretion interferes with the delivery of liver-derived triglycerides to peripheral tissues and results in an accumulation of triglycerides in the liver. However, it is unclear how interfering with hepatic triglyceride secretion affects adiposity, muscle triglyceride stores, and insulin sensitivity. To explore these issues, we examined mice that cannot secrete VLDL [due to the absence of microsomal triglyceride transfer protein (Mttp) in the liver]. These mice exhibit markedly reduced levels of apolipoprotein B-100 in the plasma, along with reduced levels of triglycerides in the plasma. Despite the low plasma triglyceride levels, triglyceride levels in skeletal muscle were unaffected. Adiposity and adipose tissue triglyceride synthesis rates were also normal, and body weight curves were unaffected. Even though the blockade of VLDL secretion caused hepatic steatosis accompanied by increased ceramides and diacylglycerols in the liver, the mice exhibited normal glucose tolerance and were sensitive to insulin at the whole-body level, as judged by hyperinsulinemic euglycemic clamp studies. Normal hepatic glucose production and insulin signaling were also maintained in the fatty liver induced by Mttp deletion. Thus, blocking VLDL secretion causes hepatic steatosis without insulin resistance, and there is little effect on muscle triglyceride stores or adiposity.     

Quantifying the damage of red deer (Cervus elaphus) grazing on grassland production in southeastern Slovenia

The influence of red deer (Cervus elaphus) grazing on grassland production for forage conservation at the forest border during the vegetation period was studied on three locations (Mala gora, Cvišlerji, and Mačkovec) in the Kočevje region (SE Slovenia). The experiment lasted from the 25th of March until the 8th of October 2002. Portable cages were used to exclude red deer from grazing the herbage. At four sampling dates in the season, herbage air dry matter (DM) yield was measured at three different observations (cage-protected plot, cage-protected plot only two to three weeks before sampling date, otherwise freely grazed (removed), and unprotected plot). The results from the experiment showed that red deer grazed on grassland through the entire season and that the regeneration capability of sward was the highest in summer, middle in spring and smallest in autumn. On unprotected plots, an average reduction of 50% of herbage DM yield was found with the most damaged sites also up to 80% reduction.     

Lead soaps formation and biodiversity in a XVIII Century wax seal coloured with minium

A multidisciplinary approach was carried out in order to study the biodeterioration and the associated microbiome of a XVIII Century wax seal coloured with minium. A small wax seal fragment was observed by scanning electron microscopy combined with energy dispersive spectroscopy in non-destructive mode. The same object was analysed by Raman and Fourier-transform infrared spectroscopy. The identification of the microbiota growing on the seal was performed with both a culture-dependent strategy, combined with hydrolytic assays, and high-throughput sequencing using the MinION platform. The whole bacterial 16S rRNA gene and the fungal markers ITS and 28S rRNA were targeted. It was observed that the carnauba wax coloured with lead tetroxide (minium) was covered by a biofilm consisting of a network of filaments and other structures of microbial origin. The culture-dependent and culture-independent investigations showed the presence of a complex microbiota composed mainly by fungal members, which demonstrated interesting properties related to lipids and lead processing. The formation of lead soaps and secondary biogenic minerals was also described.     

New inhibitors of fungal 17β-hydroxysteroid dehydrogenase based on the [1,5]-benzodiazepine scaffold

The synthesis and activity of a new series of non-steroidal inhibitors of 17β-hydroxysteroid dehydrogenase that are based on a 1,5-benzodiazepine scaffold are presented. Their inhibitory potential was screened against 17β-hydroxysteroid dehydrogenase from the fungus Cochliobolus lunatus (17β-HSDcl), a model enzyme of the short-chain dehydrogenase/reductase superfamily. Some of these compounds are potent inhibitors of 17β-HSDcl activity, with IC₅₀ values in the low micromolar range and represent promising lead compounds that should be further developed and investigated as inhibitors of human 17β-HSD isoforms, which are the enzymes associated with the development of many hormone-dependent and neuronal diseases.     

Preferential Binding of Hot Spot Mutant p53 Proteins to Supercoiled DNA In Vitro and in Cells

Hot spot mutant p53 (mutp53) proteins exert oncogenic gain-of-function activities. Binding of mutp53 to DNA is assumed to be involved in mutp53-mediated repression or activation of several mutp53 target genes. To investigate the importance of DNA topology on mutp53-DNA recognition in vitro and in cells, we analyzed the interaction of seven hot spot mutp53 proteins with topologically different DNA substrates (supercoiled, linear and relaxed) containing and/or lacking mutp53 binding sites (mutp53BS) using a variety of electrophoresis and immunoprecipitation based techniques. All seven hot spot mutp53 proteins (R175H, G245S, R248W, R249S, R273C, R273H and R282W) were found to have retained the ability of wild-type p53 to preferentially bind circular DNA at native negative superhelix density, while linear or relaxed circular DNA was a poor substrate. The preference of mutp53 proteins for supercoiled DNA (supercoil-selective binding) was further substantiated by competition experiments with linear DNA or relaxed DNA in vitro and ex vivo. Using chromatin immunoprecipitation, the preferential binding of mutp53 to a sc mutp53BS was detected also in cells. Furthermore, we have shown by luciferase reporter assay that the DNA topology influences p53 regulation of BAX and MSP/MST1 promoters. Possible modes of mutp53 binding to topologically constrained DNA substrates and their biological consequences are discussed.     

Acquired obesity is associated with changes in the serum lipidomic profile independent of genetic effects--a monozygotic twin study

Both genetic and environmental factors are involved in the etiology of obesity and the associated lipid disturbances. We determined whether acquired obesity is associated with changes in global serum lipid profiles independent of genetic factors in young adult monozygotic (MZ) twins. 14 healthy MZ pairs discordant for obesity (10 to 25 kg weight difference) and ten weight concordant control pairs aged 24-27 years were identified from a large population-based study. Insulin sensitivity was assessed by the euglycemic clamp technique, and body composition by DEXA (% body fat) and by MRI (subcutaneous and intra-abdominal fat). Global characterization of lipid molecular species in serum was performed by a lipidomics strategy using liquid chromatography coupled to mass spectrometry. Obesity, independent of genetic influences, was primarily related to increases in lysophosphatidylcholines, lipids found in proinflammatory and proatherogenic conditions and to decreases in ether phospholipids, which are known to have antioxidant properties. These lipid changes were associated with insulin resistance, a pathogonomic characteristic of acquired obesity in these young adult twins. Our results show that obesity, already in its early stages and independent of genetic influences, is associated with deleterious alterations in the lipid metabolism known to facilitate atherogenesis, inflammation and insulin resistance.     

Applications of a new subspace clustering algorithm (COSA) in medical systems biology

A novel clustering approach named Clustering Objects on Subsets of Attributes (COSA) has been proposed (Friedman and Meulman, (2004). Clustering objects on subsets of attributes. J. R. Statist. Soc. B 66, 1–25.) for unsupervised analysis of complex data sets. We demonstrate its usefulness in medical systems biology studies. Examples of metabolomics analyses are described as well as the unsupervised clustering based on the study of disease pathology and intervention effects in rats and humans. In comparison to principal components analysis and hierarchical clustering based on Euclidean distance, COSA shows an enhanced capability to trace partial similarities in groups of objects enabling a new discovery approach in systems biology as well as offering a unique approach to reveal common denominators of complex multi-factorial diseases in animal and human studies. Doris Damian, Matej Orešič, and Elwin Verheij contributed equally to this work.     

Land use intensification increasingly drives the spatiotemporal patterns of the global human appropriation of net primary production in the last century

Land use has greatly transformed Earth's surface. While spatial reconstructions of how the extent of land cover and land-use types have changed during the last century are available, much less information exists about changes in land-use intensity. In particular, global reconstructions that consistently cover land-use intensity across land-use types and ecosystems are missing. We, therefore, lack understanding of how changes in land-use intensity interfere with the natural processes in land systems. To address this research gap, we map land-cover and land-use intensity changes between 1910 and 2010 for 9 points in time. We rely on the indicator framework of human appropriation of net primary production (HANPP) to quantify and map land-use-induced alterations of the carbon flows in ecosystems. We find that, while at the global aggregate level HANPP growth slowed down during the century, the spatial dynamics of changes in HANPP were increasing, with the highest change rates observed in the most recent past. Across all biomes, the importance of changes in land-use areas has declined, with the exception of the tropical biomes. In contrast, increases in land-use intensity became the most important driver of HANPP across all biomes and settings. We conducted uncertainty analyses by modulating input data and assumptions, which indicate that the spatial patterns of land use and potential net primary production are the most critical factors, while spatial allocation rules and uncertainties in overall harvest values play a smaller role. Highlighting the increasing role of land-use intensity compared to changes in the areal extent of land uses, our study supports calls for better integration of the intensity dimension into global analyses and models. On top of that, we provide important empirical input for further analyses of the sustainability of the global land system.     

Carbon isotope variability and sedimentology of the Upper Permian carbonate rocks and changes across the Permian-Triassic boundary in the Masore section (Western Slovenia)

Carbonate and total organic carbon stable isotope analyses of the Upper Permian and Lower Triassic succession in the Masore section in western Slovenia indicate a high storage of organic matter during the Upper Permian, as well as the well known worldwide light carbon isotope event across the P/Tr boundary. The perturbations in the global carbon cycle observed in the investigated section span an approximately 50 cm thick interval (from –11 cm below to +41 cm above the lithostratigraphically determined P/Tr boundary), and coincide more or less with changes in lithology, as well as with an abrupt disappearance of Upper Permian marine fauna. In this section changes in the sedimentary environment are most probably related to Upper Permian—Lower Triassic sea level changes. The carbonate and organic carbon negative peak anomaly could be explained by accelerated changes in the end Permian carbon cycle, due to some co-occurring events, such as pronounced erosion and oxidation of organic carbon, a possible release of methane from stored hydrates, and volcanic activity, as well as by a sudden reduction in primary productivity triggered by not yet completely satisfactorily explained mechanisms.