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The chemical contents of three abdominal glands were investigated in representative species of the ponerine ants. The Dufour glands of 14 species show a wide variety of contents. In Mystrium camillae and Proceratium itoi, no volatile substances were found in either the Dufour or venom glands. In Ectatomma sp., Diacamma ceylonense, Diacamma indicum, Pachycondyla obscuricornis, and Pachycondyla striata, volatile chemicals were found in the venom glands as well as in the Dufour glands. Platythyrea punctata was examined, but unusually it does not have a Dufour gland and its venom gland contained no volatile substances. Epoxides were found in ants for the first time in the Dufour glands of Amblyopone reclinata. Venom glands of Pachycondyla tarsata were also found to contain volatile material, including bitter-tasting cyclic dipeptides. In all, 16 species have been added to the list of those examined. All of the 27 known analyses of Dufour glands, 21 analyses of venom glands, and 4 of pygidial glands of workers of ponerine ant species have been brought together in order to seek some pattern in the type of glandular contents. Although the great majority of species produce hydrocarbons in their worker Dufour glands, and some have terpenes, there is no observable pattern for this gland on a tribe or genus level. Volatile compounds have been found in the venom glands of some species of the tribe Ponerini only. The information on pygidial glands is still too fragmentary for any conclusions.

Silver nanoparticles (SNP) are among the most commercialized nanoparticles. Here, we show that peptide-coated SNP cause functional impairment of human macrophages. A dose-dependent inhibition of phagocytosis is observed after nanoparticle treatment, and pretreatment of cells with N-acetyl cysteine (NAC) can counteract the phagocytosis disturbances caused by SNP. Using the surface-sensitive mode of time-of-flight secondary ion mass spectrometry, in combination with multivariate statistical methods, we studied the composition of cell membranes in human macrophages upon exposure to SNP with and without NAC preconditioning. This method revealed characteristic changes in the lipid pattern of the cellular membrane outer leaflet in those cells challenged by SNP. Statistical analyses resulted in 19 characteristic ions, which can be used to distinguish between NAC pretreated and untreated macrophages. The present study discusses the assignments of surface cell membrane phospholipids for the identified ions and the resulting changes in the phospholipid pattern of treated cells. We conclude that the adverse effects in human macrophages caused by SNP can be partially reversed through NAC administration. Some alterations, however, remained.

Benzo[a]pyrene (B[a]P) is an environmental contaminant mainly studied for its toxic/carcinogenic effects. For a comprehensive and pathway orientated mechanistic understanding of the effects directly triggered by a toxic (5 μM) or a subtoxic (50 nM) concentration of B[a]P or indirectly by its metabolites, we conducted time series experiments for up to 24 h to study the effects in murine hepatocytes. These cells rapidly take up and actively metabolize B[a]P, which was followed by quantitative analysis of the concentration of intracellular B[a]P and seven representative degradation products. Exposure with 5 μM B[a]P led to a maximal intracellular concentration of 1604 pmol/5 × 104 cells, leveling at 55 pmol/5 × 104 cells by the end of the time course. Changes in the global proteome (>1000 protein profiles) and metabolome (163 metabolites) were assessed in combination with B[a]P degradation. Abundance profiles of 236 (both concentrations), 190 (only 5 μM), and 150 (only 50 nM) proteins were found to be regulated in response to B[a]P in a time-dependent manner. At the endogenous metabolite level amino acids, acylcarnitines and glycerophospholipids were particularly affected by B[a]P. The comprehensive chemical, proteome and metabolomic data enabled the identification of effects on the pathway level in a time-resolved manner. So in addition to known alterations, also protein synthesis, lipid metabolism, and membrane dysfunction were identified as B[a]P specific effects.

Queen-laid eggs of Melipona bees stand upright on their larval food, in part because the upper part of the egg is covered with a water-repellent layer of fatty acids and C21 to C29 hydrocarbons. The lower, wettable portion does not have these materials. Trophic eggs laid by workers are essentially devoid of this coating and tend to sink in the food, when not detected and consumed by the queen. Reproductive workers' eggs, which have about 50% of the water-repellent coating in comparison with the queen's eggs, are usually laid in the cell after oviposition by the queen, and therefore there are two eggs in the cell. Surface tension forces cause the two eggs to float towards each other so they become attached. When alone inside the cell, the reproductive worker egg often floats at an angle to the surface, reflecting the instability of this kind of egg. Attachment to a queen's egg therefore compensates this instability and enhances the reproductive worker egg's chances to develop. Such reproductive worker eggs have about 50% of the water-repellent coating in comparison with the queen's eggs. The surface of an ‘undetermined’ egg laid by a worker was much closer in composition to that of a queen's egg, from which it is deduced that this was the rarer type of reproductive worker egg, namely those that are laid before queen oviposition has taken place. The layer of hydrophobic material on a queen's egg is about one molecule thick, and probably orientated with the carboxyl groups toward the chorion of the egg and the hydrocarbon chains perpendicular to the surface.

Workers of the ant Cylindromyrmex whymperi display mass trail recruitment. Bioassays show that the trail pheromone originates from a unique gland between abdominal sternites 6 and 7. The gland has a hitherto unknown structural organization. Upon leaving the secretory cell, the duct cell widens to form a sclerotized pear-shaped reservoir chamber, lined with multiple duct cells. Each duct thus forms a miniature reservoir for the secretions of each single secretory cells, a novel structural arrangement in exocrine glands of social Hymenoptera.

The venom glands of both workers and ergatoid queens of the ant Leptogenys diminuta contain 4–methyl-3–heptanol and a mixture of esters of this alcohol and long-chain fatty acids. Only the higher proportion of 4–methyl-3–heptanone in the queens represents a chemical difference between the castes. The Dufour gland secretion of workers and queens, however, shows considerable differences. Both share a series of long-chain hydrocarbons with 9and 7–pentacosene as the major substances of the secretion but are otherwise differentiated by the presence in the workers only of three farnesene isomers, whereas queens contain a wide range of substances. The mated queen had a very complex mixture of hydrocarbons, esters and terpenes. These substances were also present in the virgin females but in smaller quantities.

Although the activation of immune cells is the first and thereby pivotal step in the immunological cascade, the current knowledge about the details of this process is quite limited. Recent studies have shown that aromatic compounds, such as B[ a ]P, influence the immune system even at low concentrations. We investigated the effect of a subtoxic B[ a ]P concentration (50 nM) on the proteome and the metabolome of non-activated and activated Jurkat T cells. The GeLC-MS/MS analysis yielded 2624 unambiguously identified proteins. In addition to typical regulatory pathways associated with T cell activation, pathway analysis by Ingenuity IPA revealed several metabolic processes, for instance purine and pyruvate metabolism. The activation process seems to be influenced by B[ a ]P suggesting an important role of the mTOR pathway in the cellular adaptation. B[ a ]P exposure of non-activated Jurkat cells induced signaling pathways such as protein ubiquitination and NRF2 mediated oxidative stress response as well as metabolic adaptation involving pyruvate, purine and fatty acid metabolism. Thus, we validated the proteome results by determining the concentrations of 183 metabolites with FIA-MS/MS and IC-MS/MS. Furthermore, we were able to show that Jurkat cells metabolize B[ a ]P to B[ a ]P-1,6-dione. The combined evaluation of proteome and metabolome data with an integrated, genome-scale metabolic model provided novel systems biological insights into the complex relation between metabolic and proteomic processes in Jurkat T cells during activation and subtoxic chemical exposure.

Background Hepatic lipidosis or fatty liver disease is a major metabolic disorder of high-producing dairy cows that compromises animal performance and, hence, causes heavy economic losses worldwide. This syndrome, occurring during the critical transition from gestation to early lactation, leads to an impaired health status, decreased milk yield, reduced fertility and shortened lifetime. Because the prevailing clinical chemistry parameters indicate advanced liver damage independently of the underlying disease, currently, hepatic lipidosis can only be ascertained by liver biopsy. We hypothesized that the condition of fatty liver disease may be accompanied by an altered profile of endogenous metabolites in the blood of affected animals. Results To identify potential small-molecule biomarkers as a novel diagnostic alternative, the serum samples of diseased dairy cows were subjected to a targeted metabolomics screen by triple quadrupole mass spectrometry. A subsequent multivariate test involving principal component and linear discriminant analyses yielded 29 metabolites (amino acids, phosphatidylcholines and sphingomyelines) that, in conjunction, were able to distinguish between dairy cows with no hepatic lipidosis and those displaying different stages of the disorder. Conclusions This proof-of-concept study indicates that metabolomic profiles, including both amino acids and lipids, distinguish hepatic lipidosis from other peripartal disorders and, hence, provide a promising new tool for the diagnosis of hepatic lipidosis. By generating insights into the molecular pathogenesis of hepatic lipidosis, metabolomics studies may also facilitate the prevention of this syndrome.

Considering the holy grail of future medical treatment being personalized medicines, biomarker research will become more and more the focus for attention not only to develop new medical treatment regimes, based on changes in biomarker patterns, but also for nutritional advice to guarantee a lifelong optimized health condition. The current review gives an outline of how personalized medicine can become established for actual medical treatment using new biomarker concepts. Starting from the development of biomarker research using mainly immunological techniques, the review gives an overview about biomarkers of prediction evolved and focuses on new methodology for the identification of biomarkers using hyphenated analytical techniques like metabolomics and lipidomics. The actual use of multivariate statistical methods in combination with metabolomics and lipidomics is discussed not only for medical treatment but also for precautionary risk identification in human biomonitoring studies.

Considering the holy grail of future medical treatment being personalized medicines, biomarker research will become more and more the focus for attention not only to develop new medical treatment regimes, based on changes in biomarker patterns, but also for nutritional advice to guarantee a lifelong optimized health condition. The current review gives an outline of how personalized medicine can become established for actual medical treatment using new biomarker concepts. Starting from the development of biomarker research using mainly immunological techniques, the review gives an overview about biomarkers of prediction evolved and focuses on new methodology for the identification of biomarkers using hyphenated analytical techniques like metabolomics and lipidomics. The actual use of multivariate statistical methods in combination with metabolomics and lipidomics is discussed not only for medical treatment but also for precautionary risk identification in human biomonitoring studies.

Oxidative stress is more and more recognized as the underlying motif for a broad variety of diseases including cancer. Medicine faces the paramount task to develop better diagnostic tools and drug treatment prediction models in the future to significantly enhance the quality of life. Special interest will focus on earlystage disease biomarkers and biomarkers that could predict healing success at the earliest time point after the treatment started. The accelerated formation of so-called reactive oxygen species (ROS) is becoming widely regarded as the underlying process associated with many diseases like myocardial infarction, Alzheimer's, Parkinson's and kidney disease, etc. Once generated within cells and tissues, ROS can react with a variety of cellular metabolites like fatty acids, proteins or DNA. This review investigates the possibilities for various oxidized metabolites as well as proteomics, genomics and bioimaging biomarkers to serve as early-stage disease biomarkers or biomarkers for drug treatment success. We also assess the value of a step-by-step or cascade biomarker approach as a new paradigm in medical diagnostics. Examples are given for possible analytical methodology and tools as well as statistical methods that could be applied. Such an approach may straighten the road toward new medical diagnostics and treatment regimes, which ultimately could lead to a significantly enhanced medical service for patients suffering from chronic and debilitating or deadly diseases including cancer. Examples from recent research are given to show the progress and possibilities for the proposed model.

Silver nanoparticles (SNP) are the subject of worldwide commercialization because of their antimicrobial effects. Yet only little data on their mode of action exist. Further, only few techniques allow for visualization and quantification of unlabeled nanoparticles inside cells. To study SNP of different sizes and coatings within human macrophages, we introduce a novel laser postionization secondary neutral mass spectrometry (Laser-SNMS) approach and prove this method superior to the widely applied confocal Raman and transmission electron microscopy. With time-of-flight secondary ion mass spectrometry (TOF-SIMS) we further demonstrate characteristic fingerprints in the lipid pattern of the cellular membrane indicative of oxidative stress and membrane fluidity changes. Increases of protein carbonyl and heme oxygenase-1 levels in treated cells confirm the presence of oxidative stress biochemically. Intriguingly, affected phagocytosis reveals as highly sensitive end point of SNP-mediated adversity In macrophages. The cellular responses monitored are. hierarchically linked, but follow individual kinetics and are partially reversible.

The chemical contents of three abdominal glands were investigated in representative species of the ponerine ants. The Dufour glands of 14 species show a wide variety of contents. In Mystrium camillae and Proceratium itoi, no volatile substances were found in either the Dufour or venom glands. In Ectatomma sp., Diacamma ceylonense, Diacamma indicum, Pachycondyla obscuricornis, and Pachycondyla striata, volatile chemicals were found in the venom glands as well as in the Dufour glands. Platythyrea punctata was examined, but unusually it does not have a Dufour gland and its venom gland contained no volatile substances. Epoxides were found in ants for the first time in the Dufour glands of Amblyopone reclinata. Venom glands of Pachycondyla tarsata were also found to contain volatile material, including bitter-tasting cyclic dipeptides. In all, 16 species have been added to the list of those examined. All of the 27 known analyses of Dufour glands, 21 analyses of venom glands, and 4 of pygidial glands of workers of ponerine ant species have been brought together in order to seek some pattern in the type of glandular contents. Although the great majority of species produce hydrocarbons in their worker Dufour glands, and some have terpenes, there is no observable pattern for this gland on a tribe or genus level. Volatile compounds have been found in the venom glands of some species of the tribe Ponerini only. The information on pygidial glands is still too fragmentary for any conclusions.

Silver nanoparticles (SNP) are among the most commercialized nanoparticles worldwide. They can be found in many diverse products, mostly because of their antibacterial properties. Despite its widespread use only little data on possible adverse health effects exist. It is difficult to compare biological data from different studies due to the great variety in sizes, coatings or shapes of the particles. Here, we applied a novel synthesis approach to obtain SNP, which are covalently stabilized by a small peptide. This enables a tight control of both size and shape. We applied these SNP in two different sizes of 20 or 40 nm (Ag20Pep and Ag40Pep) and analyzed responses of THP-1-derived human macrophages. Similar gold nanoparticles with the same coating (Au20Pep) were used for comparison and found to be non-toxic. We assessed the cytotoxicity of particles and confirmed their cellular uptake via transmission electron microscopy and confocal Raman microscopy. Importantly a majority of the SNP could be detected as individual particles spread throughout the cells. Furthermore we studied several types of oxidative stress related responses such as induction of heme oxygenase I or formation of protein carbonyls. In summary, our data demonstrate that even low doses of SNP exerted adverse effects in human macrophages.

Metabolomics, the comprehensive analysis of metabolites in a biological system, provides detailed information about the biochemical/physiological status of a biological system, and about the changes caused by chemicals. Metabolomics analysis is used in many fields, ranging from the analysis of the physiological status of genetically modified organisms in safety science to the evaluation of human health conditions. In toxicology, metabolomics is the -omics discipline that is most closely related to classical knowledge of disturbed biochemical pathways. It allows rapid identification of the potential targets of a hazardous compound. It can give information on target organs and often can help to improve our understanding regarding the mode-of-action of a given compound. Such insights aid the discovery of biomarkers that either indicate pathophysiological conditions or help the monitoring of the efficacy of drug therapies. The first toxicological applications of metabolomics were for mechanistic research, but different ways to use the technology in a regulatory context are being explored. Ideally, further progress in that direction will position the metabolomics approach to address the challenges of toxicology of the 21st century. To address these issues, scientists from academia, industry, and regulatory bodies came together in a workshop to discuss the current status of applied metabolomics and its potential in the safety assessment of compounds. We report here on the conclusions of three working groups addressing questions regarding 1) metabolomics for in vitro studies 2) the appropriate use of metabolomics in systems toxicology, and 3) use of metabolomics in a regulatory context.