Mycotoxin Adducts on Human Serum Albumin: Biomarkers of Exposure to Stachybotrys chartarum

OBJECTIVE: Despite the growing body of evidence showing adverse health effects from inhalation exposure to the trichothecene-producing mold Stachybotrys chartarum, controversy remains. Currently, there are no reliable assays suitable for clinical diagnosis of exposure. We hypothesized that satratoxin G (SG)–albumin adducts may serve as biomarkers of exposure to this fungus. DESIGN: We studied the formation of adducts of SG with serum albumin in vitro using Western blots and mass spectrometry (MS) and searched for similar adducts formed in vivo using human and animal serum. RESULTS: Samples of purified human serum albumin that had been incubated with increasing concentrations of SG showed concentration-dependent albumin bands in Western blots developed with anti-SG antibodies. MS analysis found that as many as 10 toxin molecules can be bound in vitro to one albumin molecule. The sequencing of albumin-adduct tryptic peptides and the analysis of pronase/aminopeptidase digests demonstrated that lysyl, cysteinyl, and histidyl residues are involved in the formation of these adducts. Serum samples from three patients with documented exposure to S. chartarum similarly revealed lysine–, cysteine–, and histidine–SG adducts after exhaustive digestion, affinity column enrichment, and MS analysis. These adducts were also found in the sera from rats exposed to the spores of S. chartarum in contrast to control human subjects and control animals. CONCLUSIONS: These data document the occurrence of SG–albumin adducts in both in vitro experiments and in vivo human and animal exposures to S. chartarum. RELEVANCE TO CLINICAL PRACTICE: SG–amino acid adducts may serve as reliable dosimeter biomarkers for detection of exposure to S. chartarum

Cyborg Activism: Exploring the reconfigurations of democratic subjectivity in Anonymous

This article develops the concept of cyborg activism as novel configuration of democratic subjectivity in the Information Age by exploring the online collectivity Anonymous as a prototype. By fusing elements of human/machine and organic/digital the cyborg disrupts modern logics of binary thinking. Cyborg activism emerges as the reconfiguration of equality/hierarchy, reason/emotion, and nihilism/idealism. Anonymous demonstrates how through the use of contingent and ephemeral digital personae hierarchies in cyborg activism prove more volatile than in face-to-face settings. Emotions appear as an essential part of a politics of passion, which enables pursuing laughter and joy, expressing anger, and experiencing empowerment as part of a reasoned, strategic politics. Anonymous’ political content reconfigures nihilist sentiments, frustration, and political disenchantment on the one hand with idealist world views on the other. This enables the cohabitation and partial integration of a great diversity of political claims rooted in various ideologies

Development of anisotropic structure in the Earth's lower mantle by solid-state convection

Seismological observations reveal highly anisotropic patches at the bottom of the Earth's lower mantle, whereas the bulk of the mantle has been observed to be largely isotropic(1-4). These patches have been interpreted to correspond to areas where subduction has taken place in the past or to areas where mantle plumes are upwelling, but the underlying cause for the anisotropy is unknown-both shape-preferred orientation of elastically heterogenous materials(5) and lattice-preferred orientation of a homogeneous material(6-8) have been proposed. Both of these mechanisms imply that large-strain deformation occurs within the anisotropic regions, but the geodynamic implications of the mechanisms differ. Shape-preferred orientation would imply the presence of large elastic (and hence chemical) heterogeneity whereas lattice-preferred orientation requires deformation at high stresses. Here we show, on the basis of numerical modelling incorporating mineral physics of elasticity and development of lattice-preferred orientation, that slab deformation in the deep lower mantle can account for the presence of strong anisotropy in the circum-Pacific region. In this model-where development of the mineral fabric (the alignment of mineral grains) is caused solely by solid-state deformation of chemically homogeneous mantle material-anisotropy is caused by large-strain deformation at high stresses, due to the collision of subducted slabs with the core-mantle boundary.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62804/1/416310a.pd

Impacts of climate change on plant diseases – opinions and trends

There has been a remarkable scientific output on the topic of how climate change is likely to affect plant diseases in the coming decades. This review addresses the need for review of this burgeoning literature by summarizing opinions of previous reviews and trends in recent studies on the impacts of climate change on plant health. Sudden Oak Death is used as an introductory case study: Californian forests could become even more susceptible to this emerging plant disease, if spring precipitations will be accompanied by warmer temperatures, although climate shifts may also affect the current synchronicity between host cambium activity and pathogen colonization rate. A summary of observed and predicted climate changes, as well as of direct effects of climate change on pathosystems, is provided. Prediction and management of climate change effects on plant health are complicated by indirect effects and the interactions with global change drivers. Uncertainty in models of plant disease development under climate change calls for a diversity of management strategies, from more participatory approaches to interdisciplinary science. Involvement of stakeholders and scientists from outside plant pathology shows the importance of trade-offs, for example in the land-sharing vs. sparing debate. Further research is needed on climate change and plant health in mountain, boreal, Mediterranean and tropical regions, with multiple climate change factors and scenarios (including our responses to it, e.g. the assisted migration of plants), in relation to endophytes, viruses and mycorrhiza, using long-term and large-scale datasets and considering various plant disease control methods

Adenosine A2A receptors: localization and function

Adenosine is an endogenous purine nucleoside present in all mammalian tissues, that originates from the breakdown of ATP. By binding to its four receptor subtypes (A1, A2A, A2B, and A3), adenosine regulates several important physiological functions at both the central and peripheral levels. Therefore, ligands for the different adenosine receptors are attracting increasing attention as new potential drugs to be used in the treatment of several diseases. This chapter is aimed at providing an overview of adenosine metabolism, adenosine receptors localization and their signal transduction pathways. Particular attention will be paid to the biochemistry and pharmacology of A2A receptors, since antagonists of these receptors have emerged as promising new drugs for the treatment of Parkinson's disease. The interactions of A2A receptors with other nonadenosinergic receptors, and the effects of the pharmacological manipulation of A2A receptors on different body organs will be discussed, together with the usefulness of A2A receptor antagonists for the treatment of Parkinson's disease and the potential adverse effects of these drugs

Adenosine induces growth-cone turning of sensory neurons

The formation of appropriate connections between neurons and their specific targets is an essential step during development and repair of the nervous system. Growth cones are located at the leading edges of the growing neurites and respond to environmental cues in order to be guided to their final targets. Directional information can be coded by concentration gradients of substrate-bound or diffusible-guidance molecules. Here we show that concentration gradients of adenosine stimulate growth cones of sensory neurons (dorsal root ganglia) from chicken embryos to turn towards the adenosine source. This response is mediated by adenosine receptors. The subsequent signal transduction process involves cAMP. It may be speculated that the in vivo function of this response is concerned with the formation or the repair and regeneration of the peripheral nervous system

The use of complementary and alternative medicine by 7427 Australian women with cyclic perimenstrual pain and discomfort: A cross-sectional study

© 2016 Fisher et al. Background: To assess the prevalence of cyclic perimenstrual pain and discomfort and to detail the pattern of complementary and alternative (CAM) use adopted by women for the treatment of these symptoms. Methods: Data from the 2012 national Australian Longitudinal Study of Women's Health (ALSWH) cross-sectional survey of 7427 women aged 34-39 years were analysed to estimate the prevalence of endometriosis, premenstrual syndrome (PMS), irregular or heavy periods and severe dysmenorrhoea and to examine the association between their symptoms and their visits to CAM practitioners as well as their use of CAM therapies and products in the previous 12 months. Results: The prevalence of endometriosis was 3.7 % and of the perimenstrual symptoms assessed, PMS was most prevalent at 41.2 % whilst irregular bleeding (22.2 %), heavy periods (29.8 %) and severe period pain (24.1 %) were reported at lower levels. Women with endometriosis were more likely than non-sufferers to have consulted with a massage therapist or acupuncturist and to have used vitamins/minerals, yoga/meditation or Chinese medicines (p < 0.05). PMS sufferers were more likely to consult with an osteopath, massage therapist, naturopath/herbalist or alternative health practitioner and to have used all forms of CAM therapies except Chinese medicines than women who had infrequent PMS (all p < 0.05). Women with irregular periods did not have different patterns of CAM use from non-sufferers and those with heavy periods did not favour any form of CAM but were less likely to visit a massage therapist or use yoga/meditation than non-sufferers (p < 0.05). For women with severe dysmenorrhoea there was no difference in their visits to CAM practitioners compared to non-sufferers but they were more likely to use aromatherapy oils (p < 0.05) and for more frequent dysmenorrhoea also herbal medicines, Chinese medicines and other alternative therapies compared to non-sufferers (all p < 0.05). Conclusions: There is a high prevalence of cyclic perimenstrual pain and discomfort amongst women in this age group. Women were using CAM differentially when they had specific symptoms of cyclic perimenstrual pain and discomfort. The use of CAM needs to be properly assessed to ensure their safe, effective use and to ascertain their significance as a treatment option enabling women with menstrual problems and their care providers to improve their quality of life

Biological detoxification of the mycotoxin deoxynivalenol and its use in genetically engineered crops and feed additives

Deoxynivalenol (DON) is the major mycotoxin produced by Fusarium fungi in grains. Food and feed contaminated with DON pose a health risk to humans and livestock. The risk can be reduced by enzymatic detoxification. Complete mineralization of DON by microbial cultures has rarely been observed and the activities turned out to be unstable. The detoxification of DON by reactions targeting its epoxide group or hydroxyl on carbon 3 is more feasible. Microbial strains that de-epoxidize DON under anaerobic conditions have been isolated from animal digestive system. Feed additives claimed to de-epoxidize trichothecenes enzymatically are on the market but their efficacy has been disputed. A new detoxification pathway leading to 3-oxo-DON and 3-epi-DON was discovered in taxonomically unrelated soil bacteria from three continents; the enzymes involved remain to be identified. Arabidopsis, tobacco, wheat, barley, and rice were engineered to acetylate DON on carbon 3. In wheat expressing DON acetylation activity, the increase in resistance against Fusarium head blight was only moderate. The Tri101 gene from Fusarium sporotrichioides was used; Fusarium graminearum enzyme which possesses higher activity towards DON would presumably be a better choice. Glycosylation of trichothecenes occurs in plants, contributing to the resistance of wheat to F. graminearum infection. Marker-assisted selection based on the trichothecene-3-O-glucosyltransferase gene can be used in breeding for resistance. Fungal acetyltransferases and plant glucosyltransferases targeting carbon 3 of trichothecenes remain promising candidates for engineering resistance against Fusarium head blight. Bacterial enzymes catalyzing oxidation, epimerization, and less likely de-epoxidation of DON may extend this list in future

Search for neutral MSSM Higgs bosons decaying to a pair of tau leptons in pp collisions

Peer reviewe