MicroRNAs and extracellular vesicles in the gut::New host modulators of the microbiome?

The gut microbiota plays an integral role in human health and its dysbiosis is associated with many chronic diseases. There are still large gaps in understanding the host and environmental factors that directly regulate the gut microbiota, and few effective strategies exist to modulate the microbiota in therapeutic applications. Recent reports suggest that certain microRNAs (miRNAs) released by mammalian cells can regulate bacterial gene expression to influence the microbiome composition and propose extracellular vesicles as one natural mechanism for miRNA transport in the gut. These new findings interface with a burgeoning body of data showing that miRNAs are present in a stable form in extracellular environments and can mediate cell-to-cell communication in mammals. Here, we review the literature on RNA-mediated modulation of the microbiome to bring cross-disciplinary perspective to this new type of interaction and its potential implications in biology and medicine

Host parasite communications—Messages from helminths for the immune system:Parasite communication and cell-cell interactions

Helminths are metazoan organisms many of which have evolved parasitic life styles dependent on sophisticated manipulation of the host environment. Most notably, they down-regulate host immune responses to ensure their own survival, by exporting a range of immuno-modulatory mediators that interact with host cells and tissues. While a number of secreted immunoregulatory parasite proteins have been defined, new work also points to the release of extracellular vesicles, or exosomes, that interact with and manipulate host gene expression. These recent results are discussed in the overall context of how helminths communicate effectively with the host organism

An Introduction to the Psychedelic Pastoral: Tracing Mind-Altering Plant Life into the Modern Industrialized West

My Masters thesis offers literary pastoralism as a viable entry into the conversation on psychedelic plants and their use in mind-alteration by the industrialized West. I will, first, establish that the ancient pastoral tradition can be related to the existence of psychedelic plants, and that the use of such plants has inspired a deeper communion with various levels of the natural world. Next, my analysis focuses on parallels between pastoral literature and accounts of psychedelic hallucinations, which are often comprised of ultra-pastoral visions of landscapes, arabesques, and even cosmic space. These similarities suggest that psychedelic plants initiate a peculiar and remarkable pastoral encounter with what becomes a non-natural, industrial reality. The question of obtaining a more cerebral relationship to an abandoned natural world is examined in literary figures including William Blake, Ralph Waldo Emerson, Charles Baudelaire, and Aldous Huxley. A review of the ties between the cerebral and the natural throughout these authors\u27 psychedelic and pastoral works will open our own 21st century doors of perception to a new literary mode uniting the two disciplines

Revisiting the validity of measures of social cognitive bias in schizophrenia : Additional results from the Social Cognition Psychometric Evaluation (SCOPE) study

Objective The ongoing Social Cognition Psychometric Evaluation (SCOPE) study is in the process of forming a gold-standard battery of social cognition tests for use in clinical trials. Previous SCOPE phases have not acknowledged key differences between social cognition skills and biases, and psychometric validity analyses might provide important information if tailored to bias-related outcomes. This study aims to validate these measures with such bias-related outcomes. Methods Two measures of social cognitive bias – the Ambiguous Intention Hostility Questionnaire (AIHQ; hostile attribution bias) and Trustworthiness Task (distrust bias) – were reviewed according to their relationships to (1) current and prospective symptom levels, (2) questionnaires of trait paranoia and hostility and informant-rated hostility, (3) interpersonal conflict, as well as (4) relationships to measures of trait paranoia, hostility, and interpersonal conflict above and beyond the influence of clinically rated symptoms. Results Results supported hypotheses that social cognitive bias provides information about cognition, symptoms, and functioning related to interpersonal conflict. Each bias demonstrated relationships to trait paranoia questionnaires, hostility, or interpersonal conflict outcomes, and these persisted above and beyond the influence of clinically rated symptoms. Hostile attribution bias also predicted change in symptom levels over a brief interval. Conclusions Overall, the current bias-specific psychometric analysis provides support for continued study of social cognitive biases. Practitioner points • Hostile attribution bias may play a role in important outcome variables given relationships to emotional discomfort and suspiciousness symptoms, trait paranoia and hostility, interpersonal conflict, as well as prospective hostility symptoms. • Distrust bias may also impact real-world functioning, as it is related to hostility, suspiciousness, and positive symptoms, trait paranoia, and hostility. • Relationships of social cognitive biases to interpersonal conflict outcomes exist independently of interview-rated symptoms and persist above and beyond the influence of social cognitive skills, which appear to demonstrate weaker relationships to these outcomes. • Understanding and assessing the individual's biases towards distrust or blame might help practioners predict interpersonal conflict and future increases in symptoms

The evolution of RNAi as a defence against viruses and transposable elements

RNA interference (RNAi) is an important defence against viruses and transposable elements (TEs). RNAi not only protects against viruses by degrading viral RNA, but hosts and viruses can also use RNAi to manipulate each other's gene expression, and hosts can encode microRNAs that target viral sequences. In response, viruses have evolved a myriad of adaptations to suppress and evade RNAi. RNAi can also protect cells against TEs, both by degrading TE transcripts and by preventing TE expression through heterochromatin formation. The aim of our review is to summarize and evaluate the current data on the evolution of these RNAi defence mechanisms. To this end, we also extend a previous analysis of the evolution of genes of the RNAi pathways. Strikingly, we find that antiviral RNAi genes, anti-TE RNAi genes and viral suppressors of RNAi all evolve rapidly, suggestive of an evolutionary arms race between hosts and parasites. Over longer time scales, key RNAi genes are repeatedly duplicated or lost across the metazoan phylogeny, with important implications for RNAi as an immune defence

Intracellular redox potential is correlated with miRNA expression in MCF7 cells under hypoxic conditions

Hypoxia is a ubiquitous feature of cancers, encouraging glycolytic metabolism, proliferation, and resistance to therapy. Nonetheless, hypoxia is a poorly defined term with confounding features described in the literature. Redox biology provides an important link between the external cellular microenvironment and the cell's response to changing oxygen pressures. In this paper, we demonstrate a correlation between intracellular redox potential (measured using optical nanosensors) and the concentrations of microRNAs (miRNAs) involved in the cell's response to changes in oxygen pressure. The correlations were established using surprisal analysis (an approach derived from thermodynamics and information theory). We found that measured redox potential changes reflect changes in the free energy computed by surprisal analysis of miRNAs. Furthermore, surprisal analysis identified groups of miRNAs, functionally related to changes in proliferation and metastatic potential that played the most significant role in the cell's response to changing oxygen pressure. © 2019 National Academy of Sciences. All rights reserved

Social cognition in schizophrenia : Factor structure of emotion processing and theory of mind

Factor analytic studies examining social cognition in schizophrenia have yielded inconsistent results most likely due to the varying number and quality of measures. With the recent conclusion of Phase 3 of the Social Cognition Psychometric Evaluation (SCOPE) Study, the most psychometrically sound measures of social cognition have been identified. Therefore, the aims of the present study were to: 1) examine the factor structure of social cognition in schizophrenia through the utilization of psychometrically sound measures, 2) examine the stability of the factor structure across two study visits, 3) compare the factor structure of social cognition in schizophrenia to that in healthy controls, and 4) examine the relationship between the factors and relevant outcome measures including social functioning and symptoms. Results supported a one-factor model for the patient and healthy control samples at both visits. This single factor was significantly associated with negative symptoms in the schizophrenia sample and with social functioning in both groups at both study visits

Production and application of stable isotope-labeled internal standards for RNA modification analysis

Post-transcriptional RNA modifications have been found to be present in a wide variety of organisms and in different types of RNA. Nucleoside modifications are interesting due to their already known roles in translation fidelity, enzyme recognition, disease progression, and RNA stability. In addition, the abundance of modified nucleosides fluctuates based on growth phase, external stress, or possibly other factors not yet explored. With modifications ever changing, a method to determine absolute quantities for multiple nucleoside modifications is required. Here, we report metabolic isotope labeling to produce isotopically labeled internal standards in bacteria and yeast. These can be used for the quantification of 26 different modified nucleosides. We explain in detail how these internal standards are produced and show their mass spectrometric characterization. We apply our internal standards and quantify the modification content of transfer RNA (tRNA) from bacteria and various eukaryotes. We can show that the origin of the internal standard has no impact on the quantification result. Furthermore, we use our internal standard for the quantification of modified nucleosides in mouse tissue messenger RNA (mRNA), where we find different modification profiles in liver and brain tissue