Regulation of Immune Responses by Histone Deacetylase Inhibitors

Both genetic and epigenetic factors are important regulators of the immune system. There is an increasing body of evidence attesting to epigenetic modifications that influence the development of distinct innate and adaptive immune response cells. Chromatin remodelling via acetylation, methylation, phosphorylation, and ubiquitination of histone proteins as well as DNA, methylation is epigenetic mechanisms by which immune gene expression can be controlled. In this paper, we will discuss the role of epigenetics in the regulation of host immunity, with particular emphasis on histone deacetylase inhibitors. In particular, the role of HDAC inhibitors as a new class of immunomodulatory therapeutics will also be reviewed

New Constraints on the Timing and Pattern of Deglaciation in the Húnaflói Bay Region of Northwest Iceland Using Cosmogenic 36CA Dating and Geomorphic Mapping

Understanding the evolution and timing of changes in ice sheet geometry and extent in Iceland during the Last Glacial Maximum (LGM) and subsequent deglaciation continues to stimulate much active research. Though many previous studies have advanced our knowledge of Icelandic ice sheet history preserved in marine and terrestrial settings (e.g., Andrews et al., 2000; Norðdahl et al., 2008), the timing of ice margin retreat remains largely unknown in several key regions. Recently published 36Cl surface exposure ages of bedrock surfaces and moraines in the West Fjords (Brynjólfsson et al., 2015) contribute important progress in establishing more precise age control of ice recession in northwest Iceland. In another recent study, the spatial pattern and style of deglaciation in northern Iceland have been revealed through geomorphic mapping and GIS analyses of glacial landforms (Principato et al., 2016). Additional insight comes from updated numerical modeling reconstructions, which now provide a series of glaciologically plausible Icelandic ice sheet configurations from the LGM through the last deglaciation (Patton et al., 2017). However, the optimization of ice sheet model simulations relies on critical comparisons with the available empirical record of glacial-geologic evidence and chronological control, which remains relatively limited and sparsely distributed throughout Iceland. Our investigation is motivated by the need for more accurate constraints on the deglacial history in northern Iceland, where dated terrestrial records of ice margin retreat are particularly scarce. (excerpt

Las representaciones pictóricas como recursos semióticos. Caso equilibrio químico

De acuerdo con Orlandi (1996) tres variables intervienen en el proceso de producción de sentidos: la intencionalidad del autor, la materialidad del texto y las posibilidades de resignificación del lector. Las dos primeras no pueden ser modificadas por el lector. Las posibilidades del lector para atribuir significados pueden ser modificadas conociendo los diferentes tipos de Representaciones Externas Pictóricas (REP) y los recursos semióticos que se utilizan en su construcción. Se diseña una intervención dirigida a dar a conocer este contenido para dos tipos REP y así facilitar operar con éstas. Los resultados indican que las REP ejercen una doble influencia: a) cuando la tarea se realiza a partir de una REP o b) cuando la tarea es construir la REP. En ambos casos se encuentra que cada tipo de representación permite la recuperación de una información específica y diferente

The Sensitivity of the nEXO Experiment to Majorana Neutrinos

The nEXO Collaboration is performing R&D towards a detector with ∼ 5 t of enriched liquid 136Xe to search for neutrinoless double-beta decay. The experiment is based on t

Social and AR Applications Using the User’s Context and User Generated Content

The core business of Mobile Network Operators (MNO) has moved from network management and phone services to service providing. In contrast to Information Communication Technology (ICT) service providers, MNOs handle large amounts of their customers’ context data and generated content, which can be used to bring value-added services to customers and therefore, generate solid revenues. Given this scenario, this paper describes how Telecom Italia (a major Italian MNO) has prototyped such type of services after a deep research performed in the context-awareness and context management field and using its user-generated content management facilities in federation with other platforms and systems

Epigenome targeting by probiotic metabolites

BACKGROUND: The intestinal microbiota plays an important role in immune development and homeostasis. A disturbed microbiota during early infancy is associated with an increased risk of developing inflammatory and allergic diseases later in life. The mechanisms underlying these effects are poorly understood but are likely to involve alterations in microbial production of fermentation-derived metabolites, which have potent immune modulating properties and are required for maintenance of healthy mucosal immune responses. Probiotics are beneficial bacteria that have the capacity to alter the composition of bacterial species in the intestine that can in turn influence the production of fermentation-derived metabolites. Principal among these metabolites are the short-chain fatty acids butyrate and acetate that have potent anti-inflammatory activities important in regulating immune function at the intestinal mucosal surface. Therefore strategies aimed at restoring the microbiota profile may be effective in the prevention or treatment of allergic and inflammatory diseases. PRESENTATION OF THE HYPOTHESIS: Probiotic bacteria have diverse effects including altering microbiota composition, regulating epithelial cell barrier function and modulating of immune responses. The precise molecular mechanisms mediating these probiotic effects are not well understood. Short-chain fatty acids such as butyrate are a class of histone deacetylase inhibitors important in the epigenetic control of host cell responses. It is hypothesized that the biological function of probiotics may be a result of epigenetic modifications that may explain the wide range of effects observed. Studies delineating the effects of probiotics on short-chain fatty acid production and the epigenetic actions of short-chain fatty acids will assist in understanding the association between microbiota and allergic or autoimmune disorders. TESTING THE HYPOTHESIS: We propose that treatment with specific probiotic bacteria under in vivo conditions would offer the ideal conditions to examine the microbiological, immunological and epigenetic mechanisms of action. Advances in epigenetic technology now allow investigators to better understand the complex biological properties of probiotics and their metabolites. IMPLICATIONS OF THE HYPOTHESIS: Determining the precise mechanisms of probiotic action will lead to more specific and efficacious therapeutic strategies in the prevention or treatment of chronic inflammatory conditions

Discovering geothermal supercritical fluids: a new frontier for seismic exploration

Exploiting supercritical geothermal resources represents a frontier for the next generation of geothermal electrical power plant, as the heat capacity of supercritical fluids (SCF),which directly impacts on energy production, is much higher than that of fluids at subcritical conditions. Reconnaissance and location of intensively permeable and productive horizons at depth is the present limit for the development of SCF geothermal plants. We use, for the first time, teleseismic converted waves (i.e. receiver function) for discovering those horizons in the crust. Thanks to the capability of receiver function to map buried anisotropic materials, the SCF-bearing horizon is seen as the 4km-depth abrupt termination of a shallow, thick, ultra-high (>30%) anisotropic rock volume, in the center of the Larderello geothermal field. The SCF-bearing horizon develops within the granites of the geothermal field, bounding at depth the vapor-filled heavily-fractured rock matrix that hosts the shallow steam-dominated geothermal reservoirs. The sharp termination at depth of the anisotropic behavior of granites, coinciding with a 2 km-thick stripe of seismicity and diffuse fracturing, points out the sudden change in compressibility of the fluid filling the fractures and is a key-evidence of deep fluids that locally traversed the supercritical conditions. The presence of SCF and fracture permeability in nominally ductile granitic rocks open new scenarios for the understanding of magmatic systems and for geothermal exploitation

Cross-Linked Hyaluronan Derivatives in the Delivery of Phycocyanin

An easy and viable crosslinking technology, based on the “click-chemistry” reaction copper(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition (click-crosslinking), was applied to graft copolymers of medium molecular weight (i.e., 270 kDa) hyaluronic acid (HA) grafted with ferulic acid (FA) residues bearing clickable propargyl groups, as well as caffeic acid derivatives bearing azido-terminated oligo(ethylene glycol) side chains. The obtained crosslinked materials were characterized from the point of view of their structure and aggregation liability to form hydrogels in a water environment. The most promising materials showed interesting loading capability regarding the antioxidant agent phycocyanin (PC). Two novel materials complexes (namely HA(270)-FA-TEGEC-CL-20/PC and HA(270)-FA-HEGEC-CL-20/PC) were obtained with a drug-to-material ratio of 1:2 (w/w). Zeta potential measurements of the new complexes (−1.23 mV for HA(270)-FA-TEGEC-CL-20/PC and −1.73 mV for HA(270)-FA-HEGEC-CL-20/PC) showed alterations compared to the zeta potential values of the materials on their own, suggesting the achievement of drug–material interactions. According to the in vitro dissolution studies carried out in different conditions, novel drug delivery systems (DDSs) were obtained with a variety of characteristics depending on the desired route of administration and, consequently, on the pH of the surrounding environment, thanks to the complexation of phycocyanin with these two new crosslinked materials. Both complexes showed excellent potential for providing a controlled/prolonged release of the active pharmaceutical ingredient (API). They also increased the amount of drug that reach the target location, enabling pH-dependent release. Importantly, as demonstrated by the DPPH free radical scavenging assay, the complexation process, involving freezing and freeze-drying, showed no adverse effects on the antioxidant activity of phycocyanin. This activity was preserved in the two novel materials and followed a concentration-dependent pattern similar to pure PC