The role of the neuromodulator adenosine in alcohols actions.

The interaction between the neuromodulator adenosine and adenosine receptors on the surface of neurons modifies the neurons responses to neurotransmitters. The activated adenosine receptors alter the levels of small signaling molecules (i.e., second messengers) in the cells. Depending on the receptors and cells involved, these changes can make it easier or more difficult for neurotransmitters to excite the cell. Adenosines activity is regulated by proteins called nucleoside transporters, which carry adenosine into and out of the cell. Alcohol interferes with the function of the adenosine system. For example, both acute and chronic alcohol exposure affect the function of the adenosine-carrying nucleoside transporters, thereby indirectly altering the second-messenger levels in the cells. Through this mechanism, adenosine may mediate some of alcohols effects, such as intoxication, motor incoordination, and sedation

A selective ALDH-2 inhibitor reduces anxiety in rats

CVT-10216 is a highly selective, reversible inhibitor of ALDH-2 that reduces excessive alcohol drinking. Anxiety plays a role in alcoholism. The present study asks whether CVT-10216 has anxiolytic properties, as reflected in social interaction behavior in four unrelated rodent models: endogenous anxiety-like behavior in naïve Fawn-Hooded rats, repeated alcohol-withdrawal-induced anxiety, restraint stress-induced anxiety and drug-induced anxiety. CVT-10216 counteracted anxiety in all models except that produced by the 5-HT2C agonist, mCPP. CVT-10216 exhibited both acute and prophylactic inhibitions of repeated alcohol-withdrawal-induced anxiety. Importantly, anxiogenic behavior induced by the benzodiazepine receptor inverse agonist, DMCM, was counteracted dose-dependently by CVT-10216. Thus, a non-addictive selective inhibitor of ALDH-2 has both anxiolytic and antidipsotropic properties, which may be dependent, in part on the involvement of the GABA–benzodiazepine system

Exploring the planetary boundary for chemical pollution

Rockström et al. (2009a, 2009b) have warned that humanity must reduce anthropogenic impacts defined by nine planetary boundaries if “unacceptable global change” is to be avoided. Chemical pollution was identified as one of those boundaries for which continued impacts could erode the resilience of ecosystems and humanity. The central concept of the planetary boundary (or boundaries) for chemical pollution (PBCP or PBCPs) is that the Earth has a finite assimilative capacity for chemical pollution, which includes persistent, as well as readily degradable chemicals released at local to regional scales, which in aggregate threaten ecosystem and human viability. The PBCP allows humanity to explicitly address the increasingly global aspects of chemical pollution throughout a chemical's life cycle and the need for a global response of internationally coordinated control measures. We submit that sufficient evidence shows stresses on ecosystem and human health at local to global scales, suggesting that conditions are transgressing the safe operating space delimited by a PBCP. As such, current local to global pollution control measures are insufficient. However, while the PBCP is an important conceptual step forward, at this point single or multiple PBCPs are challenging to operationalize due to the extremely large number of commercial chemicals or mixtures of chemicals that cause myriad adverse effects to innumerable species and ecosystems, and the complex linkages between emissions, environmental concentrations, exposures and adverse effects. As well, the normative nature of a PBCP presents challenges of negotiating pollution limits amongst societal groups with differing viewpoints. Thus, a combination of approaches is recommended as follows: develop indicators of chemical pollution, for both control and response variables, that will aid in quantifying a PBCP(s) and gauging progress towards reducing chemical pollution; develop new technologies and technical and social approaches to mitigate global chemical pollution that emphasize a preventative approach; coordinate pollution control and sustainability efforts; and facilitate implementation of multiple (and potentially decentralized) control efforts involving scientists, civil society, government, non-governmental organizations and international bodies

Phenotypic and functional characteristics of murine CD11c+ B cells which is suppressed by metformin

Since the description of age-associated or autoimmune-associated B cells (ABCs), there has been a growing interest in the role of these cells in autoimmunity. ABCs are differently defined depending on the research group and are heterogenous subsets. Here, we sought to characterize ABCs in Sle1/2/3 triple congenic (TC) mice, which is a well accepted mouse model of lupus. Compared to follicular (FO) B cells, ABCs have many distinct functional properties, including antigen presentation. They express key costimulatory molecules for T cell activation and a distinct profile of cytokines. Moreover, they exhibit an increased capacity for antigen uptake. ABCs were also compared with germinal center (GC) B cells, which are antigen activated B cell population. There are several phenotypic similarities between ABCs and GC B cells, but GC B cells do not produce proinflammatory cytokines or take up antigen. While T cell proliferation and activation is induced by both FO B and ABCs in an antigen-dependent manner, ABCs induce stronger T cell receptor signaling in naïve CD4+ T cells and preferentially induce differentiation of T follicular helper (Tfh) cells. We found that ABCs exhibit a distinct transcriptomic profile which is focused on metabolism, cytokine signaling and antigen uptake and processing. ABCs exhibit an increase in both glycolysis and oxidative phosphorylation compared to FO B cells. Treatment of ABCs with metformin suppresses antigen presentation by decreasing antigen uptake, resulting in decreased Tfh differentiation. Taken together, these findings define a fundamental connection between metabolism and function within ABCs

Home parenteral nutrition with an omega-3-fatty-acid-enriched MCT/LCT lipid emulsion in patients with chronic intestinal failure (the HOME study):study protocol for a randomized, controlled, multicenter, international clinical trial

BACKGROUND: Home parenteral nutrition (HPN) is a life-preserving therapy for patients with chronic intestinal failure (CIF) indicated for patients who cannot achieve their nutritional requirements by enteral intake. Intravenously administered lipid emulsions (ILEs) are an essential component of HPN, providing energy and essential fatty acids, but can become a risk factor for intestinal-failure-associated liver disease (IFALD). In HPN patients, major effort is taken in the prevention of IFALD. Novel ILEs containing a proportion of omega-3 polyunsaturated fatty acids (n-3 PUFA) could be of benefit, but the data on the use of n-3 PUFA in HPN patients are still limited. METHODS/DESIGN: The HOME study is a prospective, randomized, controlled, double-blind, multicenter, international clinical trial conducted in European hospitals that treat HPN patients. A total of 160 patients (80 per group) will be randomly assigned to receive the n-3 PUFA-enriched medium/long-chain triglyceride (MCT/LCT) ILE (Lipidem/Lipoplus® 200 mg/ml, B. Braun Melsungen AG) or the MCT/LCT ILE (Lipofundin® MCT/LCT/Medialipide® 20%, B. Braun Melsungen AG) for a projected period of 8 weeks. The primary endpoint is the combined change of liver function parameters (total bilirubin, aspartate transaminase and alanine transaminase) from baseline to final visit. Secondary objectives are the further evaluation of the safety and tolerability as well as the efficacy of the ILEs. DISCUSSION: Currently, there are only very few randomized controlled trials (RCTs) investigating the use of ILEs in HPN, and there are very few data at all on the use of n-3 PUFAs. The working hypothesis is that n-3 PUFA-enriched ILE is safe and well-tolerated especially with regard to liver function in patients requiring HPN. The expected outcome is to provide reliable data to support this thesis thanks to a considerable number of CIF patients, consequently to broaden the present evidence on the use of ILEs in HPN. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03282955. Registered on 14 September 2017

7th Annual Seminar on Securities Law

Materials from the UK/CLE 7th Annual Seminar on Securities Law held February 12-13, 1988

The Fourteenth Data Release of the Sloan Digital Sky Survey: First Spectroscopic Data from the extended Baryon Oscillation Spectroscopic Survey and from the second phase of the Apache Point Observatory Galactic Evolution Experiment

The fourth generation of the Sloan Digital Sky Survey (SDSS-IV) has been in operation since July 2014. This paper describes the second data release from this phase, and the fourteenth from SDSS overall (making this, Data Release Fourteen or DR14). This release makes public data taken by SDSS-IV in its first two years of operation (July 2014-2016). Like all previous SDSS releases, DR14 is cumulative, including the most recent reductions and calibrations of all data taken by SDSS since the first phase began operations in 2000. New in DR14 is the first public release of data from the extended Baryon Oscillation Spectroscopic Survey (eBOSS); the first data from the second phase of the Apache Point Observatory (APO) Galactic Evolution Experiment (APOGEE-2), including stellar parameter estimates from an innovative data driven machine learning algorithm known as "The Cannon"; and almost twice as many data cubes from the Mapping Nearby Galaxies at APO (MaNGA) survey as were in the previous release (N = 2812 in total). This paper describes the location and format of the publicly available data from SDSS-IV surveys. We provide references to the important technical papers describing how these data have been taken (both targeting and observation details) and processed for scientific use. The SDSS website (www.sdss.org) has been updated for this release, and provides links to data downloads, as well as tutorials and examples of data use. SDSS-IV is planning to continue to collect astronomical data until 2020, and will be followed by SDSS-V.Comment: SDSS-IV collaboration alphabetical author data release paper. DR14 happened on 31st July 2017. 19 pages, 5 figures. Accepted by ApJS on 28th Nov 2017 (this is the "post-print" and "post-proofs" version; minor corrections only from v1, and most of errors found in proofs corrected

On the Relationship Between the Optical Emission-Line and X-ray Luminosities in Seyfert 1 Galaxies

We have explored the relationship between the [O III] $\lambda$5007 and the 2--10 keV luminosities for a sample of Broad- and Narrow-Line Seyfert 1 galaxies (BLSy1 and NLSy1, respectively). We find that both types of Seyferts span the same range in luminosity and possess similar [O III]/X-ray ratios. The NLSy1s are more luminous than BLSy1s, when normalized to their central black hole masses, which is attributed to higher mass accretion rates. However, we find no evidence for elevated [O III]/X-ray ratios in NLSy1s, which would have been expected if they had excess EUV continuum emission compared to BLSy1s. Also, other studies suggest that the gas in narrow-line regions (NLR) of NLSy1s and NLSy1s span a similar range in ionization, contrary to what is expected if those of the former are exposed to a stronger flux of EUV radiation. The simplest interpretation is that, like BLSy1s, a large EUV bump is not present in NLSy1s. However, we show that the [OIII]/X-ray ratio can be lowered as a result of absorption of the ionizing continuum by gas close to the central source, although there is no evidence that intrinsic line-of-sight absorption is more common among NLSy1s, as would be expected if there were a larger amount of circumnuclear gas. Other possible explanations include: 1) anisotropic emission of the ionizing radiation, 2) higher gas densities in the NLR of NLSy1s, resulting in lower average ionization, or 3) the presence of strong winds in the the nuclei of NLSy1s which may drive off much of the gas in the narrow-line region, resulting in lower cover fraction and weaker [O III] emission.Comment: 18 pages, including 3 figures, 2 tables. Accepted for publication in The Astrophysical Journa