Methanol maps of low-mass protostellar systems: the Serpens Molecular Core

Observations of Serpens have been performed at the JCMT using Harp-B. Maps over a 4.5'x5.4' region were made in a frequency window around 338 GHz, covering the 7-6 transitions of methanol. Emission is extended over each source, following the column density of H2 but showing up also particularly strongly around outflows. The rotational temperature is low, 15-20 K, and does not vary with position within each source. The abundance is typically 10^-9 - 10^-8 with respect to H2 in the outer envelope, whereas "jumps" by factors of up to 10^2 -10^3 inside the region where the dust temperature exceeds 100 K are not excluded. A factor of up to ~ 10^3 enhancement is seen in outflow gas. In one object, SMM4, the ice abundance has been measured to be ~ 3x10^-5 with respect to H2 in the outer envelope, i.e., a factor of 10^3 larger than the gas-phase abundance. Comparison with C18O J=3-2 emission shows that strong CO depletion leads to a high gas-phase abundance of CH3OH not just for the Serpens sources, but for a larger sample of protostars. The observations illustrate the large-scale, low-level desorption of CH3OH from dust grains, extending out to and beyond 7500 AU from each source, a scenario which is consistent with non-thermal (photo-)desorption from the ice. The observations also illustrate the usefulness of CH3OH as a tracer of energetic input in the form of outflows, where methanol is sputtered from the grain surfaces. Finally, the observations provide further evidence of CH3OH formation through CO hydrogenation proceeding on grain surfaces in low-mass envelopes.Comment: Accepted for publication in A&A

Subarcsecond resolution observations of warm water towards three deeply embedded low-mass protostars

Water is present during all stages of star formation: as ice in the cold outer parts of protostellar envelopes and dense inner regions of circumstellar disks, and as gas in the envelopes close to the protostars, in the upper layers of circumstellar disks and in regions of powerful outflows and shocks. In this paper we probe the mechanism regulating the warm gas-phase water abundance in the innermost hundred AU of deeply embedded (Class~0) low-mass protostars, and investigate its chemical relationship to other molecular species during these stages. Millimeter wavelength thermal emission from the para-H2-18O 3(1,3)-2(2,0) (Eu=203.7 K) line is imaged at high angular resolution (0.75"; 190 AU) with the IRAM Plateau de Bure Interferometer towards the deeply embedded low-mass protostars NGC 1333-IRAS2A and NGC 1333-IRAS4A. Compact H2-18O emission is detected towards IRAS2A and one of the components in the IRAS4A binary; in addition CH3OCH3, C2H5CN, and SO2 are detected. Extended water emission is seen towards IRAS2A, possibly associated with the outflow. The detections in all systems suggests that the presence of water on <100 AU scales is a common phenomenon in embedded protostars. We present a scenario in which the origin of the emission from warm water is in a flattened disk-like structure dominated by inward motions rather than rotation. The gas-phase water abundance varies between the sources, but is generally much lower than a canonical abundance of 10^-4, suggesting that most water (>96 %) is frozen out on dust grains at these scales. The derived abundances of CH3OCH3 and SO2 relative to H2-18O are comparable for all sources pointing towards similar chemical processes at work. In contrast, the C2H5CN abundance relative to H2-18O is significantly lower in IRAS2A, which could be due to different chemistry in the sources.Comment: 12 pages, 9 figure

A New CYP2E1 Inhibitor, 12-Imidazolyl-1-dodecanol, Represents a Potential Treatment for Hepatocellular Carcinoma

Cytochrome P450 2E1 (CYP2E1) is a key target protein in the development of alcoholic and nonalcoholic fatty liver disease (FLD). The pathophysiological correlate is the massive production of reactive oxygen species. The role of CYP2E1 in the development of hepatocellular carcinoma (HCC), the final complication of FLD, remains controversial. Specifically, CYP2E1 has not yet been defined as a molecular target for HCC therapy. In addition, a CYP2E1-specific drug has not been developed. We have already shown that our newly developed CYP2E1 inhibitor 12-imidazolyl-1-dodecanol (I-ol) was therapeutically effective against alcoholic and nonalcoholic steatohepatitis. In this study, we investigated the effect of I-ol on HCC tumorigenesis and whether I-ol could serve as a possible treatment option for terminal-stage FLD. I-ol exerted a very highly significant antitumour effect against hepatocellular HepG2 cells. Cell viability was reduced in a dose-dependent manner, with only the highest doses causing a cytotoxic effect associated with caspase 3/7 activation. Comparable results were obtained for the model colorectal adenocarcinoma cell line, DLD-1, whose tumorigenesis is also associated with CYP2E1. Transcriptome analyses showed a clear effect of I-ol on apoptosis and cell-cycle regulation, with the increased expression of p27Kip1 being particularly noticeable. These observations were confirmed at the protein level for HepG2 and DLD-1 cells grafted on a chorioallantoic membrane. Cell-cycle analysis showed a complete loss of proliferating cells with a simultaneous increase in S-phase arrest beginning at a threshold dose of 30 μM. I-ol also reduced xenograft tumour growth in nude mice. This antitumour effect was not associated with tumour cachexia. I-ol was not toxic to healthy tissues or organs. This study demonstrates for the first time the therapeutic effect of the specific CYP2E1 inhibitor I-ol on the tumorigenesis of HCC. Our findings imply that I-ol can potentially be applied therapeutically on patients at the final stage of FLD. © 2021 Torsten Diesinger et al

Lacerated Lips and Lush Landscapes: Constructing This-Worldly Theological Identities in the Otherworld

When Irenaeus juxtaposed tradition and heresy, he moved away from the Pauline usage, which centered primarily upon incorrect behavior (See 1 Cor 11: 19, Gal 5 :20). lrenaeus\u27 definition of heresy, however, does not indicate that all early Christians prioritized belief over behavior, or even maintained orthodoxy and orthopraxis as separate categories. In the otherworldly spaces of the apocryphal apocalypses doxa and praxis seem to be intertwined, and little or no distinction is made between belief and behavior. Instead, in the Otherworld the categories of primary importance are righteous/unrighteous, good/evil, Christian/Other. The Otherworld is a place in which sins can be sorted and the identity markers which might have been overlooked or are difficult to see in this world can be seen more clearly. And yet, we are left to wonder how that otherworldly clarity maps onto the lived experience of the ancient audiences of these apocalypses. Thus, we will begin by reflecting upon the ability of these apocalyptic texts to create (and recreate) Christian identity by either describing real categories of people, or by creating the categories themselves, and so prescribing reality. In each of the apocalypses that we will discuss the reader learns that his or her identity is determined for all of eternity by the choices that are made in this world. In this regard, each depiction of the otherworld establishes its own identity markers, isolating certain beliefs and behaviors as distinctively Christian. What is startling about the definitions of Christian belief and practice that emerge from each text is that they are rather expansive, covering far more territory than any creed or council. Our discussion will demonstrate that while creedal definitions of orthodoxy ( as well as the apocalyptic definitions of correct belief that mirror them) were often aimed at labeling specific groups as other, the apocalyptic depictions of the otherworld were attempting to be either exhaustive or open-ended, imagining a host of practices that could be used to frame Christian identity. In these imaginary spaces, the theological identities that were crafted could not simply be summarized by simple binaries like orthodoxy/heterodoxy, oppressed/oppressor, or even sinner/sinless. Instead, the apocalyptic visions, which on the surface seem to deal in dichotomies, paradoxically proliferate a range of Christian practices

Preclinical evidence implicating corticotropin-releasing factor signaling in ethanol consumption and neuroadaptation

The results of many studies support the influence of the corticotropin-releasing factor (CRF) system on ethanol (EtOH) consumption and EtOH-induced neuroadaptations that are critical in the addiction process. This review summarizes the preclinical data in this area after first providing an overview of the components of the CRF system. This complex system involves hypothalamic and extra-hypothalamic mechanisms that play a role in the central and peripheral consequences of stressors, including EtOH and other drugs of abuse. In addition, several endogenous ligands and targets make up this system and show differences in their involvement in EtOH drinking and in the effects of chronic or repeated EtOH treatment. In general, genetic and pharmacological approaches paint a consistent picture of the importance of CRF signaling via type 1 CRF receptors (CRF1) in EtOH-induced neuroadaptations that result in higher levels of intake, encourage alcohol seeking during abstinence and alter EtOH sensitivity. Furthermore, genetic findings in rodents, non-human primates and humans have provided some evidence of associations of genetic polymorphisms in CRF-related genes with EtOH drinking, although additional data are needed. These results suggest that CRF1 antagonists have potential as pharmacotherapeutics for alcohol use disorders. However, given the broad and important role of these receptors in adaptation to environmental and other challenges, full antagonist effects may be too profound and consideration should be given to treatments with modulatory effects.The authors were supported by the Department of Veterans Affairs; NIH NIAAA grants P60AA010760, R24AA020245 and U01AA013519 and NIH NIDA grant P50DA018165, during the writing of this manuscript. The authors have no financial conflict of interest to disclose

Eating disorders: the current status of molecular genetic research

Anorexia nervosa (AN) and bulimia nervosa (BN) are complex disorders characterized by disordered eating behavior where the patient’s attitude towards weight and shape, as well as their perception of body shape, are disturbed. Formal genetic studies on twins and families suggested a substantial genetic influence for AN and BN. Candidate gene studies have initially focused on the serotonergic and other central neurotransmitter systems and on genes involved in body weight regulation. Hardly any of the positive findings achieved in these studies were unequivocally confirmed or substantiated in meta-analyses. This might be due to too small sample sizes and thus low power and/or the genes underlying eating disorders have not yet been analyzed. However, some studies that also used subphenotypes (e.g., restricting type of AN) led to more specific results; however, confirmation is as yet mostly lacking. Systematic genome-wide linkage scans based on families with at least two individuals with an eating disorder (AN or BN) revealed initial linkage regions on chromosomes 1, 3 and 4 (AN) and 10p (BN). Analyses on candidate genes in the chromosome 1 linkage region led to the (as yet unconfirmed) identification of certain variants associated with AN. Genome-wide association studies are under way and will presumably help to identify genes and pathways involved in these eating disorders. The elucidation of the molecular mechanisms underlying eating disorders might improve therapeutic approaches

Functional significance of the taper of vertebrate cone photoreceptors

© The Author(s), 2012. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Journal of General Physiology 139 (2012): 159-187, doi:10.1085/jgp.201110692.Vertebrate photoreceptors are commonly distinguished based on the shape of their outer segments: those of cones taper, whereas the ones from rods do not. The functional advantages of cone taper, a common occurrence in vertebrate retinas, remain elusive. In this study, we investigate this topic using theoretical analyses aimed at revealing structure–function relationships in photoreceptors. Geometrical optics combined with spectrophotometric and morphological data are used to support the analyses and to test predictions. Three functions are considered for correlations between taper and functionality. The first function proposes that outer segment taper serves to compensate for self-screening of the visual pigment contained within. The second function links outer segment taper to compensation for a signal-to-noise ratio decline along the longitudinal dimension. Both functions are supported by the data: real cones taper more than required for these compensatory roles. The third function relates outer segment taper to the optical properties of the inner compartment whereby the primary determinant is the inner segment’s ability to concentrate light via its ellipsoid. In support of this idea, the rod/cone ratios of primarily diurnal animals are predicted based on a principle of equal light flux gathering between photoreceptors. In addition, ellipsoid concentration factor, a measure of ellipsoid ability to concentrate light onto the outer segment, correlates positively with outer segment taper expressed as a ratio of characteristic lengths, where critical taper is the yardstick. Depending on a light-funneling property and the presence of focusing organelles such as oil droplets, cone outer segments can be reduced in size to various degrees. We conclude that outer segment taper is but one component of a miniaturization process that reduces metabolic costs while improving signal detection. Compromise solutions in the various retinas and retinal regions occur between ellipsoid size and acuity, on the one hand, and faster response time and reduced light sensitivity, on the other.This work was funded by the Natural Sciences and Engineering Research Council of Canada Discovery Grant 238886 and a Grass-Marine Biological Laboratory Sabbatical Fellowship in Neurosciences to I. Novales Flamarique.2012-07-1

Global wealth disparities drive adherence to COVID-safe pathways in head and neck cancer surgery

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