Effect of Lipid Raft Disruption on Ethanol Inhibition of L1 Adhesion

Background: Alcohol causes fetal alcohol spectrum disorders in part by disrupting the function of the neural cell adhesion molecule L1. Alcohol inhibits L1-mediated cell–cell adhesion in diverse cell types and inhibits L1-mediated neurite outgrowth in cerebellar granule neurons (CGNs). A recent report indicates that ethanol (EtOH) induces the translocation of L1 into CGN lipid rafts and that disruption of lipid rafts prevents EtOH inhibition of L1-mediated neurite outgrowth. The same butanol–pentanol cutoff was noted for alcohol-induced translocation of L1 into lipid rafts that was reported previously for alcohol inhibition of L1 adhesion, suggesting that EtOH might inhibit L1 adhesion by shifting L1 into lipid rafts. Methods: The NIH/3T3 cell line, 2A2-L1s, is a well-characterized EtOH-sensitive clonal cell line that stably expresses human L1. Cells were treated with 25 mM EtOH, 5 μM filipin, or both. Lipid rafts were enriched in membrane fractions by preparation of detergent-resistant membrane (DRMs) fractions. Caveolin-1 was used as a marker of lipid rafts, and L1 and Src were quantified by Western blotting in lipid-raft-enriched membrane fractions and by immunohistochemistry. Results: EtOH (25 mM) increased the percentage of L1, but not Src, in 2A2-L1s membrane fractions enriched in lipid rafts. Filipin, an agent known to disrupt lipid rafts, decreased the percentage of caveolin and L1 in DRMs from 2A2-L1s cells. Filipin also blocked EtOH-induced translocation of L1 into lipid rafts from 2A2-L1s cells but did not significantly affect L1 adhesion or EtOH inhibition of L1 adhesion. Conclusions: These findings indicate that EtOH does not inhibit L1 adhesion in NIH/3T3 cells by inducing the translocation of L1 into lipid rafts

Asymmetric Synthesis of Furan and Oxindole Derivatives with Bifunctional and Multifunctional Organic Catalysts

Ph.DDOCTOR OF PHILOSOPH

let‐7‐repressesed S hc translation delays replicative senescence

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102709/1/acel12176.pd

The Non-Coding RNA Ontology (NCRO): a comprehensive resource for the unification of non-coding RNA biology

In recent years, sequencing technologies have enabled the identification of a wide range of non-coding RNAs (ncRNAs). Unfortunately, annotation and integration of ncRNA data has lagged behind their identification. Given the large quantity of information being obtained in this area, there emerges an urgent need to integrate what is being discovered by a broad range of relevant communities. To this end, the Non-Coding RNA Ontology (NCRO) is being developed to provide a systematically structured and precisely defined controlled vocabulary for the domain of ncRNAs, thereby facilitating the discovery, curation, analysis, exchange, and reasoning of data about structures of ncRNAs, their molecular and cellular functions, and their impacts upon phenotypes. The goal of NCRO is to serve as a common resource for annotations of diverse research in a way that will significantly enhance integrative and comparative analysis of the myriad resources currently housed in disparate sources. It is our belief that the NCRO ontology can perform an important role in the comprehensive unification of ncRNA biology and, indeed, fill a critical gap in both the Open Biological and Biomedical Ontologies (OBO) Library and the National Center for Biomedical Ontology (NCBO) BioPortal. Our initial focus is on the ontological representation of small regulatory ncRNAs, which we see as the first step in providing a resource for the annotation of data about all forms of ncRNAs. The NCRO ontology is free and open to all users, accessible at: http://purl.obolibrary.org/obo/ncro.owl

A4. En tekst om å ville â og ikke ville være vanlig

People living outside conventional families have to grapple with the concept of ordinariness. If their lives are not seen as ordinary intimate lives, what life choices and narrative choices do they have in claiming and responding to this extraordinariness? The article explores ordinariness as a theoretical and cultural concept, and shows how both theoretical approaches and self-narratives can have very different as well as ambivalent attitudes towards ordinariness

Real-time Monitoring for the Next Core-Collapse Supernova in JUNO

Core-collapse supernova (CCSN) is one of the most energetic astrophysical events in the Universe. The early and prompt detection of neutrinos before (pre-SN) and during the SN burst is a unique opportunity to realize the multi-messenger observation of the CCSN events. In this work, we describe the monitoring concept and present the sensitivity of the system to the pre-SN and SN neutrinos at the Jiangmen Underground Neutrino Observatory (JUNO), which is a 20 kton liquid scintillator detector under construction in South China. The real-time monitoring system is designed with both the prompt monitors on the electronic board and online monitors at the data acquisition stage, in order to ensure both the alert speed and alert coverage of progenitor stars. By assuming a false alert rate of 1 per year, this monitoring system can be sensitive to the pre-SN neutrinos up to the distance of about 1.6 (0.9) kpc and SN neutrinos up to about 370 (360) kpc for a progenitor mass of 30$M_{\odot}$ for the case of normal (inverted) mass ordering. The pointing ability of the CCSN is evaluated by using the accumulated event anisotropy of the inverse beta decay interactions from pre-SN or SN neutrinos, which, along with the early alert, can play important roles for the followup multi-messenger observations of the next Galactic or nearby extragalactic CCSN.Comment: 24 pages, 9 figure

Schizophrenia-associated somatic copy-number variants from 12,834 cases reveal recurrent NRXN1 and ABCB11 disruptions

While germline copy-number variants (CNVs) contribute to schizophrenia (SCZ) risk, the contribution of somatic CNVs (sCNVs)—present in some but not all cells—remains unknown. We identified sCNVs using blood-derived genotype arrays from 12,834 SCZ cases and 11,648 controls, filtering sCNVs at loci recurrently mutated in clonal blood disorders. Likely early-developmental sCNVs were more common in cases (0.91%) than controls (0.51%, p = 2.68e−4), with recurrent somatic deletions of exons 1–5 of the NRXN1 gene in five SCZ cases. Hi-C maps revealed ectopic, allele-specific loops forming between a potential cryptic promoter and non-coding cis-regulatory elements upon 5′ deletions in NRXN1. We also observed recurrent intragenic deletions of ABCB11, encoding a transporter implicated in anti-psychotic response, in five treatment-resistant SCZ cases and showed that ABCB11 is specifically enriched in neurons forming mesocortical and mesolimbic dopaminergic projections. Our results indicate potential roles of sCNVs in SCZ risk

Factors Influence China’s Off-Site Construction Technology Innovation Diffusion

Technology innovation is a key to Off-Site Construction (OSC), but it can achieve economic and social benefits through diffusion. Previous research mainly focused on the optimization or on-site applications of OSC technology innovation; little on its diffusion-related analysis. Diffusion performance generally leads to a faster and deeper diffusion of OSC technology innovation. To study what influence the diffusion performance of OSC technology innovation, the authors first determined the research border and proposed four hypotheses, and then conducted a questionnaire in various China’s construction companies. After investigating 119 construction companies for three months, 151 valid responses were collected and analyzed using Hierarchical Regression and bootstrap-based mediation test approaches. The results found that both market and government had significant impacts on the diffusion performance with comparable influence degree (0.282** and 0.255**), the government played a dual-mediating effect with network power simultaneously (effect value is 0.215) and the technical versatility had a significant indirect influence (>0.204**) but weak direct impact (0.094) on the diffusion performance of OSC technology innovation. The conclusions explored the influence mechanism of different factors on the diffusion of OSC technology innovation and provided practical suggestions for both construction companies and government authorities to promote the development of OSC