Ubiquitylation, neddylation and the DNA damage response.

Failure of accurate DNA damage sensing and repair mechanisms manifests as a variety of human diseases, including neurodegenerative disorders, immunodeficiency, infertility and cancer. The accuracy and efficiency of DNA damage detection and repair, collectively termed the DNA damage response (DDR), requires the recruitment and subsequent post-translational modification (PTM) of a complex network of proteins. Ubiquitin and the ubiquitin-like protein (UBL) SUMO have established roles in regulating the cellular response to DNA double-strand breaks (DSBs). A role for other UBLs, such as NEDD8, is also now emerging. This article provides an overview of the DDR, discusses our current understanding of the process and function of PTM by ubiquitin and NEDD8, and reviews the literature surrounding the role of ubiquitylation and neddylation in DNA repair processes, focusing particularly on DNA DSB repair.J.S.B. is funded by the Wellcome Trust Clinical Fellowship (grant no. 094794/Z/10/Z). Research in the Jackson laboratory is funded by Cancer Research UK programme grant C6/A11224, the European Research Council and the European Community Seventh Framework Programme grant agreement no. HEALTH-F2-2010-259893 (DDResponse). Core funding is provided by CRUK (C6946/A14492) and the Wellcome Trust (WT092096). S.P.J. receives his salary from the University of Cambridge UK, supplemented by CRUK.This is the final published version. It first appeared at http://rsob.royalsocietypublishing.org/content/5/4/150018

Novel type of prion involved in glucose signaling and environmental sensing in S. cerevisiae

This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 2008.Includes bibliographical references.Several well-characterized fungal proteins act as prions, proteins capable of multiple conformations, each with different activities, at least one of which is selfpropagating. We report a protein-based heritable element that confers resistance to glucosamine, [GAR⁺]. Genetically it resembles other yeast prions: it appears spontaneously at a rate higher than mutations and is transmissible by non-Mendelian, cytoplasmic inheritance. However, [GAR⁺] is in other ways profoundly different from known prions. [GAR⁺] propagation involves Pmal, the plasma membrane protein pump, and [GAR⁺] formation is induced by Stdl, a member of the Snf3/Rgt2 glucose signaling pathway. Also, [GAR⁺] does not appear to involve the formation of an amyloid template and the prion state represents only a fraction of the Pmal protein in the cell,· consistent with the prion form constituting a complex between Pmal and Stdl, a much lower abundance protein. [GAR⁺] propagation is subject to a strong species barrier, as substitution of PMAl from other Saccharomyces species blocks propagation to s.. cerevisiae PMAl. Direct competition between [gar-] and [GAR⁺] cells indicate that cells carrying [GAR⁺] have an advantage under certain environmental conditions. [GAR⁺] appears spontaneously in a yeast isolated from a variety of sources and can be induced by co-culturing yeast and a number of Staphylococcus species. Overall, [GAR⁺] expands the conceptual framework for self-propagating protein-based elements of inheritance to include non-amyloid, potentially multicomponent systems such as transmembrane proteins and signal transducers.by Jessica C. S. Brown.Ph.D

Understanding the co‐occurrence of tree loss and modern slavery to improve efficacy of conservation actions and policies

Locations where populations are most reliant on forests and their ecosystem services for subsistence and development are also areas where modern slavery persists. These issues are noted within the Sustainable Development Goals (SDGs), both target 15.2 and 8.7 respectively. Often activities using slavery perpetuate deforestation, bolstering a slavery‐environment nexus; which has been examined by comparing modern slavery estimates against environmental protection levels. This study assesses the relationship between tree loss and modern slavery focusing on four countries: Brazil, Ghana, Indonesia, and Mozambique. Previously mapped levels of tree loss and predicted future levels of loss have been compared against modern slavery estimates from the Global Slavery Index 2016 and illegal logging analyses to determine an estimate of the risk for slavery related tree loss. These results provide an insight in to the co‐occurrence between modern slavery and tree loss due to a number of activities that are highlighted, including mining, illegal logging, and agricultural practices. The co‐occurrence is both complex, and yet, beyond coincidental. Implications for both national and global policy are noted assessing the benefits that could be achieved by limiting tree loss and ending modern slavery; of benefit to both the conservation and antislavery communities

Operational Radiology Recovery in Academic Radiology Departments After the COVID-19 Pandemic: Moving Toward Normalcy

This article presents a current snapshot in time, describing how radiology departments around the country are planning recovery from the baseline of the coronavirus disease 2019 pandemic, with a focus on different domains of recovery such as managing appointment availability, patient safety and workflow changes, and operational data and analytics. An e-mail survey was sent through the Society of Chairs of Academic Radiology Departments list server to 114 academic radiology departments. On the basis of data reported by the 38 survey respondents, best practices and shared experience are described for three key areas: (1) planning for recovery, (2) creating a new normal, and (3) measuring and forecasting. Radiology practices should be aware of the common approaches and preparations academic radiology departments have taken to reopening imaging in the post-coronavirus disease 2019 world. This should all be done when maintaining a safe and patient-centric environment and preparing to minimize the impact of future outbreaks or pandemics

Neddylation promotes ubiquitylation and release of Ku from DNA-damage sites.

The activities of many DNA-repair proteins are controlled through reversible covalent modification by ubiquitin and ubiquitin-like molecules. Nonhomologous end-joining (NHEJ) is the predominant DNA double-strand break (DSB) repair pathway in mammalian cells and is initiated by DSB ends being recognized by the Ku70/Ku80 (Ku) heterodimer. By using MLN4924, an anti-cancer drug in clinical trials that specifically inhibits conjugation of the ubiquitin-like protein, NEDD8, to target proteins, we demonstrate that NEDD8 accumulation at DNA-damage sites is a highly dynamic process. In addition, we show that depleting cells of the NEDD8 E2-conjugating enzyme, UBE2M, yields ionizing radiation hypersensitivity and reduced cell survival following NHEJ. Finally, we demonstrate that neddylation promotes Ku ubiquitylation after DNA damage and release of Ku and Ku-associated proteins from damage sites following repair. These studies provide insights into how the NHEJ core complex dissociates from repair sites and highlight its importance for cell survival following DSB induction.We thank Thimo Kurz (University of Dundee, UK) for providing MLN4924 and Kate Dry, Rimma Berlotserkovskaya (S.P.J.’s laboratory), and Eric Lightcap (Takeda Pharmaceuticals) for critical reading of the manuscript. We thank Sylvie Urbe and Michael Clague (University of Liverpool, UK) for providing the GFP-CSN5 plasmid, the Division of Signal Transduction Therapy (University of Dundee, UK) for providing UBE2M and UBE2F plasmids, Matthew Petroski (Sanford-Burnham Medical Research Institute, US) for providing FLAG-UBA3 wild-type (WT) and FLAG-UBA3-A171T constructs, and Nico Dantuma (Karolinska Institute, Sweden) and Changshun Shao (Rutgers University) for providing CUL4A and CUL4B plasmids, respectively. We also thank Nicola Lawrence, Alex Sossick, and Richard Butler (Gurdon Institute, Cambridge, UK) for help with microscopy, Volocity, and Fiji. Research in the S.P.J.’s laboratory is funded by Cancer Research UK programme grant C6/A11224, the European Research Council, and the European Community Seventh Framework Programme grant agreement no. HEALTH-F2-2010-259893 (DDResponse). Core funding is provided by CRUK (C6946/A14492) and the Wellcome Trust (WT092096). S.P.J. receives his salary from the University of Cambridge, UK, supplemented by CRUK. N.L. is funded by CRUK programme grant C6/A11224, J.S.B. is funded by a Wellcome Trust Clinical Fellowship (WT083416), and Y.G. and M.S.-C. are funded by European Research Council grant DDREAM. S.B. was funded by an EMBO long-term fellowship ALTF 93-2010, Cancer Research UK, and a post-doctoral grant from Ligue Nationale Contre le Cancer. P.B. is supported by the Emmy Noether Programme of the German Research Foundation (DFG, BE 5342/1-1).This is the final published version. It first appeared at http://www.sciencedirect.com/science/article/pii/S2211124715003496

(1-Bromo­naphthalen-2-yl)acetonitrile

The title compound, C12H8BrN, was prepared as a starting material for a Suzuki cross-coupling reaction with a pinacol ester. The torsion angle about the ring–methylene C—C bond is 30.7 (3)°, such that the N atom is displaced by 1.174 (4) Å from the plane of the naphthalene ring system

Increased rates of large-magnitude explosive eruptions in Japan in the late Neogene and Quaternary

Tephra layers in marine sediment cores from scientific ocean drilling largely record high-magnitude silicic explosive eruptions in the Japan arc for up to the last 20 million years. Analysis of the thickness variation with distance of 180 tephra layers from a global dataset suggests that the majority of the visible tephra layers used in this study are the products of caldera-forming eruptions with magnitude (M) >6, considering their distances at the respective drilling sites to their likely volcanic sources. Frequency of visible tephra layers in cores indicates a marked increase in rates of large magnitude explosive eruptions at ~8 Ma, 6–4 Ma and further increase after ~2 Ma. These changes are attributed to major changes in tectonic plate interactions. Lower rates of large magnitude explosive volcanism in the Miocene are related to a strike-slip dominated boundary (and temporary cessation or deceleration of subduction) between the Philippine Sea Plate and southwest Japan, combined with the possibility that much of the arc in northern Japan was submerged beneath sea level partly due to previous tectonic extension of Northern Honshu related to formation of the Sea of Japan. Changes in plate motions and subduction dynamics during the ~8 Ma to present period led to (1) increased arc-normal subduction in southwest Japan (and resumption of arc volcanism) and (2) shift from extension to compression of the upper plate in northeast Japan, leading to uplift, crustal thickening and favourable conditions for accumulation of the large volumes of silicic magma needed for explosive caldera-forming eruptions

Special Libraries, October 1922

Volume 13, Issue 8https://scholarworks.sjsu.edu/sla_sl_1922/1007/thumbnail.jp

The Albany Birth Justice Storytelling Project

The ABJS Project is participatory action research that combines a photovoice and transformative storytelling approach to collect qualitative data on the experience of Black birthing people from Albany who are impacted by racial inequities in birth outcomes. The methodology promotes self-reflective, trauma informed education and care among co-researchers, including undergraduate students and storytellers from Albany County. Sample photovoice narratives are included, along with an annotated bibliography