“Why archive?” and Other Important Questions Asked by Occupiers

As the Occupy Wall Street (OWS) movement began to take shape in Zuccotti Park—also known as Liberty Square—in New York City, an archives working group formed as a collective interested in preserving the physical and digital documents created by activists in the movement. Members of the Archives Working Group (AWG) were faced with a unique set of challenges, as well as the opportunity to address these challenges in an independent, non-hierarchical, non-institutional setting. Consensus-based decision-making drove the actions of the group, but competing visions also needed to be reconciled. Some of the most common questions about the role and function of archives required explanation, both within and beyond the working group. The desire and need to interact with the archives’ creators was integral to the establishment of the OWS AWG's collection. Managing relationships with any set of living donors is inherently complicated, and the occupiers we found ourselves working with represented a dynamic group of content creators and contributors. Activists ask a lot of questions. By definition activists are challenging the status quo. As members of the AWG, we were asked a lot of very valid questions including: “What is an archive? Is there a difference between art and archives?” “What are you collecting?” “Who will have access to what you are collecting?” “Where is this stuff going to be kept?” “Are you trying to collect all the archives produced in the movement?” “Why collect this?” and “Why not this?” “What do archivists do and why?” “Why should archives matter to people in the movement?” These questions and how we answered them serve as the foundation for this chapter. We will elaborate on our answers to activists’ questions and put forth an analysis of archival theory as related to some of the questions with especially complex implications. The formation of a digital archive also brought up some issues that are beyond those most relevant to the discussion of management of and access to analog archives. Part of this essay is dedicated to the ways in which we addressed these particular concerns. We will conclude with lessons learned in the process of creating a collection of physical and digital archives coming out of Occupy Wall Street in 2011-2012

Imprecise recombinant viruses evolve via a fitness-driven, iterative process of polymerase template-switching events

Funding: This work was supported by the Biotechnology and Biological Sciences Research Council - https://bbsrc.ukri.org/ - (BB/M009343/1 to D.J.E) and an ISSF award from The Wellcome Trust - https://wellcome.org/ - to the BSRC, University of St Andrews. F.G.A was supported by a PhD studentship from the Ministry of Education, Government of Saudi Arabia. S.J was supported by a Microbiology Society - https://microbiologysociety.org/ - Harry Smith Vacation Studentship awarded to K.B.Viruses with positive-sense RNA genomes, such as poliovirus, have several mechanisms by which they evolve. One of these is the process of recombination involving the large-scale exchange of genetic information. Recombination occurs during replication when the viral polymerase, bound to the nascent RNA chain, switches from copying one genome to another. However, the polymerase does not always accurately switch between the two, resulting in sequence duplications or deletions, and genomes that are referred to as imprecise. Over multiple rounds of replication sequence duplications are lost and genomes are resolved to wild type length, but it is unclear how this occurs. Here we used synthetic polioviruses containing defined sequence duplications to determine that the genome population undergoes repeated rounds of recombination until sequence duplications are lost and viruses with precise, wild type length genomes are selected for. This selection is based on the overall fitness of the virus population, with less fit imprecise viruses evolving more quickly. Our study suggests that recombination is a continual process where virus fitness drives the selection of a small subset of recombinant variants. These data are important for understanding how novel viruses evolve via recombination and how this process can be blocked to prevent novel and dangerous pathogens from arising.Publisher PDFPeer reviewe

The Application of a Hypothesis-driven Strategy to the Sensitive Detection and Location of Acetylated Lysine Residues

The application of a hypothesis-driven method for the sensitive determination of lysine acetylation sites on enzymatically digested proteins is described. Comparative sensitivity tests were carried out using serial dilution of an acetylated bovine serum albumin (AcBSA) digest to assess the performance of a multiple reaction monitoring (MRM)–based approach as compared to a more conventional precursor scanning (PS) method. Both methods were capable of selectively detecting an acetylated peptide at the low femtomole level when spiked into a background of 500 fmol six-protein tryptic digest. The MRM approach was roughly tenfold more sensitive than precursor scanning with one acetylated peptide detected and sequenced at the level of 2 fmol on-column. The technique was subsequently applied to a gel-derived sample of cytokeratin-8 (CK8) shown to contain acetylated lysine residues by Western blot analysis. The strategy applied herein, termed MRM-initiated detection and sequencing (MIDAS), resulted in the facile identification of novel sites of acetylation on this protein

A non-canonical ESCRT pathway, including histidine domain phosphotyrosine phosphatase (HD-PTP), is used for down-regulation of virally ubiquitinated MHC class I.

The Kaposi's sarcoma-associated herpes virus (KSHV) K3 viral gene product effectively down-regulates cell surface MHC class I. K3 is an E3 ubiquitin ligase that promotes Lys(63)-linked polyubiquitination of MHC class I, providing the signal for clathrin-mediated endocytosis. Endocytosis is followed by sorting into the intralumenal vesicles (ILVs) of multivesicular bodies (MVBs) and eventual delivery to lysosomes. The sorting of MHC class I into MVBs requires many individual proteins of the four endosomal sorting complexes required for transport (ESCRTs). In HeLa cells expressing the KSHV K3 ubiquitin ligase, the effect of RNAi-mediated depletion of individual proteins of the ESCRT-0 and ESCRT-I complexes and three ESCRT-III proteins showed that these are required to down-regulate MHC class I. However, depletion of proteins of the ESCRT-II complex or of the ESCRT-III protein, VPS20 (vacuolar protein sorting 20)/CHMP6 (charged MVB protein 6), failed to prevent the loss of MHC class I from the cell surface. Depletion of histidine domain phosphotyrosine phosphatase (HD-PTP) resulted in an increase in the cell surface concentration of MHC class I in HeLa cells expressing the KSHV K3 ubiquitin ligase. Rescue experiments with wild-type (WT) and mutant HD-PTP supported the conclusion that HD-PTP acts as an alternative to ESCRT-II and VPS20/CHMP6 as a link between the ESCRT-I and those ESCRT-III protein(s) necessary for ILV formation. Thus, the down-regulation of cell surface MHC class I, polyubiquitinated by the KSHV K3 ubiquitin ligase, does not employ the canonical ESCRT pathway, but instead utilizes an alternative pathway in which HD-PTP replaces ESCRT-II and VPS20/CHMP6.This work was supported by an MRC research grant to J.P.L. (G0900113). M.D.J.P. and J.L.E. were MRC research students and S.P. a Wellcome Trust research student. K.B. was a British Heart Foundation Intermediate Fellow and P.J.L. is a Wellcome Trust Principal Fellow. The CIMR is supported by a Wellcome Trust Strategic Award 100140 and an electron microscope was purchased with Wellcome Trust grant 093026.This is the final version of the article. It first appeared from Portland Press via http://dx.doi.org/10.1042/BJ2015033

Polymorphism in M(H2PO2)3 (M = V, Al, Ga) compounds with the perovskite-related ReO3 structure.

Trivalent metal hypophosphites with the general formula M(H2PO2)3 (M = V, Al, Ga) adopt the ReO3 structure, with each compound displaying two structural polymorphs. High-pressure synchrotron X-ray studies reveal a pressure-driven phase transition in Ga(H2PO2)3 that can be understood on the basis of ab initio thermodynamics

Open Research, and Professional and Technical Support Staff

This short report summarises some reflections of professional and technical support staff on their perspectives on open research. The reflections are based on input to, and discussions at, a community workshop and roundtable event co-convened by UKRN and Jisc on 20th February 2023. The report is intended to inform discussions within groups of staff in similar roles, across different professional and academic groupings in institutions, and with other stakeholders such as funders

Probing the interplay between factors determining reaction rates on silica gel using termolecular systems

This article was published in the journal, Photochemical and Photobiological Sciences [© Royal Society of Chemistry and Owner Societies]. The definitive version is available at: http://dx.doi.org/10.1039/c2pp25171jIn this study we have compared energy and electron transfer reactions in termolecular systems using a nanosecond diffuse reflectance laser flash photolysis technique. We have previously investigated these processes on silica gel surfaces for bimolecular systems and electron transfer in termolecular systems. The latter systems involved electron transfer between three arene molecules with azulene acting as a molecular shuttle. In this study we present an alternative electron transfer system using trans β-carotene as an electron donor in order to effectively immobilise all species except the shuttle, providing the first unambiguous evidence for radical ion mobility. In the energy transfer system we use naphthalene, a structural isomer of azulene, as the shuttle, facilitating energy transfer from a selectively excited benzophenone sensitiser to 9-cyanoanthracene. Bimolecular rate constants for all of these processes have been measured and new insights into the factors determining the rates of these reactions on silica gel have been obtained

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes

What Design Research Does ... : 62 Cards Highlighting the Power and Impact of UK-based Design Research in Addressing a Range of Complex Social, Economic, Cultural and Environmental Issues

Design research makes a significant contribution to the UK economy and society as a whole. Ever since the establishment of the Government Schools of Design in the nineteenth century, the UK has been widely acknowledged as an international leader in design research. Following this lead, the What Design Research Does… cards highlight the wide range of social, economic, cultural and environmental impacts that design research, funded and based in the UK, makes all over the world. The 62 cards illustrate unambiguously the positive changes that contemporary UK-based design researchers are making in many complex issues. Each What Design Research Does… card lists the challenges and issues faced by the design researchers, who they collaborated with, the research methods and approaches taken, the outcomes of the design research, what the main results and findings have been, and what impact the design research has had. In short, the What Design Research Does… cards clearly articulate the breadth of social, economic, cultural and environmental impacts that UK-based design researchers are achieving today