med G{alpha}q splice variants mediate phototransduction, rhodopsin synthesis, and retinal integrity in Drosophila [Signal Transduction] By www.jbc.org Published On :: 2020-04-24T06:08:45-07:00 Heterotrimeric G proteins mediate a variety of signaling processes by coupling G protein–coupled receptors to intracellular effector molecules. In Drosophila, the Gαq gene encodes several Gαq splice variants, with the Gαq1 isoform protein playing a major role in fly phototransduction. However, Gαq1 null mutant flies still exhibit a residual light response, indicating that other Gαq splice variants or additional Gq α subunits are involved in phototransduction. Here, we isolated a mutant fly with no detectable light responses, decreased rhodopsin (Rh) levels, and rapid retinal degeneration. Using electrophysiological and genetic studies, biochemical assays, immunoblotting, real-time RT-PCR, and EM analysis, we found that mutations in the Gαq gene disrupt light responses and demonstrate that the Gαq3 isoform protein is responsible for the residual light response in Gαq1 null mutants. Moreover, we report that Gαq3 mediates rhodopsin synthesis. Depletion of all Gαq splice variants led to rapid light-dependent retinal degeneration, due to the formation stable Rh1-arrestin 2 (Arr2) complexes. Our findings clarify essential roles of several different Gαq splice variants in phototransduction and retinal integrity in Drosophila and reveal that Gαq3 functions in rhodopsin synthesis. Full Article
med Withdrawal: miR-21-mediated radioresistance occurs via promoting repair of DNA double strand breaks. [Withdrawals/Retractions] By www.jbc.org Published On :: 2020-05-01T00:06:09-07:00 VOLUME 292 (2017) PAGES 3531–3540This article has been withdrawn by Shuofeng Hu, Xiaomin Ying, Xiangming Zhang, and Ya Wang. Baocheng Hu, Xiang Wang, Ping Wang, Jian Wang, and Hongyan Wang could not be reached. In Fig. 1C, the DAPI and merged images for the no IR control were switched. The DNA-PKcs and actin immunoblots on the left appear to have been spliced. In Fig. 4C, the DNA-PKcs immunoblot appears to have been spliced. In Fig. 4D, lanes 1 and 5; lanes 2, 6, and 8; and lanes 3 and 7 of the DNA-PKcs immunoblot are the same. In the p-DNA-PKcs immunoblot, lanes 1 and 8, lanes 2 and 6, and lanes 3 and 7 are the same. In the CRY2 immunoblot, lanes 5 and 7 are the same. In the CDC25A immunoblot, lanes 3 and 8 are the same. In the GSK3B immunoblot, lanes 1 and 5 and lanes 3 and 7 are the same. Also in the GSK3B immunoblot, the upper GSK3B bands in lanes 6 and 8 are the same. Lanes 4 and 8 of the cyclin D1 immunoblot are the same. In Fig. 5A, the CDC25A immunoblot appears to have been spliced. Also in Fig. 5A, lanes 2–4 and lanes 6–8 of the CDC25A immunoblot are the same. Lanes 4–6 and 7–9 of the actin immunoblot are the same. In Fig. 5C, lane 1 of the CDC25A immunoblot was reused in lane 5, and lanes 3 and 4 were reused in lanes 7 and 8. In the... Full Article
med NF-{kappa}B mediates lipopolysaccharide-induced alternative pre-mRNA splicing of MyD88 in mouse macrophages [Signal Transduction] By www.jbc.org Published On :: 2020-05-01T00:06:09-07:00 Although a robust inflammatory response is needed to combat infection, this response must ultimately be terminated to prevent chronic inflammation. One mechanism that terminates inflammatory signaling is the production of alternative mRNA splice forms in the Toll-like receptor (TLR) signaling pathway. Whereas most genes in the TLR pathway encode positive mediators of inflammatory signaling, several, including that encoding the MyD88 signaling adaptor, also produce alternative spliced mRNA isoforms that encode dominant-negative inhibitors of the response. Production of these negatively acting alternatively spliced isoforms is induced by stimulation with the TLR4 agonist lipopolysaccharide (LPS); thus, this alternative pre-mRNA splicing represents a negative feedback loop that terminates TLR signaling and prevents chronic inflammation. In the current study, we investigated the mechanisms regulating the LPS-induced alternative pre-mRNA splicing of the MyD88 transcript in murine macrophages. We found that 1) the induction of the alternatively spliced MyD88 form is due to alternative pre-mRNA splicing and not caused by another RNA regulatory mechanism, 2) MyD88 splicing is regulated by both the MyD88- and TRIF-dependent arms of the TLR signaling pathway, 3) MyD88 splicing is regulated by the NF-κB transcription factor, and 4) NF-κB likely regulates MyD88 alternative pre-mRNA splicing per se rather than regulating splicing indirectly by altering MyD88 transcription. We conclude that alternative splicing of MyD88 may provide a sensitive mechanism that ensures robust termination of inflammation for tissue repair and restoration of normal tissue homeostasis once an infection is controlled. Full Article
med Biophysical characterization of SARAH domain-mediated multimerization of Hippo pathway complexes in Drosophila [Signal Transduction] By www.jbc.org Published On :: 2020-05-01T00:06:09-07:00 Hippo pathway signaling limits cell growth and proliferation and maintains the stem-cell niche. These cellular events result from the coordinated activity of a core kinase cassette that is regulated, in part, by interactions involving Hippo, Salvador, and dRassF. These interactions are mediated by a conserved coiled-coil domain, termed SARAH, in each of these proteins. SARAH domain–mediated homodimerization of Hippo kinase leads to autophosphorylation and activation. Paradoxically, SARAH domain–mediated heterodimerization between Hippo and Salvador enhances Hippo kinase activity in cells, whereas complex formation with dRassF inhibits it. To better understand the mechanism by which each complex distinctly modulates Hippo kinase and pathway activity, here we biophysically characterized the entire suite of SARAH domain–mediated complexes. We purified the three SARAH domains from Drosophila melanogaster and performed an unbiased pulldown assay to identify all possible interactions, revealing that isolated SARAH domains are sufficient to recapitulate the cellular assemblies and that Hippo is a universal binding partner. Additionally, we found that the Salvador SARAH domain homodimerizes and demonstrate that this interaction is conserved in Salvador's mammalian homolog. Using native MS, we show that each of these complexes is dimeric in solution. We also measured the stability of each SARAH domain complex, finding that despite similarities at both the sequence and structural levels, SARAH domain complexes differ in stability. The identity, stoichiometry, and stability of these interactions characterized here comprehensively reveal the nature of SARAH domain–mediated complex formation and provide mechanistic insights into how SARAH domain–mediated interactions influence Hippo pathway activity. Full Article
med DHHC7-mediated palmitoylation of the accessory protein barttin critically regulates the functions of ClC-K chloride channels [Cell Biology] By www.jbc.org Published On :: 2020-05-01T00:06:09-07:00 Barttin is the accessory subunit of the human ClC-K chloride channels, which are expressed in both the kidney and inner ear. Barttin promotes trafficking of the complex it forms with ClC-K to the plasma membrane and is involved in activating this channel. Barttin undergoes post-translational palmitoylation that is essential for its functions, but the enzyme(s) catalyzing this post-translational modification is unknown. Here, we identified zinc finger DHHC-type containing 7 (DHHC7) protein as an important barttin palmitoyl acyltransferase, whose depletion affected barttin palmitoylation and ClC-K-barttin channel activation. We investigated the functional role of barttin palmitoylation in vivo in Zdhhc7−/− mice. Although palmitoylation of barttin in kidneys of Zdhhc7−/− animals was significantly decreased, it did not pathologically alter kidney structure and functions under physiological conditions. However, when Zdhhc7−/− mice were fed a low-salt diet, they developed hyponatremia and mild metabolic alkalosis, symptoms characteristic of human Bartter syndrome (BS) type IV. Of note, we also observed decreased palmitoylation of the disease-causing R8L barttin variant associated with human BS type IV. Our results indicate that dysregulated DHHC7-mediated barttin palmitoylation appears to play an important role in chloride channel dysfunction in certain BS variants, suggesting that targeting DHHC7 activity may offer a potential therapeutic strategy for reducing hypertension. Full Article
med Transcript of remarks by CS, S for S, STH and SED at media session By www.info.gov.hk Published On :: Wed, 13 Nov 2019 15:38:45 Full Article
med Transcript of remarks by CS, S for S, SCED and SED at media session By www.info.gov.hk Published On :: Wed, 20 Nov 2019 17:35:57 Full Article
med Transcript of remarks by CS and SED at media session By www.info.gov.hk Published On :: Thu, 21 Nov 2019 19:39:28 Full Article
med SED's opening remarks at media session By www.info.gov.hk Published On :: Thu, 13 Feb 2020 12:54:30 Full Article
med Transcript of remarks by SFH, SCED and SED at media session By www.info.gov.hk Published On :: Wed, 29 Apr 2020 19:17:46 Full Article
med Meteorological dev't plan welcomed By www.news.gov.hk Published On :: Wed, 29 Apr 2020 00:00:00 +0800 The Hong Kong Special Administrative Region Government today welcomed the promulgation of the Meteorological Development Plan for the Guangdong-Hong Kong-Macao Greater Bay Area (2020-2035) by the China Meteorological Administration. In a statement, the Hong Kong SAR Government said the promulgation of the plan would further strengthen meteorological co-operation among Guangdong, Hong Kong and Macau in areas such as data sharing, scientific research and innovation, and training of meteorological personnel. Such co-operation would in turn enhance the meteorological services in the three places, it added. The relevant co-operation initiatives will benefit the Hong Kong Observatory (HKO) in its development of fine-scale meteorological monitoring, warning and forecasting services, and will further enhance Hong Kong's capability in forecasting extreme weather events, the statement said, adding the HKO will take forward the initiatives in collaboration with the relevant authorities in Guangdong and Macau. The full text of the meteorological plan is available on the China Meteorological Administration's website. It can also be accessed via the Hong Kong SAR Government's Greater Bay Area and HKO websites. Full Article
med Inside Jakk Media's Unusual Brand Marketing Strategy By www8.gsb.columbia.edu Published On :: Tue, 17 Sep 2019 01:00:49 +0000 Entrepreneurship Marketing Tuesday, September 10, 2019 - 21:00 Full Article
med Software flaws often first reported on social media networks, PNNL researchers find By www.eurekalert.org Published On :: Mon, 04 May 2020 00:00:00 EDT (DOE/Pacific Northwest National Laboratory) Software vulnerabilities are more likely to be discussed on social media before they're revealed on a government reporting site, a practice that could pose a national security threat, according to computer scientists at Pacific Northwest National Laboratory. Full Article
med Deformed skulls in an ancient cemetery reveal a multicultural community in transition By www.eurekalert.org Published On :: Wed, 29 Apr 2020 00:00:00 EDT (PLOS) The ancient cemetery of Mözs-Icsei d?l? in present-day Hungary holds clues to a unique community formation during the beginnings of Europe's Migration Period, according to a study published April 29, 2020 in the open-access journal PLOS ONE by Corina Knipper from the Curt-Engelhorn-Center for Archaeometry, Germany, István Koncz, Tivadar Vida from the Eötvös Loránd University, Budapest, Hungary and colleagues. Full Article
med University of Tennessee extension forester named 2020 Forester of the Year By www.eurekalert.org Published On :: Thu, 07 May 2020 00:00:00 EDT (University of Tennessee Institute of Agriculture) David Mercker, an Extension forestry specialist with the University of Tennessee Department of Forestry, Wildlife and Fisheries, has been named 2020 Extension Forester of the Year by the Forest Landowners Association (FLA). FLA is a national organization that promotes and protects the interests of private forest landowners and bestows this award annually as determined by its board of directors. Full Article
med LECOM's Dr. James Lin named AGS Geriatrics Clinician of the Year By www.eurekalert.org Published On :: Fri, 08 May 2020 00:00:00 EDT (American Geriatrics Society) The American Geriatrics Society (AGS) today named James Lin, DO, MS, MHSA, president of the Lake Erie College of Osteopathic Medicine (LECOM) Institute for Successful Aging in Erie, Pa., its 2020 Clinician of the Year. Lin will be honored at the AGS 2021 Annual Scientific Meeting (#AGS21), May 13-15, 2021, in Chicago, Ill., following the cancellation of the AGS 2020 Annual Scientific Meeting due to COVID-19. Full Article
med OU Reproductive Medicine physician receives grant to further study frozen embryo transfers By www.eurekalert.org Published On :: Fri, 08 May 2020 00:00:00 EDT (University of Oklahoma) OU Medicine recently received a $1.4 million grant from the National Institutes of Health to study one method of embryo transfer involved in IVF: cryopreserved (frozen) embryo transfer. Full Article
med Benefits of higher doses of certain medicines fail to justify costs and risks, study shows By www.eurekalert.org Published On :: Tue, 05 May 2020 00:00:00 EDT (Oregon State University) Clinical trial data behind drug dose recommendations for elevated cholesterol and chronic obstructive pulmonary disease illustrate how larger doses may not be worth the extra costs for many types of patients. Full Article
med Drug Interactions of Medications Commonly Used in Diabetes By spectrum.diabetesjournals.org Published On :: 2006-10-01 Curtis TriplittOct 1, 2006; 19:202-211Pharmacy Update Full Article
med Iatrogenic Inpatient Hypoglycemia: Risk Factors, Treatment, and Prevention: Analysis of Current Practice at an Academic Medical Center With Implications for Improvement Efforts By spectrum.diabetesjournals.org Published On :: 2008-10-01 Gregory A. MaynardOct 1, 2008; 21:241-247Articles Full Article
med Complementary and Integrative Medicine: Emerging Therapies for Diabetes, Part 1: Preface By spectrum.diabetesjournals.org Published On :: 2001-08-01 Cynthia PayneAug 1, 2001; 14:Preface Full Article
med Redesign of a Diabetes System of Care Using an All-or-None Diabetes Bundle to Build Teamwork and Improve Intermediate Outcomes By spectrum.diabetesjournals.org Published On :: 2010-07-01 Frederick J. BloomJul 1, 2010; 23:165-169From Research to Practice Full Article
med Insulin-Related Knowledge Among Health Care Professionals in Internal Medicine By spectrum.diabetesjournals.org Published On :: 2007-07-01 Rachel L. DerrJul 1, 2007; 20:177-185Feature Articles Full Article
med Comedians to provide ‘COVID’ relief By jamaica-star.com Published On :: Thu, 07 May 2020 05:01:30 -0500 Comedians Over Viruses and Infectious Diseases (COVID) is the message behind the latest project from comedian duo Ity and Fancy Cat. Recognising that stress levels are on the rise due to the effects of the... Full Article
med 488 confirmed COVID-19 cases in Jamaica By jamaica-star.com Published On :: Thu, 07 May 2020 18:37:50 -0500 The Ministry of Health and Wellness has reported ten new positive COVID-19 test results, pushing the tally of confirmed cases to 488. Among the ten new cases, eight are females, and two are males. Their ages range from four years to 39-years-... Full Article
med Setting Policy for What Comes After COVID-19: Dr. Faheem Ahmed ’20 By www8.gsb.columbia.edu Published On :: Thu, 23 Apr 2020 00:00:00 -0400 Like many of his classmates, Dr. Faheem Ahmed started the spring semester, primed to put the finishing touches on his MBA. But after COVID-19 began to spread, he relocated to his home in London to complete his degree remotely and work on the frontline of the crisis. Full Article
med Armed Conflict and Starvation: What Does the Law Say? By feedproxy.google.com Published On :: Wed, 18 Jul 2018 15:05:01 +0000 Research Event 12 October 2018 - 5:30pm to 7:00pm Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Professor Dapo Akande, Co-Director, Oxford Institute for Ethics, Law and Armed Conflict Emanuela-Chiara Gillard, Associate Fellow, International Law Programme, Chatham HouseAhila Sornarajah, Senior Lawyer, International and EU LawChair: Elizabeth Wilmshurst, Distinguished Fellow, International Law Programme, Chatham House Millions of civilians suffer hunger and starvation in times of armed conflict. This panel discusses the legal prohibitions on the use of starvation as a method of war, and the obligations on the warring parties to allow access for humanitarian relief. Department/project International Law Programme Chanu Peiris Programme Manager, International Law +44 (0)20 7314 3686 Email Full Article
med Protection of the Wounded and Medical Care-Givers in Armed Conflict: Is the Law Up to the Job? By feedproxy.google.com Published On :: Wed, 27 Feb 2019 10:21:55 +0000 Research Event 16 May 2019 - 5:30pm to 7:00pm Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Françoise Bouchet-Saulnier, Legal Director, Médecins Sans FrontièresEzequiel Heffes, Thematic Legal Adviser, Geneva CallRain Liivoja, Associate Professor, University of QueenslandMaciej Polkowski, Head, Health Care in Danger Initiative, International Committee of the Red CrossChair: Elizabeth Wilmshurst, Distinguished Fellow, International Law Programme, Chatham House This meeting, supported by the British Red Cross, is the first in a series of three to commemorate the 70th anniversary of the 1949 Geneva Conventions. The meeting will focus on the protection of the wounded and sick in armed conflict and will also include discussion of challenges to the protection of medical care and of health providers.Attacks on health care personnel and facilities have increased in recent years, as have the instances in which proceedings have been brought against those providing medical care to wounded fighters, including under counter-terrorism measures.The Geneva Conventions and their Protocols give protection to the wounded and sick and to healthcare providers, but is the law adequate? Is the law sufficiently widely known? How can the law be more fully implemented? What particular challenges arise in non-international armed conflicts?This event will be followed by a drinks reception. Department/project International Law Programme, The Limits on War and Preserving the Peace Full Article
med The Protection of Children in Armed Conflict By feedproxy.google.com Published On :: Tue, 25 Jun 2019 18:10:01 +0000 Research Event 25 September 2019 - 5:30pm to 7:00pm Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Emanuela-Chiara Gillard, Associate Fellow, International Law Programme, Chatham HouseJoanne Neenan, Legal Adviser, UK Foreign and Commonwealth OfficeDarren Stewart, Head of Operational Law, UK Army HeadquartersChair: Elizabeth Wilmshurst, Distinguished Fellow, International Law Programme, Chatham House With more protracted and urbanized conflicts, the character of warfare is changing in a manner that is having a greater impact on children. Aside from physical harm, they face the trauma of family separation and displacement, are vulnerable to sexual abuse and recruitment as soldiers and suffer severe disruption to their education. This event will discuss how international humanitarian law applies to the protection of children. Are offences against children in armed conflict being prosecuted adequately? Are there better ways of ensuring compliance with the law?This meeting is the second in a series of three commemorating the 70th anniversary of the 1949 Geneva Conventions.This event, which is supported by the British Red Cross, will be followed by a drinks reception.THIS EVENT IS NOW FULL AND REGISTRATION HAS CLOSED. Department/project International Law Programme, The Limits on War and Preserving the Peace Chanu Peiris Programme Manager, International Law +44 (0)20 7314 3686 Email Full Article
med Arginine in C9ORF72 Dipolypeptides Mediates Promiscuous Proteome Binding and Multiple Modes of Toxicity By feedproxy.google.com Published On :: 2020-04-01 Mona RadwanApr 1, 2020; 19:640-654Research Full Article
med Immediate adaptation analysis implicates BCL6 as an EGFR-TKI combination therapy target in NSCLC By feedproxy.google.com Published On :: 2020-03-31 Yan Zhou TranMar 31, 2020; 0:RA120.002036v1-mcp.RA120.002036Research Full Article
med Policy Implications of Armed Drone Use By feedproxy.google.com Published On :: Thu, 01 Aug 2019 13:15:02 +0000 This project brings together experts on the use of armed drones, including current and former military officials, academia, think-tanks and NGOs, to discuss and exchange perspectives based on their different experiences, with the aim of sharing knowledge and increasing understanding on these issues, and to inform and provide input into the European debate. With the increased use of armed drones in recent years, ethical and legal concerns have been raised in regard to civilian casualties, secrecy and lack of transparency and accountability for drone strikes.This project brings together experts on the use of armed drones, including current and former military officials, academia, think-tanks and NGOs, to discuss and exchange perspectives based on their different experiences, with the aim of sharing knowledge and increasing understanding on these issues, and to inform and provide input into the European debate. The experts explore the issues and controversies surrounding the use of drones outside formal armed conflict and study the broader policy implications in detail, particularly with regards to what this means for the UK and other European countries.Building on the findings from the workshops, this project will hold a simulation exercise to stress test critical areas of concern around the use of armed drones that are relevant for the UK and other EU member states.The discussions and the simulation exercise will provide opportunities for policy input on areas of mutual concern and feed into practical policy recommendations on the use of armed drones.This project builds on previous work on armed drones by the International Security Department and is funded by the Open Society Foundations. Past events (2) Research Event The Implications of Drone Proliferation in Europe 20 May 2019 Research Event Transparency and Accountability for Drone Use: European Approaches 11 March 2019 More on Policy Implications of Armed Drone Use Full Article
med AI-driven Personalization in Digital Media: Political and Societal Implications By feedproxy.google.com Published On :: Mon, 02 Dec 2019 12:18:52 +0000 2 December 2019 The fallout from disinformation and online manipulation strategies have alerted Western democracies to the novel, nuanced vulnerabilities of our information society. This paper outlines the implications of the adoption of AI by the the legacy media, as well as by the new media, focusing on personalization. Download PDF Sophia Ignatidou Academy Associate, International Security Programme @SophiaIgnatidou LinkedIn 2019-12-02-AI-Driven-Personalization-small.jpg The Reuters and other news apps seen on an iPhone, 29 January 2019. Photo: Getty Images. SummaryMachine learning (ML)-driven personalization is fast expanding from social media to the wider information space, encompassing legacy media, multinational conglomerates and digital-native publishers: however, this is happening within a regulatory and oversight vacuum that needs to be addressed as a matter of urgency.Mass-scale adoption of personalization in communication has serious implications for human rights, societal resilience and political security. Data protection, privacy and wrongful discrimination, as well as freedom of opinion and of expression, are some of the areas impacted by this technological transformation.Artificial intelligence (AI) and its ML subset are novel technologies that demand novel ways of approaching oversight, monitoring and analysis. Policymakers, regulators, media professionals and engineers need to be able to conceptualize issues in an interdisciplinary way that is appropriate for sociotechnical systems.Funding needs to be allocated to research into human–computer interaction in information environments, data infrastructure, technology market trends, and the broader impact of ML systems within the communication sector.Although global, high-level ethical frameworks for AI are welcome, they are no substitute for domain- and context-specific codes of ethics. Legacy media and digital-native publishers need to overhaul their editorial codes to make them fit for purpose in a digital ecosystem transformed by ML. Journalistic principles need to be reformulated and refined in the current informational context in order to efficiently inform the ML models built for personalized communication.Codes of ethics will not by themselves be enough, so current regulatory and legislative frameworks as they relate to media need to be reassessed. Media regulators need to develop their in-house capacity for thorough research and monitoring into ML systems, and – when appropriate –proportionate sanctions for actors found to be employing such systems towards malign ends. Collaboration with data protection authorities, competition authorities and national electoral commissions is paramount for preserving the integrity of elections and of a political discourse grounded on democratic principles.Upskilling senior managers and editorial teams is fundamental if media professionals are to be able to engage meaningfully and effectively with data scientists and AI engineers. Department/project International Security Programme, Internet Governance Full Article
med Building LGBTIQ+ Inclusivity in the Armed Forces, 20 Years After the Ban Was Lifted By feedproxy.google.com Published On :: Thu, 16 Jan 2020 12:27:18 +0000 16 January 2020 Will Davies Army Chief of General Staff Research Fellow, International Security Programme @williamhldavies LinkedIn Change was slow to come but progress has since been swift. Not only can a continuing focus on inclusivity benefit service people and the organization, it is also an essential element of a values-based foreign policy. 2020-01-16-Westminster.jpg Crew members from HMS Westminster march through Admiralty Arch as they exercise their freedom of the city in August 2019 in London. Photo: Getty Images. The new UK government will conduct a review of foreign, security and defence policy in 2020. If the UK decides to use values as a framework for foreign policy this needs to be reflected in its armed forces. One area where this is essential is continuing to deepen inclusivity for LGBTIQ+ personnel, building on the progress made since the ban on their service was lifted in 2000.I witnessed the ban first-hand as a young officer in the British Army in 1998. As the duty officer I visited soldiers being held in the regimental detention cells to check all was well. One day a corporal, who I knew, was there awaiting discharge from the army having been convicted of being gay. On the one hand, here was service law in action, which was officially protecting the army’s operational effectiveness and an authority not to be questioned at my level. On the other, here was an excellent soldier in a state of turmoil and public humiliation. How extreme this seems now.On 12 January 2000 Tony Blair’s Labour government announced an immediate lifting of the ban for lesbian, gay and bisexual personnel (LGB) and introduced a new code of conduct for personal relationships. (LGB is the term used by the armed forces to describe those personnel who had been banned prior to 2000.) This followed a landmark ruling in a case taken to the European Court of Human Rights in 1999 by four LGB ex-service personnel – supported by Stonewall – who had been dismissed from service for their sexuality.Up to that point the Ministry of Defence's long-held position had been that LGB personnel had a negative impact on the morale and cohesion of a unit and damaged operational effectiveness. Service personnel were automatically dismissed if it was discovered they were LGB, even though homosexuality had been decriminalized in the UK by 1967.Proof that the armed forces had been lagging behind the rest of society was confirmed by the positive response to the change among service personnel, despite a handful of vocal political and military leaders who foresaw negative impacts. The noteworthy service of LGBTIQ+ people in Iraq and Afghanistan only served to debunk any residual myths.Twenty years on, considerable progress has been made and my memories from 1998 now seem alien. This is a story to celebrate – however in the quest for greater inclusivity there is always room for improvement.Defence Minister Johnny Mercer last week apologized following recent calls from campaign group Liberty for a fuller apology. In December 2019, the Ministry of Defence announced it was putting in place a scheme to return medals stripped from veterans upon their discharge.The armed forces today have a range of inclusivity measures to improve workplace culture including assessments of workplace climate and diversity networks supported by champions drawn from senior leadership.But assessing the actual lived experience for LGBTIQ+ people is challenging due to its subjectivity. This has not been helped by low participation in the 2015 initiative to encourage people to declare confidentially their sexual orientation, designed to facilitate more focused and relevant policies. As of 1 October 2019, only 20.3 per cent of regular service people had declared a sexual orientation.A measure of positive progress is the annual Stonewall Workplace Equality Index, the definitive benchmarking tool for employers to measure their progress on LGBTIQ+ inclusion in the workplace; 2015 marked the first year in which all three services were placed in the top 100 employers in the UK and in 2019 the Royal Navy, British Army and Royal Air Force were placed 15th=, 51st= and 68th respectively.Nevertheless, LGBTIQ+ service people and those in other protected groups still face challenges. The 2019 Ministry of Defence review of inappropriate behaviour in the armed forces, the Wigston Report, concluded there is an unacceptable level of sexual harassment, bullying and discrimination. It found that 26-36% of LGBTIQ+ service people have experienced negative comments or conduct at work because of their sexual orientation.The Secretary of State for Defence accepted the report’s 36 recommendations on culture, incident reporting, training and a more effective complaints system. Pivotal to successful implementation will be a coherent strategy driven by fully engaged leaders.Society is also expecting ever higher standards, particularly in public bodies. The armed forces emphasise their values and standards, including ‘respect for others’, as defining organisational characteristics; individuals are expected to live by them. Only in a genuinely inclusive environment can an individual thrive and operate confidently within a team.The armed forces also recognize as a priority the need to connect to and reflect society more closely in order to attract and retain talent from across all of society. The armed forces’ active participation in UK Pride is helping to break down barriers in this area.In a post-Brexit world, the UK’s values, support for human rights and reputation for fairness are distinctive strengths that can have an impact on the world stage and offer a framework for future policy. The armed forces must continue to push and promote greater inclusivity in support. When operating overseas with less liberal regimes, this will be sensitive and require careful handling; however it will be an overt manifestation of a broader policy and a way to communicate strong and consistent values over time.The armed forces were damagingly behind the times 20 years ago. But good progress has been made since. Inclusion initiatives must continue to be pushed to bring benefits to the individual and the organization as well as demonstrate a values-based foreign policy. Full Article
med Mohammed Abdalfatah By feedproxy.google.com Published On :: Mon, 03 Feb 2020 13:13:07 +0000 Asfari Foundation Academy Fellow Biography Mohammed’s research examines the potentials and the role of cities in driving inclusive sustainable development in the Gaza Strip and how cities can bring about innovative genuine solutions to encountered local and national challenges.Before joining Chatham House and since 2006, Mohammed has been the director of international cooperation at the Municipality of Gaza, where he headed the planning team for the Gaza local development plan 2019-2022.From 2002-06 he was international relations officer at the Municipality of Gaza and, prior to this, he held positions with UNDP and the Palestinian Ministry of Planning & International Cooperation.He was a full time visiting research fellow at ICSR non-award research programme in the War Studies Department at King's College London from February-June 2014.Mohammed holds a post-graduate diploma in Management of Local Development from the International Training Centre, ILO, Turin and earned his BA in Languages from Ain Shams University, Cairo. Areas of expertise Local developmentDecentralized cooperationInternational relations of the Middle EastPalestinian affairs with a particular focus on GazaPublic policy and local governance Past experience 2006-19Director of International Cooperation, Municipality of Gaza, Palestine2014Visiting Research Fellow, ICSR, Department of War Studies at King's College London2002-06International Relations Officer, Municipality of Gaza, Palestine2001-02Programme Management Assistant, UNDP/PAPP, Gaza, Palestine2000-01Desk Officer in Eastern Europe Dept., Palestinian Ministry of Planning & International Cooperation +44(0)20 7314 3655 Email @mhalabi258 LinkedIn Full Article
med POSTPONED: The Development of Libyan Armed Groups since 2014: Community Dynamics and Economic Interests By feedproxy.google.com Published On :: Wed, 04 Mar 2020 14:15:01 +0000 Invitation Only Research Event 18 March 2020 - 9:00am to 10:30am Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Abdul Rahman Alageli, Associate Fellow, MENA Programme, Chatham HouseEmaddedin Badi, Non-Resident Scholar, Middle East InstituteTim Eaton, Senior Research Fellow, MENA Programme Chatham HouseValerie Stocker, Independent Researcher Since the overthrow of the regime of Muammar Gaddafi in 2011, Libya’s multitude of armed groups have followed a range of paths. While many of these have gradually demobilized, others have remained active, and others have expanded their influence. In the west and south of the country, armed groups have used their state affiliation to co-opt the state and professionals from the state security apparatus into their ranks.In the east, the Libyan Arab Armed Forces projects a nationalist narrative yet is ultimately subservient to its leader, Field Marshal Khalifa Haftar. Prevailing policy narratives presuppose that the interests of armed actors are distinct from those of the communities they claim to represent. Given the degree to which most armed groups are embedded in local society, however, successful engagement will need to address the fears, grievances and desires of the surrounding communities, even while the development of armed groups’ capacities dilutes their accountability to those communities.This roundtable will discuss the findings of a forthcoming Chatham House research paper, ‘The Development of Libyan Armed Groups Since 2014: Community Dynamics and Economic Interests’, which presents insights from over 200 interviews of armed actors and members of local communities and posits how international policymakers might seek to curtail the continued expansion of the conflict economy.PLEASE NOTE THIS EVENT IS POSTPONED UNTIL FURTHER NOTICE. Event attributes Chatham House Rule Department/project Middle East and North Africa Programme, Countering Conflict Economies in MENA, Libya’s Conflict Economy Georgia Cooke Project Manager, Middle East and North Africa Programme +44 (0)20 7957 5740 Email Full Article
med The Development of Libyan Armed Groups Since 2014: Community Dynamics and Economic Interests By feedproxy.google.com Published On :: Mon, 16 Mar 2020 17:25:16 +0000 17 March 2020 This paper explores armed group–community relations in Libya and the sources of revenue that have allowed armed groups to grow in power and influence. It draws out the implications for policy and identifies options for mitigating conflict dynamics. Read online Download PDF Tim Eaton Senior Research Fellow, Middle East and North Africa Programme @el_khawaga LinkedIn Abdul Rahman Alageli Associate Fellow, Middle East and North Africa Programme @abdulrahmanlyf Emadeddin Badi Policy Leader Fellow, School of Transnational Governance, European University Institute Mohamed Eljarh Co-founder and CEO, Libya Outlook Valerie Stocker Researcher Amru_24-2_13.jpg Fighters of the UN-backed Government of National Accord patrol in Ain Zara suburb in Tripoli, February 2020. Photo: Amru Salahuddien SummaryLibya’s multitude of armed groups have followed a range of paths since the emergence of a national governance split in 2014. Many have gradually demobilized, others have remained active, and others have expanded their influence. However, the evolution of the Libyan security sector in this period remains relatively understudied. Prior to 2011, Libya’s internal sovereignty – including the monopoly on force and sole agency in international relations – had been personally vested in the figure of Muammar Gaddafi. After his death, these elements of sovereignty reverted to local communities, which created armed organizations to fill that central gap. National military and intelligence institutions that were intended to protect the Libyan state have remained weak, with their coherence undermined further by the post-2014 governance crisis and ongoing conflict. As a result, the most effective armed groups have remained localized in nature; the exception is the Libyan Arab Armed Forces (LAAF), which has combined and amalgamated locally legitimate forces under a central command.In the west and south of the country, the result of these trends resembles a kind of inversion of security sector reform (SSR) and disarmament, demobilization and reintegration (DDR): the armed groups have used their state affiliation to co-opt the state and professionals from the state security apparatus into their ranks; and have continued to arm, mobilize and integrate themselves into the state’s security apparatus without becoming subservient to it. In the eastern region, the LAAF projects a nationalist narrative yet is ultimately subservient to its leader, Field Marshal Khalifa Haftar. The LAAF has co-opted social organizations to dominate political and economic decision-making.The LAAF has established a monopoly over the control of heavy weapons and the flow of arms in eastern Libya, and has built alliances with armed groups in the east. Armed groups in the south have been persuaded to join the LAAF’s newly established command structure. The LAAF’s offensive on the capital, which started in April 2019, represents a serious challenge to armed groups aligned with the Tripoli-based Government of National Accord (GNA). The fallout from the war will be a challenge to the GNA or any future government, as groups taking part in the war will expect to be rewarded. SSR is thus crucial in the short term: if the GNA offers financial and technical expertise and resources, plus legal cover, to armed groups under its leadership, it will increase the incentive for armed groups to be receptive to its plans for reform.Prevailing policy narratives presuppose that the interests of armed actors are distinct from those of the communities they claim to represent. Given the degree to which most armed groups are embedded in local society, however, successful engagement will necessarily rely on addressing the fears, grievances and desires of the surrounding communities. Yet the development of armed groups’ capacities, along with their increasing access to autonomous means of generating revenue, has steadily diluted their accountability to local communities. This process is likely to be accelerated by the ongoing violence around Tripoli.Communities’ relationship to armed groups varies across different areas of the country, reflecting the social, political, economic and security environment:Despite their clear preference for a more formal, state-controlled security sector, Tripoli’s residents broadly accept the need for the presence of armed groups to provide security. The known engagement of the capital’s four main armed groups in criminal activity is a trade-off that many residents seem able to tolerate, providing that overt violence remains low. Nonetheless, there is a widespread view that the greed of Tripoli’s armed groups has played a role in stoking the current conflict.In the east, many residents appear to accept (or even welcome) the LAAF’s expansion beyond the security realm, provided that it undertakes these roles effectively. That said, such is the extent of LAAF control that opposition to the alliance comes at a high price.In the south, armed groups draw heavily on social legitimacy, acting as guardians of tribal zones of influence and defenders of their respective communities against outside threats, while also at times stoking local conflicts. Social protections continue to hold sway, meaning that accountability within communities is also limited.To varying extents since 2014, Libya’s armed groups have developed networks that enmesh political and business stakeholders in revenue-generation models:Armed groups in Tripoli have compensated for reduced financial receipts from state budgets by cultivating unofficial and illicit sources of income. They have also focused on infiltrating state institutions to ensure access to state budgets and contracts dispersed in the capital.In the east of the country, the LAAF has developed a long-term strategy to dominate the security, political and economic spheres through the establishment of a quasi-legal basis for receiving funds from Libya’s rival state authorities. It has supplemented this with extensive intervention in the private sector. External patronage supports military operations, but also helps to keep this financial system, based on unsecured debt, afloat.In the south, limited access to funds from the central state has spurred armed groups to become actively involved in the economy. This has translated into the taxation of movement and the imposition of protection fees, particularly on informal (and often illicit) activity.Without real commitment from international policymakers to enforcing the arms embargo and protecting the economy from being weaponized, Libya will be consigned to sustained conflict, further fragmentation and potential economic collapse. Given the likely absence of a political settlement in the short term, international policymakers should seek to curtail the continued expansion of the conflict economy by reducing armed groups’ engagement in economic life.In order to reduce illicit activities, international policymakers should develop their capacity to identify and target chokepoints along illicit supply chains, with a focus on restraining activities and actors in closest proximity to violence. Targeted sanctions against rent maximizers (both armed and unarmed) is likely to be the most effective strategy. More effective investigation and restraint of conflict economy actors will require systemic efforts to improve transparency and enhance the institutional capacity of anti-corruption authorities. International policymakers should also support the development of tailored alternative livelihoods that render conflict economy activities less attractive. Department/project Middle East and North Africa Programme, Chaos States, Countering Conflict Economies in MENA, Libya’s Conflict Economy Full Article
med Mohamed El Dahshan By feedproxy.google.com Published On :: Sat, 02 May 2020 09:17:19 +0000 Associate Fellow, Middle East and North Africa Programme Biography Mohamed El Dahshan is an associate fellow with the Chatham House Middle East and North Africa Programme, where he focuses on economic development, regional cooperation, and fragile states.He is also managing director of OXCON, a public sector consulting firm, advising governments and international organisations on Africa and the Middle East. Prior to this, he was senior cooperation advisor at the African Development Bank, and senior research fellow at Harvard University.He is an award-winning writer and columnist, and the co-author of Diaries of the Revolution (2012), a memoir of the Egyptian revolution, as well as several book chapters, academic papers, and more than 100 media articles for outlets such as Foreign Policy the New York Times, and the Guardian, among others.He was honoured as an Archbishop Desmond Tutu fellow, a fellow of the United Nations Alliance of Civilisations, and is listed among the 100 Africa Future Economic Leaders by the Institut Choiseul.Mohamed holds Master degrees from Oxford, Harvard and Sciences-Po Paris. Areas of expertise Economic developmentEgyptSMEs and private sector developmentFragile states Past experience 2017 - presentManaging director, OXCON Frontier Markets & Fragile States Consulting2014-15Regional economist / Senior cooperation officer, African Development Bank2012-13Middle East manager, Senior research fellow, Center for International Development, Harvard University Email @eldahshan LinkedIn Google Scholar Full Article
med OpenDose: open access resources for nuclear medicine dosimetry By jnm.snmjournals.org Published On :: 2020-03-13T14:12:30-07:00 Background: Radiopharmaceutical dosimetry depends on the localization in space and time of radioactive sources and requires the estimation of the amount of energy emitted by the sources deposited within targets. In particular, when computing resources are not accessible, this task can be carried out using precomputed tables of Specific Absorbed Fractions (SAFs) or S values based on dosimetric models. The OpenDose collaboration aims to generate and make freely available a range of dosimetric data and tools. Methods: OpenDose brings together resources and expertise from 18 international teams to produce and compare traceable dosimetric data using 6 of the most popular Monte Carlo codes in radiation transport (EGSnrc/EGS++, FLUKA, GATE, Geant4, MCNP/MCNPX and PENELOPE). SAFs are uploaded, together with their associated statistical uncertainties, in a relational database. S values are then calculated from mono-energetic SAFs, based on the radioisotope decay data presented in the International Commission on Radiological Protection (ICRP) publication 107. Results: The OpenDose collaboration produced SAFs for all source regions and targets combinations of the two ICRP 110 adult reference models. SAFs computed from the different Monte Carlo codes were in good agreement at all energies, with standard deviations below individual statistical uncertainties. Calculated S values were in good agreement with OLINDA 2 (commercial) and IDAC 2.1 (free) software. A dedicated website (www.opendose.org) has been developed to provide easy and open access to all data. Conclusion: The OpenDose website allows the display and download of SAFs and the corresponding S values for 1252 radionuclides. The OpenDose collaboration, open to new research teams, will extend data production to other dosimetric models and implement new free features, such as online dosimetric tools and patient-specific absorbed dose calculation software, together with educational resources. Full Article
med The Changing Face of Nuclear Cardiology: Guiding Cardiovascular Care towards Molecular Medicine By jnm.snmjournals.org Published On :: 2020-04-17T08:32:41-07:00 Radionuclide imaging of myocardial perfusion, function, and viability has been established for decades and remains a robust, evidence-based and broadly available means for clinical workup and therapeutic guidance in ischemic heart disease. Yet, powerful alternative modalities have emerged for this purpose, and their growth has resulted in increasing competition. But the potential of the tracer principle goes beyond the assessment of physiology and function, towards the interrogation of biology and molecular pathways. This is a unique selling point of radionuclide imaging, which has been under-recognized in cardiovascular medicine until recently. Now, molecular imaging methods for the detection of myocardial infiltration, device infection and cardiovascular inflammation are successfully gaining clinical acceptance. This is further strengthened by the symbiotic quest of cardiac imaging and therapy for an increasing implementation of molecular-targeted procedures, where specific therapeutic interventions require specific diagnostic guidance towards the most suitable candidates. This review will summarize the current advent of clinical cardiovascular molecular imaging and highlight its transformative contribution to the evolution of cardiovascular therapy beyond mechanical interventions and broad "blockbuster" medication, towards a future of novel, individualized molecular targeted and molecular imaging-guided therapies. Full Article
med The role of Nuclear Medicine for COVID-19 - Time to act now. By jnm.snmjournals.org Published On :: 2020-04-17T08:32:41-07:00 Full Article
med Yttrium-90 Radioembolization: Telemedicine during COVID-19 outbreak, opportunity for prime time. By jnm.snmjournals.org Published On :: 2020-04-24T14:33:41-07:00 Full Article
med The Impact of Radiobiologically-Informed Dose Prescription on the Clinical Benefit of Yttrium-90 SIRT in Colorectal Cancer Patients By jnm.snmjournals.org Published On :: 2020-05-01T11:16:57-07:00 The purpose of this study was to establish the dose-response relationship of selective internal radiation therapy (SIRT) in patients with metastatic colorectal cancer (mCRC), when informed by radiobiological sensitivity parameters derived from mCRC cell lines exposed to yttrium-90 (90Y). Methods: 23 mCRC patients with liver metastases refractory to chemotherapy were included. 90Y bremsstrahlung SPECT images were transformed into dose maps assuming the local dose deposition method. Baseline and follow-up CT scans were segmented to derive liver and tumor volumes. Mean, median, and D70 (minimum dose to 70% of tumor volume) values determined from dose maps were correlated with change in tumor volume and vRECIST response using linear and logistic regression, respectively. Radiosensitivity parameters determined by clonogenic assays of mCRC cell lines HT-29 and DLD-1 after exposure to 90Y or external beam radiotherapy (EBRT; 6MV photons) were used in biological effective dose (BED) calculations. Results: Mean administered radioactivity was 1469±428 MBq (847-2185 MBq), achieving a mean radiation absorbed tumor dose of 35.5±9.4 Gy and mean normal liver dose of 26.4±6.8 Gy. A 1.0 Gy increase in mean, median, and D70 absorbed dose was associated with reduction in tumor volume of 1.8%, 1.8%, and 1.5%, respectively, and increased probability of vRECIST response (odds ratio: 1.09, 1.09, and 1.10 respectively). Threshold mean, median and D70 doses for response were 48.3, 48.8, and 41.8 Gy respectively. EBRT-equivalent BEDs for 90Y are up to 50% smaller than those calculated by applying protraction-corrected radiobiological parameters derived from EBRT alone. Conclusion: Dosimetric studies have assumed equivalence between 90Y SIRT and EBRT, leading to inflation of BED for SIRT and possible under-treatment. Radiobiological parameters for 90Y were applied to a BED model, providing a calculation method that has the potential to improve assessment of tumor control. Full Article
med Time for a Next-Generation Nuclear Medicine Gamma Camera? [NEWSLINE] By jnm.snmjournals.org Published On :: 2020-05-08T13:18:58-07:00 Full Article
med African Agency Holds Power to Account in a Social Media Age By feedproxy.google.com Published On :: Wed, 18 Dec 2019 09:03:54 +0000 18 December 2019 Yusuf Hassan Parliamentary and Media Outreach Assistant, Africa Programme Waihiga Mwaura News Anchor, Citizen TV Kenya Structures to support more in-depth investigative journalism are vital in Africa because that seems to be the only thing those in power still truly fear. 2019-12-17-Africa-Ivory-Coast-Media.jpg Broadcast technicians work in a control room during the official launch of the Digital Terrestrial Television (TNT) in February 2019 near Abidjan, Ivory Coast. Photo by ISSOUF SANOGO/AFP via Getty Images. Africa’s media landscape has undergone a significant change over the last decade as digitalization and new forms of media consumption have weakened state control of information. Social media has provided an opportunity for African citizens and journalists to take agency over how the continent is presented to the wider world, and many emerging African voices bring clarity to this digitally disrupted marketplace. But significant external support is required to make these efforts sustainable. There is no one ‘African’ story. African media remains as diverse as the 55 states in the African Union, with each national media ecosystem dependent on patterns of culture and governance - most importantly the power gap between those in leadership and their voters.Journalists from Egypt, Eritrea and Cameroon - states in the 2019 global top 10 for putting their colleagues in prison - have different perspectives from those in other more liberal African countries.This is most visible in traditional media where a business model based on advertising revenue has allowed African media houses to grow. But it is susceptible to manipulation from state and business actors holding outlets to ransom in exchange for editorial influence or control – a particularly acute problem in states where business and political elites are closely intertwined, and a middle-class consumer base to fund market-driven advertising has yet to develop.Those African countries with relatively open borders, stronger passports and a more vibrant civil society also tend to have a more diverse and vibrant media environment. Open borders allow for easier movement, granting journalists the opportunity to travel, benchmark and participate in exchange programs.The power of online networkingThe advent of the social media age has begun to disrupt the links between governance and media health, as the large operations required by ‘serious’ media organizations have been replaced by mobile phone cameras and social media timelines.Many African journalists are at the forefront of this innovation, unrestricted by historical perceptions of how journalism should be presented, and free to disrupt and change the established narratives to better engage with their ever-growing audiences.And, far from replacing journalism, social media has actively empowered African journalists and media professionals. Instead of acting as sources for international media outlets as in the past, African journalists can publish their work on their own platforms, enabling greater ownership of how issues in their localities are globally framed. This local voice is often the key to avoiding the endemic oversimplifications and generalisations that have coloured much external coverage of the continent.Obviously, these changes bring risks. Individual uploaders are largely free to publish what they like, and misinformation can - and often has - lead to devastating consequences, evident in recent violence across central Mali, South Africa and the middle belt of Nigeria.But journalists on the African continent have an increasingly important role in preventing the spread of misinformation, not only as purveyors of news but also as fact-checkers, able to discern the difference between valid opinion and dubious rhetoric on social media, while new pan-African digital networks and discussion groups enable journalists to share knowledge, expertise, and story ideas, or quickly verify information from across the continent.It is now possible to quickly find authentic voices for TV, radio or online commentary through digital platforms, present on the ground and able to speak with real authority. Many online networks also include Africa-focused journalists from outside the continent, and any biased or incorrect coverage of the African continent can be ‘called out’ and heavily critiqued, with challenges shared and solutions generated. While journalists remain independent, their working practices and professional standards are being shaped by the discourse in the groups like never before.Online networking has also exposed the existence of lingering cultural differences between journalists of different national backgrounds, such as a hesitancy to discuss sensitive issues – the health of leaders for instance – for fear of being targeted by the authorities, or the level to which government statements are uncritically accepted.While journalists search for truth, how they go about it is still very dependent on the state of democracy in their country. Though the cross-fertilisation of best practices and critical scrutiny can only improve the quality of journalism on the continent, in many places there remains a long way to go.Drive for better resourcesAcross the world, digital media has struggled to create models which can provide news free at the point of access while also successfully monetizing content. This is even more palpable on the African continent, as the subscription-based models employed as a remedy elsewhere are not feasible on such a large scale in countries without a well-established middle-class.African media needs resources to keep operating at a time when revenue is dwindling, and talented journalists are decamping to join the marketing, communication and sales sectors in search of better wages. Structures to support more in-depth investigative journalism are vital in Africa because that seems to be the only thing those in power still truly fear.This means more training opportunities, fellowships, and exchange programs to allow the exchange of ideas and expertise. And, as social media has given a platform to talented local voices from across Africa, then an international community which truly wants to understand the nuances of the continent must hire them. Full Article
med Blistering1 Modulates Penicillium expansum Virulence Via Vesicle-mediated Protein Secretion [Research] By feedproxy.google.com Published On :: 2020-02-01T00:05:30-08:00 The blue mold fungus, Penicillium expansum, is a postharvest apple pathogen that contributes to food waste by rotting fruit and by producing harmful mycotoxins (e.g. patulin). To identify genes controlling pathogen virulence, a random T-DNA insertional library was created from wild-type P. expansum strain R19. One transformant, T625, had reduced virulence in apples, blistered mycelial hyphae, and a T-DNA insertion that abolished transcription of the single copy locus in which it was inserted. The gene, Blistering1, encodes a protein with a DnaJ domain, but otherwise has little homology outside the Aspergillaceae, a family of fungi known for producing antibiotics, mycotoxins, and cheese. Because protein secretion is critical for these processes and for host infection, mass spectrometry was used to monitor proteins secreted into liquid media during fungal growth. T625 failed to secrete a set of enzymes that degrade plant cell walls, along with ones that synthesize the three final biosynthetic steps of patulin. Consequently, the culture broth of T625 had significantly reduced capacity to degrade apple tissue and contained 30 times less patulin. Quantitative mass spectrometry of 3,282 mycelial proteins revealed that T625 had altered cellular networks controlling protein processing in the endoplasmic reticulum, protein export, vesicle-mediated transport, and endocytosis. T625 also had reduced proteins controlling mRNA surveillance and RNA processing. Transmission electron microscopy of hyphal cross sections confirmed that T625 formed abnormally enlarged endosomes or vacuoles. These data reveal that Blistering1 affects internal and external protein processing involving vesicle-mediated transport in a family of fungi with medical, commercial, and agricultural importance. Full Article
med Arginine in C9ORF72 Dipolypeptides Mediates Promiscuous Proteome Binding and Multiple Modes of Toxicity [Research] By feedproxy.google.com Published On :: 2020-04-01T00:05:32-07:00 C9ORF72-associated Motor Neuron Disease patients feature abnormal expression of 5 dipeptide repeat (DPR) polymers. Here we used quantitative proteomics in a mouse neuronal-like cell line (Neuro2a) to demonstrate that the Arg residues in the most toxic DPRS, PR and GR, leads to a promiscuous binding to the proteome compared with a relative sparse binding of the more inert AP and GA. Notable targets included ribosomal proteins, translation initiation factors and translation elongation factors. PR and GR comprising more than 10 repeats appeared to robustly stall on ribosomes during translation suggesting Arg-rich peptide domains can electrostatically jam the ribosome exit tunnel during synthesis. Poly-GR also recruited arginine methylases, induced hypomethylation of endogenous proteins, and induced a profound destabilization of the actin cytoskeleton. Our findings point to arginine in GR and PR polymers as multivalent toxins to translation as well as arginine methylation that may explain the dysfunction of biological processes including ribosome biogenesis, mRNA splicing and cytoskeleton assembly. Full Article
med Decreased Immunoglobulin G Core Fucosylation, A Player in Antibody-dependent Cell-mediated Cytotoxicity, is Associated with Autoimmune Thyroid Diseases [Research] By feedproxy.google.com Published On :: 2020-05-01T00:05:26-07:00 Autoimmune thyroid diseases (AITD) are the most common group of autoimmune diseases, associated with lymphocyte infiltration and the production of thyroid autoantibodies, like thyroid peroxidase antibodies (TPOAb), in the thyroid gland. Immunoglobulins and cell-surface receptors are glycoproteins with distinctive glycosylation patterns that play a structural role in maintaining and modulating their functions. We investigated associations of total circulating IgG and peripheral blood mononuclear cells glycosylation with AITD and the influence of genetic background in a case-control study with several independent cohorts and over 3,000 individuals in total. The study revealed an inverse association of IgG core fucosylation with TPOAb and AITD, as well as decreased peripheral blood mononuclear cells antennary α1,2 fucosylation in AITD, but no shared genetic variance between AITD and glycosylation. These data suggest that the decreased level of IgG core fucosylation is a risk factor for AITD that promotes antibody-dependent cell-mediated cytotoxicity previously associated with TPOAb levels. Full Article
med 'Public servants should get off social media': warning after Islamic State hack By www.smh.com.au Published On :: Fri, 14 Aug 2015 05:35:35 GMT Terrorists and criminals are looking for people to blackmail or seduce into stealing data. Full Article
med Medicare details available on dark web is just tip of data breach iceberg By www.smh.com.au Published On :: Mon, 17 Jul 2017 14:00:00 GMT The next wave of government reform will have to focus on data management. Full Article