cr Screening Room: About a War By f1.media.brightcove.com Published On :: Tue, 19 Feb 2019 00:00:00 +0000 Full Article
cr Stacey Abrams: Democracy and the Politics of Identity By f1.media.brightcove.com Published On :: Wed, 06 Mar 2019 00:00:00 +0000 Full Article
cr The Militarization of the Black Sea After the Annexation of Crimea By f1.media.brightcove.com Published On :: Wed, 13 Mar 2019 00:00:00 +0000 Full Article
cr Screening Room: Inside Europe - We Quit By f1.media.brightcove.com Published On :: Thu, 28 Mar 2019 00:00:00 +0000 Full Article
cr What Brexit Satisfies the Democratic Will of the People? By f1.media.brightcove.com Published On :: Tue, 02 Apr 2019 00:00:00 +0100 Full Article
cr Undercurrents: Episode 30 - The Crisis in Kashmir, and How to Regulate Big Tech By f1.media.brightcove.com Published On :: Thu, 04 Apr 2019 00:00:00 +0100 Full Article
cr Are ‘Digital Parties’ the Future of Democracy in Europe? By f1.media.brightcove.com Published On :: Tue, 07 May 2019 00:00:00 +0100 Full Article
cr Screening Room: RBG By f1.media.brightcove.com Published On :: Wed, 08 May 2019 00:00:00 +0100 Full Article
cr Screening Room: Displaced By f1.media.brightcove.com Published On :: Wed, 29 May 2019 00:00:00 +0100 Full Article
cr A Gulf Divided: The Anatomy of a Crisis By f1.media.brightcove.com Published On :: Thu, 06 Jun 2019 00:00:00 +0100 Full Article
cr Direct Democracy: Participation Without Populism? By f1.media.brightcove.com Published On :: Mon, 24 Jun 2019 00:00:00 +0100 Full Article
cr Screening Room: Brexit - Behind Closed Doors By f1.media.brightcove.com Published On :: Thu, 27 Jun 2019 00:00:00 +0100 Full Article
cr Iran, Islam and Democracy: The Politics of Managing Change 20 Years On By f1.media.brightcove.com Published On :: Tue, 02 Jul 2019 00:00:00 +0100 Full Article
cr How Democratic Is the EU? By f1.media.brightcove.com Published On :: Wed, 25 Sep 2019 00:00:00 +0100 Full Article
cr Screening Room: For Sama By f1.media.brightcove.com Published On :: Tue, 01 Oct 2019 00:00:00 +0100 Full Article
cr Screening Room: Port of Destiny By f1.media.brightcove.com Published On :: Tue, 29 Oct 2019 00:00:00 +0000 Full Article
cr Undercurrents: Episode 44 - The Iran Crisis, and Politics in Iraq By f1.media.brightcove.com Published On :: Thu, 23 Jan 2020 00:00:00 +0000 Full Article
cr A Conversation With: Steven T Mnuchin, Secretary, US Treasury By f1.media.brightcove.com Published On :: Sat, 25 Jan 2020 00:00:00 +0000 Full Article
cr The State of Democracy in Turkey By f1.media.brightcove.com Published On :: Mon, 03 Feb 2020 00:00:00 +0000 Full Article
cr Chatham House Primer: Democratic Socialism By f1.media.brightcove.com Published On :: Thu, 13 Feb 2020 00:00:00 +0000 Full Article
cr Screening Room: Parts of a Circle - History of the Karabakh Conflict By f1.media.brightcove.com Published On :: Tue, 18 Feb 2020 00:00:00 +0000 Full Article
cr Undercurrents: Episode 50 - The Coronavirus Communications Crisis, and Justice in Myanmar By brightcove.hs.llnwd.net Published On :: Thu, 23 Apr 2020 00:00:00 +0100 Full Article
cr Design in an Age of Crisis: The Search for Radical Solutions By brightcove.hs.llnwd.net Published On :: Fri, 14 Aug 2020 00:00:00 +0100 Full Article
cr Design in an Age of Crisis: Rethinking Work and the Environment By brightcove.hs.llnwd.net Published On :: Mon, 17 Aug 2020 00:00:00 +0100 Full Article
cr Design in an Age of Crisis: Rethinking Health and Society By brightcove.hs.llnwd.net Published On :: Tue, 18 Aug 2020 00:00:00 +0100 Full Article
cr Procedure for determination of free and total cholesterol in micro- or nanogram amounts suitable for studies with cultured cells By www.jlr.org Published On :: 1978-11-01 W GambleNov 1, 1978; 19:1068-1070Articles Full Article
cr Fish oils and plasma lipid and lipoprotein metabolism in humans: a critical review By www.jlr.org Published On :: 1989-06-01 WS HarrisJun 1, 1989; 30:785-807Reviews Full Article
cr Microsomal triglyceride transfer protein and its role in apoB-lipoprotein assembly By www.jlr.org Published On :: 2003-01-01 M. Mahmood HussainJan 1, 2003; 44:22-32Reviews Full Article
cr Regulation of hepatic secretion of apolipoprotein B-containing lipoproteins: information obtained from cultured liver cells By www.jlr.org Published On :: 1993-02-01 JL DixonFeb 1, 1993; 34:167-179Reviews Full Article
cr The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism By www.jlr.org Published On :: 2013-09-01 Gijs den BestenSep 1, 2013; 54:2325-2340Reviews Full Article
cr Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans By www.jlr.org Published On :: 2005-11-01 Saverio CintiNov 1, 2005; 46:2347-2355Research Articles Full Article
cr Chatham House Commission on Democracy and Technology in Europe By www.chathamhouse.org Published On :: Thu, 25 Jul 2019 14:47:34 +0000 Chatham House Commission on Democracy and Technology in Europe News Release sysadmin 25 July 2019 Our project on Democracy and Technology in Europe is now entering its final phase. Now we want your help in shaping the final report. Full Article
cr Creon Butler appointed to lead Global Economy and Finance Programme By www.chathamhouse.org Published On :: Tue, 22 Oct 2019 10:22:32 +0000 Creon Butler appointed to lead Global Economy and Finance Programme News Release sysadmin 22 October 2019 Creon Butler has been appointed to lead the Global Economy and Finance programme at Chatham House, joining the institute at the beginning of December. He will also form part of the institute’s senior leadership team. Full Article
cr Announcing Design Resonance in an Age of Crisis By www.chathamhouse.org Published On :: Mon, 01 Jun 2020 08:33:16 +0000 Announcing Design Resonance in an Age of Crisis News Release sysadmin 1 June 2020 London Design Biennale and Chatham House announce Design Resonance in an Age of Crisis, which calls for action by designers around the world to create radical design solutions to critical problems across four key areas: Health, Environment, Society and Work. Full Article
cr Design In An Age of Crisis - Open Call By www.chathamhouse.org Published On :: Tue, 21 Jul 2020 15:14:40 +0000 Design In An Age of Crisis - Open Call News Release sysadmin 21 July 2020 Chatham House and London Design Biennale announce full details of 'Design In An Age of Crisis,' a global Open Call for radical design thinking. Full Article
cr Design in an Age of Crisis Launches By www.chathamhouse.org Published On :: Wed, 13 Jan 2021 17:09:05 +0000 Design in an Age of Crisis Launches News Release jon.wallace 13 January 2021 Design open call receives 500 submissions from over 50 countries across six continents. Full Article
cr Deplatforming Trump puts big tech under fresh scrutiny By www.chathamhouse.org Published On :: Fri, 22 Jan 2021 16:32:14 +0000 Deplatforming Trump puts big tech under fresh scrutiny Expert comment NCapeling 22 January 2021 The response of digital platforms to the US Capitol riots raises questions about online content governance. The EU and UK are starting to come up with answers. The ‘deplatforming’ of Donald Trump – including Twitter’s announcement that it has permanently banned him due to ‘the risk of further incitement of violence’ after the riots in the US – shows once more not only the sheer power of online platforms but also the lack of a coherent and consistent framework for online content governance. Taking the megaphone away from Trump during the Capitol riots seems sensible, but was it necessary or proportionate to ban him from the platform permanently? Or consistent with the treatment of other ‘strongmen’ world leaders such as Modi, Duterte and Ayatollah Ali Khamenei who have overseen nationalistic violence but whose accounts remain intact? Such complex decisions on online expression should not made unilaterally by powerful and unregulated tech actors, but instead should be subject to democratic oversight and grounded in the obligations of states and responsibilities of companies under international human rights law. The speed and scale of digital information has left governments across the world struggling with how to tackle online harms such as hate speech, extremist content and disinformation since the emergence of mass social media 15 years ago. The US’s hallowed approach to the First Amendment, under which speech on public issues – even hate speech – occupies the highest rank and is entitled to special protection, has contributed to a reluctance to regulate Silicon Valley’s digital platforms. But the irony is that by not regulating them, the government harmed freedom of expression by leaving complex speech decisions in the hands of private actors. Meanwhile at the other extreme is the growing number of illiberal and authoritarian governments using a combination of vague laws, censorship, propaganda, and internet blackouts to severely restrict online freedom of expression, control the narrative and, in some cases, incite atrocities. Regulation is on the way The happy medium – flexible online content regulation providing clarity, predictability, transparency, and accountability – has until now been elusive. But even before the deplatforming of Trump, 2021 was set to be the year when this approach finally gained some traction, at least in Europe. The EU’s recently-published draft Digital Services Act puts obligations on dominant social media platforms to manage ‘systemic risks’, for example through requirements for greater transparency about their content decisions, algorithms used for recommendations, and online advertising systems. The UK will shortly publish its Online Safety Bill, which will establish a new regulatory framework for tackling online harms, including the imposition of a duty of care and codes of conduct on Big Tech, to be overseen by an independent regulator (Ofcom). Both proposals are based on a ‘co-regulatory’ model under which the regulator sets out a framework substantiated with rules by the private sector, with the regulator performing a monitoring function to ensure the rules are complied with. Both also draw on international human rights standards and the work of civil society in applying these standards in relation to the online public square, with the aim of increasing control for users over what they see online, requiring transparency about tech companies’ policies in a number of areas, and strengthening the accountability of platforms when they fall foul of the regulation. The procedure for both proposals has also been inclusive, involving extensive multi-stakeholder consultations with civil society organizations and Big Tech, and the proposals will be subject to scrutiny in 2021, notably from the EU and UK parliaments. Both proposals are at an early stage, and it remains to be seen whether they go far enough – or indeed will have a chilling effect on online platforms. But as an attempt to initiate a dialogue on globally coherent principles, they are positive first steps. They also provide food for thought for the new Joe Biden administration in the US as it turns its attention to the regulation of Big Tech. For some time civil society – most prominently David Kaye, the former UN Special Rapporteur on freedom of expression and opinion – have called for content regulation to be informed by universal international human rights law standards. The EU and UK are peculiarly well-placed to take the lead in this area because European countries have for decades been on the receiving end of judgments from the European Court of Human Rights on the appropriate limits to freedom of expression in cases brought under the European Convention on Human Rights. In deciding these cases, the court has to balance the right to freedom of expression against the restrictions imposed – for example in the context of incitement to violence, political debate, and satire. Deciding where to draw the line on what can and cannot be expressed in a civilised society which prizes freedom of expression is inevitably a difficult exercise. International human rights law provides a methodology that inquires whether the interference to freedom of expression was prescribed by law and pursues a legitimate aim, and also whether it was necessary in a democratic society to achieve those aims – including whether the interference was necessary and proportionate (as for example in Delfi AS v Estonia, which involved a news portal failing to take down unlawful hate speech). To be effective, online content regulation has to bite on tech companies, which is a challenge given the internet is global but domestic law normally applies territorially. The EU’s proposals have an extraterritorial element as they apply to any online platforms providing services in the EU regardless of where the platform is headquartered. Further, both the EU and UK want to give the regulator strong enforcement powers – it is proposed for example that Ofcom will have powers to fine platforms up to ten per cent of their turnover for breaches. Although the proposals would not apply directly to the deplatforming of Trump which occurred in the US, the philosophy behind the EU and UK approach is likely to have an impact beyond European shores in promoting a co-regulatory model that some of the bigger tech companies have been inviting for some time, reluctant as they are to ‘play God’ on content moderation decisions without reference to any regulatory framework. In the absence of regulation, the standards of tech platforms such as Facebook and Twitter have already evolved over time in response to pressure from civil rights groups, users, and advertisers, including updated policies on protecting civic conversation and hate speech. Facebook has also set up an independent Oversight Board, whose members include leading human rights lawyers, to review decisions on content including – at its own request – the decision to indefinitely suspend Trump from Facebook and Instagram. Decisions on the Board’s first tranche of cases are expected imminently. Gatekeeper status is key Online content regulation also needs to address the role of Big Tech as the ‘digital gatekeepers’, because their monopoly power extends not just to editorial control of the news and information we consume, but also to market access. The decision of Apple, Google, and Amazon to stop hosting right-wing social network Parler after it refused to combat calls for violence during the US Capitol riots was understandable in the circumstances, but also underlined the unilateral ability of Big Tech to decide the rules of the market. Again, it is Europe where efforts are underway to tackle this issue: the EU’s draft Digital Market Act imposes obligations on online gatekeepers to avoid certain unfair practices, and the UK’s new Digital Markets Unit will have powers to write and enforce a new code of practice on those technology companies with ‘substantial and enduring’ market power. Subscribe to our weekly newsletterOur flagship newsletter provides a weekly round-up of content, plus receive the latest on events and how to connect with the institute. Enter email address Subscribe In the US, Biden’s team will be following these developments with interest, given the growing bipartisan support for strengthening US antitrust rules and reviving antitrust enforcement. The EU’s recently published proposals for an EU-US tech agenda include a transatlantic dialogue on the responsibility of tech platforms and strengthened cooperation between antitrust authorities on digital markets. Ultimately a consistent – and global – approach to online content is needed instead of fragmented approaches by different companies and governments. It is also important the framework is flexible so that it is capable of applying not only to major democracies but also to countries where too often sweeping state regulation has been used as a pretext to curtail online expression online. The pursuit of a pluralistic framework tailored to different political and cultural contexts is challenging, and international human rights law cannot provide all the answers but, as a universal framework, it is a good place to start. The raft of regulatory measures from the EU and UK means that, regardless of whether Trump regains his online megaphone, 2021 is set to be a year of reckoning for Big Tech. Full Article
cr The Implication of Greater Use of Investment Screening By www.chathamhouse.org Published On :: Thu, 11 Feb 2021 13:59:17 +0000 The Implication of Greater Use of Investment Screening 26 June 2020 — 9:00AM TO 10:30AM Anonymous (not verified) 11 February 2021 Online What is driving the trend towards greater use of investment screening by nation states and regional economic groupings? How is the COVID-19 crisis affecting this trend? What will the economic implications be? Will this help or hinder inclusivity and transparency in investment governance? Is there a role for international safeguards and/or international coordination of national/regional approaches to investment screening? This event is part of the Inclusive Governance Initiative, which is examining how to build more inclusive models and mechanisms of global governance fit for purpose in today’s world. Full Article
cr Facebook's power under scrutiny as Trump ban upheld By www.chathamhouse.org Published On :: Thu, 06 May 2021 09:04:43 +0000 Facebook's power under scrutiny as Trump ban upheld Expert comment NCapeling 6 May 2021 Keeping Donald Trump’s Facebook ban in place shows the vast power social media platforms hold, raising questions of whether that power is appropriately used. Kate Jones From a human rights perspective, the Oversight Board’s decision is a strong one, and not at all surprising. The board decided Facebook was right to suspend the former president’s access to post content on Facebook and Instagram, but not indefinitely. It found Donald Trump’s posts violated Facebook’s community standards because they amounted to praise or support of people engaged in violence and that, applying a human rights assessment, Facebook’s suspension of Trump was a necessary and proportionate restriction of his right to freedom of expression. It is in content amplification, not just content moderation, that Facebook should face scrutiny and accountability for the sake of the human rights of its users However the board also found Trump’s indefinite suspension was neither in conformity with a clear Facebook procedure nor consistent with its commitment to respect human rights. Its decision requires Facebook to make a new decision on the future of Donald Trump’s account, grounded in its rules. While opinions on this result will differ, the increased call for clear and accessible rules and respect for human rights in their implementation that the Oversight Board brings to Facebook’s operations is welcome. But the Oversight Board’s powers are limited to content moderation – Facebook declined to answer the board’s questions about amplification of Trump’s posts through the platform’s design decisions and algorithms. This limitation on the board’s role should be lifted. It is in content amplification, not just content moderation, that Facebook should face scrutiny and accountability for the sake of the human rights of its users. Fundamentally, human rights is not a veneer which can mask or legitimize underlying power dynamics or public policy – those still fall to be assessed for themselves. The Trump/Facebook saga does highlight the vast power Facebook and other major social media platforms have over political discussion and persuasion. Through granting or denying, or through amplifying or quietening the voices of political figures, Facebook has the power to shape politics, electorates, and democratic processes. Improving content moderation through the Oversight Board, although important, does little to constrain that power. Facebook itself, unlike a government, has no accountability to the general public, and the Oversight Board must not distract us from the need for a full conversation about the extent to which Facebook’s power is appropriately held and properly wielded. Emily Taylor This decision marks a coming of age for Facebook’s content moderation process. For years, decisions to take down content or ban users have been opaque, conducted by a human workforce that Facebook and other platforms have been hesitant to acknowledge. The platforms have also been worried that being seen to exercise an editorial function might put at risk the legal protections which prevent the platforms being held responsible for user-generated content. When the Oversight Board was first posited, observers questioned whether a body funded by Facebook could properly exercise a legitimate appeals function. Now there is a reasoned decision which partly supports the decision to de-platform a serving president, but also takes issue with the indefinite nature of the ban. If the process is to gain respect as a truly independent oversight on the platform’s decisions, greater transparency over the identity of decision-makers will be needed Facebook specifically asked the Oversight Board to consider specific challenges involved when the person involved is a political leader. The board concluded that Trump’s ‘status as head of state with a high position of trust not only imbued his words with greater force and credibility but also created risks that his followers would understand they could act with impunity’. The storming of the US Capitol and role President Trump played in stirring up the violence underlined that political leaders’ words can motivate others to take harmful actions. Just as the events of January 6 remain shocking, it remains shocking that private platforms have exercised the power to curb the speech of a US president. It also remains shocking that the platforms sat back and took no action over the previous four years, but waited until the final days of the transition. The board’s decision is an evolution in private-sector content moderation, with a diverse board giving a reasoned opinion on a Facebook decision. But to fully comply with the principles of open justice, board decisions should include more detail on the individuals who have made the decision – at present, it appears all members of the board review the decision but it is not clear which individuals were involved in its drafting, or that they were clear from conflicts. If the process is to gain respect as a truly independent oversight on the platform’s decisions, greater transparency over the identity of decision-makers will be needed. Subscribe to our weekly newsletterOur flagship newsletter provides a weekly round-up of content, plus receive the latest on events and how to connect with the institute. Enter email address Subscribe Mark Zuckerberg expressed concern about Facebook becoming an arbiter of truth or free speech and, overall, the difficulty of having private companies managing the application of fundamental rights on their platforms has not been solved. Just because companies have the financial resources to do it, does not mean they necessarily should. Yet no other international governance or arbitration system has emerged to handle the complexities of platform power over speech. In the context of that vacuum, the Oversight Board’s decision is a welcome step. Full Article
cr How are war crimes prosecuted? By www.chathamhouse.org Published On :: Tue, 26 Apr 2022 10:29:49 +0000 How are war crimes prosecuted? Explainer Video NCapeling 26 April 2022 Explaining what war crimes are and how, in the circumstances of Ukraine, could war crimes be prosecuted. The Geneva Conventions and Protocol 1 describe what they call ‘grave breaches’ of international humanitarian law, and both Ukraine and Russia are parties to these treaties. Grave breaches include directly attacking civilians and launching an indiscriminate attack affecting the civilian population or civilian property. Many states and the International Criminal Court (ICC) also have the possibility to prosecute a wider set of war crimes although, in the past, states have not prosecuted many such crimes committed outside their own territory. Neither Russia nor Ukraine is a party to the ICC Statute, but Ukraine did declared it accepted the Court’s jurisdiction for crimes on its territory, and and investigations have now started. But there are several problems to be overcome to achieve successful prosecutions, such as the collection and preservation of evidence, proof of the intent of the suspects in the heat of war, how to be arrest suspects, and the issue of immunity. Full Article
cr The Arg-293 of Cryptochrome1 is responsible for the allosteric regulation of CLOCK-CRY1 binding in circadian rhythm [Computational Biology] By www.jbc.org Published On :: 2020-12-11T00:06:20-08:00 Mammalian circadian clocks are driven by transcription/translation feedback loops composed of positive transcriptional activators (BMAL1 and CLOCK) and negative repressors (CRYPTOCHROMEs (CRYs) and PERIODs (PERs)). CRYs, in complex with PERs, bind to the BMAL1/CLOCK complex and repress E-box–driven transcription of clock-associated genes. There are two individual CRYs, with CRY1 exhibiting higher affinity to the BMAL1/CLOCK complex than CRY2. It is known that this differential binding is regulated by a dynamic serine-rich loop adjacent to the secondary pocket of both CRYs, but the underlying features controlling loop dynamics are not known. Here we report that allosteric regulation of the serine-rich loop is mediated by Arg-293 of CRY1, identified as a rare CRY1 SNP in the Ensembl and 1000 Genomes databases. The p.Arg293His CRY1 variant caused a shortened circadian period in a Cry1−/−Cry2−/− double knockout mouse embryonic fibroblast cell line. Moreover, the variant displayed reduced repressor activity on BMAL1/CLOCK driven transcription, which is explained by reduced affinity to BMAL1/CLOCK in the absence of PER2 compared with CRY1. Molecular dynamics simulations revealed that the p.Arg293His CRY1 variant altered a communication pathway between Arg-293 and the serine loop by reducing its dynamicity. Collectively, this study provides direct evidence that allosterism in CRY1 is critical for the regulation of circadian rhythm. Full Article
cr A novel stress-inducible CmtR-ESX3-Zn2+ regulatory pathway essential for survival of Mycobacterium bovis under oxidative stress [Microbiology] By www.jbc.org Published On :: 2020-12-11T00:06:20-08:00 Reactive oxygen species (ROS) are an unavoidable host environmental cue for intracellular pathogens such as Mycobacterium tuberculosis and Mycobacterium bovis; however, the signaling pathway in mycobacteria for sensing and responding to environmental stress remains largely unclear. Here, we characterize a novel CmtR-Zur-ESX3-Zn2+ regulatory pathway in M. bovis that aids mycobacterial survival under oxidative stress. We demonstrate that CmtR functions as a novel redox sensor and that its expression can be significantly induced under H2O2 stress. CmtR can physically interact with the negative regulator Zur and de-represses the expression of the esx-3 operon, which leads to Zn2+ accumulation and promotion of reactive oxygen species detoxication in mycobacterial cells. Zn2+ can also act as an effector molecule of the CmtR regulator, using which the latter can de-repress its own expression for further inducing bacterial antioxidant adaptation. Consistently, CmtR can induce the expression of EsxH, a component of esx-3 operon involved in Zn2+ transportation that has been reported earlier, and inhibit phagosome maturation in macrophages. Lastly, CmtR significantly contributes to bacterial survival in macrophages and in the lungs of infected mice. Our findings reveal the existence of an antioxidant regulatory pathway in mycobacteria and provide novel information on stress-triggered gene regulation and its association with host–pathogen interaction. Full Article
cr Hepatocyte nuclear factor 1{beta} suppresses canonical Wnt signaling through transcriptional repression of lymphoid enhancer-binding factor 1 [Molecular Bases of Disease] By www.jbc.org Published On :: 2020-12-18T00:06:18-08:00 Hepatocyte nuclear factor-1β (HNF-1β) is a tissue-specific transcription factor that is required for normal kidney development and renal epithelial differentiation. Mutations of HNF-1β produce congenital kidney abnormalities and inherited renal tubulopathies. Here, we show that ablation of HNF-1β in mIMCD3 renal epithelial cells results in activation of β-catenin and increased expression of lymphoid enhancer–binding factor 1 (LEF1), a downstream effector in the canonical Wnt signaling pathway. Increased expression and nuclear localization of LEF1 are also observed in cystic kidneys from Hnf1b mutant mice. Expression of dominant-negative mutant HNF-1β in mIMCD3 cells produces hyperresponsiveness to exogenous Wnt ligands, which is inhibited by siRNA-mediated knockdown of Lef1. WT HNF-1β binds to two evolutionarily conserved sites located 94 and 30 kb from the mouse Lef1 promoter. Ablation of HNF-1β decreases H3K27 trimethylation repressive marks and increases β-catenin occupancy at a site 4 kb upstream to Lef1. Mechanistically, WT HNF-1β recruits the polycomb-repressive complex 2 that catalyzes H3K27 trimethylation. Deletion of the β-catenin–binding domain of LEF1 in HNF-1β–deficient cells abolishes the increase in Lef1 transcription and decreases the expression of downstream Wnt target genes. The canonical Wnt target gene, Axin2, is also a direct transcriptional target of HNF-1β through binding to negative regulatory elements in the gene promoter. These findings demonstrate that HNF-1β regulates canonical Wnt target genes through long-range effects on histone methylation at Wnt enhancers and reveal a new mode of active transcriptional repression by HNF-1β. Full Article
cr MicroRNA-98 reduces nerve growth factor expression in nicotine-induced airway remodeling [Gene Regulation] By www.jbc.org Published On :: 2020-12-25T00:06:30-08:00 Evolving evidence suggests that nicotine may contribute to impaired asthma control by stimulating expression of nerve growth factor (NGF), a neurotrophin associated with airway remodeling and airway hyperresponsiveness. We explored the hypothesis that nicotine increases NGF by reducing lung fibroblast (LF) microRNA-98 (miR-98) and PPARγ levels, thus promoting airway remodeling. Levels of NGF, miR-98, PPARγ, fibronectin 1 (FN1), endothelin-1 (EDN1, herein referred to as ET-1), and collagen (COL1A1 and COL3A1) were measured in human LFs isolated from smoking donors, in mouse primary LFs exposed to nicotine (50 μg/ml), and in whole lung homogenates from mice chronically exposed to nicotine (100 μg/ml) in the drinking water. In selected studies, these pathways were manipulated in LFs with miR-98 inhibitor (anti-miR-98), miR-98 overexpression (miR-98 mimic), or the PPARγ agonist rosiglitazone. Compared with unexposed controls, nicotine increased NGF, FN1, ET-1, COL1A1, and COL3A1 expression in human and mouse LFs and mouse lung homogenates. In contrast, nicotine reduced miR-98 levels in LFs in vitro and in lung homogenates in vivo. Treatment with anti-miR-98 alone was sufficient to recapitulate increases in NGF, FN1, and ET-1, whereas treatment with a miR-98 mimic significantly suppressed luciferase expression in cells transfected with a luciferase reporter linked to the putative seed sequence in the NGF 3'UTR and also abrogated nicotine-induced increases in NGF, FN1, and ET-1 in LFs. Similarly, rosiglitazone increased miR-98 and reversed nicotine-induced increases in NGF, FN1, and ET-1. Taken together, these findings demonstrate that nicotine-induced increases in NGF and other markers of airway remodeling are negatively regulated by miR-98. Full Article
cr Inhibition of the SUV4-20 H1 histone methyltransferase increases frataxin expression in Friedreich's ataxia patient cells [Gene Regulation] By www.jbc.org Published On :: 2020-12-25T00:06:30-08:00 The molecular mechanisms of reduced frataxin (FXN) expression in Friedreich's ataxia (FRDA) are linked to epigenetic modification of the FXN locus caused by the disease-associated GAA expansion. Here, we identify that SUV4-20 histone methyltransferases, specifically SUV4-20 H1, play an important role in the regulation of FXN expression and represent a novel therapeutic target. Using a human FXN–GAA–Luciferase repeat expansion genomic DNA reporter model of FRDA, we screened the Structural Genomics Consortium epigenetic probe collection. We found that pharmacological inhibition of the SUV4-20 methyltransferases by the tool compound A-196 increased the expression of FXN by ∼1.5-fold in the reporter cell line. In several FRDA cell lines and patient-derived primary peripheral blood mononuclear cells, A-196 increased FXN expression by up to 2-fold, an effect not seen in WT cells. SUV4-20 inhibition was accompanied by a reduction in H4K20me2 and H4K20me3 and an increase in H4K20me1, but only modest (1.4–7.8%) perturbation in genome-wide expression was observed. Finally, based on the structural activity relationship and crystal structure of A-196, novel small molecule A-196 analogs were synthesized and shown to give a 20-fold increase in potency for increasing FXN expression. Overall, our results suggest that histone methylation is important in the regulation of FXN expression and highlight SUV4-20 H1 as a potential novel therapeutic target for FRDA. Full Article
cr The Democrats have set themselves up to fail in November's election — and they don't seem to realize it By www.chathamhouse.org Published On :: Mon, 24 Feb 2020 14:52:24 +0000 Source The Independent URL https://www.independent.co.uk/voices/democrats-buttigieg-sanders-trump-biden-str... Release date 21 February 2020 Expert Dr Lindsay Newman In the news type Op-ed Hide date on homepage Full Article
cr Assad’s extortion fails to ease Syria’s financial crisis By www.chathamhouse.org Published On :: Mon, 24 Feb 2020 14:55:32 +0000 Source Arab News URL https://www.arabnews.com/node/1625786 Release date 10 February 2020 Expert Haid Haid In the news type Op-ed Hide date on homepage Full Article
cr Will the ICJ Myanmar Ruling Help Bring Accountability for the Rohingya Crisis? By www.chathamhouse.org Published On :: Wed, 06 May 2020 17:30:43 +0000 Source The Diplomat URL https://thediplomat.com/2020/03/will-the-icj-myanmar-ruling-help-bring-accountab... Release date 18 March 2020 Expert Dr Champa Patel In the news type Op-ed Hide date on homepage Full Article
cr A Deep-Diving Sub. A Deadly Fire. And Russia’s Secret Undersea Agenda By www.chathamhouse.org Published On :: Wed, 13 May 2020 15:37:45 +0000 Source New York Times URL https://www.nytimes.com/2020/04/20/world/europe/russian-submarine-fire-losharik.... Release date 20 April 2020 Expert Mathieu Boulègue In the news type Op-ed Hide date on homepage Full Article
cr Why democracies do better at surviving pandemics By www.chathamhouse.org Published On :: Wed, 27 May 2020 11:59:28 +0000 Source Los Angeles Times URL https://www.latimes.com/opinion/story/2020-05-26/democracies-autocracies-coronav... Release date 26 May 2020 Expert Robin Niblett Dr Leslie Vinjamuri In the news type Op-ed Hide date on homepage Full Article