orm Resetting Africa-Europe relations: From self-deception to economic transformation By www.chathamhouse.org Published On :: Wed, 16 Oct 2024 10:47:14 +0000 Resetting Africa-Europe relations: From self-deception to economic transformation 28 October 2024 — 12:30PM TO 1:30PM Anonymous (not verified) 16 October 2024 Chatham House and Online Experts assess the status of ties between Africa and Europe in a rapidly changing world, launching a new book that explores how misconceptions in the relationship can harm Africa’s economic agenda. The relationship between Africa and Europe has long been shaped by colonial legacies, power imbalance and shifting geopolitical interests.Almost three years on from the last EU-AU summit in Brussels in February 2022, questions remain over the delivery of headline commitments under the continent-to-continent partnership – ranging from the EU’s Global Gateway infrastructure strategy to wider climate financing promises.As Africa seeks to strengthen its standing on the global stage, marked by the African Union’s upcoming debut at the G20 summit in November, a critical reassessment of these dynamics is needed to examine whether the continent’s relationship with Europe can overcome stigmatized narratives in search of genuine economic benefit.At this event, which launches a new book by Professor Carlos Lopes: The Self-Deception Trap: Exploring the Economic Dimensions of Charity Dependency within Africa-Europe Relations, speakers assess the prospects for a transformative shift towards a more equitable and mutually beneficial Africa-Europe partnership. Full Article
orm Reforming the EU: A View From Poland By f1.media.brightcove.com Published On :: Fri, 11 May 2018 00:00:00 +0100 Full Article
orm Outperformers and New Contenders in Emerging Markets By f1.media.brightcove.com Published On :: Tue, 04 Dec 2018 00:00:00 +0000 Full Article
orm Icebreaker Lecture: China’s Financial Sector – Reform and Opening Up By f1.media.brightcove.com Published On :: Tue, 12 Mar 2019 00:00:00 +0000 Full Article
orm Operation Decisive Storm: Analysing Four Years of Conflict in Yemen By f1.media.brightcove.com Published On :: Thu, 21 Mar 2019 00:00:00 +0000 Full Article
orm Preparing for Digital Transformation By f1.media.brightcove.com Published On :: Wed, 10 Jul 2019 00:00:00 +0100 Full Article
orm Ukraine’s Reform Agenda: Shaping the Future By f1.media.brightcove.com Published On :: Thu, 21 Nov 2019 00:00:00 +0000 Full Article
orm Angola's Business Promise: Evaluating the Progress of Privatization and Other Economic Reforms By f1.media.brightcove.com Published On :: Tue, 21 Jan 2020 00:00:00 +0000 Full Article
orm Normal high density lipoprotein inhibits three steps in the formation of mildly oxidized low density lipoprotein: steps 2 and 3 By www.jlr.org Published On :: 2000-09-01 Mohamad NavabSep 1, 2000; 41:1495-1508Articles Full Article
orm Normal high density lipoprotein inhibits three steps in the formation of mildly oxidized low density lipoprotein: step 1 By www.jlr.org Published On :: 2000-09-01 Mohamad NavabSep 1, 2000; 41:1481-1494Articles Full Article
orm 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
orm Identification of multiple subclasses of plasma low density lipoproteins in normal humans By www.jlr.org Published On :: 1982-01-01 Ronald M. KraussJan 1, 1982; 23:97-104Articles Full Article
orm Bile salt biotransformations by human intestinal bacteria By www.jlr.org Published On :: 2006-02-01 Jason M. RidlonFeb 1, 2006; 47:241-259Reviews Full Article
orm 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
orm Insights from Climate Policy: Engaging Subnational Governments in Global Platforms By www.chathamhouse.org Published On :: Tue, 09 Feb 2021 12:54:17 +0000 Insights from Climate Policy: Engaging Subnational Governments in Global Platforms 10 June 2020 — 2:45PM TO 6:00PM Anonymous (not verified) 9 February 2021 Online How have subnational governments shaped the global agenda and created momentum on climate change where national and international governance processes could not? Can these advances be converted into meaningful collaboration channels for policy development? What works, or does not, when it comes to engagement with multilateral negotiation processes? What ingredients are necessary for success? What are the broader implications of these trends for inclusivity and innovation in international governance? 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
orm Stop codon read-through of mammalian MTCH2 leading to an unstable isoform regulates mitochondrial membrane potential [Gene Regulation] By www.jbc.org Published On :: 2020-12-11T00:06:20-08:00 Stop codon read-through (SCR) is a process of continuation of translation beyond a stop codon. This phenomenon, which occurs only in certain mRNAs under specific conditions, leads to a longer isoform with properties different from that of the canonical isoform. MTCH2, which encodes a mitochondrial protein that regulates mitochondrial metabolism, was selected as a potential read-through candidate based on evolutionary conservation observed in the proximal region of its 3' UTR. Here, we demonstrate translational read-through across two evolutionarily conserved, in-frame stop codons of MTCH2 using luminescence- and fluorescence-based assays, and by analyzing ribosome-profiling and mass spectrometry (MS) data. This phenomenon generates two isoforms, MTCH2x and MTCH2xx (single- and double-SCR products, respectively), in addition to the canonical isoform MTCH2, from the same mRNA. Our experiments revealed that a cis-acting 12-nucleotide sequence in the proximal 3' UTR of MTCH2 is the necessary signal for SCR. Functional characterization showed that MTCH2 and MTCH2x were localized to mitochondria with a long t1/2 (>36 h). However, MTCH2xx was found predominantly in the cytoplasm. This mislocalization and its unique C terminus led to increased degradation, as shown by greatly reduced t1/2 (<1 h). MTCH2 read-through–deficient cells, generated using CRISPR-Cas9, showed increased MTCH2 expression and, consistent with this, decreased mitochondrial membrane potential. Thus, double-SCR of MTCH2 regulates its own expression levels contributing toward the maintenance of normal mitochondrial membrane potential. Full Article
orm Iraq is trying yet again to form a government. Why is it so hard? By www.chathamhouse.org Published On :: Wed, 06 May 2020 17:33:52 +0000 Source The Washington Post URL https://www.washingtonpost.com/politics/2020/04/15/iraq-is-trying-yet-again-form... Release date 15 April 2020 Expert Dr Renad Mansour In the news type Op-ed Hide date on homepage Full Article
orm Novel fluorescent GPCR biosensor detects retinal equilibrium binding to opsin and active G protein and arrestin signaling conformations [Molecular Biophysics] By www.jbc.org Published On :: 2020-12-18T00:06:18-08:00 Rhodopsin is a canonical class A photosensitive G protein–coupled receptor (GPCR), yet relatively few pharmaceutical agents targeting this visual receptor have been identified, in part due to the unique characteristics of its light-sensitive, covalently bound retinal ligands. Rhodopsin becomes activated when light isomerizes 11-cis-retinal into an agonist, all-trans-retinal (ATR), which enables the receptor to activate its G protein. We have previously demonstrated that, despite being covalently bound, ATR can display properties of equilibrium binding, yet how this is accomplished is unknown. Here, we describe a new approach for both identifying compounds that can activate and attenuate rhodopsin and testing the hypothesis that opsin binds retinal in equilibrium. Our method uses opsin-based fluorescent sensors, which directly report the formation of active receptor conformations by detecting the binding of G protein or arrestin fragments that have been fused onto the receptor's C terminus. We show that these biosensors can be used to monitor equilibrium binding of the agonist, ATR, as well as the noncovalent binding of β-ionone, an antagonist for G protein activation. Finally, we use these novel biosensors to observe ATR release from an activated, unlabeled receptor and its subsequent transfer to the sensor in real time. Taken together, these data support the retinal equilibrium binding hypothesis. The approach we describe should prove directly translatable to other GPCRs, providing a new tool for ligand discovery and mutant characterization. Full Article
orm The Impact of Brexit on Energy Transformation in the UK and EU By www.chathamhouse.org Published On :: Mon, 03 Dec 2018 14:20:01 +0000 The Impact of Brexit on Energy Transformation in the UK and EU 28 March 2019 — 8:15AM TO 9:45AM Anonymous (not verified) 3 December 2018 Chatham House | 10 St James's Square | London | SW1Y 4LE The UK’s decision to leave the EU will fundamentally reshape many of the UK’s policies and its relations with countries around the world. For energy and climate, the changes could be significant and will need to be managed carefully to secure ongoing investment, stable energy prices and ambitious climate objectives. The UK’s departure will also affect the balance of political support for climate and energy policies with the EU institutions and potentially impact upon regional initiatives. This roundtable will discuss:The impact on the energy sector of Brexit during the transition period through until December 2020 including the operation of interconnectors and access to the Internal energy market, ongoing engagement in European research collaboration and the replacement of European financial resources.The possible opportunities and risks for the UK’s energy sector in 2021 and beyond.The implications of Brexit on the EU’s energy and climate policy.The roundtable will discuss the role of the public and business in shaping the future deal as it will need to be ratified by the parliaments of all member states.Attendance at this event is by invitation only. Full Article
orm Power Sector Transformation, New Market Dynamics and Geopolitical Implications By www.chathamhouse.org Published On :: Thu, 06 Dec 2018 13:45:01 +0000 Power Sector Transformation, New Market Dynamics and Geopolitical Implications 7 November 2018 — 8:00AM TO 9:30AM Anonymous (not verified) 6 December 2018 Chatham House | 10 St James's Square | London | SW1Y 4LE The global electricity sector is experiencing profound change due to a confluence of technological innovation, environmental policies and regulatory reform. The effect is most obvious in the EU28, Australia and parts of North America.However, this is just the beginning and the success of the next phase of electricity sector transformations hinges on enhancing system flexibility to facilitate unhindered low-cost deployment of renewables. It remains to be seen how utilities will seek to navigate this second phase of electricity transformations.This session starts with a presentation and discussion that focuses on:Public and private sector risks of the transformation of the power sector, changes in generation mix and their implications for supply chain, employments and investment patterns.The role of government and the regulatory framework in light of changing market structure, new entrants and big data.Wider geopolitical issues including the implication for fossil fuel producers and the rise in demand for new materials and changes in land use. The possible implications on the power sector on the electrification of heat and transport.The discussion then moves to the speed of transformation and what this means for existing and new market actors. Full Article
orm Food system transformation: A blind spot for climate and biodiversity action? By www.chathamhouse.org Published On :: Wed, 05 Oct 2022 10:57:14 +0000 Food system transformation: A blind spot for climate and biodiversity action? 20 October 2022 — 12:00PM TO 1:00PM Anonymous (not verified) 5 October 2022 Chatham House and Online How can COP27 and COP15 accelerate the agenda for sustainable food systems and land use? Tackling the dual crises of climate change and biodiversity loss requires extraordinary levels of action at an unprecedented speed. Agriculture is the biggest user of land, the biggest source of methane emissions, a major contributor to total greenhouse gas emissions and the leading driver of biodiversity loss. Anything short of a food system transformation puts climate and biodiversity objectives in peril. However, governments have not yet produced credible pathways and strong policies for tackling our growing ‘foodprint’ – the negative impacts of what we grow and eat. In advance of COP27 in Sharm El-Sheikh for climate and COP15 in Montreal for biodiversity, Chatham House has published a new briefing paper which examines aligning food systems with climate and biodiversity targets. The paper reviews the climate and biodiversity policy landscape to 2030, with a focus on land-based aspects and the inclusion of food and agriculture. The paper highlights serious conflicts between the impacts of the food system and goals to protect and restore biodiversity and mitigate climate change. In light of this, opportunities for joined-up action on food, climate and biodiversity are identified, including three key steps for countries to take this decade to produce suitably ambitious and effective policies across the climate–biodiversity–food nexus. This event brings together leading voices from the international policy arenas for climate and biodiversity to react to the briefing paper and discuss how COP27 and COP15 can accelerate the agenda for sustainable food systems and land use. Full Article
orm Deformation of Artinian Algebras and Jordan Type By www.ams.org Published On :: Fri, 30 Aug 2024 09:28 EDT Anthony Iarrobino, Pedro Macias Marques, Maria Evelina Rossi and Jean Vallès, editors. American Mathematical Society, 2024, CONM, volume 805, approx. 252 pp. ISBN: 978-1-4704-7356-3 (print), 978-1-4704-7665-6 (online). This volume contains the proceedings of the AMS-EMS-SMF Special Session on Deformations of Artinian Algebras and Jordan Type, held July 18–22,... Full Article
orm Corrigendum to “The Class Number one Problem for the Normal CM-fields of degree 32” By www.ams.org Published On :: Thu, 31 Oct 2024 16:22 EDT Soun-Hi Kwon Trans. Amer. Math. Soc. 377 (), 6021-6022. Abstract, references and article information Full Article
orm Colength one deformation rings By www.ams.org Published On :: Thu, 31 Oct 2024 16:22 EDT Daniel Le, Bao V. Le Hung, Stefano Morra, Chol Park and Zicheng Qian Trans. Amer. Math. Soc. 377 (), 5749-5786. Abstract, references and article information Full Article
orm On Lamperti transformation and AR(1) type characterisations of discrete random fields By www.ams.org Published On :: Tue, 05 Nov 2024 14:10 EST Marko Voutilainen, Lauri Viitasaari and Pauliina Ilmonen Theor. Probability and Math. Statist. 111 (), 181-197. Abstract, references and article information Full Article
orm Asymptotic normality of estimators for all parameters in the Vasicek model by discrete observations By www.ams.org Published On :: Tue, 05 Nov 2024 14:10 EST Olha Prykhodko and Kostiantyn Ralchenko Theor. Probability and Math. Statist. 111 (), 123-135. Abstract, references and article information Full Article
orm A convolution inequality, yielding a sharper Berry–Esseen theorem for summands Zolotarev-close to normal By www.ams.org Published On :: Tue, 05 Nov 2024 14:10 EST Lutz Mattner Theor. Probability and Math. Statist. 111 (), 45-122. Abstract, references and article information Full Article
orm Multivariate asymptotic normality determined by high moments By www.ams.org Published On :: Tue, 05 Nov 2024 15:05 EST Paweł Hitczenko and Nick Wormald Proc. Amer. Math. Soc. 152 (), 5411-5427. Abstract, references and article information Full Article
orm Brylinski-Radon transformation and generic projections By www.ams.org Published On :: Tue, 05 Nov 2024 15:05 EST Yongqiang Liu, Laurentiu Maxim and Botong Wang Proc. Amer. Math. Soc. 152 (), 5279-5288. Abstract, references and article information Full Article
orm Non-uniformly continuous nearest point maps By www.ams.org Published On :: Tue, 05 Nov 2024 15:05 EST Rubén Medina and Andrés Quilis Proc. Amer. Math. Soc. 152 (), 5137-5148. Abstract, references and article information Full Article
orm On Rankin-Cohen brackets of Hecke eigenforms and modular forms of half-integral weight By www.ams.org Published On :: Tue, 05 Nov 2024 15:05 EST YoungJu Choie, Winfried Kohnen and Yichao Zhang Proc. Amer. Math. Soc. 152 (), 5025-5037. Abstract, references and article information Full Article
orm Norm inequalities with fractional integrals By www.ams.org Published On :: Fri, 08 Nov 2024 14:08 EST E. P. Ushakova and K. E. Ushakova St. Petersburg Math. J. 35 (), 571-595. Abstract, references and article information Full Article
orm Michael Grimm, former House member convicted of tax fraud, is paralyzed in fall from horse By www.yahoo.com Published On :: 2024-11-11T17:51:20Z Full Article
orm Biochemical transformation of bacterial lipopolysaccharides by acyloxyacyl hydrolase reduces host injury and promotes recovery [Enzymology] By www.jbc.org Published On :: 2020-12-18T00:06:18-08:00 Animals can sense the presence of microbes in their tissues and mobilize their own defenses by recognizing and responding to conserved microbial structures (often called microbe-associated molecular patterns (MAMPs)). Successful host defenses may kill the invaders, yet the host animal may fail to restore homeostasis if the stimulatory microbial structures are not silenced. Although mice have many mechanisms for limiting their responses to lipopolysaccharide (LPS), a major Gram-negative bacterial MAMP, a highly conserved host lipase is required to extinguish LPS sensing in tissues and restore homeostasis. We review recent progress in understanding how this enzyme, acyloxyacyl hydrolase (AOAH), transforms LPS from stimulus to inhibitor, reduces tissue injury and death from infection, prevents prolonged post-infection immunosuppression, and keeps stimulatory LPS from entering the bloodstream. We also discuss how AOAH may increase sensitivity to pulmonary allergens. Better appreciation of how host enzymes modify LPS and other MAMPs may help prevent tissue injury and hasten recovery from infection. Full Article
orm Carnosine synthase deficiency is compatible with normal skeletal muscle and olfactory function but causes reduced olfactory sensitivity in aging mice [Developmental Biology] By www.jbc.org Published On :: 2020-12-11T00:06:20-08:00 Carnosine (β-alanyl-l-histidine) and anserine (β-alanyl-3-methyl-l-histidine) are abundant peptides in the nervous system and skeletal muscle of many vertebrates. Many in vitro and in vivo studies demonstrated that exogenously added carnosine can improve muscle contraction, has antioxidant activity, and can quench various reactive aldehydes. Some of these functions likely contribute to the proposed anti-aging activity of carnosine. However, the physiological role of carnosine and related histidine-containing dipeptides (HCDs) is not clear. In this study, we generated a mouse line deficient in carnosine synthase (Carns1). HCDs were undetectable in the primary olfactory system and skeletal muscle of Carns1-deficient mice. Skeletal muscle contraction in these mice, however, was unaltered, and there was no evidence for reduced pH-buffering capacity in the skeletal muscle. Olfactory tests did not reveal any deterioration in 8-month-old mice lacking carnosine. In contrast, aging (18–24-month-old) Carns1-deficient mice exhibited olfactory sensitivity impairments that correlated with an age-dependent reduction in the number of olfactory receptor neurons. Whereas we found no evidence for elevated levels of lipoxidation and glycation end products in the primary olfactory system, protein carbonylation was increased in the olfactory bulb of aged Carns1-deficient mice. Taken together, these results suggest that carnosine in the olfactory system is not essential for information processing in the olfactory signaling pathway but does have a role in the long-term protection of olfactory receptor neurons, possibly through its antioxidant activity. Full Article
orm Evolving the naturally compromised chorismate mutase from Mycobacterium tuberculosis to top performance [Protein Structure and Folding] By www.jbc.org Published On :: 2020-12-18T00:06:18-08:00 Chorismate mutase (CM), an essential enzyme at the branch-point of the shikimate pathway, is required for the biosynthesis of phenylalanine and tyrosine in bacteria, archaea, plants, and fungi. MtCM, the CM from Mycobacterium tuberculosis, has less than 1% of the catalytic efficiency of a typical natural CM and requires complex formation with 3-deoxy-d-arabino-heptulosonate 7-phosphate synthase for high activity. To explore the full potential of MtCM for catalyzing its native reaction, we applied diverse iterative cycles of mutagenesis and selection, thereby raising kcat/Km 270-fold to 5 × 105 m−1s−1, which is even higher than for the complex. Moreover, the evolutionarily optimized autonomous MtCM, which had 11 of its 90 amino acids exchanged, was stabilized compared with its progenitor, as indicated by a 9 °C increase in melting temperature. The 1.5 Å crystal structure of the top-evolved MtCM variant reveals the molecular underpinnings of this activity boost. Some acquired residues (e.g. Pro52 and Asp55) are conserved in naturally efficient CMs, but most of them lie beyond the active site. Our evolutionary trajectories reached a plateau at the level of the best natural enzymes, suggesting that we have exhausted the potential of MtCM. Taken together, these findings show that the scaffold of MtCM, which naturally evolved for mediocrity to enable inter-enzyme allosteric regulation of the shikimate pathway, is inherently capable of high activity. Full Article
orm Formal Representation for Young People Enhances Politics for All By www.chathamhouse.org Published On :: Thu, 10 Sep 2020 11:38:51 +0000 10 September 2020 Ben Horton Communications Manager, Communications and Publishing @BenRHorton LinkedIn Michel Alimasi Member, Common Futures Conversations, Italy Gift Jedida Member, Common Futures Conversations, Kenya Sanne Thijssen Member, Common Futures Conversations, Netherlands Mondher Tounsi Member, Common Futures Conversations, Tunisia Despite grassroots associations, community organizing and online groups offering pathways for political engagement, the room for youth representation in international politics remains narrow, with many young people still left feeling they are passive participants in policymaking. CFC Youth Participation EC_10092020.png Youth protests at Parliament square against a new exam rating system which has been introduced in British education system - London, England on August 16, 2020. Photo by Dominika Zarzycka/NurPhoto via Getty Images. According to UN Youth, people aged 15-24 make up one-sixth of the world’s population but, in roughly one-third of countries, the eligibility for parliamentarians begins at 25 years old and only 1.6% of parliamentarians are in their twenties. Young people are largely being excluded and overlooked, both as political candidates and even as participants in political processes, giving them limited political control over their own futures. If politics continues to be regarded as a space for older, more politically experienced individuals from particular backgrounds, young people will continue to be left systematically marginalized, and overall disengagement with politics within societies will continue to grow. Global leaders may increasingly point out the importance of youth representation in national and international fora, but the reality is their real policymaking impact still comes mainly from self-organized and informal activities.And yet, despite this continued exclusion, huge numbers of young people are interested in political and civic engagement, and they have been driven to create new spaces. Youth networks, movements, and constituencies have emerged which provide the opportunity for younger voices to express political stances, and thus enhance the diversity and inclusivity of political debate. From the global Extinction Rebellion protests, to the student-led Rhodes Must Fall movement in South Africa and the UK, there are numerous examples of the power of informal youth networks and movements pushing for change. In certain cases, such as Sudan’s political revolution in 2019, we can see how direct action by young people creates major impact, but unfortunately these successes are few as most informal initiatives remain overlooked and undervalued. Putting youth representation into governmentCreating diverse representation requires the linking of vital informal networks to formal political processes. In response to a recent Common Futures Conversations challenge, one mechanism with the potential to achieve this aim that emerged is creating dedicated youth representatives within government departments, so that qualified young people with relevant expertise are formally appointed to act as the link between government and informal youth movements. These individuals should be hired as employees rather than volunteers and take up the responsibilities of a government employee, supported by a large network of youth-led movements and initiatives as well as a smaller, voluntary advisory board of young people. This network then acts as a sounding board for the representative, gathering the opinions in their local communities and bringing forward crucial concerns so the youth representatives can confidently feed into policymaking processes with a clear sense of the substance of youth opinion. Alongside the network, a voluntary board of young people could provide additional support to the representatives when required to consult a broader range of youth organizations.Both in the youth network and the board, a key priority is to involve different movements and initiatives reflecting diversities such as geographic spread, people who are marginalized due to ethnicity, gender or sexuality, educational and professional backgrounds, and other factors. Implementing such a structure would ensure more diversity in youth representation, something which is missing in many existing youth participation and formal political structures. Representation needs to move away from only highly-educated youth living in cities to ensure more influence for those young people usually left on the sidelines. Youth involvement in politics leads to better civic engagement overall. It improves the influence and access of young people, and supports governments becoming more inclusive and responsive to the plurality of voices they are representing. It also has the potential of encouraging millions more people to become properly engaged with politics. In order to gain support from parliamentarians and policymakers, it is crucial to highlight these benefits and demonstrate how the support of young people helps shift the political landscape for the better. All the necessary parties already exist in most countries, so all that is required is to drive a collective initiative and for both governments and the youth to take responsibility for making it work.As the former president of Ireland Mary Robinson said during a recent Chatham House Centenary event: ‘We need to make space for young people so we can hear their voices, their imagination, their commitment to question and speak truth to power. We need young people to feel that they are part of the solution.’ Building formal structures is a necessary step to achieving this vision, as it provides practical solutions to realize a more diverse, inclusive and meaningful participation of the youth in politics, and also creates more representative and responsive governments. Full Article
orm Guidance and best practices for nuclear cardiology laboratories during the coronavirus disease 2019 (COVID-19) pandemic: An Information Statement from ASNC and SNMMI By jnm.snmjournals.org Published On :: 2020-05-15T05:25:22-07:00 Full Article
orm MIRD Pamphlet No. 31: MIRDcell V4--Artificial Intelligence Tools to Formulate Optimized Radiopharmaceutical Cocktails for Therapy By jnm.snmjournals.org Published On :: 2024-10-24T11:58:49-07:00 Visual Abstract Full Article
orm Performance Characteristics of a New Generation 148-cm Axial Field-of-View uMI Panorama GS PET/CT System with Extended NEMA NU 2-2018 and EARL Standards By jnm.snmjournals.org Published On :: 2024-11-07T04:28:32-08:00 Visual Abstract Full Article
orm Pacific Rim timeline: Information for defenders from a braid of interlocking attack campaigns By news.sophos.com Published On :: Thu, 31 Oct 2024 12:31:52 +0000 Sophos X-Ops unveils five-year investigation tracking China-based groups targeting perimeter devices Full Article Security Operations Chinese APT Cyberoam featured Pacific Rim Story Sophos Firewall state-sponsored attackers
orm Novel Proteomic Profiling of Epididymal Extracellular Vesicles in the Domestic Cat Reveals Proteins Related to Sequential Sperm Maturation with Differences Observed between Normospermic and Teratospermic Individuals By www.mcponline.org Published On :: 2020-12-01 Tricia RowlisonDec 1, 2020; 19:2090-2103Research Full Article
orm Thyroglobulin interactome profiling defines altered proteostasis topology associated with thyroid dyshormonogenesis By www.mcponline.org Published On :: 2020-11-18 Madison T WrightNov 18, 2020; 0:RA120.002168v1-mcp.RA120.002168Research Full Article
orm Plasma proteomic data can contain personally identifiable, sensitive information and incidental findings By www.mcponline.org Published On :: 2020-12-17 Philipp Emanuel GeyerDec 17, 2020; 0:RA120.002359v1-mcp.RA120.002359Research Full Article
orm Mycobacterium tuberculosis infection up-regulates MFN2 expression to promote NLRP3 inflammasome formation [Cell Biology] By www.jbc.org Published On :: 2020-12-18T00:06:18-08:00 Tuberculosis (TB), caused by the infection of Mycobacterium tuberculosis (MTB), is one of the leading causes of death worldwide, especially in children. However, the mechanisms by which MTB infects its cellular host, activates an immune response, and triggers inflammation remain unknown. Mitochondria play important roles in the initiation and activation of the nucleotide-binding oligomerization domain-like receptor with a pyrin domain 3 (NLRP3) inflammasome, where mitochondria-associated endoplasmic reticulum membranes (MAMs) may serve as the platform for inflammasome assembly and activation. Additionally, mitofusin 2 (MFN2) is implicated in the formation of MAMs, but, the roles of mitochondria and MFN2 in MTB infection have not been elucidated. Using mircroarry profiling of TB patients and in vitro MTB stimulation of macrophages, we observed an up-regulation of MFN2 in the peripheral blood mononuclear cells of active TB patients. Furthermore, we found that MTB stimulation by MTB-specific antigen ESAT-6 or lysate of MTB promoted MFN2 interaction with NLRP3 inflammasomes, resulting in the assembly and activation of the inflammasome and, subsequently, IL-1β secretion. These findings suggest that MFN2 and mitochondria play important role in the pathogen-host interaction during MTB infection. Full Article
orm AMPK{beta}1 and AMPK{beta}2 define an isoform-specific gene signature in human pluripotent stem cells, differentially mediating cardiac lineage specification [Cell Biology] By www.jbc.org Published On :: 2020-12-18T00:06:18-08:00 AMP-activated protein kinase (AMPK) is a key regulator of energy metabolism that phosphorylates a wide range of proteins to maintain cellular homeostasis. AMPK consists of three subunits: α, β, and γ. AMPKα and β are encoded by two genes, the γ subunit by three genes, all of which are expressed in a tissue-specific manner. It is not fully understood, whether individual isoforms have different functions. Using RNA-Seq technology, we provide evidence that the loss of AMPKβ1 and AMPKβ2 lead to different gene expression profiles in human induced pluripotent stem cells (hiPSCs), indicating isoform-specific function. The knockout of AMPKβ2 was associated with a higher number of differentially regulated genes than the deletion of AMPKβ1, suggesting that AMPKβ2 has a more comprehensive impact on the transcriptome. Bioinformatics analysis identified cell differentiation as one biological function being specifically associated with AMPKβ2. Correspondingly, the two isoforms differentially affected lineage decision toward a cardiac cell fate. Although the lack of PRKAB1 impacted differentiation into cardiomyocytes only at late stages of cardiac maturation, the availability of PRKAB2 was indispensable for mesoderm specification as shown by gene expression analysis and histochemical staining for cardiac lineage markers such as cTnT, GATA4, and NKX2.5. Ultimately, the lack of AMPKβ1 impairs, whereas deficiency of AMPKβ2 abrogates differentiation into cardiomyocytes. Finally, we demonstrate that AMPK affects cellular physiology by engaging in the regulation of hiPSC transcription in an isoform-specific manner, providing the basis for further investigations elucidating the role of dedicated AMPK subunits in the modulation of gene expression. Full Article
orm Murine GFP-Mx1 forms nuclear condensates and associates with cytoplasmic intermediate filaments: Novel antiviral activity against VSV [Immunology] By www.jbc.org Published On :: 2020-12-25T00:06:30-08:00 Type I and III interferons induce expression of the “myxovirus resistance proteins” MxA in human cells and its ortholog Mx1 in murine cells. Human MxA forms cytoplasmic structures, whereas murine Mx1 forms nuclear bodies. Whereas both HuMxA and MuMx1 are antiviral toward influenza A virus (FLUAV) (an orthomyxovirus), only HuMxA is considered antiviral toward vesicular stomatitis virus (VSV) (a rhabdovirus). We previously reported that the cytoplasmic human GFP-MxA structures were phase-separated membraneless organelles (“biomolecular condensates”). In the present study, we investigated whether nuclear murine Mx1 structures might also represent phase-separated biomolecular condensates. The transient expression of murine GFP-Mx1 in human Huh7 hepatoma, human Mich-2H6 melanoma, and murine NIH 3T3 cells led to the appearance of Mx1 nuclear bodies. These GFP-MuMx1 nuclear bodies were rapidly disassembled by exposing cells to 1,6-hexanediol (5%, w/v), or to hypotonic buffer (40–50 mosm), consistent with properties of membraneless phase-separated condensates. Fluorescence recovery after photobleaching (FRAP) assays revealed that the GFP-MuMx1 nuclear bodies upon photobleaching showed a slow partial recovery (mobile fraction: ∼18%) suggestive of a gel-like consistency. Surprisingly, expression of GFP-MuMx1 in Huh7 cells also led to the appearance of GFP-MuMx1 in 20–30% of transfected cells in a novel cytoplasmic giantin-based intermediate filament meshwork and in cytoplasmic bodies. Remarkably, Huh7 cells with cytoplasmic murine GFP-MuMx1 filaments, but not those with only nuclear bodies, showed antiviral activity toward VSV. Thus, GFP-MuMx1 nuclear bodies comprised phase-separated condensates. Unexpectedly, GFP-MuMx1 in Huh7 cells also associated with cytoplasmic giantin-based intermediate filaments, and such cells showed antiviral activity toward VSV. Full Article
orm Palmitoylation of acetylated tubulin and association with ceramide-rich platforms is critical for ciliogenesis By www.jlr.org Published On :: 2020-12-30 Priyanka TripathiDec 30, 2020; 0:jlr.RA120001190v1-jlr.RA120001190Research Articles Full Article
orm Human glucocerebrosidase mediates formation of xylosyl-cholesterol by {beta}-xylosidase and transxylosidase reactions. By www.jlr.org Published On :: 2020-12-23 Daphne E.C. BoerDec 23, 2020; 0:jlr.RA120001043v1-jlr.RA120001043Research Articles Full Article
orm Insights on the kinetics and dynamics of the furin-cleaved form of PCSK9 By www.jlr.org Published On :: 2020-11-17 Carlota OleagaNov 17, 2020; 0:jlr.RA120000964v1-jlr.RA120000964Research Articles Full Article