b Tackling Cyber Disinformation in Elections: Applying International Human Rights Law By feedproxy.google.com Published On :: Wed, 18 Sep 2019 10:30:02 +0000 Research Event Tackling Cyber Disinformation in Elections: Applying International Human Rights Law 6 November 2019 - 5:30pm to 7:00pm Chatham House | 10 St James's Square | London | SW1Y 4LE Susie Alegre, Barrister and Associate Tenant, Doughty Street ChambersEvelyn Aswad, Professor of Law and the Herman G. Kaiser Chair in International Law, University of OklahomaBarbora Bukovská, Senior Director for Law and Policy, Article 19Kate Jones, Director, Diplomatic Studies Programme, University of OxfordChair: Harriet Moynihan, Associate Fellow, International Law Programme, Chatham House Register Interest Cyber operations are increasingly used by political parties, their supporters and foreign states to influence electorates – from algorithms promoting specific messages to micro-targeting based on personal data and the creation of filter bubbles. The risks of digital tools spreading disinformation and polarizing debate, as opposed to deepening democratic engagement, have been highlighted by concerns over cyber interference in the UK’s Brexit referendum, the 2016 US presidential elections and in Ukraine. While some governments are adopting legislation in an attempt to address some of these issues, for example Germany’s ‘NetzDG’ law and France’s ‘Law against the manipulation of information’, other countries have proposed an independent regulator as in the case of the UK’s Online Harms white paper. Meanwhile, the digital platforms, as the curators of content, are under increasing pressure to take their own measures to address data mining and manipulation in the context of elections. How do international human rights standards, for example on freedom of thought, expression and privacy, guide the use of digital technology in the electoral context? What practical steps can governments and technology actors take to ensure policies, laws and practices are in line with these fundamental standards? And with a general election looming in the UK, will these steps come soon enough? This event brings together a wide range of stakeholders including civil society, the tech sector, legal experts and government, coincides with the publication of a Chatham House research paper on disinformation, elections and the human rights framework. Jacqueline Rowe Programme Assistant, International Law Programme 020 7389 3287 Email Department/project International Law Programme, Cyber, Sovereignty and Human Rights, Rights, Accountability and Justice Full Article
b Cyber, Sovereignty and Human Rights By feedproxy.google.com Published On :: Fri, 20 Sep 2019 14:01:20 +0000 Our work in this area explores how international law regulates cyber operations by states - such as electoral disinformation campaigns or attacks on critical infrastructure - and asks whether new rules are required. Rapid technological change raises urgent questions around equity, transparency, privacy and security. We are looking at the human rights dividend from new technologies as well as how international human rights law standards, for example on freedom of thought, expression and privacy, guide the use of digital technology in the electoral context. Latest (3) Expert comment Power Politics Could Impede Progress on Responsible Regulation of Cyberspace 3 December 2019 Research paper The Application of International Law to State Cyberattacks: Sovereignty and Non-Intervention 2 December 2019 Research paper Online Disinformation and Political Discourse: Applying a Human Rights Framework 6 November 2019 Expert comment (1) Expert comment Power Politics Could Impede Progress on Responsible Regulation of Cyberspace 3 December 2019 Research & Publications (2) Research paper The Application of International Law to State Cyberattacks: Sovereignty and Non-Intervention 2 December 2019 Research paper Online Disinformation and Political Discourse: Applying a Human Rights Framework 6 November 2019 Past events (2) Research Event Sovereignty and Non-Intervention: The Application of International Law to State Cyberattacks 4 December 2019 Research Event Tackling Cyber Disinformation in Elections: Applying International Human Rights Law 6 November 2019 Video & audio (1) Video Tackling Cyber Disinformation in Elections: Applying International Human Rights Law 6 November 2019 Full Article
b Sovereignty and Non-Intervention: The Application of International Law to State Cyberattacks By feedproxy.google.com Published On :: Fri, 01 Nov 2019 10:55:01 +0000 Research Event 4 December 2019 - 5:30pm to 7:00pm Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Douglas, Legal Director, GCHQZhixiong Huang, Luojia Chair of International Law, Wuhan UniversityNemanja Malisevic, Director of Digital Diplomacy, MicrosoftHarriet Moynihan, Associate Fellow, International Law Programme, Chatham HouseChair: Elizabeth Wilmshurst, Distinguished Fellow, International Law Programme, Chatham House International law applies to cyber operations – but views differ on exactly how. Does state-sponsored interference in another state's affairs using cyber means – for example, disinformation campaigns in elections, disabling government websites, or disrupting transport systems – breach international law? If so, on what basis and how are the principles of sovereignty and non-intervention relevant? States are increasingly attributing cyber operations to other states and engaging in the debate on how international law applies, including circumstances that would justify countermeasures.As states meet to debate these issues at the UN, the panel will explore how international law regulates cyberoperations by states, consider the prospects of progress at the UN, and assess the value of other initiatives.This event coincides with the launch of a Chatham House research paper which analyses how the principles of sovereignty and intervention apply in the context of cyberoperations, and considers a way forward for agreeing a common understanding of cyber norms.This event will bring together a broad group of actors, including policymakers, the private sector, legal experts and civil society, and will be followed by a drinks reception. Department/project International Law Programme, Cyber, Sovereignty and Human Rights Jacqueline Rowe Programme Assistant, International Law Programme 020 7389 3287 Email Full Article
b The Application of International Law to State Cyberattacks: Sovereignty and Non-Intervention By feedproxy.google.com Published On :: Fri, 29 Nov 2019 16:56:12 +0000 2 December 2019 Hostile cyber operations by one state against another state are increasingly common. This paper analyzes the application of the sovereignty and non-intervention principles in relation to states’ cyber operations in another state below the threshold of the use of force. Read online Download PDF Harriet Moynihan Senior Research Fellow, International Law Programme @HarrietMoyniha9 2019-11-29-Intl-Law-Cyberattacks.jpg A computer hacked by a virus known as Petya. The Petya ransomware cyberattack hit computers of Russian and Ukrainian companies on 27 June 2017. Photo: Getty Images. SummaryThe vast majority of state-to-state cyberattacks consist of persistent, low-level intrusions that take place below the threshold of use of force. International law, including the principle of non-intervention in another state’s internal affairs and the principle of sovereignty, applies to these cyber operations.It is not clear whether any unauthorized cyber intrusion would violate the target state’s sovereignty, or whether there is a threshold in operation. While some would like to set limits by reference to effects of the cyber activity, at this time such limits are not reflected in customary international law. The assessment of whether sovereignty has been violated therefore has to be made on a case by case basis, if no other more specific rules of international law apply.In due course, further state practice and opinio iuris may give rise to an emerging cyber-specific understanding of sovereignty, just as specific rules deriving from the sovereignty principle have crystallized in other areas of international law.Before a principle of due diligence can be invoked in the cyber context, further work is needed by states to agree upon rules as to what might be expected of a state in this context.The principle of non-intervention applies to a state’s cyber operations as it does to other state activities. It consists of coercive behaviour by one state that deprives the target state of its free will in relation to the exercise of its sovereign functions in order to compel an outcome in, or conduct with respect to, a matter reserved to the target state.In practice, activities that contravene the non-intervention principle and activities that violates sovereignty will often overlap.In order to reach agreement on how international law applies to states’ cyber operations below the level of use of force, states should put their views on record, where possible giving examples of when they consider that an obligation may be breached, as states such as the UK, Australia, France and the Netherlands have done.Further discussion between states should focus on how the rules apply to practical examples of state-sponsored cyber operations. There is likely to be more commonality about specific applications of the law than there is about abstract principles.The prospects of a general treaty in this area are still far off. In due course, there may be benefit in considering limited rules, for example on due diligence and a prohibition on attacking critical infrastructure, before tackling broad principles. Department/project International Law Programme, Cyber, Sovereignty and Human Rights Full Article
b Power Politics Could Impede Progress on Responsible Regulation of Cyberspace By feedproxy.google.com Published On :: Tue, 03 Dec 2019 14:34:13 +0000 3 December 2019 Harriet Moynihan Senior Research Fellow, International Law Programme @HarrietMoyniha9 A new Chatham House paper examines the prospects of countries reaching agreement on issues of sovereignty and non-intervention in cyberspace in the face of persistent, low-level, state-to-state cyber attacks. 2019-11-29-Intl-Law-Cyberattacks.jpg A computer hacked by a virus known as Petya. The Petya ransomware cyberattack hit computers of Russian and Ukrainian companies on 27 June 2017. Photo: Getty Images. In discussions to date about how international law applies in cyberspace, commentators have tended to focus their attention on how the rules on the use of force, or the law of armed conflict, apply to cyber activities conducted by states that give rise to physical damage, injury or death.But in practice, the vast majority of state cyberattacks fall below this threshold. Far more common are persistent, low-level attacks that may leave no physical trace but that are capable of doing significant damage to a state’s ability to control its systems, often at serious economic cost.Such cyber incursions might include network disruptions in the operation of another government’s websites; tampering with electoral infrastructure to change or undermine the result; or using cyber means to destabilize another state’s financial sector.For these kinds of cyber operation, the principle of sovereignty, and the principle of non-intervention in another state’s internal affairs, are the starting point.A UN Group of Government Experts (GGE) agreed in 2013 and 2015 that the principles in the UN Charter, including sovereignty and the prohibition on intervention in another state’s affairs, apply to states’ activities in cyberspace. The 2015 GGE also recommended eleven (non-binding) norms of responsible state behaviour in cyberspace.However, states have not yet reached agreement on how to apply these principles. Until recently, there has also been very little knowledge of what states actually do in cyberspace, as they usually conduct cyber operations covertly and have been reluctant to put their views on record.A new Chatham House research paper analyses the application of the principles of sovereignty and non-intervention to state cyberattacks that fall below the principle of use of force. As well as analysing the application of the law in this area, the paper also makes recommendations to governments on how they might best make progress in reaching agreement in this area.Existing rules or new rules?As the research paper makes clear, there is currently some debate, principally between countries in the West, about the extent to which sovereignty is a legally binding rule in the context of cyberspace and, if so, how it and the principle of non-intervention might apply in practice.In the last few years, certain states have put on record how they consider international law to apply to states’ activities in cyberspace, namely the UK, Australia, France and the Netherlands. While there may be some differences in their approaches, which are discussed in the paper, there also remains important common ground: namely, that existing international law already provides a solid framework for regulating states’ cyber activities, as it regulates every other domain of state-to-state activity.There is also an emerging trend for states to work together when attributing cyberattacks to hostile states, enabling them to call out malign cyber activity when it violates international law. (See, for example, the joint statements made in relation to the NotPetya cyber attack and malicious cyber activity attributed to the Russian government).However, other countries have questioned whether existing international law as it stands is capable of regulating states’ cyber interactions and have called for ‘new legal instruments’ in this area.This includes a proposal by the Shanghai Cooperation Organization (led by Russia and China) for an International Code of Conduct on Information Security, a draft of which was submitted to the UN in 2011 and 2015, without success. The UN has also formed a new Open-Ended Working Group (OEWG) under a resolution proposed by Russia to consider how international law applies to states’ activities in cyberspace.The resolution establishing the OEWG, which began work earlier this year, includes the possibility of the group ‘introducing changes to the rules, norms and principles of responsible behaviour of States’ agreed in the 2013 and 2015 GGE reports. In the OEWG discussions at the UN in September, several countries claimed that a new legal instrument was needed to fill the ‘legal vacuum’ (Cuba) or ‘the gap of ungoverned areas’ (Indonesia).It would be concerning if the hard-won consensus on the application of international law to cyberspace that has been reached at past GGEs started to unravel. In contrast to 2013 and 2015, the 2017 meeting failed to reach an agreement.On 9 December, a renewed GGE will meet in New York, but the existence of the OEWG exploring the same issues in a separate process reflects the fact that cyber norms have become an area of geopolitical rivalry.Aside from the application of international law, states are also adopting divergent approaches to the domestic regulation of cyberspace within their own territory. The emerging trend towards a ‘splinternet’ – i.e. between states that believe the internet should be global and open on the hand, and those that favour a ‘sovereignty and control’ model on the other – is also likely to make discussions at the GGE more challenging.Distinct from the international law concept of sovereignty is the notion of ‘cybersovereignty’, a term coined by China to describe the wide-ranging powers it assumes under domestic law to regulate its citizens’ access to the internet and personal data within its territory. This approach is catching on (as reflected in Russia’s recently enacted ‘Sovereign Internet Law’), with other authoritarian states likely to follow suit.The importance of non-state actorsIn parallel with regional and UN discussions on how international law applies, a number of initiatives by non-state actors have also sought to establish voluntary principles about responsible state behaviour in cyberspace.The Global Commission on the Stability of Cyberspace, a multi-stakeholder body that has proposed principles, norms and recommendations to guide responsible behaviour by all parties in cyberspace, recently published its final report. The Cybersecurity Tech Accord aims to promote collaboration between tech companies on stability and resilience in cyberspace. President Macron’s ‘Paris Call for Trust and Security in Cyberspace’ has to date received the backing of 67 states, 139 international and civil society organizations, and 358 private-sector organizations.It remains to be seen in the long term whether the parallel processes at the UN will work constructively together or be competitive. But notwithstanding the challenging geopolitical backdrop, the UN GGE meeting next week at the least offers states the opportunity to consolidate and build on the results of past meetings; to increase knowledge and discussion about how international law might apply; and to encourage more states to put their own views of these issues on the record. Full Article
b COVID-19 Brings Human Rights into Focus By feedproxy.google.com Published On :: Thu, 09 Apr 2020 10:59:58 +0000 9 April 2020 Sonya Sceats Associate Fellow, International Law Programme @SonyaSceats With a reawakened sense of our shared humanity and vulnerability, and the benefits of collective action, this crisis may translate into a comeback for human rights as a popular idea. 2020-04-09-US-COVID-homeless A previously homeless family in the backyard of their newly reclaimed home in Los Angeles, where officials are trying to find homes to protect the state's huge homeless population from COVID-19. Photo by FREDERIC J. BROWN/AFP via Getty Images. During this extraordinary global public health emergency, governments must strike the right balance between assertive measures to slow the spread of the virus and protect lives on the one hand, and respect for human autonomy, dignity and equality on the other.International law already recognises the grave impact of pandemics and other catastrophic events on social order and provides criteria to guide states in their emergency action. The International Covenant on Civil and Political Rights permits curbs on the right to ‘liberty of movement’ so long as restrictions are provided by law, deemed necessary to protect public health, and consistent with other rights in that treaty.Freedom of expression and association, and the rights to privacy and family life are also qualified in these terms under international and regional human rights treaties. But, as emphasised in the Siracusa Principles, any limitations must not be applied in an arbitrary or discriminatory way, and must be of limited duration and subject to review.International law also guarantees the right to the highest attainable standard of health, while states are specifically required to take steps to prevent, treat and control epidemics under the International Covenant on Economic, Social and Cultural Rights. Even in health emergencies, access to health services must be ensured on a non-discriminatory basis, especially for vulnerable or marginalised groups.Abuse of coronavirus emergency measuresMany governments have taken pains to craft emergency laws that respect human rights, such as permitting reasonable exceptions to lockdowns for essential shopping and exercise, and making them subject to ongoing parliamentary review and sunset clauses. But even laws that appear to be human rights compliant can still easily be misapplied, as the recent debates about over-zealous policing of people walking and travelling in the UK illustrate.And disturbing stories are emerging from states where police brutality is entrenched. In Kenya, a 13-year-old boy was reportedly shot on the balcony of his home by police enforcing a coronavirus curfew. Authorities in the Philippines' are allegedly locking those caught defying the curfew in dog cages.As the recent history of counterterrorism demonstrates, emergency laws tend to be sticky, remaining on the statute books far longer than desirable.The virus is also proving a powerful accelerant for the current global authoritarian drift which is so detrimental to progress on human rights. Many authoritarian leaders have seized the opportunity to further reduce constraints on their power.Hungary's prime minister Viktor Orbán has used the pandemic as a pretext for new laws enabling him to rule by decree, completing the country's transition to an elected dictatorship. In Brazil, president Jair Bolsonaro has suspended deadlines for public bodies to reply to freedom of information requests. Iran is the latest of many repressive states in the Middle East to ban the printing and distribution of all newspapers. In China, the government brushed off criticism over ‘disappearances’ of whistleblowers and citizen journalists who questioned its response to the crisis.Others have exploited the turmoil to undermine justice for human rights abuses - Sri Lanka's president Gotabaya Rajapaksa pardoned one of the only soldiers held accountable for crimes during the country's brutal civil war.Coronavirus also places liberal values under further strain. Fear is a major driver in the appeal of populist authoritarians and the virus is stoking it. One poll showed 73% of British citizens agreed coronavirus is just the latest sign that the world we live in is increasingly dangerous. Extremists are exploiting these fears to spread hate by blaming the outbreak on ethnic or religious groups, and encouraging those infected to spread it to these groups.The closure of borders helps reinforce xenophobic tendencies, and high public tolerance of emergency measures could easily spill into normalisation of intrusive digital surveillance and restrictions on liberty for other reasons well into the future.Disadvantaged groups face a higher level of risk from the crisis. The health of aboriginal Australians is so poor that those aged 50 and above are being urged to stay home, advice otherwise given to those over 70 in the general population. The Moria refugee camp on Lesbos is reporting no soap and just one water tap for 1,300 refugees. In the UK, asylum seekers struggle to self-isolate in shared accommodation and have a daily allowance of just £5.40 for food, medicine and toiletries. Women's rights groups are reporting a spike in domestic violence.For countries racked by war and extreme poverty, the impact is catastrophic. The virus is set to run rampant in slums, refugee camps and informal settlements where public health systems - if they exist at all - will struggle to cope. And detainees are among the most at risk, with the UN calling for release of political prisoners and anyone detained without sufficient legal basis.But the crisis has galvanised debate around the right to health and universal health coverage. Many governments have quickly bankrolled generous relief packages which will actually safeguard the socio-economic rights of many, even if they are not being justified in those terms. Portugal and Ireland have rolled back barriers to accessing healthcare for asylum seekers and other marginalised migrants.The pandemic strikes as many powerful governments have become increasingly nationalistic, undermining or retreating from international rules and institutions on human rights. But as the crisis spreads, the role of well-established international human rights standards in shaping and implementing effective - but also legitimate - measures is becoming ever clearer.The virus has reminded us of our interconnectedness as human beings and the need for global cooperation to protect our lives and health. This may help to revive popular support for human rights, creating momentum for the efforts to tackle inequality and repression - factors which have made the global impact of coronavirus so much worse than it might have been. Full Article
b Bulletin updated at 19:45 HKT - 03/05/2020 By www.weather.gov.hk Published On :: Sun, 03 May 2020 11:45:05 GMT There is no warning in force. Full Article W
b 12-LOX catalyzes the oxidation of 2-arachidonoyl-lysolipids in platelets generating eicosanoid-lysolipids that are attenuated by iPLA2{gamma} knockout [Signal Transduction] By feedproxy.google.com Published On :: 2020-04-17T00:06:05-07:00 The canonical pathway of eicosanoid production in most mammalian cells is initiated by phospholipase A2-mediated release of arachidonic acid, followed by its enzymatic oxidation resulting in a vast array of eicosanoid products. However, recent work has demonstrated that the major phospholipase in mitochondria, iPLA2γ (patatin-like phospholipase domain containing 8 (PNPLA8)), possesses sn-1 specificity, with polyunsaturated fatty acids at the sn-2 position generating polyunsaturated sn-2-acyl lysophospholipids. Through strategic chemical derivatization, chiral chromatographic separation, and multistage tandem MS, here we first demonstrate that human platelet-type 12-lipoxygenase (12-LOX) can directly catalyze the regioselective and stereospecific oxidation of 2-arachidonoyl-lysophosphatidylcholine (2-AA-LPC) and 2-arachidonoyl-lysophosphatidylethanolamine (2-AA-LPE). Next, we identified these two eicosanoid-lysophospholipids in murine myocardium and in isolated platelets. Moreover, we observed robust increases in 2-AA-LPC, 2-AA-LPE, and their downstream 12-LOX oxidation products, 12(S)-HETE-LPC and 12(S)-HETE-LPE, in calcium ionophore (A23187)-stimulated murine platelets. Mechanistically, genetic ablation of iPLA2γ markedly decreased the calcium-stimulated production of 2-AA-LPC, 2-AA-LPE, and 12-HETE-lysophospholipids in mouse platelets. Importantly, a potent and selective 12-LOX inhibitor, ML355, significantly inhibited the production of 12-HETE-LPC and 12-HETE-LPE in activated platelets. Furthermore, we found that aging is accompanied by significant changes in 12-HETE-LPC in murine serum that were also markedly attenuated by iPLA2γ genetic ablation. Collectively, these results identify previously unknown iPLA2γ-initiated signaling pathways mediated by direct 12-LOX oxidation of 2-AA-LPC and 2-AA-LPE. This oxidation generates previously unrecognized eicosanoid-lysophospholipids that may serve as biomarkers for age-related diseases and could potentially be used as targets in therapeutic interventions. Full Article
b Glucocerebrosidases catalyze a transgalactosylation reaction that yields a newly-identified brain sterol metabolite, galactosylated cholesterol [Glycobiology and Extracellular Matrices] By feedproxy.google.com Published On :: 2020-04-17T00:06:05-07:00 β-Glucocerebrosidase (GBA) hydrolyzes glucosylceramide (GlcCer) to generate ceramide. Previously, we demonstrated that lysosomal GBA1 and nonlysosomal GBA2 possess not only GlcCer hydrolase activity, but also transglucosylation activity to transfer the glucose residue from GlcCer to cholesterol to form β-cholesterylglucoside (β-GlcChol) in vitro. β-GlcChol is a member of sterylglycosides present in diverse species. How GBA1 and GBA2 mediate β-GlcChol metabolism in the brain is unknown. Here, we purified and characterized sterylglycosides from rodent and fish brains. Although glucose is thought to be the sole carbohydrate component of sterylglycosides in vertebrates, structural analysis of rat brain sterylglycosides revealed the presence of galactosylated cholesterol (β-GalChol), in addition to β-GlcChol. Analyses of brain tissues from GBA2-deficient mice and GBA1- and/or GBA2-deficient Japanese rice fish (Oryzias latipes) revealed that GBA1 and GBA2 are responsible for β-GlcChol degradation and formation, respectively, and that both GBA1 and GBA2 are responsible for β-GalChol formation. Liquid chromatography–tandem MS revealed that β-GlcChol and β-GalChol are present throughout development from embryo to adult in the mouse brain. We found that β-GalChol expression depends on galactosylceramide (GalCer), and developmental onset of β-GalChol biosynthesis appeared to be during myelination. We also found that β-GlcChol and β-GalChol are secreted from neurons and glial cells in association with exosomes. In vitro enzyme assays confirmed that GBA1 and GBA2 have transgalactosylation activity to transfer the galactose residue from GalCer to cholesterol to form β-GalChol. This is the first report of the existence of β-GalChol in vertebrates and how β-GlcChol and β-GalChol are formed in the brain. Full Article
b Deletion of fatty acid transport protein 2 (FATP2) in the mouse liver changes the metabolic landscape by increasing the expression of PPAR{alpha}-regulated genes [Lipids] By feedproxy.google.com Published On :: 2020-04-24T06:08:45-07:00 Fatty acid transport protein 2 (FATP2) is highly expressed in the liver, small intestine, and kidney, where it functions in both the transport of exogenous long-chain fatty acids and the activation of very-long-chain fatty acids. Here, using a murine model, we investigated the phenotypic impacts of deleting FATP2, followed by a transcriptomic analysis using unbiased RNA-Seq to identify concomitant changes in the liver transcriptome. WT and FATP2-null (Fatp2−/−) mice (5 weeks) were maintained on a standard chow diet for 6 weeks. The Fatp2−/− mice had reduced weight gain, lowered serum triglyceride, and increased serum cholesterol levels and attenuated dietary fatty acid absorption. Transcriptomic analysis of the liver revealed 258 differentially expressed genes in male Fatp2−/− mice and a total of 91 in female Fatp2−/− mice. These genes mapped to the following gene ontology categories: fatty acid degradation, peroxisome biogenesis, fatty acid synthesis, and retinol and arachidonic acid metabolism. Targeted RT-quantitative PCR verified the altered expression of selected genes. Of note, most of the genes with increased expression were known to be regulated by peroxisome proliferator–activated receptor α (PPARα), suggesting that FATP2 activity is linked to a PPARα-specific proximal ligand. Targeted metabolomic experiments in the Fatp2−/− liver revealed increases of total C16:0, C16:1, and C18:1 fatty acids; increases in lipoxin A4 and prostaglandin J2; and a decrease in 20-hydroxyeicosatetraenoic acid. We conclude that the expression of FATP2 in the liver broadly affects the metabolic landscape through PPARα, indicating that FATP2 provides an important role in liver lipid metabolism through its transport or activation activities. Full Article
b Determination of globotriaosylceramide analogs in the organs of a mouse model of Fabry disease [Lipids] By feedproxy.google.com Published On :: 2020-04-24T06:08:45-07:00 Fabry disease is a heritable lipid disorder caused by the low activity of α-galactosidase A and characterized by the systemic accumulation of globotriaosylceramide (Gb3). Recent studies have reported a structural heterogeneity of Gb3 in Fabry disease, including Gb3 isoforms with different fatty acids and Gb3 analogs with modifications on the sphingosine moiety. However, Gb3 assays are often performed only on the selected Gb3 isoforms. To precisely determine the total Gb3 concentration, here we established two methods for determining both Gb3 isoforms and analogs. One was the deacylation method, involving Gb3 treatment with sphingolipid ceramide N-deacylase, followed by an assay of the deacylated products, globotriaosylsphingosine (lyso-Gb3) and its analogs, by ultra-performance LC coupled to tandem MS (UPLC-MS/MS). The other method was a direct assay established in the present study for 37 Gb3 isoforms and analogs/isoforms by UPLC-MS/MS. Gb3s from the organs of symptomatic animals of a Fabry disease mouse model were mainly Gb3 isoforms and two Gb3 analogs, such as Gb3(+18) containing the lyso-Gb3(+18) moiety and Gb3(−2) containing the lyso-Gb3(−2) moiety. The total concentrations and Gb3 analog distributions determined by the two methods were comparable. Gb3(+18) levels were high in the kidneys (24% of total Gb3) and the liver (13%), and we observed Gb3(−2) in the heart (10%) and the kidneys (5%). These results indicate organ-specific expression of Gb3 analogs, insights that may lead to a deeper understanding of the pathophysiology of Fabry disease. Full Article
b MtrP, a putative methyltransferase in Corynebacteria, is required for optimal membrane transport of trehalose mycolates [Lipids] By feedproxy.google.com Published On :: 2020-05-01T00:06:09-07:00 Pathogenic bacteria of the genera Mycobacterium and Corynebacterium cause severe human diseases such as tuberculosis (Mycobacterium tuberculosis) and diphtheria (Corynebacterium diphtheriae). The cells of these species are surrounded by protective cell walls rich in long-chain mycolic acids. These fatty acids are conjugated to the disaccharide trehalose on the cytoplasmic side of the bacterial cell membrane. They are then transported across the membrane to the periplasm where they act as donors for other reactions. We have previously shown that transient acetylation of the glycolipid trehalose monohydroxycorynomycolate (hTMCM) enables its efficient transport to the periplasm in Corynebacterium glutamicum and that acetylation is mediated by the membrane protein TmaT. Here, we show that a putative methyltransferase, encoded at the same genetic locus as TmaT, is also required for optimal hTMCM transport. Deletion of the C. glutamicum gene NCgl2764 (Rv0224c in M. tuberculosis) abolished acetyltrehalose monocorynomycolate (AcTMCM) synthesis, leading to accumulation of hTMCM in the inner membrane and delaying its conversion to trehalose dihydroxycorynomycolate (h2TDCM). Complementation with NCgl2764 normalized turnover of hTMCM to h2TDCM. In contrast, complementation with NCgl2764 derivatives mutated at residues essential for methyltransferase activity failed to rectify the defect, suggesting that NCgl2764/Rv0224c encodes a methyltransferase, designated here as MtrP. Comprehensive analyses of the individual mtrP and tmaT mutants and of a double mutant revealed strikingly similar changes across several lipid classes compared with WT bacteria. These findings indicate that both MtrP and TmaT have nonredundant roles in regulating AcTMCM synthesis, revealing additional complexity in the regulation of trehalose mycolate transport in the Corynebacterineae. Full Article
b COQ11 deletion mitigates respiratory deficiency caused by mutations in the gene encoding the coenzyme Q chaperone protein Coq10 [Lipids] By feedproxy.google.com Published On :: 2020-05-01T00:06:09-07:00 Coenzyme Q (Qn) is a vital lipid component of the electron transport chain that functions in cellular energy metabolism and as a membrane antioxidant. In the yeast Saccharomyces cerevisiae, coq1–coq9 deletion mutants are respiratory-incompetent, sensitive to lipid peroxidation stress, and unable to synthesize Q6. The yeast coq10 deletion mutant is also respiratory-deficient and sensitive to lipid peroxidation, yet it continues to produce Q6 at an impaired rate. Thus, Coq10 is required for the function of Q6 in respiration and as an antioxidant and is believed to chaperone Q6 from its site of synthesis to the respiratory complexes. In several fungi, Coq10 is encoded as a fusion polypeptide with Coq11, a recently identified protein of unknown function required for efficient Q6 biosynthesis. Because “fused” proteins are often involved in similar biochemical pathways, here we examined the putative functional relationship between Coq10 and Coq11 in yeast. We used plate growth and Seahorse assays and LC-MS/MS analysis to show that COQ11 deletion rescues respiratory deficiency, sensitivity to lipid peroxidation, and decreased Q6 biosynthesis of the coq10Δ mutant. Additionally, immunoblotting indicated that yeast coq11Δ mutants accumulate increased amounts of certain Coq polypeptides and display a stabilized CoQ synthome. These effects suggest that Coq11 modulates Q6 biosynthesis and that its absence increases mitochondrial Q6 content in the coq10Δcoq11Δ double mutant. This augmented mitochondrial Q6 content counteracts the respiratory deficiency and lipid peroxidation sensitivity phenotypes of the coq10Δ mutant. This study further clarifies the intricate connection between Q6 biosynthesis, trafficking, and function in mitochondrial metabolism. Full Article
b AIG1 and ADTRP are endogenous hydrolases of fatty acid esters of hydroxy fatty acids (FAHFAs) in mice [Metabolism] By feedproxy.google.com Published On :: 2020-05-01T00:06:09-07:00 Fatty acid esters of hydroxy fatty acids (FAHFAs) are a newly discovered class of signaling lipids with anti-inflammatory and anti-diabetic properties. However, the endogenous regulation of FAHFAs remains a pressing but unanswered question. Here, using MS-based FAHFA hydrolysis assays, LC-MS–based lipidomics analyses, and activity-based protein profiling, we found that androgen-induced gene 1 (AIG1) and androgen-dependent TFPI-regulating protein (ADTRP), two threonine hydrolases, control FAHFA levels in vivo in both genetic and pharmacologic mouse models. Tissues from mice lacking ADTRP (Adtrp-KO), or both AIG1 and ADTRP (DKO) had higher concentrations of FAHFAs particularly isomers with the ester bond at the 9th carbon due to decreased FAHFA hydrolysis activity. The levels of other lipid classes were unaltered indicating that AIG1 and ADTRP specifically hydrolyze FAHFAs. Complementing these genetic studies, we also identified a dual AIG1/ADTRP inhibitor, ABD-110207, which is active in vivo. Acute treatment of WT mice with ABD-110207 resulted in elevated FAHFA levels, further supporting the notion that AIG1 and ADTRP activity control endogenous FAHFA levels. However, loss of AIG1/ADTRP did not mimic the changes associated with pharmacologically administered FAHFAs on extent of upregulation of FAHFA levels, glucose tolerance, or insulin sensitivity in mice, indicating that therapeutic strategies should weigh more on FAHFA administration. Together, these findings identify AIG1 and ADTRP as the first endogenous FAHFA hydrolases identified and provide critical genetic and chemical tools for further characterization of these enzymes and endogenous FAHFAs to unravel their physiological functions and roles in health and disease. Full Article
b Certain ortho-hydroxylated brominated ethers are promiscuous kinase inhibitors that impair neuronal signaling and neurodevelopmental processes [Cell Biology] By feedproxy.google.com Published On :: 2020-05-01T00:06:09-07:00 The developing nervous system is remarkably sensitive to environmental signals, including disruptive toxins, such as polybrominated diphenyl ethers (PBDEs). PBDEs are an environmentally pervasive class of brominated flame retardants whose neurodevelopmental toxicity mechanisms remain largely unclear. Using dissociated cortical neurons from embryonic Rattus norvegicus, we found here that chronic exposure to 6-OH–BDE-47, one of the most prevalent hydroxylated PBDE metabolites, suppresses both spontaneous and evoked neuronal electrical activity. On the basis of our previous work on mitogen-activated protein kinase (MAPK)/extracellular signal-related kinase (ERK) (MEK) biology and our observation that 6-OH–BDE-47 is structurally similar to kinase inhibitors, we hypothesized that certain hydroxylated PBDEs mediate neurotoxicity, at least in part, by impairing the MEK–ERK axis of MAPK signal transduction. We tested this hypothesis on three experimental platforms: 1) in silico, where modeling ligand–protein docking suggested that 6-OH–BDE-47 is a promiscuous ATP-competitive kinase inhibitor; 2) in vitro in dissociated neurons, where 6-OH–BDE-47 and another specific hydroxylated BDE metabolite similarly impaired phosphorylation of MEK/ERK1/2 and activity-induced transcription of a neuronal immediate early gene; and 3) in vivo in Drosophila melanogaster, where developmental exposures to 6-OH–BDE-47 and a MAPK inhibitor resulted in offspring displaying similarly increased frequency of mushroom-body β–lobe midline crossing, a metric of axonal guidance. Taken together, our results support that certain ortho-hydroxylated PBDE metabolites are promiscuous kinase inhibitors and can cause disruptions of critical neurodevelopmental processes, including neuronal electrical activity, pre-synaptic functions, MEK–ERK signaling, and axonal guidance. Full Article
b The testis-specific LINC component SUN3 is essential for sperm head shaping during mouse spermiogenesis [Cell Biology] By feedproxy.google.com Published On :: 2020-05-08T03:41:14-07:00 Sperm head shaping is a key event in spermiogenesis and is tightly controlled via the acrosome–manchette network. Linker of nucleoskeleton and cytoskeleton (LINC) complexes consist of Sad1 and UNC84 domain–containing (SUN) and Klarsicht/ANC-1/Syne-1 homology (KASH) domain proteins and form conserved nuclear envelope bridges implicated in transducing mechanical forces from the manchette to sculpt sperm nuclei into a hook-like shape. However, the role of LINC complexes in sperm head shaping is still poorly understood. Here we assessed the role of SUN3, a testis-specific LINC component harboring a conserved SUN domain, in spermiogenesis. We show that CRISPR/Cas9-generated Sun3 knockout male mice are infertile, displaying drastically reduced sperm counts and a globozoospermia-like phenotype, including a missing, mislocalized, or fragmented acrosome, as well as multiple defects in sperm flagella. Further examination revealed that the sperm head abnormalities are apparent at step 9 and that the sperm nuclei fail to elongate because of the absence of manchette microtubules and perinuclear rings. These observations indicate that Sun3 deletion likely impairs the ability of the LINC complex to transduce the cytoskeletal force to the nuclear envelope, required for sperm head elongation. We also found that SUN3 interacts with SUN4 in mouse testes and that the level of SUN4 proteins is drastically reduced in Sun3-null mice. Altogether, our results indicate that SUN3 is essential for sperm head shaping and male fertility, providing molecular clues regarding the underlying pathology of the globozoospermia-like phenotype. Full Article
b Bulletin updated at 00:00 HKT 10/May/2020 By www.weather.gov.hk Published On :: Sat, 09 May 2020 16:00:00 GMT General Situation:A trough of low pressure will edge towards the coast of Guangdong today and linger over the region in the following couple of days. There will be thundery showers over Guangdong. With the anticyclone aloft strengthening in the middle and latter parts of this week, the weather over southern China will improve and it will be hot. Date/Month: 10/05 (Sunday) Wind: South force 3. Weather: Sunny intervals and a few showers. Isolated thunderstorms later. Temp range: 28 - 32 C R.H. range: 65 - 95 per Cent Date/Month: 11/05 (Monday) Wind: South force 2 to 3. Weather: Mainly cloudy with occasional showers and a few squally thunderstorms. Temp range: 26 - 30 C R.H. range: 70 - 95 per Cent Date/Month: 12/05 (Tuesday) Wind: Light winds force 2. Weather: Mainly cloudy with a few showers and thunderstorms. Temp range: 25 - 29 C R.H. range: 70 - 95 per Cent Date/Month: 13/05 (Wednesday) Wind: Southeast force 3. Weather: Sunny intervals and one or two showers. Temp range: 26 - 30 C R.H. range: 65 - 90 per Cent Date/Month: 14/05 (Thursday) Wind: Southeast force 3. Weather: Sunny periods. Temp range: 26 - 31 C R.H. range: 60 - 85 per Cent Date/Month: 15/05 (Friday) Wind: South to southeast force 3. Weather: Sunny periods. Temp range: 27 - 32 C R.H. range: 60 - 85 per Cent Date/Month: 16/05 (Saturday) Wind: South force 3. Weather: Sunny periods. Temp range: 27 - 32 C R.H. range: 60 - 85 per Cent Date/Month: 17/05 (Sunday) Wind: South force 3 to 4. Weather: Sunny periods. Temp range: 28 - 32 C R.H. range: 70 - 90 per Cent Date/Month: 18/05 (Monday) Wind: South force 3 to 4. Weather: Sunny periods and isolated showers. Temp range: 28 - 32 C R.H. range: 70 - 90 per Cent Sea surface temperature at 2 P.M. 09/05/2020 at North Point was 25 degrees C.Soil temperatures at 7 A.M. 09/05/2020 at Hong Kong Observatory :0.5 M below surface was 27.6 degrees C 1.0 M below surface was 26.4 degrees C Full Article F
b Bulletin updated at 00:45 HKT 10/05/2020 By www.weather.gov.hk Published On :: Sat, 09 May 2020 16:45:00 GMT An anticyclone aloft brought hot weather to southern China yesterday. Locally, it was hot with sunny periods and isolated showers. A trough of low pressure will edge towards the coast of Guangdong today and linger over the region in the following couple of days. There will be thundery showers over Guangdong. Weather forecast for Hong Kong:Mainly cloudy with a few showers. Sunny intervals during the day. There will be isolated thunderstorms later. Hot with temperatures ranging between 28 and 32 degrees. Moderate southerly winds. Outlook: There will be showers and thunderstorms on Monday and Tuesday. The weather will improve gradually in the following couple of days. Full Article F
b WYSIWYG Web Builder 7.0 released! By www.wysiwygwebbuilder.com Published On :: Wed, 23 Jun 2010 10:40:59 GMT We are pleased to announce a major new release with more than 150 new features and improvements! Full Article
b WYSIWYG Web Builder 7.5 available now! By www.wysiwygwebbuilder.com Published On :: Mon, 20 Dec 2010 10:58:56 GMT WYSIWYG Web Builder 7.5 is a major update with more than 50 new features and improvements (compared to version 7.2.1). Our christmas gift to you! Full Article
b WYSIWYG Web Builder 8.0 released! By www.wysiwygwebbuilder.com Published On :: Mon, 21 Nov 2011 12:08:05 GMT We are pleased to announce a major new release with more than 150 new features and improvements! Full Article
b WYSIWYG Web Builder 8.5 available now! By www.wysiwygwebbuilder.com Published On :: Mon, 01 Oct 2012 08:23:59 GMT WYSIWYG Web Builder 8.5 is a major update with more than 50 new features and improvements (compared to version 8.2.1). Full Article
b WYSIWYG Web Builder 9.0 released! By www.wysiwygwebbuilder.com Published On :: Mon, 17 Jun 2013 10:53:50 GMT We are pleased to announce a major new release with more than 150 new features and improvements! Full Article
b WYSIWYG Web Builder 9.1 update By www.wysiwygwebbuilder.com Published On :: Mon, 23 Sep 2013 09:35:20 GMT WYSIWYG Web Builder 9.1 fixes known problems, adds new features and includes other improvements. Full Article
b WYSIWYG Web Builder 9.2 update By wysiwygwebbuilder.com Published On :: Thu, 12 Dec 2013 16:57:15 GMT WYSIWYG Web Builder 9.2 fixes known problems, adds new features and includes other improvements. Full Article
b WYSIWYG Web Builder 9.3 update By wysiwygwebbuilder.com Published On :: Fri, 14 Feb 2014 12:11:19 GMT WYSIWYG Web Builder 9.3 fixes known problems, adds new features and includes other improvements. Full Article
b WYSIWYG Web Builder 9.4 update By wysiwygwebbuilder.com Published On :: Fri, 28 Mar 2014 12:02:13 GMT WYSIWYG Web Builder 9.4 fixes known problems, adds new features and includes other improvements. Full Article
b WYSIWYG Web Builder 10.0 released! By www.wysiwygwebbuilder.com Published On :: Tue, 14 Oct 2014 12:21:00 GMT We are pleased to announce a major new release with more than 100 new features and improvements! Full Article
b WYSIWYG Web Builder 10.1 update By wysiwygwebbuilder.com Published On :: Mon, 17 Nov 2014 08:26:33 GMT WYSIWYG Web Builder 10.1 fixes known problems, adds new features and includes other improvements. Full Article
b WYSIWYG Web Builder 10.2 update By wysiwygwebbuilder.com Published On :: Mon, 12 Jan 2015 12:27:46 GMT WYSIWYG Web Builder 10.2 fixes known problems, adds new features and includes other improvements. Full Article
b WYSIWYG Web Builder 10.3 update By wysiwygwebbuilder.com Published On :: Thu, 18 Jun 2015 09:42:33 GMT WYSIWYG Web Builder 10.3 fixes known problems, adds new features and includes other improvements. Full Article
b WYSIWYG Web Builder 10.4 update By wysiwygwebbuilder.com Published On :: Thu, 18 Jun 2015 09:48:51 GMT WYSIWYG Web Builder 10.4 fixes known problems, adds new features and includes other improvements. Full Article
b WYSIWYG Web Builder 11.0 released! By wysiwygwebbuilder.com Published On :: Mon, 25 Jan 2016 09:47:12 GMT We are pleased to announce a major new release with more than 150 new features and improvements! Full Article
b WYSIWYG Web Builder 12.0 released! By wysiwygwebbuilder.com Published On :: Tue, 04 Apr 2017 11:41:47 GMT We are pleased to announce a major new release with more than 125 new features and improvements! Full Article
b A Quantitative Tri-fluorescent Yeast Two-hybrid System: From Flow Cytometry to In cellula Affinities By feedproxy.google.com Published On :: 2020-04-01 David CluetApr 1, 2020; 19:701-715Technological Innovation and Resources Full Article
b Phenotypic Adaption of Pseudomonas aeruginosa by Hacking Siderophores Produced by Other Microorganisms By feedproxy.google.com Published On :: 2020-04-01 Quentin PerraudApr 1, 2020; 19:589-607Research Full Article
b Tandem Mass Tag Approach Utilizing Pervanadate BOOST Channels Delivers Deeper Quantitative Characterization of the Tyrosine Phosphoproteome By feedproxy.google.com Published On :: 2020-04-01 Xien Yu ChuaApr 1, 2020; 19:730-743Technological Innovation and Resources Full Article
b Integrative Metabolic Pathway Analysis Reveals Novel Therapeutic Targets in Osteoarthritis By feedproxy.google.com Published On :: 2020-04-01 Beatriz RochaApr 1, 2020; 19:574-588Research Full Article
b Peptide-based interaction proteomics By feedproxy.google.com Published On :: 2020-04-28 Katrina MeyerApr 28, 2020; 0:R120.002034v1-mcp.R120.002034Review Full Article
b The DNA sensor cGAS is decorated by acetylation and phosphorylation modifications in the context of immune signaling By feedproxy.google.com Published On :: 2020-04-28 Bokai SongApr 28, 2020; 0:RA120.001981v1-mcp.RA120.001981Research Full Article
b Modulation of natural HLA-B*27:05 ligandome by ankylosing spondylitis-associated endoplasmic reticulum aminopeptidase 2 (ERAP2) By feedproxy.google.com Published On :: 2020-04-07 Elena LorenteApr 7, 2020; 0:RA120.002014v1-mcp.RA120.002014Research Full Article
b HIGD2A is required for assembly of the COX3 module of human mitochondrial complex IV By feedproxy.google.com Published On :: 2020-04-21 Daniella H HockApr 21, 2020; 0:RA120.002076v1-mcp.RA120.002076Research Full Article
b Characterization of Prenylated C-terminal Peptides Using a Thiopropyl-based Capture Technique and LC-MS/MS By feedproxy.google.com Published On :: 2020-04-13 James A. WilkinsApr 13, 2020; 0:RA120.001944v1-mcp.RA120.001944Research Full Article
b Flow-induced reorganization of laminin-integrin networks within the endothelial basement membrane uncovered by proteomics By feedproxy.google.com Published On :: 2020-04-24 Eelke P. BéguinApr 24, 2020; 0:RA120.001964v1-mcp.RA120.001964Research Full Article
b Robust summarization and inference in proteome-wide label-free quantification By feedproxy.google.com Published On :: 2020-04-22 Adriaan StickerApr 22, 2020; 0:RA119.001624v1-mcp.RA119.001624Research Full Article
b Investigation of inter- and intra-tumoral heterogeneity of glioblastoma using TOF-SIMS By feedproxy.google.com Published On :: 2020-04-06 Samvel K GularyanApr 6, 2020; 0:RA120.001986v1-mcp.RA120.001986Research Full Article
b Dysregulation of Exosome Cargo by Mutant Tau Expressed in Human-Induced Pluripotent Stem Cell (iPSC) Neurons Revealed by Proteomics Analyses By feedproxy.google.com Published On :: 2020-04-15 Sonia PodvinApr 15, 2020; 0:RA120.002079v1-mcp.RA120.002079Research Full Article
b Identification of an Unconventional Subpeptidome Bound to the Behcet's Disease-associated HLA-B*51:01 that is Regulated by Endoplasmic Reticulum Aminopeptidase 1 (ERAP1) By feedproxy.google.com Published On :: 2020-05-01 Liye ChenMay 1, 2020; 19:871-883Research Full Article
b Quantitative proteomics of human heart samples collected in vivo reveal the remodeled protein landscape of dilated left atrium without atrial fibrillation By feedproxy.google.com Published On :: 2020-04-14 Nora LinscheidApr 14, 2020; 0:RA119.001878v1-mcp.RA119.001878Research Full Article
b 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
