rn Extremely rare 'failed supernova' may have erased a star from the night sky without a trace By www.yahoo.com Published On :: 2024-11-12T20:05:32Z Full Article
rn Woman, 23, had a 'burning sensation' in her stomach. It was the first sign of a rare cancer By www.yahoo.com Published On :: 2024-11-11T22:54:21Z Full Article
rn Look Up! The Northern Lights May Be Visible in the U.S. Tonight—Here's Where to See Them By www.yahoo.com Published On :: 2024-11-12T16:20:24Z Full Article
rn The Morning After: Apple makes its iOS Find My features much more useful By www.yahoo.com Published On :: 2024-11-12T12:15:25Z Full Article
rn Toyota, A Company With Almost No EVs, Says California's EV Mandates Are 'Impossible' To Meet By autos.yahoo.com Published On :: 2024-11-12T14:30:00Z Full Article
rn Ski resort announces immediate closure as relentless threat brings fewer visitors and increases debts: 'I feel like I'm in mourning' By www.yahoo.com Published On :: 2024-11-11T10:30:46Z Full Article
rn Northern California man goes missing after Uber ride from Bay Area to Placer County By www.yahoo.com Published On :: 2024-11-12T00:34:02Z Full Article
rn ‘One-burner’ life - Vybz Kartel credits fiancée for new chapter By jamaica-star.com Published On :: Mon, 11 Nov 2024 05:01:17 -0500 Long hailed as dancehall's most controversial figure, Vybz Kartel has always commanded the spotlight with his edgy lyrics and unfiltered persona. But since his release from prison in July, Kartel has begun to show a surprising transformation that'... Full Article
rn A mom’s worst nightmare - East Kingston mother mourns teen son after deadly clash with cops By jamaica-star.com Published On :: Mon, 11 Nov 2024 05:01:19 -0500 Kadian Morgan was overwhelmed with grief as she leaned against a wall outside her gate on Jackson Lane, East Kingston, yesterday, tears streaming down her face. Her 19-year-old son, Kayshan 'Bem Bem' Smith, was lying in the morgue after being... Full Article
rn Childhood rape survivor earns university degree By jamaica-star.com Published On :: Mon, 11 Nov 2024 05:01:23 -0500 Earlier this month when Alicea Samaru-Brown walked across the stage at The University of the West Indies (UWI) graduation, she beamed with pride. Her husband, Dennis Brown, and her son, Orlando Brown, cheered the loudest from the audience and this... Full Article
rn Mouse Ifit1b is a cap1-RNA-binding protein that inhibits mouse coronavirus translation and is regulated by complexing with Ifit1c [RNA] By www.jbc.org Published On :: 2020-12-18T00:06:18-08:00 Knockout mouse models have been extensively used to study the antiviral activity of IFIT (interferon-induced protein with tetratricopeptide repeats). Human IFIT1 binds to cap0 (m7GpppN) RNA, which lacks methylation on the first and second cap-proximal nucleotides (cap1, m7GpppNm, and cap2, m7GpppNmNm, respectively). These modifications are signatures of “self” in higher eukaryotes, whereas unmodified cap0-RNA is recognized as foreign and, therefore, potentially harmful to the host cell. IFIT1 inhibits translation at the initiation stage by competing with the cap-binding initiation factor complex, eIF4F, restricting infection by certain viruses that possess “nonself” cap0-mRNAs. However, in mice and other rodents, the IFIT1 orthologue has been lost, and the closely related Ifit1b has been duplicated twice, yielding three paralogues: Ifit1, Ifit1b, and Ifit1c. Although murine Ifit1 is similar to human IFIT1 in its cap0-RNA–binding selectivity, the roles of Ifit1b and Ifit1c are unknown. Here, we found that Ifit1b preferentially binds to cap1-RNA, whereas binding is much weaker to cap0- and cap2-RNA. In murine cells, we show that Ifit1b can modulate host translation and restrict WT mouse coronavirus infection. We found that Ifit1c acts as a stimulatory cofactor for both Ifit1 and Ifit1b, promoting their translation inhibition. In this way, Ifit1c acts in an analogous fashion to human IFIT3, which is a cofactor to human IFIT1. This work clarifies similarities and differences between the human and murine IFIT families to facilitate better design and interpretation of mouse models of human infection and sheds light on the evolutionary plasticity of the IFIT family. Full Article
rn 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
rn 12th International Forum on Illegal, Unreported and Unregulated Fishing By www.chathamhouse.org Published On :: Fri, 27 Sep 2019 09:15:01 +0000 12th International Forum on Illegal, Unreported and Unregulated Fishing 18 May 2020 TO 22 May 2020 — 2:00PM TO 3:30PM Anonymous (not verified) 27 September 2019 The Chatham House 12th International Forum on Illegal, Unreported and Unregulated (IUU) Fishing took place over the week of 18–22 May 2020. Due to COVID-19, it took the form of a series of daily webinars. The digital conference, which comprised six sessions and three keynote speeches, brought together more than 750 representatives of international organizations, governments, civil society organizations, businesses and academia – from 87 different countries – to discuss the latest initiatives, regulations and research in the areas of fisheries governance and trade in illegal fish products. Full Article
rn Structural and biochemical characteristics of two Staphylococcus epidermidis RNase J paralogs RNase J1 and RNase J2 [Protein Structure and Folding] By www.jbc.org Published On :: 2020-12-04T00:06:06-08:00 RNase J enzymes are metallohydrolases that are involved in RNA maturation and RNA recycling, govern gene expression in bacteria, and catalyze both exonuclease and endonuclease activity. The catalytic activity of RNase J is regulated by multiple mechanisms which include oligomerization, conformational changes to aid substrate recognition, and the metal cofactor at the active site. However, little is known of how RNase J paralogs differ in expression and activity. Here we describe structural and biochemical features of two Staphylococcus epidermidis RNase J paralogs, RNase J1 and RNase J2. RNase J1 is a homodimer with exonuclease activity aided by two metal cofactors at the active site. RNase J2, on the other hand, has endonuclease activity and one metal ion at the active site and is predominantly a monomer. We note that the expression levels of these enzymes vary across Staphylococcal strains. Together, these observations suggest that multiple interacting RNase J paralogs could provide a strategy for functional improvisation utilizing differences in intracellular concentration, quaternary structure, and distinct active site architecture despite overall structural similarity. Full Article
rn Representative cancer-associated U2AF2 mutations alter RNA interactions and splicing [Molecular Bases of Disease] By www.jbc.org Published On :: 2020-12-11T00:06:20-08:00 High-throughput sequencing of hematologic malignancies and other cancers has revealed recurrent mis-sense mutations of genes encoding pre-mRNA splicing factors. The essential splicing factor U2AF2 recognizes a polypyrimidine-tract splice-site signal and initiates spliceosome assembly. Here, we investigate representative, acquired U2AF2 mutations, namely N196K or G301D amino acid substitutions associated with leukemia or solid tumors, respectively. We determined crystal structures of the wild-type (WT) compared with N196K- or G301D-substituted U2AF2 proteins, each bound to a prototypical AdML polypyrimidine tract, at 1.5, 1.4, or 1.7 Å resolutions. The N196K residue appears to stabilize the open conformation of U2AF2 with an inter-RNA recognition motif hydrogen bond, in agreement with an increased apparent RNA-binding affinity of the N196K-substituted protein. The G301D residue remains in a similar position as the WT residue, where unfavorable proximity to the RNA phosphodiester could explain the decreased RNA-binding affinity of the G301D-substituted protein. We found that expression of the G301D-substituted U2AF2 protein reduces splicing of a minigene transcript carrying prototypical splice sites. We further show that expression of either N196K- or G301D-substituted U2AF2 can subtly alter splicing of representative endogenous transcripts, despite the presence of endogenous, WT U2AF2 such as would be present in cancer cells. Altogether, our results demonstrate that acquired U2AF2 mutations such as N196K and G301D are capable of dysregulating gene expression for neoplastic transformation. Full Article
rn Molecular characterization of the RNA-protein complex directing -2/-1 programmed ribosomal frameshifting during arterivirus replicase expression [Protein Structure and Folding] By www.jbc.org Published On :: 2020-12-25T00:06:30-08:00 Programmed ribosomal frameshifting (PRF) is a mechanism used by arteriviruses like porcine reproductive and respiratory syndrome virus (PRRSV) to generate multiple proteins from overlapping reading frames within its RNA genome. PRRSV employs −1 PRF directed by RNA secondary and tertiary structures within its viral genome (canonical PRF), as well as a noncanonical −1 and −2 PRF that are stimulated by the interactions of PRRSV nonstructural protein 1β (nsp1β) and host protein poly(C)-binding protein (PCBP) 1 or 2 with the viral genome. Together, nsp1β and one of the PCBPs act as transactivators that bind a C-rich motif near the shift site to stimulate −1 and −2 PRF, thereby enabling the ribosome to generate two frameshift products that are implicated in viral immune evasion. How nsp1β and PCBP associate with the viral RNA genome remains unclear. Here, we describe the purification of the nsp1β:PCBP2:viral RNA complex on a scale sufficient for structural analysis using small-angle X-ray scattering and stochiometric analysis by analytical ultracentrifugation. The proteins associate with the RNA C-rich motif as a 1:1:1 complex. The monomeric form of nsp1β within the complex differs from previously reported homodimer identified by X-ray crystallography. Functional analysis of the complex via mutational analysis combined with RNA-binding assays and cell-based frameshifting reporter assays reveal a number of key residues within nsp1β and PCBP2 that are involved in complex formation and function. Our results suggest that nsp1β and PCBP2 both interact directly with viral RNA during formation of the complex to coordinate this unusual PRF mechanism. Full Article
rn Tackling Malnutrition: Harnessing the Power of Business By www.chathamhouse.org Published On :: Tue, 07 Jul 2020 08:56:38 +0000 8 July 2020 Simon Pringle Associate Fellow, Energy, Environment and Resources Programme @simonpringle LinkedIn Malnutrition negatively impacts individuals, families, societies and economies around the world. Now is the time to align corporate, government and third sector efforts to relegate it to the past. GettyImages-1175994321.jpg A view of a market area in Goma, Democratic Republic of Congo on 10 October 2019. Congo is among the countries with the highest number of acutely malnourished people on a global level. Photo by JC Wenga/Anadolu Agency via Getty Images. Many people are aware that the scourge of malnutrition affects a vast number of individuals and communities around the world. However, most tend to view it as a problem to be addressed by governments, charities or donors, rather than the corporate sector.Certainly, when considered at a societal scale, malnutrition makes the complexities of delivering inclusive growth all the harder. It ratchets up the public health burden while restricting the potential for at-risk populations to take part in productive employment. Economies are hindered, lives are blighted and the potential for people to reach their full potential can be severely limited.A number of upcoming summits represent a window of opportunity to address nutrition in the context of resilience, particularly in the wake of COVID-19 and the much-referenced ambition for governments to ‘build back better’. The opportunity is there to foster a true partnership between governments, third sector organizations and businesses of all sizes, sectors and geographies to work for the betterment of society and deliver benefits to all participants in such a partnership. So what is the role of business in relation to nutrition - where does it sit on their list of priorities and why should it matter to them? A new Chatham House report represents an important contribution to the discussion about the role of business in addressing malnutrition. Through thorough research and direct engagement with businesses, it seeks to find out if malnutrition is on the corporate radar and the extent to which it is considered a material issue.Surprisingly, whilst many large corporates recognize malnutrition as a matter for concern, this is typically defined only in the context of CSR programmes or related ambitions. These types of commitments have their limitations though; most notably the fact that the communities more severely affected by malnutrition typically sit outside of the sphere of influence of the multi-national companies with the greatest ability to mobilize resources and make an impact. Where populations are marginalized, operating within the informal economy and living in settings that are too fragile for large-scale business investment, corporate CSR programmes are unlikely to have a meaningful impact. Report Launch: The Business Case for Investment in Nutrition As COVID-19 pushes UN targets to end global hunger and malnutrition even further off-course, now is the time for businesses to step up and improve nutrition in their workforce and beyond. The report also asked businesses whether they considered malnutrition to have a material impact on their ability to create value, protect value and manage risk. In the majority of instances the answer was no. This may be surprising, particularly given the evidence provided by new modelling – done for this report using a purpose-built model by Vivid Economics – that illustrates the costs posed to business by malnutrition within a population. On an immediate and direct level, the impacts can be considerable due to lost or reduced productivity from the employee base. However, if even that immediate impact is addressed, the externalities associated with malnutrition can come back and have a negative effect on businesses and investors alike.When reflecting on externalities and the landscape of risk within which business operates, it is worth considering climate change by way of comparison. Climate change is well embedded in the risk profiling of most progressive and well-managed corporates – although in some instances meaningful action may be well overdue. That said, it is recognized that the direct and indirect impacts have the potential to conspire and permanently reduce shareholder, stakeholder and societal value. Similarly, if left unchecked, the externalities associated with malnutrition will undoubtedly contribute to an increased level of risk in terms of both operating and investment environments. This is both an issue of social equity and enlightened self-interest given that good nutrition is key to the success of many of the Sustainable Development Goals (SDGs), and is essential to driving sustainable economic growth. One of the lessons of the COVID-19 pandemic is the manner in which widespread malnutrition can significantly reduce the resilience of populations to external risks, including the outbreaks of infectious disease. We need only to look at the impact of climate stress and related events to understand how closely linked malnutrition is – or may become – to the incidence of social unrest and armed conflict in low-income countries.Progressive companies and investors have already identified the ability to drive inclusive and sustainable growth as a compelling imperative for investment. In this context, the potential for improved nutrition – both in the workforce and amongst the communities upon which the firms depend – should be a true priority. As fund managers seek increasingly meaningful insight into the way that companies within their portfolio(s) create value, protect value and manage risk, the scope of environmental and social governance is expanding. Many recognize the link between delivering on the SDG agenda and protecting or enhancing shareholder value into the longer term. This is a powerful lever for change, particularly when considering that good nutrition is integral to the success of the ambitions laid out by the various SDGs. Successfully delivering against nutrition-focused targets could unlock growth in developing markets and create an enabling environment for achieving the broader SDG agenda. This may in turn help companies to deliver enduring shareholder value in a way that does not undermine their corporate sustainability commitments.So, given the insights provided by this report, what can businesses do that have the potential to make a practical and effective impact? There are three main action points around which the private sector can galvanize its efforts and work in partnership to deliver a meaningful impact. The first action point is a basic requirement to be proactive and make supportive interventions with existing and future workforces, ensuring that staff are well fed and have appropriate facilities for breastfeeding and childcare. Beyond that foundational commitment, the second action point is to work to build impactful and well-governed partnerships to work within local communities and deliver outcomes at an appropriate scale. The third and final action point sets out the importance of reporting. Businesses should thoroughly assess the impacts of their operations, investments and influence. They should be transparent about those impacts and report both on the current situation and the commitments made to deliver on measurable targets.Malnutrition is a scourge; it negatively impacts individuals, families, societies and economies. Now is the time to align corporate, government and third sector efforts to consign it to the past. We just need leaders to be bold enough to seize the opportunity. Full Article
rn West Bank Annexation: International Rhetoric vs. Action By www.chathamhouse.org Published On :: Mon, 13 Jul 2020 16:30:48 +0000 14 July 2020 Reni Zhelyazkova Programme Coordinator, Middle East and North Africa Programme @renizhelyazkova Professor Yossi Mekelberg Senior Consulting Research Fellow, Middle East and North Africa Programme @YMekelberg Israel may have delayed announcing its plans to annex West Bank lands but the international community now needs to transform its rhetoric into action if there is to be a lasting solution to the Israel-Palestine conflict, argue Reni Zhelyazkova and Yossi Mekelberg. GettyImages-1223719050.jpg Houses are pictured in the Maale Adumim settlement in the West Bank east of Jerusalem. The Israeli government has delayed plans to annex Jewish settlements in the West Bank and in the Jordan Valley. Photo: Getty Images Observers of the Israel-Palestine conflict have been anticipating Israeli Prime Minister, Benjamin Netanyahu’s, announcement to annex parts of the West Bank. It has been a tumultuous year for Israeli politics which has seen three inconclusive elections and resulted in a sharing of power between Netanyahu and Benny Gantz of the Blue and White party. However, since the coalition government was sworn in, Netanyahu has appeared to not lose any time in moving forward with his plans.Annexation has long been Netanyahu’s political aspiration and was part of his recent re-election platform but the anticipated announcement from the Israeli government didn’t come straight away. The determining factor in the delay was the inability to reach an agreement with Washington about the scope of the annexation while divisions within the Israeli government itself, in addition to international condemnation from the region and beyond, has also played a part.Discussions around annexation have so far yielded one major outcome: it has introduced a different rhetoric by the Trump-Netanyahu axis even though things on the ground don’t necessarily follow. Ever since President Donald Trump took office in 2016, there has been a marked change in Washington’s language around the Israel-Palestine conflict. It has shifted towards legitimizing Israel’s expansionist ambitions in the West Bank while marginalizing, and considerably weakening, the Palestinian Authority (PA) through a series of punitive measures.This has further damaged relations between Israel and Palestine and has resulted in a fundamental change in the public discourse around the conflict, from emphasizing a just solution based on self-determination for both sides, to focusing on a de-facto one-state solution.But how has the discourse shifted so dramatically in less than four years? First came the announcement of the US embassy move to Jerusalem, and with it, recognition of the city as Israel’s capital. In his statement, President Trump avoided recognizing Palestinian claims over Jerusalem and did not acknowledge their historical connection with the city. When the PA rejected the move, the US administration then retaliated by cutting aid and development funding and closing the PLO mission in Washington stating: ‘We have permitted the PLO office to conduct operations that support the objective of achieving a lasting...peace between Israelis and the Palestinians … However, the PLO has not taken steps to advance the start of...meaningful negotiations with Israel.’ On the question of Israel’s settlements in the West Bank, the current US administration has shied away from calling them ‘illegal’ despite being deemed illegitimate under international law and condemned on numerous occasions by the UN Security Council, the UN General Assembly, the EU, the Arab League and the Palestinians themselves. US Secretary of State, Mike Pompeo, has even gone as far as saying that the establishment of Israeli settlements in the West Bank is not inconsistent with international law.The culmination of US discourse in recent months has been the unveiling of the ‘Peace to Prosperity’ plan. The language of the proposal, once again, has shown partiality towards Israel by not mentioning the illegality of Israel’s occupation of the West Bank, or that of settlements, and entirely ignoring previous Palestinian positions or acknowledging their sensitivities. There is little doubt that the current US administration understands the power of rhetoric and has been using it to change the trajectory of discussions away from a two-state solution towards an outcome that would only serve Israeli interests.Indeed, US rhetoric has empowered Netanyahu immensely too, ushering in a new reality that has rendered a Palestinian state nothing more than a hypothetical option. The language, combined with a multitude of unilateral actions, is helping to dismantle any efforts towards a two-state solution and the upholding of previous international agreements.Many European and regional governments have condemned any move towards annexation. Indeed, 1,000 European parliamentarians from across political lines have urged Israel to abandon its plans. This has notably included, German Foreign Minister, Heiko Mass, whose first overseas visit during the coronavirus crisis was to Israel to reinforce Germany’s position against unilateral action.But actions speak louder than words, and in the case of the US, its rhetoric has been matched by action unlike its EU counterparts whose statements of condemnation have rarely been followed by concrete action. For instance, the EU ratified a landmark aviation agreement with Israel just days before 1 July and economic, technological and scientific cooperation between Israel and Europe has never been stronger casting doubt on the strength of political will among EU countries to take action against Israel.In the Middle East, the United Arab Emirates has been the most vociferous in disapproving Israel’s annexation plans. However, again, it is important to look beyond the rhetoric. Cooperation between the UAE and Israel has in fact increased in recent years mainly due to common opposition to Iran’s regional influence but also due to shared interests. In May, for instance, the first publicly acknowledged commercial flight between the UAE and Israel landed at Ben Gurion airport carrying aid aimed at mitigating the effects of COVID-19 in the Palestinian territories. But, to many, it looked like a stepping-stone towards a normalization of relations between Abu Dhabi and Jerusalem.Similarly, Jordan and Egypt have also expressed their concern but it is difficult to imagine a scenario where either country would go as far as abrogating peace agreements that they currently have in place with Israel.In spite of this, the global response has overwhelmingly been critical of Israel’s plans to annex parts of the West Bank. This has demonstrated some level of unity among world leaders which has not been seen for some time and may have played a significant role in delaying the Israeli government’s plans. In parallel, united international condemnation has also prevented the US from dominating the Israeli-Palestinian conflict entirely.While the US approach has played a key role in the Israel-Palestine conflict so far, it remains to be seen how the international community will translate its voice into action to prevent the annexation of occupied Palestinian land. Full Article
rn EU Budget Battle Could Undermine its International Ambitions By www.chathamhouse.org Published On :: Fri, 17 Jul 2020 13:09:58 +0000 17 July 2020 Alice Billon-Galland Research Associate, Europe Programme @alicebillon LinkedIn Vassilis Ntousas Stavros Niarchos Foundation Academy Fellow, Europe Programme @vntousas LinkedIn EU’s heated budget negotiations risk producing a compromise at the expense of its longer-term international agenda. GettyImages-1227664182-edit.jpg German Chancellor Angela Merkel (L) talks with French President Emmanuel Macron (C) and President of European Council Charles Michel (R) during an EU summit on 17 July 2020 in Brussels, Belgium. Photo by Thierry Monasse/Getty Images. With all EU economies still reeling from COVID-19, the ongoing heated deliberations on the bloc’s next budget, which will determine the amount of money matching its priorities for the next seven years, have taken on an urgency rarely felt in Brussels.Relying in part on an unprecedentedly large volume of jointly issued debt, the European Commission’s plan for a €750 billion coronavirus recovery instrument is embedded within a revamped proposal for the EU’s long-term budget, of €1.1 trillion for the 2021-27 period. Now the ball is in the member states’ court. All seem to agree that getting the EU budget right is crucial to fostering an economic recovery and ensuring the Union is on the right track towards its long-term pre-COVID objectives, from increasing its strategic autonomy to reaching climate neutrality by 2050. However, stark differences persist as to what that means in practice.Most of the core divisions predate the pandemic’s outbreak. In a special European Council meeting in February, leaders failed to find common ground on the Union’s first post-Brexit budget. Net contributor countries, such as Austria, Denmark, Sweden and the Netherlands — the so-called ‘Frugal Four’— refused to agree to higher overall spending and instead advocated for cuts in the Common Agricultural Policy or cohesion funds, meeting the resistance of states like France and Portugal.These early divisions foreshadowed the risk of a budget compromise that would leave little space for new policy priorities. The COVID-induced economic crisis has made a traditionally fraught political process even more difficult, putting the squeeze on what were previously priority areas of funding.The Frugal Four agree on the need for the coronavirus recovery plan but vehemently oppose the volume of grants or the issuance of too much common debt in the proposed instrument, reflecting the unpopularity of these proposals with their domestic audiences. Hungary has also threatened to derail progress on the EU’s rescue plan if rule of law criteria are weaved into mechanisms for the allocation of EU funding.As European leaders reconvene at the 17-18 July Council meeting, EU Council President Michel proposed a revised 'negotiating box' in preparation for the discussions. The document, which tries to bridge these intra-bloc divisions, bolts the demands for short-term recovery onto the EU’s longer-term ambitions. For instance, it sets an increased target of 30 per cent of funding to go toward climate-related projects, which is necessary for the Union’s green transformation. It also retains the link between the rule of law and EU funding — despite Budapest’s opposition — which is critical for the bloc’s internal accountability and transparency, and external credibility. Furthermore, it proposes a set of new mechanisms through which the EU can sustainably raise its own revenue, including a plastics levy as well as more controversial carbon border tax and digital levy.Yet in several other critical ways, Michel’s proposals fall short. This is particularly true for some of the more ‘geopolitical’ goals of the Union, as previously expressed by Commission president Ursula von der Leyen, or the repeated calls by the Union’s high representative that the EU should learn to use the language of power.For all the rhetoric around the EU’s need to boost its ability to act more autonomously in the field of security and defence, reductions in important thematic programmes in this domain could result in a critical loss of momentum, if confirmed. For instance, in Michel’s proposals, flagship defence initiatives such as the European defence fund and the military mobility plan are facing cuts of about 39 per cent and 74 per cent respectively (to some €7 billion for the former and €1.5 billion for the latter) compared with the initial Commission proposal of 2018.Moreover, the tragic developments at the Greece-Turkey border in the beginning of the year might have brought migration back to the forefront of the EU’s attention, but the overall funding for migration and border management is also significantly lower compared to initial proposals. This serves as another example of a discrepancy between the figures on the table today and those that the EU commission had previously regarded as necessary to address the challenges the bloc faces.Similarly, under the Council president’s latest proposal, the combined funding allocated for the EU’s external action (under the ‘Neighbourhood and the World’ heading) is lower than the figures in the Commission’s May announcements – from €118.2 billion to €113.9 billion overall. This represents an increase compared to the previous EU budget, but it is not in line with the elevated ambitions recognized by the Commission in May, which have only been made more compelling by the pandemic.Brokering a deal in EU budget negotiations has always been a brutal affair, requiring sacrifices and compromise under the pressure of a ticking clock. 2020 was never likely to be an exception to this rule; but the pandemic has complicated the politics and raised the stakes.The risk is that the budget negotiations lead to a compromise which, while delivering a historic coronavirus package, does not adequately support some of the key elements of the Union’s long-term agenda, especially its international ambitions. Full Article
rn International Donors Can End Lebanon's Corruption By www.chathamhouse.org Published On :: Mon, 10 Aug 2020 19:46:51 +0000 10 August 2020 Dr Lina Khatib Director, Middle East and North Africa Programme @LinaKhatibUK Change must come from within Lebanon, but Emmanuel Macron and others can help by ending their patronage of a disastrous regime. 2020-08-10-Lebanon-Beirut-Corruption-Protest An anti-government protester in Beirut puts up a poster accusing corruption in Lebanon's state judiciary. Photo by Sam Tarling/Getty Images. In the aftermath of the devastating Beirut port explosion last week, it is not just the role of the Lebanese political class that has come under scrutiny, but that of their international peers too.Sunday’s international donor conference led by the French president, Emmanuel Macron, raised €253m (£228m) in relief funds, but it also signalled an important change in rhetoric. For the first time, donors affirmed that relief funds would directly go to the Lebanese people, and that longer-term economic assistance would be dependent on Lebanon implementing structural reforms.This affirmation came hot on the heels of growing international attention on rampant corruption among Lebanon’s ruling political class, which is widely blamed for the port explosion. It sends the message to Lebanon’s rulers that, while their country desperately needs foreign assistance to stand on its feet, no one can help Lebanon if it does not also help itself.But the communique issued following the conference glossed over the international community’s own role in sustaining Lebanon’s corrupt political class over a period of decades. At the aid conference, Macron said that Lebanon’s future is at stake. What donors need to recognise is that this future is a shared responsibility for them and Lebanon’s leaders alike.With Lebanon’s debt greater than 170% of its GDP, and with the port explosion costing an estimated $15bn of damage, Lebanon needs foreign assistance to prevent it becoming a failed state. But what it needs even more desperately are reforms that would counter the corruption and lack of accountability that led it to this sorry state of affairs in the first place.It is Lebanon’s existing political system – a power-sharing pact between different sects rather than a system of governance on the basis of competence – that facilitates its leaders’ reckless behaviour.The international community is partly responsible for sustaining this system through cascading patronage. For decades, Lebanese leaders grew accustomed to neglecting the national interest and eventually being bailed out by international assistance. Dollar deposits would land in the central bank from Gulf donors, loans would be offered by European countries and foreign aid packages would flow to Lebanese state institutions – only for the majority of this money to end up lining the pockets of the country’s rulers, who frequently overcame their political differences to share state resources between them. The Lebanese state came to exist as a shell in the eyes of its citizens.Lebanon’s rulers benefited from citizens’ low expectations from the state and the lack of measures ensuring transparency and accountability in the country. They brokered a social contract that cast the leaders as patrons and the people as clients rather than citizens. Foreign powers were well aware of this dynamic but they often turned a blind eye to it, and even nurtured it, because they believed the Lebanese political system brought stability and predictability following the tumultuous civil war.With time the leaders’ greed grew, and with that the economic situation worsened. Leaders who behaved as de facto local authorities, granting constituents civil service jobs or minor privileges, provided them less and less. There was some international recognition that this dynamic was becoming unsustainable – international donors pledged $11bn during the CEDRE conference of 2018 on condition that Lebanon implemented structural reforms.And in the wake of Lebanon’s recent economic deterioration, the International Monetary Fund said in April that any discussion of a loan to Lebanon would be subject to more reforms. On both occasions, Lebanon’s rulers ignored the calls for reform, counting on foreign support eventually coming in unconditionally as it used to in the past. International donor follow-up was sluggish.The port explosion needs to be a wake-up call for any international entity seeking a stable Lebanon. The blast is ultimately the result of the decades during which political classes in Lebanon and outside it fostered the country’s dysfunctional political system. No long-term assistance should flow into Lebanon without strong conditions on transparency and accountability in how this assistance would be employed.Foreign support is not the problem per se, but rather when it is handed on a plate unconditionally, maintaining the patronage cascade, exacerbating the weakness of state institutions, and further impoverishing Lebanese citizens.With Lebanon’s economy almost crumbling in the aftermath of the explosion, there is an opportunity for the international community to exert leverage over Lebanese leaders – whose personal wealth grew partially from legal and illegal transactions through the devastated port – so that necessary reforms are implemented. Such leverage would not remove Lebanon’s defective political system, but would pressure its leaders to accept at least some basic reforms.But for Lebanon to really turn a new page, it needs a new social contract and a new political system based on fairness, transparency and accountability. This is a change that can only start from within Lebanon, but it also depends on the international community abandoning their tacit support of a disastrous political status quo.This article was originally published in The Guardian. Full Article
rn Can the International Criminal Court Help Belarus? By www.chathamhouse.org Published On :: Wed, 26 Aug 2020 13:47:54 +0000 26 August 2020 Kateryna Busol Robert Bosch Stiftung Academy Fellow, Russia and Eurasia Programme @KaterynaBusol LinkedIn A referral of election violence in Belarus to the International Criminal Court could enhance the support for the Belarusian people at other crucial platforms. 2020-08-26-belarus-icc.jpg A protester carries a former Belarusian flag during an opposition rally by the Minsk Hero City Obelisk. Photo by Valery SharifulinTASS via Getty Images. Making the caseThe recent election results in Belarus have triggered revolution in yet another post-Soviet country and Aliaksandr Lukashenka’s response has been devastatingly brutal. However, the Belarusian people’s resilience and Western sanctions – adopted on 14 August – have proved effective. As some of the 6,700 jailed protesters were released, accounts of horrific treatment by law enforcement emerged: overcrowded cells, no food, torture, forced confessions, severe beatings , and threats of rape.With reports of mounting violence, Polish MEP Radosław Sikorski warned Lukashenka to expect not just sanctions but also the possible intervention of the International Criminal Court (ICC), an idea supported by the opposition-led Belarus’ National Salvation. While there are significant impediments to the Court’s involvement, the impact of such an initiative could be ground-breaking.Legal frameworkThe ICC considers criminal responsibility of top civilian or military leaders for only the most serious atrocities - war crimes, genocide, crimes against humanity and, in certain cases, the crime of aggression. In the context of Belarus, the Court’s jurisdiction over crimes against humanity might be relevant. According to the Rome Statute, the ICC’s founding treaty, crimes against humanity include widespread or systematic abuses directed against a civilian population. Atrocities relevant to Belarus include arbitrary imprisonment, torture, inhuman treatment, sexual violence, and enforced disappearances.The ICC is a last resort. It can intervene only if states are unable or unwilling to properly investigate and prosecute serious crimes themselves. Although Belarus’s Criminal Code punishes crimes against humanity, as Lukashenka himself is implicated, impartial trials in the country are impossible while he is still in power. Other countries may investigate specific atrocities in Belarus under the universal jurisdiction principle. Universal jurisdiction greenlights investigations into the most serious crimes regardless of where they are perpetrated. German, Swedish and French proceedings on Syria are illustrative examples of this. Protesters may also file individual complaints of abuse to UN bodies under the protocols of the International Covenant on Civil and Political Rights and the Convention on the Elimination of All Forms of Discrimination against Women. The European Court of Human Rights is not an option for the protesters because Belarus is not a member of the Council of Europe.As the UN mechanisms are yet to be triggered and there has not yet been any talk of universal jurisdiction proceedings, the question of recourse to the ICC remains. But as Belarus is not party to the Rome Statute, the only way to trigger the Court’s jurisdiction is a referral by the UN Security Council (UNSC). Even though it would be vetoed by Russia – and, almost certainly, China – it could be worth pursuing.The importance of symbolismSo far, the UNSC has referred to the ICC two situations in non-party states – Sudan and Libya. But for cases that do not end up being referred to the Court, the UNSC debates are as significant for what they manage to agree upon as they are for what they do not. Regarding Belarus, two impeded UNSC accountability initiatives are relevant: on Syria and MH17.In 2014, Russia and China vetoed the referral of cases of violence in Syria to the ICC. In 2015, Russia was the only country to block the creation by the UNSC of a special tribunal to investigate Malaysian Airlines flight MH17, downed by a Russian missile over war-affected eastern Ukraine. In both cases, the vetoes delayed justice, but they did not prevent it. For Syria, special independent mechanisms to collect evidence for adjudication were developed. Although justice has yet to be done, except in states like Germany, the evidence is ready for any future court. For MH17, a proceeding at a domestic Dutch court became an alternative. Parallel to that, new evidence of Russia’s role in both Syria and the downing of MH17 emerged - contextualising its UNSC vetoes.Russia’s stakes in the Belarusian elections are probably even higher: the victory of democracy in Belarus will deprive it of one of its closest and most dependent post-Soviet allies.Even if Russia destroys any chance of Belarusian citizens using the ICC, the attempted ICC-Belarus discussion will not have been in vain. Russia’s opposition to the respective UNSC resolution would be a self-defeating validation of Lukashenka’s atrocities against his own people, unashamedly restated at one of the world’s top diplomatic negotiation tables. Similar to Syria and MH17, the UNSC would reconfirm its self-imposed impotency to defend basic human rights amid political conjuncture. This would bring more attention to the issue and catalyse action through other platforms, including the discussions across UN bodies and the consideration of Belarusians’ individual complaints of abuse, and could lead to tougher sanctions. It could also further make the case for universal jurisdiction proceedings in other countries. Supporting civil societyBelarusian civil society will need stronger support from democratic governments and human rights organizations in reporting and documenting the crimes. Other countries, neighbouring states in particular, should be ready to welcome Belarusian protesters through refugee schemes, so they are able to continue their activities from abroad.When nationwide strikes enveloped Belarus, singers from the Minsk Opera supported protesters by singing Va, pensiero, the famed chorus of the Hebrew slaves from Verdi’s Nabucco – and a symbol of united Italy’s revival. The people of Belarus also want to live in a democratic state ‘where the mind is without fear and the head is held high’. And they deserve all the support they can get. The inevitable fall of Lukashenka’s regime might take time but it should not take more lives. Full Article
rn Is the Juba Peace Agreement a Turning Point for Sudan? By www.chathamhouse.org Published On :: Mon, 14 Sep 2020 13:34:19 +0000 14 September 2020 Dame Rosalind Marsden Associate Fellow, Africa Programme @MarsdenRosalind Sudan is looking towards a brighter future after the initialling of the Juba peace agreement on August 31, an important first step towards bringing peace to the conflict zones and laying the foundation for democratic transition and economic reform throughout the country. 2020-09-14-Sudan-Peace-Deal-Juba Chairman of Sudan’s Sovereign Council, Lt General Abdel Fattah al Burhan (left), South Sudan President Salva Kiir (centre) and the Sudanese Prime Minister Dr Abdalla Hamdok (right) greet people gathering during the initialling of the Sudan peace deal with the rebel groups in Juba, South Sudan. Photo by AKUOT CHOL/AFP via Getty Images. Although there is a long road ahead to achieve sustainable peace and formidable challenges remain, the hope is Sudan can turn the page on decades of war that has left hundreds of thousands dead and millions displaced, particularly in Darfur and the Two Areas (South Kordofan and Blue Nile).The peace agreement, between Sudan’s transitional government and the Sudan Revolutionary Front (SRF), a broad alliance of armed and other movements, and Minni Minawi’s Sudan Liberation Movement, is not yet comprehensive as it did not include two other important armed movements.Expected to be formally signed in early October, the deal has been hailed as a ’historic achievement’ by the UN secretary-general, and the international community also commended the government of South Sudan for its positive role as mediator and urged hold-out groups to join the peace process. Much does depend on delivering on the agreement, and the experience of implementing past peace accords in Sudan has been dismal, particularly when it comes to bringing tangible benefits to people on the ground.What potentially makes the Juba agreement different is that Sudan’s civilian-led transitional government aspires to deliver peace, justice and democracy in line with the goals of the revolution; that the agreement was negotiated between the Sudanese themselves, with a light touch from the South Sudanese mediation and low-key logistical and technical support from the international community; and that much of the negotiations were conducted between former comrades, in marked contrast to the confrontational atmosphere that prevailed during the Bashir era.As Prime Minister Abdalla Hamdok put it: ’This is a Sudanese peace, made with our own hands and by our own efforts’ and: ’This is not a paper agreement, but is a living organism that needs care, attention and political will from all of us’.Achievements of the agreementThe result of almost one year’s hard work in Juba, the agreement is comprehensive in scope and addresses the fundamental issues of Sudan’s crises in Darfur, the Two Areas and other marginalized regions, albeit in a mixture of regional and national protocols. It goes a long way to realizing the vision of a democratic ‘New Sudan’ based on respect for the diversity of the Sudanese people and equal citizenship without religious, ethnic, cultural or gender discrimination.There is a focus on the concerns of historically marginalized populations in Sudan’s conflict zones and disadvantaged areas, and it addresses root causes of conflict, such as issues of identity, marginalization, the relationship between religion and state, governance, resource-sharing, land issues, social justice, and equality at the national level.The deal also looks to resolve the consequences of conflict, such as humanitarian relief, the safe and voluntary return of IDPs and refugees to their original lands and compensation, eviction of illegal settlers and the development and reconstruction of the conflict-affected areas. It provides for significant devolution of power and resources to the regions, including autonomy for the Two Areas and restoration of a single Darfur region. On transitional justice, the government has committed to cooperate fully with the International Criminal Court (ICC) and ensure Bashir and others subject to arrest warrants will ‘appear before’ the ICC.This deal will change the face of the transitional government by bringing marginalized forces to the centre of the political process. The transitional period will extend to 2023, with the armed movements having three seats in the (currently 11-member) Sovereign Council and 25% of seats in the Cabinet and soon-to-be-formed Legislative Assembly.The power-sharing provisions have been criticized as disproportionate to the size of the movements’ political constituencies and military presence inside Sudan. But the movements argue significant representation in the government is necessary to support implementation and that their arrival in Khartoum will help to strengthen the transition to democracy.Establishing a single, national professional army, reflective of the diversity of Sudan and with a new military doctrine opens the way for much-needed comprehensive security sector reform. During the transition, this will include the creation of a 12,000 strong joint force between government security forces and the armed movements to help protect civilians in Darfur. Importantly, mechanisms allowing for civilian input on security reforms are also established.The deal also guarantees religious freedom and the separation of religion from politics. This ensures religion will not be exploited by state institutions as it was during the Bashir-era, provides for the constitution to be based on equal citizenship, and for the establishment of a National Commission for Religious Freedom to protect the rights of Christians and other minorities. In the Two Areas, the autonomous government will have special legislative powers to pass laws based on the secular 1973 Constitution.Increasing inclusivityKey to achieving inclusive and sustainable peace is ensuring popular ownership and finding ways to engage civil society stakeholders and marginalized communities such as nomads in dialogue, reconciliation and social peace initiatives. The negotiations were mainly a top-down elitist process. Although the UN brought IDPs, tribal leaders and women’s groups to Juba for short periods, there was limited participation by civil society. However, the agreement provides for a wider range of stakeholders to feed into a comprehensive peace through reconciliation and transitional justice mechanisms, follow-on conferences and an inclusive National Constitutional Conference.Achieving a comprehensive peace will also mean bringing other armed movements on board, particularly those led by Abdel Aziz Al Hilu and Abdel Wahid Al Nur, both of whom hold significant territory, forces and support (in the Two Areas and Darfur respectively). Negotiations in Juba with Abdel Aziz had stalled over his demands for a secular state or, failing that, the right to self-determination, but he has now reached a preliminary agreement with Prime Minister Hamdok on a way forward.Other challenges of implementing peaceTurning the peace agreement into reality on the ground will face many other challenges given the fragility of a civilian-military transitional government, distrust, and competition between the signatory movements and some political parties, as well as increasing insecurity in many parts of the country caused by armed militias, inter-tribal violence, the proliferation of weapons, and sabotage by elements of the former regime. There is also likely to be resistance from groups such as illegal settlers who see their interests being threatened.With its economy in meltdown because of economic mismanagement by the Bashir regime, COVID-19, and unprecedented floods, finding resources to implement the peace deal is far beyond the means of Sudan’s cash-strapped government. Implementation therefore requires sustained and generous support from its regional and international partners, including the country’s urgent removal from the US State Sponsors of Terrorism list, which is preventing debt relief, access to concessionary loans and large-scale foreign investment. With donor budgets under heavy pressure, raising money will be hard, but by continuing to support a nascent democracy in a strategically important but unstable region, Sudan’s allies will be safeguarding their long-term interests.If properly implemented, the Juba peace agreement is a major first step towards creating a ‘New Sudan’ based on peace, equal citizenship and social justice. Key tests of whether Sudan can finally turn the page are whether the signatory movements and other revolutionary forces can unite to deliver the dividends of peace for the victims of Sudan’s conflicts, and embrace inclusion rather than tribalism and narrow political affiliation; whether the remaining armed movements are ready to start serious negotiations for a comprehensive peace; and whether Sudan now receives the support and attention it deserves from the international community. Surely Sudan has already come too far for this historic opportunity to be lost. Full Article
rn What will authorizing the return of US troops mean for Somalia? By www.chathamhouse.org Published On :: Fri, 17 Jun 2022 12:47:32 +0000 What will authorizing the return of US troops mean for Somalia? Explainer Video aboudiaf.drupal 17 June 2022 Ahmed Soliman examines what the reintroduction of US military means for Somalia. He says the strategy remains to try and reduce al-Shabaab’s threat, suppress its ability to carry out operations, and target its senior leadership. There is more of a recognition now that the focus needs to be on restoring an effective security sector within Somalia and ensuring their forces are ready, but this also requires better coordination between the federal government and federal member states which it is hoped will happen in this new administration. Full Article
rn Africa Aware: Drought in the Horn of Africa By www.chathamhouse.org Published On :: Mon, 31 Oct 2022 11:25:53 +0000 Africa Aware: Drought in the Horn of Africa Audio aboudiaf.drupal 31 October 2022 This episode discusses how the Horn of Africa’s worst drought in 40 years is affecting more than 20 million people across several countries. Abdirahman Abdishakur, Special Presidential Envoy for Drought Response for the Federal Republic of Somalia, outlines the Somali government’s planning to prevent famine. Parvin Ngala, Regional Director at Oxfam International, highlights international efforts to respond to the drought, the importance of empowering civil society in these circumstances, and what long-term mitigation measures are necessary to avoid a return to this situation. Full Article
rn The Annual Journal Impact Factor Saga By jnm.snmjournals.org Published On :: 2021-07-08T14:20:31-07:00 Full Article
rn Pattern of Failure in Patients with Biochemical Recurrence After PSMA Radioguided Surgery By jnm.snmjournals.org Published On :: 2024-09-26T12:46:37-07:00 Visual Abstract Full Article
rn Oncologist, Business Leader, and Investor Arie S. Belldegrun Discusses a Career in Innovative Medical Entrepreneurship: A Conversation with Ken Herrmann and Johannes Czernin By jnm.snmjournals.org Published On :: 2024-10-30T08:04:15-07:00 Full Article
rn International Metabolic Prognostic Index Is Superior to Other Metabolic Tumor Volume-Based Prognostication Methods in a Real-Life Cohort of Diffuse Large B-Cell Lymphoma By jnm.snmjournals.org Published On :: 2024-11-07T04:28:32-08:00 Visual Abstract Full Article
rn Pacific Rim: Learning to eat soup with a knife By news.sophos.com Published On :: Thu, 31 Oct 2024 12:36:53 +0000 What our incident responders know from five years of fighting an octopus Full Article Security Operations Pacific Rim Pacific Rim Defense PSIRT Sophos X-Ops
rn Addressing Climate Catastrophe Concerns in Asthma Medication Delivery: Rethinking Inhaler Use for Environmental and Clinical Efficacy By www.bmj.com Published On :: Tuesday, November 12, 2024 - 13:24 Full Article
rn Re: Scandal of “newborn gang” that put profits ahead of babies’ lives rocks Turkey’s health system By www.bmj.com Published On :: Tuesday, November 12, 2024 - 14:09 Full Article
rn Re: Scandal of “newborn gang” that put profits ahead of babies’ lives rocks Turkey’s health system By www.bmj.com Published On :: Tuesday, November 12, 2024 - 14:09 Full Article
rn Re: Scandal of “newborn gang” that put profits ahead of babies’ lives rocks Turkey’s health system By www.bmj.com Published On :: Tuesday, November 12, 2024 - 14:09 Full Article
rn Re: Scandal of “newborn gang” that put profits ahead of babies’ lives rocks Turkey’s health system By www.bmj.com Published On :: Tuesday, November 12, 2024 - 14:09 Full Article
rn Interspecies differences in proteome turnover kinetics are correlated with lifespans and energetic demands By www.mcponline.org Published On :: 2020-12-28 Kyle SwovickDec 28, 2020; 0:RA120.002301v1-mcp.RA120.002301Research Full Article
rn Proteome-wide Analysis Reveals Substrates of E3 Ligase RNF146 Targeted for Degradation By www.mcponline.org Published On :: 2020-12-01 Litong NieDec 1, 2020; 19:2015-2029Research Full Article
rn Proteomic identification of Coxiella burnetii effector proteins targeted to the host cell mitochondria during infection By www.mcponline.org Published On :: 2020-11-11 Laura F FieldenNov 11, 2020; 0:RA120.002370v1-mcp.RA120.002370Research Full Article
rn Proteome Turnover in the Spotlight: Approaches, Applications & Perspectives By www.mcponline.org Published On :: 2020-11-30 Alison B. RossNov 30, 2020; 0:R120.002190v1-mcp.R120.002190Review Full Article
rn ProAlanase is an Effective Alternative to Trypsin for Proteomics Applications and Disulfide Bond Mapping By www.mcponline.org Published On :: 2020-12-01 Diana SamodovaDec 1, 2020; 19:2139-2156Technological Innovation and Resources Full Article
rn Functions of Gle1 are governed by two distinct modes of self-association [Gene Regulation] By www.jbc.org Published On :: 2020-12-04T00:06:06-08:00 Gle1 is a conserved, essential regulator of DEAD-box RNA helicases, with critical roles defined in mRNA export, translation initiation, translation termination, and stress granule formation. Mechanisms that specify which, where, and when DDXs are targeted by Gle1 are critical to understand. In addition to roles for stress-induced phosphorylation and inositol hexakisphosphate binding in specifying Gle1 function, Gle1 oligomerizes via its N-terminal domain in a phosphorylation-dependent manner. However, a thorough analysis of the role for Gle1 self-association is lacking. Here, we find that Gle1 self-association is driven by two distinct regions: a coiled-coil domain and a novel 10-amino acid aggregation-prone region, both of which are necessary for proper Gle1 oligomerization. By exogenous expression in HeLa cells, we tested the function of a series of mutations that impact the oligomerization domains of the Gle1A and Gle1B isoforms. Gle1 oligomerization is necessary for many, but not all aspects of Gle1A and Gle1B function, and the requirements for each interaction domain differ. Whereas the coiled-coil domain and aggregation-prone region additively contribute to competent mRNA export and stress granule formation, both self-association domains are independently required for regulation of translation under cellular stress. In contrast, Gle1 self-association is dispensable for phosphorylation and nonstressed translation initiation. Collectively, we reveal self-association functions as an additional mode of Gle1 regulation to ensure proper mRNA export and translation. This work also provides further insight into the mechanisms underlying human gle1 disease mutants found in prenatally lethal forms of arthrogryposis. Full Article
rn Transcription factor NF-{kappa}B promotes acute lung inȷury via microRNA-99b-mediated PRDM1 down-regulation [Developmental Biology] By www.jbc.org Published On :: 2020-12-25T00:06:31-08:00 Acute lung injury (ALI), is a rapidly progressing heterogenous pulmonary disorder that possesses a high risk of mortality. Accumulating evidence has implicated the activation of the p65 subunit of NF-κB [NF-κB(p65)] activation in the pathological process of ALI. microRNAs (miRNAs), a group of small RNA molecules, have emerged as major governors due to their post-transcriptional regulation of gene expression in a wide array of pathological processes, including ALI. The dysregulation of miRNAs and NF-κB activation has been implicated in human diseases. In the current study, we set out to decipher the convergence of miR-99b and p65 NF-κB activation in ALI pathology. We measured the release of pro-inflammatory cytokines (IL-1β, IL-6, and TNFα) in bronchoalveolar lavage fluid using ELISA. MH-S cells were cultured and their viability were detected with cell counting kit 8 (CCK8) assays. The results showed that miR-99b was up-regulated, while PRDM1 was down-regulated in a lipopolysaccharide (LPS)-induced murine model of ALI. Mechanistic investigations showed that NF-κB(p65) was enriched at the miR-99b promoter region, and further promoted its transcriptional activity. Furthermore, miR-99b targeted PRDM1 by binding to its 3'UTR, causing its down-regulation. This in-creased lung injury, as evidenced by increased wet/dry ratio of mouse lung, myeloperoxidase activity and pro-inflammatory cytokine secretion, and enhanced infiltration of inflammatory cells in lung tissues. Together, our findings indicate that NF-κB(p65) promotion of miR-99b can aggravate ALI in mice by down-regulating the expression of PRDM1. Full Article
rn Distant coupling between RNA editing and alternative splicing of the osmosensitive cation channel Tmem63b [Cell Biology] By www.jbc.org Published On :: 2020-12-25T00:06:30-08:00 Post-transcriptional modifications of pre-mRNAs expand the diversity of proteomes in higher eukaryotes. In the brain, these modifications diversify the functional output of many critical neuronal signal molecules. In this study, we identified a brain-specific A-to-I RNA editing that changed glutamine to arginine (Q/R) at exon 20 and an alternative splicing of exon 4 in Tmem63b, which encodes a ubiquitously expressed osmosensitive cation channel. The channel isoforms lacking exon 4 occurred in ∼80% of Tmem63b mRNAs in the brain but were not detected in other tissues, suggesting a brain-specific splicing. We found that the Q/R editing was catalyzed by Adar2 (Adarb1) and required an editing site complementary sequence located in the proximal 5' end of intron 20. Moreover, the Q/R editing was almost exclusively identified in the splicing isoform lacking exon 4, indicating a coupling between the editing and the splicing. Elimination of the Q/R editing in brain-specific Adar2 knockout mice did not affect the splicing efficiency of exon 4. Furthermore, transfection with the splicing isoform containing exon 4 suppressed the Q/R editing in primary cultured cerebellar granule neurons. Thus, our study revealed a coupling between an RNA editing and a distant alternative splicing in the Tmem63b pre-mRNA, in which the splicing plays a dominant role. Finally, physiological analysis showed that the splicing and the editing coordinately regulate Ca2+ permeability and osmosensitivity of channel proteins, which may contribute to their functions in the brain. Full Article
rn NSun2 promotes cell migration through methylating autotaxin mRNA [Cell Biology] By www.jbc.org Published On :: 2020-12-25T00:06:30-08:00 NSun2 is an RNA methyltransferase introducing 5-methylcytosine into tRNAs, mRNAs, and noncoding RNAs, thereby influencing the levels or function of these RNAs. Autotaxin (ATX) is a secreted glycoprotein and is recognized as a key factor in converting lysophosphatidylcholine into lysophosphatidic acid (LPA). The ATX-LPA axis exerts multiple biological effects in cell survival, migration, proliferation, and differentiation. Here, we show that NSun2 is involved in the regulation of cell migration through methylating ATX mRNA. In the human glioma cell line U87, knockdown of NSun2 decreased ATX protein levels, whereas overexpression of NSun2 elevated ATX protein levels. However, neither overexpression nor knockdown of NSun2 altered ATX mRNA levels. Further studies revealed that NSun2 methylated the 3'-UTR of ATX mRNA at cytosine 2756 in vitro and in vivo. Methylation by NSun2 enhanced ATX mRNA translation. In addition, NSun2-mediated 5-methylcytosine methylation promoted the export of ATX mRNA from nucleus to cytoplasm in an ALYREF-dependent manner. Knockdown of NSun2 suppressed the migration of U87 cells, which was rescued by the addition of LPA. In summary, we identify NSun2-mediated methylation of ATX mRNA as a novel mechanism in the regulation of ATX. Full Article
rn Hsa-miRNA-23a-3p promotes atherogenesis in a novel mouse model of atherosclerosis By www.jlr.org Published On :: 2020-12-01 Jiayan GuoDec 1, 2020; 61:1764-1775Research Articles Full Article
rn LDL apheresis as an alternate method for plasma LPS purification in healthy volunteers and dyslipidemic and septic patients By www.jlr.org Published On :: 2020-12-01 Auguste DargentDec 1, 2020; 61:1776-1783Research Articles Full Article
rn Distinct patterns of apolipoprotein C-I, C-II and C-III isoforms are associated with markers of Alzheimers disease By www.jlr.org Published On :: 2020-12-11 Yueming HuDec 11, 2020; 0:jlr.RA120000919v1-jlr.RA120000919Research Articles Full Article
rn Problem Notes for SAS®9 - 66544: You cannot clear warnings for decision campaign nodes in SAS Customer Intelligence Studio By Published On :: Tue, 1 Sep 2020 13:41:53 EST In SAS Customer Intelligence Studio, you might notice that you cannot clear warnings for decision campaign nodes by selecting either the Clear Warnings option or the Clear All Warnin Full Article CAMPAIGNSDO+SAS+Customer+Intelligence+St
rn Problem Notes for SAS®9 - 66540: SAS Management Console and SAS Data Integration Studio might return the message "table failed to update" when you use the Update Metadata tool By Published On :: Tue, 1 Sep 2020 09:06:18 EST You encounter this issue when the table metadata matches the data source. In this scenario, no metadata update is required. Full Article MGMTCONSOLE+SAS+Management+Console
rn Problem Notes for SAS®9 - 66391: Opening a database table returns a Segmentation Violation when you use the Metadata LIBNAME engine (META) By Published On :: Wed, 26 Aug 2020 16:39:25 EST You might receive a Segmentation Violation when opening a database table in SAS. The SAS Log contains the error and traceback: ERR Full Article METADATASRV+SAS+Metadata+Server
rn Problem Notes for SAS®9 - 66504: Clicking a link to pass a group break value to a SAS Web Report Studio report returns an HTTP 400 error By Published On :: Thu, 20 Aug 2020 14:07:26 EST SAS Web Report Studio enables you to link reports based on a group break value. However, when you click the link, it might fail with an HTTP 400 error. The exact message you see depends on which browser you are u Full Article CITATIONWEB+SAS+Web+Report+Studio