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Sport24.co.za | AC Milan announce no first team coronavirus cases

AC Milan have revealed that none of their first-team footballers or staff were positive for coronavirus.




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Council votes against proposed cannabis store location in Lakeshore

In Lakeshore, it may be a little while longer before a retail cannabis store opens.




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Repression of sphingosine kinase (SK)-interacting protein (SKIP) in acute myeloid leukemia diminishes SK activity and its re-expression restores SK function [Molecular Bases of Disease]

Previous studies have shown that sphingosine kinase interacting protein (SKIP) inhibits sphingosine kinase (SK) function in fibroblasts. SK phosphorylates sphingosine producing the potent signaling molecule sphingosine-1-phosphate (S1P). SKIP gene (SPHKAP) expression is silenced by hypermethylation of its promoter in acute myeloid leukemia (AML). However, why SKIP activity is silenced in primary AML cells is unclear. Here, we investigated the consequences of SKIP down-regulation in AML primary cells and the effects of SKIP re-expression in leukemic cell lines. Using targeted ultra-HPLC-tandem MS (UPLC-MS/MS), we measured sphingolipids (including S1P and ceramides) in AML and control cells. Primary AML cells had significantly lower SK activity and intracellular S1P concentrations than control cells, and SKIP-transfected leukemia cell lines exhibited increased SK activity. These findings show that SKIP re-expression enhances SK activity in leukemia cells. Furthermore, other bioactive sphingolipids such as ceramide were also down-regulated in primary AML cells. Of note, SKIP re-expression in leukemia cells increased ceramide levels 2-fold, inactivated the key signaling protein extracellular signal-regulated kinase, and increased apoptosis following serum deprivation or chemotherapy. These results indicate that SKIP down-regulation in AML reduces SK activity and ceramide levels, an effect that ultimately inhibits apoptosis in leukemia cells. The findings of our study contrast with previous results indicating that SKIP inhibits SK function in fibroblasts and therefore challenge the notion that SKIP always inhibits SK activity.




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The FKH domain in FOXP3 mRNA frequently contains mutations in hepatocellular carcinoma that influence the subcellular localization and functions of FOXP3 [Molecular Bases of Disease]

The transcription factor forkhead box P3 (FOXP3) is a biomarker for regulatory T cells and can also be expressed in cancer cells, but its function in cancer appears to be divergent. The role of hepatocyte-expressed FOXP3 in hepatocellular carcinoma (HCC) is unknown. Here, we collected tumor samples and clinical information from 115 HCC patients and used five human cancer cell lines. We examined FOXP3 mRNA sequences for mutations, used a luciferase assay to assess promoter activities of FOXP3's target genes, and employed mouse tumor models to confirm in vitro results. We detected mutations in the FKH domain of FOXP3 mRNAs in 33% of the HCC tumor tissues, but in none of the adjacent nontumor tissues. None of the mutations occurred at high frequency, indicating that they occurred randomly. Notably, the mutations were not detected in the corresponding regions of FOXP3 genomic DNA, and many of them resulted in amino acid substitutions in the FKH region, altering FOXP3's subcellular localization. FOXP3 delocalization from the nucleus to the cytoplasm caused loss of transcriptional regulation of its target genes, inactivated its tumor-inhibitory capability, and changed cellular responses to histone deacetylase (HDAC) inhibitors. More complex FKH mutations appeared to be associated with worse prognosis in HCC patients. We conclude that mutations in the FKH domain of FOXP3 mRNA frequently occur in HCC and that these mutations are caused by errors in transcription and are not derived from genomic DNA mutations. Our results suggest that transcriptional mutagenesis of FOXP3 plays a role in HCC.




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Effects of deficiency in the RLBP1-encoded visual cycle protein CRALBP on visual dysfunction in humans and mice [Cell Biology]

Mutations in retinaldehyde-binding protein 1 (RLBP1), encoding the visual cycle protein cellular retinaldehyde-binding protein (CRALBP), cause an autosomal recessive form of retinal degeneration. By binding to 11-cis-retinoid, CRALBP augments the isomerase activity of retinoid isomerohydrolase RPE65 (RPE65) and facilitates 11-cis-retinol oxidation to 11-cis-retinal. CRALBP also maintains the 11-cis configuration and protects against unwanted retinaldehyde activity. Studying a sibling pair that is compound heterozygous for mutations in RLBP1/CRALBP, here we expand the phenotype of affected individuals, elucidate a previously unreported phenotype in RLBP1/CRALBP carriers, and demonstrate consistencies between the affected individuals and Rlbp1/Cralbp−/− mice. In the RLBP1/CRALBP-affected individuals, nonrecordable rod-specific electroretinogram traces were recovered after prolonged dark adaptation. In ultrawide-field fundus images, we observed radially arranged puncta typical of RLBP1/CRALBP-associated disease. Spectral domain-optical coherence tomography (SD-OCT) revealed hyperreflective aberrations within photoreceptor-associated bands. In short-wavelength fundus autofluorescence (SW-AF) images, speckled hyperautofluorescence and mottling indicated macular involvement. In both the affected individuals and their asymptomatic carrier parents, reduced SW-AF intensities, measured as quantitative fundus autofluorescence (qAF), indicated chronic impairment in 11-cis-retinal availability and provided information on mutation severity. Hypertransmission of the SD-OCT signal into the choroid together with decreased near-infrared autofluorescence (NIR-AF) provided evidence for retinal pigment epithelial cell (RPE) involvement. In Rlbp1/Cralbp−/− mice, reduced 11-cis-retinal levels, qAF and NIR-AF intensities, and photoreceptor loss were consistent with the clinical presentation of the affected siblings. These findings indicate that RLBP1 mutations are associated with progressive disease involving RPE atrophy and photoreceptor cell degeneration. In asymptomatic carriers, qAF disclosed previously undetected visual cycle deficiency.




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Report Launch – Owners of the Republic: An Anatomy of Egypt's Military Economy

Research Event

12 December 2019 - 5:30pm to 6:30pm

Chatham House | 10 St James's Square | London | SW1Y 4LE

Event participants

Yezid Sayigh, Senior Fellow, Carnegie Middle East Center
David Butter, Associate Fellow, Middle East and North Africa Programme, Chatham House
Chair: Lina Khatib, Head, Middle East and North Africa Programme, Chatham House

The Egyptian military accounts for far less of the national economy than is commonly believed but transformations in its role and scope since 2013 have turned it into an autonomous economic actor that can reshape markets and influence government policy and investment strategies. Will the military economy contract to its former enclave status if Egypt achieves successful economic growth or has it acquired a permanent stake that it will defend or even expand?

This roundtable will mark the London launch of a Carnegie Middle East Center report on Egypt’s military economy. The report author, Yezid Sayigh, will begin the discussion with remarks on Egypt’s military economy model and offer thoughts on how external actors can engage the country’s formal and informal networks. David Butter will serve as discussant and the roundtable will be moderated by Lina Khatib.

To attend this event, please e-mail Reni Zhelyazkova

Reni Zhelyazkova

Programme Coordinator, Middle East and North Africa Programme
+44 (0)20 7314 3624




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Lebanon Is Paying the Cost of Its Dysfunctional Politics

26 February 2020

Nadim Shehadi

Associate Fellow, Middle East and North Africa Programme
A series of fights to political stalemate have led its economy to the brink and cut it off from its natural economic partners in the Gulf.

2020-02-25-Leb1.jpg

Protests against economic conditions and government inaction turned violent in January. Photo: Getty Images.

To understand Lebanon’s financial collapse, look to its politics.

The country has been deeply damaged by an increasingly dysfunctional political system. A series of compromises have alienated it from its main markets in the Gulf and strangled its economy; anyone that has glanced at fluctuations in Lebanese bank deposits over the last 10 years can see the correlation.

Imagine if Boris Johnson or Donald Trump were obliged to form joint governments with Jeremy Corbyn or Bernie Sanders. The result would be paralysis and lack of accountability as each party pulls the country in opposite directions and blames the other for the state of limbo. This has been the state of affairs in Lebanon since the Doha agreement of 2008. 

That agreement followed an 18-month siege that paralyzed Beirut and an attack on the city by Hezbollah’s ‘black shirts’. The Doha formula imposed governments of national unity between Prime Minister Saad Hariri’s pro-Saudi camp and Hezbollah’s pro-Iran camp and their respective internal allies.

The pattern was set: each period of subsequent paralysis was followed by further compromise as the tug of war pulled the country away from its principal economic partners, the Arab Gulf states, with the regional balance of power tilting towards Hezbollah. 

It was not supposed to be like this. The Baabda Declaration in June 2012, reached after a process of national dialogue, was meant to secure Lebanon’s neutrality in regional conflicts, with both sides promising to hold back on external alliances and coexist despite difference over major regional issues like the war in Syria, the standoff between the US and Iran or relations with Israel or the Gulf states.

This has worn away. The Baabda declaration itself became a sham when Hezbollah inserted itself into the war in Syria in support of the Assad regime and overtly got involved in Iraq and Yemen as an Iranian proxy. This was followed by Saudi opposition to concessions by Hariri that led to the election of General Michel Aoun, an ally of Hezbollah, as president in October 2016; again, after a political paralysis that lasted 29 months with no active government and no head of state.  

The Saudis were also furious when President Aoun’s son-in-law, Foreign Minister Gebran Bassil, abstained from condemning the burning of the Saudi embassy in Tehran at an Arab League meeting in Cairo in January 2016, citing the need to preserve national unity.

Fearing that he was simply providing Hezbollah with protection in the guise of compromise, the Saudis pressured Hariri to resign in November 2017 during a trip to Riyadh, but he later challenged that by retracting on his resignation when back in Beirut. Lebanon was caught between two sides, and as the regional conflict intensified from tension to open confrontation, neutrality was no longer an option.

Gulf connections

An estimated 350,000 Lebanese expats live and work in Saudi Arabia, the UAE, Qatar and Kuwait. These countries are also the main clients for Lebanese contractors, consultants and advertising companies, some of which have offices there. The domestic tourism industry relies heavily on Arab Gulf visitors and they are a principal source of foreign investments especially in the real estate sector.

Lebanon also enjoyed a certain degree of political and economic protection from the US and the Gulf, and Hezbollah benefited indirectly from that protection, as it also shielded it to a certain degree from sanctions.

The deterioration of relations meant that the country was cut off by its Gulf partners. This was manifested in travel bans for Gulf Cooperation Council (GCC) nationals to Lebanon and a decrease in investments and bank deposits, as well as a decrease in remittances from Lebanese expats, partly because of economic crisis in the Gulf countries themselves.

Saudi Arabia withdrew $4 billion of aid to the Lebanese army and internal security forces, and no aid or deposits were forthcoming as the economic and financial situation deteriorated. 

The costs to the Lebanese economy include the opportunity cost created by the annual threat of war with Israel, after which trips are cancelled and projects postponed. Hezbollah also controls a section of Beirut port where it pays no duty or taxes. Add to that the economic fallout from the war in Syria, such as the impact on exports, the inflow of refugees and the cost of Hezbollah’s involvement.

The burden of these political factors is difficult to estimate but it constitutes the ransom that the Lebanese economy bears as a cost of the compromise. This is not to absolve Lebanese politicians from corruption or bankers of mismanagement but to add that political factors cannot be ignored.

The cumulative cost and economic impact of being cut off from its main economic partner eventually bankrupted the country. The fiscal and financial aspects, with Lebanon’s inability to service its debt, are but a reflection of these political factors. In the long run, the key to avoiding complete collapse is to restore relations with the GCC and free Lebanon from that very costly grip.




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Virtual Roundtable: Iraq in Uncertain Times

Invitation Only Research Event

30 March 2020 - 2:00pm to 3:30pm

Event participants

Toby Dodge, Associate Fellow, MENA Programme, Chatham House
Mac Skelton, Director, IRIS, American University of Iraq-Sulaimani
Ahmed Tabaqchali, Chief Investment Officer, AFC Iraq Fund
Hanaa Edwar, Co-founder and Chairperson, Iraqi Al-Amal Association
Chair: Renad Mansour, Senior Research Fellow, MENA Programme, Chatham House

The first months of 2020 have proven tumultuous for Iraq. The US killing of Iranian General Qassem Soleimani in January threatened to engulf the region in war and led to continued tit-for-tat violence between the US and Iran that has become almost a daily reality in Baghdad.

Amid the ongoing protests that since last October have challenged the social contract and led to a violent response claiming 600 deaths and injuring tens of thousands, the government is still without a prime minister after Adil abd al-Mehdi's resignation in November 2019, leaving the country directionless.

Most recently, the spread of COVID-19 threatens to expose a mismanaged healthcare system. At the same time, the rapid fall in the price of oil has impacted the government's ability to respond to or cope with these crises.

At this virtual roundtable, part of the Chatham House Iraq Initiative, experts explore these developments and try to unpack the implications for Iraq’s fragile peace and stability.

Reni Zhelyazkova

Programme Coordinator, Middle East and North Africa Programme
+44 (0)20 7314 3624




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Chatham House Prize 2015 Nominees Announced

20 March 2015

Chatham House is pleased to announce the nominees for the 2015 Chatham House Prize. 

The nominees are: 

  • Mahamadou Issoufou, President of the Republic of Niger
  • Médecins Sans Frontières
  • Angela Merkel, Chancellor of the Federal Republic of Germany
  • Juan Manuel Santos, President of the Republic of Colombia 

The Chatham House Prize is awarded to the person or organization deemed to have made the most significant contribution to the improvement of international relations in the previous year. 

The winner will be announced later this year and an award ceremony will take place in the autumn. 

More about the 2015 nominees 


About the Chatham House Prize 

The selection proceed for the nominees draws on the expertise of Chatham House's research teams and three presidents - Lord Ashdown, Sir John Major and Baroness Scotland. Our members are then invited to vote for the winner in a ballot. The winner will be announced later this year. 

The winner will receive a crystal award and a scroll signed by our Patron, Her Majesty the Queen. An award ceremony will take place in London with keynote speeches by leading figures in international affairs. 

Previous winners include: Melinda Gates (2014); Hillary Rodham Clinton, former US Secretary of State (2013); Sheikh Rached Ghannouchi, Head of the Ennahdha movement, Tunisia and Dr Moncef Marzouki, President of Tunisia (2012); Aung San Suu Kyi, Burmese democracy campaigner (2011); HE Abdullah Gül, President of Turkey (2010), HE President Luiz Inácio Lula da Silva of Brazil (2009), President John Kufuor of Ghana (2008), HH Sheikha Mozah, Chairperson, Qatar Foundation (2007), HE Joaquim Chissano, former President of Mozambique (2006) and HE President Victor Yushchenko of Ukraine (2005). 

More about the Prize and previous winners




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Connecting the digital divides: Technology and cyber policy experts launch new journal

30 June 2015

Chatham House and Routledge, Taylor & Francis are launching the Journal of Cyber Policy on 2 July.

Fifteen years ago it would be unthinkable for cyber security to top the list of priorities at the annual US-China Security and Economic Dialogue, as it did last week. But, in the intervening years, cyber technologies and the internet have become fundamental tools for everything from running critical infrastructure such as energy grids and satellite systems, to political, economic and social interactions. Given the pace of change, it should not surprise us that we have barely started to understand how to govern this new order and manage the global internet in ways that both empower and protect us.

In response, Chatham House and Routledge (part of the Taylor & Francis Group) are launching the Journal of Cyber Policy, addressing a rapidly changing situation and connecting creative, technical and policy experts.

Informing the growing security challenges of an interconnected digital world, this new peer-reviewed journal will provide a valuable resource to decision-makers in the public and private sectors grappling with the challenges of cyber security, online privacy, surveillance and internet access. The journal will offer informed and rigorous thinking, supported by the journal’s internationally renowned editorial board.

'The Journal of Cyber Policy will empower experts with new thinking and diverse ideas delivered in a way which is practically relevant as well as academically rigorous,' Dr Patricia Lewis, research director, International Security Department at Chatham House and co-editor of the journal, said. 'It will change the game for those working on cyber issues.' 

'As the preferred publisher for think tanks around the world, we are proud to be Chatham House’s partner on this new journal, which seeks to address issues that touch upon all our lives on a daily basis,' said Leon Heward-Mills, Global Publishing Director (Journals) at Taylor & Francis Group.

The Journal of Cyber Policy launches on the evening of 2 July at a reception at Chatham House.

Editor's notes

Patricia Lewis, research director, International Security, Chatham House, is available for interview on cyber issues. To request an interview, please contact the press office.

Reflecting the global nature of cyber issues, the Journal of Cyber Policy is intent on drawing upon a geographically and culturally diverse set of contributors.

The editorial board includes:

  • Subimal Bhattacharjee, independent consultant on defense and cyber security issues, New Delhi (India)
  • Pablo Bello, secretary general, Asociación Iberoamericana de Centros de Investigación y Empresas de Telecomunicaciones (AHCIET) [and former vice minister of telecommunications] (Chile)
  • Dr Myriam Dunn Cavelty, lecturer for security studies and senior researcher in the field of risk and resilience at the Center for Security Studies, Zurich (Switzerland)
  • Prof Richard Dasher, director, US-Asia Technology Management Center, Stanford University (USA)
  • Dorothy Gordon, director-general, Ghana-India Kofi Annan Centre of Excellence in ICT (Ghana)
  • Alexandra Kulikova, programme coordinator, Global Internet Governance and International Information Security, PIR Center (Russia)
  • Dr Victoria Nash, deputy director, Oxford Internet Institute (UK)
  • Prof Motohiro Tsuchiya, professor, Graduate School of Media and Governance, Keio University (Japan)

Editor, the Journal of Cyber Policy: Caroline Baylon, Chatham House
Co-editors, the Journal of Cyber Policy: Dr Patricia Lewis and Emily Taylor, Chatham House

Topics for the first edition are as follows:

  • How did we get here?
  • Cyber crime – the impact so far
  • How does the internet run and who owns it?
  • Privacy vs security
  • Vulnerability and resilience of critical infrastructure
  • Cyber war is already underway
  • The next billion online
  • ​Cyber security awareness: Are politicians fit for purpose?
  • Internet of Things

The first two issues of the Journal on Cyber Policy will be published in 2016 and subscriptions to the journal can be placed in August 2015.

Chatham House 

Chatham House, the Royal Institute of International Affairs, is an independent policy institute based in London. It is renowned for open debate, independent analysis and new ideas. Chatham House experts develop new ideas on how best to confront critical international challenges and take advantage of opportunities from the near- to the long-term. Policy recommendations are developed in collaboration with policy-makers, experts and stakeholders in each area. Chatham House staff regularly brief government officials, legislators and other decision-makers on their conclusions.

Taylor & Francis Group

Taylor & Francis Group partners with researchers, scholarly societies, universities and libraries worldwide to bring knowledge to life.  As one of the world’s leading publishers of scholarly journals, books, ebooks and reference works our content spans all areas of Humanities, Social Sciences, Behavioural Sciences, Science, and Technology and Medicine.

From our network of offices in Oxford, New York, Philadelphia, Boca Raton, Boston, Melbourne, Singapore, Beijing, Tokyo, Stockholm, New Delhi and Johannesburg, Taylor & Francis staff provide local expertise and support to our editors, societies and authors and tailored, efficient customer service to our library colleagues.

Contacts

Press Office

+44 (0)20 7957 5739




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Chatham House Prize 2016 Nominees Announced

5 April 2016

Chatham House is pleased to announce the nominees for the 2016 Chatham House Prize.

The nominees are:

  • Laurent Fabius & Christiana Figueres: nominated for their pivotal role in delivering a global climate agreement at the COP 21 meeting in Paris in December 2015.
  • Attahiru Muhammadu Jega: nominated for his professionalism, determination and integrity as chairman of Nigeria’s electoral commission, which, in 2015, ensured the conduct of Nigeria’s most credible election since the country’s return to civilian rule in 1999.
  • John Kerry & Mohammad Javad Zarif: nominated for their crucial roles, throughout 2015, in successfully negotiating the historic nuclear deal between Iran and the P5+1.

The Chatham House Prize is awarded to the person, persons or organization deemed to have made the most significant contribution to the improvement of international relations in the previous year.

The winner will be announced later this year and an award ceremony will take place in the autumn.

More about the 2016 nominees

More about the Prize and previous winners




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Chatham House is pleased to announce Koc Holding’s support for the Turkey Project

22 February 2017

Chatham House is delighted to announce Koc Holding’s support for the Turkey Project, based in the Europe Programme.

The project aims to analyze and highlight important issues emanating from Turkey’s geostrategic position and bring a Turkish perspective to important regional developments. Areas of research include Turkey’s evolving relationship with Europe and its contribution to the new ‘silk road’ known as the Belt and Road initiative, aimed at strengthening trade and infrastructure links between Asia and Europe.

Mr Ali Y Koc, vice chairman of Koc Holding, has also joined the Chatham House Panel of Senior Advisers, to which he will bring his experience and perspectives on Turkey and on wider global political, economic and social issues.

Koc Holding is the leading business group in Turkey with extensive activities in the manufacturing, energy, defence and finance sectors. Mr Ali Y Koc is a board member and executive committee member of Koc Holding and chairman of the 1907 Fenerbahce Association and the National Competitiveness Research Association. He is a board member of the Foreign Economic Relations Board (DEIK), Endeavor Turkey and vice president of the Turkish Industrialists' and Business Association (TUSIAD). He is also a member of the Bank of America Global Advisory Council.

Robin Niblett, director of Chatham House, said: 'We are grateful to Mr Ali Y Koc and Koc Holding for supporting this initiative, which builds on our established track record of work on Turkey. Turkey plays an increasingly important strategic role, and through this project, Chatham House will be able to expand its analysis and activities in this area. I am also delighted that Chatham House will benefit from the input and expertise of Mr Koc as a member of the institute’s Panel of Senior Advisers.'

Mr Ali Y Koc said: 'Koc Holding is pleased to establish a long-term partnership with Chatham House and support a distinctive research project on Turkey at a world-leading think-tank. We look forward to sharing our insights on Turkey and other significant issues in international affairs among such a distinguished globally-renowned group of individuals in foreign policy, business and civil society on the Panel of Senior Advisers.'




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Chatham House Prize 2017 Nominees Announced

3 April 2017

Chatham House is pleased to announce the nominees for the 2017 Chatham House Prize.

The Chatham House Prize is awarded to the person, persons or organization deemed to have made the most significant contribution to the improvement of international relations in the previous year.

The nominees are:

  • Charlotte Osei, Chairperson of the Electoral Commission of Ghana: nominated for ensuring a peaceful and transparent electoral process in Ghana in December 2016, further consolidating Ghana’s 24-year long democratic journey.
  • Juan Manuel Santos, President of Colombia: nominated for formally ratifying a peace agreement with the FARC rebel group and bringing an end to the war in Colombia.
  • Jens Stoltenberg, Secretary-General of NATO: nominated for steering NATO through one of the most complicated periods in its recent history.

The winner will be announced later this year, and an award ceremony will take place in the autumn.

More about the 2017 nominees

More about the Prize and previous winners




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Queen Elizabeth II Academy for Leadership Announces 2018/19 Fellows

1 October 2018

The Queen Elizabeth II Academy for Leadership in International Affairs, based at Chatham House, is delighted to announce the arrival of its new cohort of Academy fellows.

The Academy was launched by Her Majesty the Queen in November 2014 to offer potential and established leaders from around the world the opportunity to spend ten months as Academy fellows and develop the tools needed to address the major policy challenges and critical issues facing the world today.

Academy fellows are drawn from government and the broader policy community, the private sector, media and civil society. During their time at the Academy, fellows deepen their understanding of critical issues, learn new skills, develop their networks and propose new ideas and solutions to complex policy challenges and opportunities.

Dr Leslie Vinjamuri, Dean, QEII Academy for Leadership in International Affairs says:

'Chatham House recognizes the need for inspirational and effective leadership in today’s complex and rapidly changing global environment. We remain absolutely committed to the mission of developing leadership skills and feel privileged to welcome the 2018-19 Academy Fellows. The Queen Elizabeth II Academy is uniquely well-positioned, drawing on the historical depth of expertise at Chatham House, our international and national networks, and the dynamism of London to develop skills, knowledge, and global insights that benefit emerging and accomplished leaders across diverse sectors in Europe, Africa, the Middle East, Asia and the Americas.'

Academy Fellows 2018/19

Rustam Anshba
Rustam’s research will explore the prospects for transforming the Georgian-Abkhaz conflict. He will be hosted by the Russia and Eurasia Programme. His fellowship is supported by the Robert Bosch Stiftung.

Rita Dayoub
Rita will analyse attacks against healthcare systems during conflicts in Syria and South Sudan. She will be hosted by the Centre on Global Health Security. Her fellowship is supported by the Asfari Foundation.

Isabel Dunstan
Isabel’s research will focus on digital literacy among women as a means to counter radicalization and intolerance in Indonesia. She will be hosted by the Asia-Pacific Programme. Her fellowship is supported by Mr Richard Hayden.

Sophia Ignatidou
Sophia will examine the political and security implications of Artificial Intelligence. She will be hosted by the International Security Department. Her fellowship is supported by the Stavros Niarchos Foundation.

Anna Korbut
Anna’s research will examine the current media landscape in Ukraine and its transformative potential. She will be hosted by the Russia and Eurasia Programme. Her fellowship is supported by the Robert Bosch Stiftung.

Damir Kurtagic
Damir will research the challenges and possibilities of private sector engagement in Sub-Saharan Africa. He will be hosted by the Africa Programme. His fellowship is supported by the Robert Bosch Stiftung.

Zaki Mehchy
Zaki will research the role and dynamics of non-state actors in Syria and their relationship with state institutions. He will be hosted by the Middle East and North Africa Programme. His fellowship is supported by the Asfari Foundation.

Anne Nyambane
Anne will examine the synergies and trade-offs involved in the implementation of the Sustainable Development Goals (SDGs). She will be hosted by the Energy, Environment and Resources Department. Her fellowship is supported by the Mo Ibrahim Foundation.

Masterclass
The Academy is also pleased to welcome three Masterclass participants from the European Bank for Reconstruction and Development.





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High Resolution Clear Native Electrophoresis for In-gel Functional Assays and Fluorescence Studies of Membrane Protein Complexes

Ilka Wittig
Jul 1, 2007; 6:1215-1225
Research




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A Versatile Nanotrap for Biochemical and Functional Studies with Fluorescent Fusion Proteins

Ulrich Rothbauer
Feb 1, 2008; 7:282-289
Research




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SUMOylation of the transcription factor ZFHX3 at Lys-2806 requires SAE1, UBC9, and PIAS2 and enhances its stability and function in cell proliferation [Protein Synthesis and Degradation]

SUMOylation is a posttranslational modification (PTM) at a lysine residue and is crucial for the proper functions of many proteins, particularly of transcription factors, in various biological processes. Zinc finger homeobox 3 (ZFHX3), also known as AT motif-binding factor 1 (ATBF1), is a large transcription factor that is active in multiple pathological processes, including atrial fibrillation and carcinogenesis, and in circadian regulation and development. We have previously demonstrated that ZFHX3 is SUMOylated at three or more lysine residues. Here, we investigated which enzymes regulate ZFHX3 SUMOylation and whether SUMOylation modulates ZFHX3 stability and function. We found that SUMO1, SUMO2, and SUMO3 each are conjugated to ZFHX3. Multiple lysine residues in ZFHX3 were SUMOylated, but Lys-2806 was the major SUMOylation site, and we also found that it is highly conserved among ZFHX3 orthologs from different animal species. Using molecular analyses, we identified the enzymes that mediate ZFHX3 SUMOylation; these included SUMO1-activating enzyme subunit 1 (SAE1), an E1-activating enzyme; SUMO-conjugating enzyme UBC9 (UBC9), an E2-conjugating enzyme; and protein inhibitor of activated STAT2 (PIAS2), an E3 ligase. Multiple analyses established that both SUMO-specific peptidase 1 (SENP1) and SENP2 deSUMOylate ZFHX3. SUMOylation at Lys-2806 enhanced ZFHX3 stability by interfering with its ubiquitination and proteasomal degradation. Functionally, Lys-2806 SUMOylation enabled ZFHX3-mediated cell proliferation and xenograft tumor growth of the MDA-MB-231 breast cancer cell line. These findings reveal the enzymes involved in, and the functional consequences of, ZFHX3 SUMOylation, insights that may help shed light on ZFHX3's roles in various cellular and pathophysiological processes.




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Reduction of protein phosphatase 2A (PP2A) complexity reveals cellular functions and dephosphorylation motifs of the PP2A/B'{delta} holoenzyme [Enzymology]

Protein phosphatase 2A (PP2A) is a large enzyme family responsible for most cellular Ser/Thr dephosphorylation events. PP2A substrate specificity, localization, and regulation by second messengers rely on more than a dozen regulatory subunits (including B/R2, B'/R5, and B″/R3), which form the PP2A heterotrimeric holoenzyme by associating with a dimer comprising scaffolding (A) and catalytic (C) subunits. Because of partial redundancy and high endogenous expression of PP2A holoenzymes, traditional approaches of overexpressing, knocking down, or knocking out PP2A regulatory subunits have yielded only limited insights into their biological roles and substrates. To this end, here we sought to reduce the complexity of cellular PP2A holoenzymes. We used tetracycline-inducible expression of pairs of scaffolding and regulatory subunits with complementary charge-reversal substitutions in their interaction interfaces. For each of the three regulatory subunit families, we engineered A/B charge–swap variants that could bind to one another, but not to endogenous A and B subunits. Because endogenous Aα was targeted by a co-induced shRNA, endogenous B subunits were rapidly degraded, resulting in expression of predominantly a single PP2A heterotrimer composed of the A/B charge–swap pair and the endogenous catalytic subunit. Using B'δ/PPP2R5D, we show that PP2A complexity reduction, but not PP2A overexpression, reveals a role of this holoenzyme in suppression of extracellular signal–regulated kinase signaling and protein kinase A substrate dephosphorylation. When combined with global phosphoproteomics, the PP2A/B'δ reduction approach identified consensus dephosphorylation motifs in its substrates and suggested that residues surrounding the phosphorylation site play roles in PP2A substrate specificity.




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DHHC7-mediated palmitoylation of the accessory protein barttin critically regulates the functions of ClC-K chloride channels [Cell Biology]

Barttin is the accessory subunit of the human ClC-K chloride channels, which are expressed in both the kidney and inner ear. Barttin promotes trafficking of the complex it forms with ClC-K to the plasma membrane and is involved in activating this channel. Barttin undergoes post-translational palmitoylation that is essential for its functions, but the enzyme(s) catalyzing this post-translational modification is unknown. Here, we identified zinc finger DHHC-type containing 7 (DHHC7) protein as an important barttin palmitoyl acyltransferase, whose depletion affected barttin palmitoylation and ClC-K-barttin channel activation. We investigated the functional role of barttin palmitoylation in vivo in Zdhhc7−/− mice. Although palmitoylation of barttin in kidneys of Zdhhc7−/− animals was significantly decreased, it did not pathologically alter kidney structure and functions under physiological conditions. However, when Zdhhc7−/− mice were fed a low-salt diet, they developed hyponatremia and mild metabolic alkalosis, symptoms characteristic of human Bartter syndrome (BS) type IV. Of note, we also observed decreased palmitoylation of the disease-causing R8L barttin variant associated with human BS type IV. Our results indicate that dysregulated DHHC7-mediated barttin palmitoylation appears to play an important role in chloride channel dysfunction in certain BS variants, suggesting that targeting DHHC7 activity may offer a potential therapeutic strategy for reducing hypertension.




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Structural and mutational analyses of the bifunctional arginine dihydrolase and ornithine cyclodeaminase AgrE from the cyanobacterium Anabaena [Enzymology]

In cyanobacteria, metabolic pathways that use the nitrogen-rich amino acid arginine play a pivotal role in nitrogen storage and mobilization. The N-terminal domains of two recently identified bacterial enzymes: ArgZ from Synechocystis and AgrE from Anabaena, have been found to contain an arginine dihydrolase. This enzyme provides catabolic activity that converts arginine to ornithine, resulting in concomitant release of CO2 and ammonia. In Synechocystis, the ArgZ-mediated ornithine–ammonia cycle plays a central role in nitrogen storage and remobilization. The C-terminal domain of AgrE contains an ornithine cyclodeaminase responsible for the formation of proline from ornithine and ammonia production, indicating that AgrE is a bifunctional enzyme catalyzing two sequential reactions in arginine catabolism. Here, the crystal structures of AgrE in three different ligation states revealed that it has a tetrameric conformation, possesses a binding site for the arginine dihydrolase substrate l-arginine and product l-ornithine, and contains a binding site for the coenzyme NAD(H) required for ornithine cyclodeaminase activity. Structure–function analyses indicated that the structure and catalytic mechanism of arginine dihydrolase in AgrE are highly homologous with those of a known bacterial arginine hydrolase. We found that in addition to other active-site residues, Asn-71 is essential for AgrE's dihydrolase activity. Further analysis suggested the presence of a passage for substrate channeling between the two distinct AgrE active sites, which are situated ∼45 Å apart. These results provide structural and functional insights into the bifunctional arginine dihydrolase–ornithine cyclodeaminase enzyme AgrE required for arginine catabolism in Anabaena.




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Detailed analyses of the crucial functions of Zn transporter proteins in alkaline phosphatase activation [Enzymology]

Numerous zinc ectoenzymes are metalated by zinc and activated in the compartments of the early secretory pathway before reaching their destination. Zn transporter (ZNT) proteins located in these compartments are essential for ectoenzyme activation. We have previously reported that ZNT proteins, specifically ZNT5–ZNT6 heterodimers and ZNT7 homodimers, play critical roles in the activation of zinc ectoenzymes, such as alkaline phosphatases (ALPs), by mobilizing cytosolic zinc into these compartments. However, this process remains incompletely understood. Here, using genetically-engineered chicken DT40 cells, we first determined that Zrt/Irt-like protein (ZIP) transporters that are localized to the compartments of the early secretory pathway play only a minor role in the ALP activation process. These transporters included ZIP7, ZIP9, and ZIP13, performing pivotal functions in maintaining cellular homeostasis by effluxing zinc out of the compartments. Next, using purified ALP proteins, we showed that zinc metalation on ALP produced in DT40 cells lacking ZNT5–ZNT6 heterodimers and ZNT7 homodimers is impaired. Finally, by genetically disrupting both ZNT5 and ZNT7 in human HAP1 cells, we directly demonstrated that the tissue-nonspecific ALP-activating functions of both ZNT complexes are conserved in human cells. Furthermore, using mutant HAP1 cells, we uncovered a previously-unrecognized and unique spatial regulation of ZNT5–ZNT6 heterodimer formation, wherein ZNT5 recruits ZNT6 to the Golgi apparatus to form the heterodimeric complex. These findings fill in major gaps in our understanding of the molecular mechanisms underlying zinc ectoenzyme activation in the compartments of the early secretory pathway.




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Reduction of protein phosphatase 2A (PP2A) complexity reveals cellular functions and dephosphorylation motifs of the PP2A/B'{delta} holoenzyme [Enzymology]

Protein phosphatase 2A (PP2A) is a large enzyme family responsible for most cellular Ser/Thr dephosphorylation events. PP2A substrate specificity, localization, and regulation by second messengers rely on more than a dozen regulatory subunits (including B/R2, B'/R5, and B″/R3), which form the PP2A heterotrimeric holoenzyme by associating with a dimer comprising scaffolding (A) and catalytic (C) subunits. Because of partial redundancy and high endogenous expression of PP2A holoenzymes, traditional approaches of overexpressing, knocking down, or knocking out PP2A regulatory subunits have yielded only limited insights into their biological roles and substrates. To this end, here we sought to reduce the complexity of cellular PP2A holoenzymes. We used tetracycline-inducible expression of pairs of scaffolding and regulatory subunits with complementary charge-reversal substitutions in their interaction interfaces. For each of the three regulatory subunit families, we engineered A/B charge–swap variants that could bind to one another, but not to endogenous A and B subunits. Because endogenous Aα was targeted by a co-induced shRNA, endogenous B subunits were rapidly degraded, resulting in expression of predominantly a single PP2A heterotrimer composed of the A/B charge–swap pair and the endogenous catalytic subunit. Using B'δ/PPP2R5D, we show that PP2A complexity reduction, but not PP2A overexpression, reveals a role of this holoenzyme in suppression of extracellular signal–regulated kinase signaling and protein kinase A substrate dephosphorylation. When combined with global phosphoproteomics, the PP2A/B'δ reduction approach identified consensus dephosphorylation motifs in its substrates and suggested that residues surrounding the phosphorylation site play roles in PP2A substrate specificity.




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A single amino acid substitution uncouples catalysis and allostery in an essential biosynthetic enzyme in Mycobacterium tuberculosis [Enzymology]

Allostery exploits the conformational dynamics of enzymes by triggering a shift in population ensembles toward functionally distinct conformational or dynamic states. Allostery extensively regulates the activities of key enzymes within biosynthetic pathways to meet metabolic demand for their end products. Here, we have examined a critical enzyme, 3-deoxy-d-arabino-heptulosonate 7-phosphate synthase (DAH7PS), at the gateway to aromatic amino acid biosynthesis in Mycobacterium tuberculosis, which shows extremely complex dynamic allostery: three distinct aromatic amino acids jointly communicate occupancy to the active site via subtle changes in dynamics, enabling exquisite fine-tuning of delivery of these essential metabolites. Furthermore, this allosteric mechanism is co-opted by pathway branchpoint enzyme chorismate mutase upon complex formation. In this study, using statistical coupling analysis, site-directed mutagenesis, isothermal calorimetry, small-angle X-ray scattering, and X-ray crystallography analyses, we have pinpointed a critical node within the complex dynamic communication network responsible for this sophisticated allosteric machinery. Through a facile Gly to Pro substitution, we have altered backbone dynamics, completely severing the allosteric signal yet remarkably, generating a nonallosteric enzyme that retains full catalytic activity. We also identified a second residue of prime importance to the inter-enzyme communication with chorismate mutase. Our results reveal that highly complex dynamic allostery is surprisingly vulnerable and provide further insights into the intimate link between catalysis and allostery.




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The Security Council's peacekeeping trilemma

4 March 2020 , Volume 96, Number 2

Paul D. Williams

The United Nations (UN) Security Council is stuck in a peacekeeping trilemma. This is a situation where the Council's three strategic goals for peacekeeping operations—implementing broad mandates, minimizing peacekeeper casualties and maximizing cost-effectiveness—cannot be achieved simultaneously. This trilemma stems from longstanding competing pressures on how the Council designs UN peacekeeping operations as well as political divisions between peacekeeping's three key groups of stakeholders: the states that authorize peacekeeping mandates, those that provide most of the personnel and field capabilities, and those that pay the majority of the bill. Fortunately, the most negative consequences of the trilemma can be mitigated and perhaps even transcended altogether. Mitigation would require the Council to champion and implement four main reforms: improving peacekeeper performance, holding peacekeepers accountable for misdeeds, adopting prioritized and sequenced mandates, and strengthening the financial basis for UN peacekeeping. Transcending the trilemma would require a more fundamental reconfiguration of the key stakeholder groups in order to create much greater unity of effort behind a re-envisaged peacekeeping enterprise. This is highly unlikely in the current international political context.




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China and Russia in R2P debates at the UN Security Council

7 May 2020 , Volume 96, Number 3

Zheng Chen and Hang Yin

While China and Russia's general policies towards the Responsibility to Protect (R2P) are similar, the two reveal nuanced differences in addressing specific emergencies. Both express support for the first two pillars of R2P while resisting coercive intervention under its aegis, as they share anxieties of domestic political security and concerns about their international image. Nonetheless, addressing cases like the Syrian crisis, Russian statements are more assertive and even aggressive while Chinese ones are usually vague and reactive. This article highlights the two states’ different tones through computer-assisted text analyses. It argues that diplomatic styles reflect Russian and Chinese perceptions of their own place in the evolving international order. Experiences in past decades create divergent reference points and status prospects for them, which leads to their different strategies in signalling Great Power status. As Beijing is optimistic about its status-rising prospects, it exercises more self-restraint in order to avoid external containments and is reluctant to act as an independent ‘spoiler’. Meanwhile, Moscow interprets its Great Power status more from a frame of ‘loss’ and therefore is inclined to adopt a sterner approach to signal its status. Although their policies complement each other on many occasions, there is nothing akin to a Sino–Russian ‘bloc’.




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Cytochrome P450 and arachidonic acid bioactivation: molecular and functional properties of the arachidonate monooxygenase

Jorge H. Capdevila
Feb 1, 2000; 41:163-181
Reviews




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Rafts defined: a report on the Keystone symposium on lipid rafts and cell function

Linda J. Pike
Jul 1, 2006; 47:1597-1598
Report




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The amphipathic helix in the exchangeable apolipoproteins: a review of secondary structure and function

JP Segrest
Feb 1, 1992; 33:141-166
Reviews




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Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans

Saverio Cinti
Nov 1, 2005; 46:2347-2355
Research Articles




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China and Russia in R2P debates at the UN Security Council

7 May 2020 , Volume 96, Number 3

Zheng Chen and Hang Yin

While China and Russia's general policies towards the Responsibility to Protect (R2P) are similar, the two reveal nuanced differences in addressing specific emergencies. Both express support for the first two pillars of R2P while resisting coercive intervention under its aegis, as they share anxieties of domestic political security and concerns about their international image. Nonetheless, addressing cases like the Syrian crisis, Russian statements are more assertive and even aggressive while Chinese ones are usually vague and reactive. This article highlights the two states’ different tones through computer-assisted text analyses. It argues that diplomatic styles reflect Russian and Chinese perceptions of their own place in the evolving international order. Experiences in past decades create divergent reference points and status prospects for them, which leads to their different strategies in signalling Great Power status. As Beijing is optimistic about its status-rising prospects, it exercises more self-restraint in order to avoid external containments and is reluctant to act as an independent ‘spoiler’. Meanwhile, Moscow interprets its Great Power status more from a frame of ‘loss’ and therefore is inclined to adopt a sterner approach to signal its status. Although their policies complement each other on many occasions, there is nothing akin to a Sino–Russian ‘bloc’.




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Leaders Who Lunch: Seth Thomas




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Leaders Who Lunch: Robert Barrington




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Unconstrained Presidency? Checks and Balances in the Trump Era




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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) [Research]

Human leukocyte antigen (HLA) B*51:01 and endoplasmic reticulum aminopeptidase 1 (ERAP1) are strongly genetically associated with Behcet's disease (BD). Previous studies have defined two subgroups of HLA-B*51 peptidome containing proline (Pro) or alanine (Ala) at position 2 (P2). Little is known about the unconventional non-Pro/Ala2 HLA-B*51-bound peptides. We aimed to study the features of this novel subpeptidome, and investigate its regulation by ERAP1. CRISPR-Cas9 was used to generate an HLA-ABC-triple knockout HeLa cell line (HeLa.ABC-KO), which was subsequently transduced to express HLA-B*51:01 (HeLa.ABC-KO.B51). ERAP1 was silenced using lentiviral shRNA. Peptides bound to HLA-B*51:01 were eluted and analyzed by mass spectrometry. The characteristics of non-Pro/Ala2, Pro2, and Ala2 peptides and their alteration by ERAP1 silencing were investigated. Effects of ERAP1 silencing on cell surface expression of HLA-B*51:01 were studied using flow cytometry. More than 20% of peptides eluted from HLA-B*51:01 lacked Pro or Ala at P2. This unconventional group of HLA-B*51:01-bound peptides was relatively enriched for 8-mers (with relatively fewer 9-mers) compared with the Pro2 and Ala2 subpeptidomes and had similar N-terminal and C-terminal residue usages to Ala2 peptides (with the exception of the less abundant leucine at position ). Knockdown of ERAP1 increased the percentage of non-Pro/Ala2 from 20% to ~40%, increased the percentage of longer (10-mer and 11-mer) peptides eluted from HLA-B*51:01 complexes, and abrogated the predominance of leucine at P1. Interestingly knockdown of ERAP1 altered the length and N-terminal residue usage of non-Ala2&Pro2 and Ala2 but not the Pro2 peptides. Finally, ERAP1 silencing regulated the expression levels of cell surface HLA-B*51 in a cell-type-dependent manner. In conclusion, we have used a novel methodology to identify an unconventional but surprisingly abundant non-Pro/Ala2 HLA-B*51:01 subpeptidome. It is increased by knockdown of ERAP1, a gene affecting the risk of developing BD. This has implications for theories of disease pathogenesis.




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Human Hepatocyte Nuclear Factor 4-{alpha} Encodes Isoforms with Distinct Transcriptional Functions [Research]

HNF4α is a nuclear receptor produced as 12 isoforms from two promoters by alternative splicing. To characterize the transcriptional capacities of all 12 HNF4α isoforms, stable lines expressing each isoform were generated. The entire transcriptome associated with each isoform was analyzed as well as their respective interacting proteome. Major differences were noted in the transcriptional function of these isoforms. The α1 and α2 isoforms were the strongest regulators of gene expression whereas the α3 isoform exhibited significantly reduced activity. The α4, α5, and α6 isoforms, which use an alternative first exon, were characterized for the first time, and showed a greatly reduced transcriptional potential with an inability to recognize the consensus response element of HNF4α. Several transcription factors and coregulators were identified as potential specific partners for certain HNF4α isoforms. An analysis integrating the vast amount of omics data enabled the identification of transcriptional regulatory mechanisms specific to certain HNF4α isoforms, hence demonstrating the importance of considering all isoforms given their seemingly diverse functions.




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Episode 19: Django Unchained

  • Django Unchained Review
  • Discussion on Tarantino: The Director
  • What We Watched: Not Much
  • What Game Jason Loves? A: Tokyo Jungle

Email us at thefilmclubpodcast@gmail.com or leave us a voicemail at 773-245-3476.




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The grease trap: uncovering the mechanism of the hydrophobic lid in Cutibacterium acnes lipase [Research Articles]

Acne is one of the most common dermatological conditions, but the details of its pathology are unclear, and current management regimens often have adverse effects. Cutibacterium acnes is known as a major acne-associated bacterium that derives energy from lipase-mediated sebum lipid degradation. C. acnes is commensal, but lipase activity has been observed to differ among C. acnes types. For example, higher populations of the type IA strains are present in acne lesions with higher lipase activity. In the present study, we examined a conserved lipase in types IB and II that was truncated in type IA C. acnes strains. Closed, blocked, and open structures of C. acnes ATCC11828 lipases were elucidated by X-ray crystallography at 1.6–2.4 Å. The closed crystal structure, which is the most common form in aqueous solution, revealed that a hydrophobic lid domain shields the active site. By comparing closed, blocked, and open structures, we found that the lid domain-opening mechanisms of C. acnes lipases (CAlipases) involve the lid-opening residues, Phe-179 and Phe-211. To the best of our knowledge, this is the first structure-function study of CAlipases, which may help to shed light on the mechanisms involved in acne development and may aid in future drug design.




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The ins and outs of lipid rafts: functions in intracellular cholesterol homeostasis, microparticles, and cell membranes [Thematic Reviews]

Cellular membranes are not homogenous mixtures of proteins; rather, they are segregated into microdomains on the basis of preferential association between specific lipids and proteins. These microdomains, called lipid rafts, are well known for their role in receptor signaling on the plasma membrane (PM) and are essential to such cellular functions as signal transduction and spatial organization of the PM. A number of disease states, including atherosclerosis and other cardiovascular disorders, may be caused by dysfunctional maintenance of lipid rafts. Lipid rafts do not occur only in the PM but also have been found in intracellular membranes and extracellular vesicles (EVs). Here, we focus on discussing newly discovered functions of lipid rafts and microdomains in intracellular membranes, including lipid and protein trafficking from the ER, Golgi bodies, and endosomes to the PM, and we examine lipid raft involvement in the production and composition of EVs. Because lipid rafts are small and transient, visualization remains challenging. Future work with advanced techniques will continue to expand our knowledge about the roles of lipid rafts in cellular functioning.




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Lipid rafts and neurodegeneration: structural and functional roles in physiologic aging and neurodegenerative diseases [Thematic Reviews]

Lipid rafts are small, dynamic membrane areas characterized by the clustering of selected membrane lipids as the result of the spontaneous separation of glycolipids, sphingolipids, and cholesterol in a liquid-ordered phase. The exact dynamics underlying phase separation of membrane lipids in the complex biological membranes are still not fully understood. Nevertheless, alterations in the membrane lipid composition affect the lateral organization of molecules belonging to lipid rafts. Neural lipid rafts are found in brain cells, including neurons, astrocytes, and microglia, and are characterized by a high enrichment of specific lipids depending on the cell type. These lipid rafts seem to organize and determine the function of multiprotein complexes involved in several aspects of signal transduction, thus regulating the homeostasis of the brain. The progressive decline of brain performance along with physiological aging is at least in part associated with alterations in the composition and structure of neural lipid rafts. In addition, neurodegenerative conditions, such as lysosomal storage disorders, multiple sclerosis, and Parkinson’s, Huntington’s, and Alzheimer’s diseases, are frequently characterized by dysregulated lipid metabolism, which in turn affects the structure of lipid rafts. Several events underlying the pathogenesis of these diseases appear to depend on the altered composition of lipid rafts. Thus, the structure and function of lipid rafts play a central role in the pathogenesis of many common neurodegenerative diseases.




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The single CCA-adding enzyme of T. brucei has distinct functions in the cytosol and in mitochondria [RNA]

tRNAs universally carry a CCA nucleotide triplet at their 3'-ends. In eukaryotes, the CCA is added post-transcriptionally by the CCA-adding enzyme (CAE). The mitochondrion of the parasitic protozoan Trypanosoma brucei lacks tRNA genes and therefore imports all of its tRNAs from the cytosol. This has generated interest in the tRNA modifications and their distribution in this organism, including how CCA is added to tRNAs. Here, using a BLAST search for genes encoding putative CAE proteins in T. brucei, we identified a single ORF, Tb927.9.8780, as a potential candidate. Knockdown of this putative protein, termed TbCAE, resulted in the accumulation of truncated tRNAs, abolished translation, and inhibited both total and mitochondrial CCA-adding activities, indicating that TbCAE is located both in the cytosol and mitochondrion. However, mitochondrially localized tRNAs were much less affected by the TbCAE ablation than the other tRNAs. Complementation assays revealed that the N-terminal 10 amino acids of TbCAE are dispensable for its activity and mitochondrial localization and that deletion of 10 further amino acids abolishes both. A growth arrest caused by the TbCAE knockdown was rescued by the expression of the cytosolic isoform of yeast CAE, even though it was not imported into mitochondria. This finding indicated that the yeast enzyme complements the essential function of TbCAE by adding CCA to the primary tRNA transcripts. Of note, ablation of the mitochondrial TbCAE activity, which likely has a repair function, only marginally affected growth.




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An explicit form for extremal functions in the embedding constant problem for Sobolev spaces

I. A. Sheipak and T. A. Garmanova
Trans. Moscow Math. Soc. 80 (2020), 189-210.
Abstract, references and article information




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Folding for Fun and Function

Origami paper-folding may not seem like a subject for mathematical investigation or one with sophisticated applications, yet anyone who has tried to fold a road map or wrap a present knows that origami is no trivial matter. Mathematicians, computer scientists, and engineers have recently discovered that this centuries-old subject can be used to solve many modern problems.The methods of origami are now used to fold objects such as automobile air bags and huge space telescopes efficiently, and may be related to how proteins fold. Manufacturers often want to make a product out of a single piece of material. The manufacturing problem then becomes one of deciding whether a shape can be folded and if so, is there an efficient way to find a good fold? Thus, many origami research problems have to do with algorithm complexity and optimization theory. A testament to the diversity of origami, as well as the power of mathematics, is its applicability to problems at the molecular level, in manufacturing, and in outer space. For More Information: http://db.uwaterloo.ca/~eddemain/papers/MapFolding/




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Unbunching Buses

Researchers: Vikash V. Gayah and S. Ilgin Guler, Pennsylvania State University Description: Gayah and Guler talk about mitigating the clustering of buses on a route.




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Launch of the Website of the Online Survey on the Application of and Experience in the Use of Socio-Economic Considerations in Decision-Making on Living Modified Organisms




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Launch of the Forum on the Strategic Plan and the Assessment and Review, 1-28 February 2010.




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Launch of the COP-MOP 6 Website




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Housing minister announces plans to boost UK proptech sector with data

Esther McVey said the government will release local data on properties and land to help the proptech sector thrive




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Natwest's newly launched Bó app looks a lot like Monzo

From its brightly coloured card to the user experience of its app and the benefits it offers, the long-gestating Natwest fintech project looks like little more than a Monzo copycat




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CBD Press release: Germany and the United Nations Biodiversity Secretariat announce a "Green COP".