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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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The Indo-Pacific: Geostrategic Perspectives to 2024 - Workshop 3
Invitation Only Research Event
17 October 2019 - 9:30am to 2:00pm
Institut Francais des Relations Internationales, 27 rue de la Procession, 75740 Paris Cedex 15, France
This closed-door roundtable explores possible strategic shifts in the Indo-Pacific between now and 2024. Focusing on trade security, climate change disruptions and security cooperation, it aims to enhance the understanding of the regional goals of, and strategic relationships between, the key countries active in the region.
The workshop is part of a larger project funded by the Strategic Policy Division of the Australian Department of Defence. The project includes workshops in the United States, the United Kingdom, France, Japan, India and the Pacific Islands (Tonga).
Attendance at this event is by invitation only.
Department/project
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The Indo-Pacific: Geostrategic Outlook to 2024 - Workshop 4
Invitation Only Research Event
26 November 2019 - 9:30am to 12:00pm
Gateway House, Stevens Street, Colaba
This closed-door roundtable explores possible strategic shifts in the Indo-Pacific between now and 2024.
Focusing on trade security, climate change disruptions and security cooperation, it aims to enhance the understanding of the regional goals of, and strategic relationships between, the key countries active in the region.
The workshop is part of a larger project funded by the Strategic Policy Division of the Australian Department of Defence.
The project includes workshops in the United States, the United Kingdom, France, Japan, India and the Pacific Islands (Tonga).
Department/project
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The Indo-Pacific: Geostrategic Outlook From Now to 2024 - Workshop 5
Invitation Only Research Event
18 February 2020 - 12:00pm to 4:30pm
Langafonua Centre
This roundtable explores possible strategic shifts in the Indo-Pacific between now and 2024. Focusing on trade security, climate change disruptions and security cooperation, it aims to enhance the understanding of the regional goals of, and strategic relationships between, the key countries active in the region.
The workshop is part of a larger project funded by the Strategic Policy Division of the Australian Department of Defence. The project includes workshops in the United States, the United Kingdom, France, Japan, India and the Pacific Islands (Tonga).
Department/project
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PANDORA
The PANDORA consortium aims to develop and strengthen effective outbreak response capacities across all geographical regions in sub-Saharan Africa, in partnership with national governments and other international stakeholders.
The Pan-African Network For Rapid Research, Response, Relief and Preparedness for Infectious Disease Epidemics is a novel multidisciplinary ‘One Health’ initiative consisting of 13 African institutions and 9 European institutions, including Chatham House.
The Centre leads on the consortium’s efforts to engage policy makers, global public health bodies and communities, focusing on the ethical, administrative, regulatory and operational obstacles during outbreaks.
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Hepatic monoamine oxidase B is involved in endogenous geranylgeranoic acid synthesis in mammalian liver cells [Research Articles]
Geranylgeranoic acid (GGA) originally was identified in some animals and has been developed as an agent for preventing second primary hepatoma. We previously have also identified GGA as an acyclic diterpenoid in some medicinal herbs. Recently, we reported that in human hepatoma-derived HuH-7 cells, GGA is metabolically labeled from 13C-mevalonate. Several cell-free experiments have demonstrated that GGA is synthesized through geranylgeranial by oxygen-dependent oxidation of geranylgeraniol (GGOH), but the exact biochemical events giving rise to GGA in hepatoma cells remain unclear. Monoamine oxidase B (MOAB) has been suggested to be involved in GGOH oxidation. Here, using two human hepatoma cell lines, we investigated whether MAOB contributes to GGA biosynthesis. Using either HuH-7 cell lysates or recombinant human MAOB, we found that: 1) the MAO inhibitor tranylcypromine dose-dependently downregulates endogenous GGA levels in HuH-7 cells; and 2) siRNA-mediated MAOB silencing reduces intracellular GGA levels in HuH-7 and Hep3B cells. Unexpectedly, however, CRISPR/Cas9-generated MAOB-KO human hepatoma Hep3B cells had GGA levels similar to those in MAOB-WT cells. A sensitivity of GGA levels to siRNA-mediated MAOB downregulation was recovered when the MAOB-KO cells were transfected with a MAOB-expression plasmid, suggesting that MAOB is the enzyme primarily responsible for GGOH oxidation and that some other latent metabolic pathways may maintain endogenous GGA levels in the MAOB-KO hepatoma cells. Along with the previous findings, these results provide critical insights into the biological roles of human MAOB and provide evidence that hepatic MAOB is involved in endogenous GGA biosynthesis via GGOH oxidation.
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GPIHBP1, a partner protein for lipoprotein lipase, is expressed only in capillary endothelial cells [Images In Lipid Research]
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It takes two (Las1 HEPN endoribonuclease domains) to cut RNA correctly [RNA]
The ribosome biogenesis factor Las1 is an essential endoribonuclease that is well-conserved across eukaryotes and a newly established member of the higher eukaryotes and prokaryotes nucleotide-binding (HEPN) domain-containing nuclease family. HEPN nucleases participate in diverse RNA cleavage pathways and share a short HEPN nuclease motif (RφXXXH) important for RNA cleavage. Most HEPN nucleases participate in stress-activated RNA cleavage pathways; Las1 plays a fundamental role in processing pre-rRNA. Underscoring the significance of Las1 function in the cell, mutations in the human LAS1L (LAS1-like) gene have been associated with neurological dysfunction. Two juxtaposed HEPN nuclease motifs create Las1's composite nuclease active site, but the roles of the individual HEPN motif residues are poorly defined. Here using a combination of in vivo experiments in Saccharomyces cerevisiae and in vitro assays, we show that both HEPN nuclease motifs are required for Las1 nuclease activity and fidelity. Through in-depth sequence analysis and systematic mutagenesis, we determined the consensus HEPN motif in the Las1 subfamily and uncovered its canonical and specialized elements. Using reconstituted Las1 HEPN-HEPN' chimeras, we defined the molecular requirements for RNA cleavage. Intriguingly, both copies of the Las1 HEPN motif were important for nuclease function, revealing that both HEPN motifs participate in coordinating the RNA within the Las1 active site. We also established that conformational flexibility of the two HEPN domains is important for proper nuclease function. The results of our work reveal critical information about how dual HEPN domains come together to drive Las1-mediated RNA cleavage.
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The recalibration of Chinese assertiveness: China's responses to the Indo-Pacific challenge
8 January 2020 , Volume 96, Number 1
In response to the changing geopolitical landscape in Asia, both China and the United States attempt to alter the regional order in their own favour, both in the economic and security realms. This article shows how diverging views on future arrangements are leading to strategic shifts and increasing tension between these two Great Powers. As part of its quest for Great-Power status, China has been actively pushing its regional initiatives such as the Belt and Road Initiative (BRI) and the Asian Infrastructure Investment Bank (AIIB), as well as adopting assertive security policies towards its neighbours. In contrast, in order to counter China's growing influence America's regional strategy is undergoing a subtle shift from ‘rebalancing to Asia’ to focusing on the ‘Indo-Pacific’ region. However, amid an intensifying trade war and other challenges facing the region, China has chosen to moderate its proactive foreign policy-orientation in the past few years. In particular, China has made attempts to downplay its domestic rhetoric, rebuild strategic relationship with India and Japan, and to reassure ASEAN states in the South China Sea. In response to the Indo-Pacific strategy, it would be more effective for China to articulate a more inclusive regional vision and promote an institutional framework that also accommodates a US presence in the region.
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Non-traditional security cooperation between China and south-east Asia: implications for Indo-Pacific geopolitics
8 January 2020 , Volume 96, Number 1
The ‘free and open Indo-Pacific’ (FOIP) strategy, actively promoted by the United States with support from its allies and partners, is a significant geopolitical response to China's growing power and expanding influence in Asia and beyond. Beijing has adopted various new strategies to cope with the challenges related to FOIP. One of these strategies is to secure a robust relationship with south-east Asia in order to make these regional states either neutral to or less supportive of the Indo-Pacific vision. In addition to economic statecraft and soft power, Beijing believes that it can also tap into the domain of non-traditional security (NTS) to strengthen relations with this region to position itself better in the intensifying regional geopolitical competition. The article addresses the following question: what is the impact of China's NTS cooperation with south-east Asia on Beijing's geopolitical rivalry with other major powers in the Indo-Pacific region? The article argues that China's NTS cooperation with south-east Asian countries may help China maintain its geopolitical standing in the region, but it is unlikely to lead to any dramatic increase of China's strategic influence in the region. This essentially means that Beijing may be able to prevent ASEAN or most ASEAN member states from lending substantive and strong support to the Indo-Pacific construct, but it will not be able to stop ASEAN states from supporting some elements of the FOIP.
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Japan's ‘Indo-Pacific’ question: countering China or shaping a new regional order?
8 January 2020 , Volume 96, Number 1
Japan's primary objective of the ‘free and open Indo-Pacific’ (FOIP) strategy is to shape and consolidate regional order in the Indo-Pacific region based on the existing rules-based international order. The concept initially aimed to achieve two different objectives—shaping a regional order in the Indo-Pacific and ensuring the defence of Japan; however, Japan has gradually shifted its strategic focus onto the former, separating national defence from the FOIP concept, which reflects a change in the degree of its commitment to the two objectives. On the one hand, as its overall security strategy, Japan has determined to steadily enhance its national defence by increasing its own defence capabilities and strengthening the US–Japan alliance, while transforming its partnerships with like-minded states, such as Australia and India, into a diplomatic, and potentially military, alignment. This has been brought about by shifts in the regional balance of power, particularly the rise of China and the relative decline of the United States. On the other hand, as part of its FOIP strategy, Japan's attempts to build a new regional order in the Indo-Pacific region aim to defend the existing rules-based order established by the United States from challengers, particularly China. Yet, given the strategic uncertainty over Japan's international coalition-building efforts to create a new regional order, Japan has made its approach flexible; Tokyo is using its ambiguous FOIP concept to gauge other states' responses, understand their perspectives, and change its strategic emphases accordingly—so-called ‘tactical hedging’. Japan has pursued similar means to achieve the two key objectives. Nevertheless, the country's core interest, the defence of Japan, is more imperative than building a regional order in the Indo-Pacific region, and Japan faces different types of challenges in the future.
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Evasive balancing: India's unviable Indo-Pacific strategy
8 January 2020 , Volume 96, Number 1
India has adopted the Indo-Pacific concept with uncharacteristic speed. This article examines India's Indo-Pacific strategy, which evolved out of its earlier ‘Look East’ and ‘Act East’ policies but is much more focused on strategic concerns than on trade or connectivity. As such, the strategy is subset of its China policy, and includes contradictory elements of balancing China by building partnerships with the United States as well as with regional powers, while simultaneously pursuing a reassurance strategy to convince Beijing that India is not really balancing China. The combination of these contradictory elements is characterized as evasive balancing, which is a more useful concept than either pure balancing or hedging for understanding the policies of India and of many other countries in the region that are trying to manage China's rise. However, reassurance strategies rarely work and the combination of balancing and reassurance is even less likely to be viable.
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Is Australia's Indo-Pacific strategy an illusion?
8 January 2020 , Volume 96, Number 1
Australia has been among the most prominent advocates of the increasingly popular Indo-Pacific concept. This article argues that Canberra's enthusiasm for the concept stems from its appeal to the two dominant traditions of Australian foreign policy—a ‘dependent ally’ tradition and a ‘middle power’ approach. While these two traditions are typically seen as being in tension, the Indo-Pacific concept provides a rare point of convergence between them. The article begins by outlining the appeal of the Indo-Pacific concept to each of these traditions. Using a case-study of recent Australian policy toward the South China Sea disputes, however, the article then demonstrates that Australia has in practice implemented its stated Indo-Pacific strategy far less consistently than its very vocal support would appear to suggest. This disjuncture is attributed to the growing influence of a third, generally understudied, ‘pragmatic’ Australian foreign policy tradition. Because Australia has been such a prominent champion of the Indo-Pacific concept, the article concludes that this divergence between the rhetoric and the reality of Australia's Indo-Pacific strategy threatens to have a negative impact on the concept's broader international appeal and sustainability, particularly among Australia's south-east Asian neighbours.
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Indonesia and the ASEAN outlook on the Indo-Pacific
8 January 2020 , Volume 96, Number 1
Indonesia has taken a leadership role within the Association of Southeast Asian Nations (ASEAN) in drafting a common outlook on the Indo-Pacific concept. The widening of Indonesia's geostrategic canvas from the Asia–Pacific to the Indo-Pacific is in line with President Joko Widodo's intent to make Indonesia a Global Maritime Fulcrum (GMF). In view of the rivalry between the US and China and the emergence of various Indo-Pacific initiatives from other countries, Indonesia believes that ASEAN must try to maintain its centrality. The draft of Indonesia's perspective for an ASEAN outlook on the Indo-Pacific: towards a peaceful, prosperous, and inclusive region was submitted for considerations by ASEAN, and after 18 months of intensive lobbying by Indonesia the concept was finally adopted at the ASEAN Summit in June 2019. The ASEAN outlook promotes the principles of openness, inclusiveness, transparency, respect for international law and ASEAN centrality in the Indo-Pacific region. It proposes a building-block approach, seeking commonalities between existing regional initiatives in which ASEAN-led mechanisms will act as a fulcrum for both norm-setting and concrete cooperation. Rather than creating a new regional architecture, the East Asia Summit (EAS) is proposed as the platform for advancing the Indo-Pacific discourse and cooperation. Indonesia's ASEAN outlook on the Indo-Pacific marks its renewed foreign policy activism as a middle power and underlines the continuing importance that Indonesia places on ASEAN as the cornerstone of its foreign policy, emphasising ASEAN's centrality as the primary vehicle for managing relations with the major powers in the Indo-Pacific region.
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Consigned to hedge: south-east Asia and America's ‘free and open Indo-Pacific’ strategy
8 January 2020 , Volume 96, Number 1
This article assesses how south-east Asian countries and the Association of Southeast Asian Nations (ASEAN) have responded to the ‘free and open Indo-Pacific’ (FOIP) strategies promoted by the United States and the other countries in the Quadrilateral Security Dialogue (the ‘Quad’: US, Japan, Australia and India). Their nuanced ripostes imply a persistent commitment to hedging and shifting limited alignments in the face of growing great rivalry and the lack of a clear FOIP vision among Quad members. In the face of external pressure to take sides, the ASEAN states are likely to keep hedging through working selectively with China and the United States. Given the United States' apparent preference to balance China and Trump's disregard for multilateralism, ASEAN's ability to maintain its centrality in the evolving regional architecture is in doubt—despite the Quad countries' (belated) accommodation of ASEAN in their FOIP strategies. However, the success of the US strategy depends on Washington's ability to build and sustain the requisite coalition to balance Beijing. ASEAN has undertaken efforts to enhance bilateral security collaboration with China and the United States respectively. In doing so, ASEAN is arguably seeking to informally redefine its centrality in an era of Great Power discord and its ramifications for multilateralism.
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The institutionalization of the Indo-Pacific: problems and prospects
8 January 2020 , Volume 96, Number 1
Although the term ‘Indo-Pacific’ has become popular in the foreign policy discourse of some countries, we have yet to see any significant institution-building in the Indo-Pacific region. Borrowing insights from functional institutionalism and political leadership studies of international regimes, we introduce a ‘leadership–institution’ model to explore the problems and prospects of institutionalizing the Indo-Pacific. Through a comparative case study of the institutionalization of the Asia–Pacific vs the Indo-Pacific, we argue that two crucial factors contributed to the slow institutionalization of the Indo-Pacific as a regional system in world politics: the lack of ideational leadership from an epistemic community and the weak executive leadership from a powerful state. While ideational leaders can help states identify and expand common interests in cooperation, executive leadership will facilitate states to overcome operational obstacles in cooperation, such as the ‘collective action’ problem and the ‘relative gains’ concern. The future of institution-building in the Indo-Pacific will depend on whether and how these two leadership roles are played by scholars and states in the region. In the conclusion, we discuss the challenges of institutionalizing the Indo-Pacific and highlight China as a wild card in the future of Indo-Pacific regionalism.
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The Belt and Road Initiative: geo-economics and Indo-Pacific security competition
8 January 2020 , Volume 96, Number 1
The Belt and Road Initiative (BRI) has been regarded by international society as a major policy tool in China's geo-economic strategy. Under this policy platform, Beijing has pledged to invest billions of dollars in the infrastructure and industrial sectors across Eurasia and in the Indo-Pacific nations. It is widely believed that such huge amount of investment will inevitably generate significant geostrategic repercussions in these regions. In response to the BRI, the United States and other powers have come up with a ‘free and open Indo-Pacific’ strategy. This article attempts to address the following question: what impact is the BRI likely to have on the security ties between China and the other major players in the Indo-Pacific? The author finds that the BRI may significantly transform China's international security policy and the expansion of Beijing's security influence may further intensify the security competition between China and other major powers in the Indo-Pacific region. The article also proposes a new analytical angle for the study of geo-economics that unpacks the role of economic activities and processes in generating geopolitical intentions and catalysing geopolitical competition.
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Developmental peace in east Asia and its implications for the Indo-Pacific
8 January 2020 , Volume 96, Number 1
This article adopts a constructive approach to examining the problem of the Indo-Pacific construct. Through reflection on the east Asian experience, it proposes an analytical framework of developmental peace as a constellation of international practices, which means that the more economic development is prioritized by states in regional processes, the more likely it is that a sustainable peace will be achieved. States participating in regional integration comprise a community of practice. On the basis of a shared understanding that development is of overriding importance and underpins security and state legitimacy, the community takes economic development as the anchoring practice; this practice embodies and enacts constitutive rules and fundamental norms for a broader set of practices in regional processes, such as peaceful coexistence and non-interference. The more economic development is prioritized on domestic and regional agendas, the more likely it is that conflicts in the security realm will be relaxed or even resolved to protect security interests. The author draws some useful implications from the developmental peace in east Asia for the Indo-Pacific construct, among which the most important include building shared understandings on the prioritization of economic development, taking advantage of the Regional Comprehensive Economic Partnership (RCEP), Comprehensive and Progressive Agreement for Trans-Pacific Partnership (CPTPP) and the Asian Infrastructure Investment Bank, and using the code of conduct process as a vehicle and best practice to facilitate rule-making for the maritime order. Finally, the author briefly discusses the contributions of the study and limitations of the model.
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Understanding the dynamics of the Indo-Pacific: US–China strategic competition, regional actors, and beyond
6 November 2019 , Volume 96, Number 1
The first issue of International Affairs in 2020 explores the geopolitics of the 'Indo-Pacific' region.
As a geographical concept, ‘Indo-Pacific’ has existed for decades. As a political and strategic concept, it has since 2010 gradually become established in the foreign policy lexicon of some countries, especially Australia, India, Japan and the United States. However, China seems to be reluctant to identify itself as part of the Indo-Pacific; Chinese leaders believe that the US-led Indo-Pacific strategy aims to contain China's rise. While the battle between the two geographical concepts ‘Indo-Pacific’ and ‘Asia–Pacific’ may be fairly easily settled in the future, US–China strategic competition has just begun. Will the Indo-Pacific become a battlefield for US–China rivalry? How will China cope with the US ‘free and open Indo-Pacific’ (FOIP) strategy? How will other regional actors respond to the US–China strategic competition in the Indo-Pacific? What are the strategic implications of the ‘Indo-Pacific’ concept for regional order transformation? How will the Indo-Pacific be institutionalized, economically, politically and strategically? This article introduces the January 2020 special issue of International Affairs, which aims to address those questions, using both country-specific and regional perspectives. Seven articles focus on the policy responses of major players (Australia, China, India, Indonesia, Japan and ASEAN) to the US FOIP strategy and related US–China rivalry in the region. A further three articles examine the profound implications of Indo-Pacific dynamics for regional institution-building and for geopolitical and geo-economic architecture.
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The Indo-Pacific: Geostrategic Outlook to 2024 - Workshop 4
Invitation Only Research Event
26 November 2019 - 9:30am to 12:00pm
Gateway House, Stevens Street, Colaba
This closed-door roundtable explores possible strategic shifts in the Indo-Pacific between now and 2024.
Focusing on trade security, climate change disruptions and security cooperation, it aims to enhance the understanding of the regional goals of, and strategic relationships between, the key countries active in the region.
The workshop is part of a larger project funded by the Strategic Policy Division of the Australian Department of Defence.
The project includes workshops in the United States, the United Kingdom, France, Japan, India and the Pacific Islands (Tonga).
Department/project
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The Indo-Pacific: Geostrategic Outlook From Now to 2024 - Workshop 5
Invitation Only Research Event
18 February 2020 - 12:00pm to 4:30pm
Langafonua Centre
This roundtable explores possible strategic shifts in the Indo-Pacific between now and 2024. Focusing on trade security, climate change disruptions and security cooperation, it aims to enhance the understanding of the regional goals of, and strategic relationships between, the key countries active in the region.
The workshop is part of a larger project funded by the Strategic Policy Division of the Australian Department of Defence. The project includes workshops in the United States, the United Kingdom, France, Japan, India and the Pacific Islands (Tonga).
Department/project
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Wildlife through the window: what readers have spotted during lockdown
We asked Guardian readers living in cities and towns across the world to share their images of the wildlife they can see from their homes. You answered in your droves, from Canada to Cardiff, and here are some of the best.
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CBD News: Statement by the Executive Secretary, Dr. Ahmed Djoghlaf, on the occasion of the First Meeting of the Ad Hoc Technical Expert Group on Biodiversity and Climate Change, London, United Kingdom , 17 - 21 November 2008.
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CBD News: Summary results and conclusions of the Airbus-commissioned survey referred to in the address of the Executive Secretary delivered at the Royal Geographical Society, London, on 3 September 2009.
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CBD News: Address by Mr. Ahmed Djoghlaf on the occasion "the Biodiversity Debate: Engaging and Educating Children on Biodiversity as the Future Guardians of our Planet", held on 3 September 2009 at the Royal Geographical Society, London, UK.
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CBD Notification: Expert consultation on the revision and updating of the Strategic Plan of the Convention, 18 - 20 January 2010, London, the United Kingdom.
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CBD News: Statement by Mr Ahmed Djoghlaf, Executive Secretary of the Convention on Biological Diversity, on the occasion of the Launch of the UK Partnership Supporting Biodiversity is Life - the International Year of Biodiversity 2010, London, 25 November
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CBD News: Statement by Dr. Ahmed Djoghlaf, Executive Secretary of the Convention on Biological Diversity, on the occasion of the Third Business and the 2010 Biodiversity Challenge Conference, 30 November 2009, Jakarta, Indonesia.
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CBD News: Statement by Mr. Ahmed Djoghlaf, Executive Secretary of the Convention on Biological Diversity, on the occasion of Informal Expert Workshop on the Updating of the Strategic Plan of the Convention for the Post-2010 Period, London, 18 January 2010
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CBD News: Statement by Mr Ahmed Djoghlaf, the Executive Secretary of the Convention on Biological Diversity, on the occasion of the Reception at the London Zoo in Anticipation of the International Day for Biological Diversity, 17 May 2010, London, England
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CBD Communiqué: London's world renowned Natural History Museum joins forces with CBD for the implementation of the Aichi Biodiversity Targets.
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CBD News: Statement by Mr. Ahmed Djoghlaf, CBD Executive Secretary, on the occasion of the Opening of the Fourth Session of the Governing Body of the International Treaty on Plant Genetic Resources for Food and Agriculture, 14 March 2011, Bali, Indonesia.
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CBD News: Seminar-Workshop on Harmonizing Methods in Risk Assessment and Management of Forest Invasive Alien Plant Species in South East Asia, 2-5 December 2014, Bogor, Indonesia
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CBD News: We, the Heads of State/Government of Brunei Darussalam, the Kingdom of Cambodia, the Republic of Indonesia, the Lao People's Democratic Republic, Malaysia, the Republic of the Union of Myanmar, the Republic of the Philippines, the Republic o
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CBD News: The ASEAN Biodiversity Outlook second edition was recently endorsed by the ASEAN Working Group on Nature Conservation and Biodiversity.
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Ehrenfest–Brillouin-type correlated continuous time random walk and fractional Jacobi diffusion
N. N. Leonenko, I. Papić, A. Sikorskii and N. Šuvak
Theor. Probability and Math. Statist. 99 (2020), 137-147.
Abstract, references and article information
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Development of a novel {beta}-1,6-glucan-specific detection system using functionally-modified recombinant endo-{beta}-1,6-glucanase [Methods and Resources]
β-1,3-d-Glucan is a ubiquitous glucose polymer produced by plants, bacteria, and most fungi. It has been used as a diagnostic tool in patients with invasive mycoses via a highly-sensitive reagent consisting of the blood coagulation system of horseshoe crab. However, no method is currently available for measuring β-1,6-glucan, another primary β-glucan structure of fungal polysaccharides. Herein, we describe the development of an economical and highly-sensitive and specific assay for β-1,6-glucan using a modified recombinant endo-β-1,6-glucanase having diminished glucan hydrolase activity. The purified β-1,6-glucanase derivative bound to the β-1,6-glucan pustulan with a KD of 16.4 nm. We validated the specificity of this β-1,6-glucan probe by demonstrating its ability to detect cell wall β-1,6-glucan from both yeast and hyphal forms of the opportunistic fungal pathogen Candida albicans, without any detectable binding to glucan lacking the long β-1,6-glucan branch. We developed a sandwich ELISA-like assay with a low limit of quantification for pustulan (1.5 pg/ml), and we successfully employed this assay in the quantification of extracellular β-1,6-glucan released by >250 patient-derived strains of different Candida species (including Candida auris) in culture supernatant in vitro. We also used this assay to measure β-1,6-glucan in vivo in the serum and in several organs in a mouse model of systemic candidiasis. Our work describes a reliable method for β-1,6-glucan detection, which may prove useful for the diagnosis of invasive fungal infections.
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Catabolic degradation of endothelial VEGFA via autophagy [Glycobiology and Extracellular Matrices]
Extracellular matrix-evoked angiostasis and autophagy within the tumor microenvironment represent two critical, but unconnected, functions of the small leucine-rich proteoglycan, decorin. Acting as a partial agonist of vascular endothelial growth factor 2 (VEGFR2), soluble decorin signals via the energy sensing protein, AMP-activated protein kinase (AMPK), in the autophagic degradation of intracellular vascular endothelial growth factor A (VEGFA). Here, we discovered that soluble decorin evokes intracellular catabolism of endothelial VEGFA that is mechanistically independent of mTOR, but requires an autophagic regulator, paternally expressed gene 3 (PEG3). We found that administration of autophagic inhibitors such as chloroquine or bafilomycin A1, or depletion of autophagy-related 5 (ATG5), results in accumulation of intracellular VEGFA, indicating that VEGFA is a basal autophagic substrate. Mechanistically, decorin increased the VEGFA clearance rate by augmenting autophagic flux, a process that required RAB24 member RAS oncogene family (RAB24), a small GTPase that facilitates the disposal of autophagic compartments. We validated these findings by demonstrating the physiological relevance of this process in vivo. Mice starved for 48 h exhibited a sharp decrease in overall cardiac and aortic VEGFA that could be blocked by systemic chloroquine treatment. Thus, our findings reveal a unified mechanism for the metabolic control of endothelial VEGFA for autophagic clearance in response to decorin and canonical pro-autophagic stimuli. We posit that the VEGFR2/AMPK/PEG3 axis integrates the anti-angiogenic and pro-autophagic bioactivities of decorin as the molecular basis for tumorigenic suppression. These results support future therapeutic use of decorin as a next-generation protein therapy to combat cancer.
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AIG1 and ADTRP are endogenous hydrolases of fatty acid esters of hydroxy fatty acids (FAHFAs) in mice [Metabolism]
Fatty acid esters of hydroxy fatty acids (FAHFAs) are a newly discovered class of signaling lipids with anti-inflammatory and anti-diabetic properties. However, the endogenous regulation of FAHFAs remains a pressing but unanswered question. Here, using MS-based FAHFA hydrolysis assays, LC-MS–based lipidomics analyses, and activity-based protein profiling, we found that androgen-induced gene 1 (AIG1) and androgen-dependent TFPI-regulating protein (ADTRP), two threonine hydrolases, control FAHFA levels in vivo in both genetic and pharmacologic mouse models. Tissues from mice lacking ADTRP (Adtrp-KO), or both AIG1 and ADTRP (DKO) had higher concentrations of FAHFAs particularly isomers with the ester bond at the 9th carbon due to decreased FAHFA hydrolysis activity. The levels of other lipid classes were unaltered indicating that AIG1 and ADTRP specifically hydrolyze FAHFAs. Complementing these genetic studies, we also identified a dual AIG1/ADTRP inhibitor, ABD-110207, which is active in vivo. Acute treatment of WT mice with ABD-110207 resulted in elevated FAHFA levels, further supporting the notion that AIG1 and ADTRP activity control endogenous FAHFA levels. However, loss of AIG1/ADTRP did not mimic the changes associated with pharmacologically administered FAHFAs on extent of upregulation of FAHFA levels, glucose tolerance, or insulin sensitivity in mice, indicating that therapeutic strategies should weigh more on FAHFA administration. Together, these findings identify AIG1 and ADTRP as the first endogenous FAHFA hydrolases identified and provide critical genetic and chemical tools for further characterization of these enzymes and endogenous FAHFAs to unravel their physiological functions and roles in health and disease.
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It takes two (Las1 HEPN endoribonuclease domains) to cut RNA correctly [RNA]
The ribosome biogenesis factor Las1 is an essential endoribonuclease that is well-conserved across eukaryotes and a newly established member of the higher eukaryotes and prokaryotes nucleotide-binding (HEPN) domain-containing nuclease family. HEPN nucleases participate in diverse RNA cleavage pathways and share a short HEPN nuclease motif (RφXXXH) important for RNA cleavage. Most HEPN nucleases participate in stress-activated RNA cleavage pathways; Las1 plays a fundamental role in processing pre-rRNA. Underscoring the significance of Las1 function in the cell, mutations in the human LAS1L (LAS1-like) gene have been associated with neurological dysfunction. Two juxtaposed HEPN nuclease motifs create Las1's composite nuclease active site, but the roles of the individual HEPN motif residues are poorly defined. Here using a combination of in vivo experiments in Saccharomyces cerevisiae and in vitro assays, we show that both HEPN nuclease motifs are required for Las1 nuclease activity and fidelity. Through in-depth sequence analysis and systematic mutagenesis, we determined the consensus HEPN motif in the Las1 subfamily and uncovered its canonical and specialized elements. Using reconstituted Las1 HEPN-HEPN' chimeras, we defined the molecular requirements for RNA cleavage. Intriguingly, both copies of the Las1 HEPN motif were important for nuclease function, revealing that both HEPN motifs participate in coordinating the RNA within the Las1 active site. We also established that conformational flexibility of the two HEPN domains is important for proper nuclease function. The results of our work reveal critical information about how dual HEPN domains come together to drive Las1-mediated RNA cleavage.
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Window to another world: Life is bubbling up to seafloor with petroleum from deep below
(Marine Biological Laboratory) Microbial life is bubbling up to the ocean floor along with fluids from deeply buried petroleum reservoirs, reports a team of scientists from the University of Calgary and the Marine Biological Laboratory, Woods Hole.
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Going Mobile With Diabetes Support: A Randomized Study of a Text Message-Based Personalized Behavioral Intervention for Type 2 Diabetes Self-Care
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Bad Gyal Jade gets boost from Bounty endorsement
In an interview with THE STAR last August, up-and-coming artiste Bad Gyal Jade dubbed herself the 'female Kartel'. Drawing comparisons between her style and flow and that of the incarcerated deejay, Jade said the label was a fitting one. Though...
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Quick Earthquake Messages M6.7 [7.0S, 130.0E] in Tanimbar Islands Region, Indonesia (21:54 HKT 06/05/2020)
Earthquake: 2020-05-06 21:54HKT M6.7 [7.0S, 130.0E] in Tanimbar Islands Region, Indonesia http://openstreetmap.org/?mlat=-7&mlon=130.
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Recommitting to International Criminal Justice and Human Rights in Indonesia
6 April 2018
Agantaranansa Juanda speaks to Jason Naselli about the promises the government has made and the steps that still need to be taken for the country to deliver justice for past violations of human rights.2018-04-06-Jokowi.jpg
Indonesian PM Joko Widodo. Photo: Getty Images.
Does the Indonesian government adequately protect human rights?
It does and it does not; it really depends on the context. Indonesia looks good among its neighbours in Southeast Asia in terms of protection of civil and political rights, and to some extent economic, social and cultural rights, although room for improvements exists.
But one of the promises of the current president, Joko Widodo, during his 2014 campaign was about international criminal justice, which involves rights for many victims of past cases of human rights abuses in Indonesia. In that sense, it does not protect these rights, including the rights to justice, truth, reparations or guarantees of non-recurrence.
For example, in the case of the conflict over independence for East Timor in 1999, there were many gross violations of human rights. However, there has never been any sort of effective judicial process to address gross violations of human rights, and crimes against humanity in particular.
In 1965–66, during the government’s violent anti-communist operations, 500,000 people or more were killed. Indonesia’s National Commission on Human Rights was tasked with conducting an investigation into this period within its limited mandate, but it led to nothing; there have never been any prosecutions relating to these crimes.
The election promise of the current president was to deal with a number of these past human rights cases, and this promise has not been met at all. His opponent in 2014, Prabowo Subianto, was a former military general involved in alleged past human rights abuses, so it was politically expedient to make such a promise. But it has not been pursued in office.
In 2000, Indonesia established its own Human Rights Court. What is your assessment of its record?
Some human rights activists suggested that the establishment of the Human Rights Court took place under international pressure following the independence of East Timor. To avoid international scrutiny, for example the creation of an ad hoc international tribunal, the government established this court.
Based on the report of the International Commission of Inquiry on East Timor in 2000, it was indeed recommended that an international human rights tribunal be set up. Indonesian government rejected the proposal with strong assurances that it would provide justice for atrocities committed by its nationals. So it is fair for some to see the establishment of Indonesia’s Human Rights Court as a political move by the government at that time, in order to avoid scrutiny by the international community.
When it comes to performance, the Human Rights Court actually investigated and prosecuted cases relating to atrocities in East Timor. There were around 100 suspects identified, and 18 were put on trial. Out of these 18, only one trial, of Eurico Guterres, ended in a conviction for crimes against humanity. However, the Indonesian Supreme Court cleared Guterres of all charges in 2008. So the Human Rights Court did take steps, but the net result amounted to essentially nothing. Impunity remains.
So it has not lived up to its mandate, but there is another factor, which is that the founding law of the Human Rights Court does not accommodate international standards of criminal justice. It only covers two of the four categories of crime as outlined in the Rome Statute – crimes against humanity and genocide. It also does not provide adequate protection for victims and witnesses. So there are issues not only with the performance of the Human Rights Court but also with the legislation establishing it.
Why hasn’t Indonesia become a party to the Rome Statute to join the ICC?
The main opposition came from the military, because they were afraid of being targeted by the ICC. There was also a lot of discussion about Indonesia’s ‘sovereign right to prosecute’.
But what those opposing failed to understand is that the ICC is bound by temporal and territorial boundaries, meaning that it will not intervene if the state in question is able and willing to prosecute. So I think accession to the Rome Statute has not taken place because of this misunderstanding.
I think another factor since this was initially raised is there is a focus on other issues. Indonesia is an emerging country economically; there is a focus on building infrastructure. So many in government feel like they are done with the past. But for the millions of victims of past crimes and their families, the past is not done.
So it’s very important at this point in the country’s history to revisit the commitment to international criminal justice to be able to contribute to sustainable peace and development.
What steps could the Indonesian government take to improve how it handles these issues?
The establishment of the Human Rights Court was an important starting point, but clearly there has to be significant reform, both in terms of the substantive law underpinning it and its procedures.
Clearly the domestic laws need to be reformed, but also, an effort needs to be made to improve the courts capacity in terms of manpower and logistical support. This is why the government needs to restart the discussion about becoming a party to the Rome Statute. Through the outreach programme of the ICC, this would give the Human Rights Court the capacity, in terms of manpower and logistical support, to tackle past human rights violations in Indonesia, which the Human Rights Court is currently lacking.
Only if these two steps are taken – reforming the domestic Human Rights Court and restarting discussion about becoming a party to the Rome Statute – will the Indonesian government be able to say it has made progress on international criminal justice.
The Indonesian government is actually running for a seat on the UN Security Council for the period of 2019–20. So I think it is an urgent discussion that the Indonesian government needs to have before it makes another pledge to contribute to the maintenance of international peace and security. It is difficult to have sustainable peace without justice.