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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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A novel GPER antagonist protects against the formation of estrogen-induced cholesterol gallstones in female mice [Research Articles]

Many clinical studies and epidemiological investigations have clearly demonstrated that women are twice as likely to develop cholesterol gallstones as men, and oral contraceptives and other estrogen therapies dramatically increase that risk. Further, animal studies have revealed that estrogen promotes cholesterol gallstone formation through the estrogen receptor (ER) α, but not ERβ, pathway. More importantly, some genetic and pathophysiological studies have found that G protein-coupled estrogen receptor (GPER) 1 is a new gallstone gene, Lith18, on chromosome 5 in mice and produces additional lithogenic actions, working independently of ERα, to markedly increase cholelithogenesis in female mice. Based on computational modeling of GPER, a novel series of GPER-selective antagonists were designed, synthesized, and subsequently assessed for their therapeutic effects via calcium mobilization, cAMP, and ERα and ERβ fluorescence polarization binding assays. From this series of compounds, one new compound, 2-cyclohexyl-4-isopropyl-N-(4-methoxybenzyl)aniline (CIMBA), exhibits superior antagonism and selectivity exclusively for GPER. Furthermore, CIMBA reduces the formation of 17β-estradiol-induced gallstones in a dose-dependent manner in ovariectomized mice fed a lithogenic diet for 8 weeks. At 32 μg/day/kg CIMBA, no gallstones are found, even in ovariectomized ERα (–/–) mice treated with 6 μg/day 17β-estradiol and fed the lithogenic diet for 8 weeks. In conclusion, CIMBA treatment protects against the formation of estrogen-induced cholesterol gallstones by inhibiting the GPER signaling pathway in female mice. CIMBA may thus be a new agent for effectively treating cholesterol gallstone disease in women.­




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Nanodomains can persist at physiologic temperature in plasma membrane vesicles and be modulated by altering cell lipids [Research Articles]

The formation and properties of liquid-ordered (Lo) lipid domains (rafts) in the plasma membrane are still poorly understood. This limits our ability to manipulate ordered lipid domain-dependent biological functions. Giant plasma membrane vesicles (GPMVs) undergo large-scale phase separations into coexisting Lo and liquid-disordered lipid domains. However, large-scale phase separation in GPMVs detected by light microscopy is observed only at low temperatures. Comparing Förster resonance energy transfer-detected versus light microscopy-detected domain formation, we found that nanodomains, domains of nanometer size, persist at temperatures up to 20°C higher than large-scale phases, up to physiologic temperature. The persistence of nanodomains at higher temperatures is consistent with previously reported theoretical calculations. To investigate the sensitivity of nanodomains to lipid composition, GPMVs were prepared from mammalian cells in which sterol, phospholipid, or sphingolipid composition in the plasma membrane outer leaflet had been altered by cyclodextrin-catalyzed lipid exchange. Lipid substitutions that stabilize or destabilize ordered domain formation in artificial lipid vesicles had a similar effect on the thermal stability of nanodomains and large-scale phase separation in GPMVs, with nanodomains persisting at higher temperatures than large-scale phases for a wide range of lipid compositions. This indicates that it is likely that plasma membrane nanodomains can form under physiologic conditions more readily than large-scale phase separation. We also conclude that membrane lipid substitutions carried out in intact cells are able to modulate the propensity of plasma membranes to form ordered domains. This implies lipid substitutions can be used to alter biological processes dependent upon ordered domains.




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Lipid rafts as a therapeutic target [Thematic Reviews]

Lipid rafts regulate the initiation of cellular metabolic and signaling pathways by organizing the pathway components in ordered microdomains on the cell surface. Cellular responses regulated by lipid rafts range from physiological to pathological, and the success of a therapeutic approach targeting "pathological" lipid rafts depends on the ability of a remedial agent to recognize them and disrupt pathological lipid rafts without affecting normal raft-dependent cellular functions. In this article, concluding the Thematic Review Series on Biology of Lipid Rafts, we review current experimental therapies targeting pathological lipid rafts, including examples of inflammarafts and clusters of apoptotic signaling molecule-enriched rafts. The corrective approaches include regulation of cholesterol and sphingolipid metabolism and membrane trafficking by using HDL and its mimetics, LXR agonists, ABCA1 overexpression, and cyclodextrins, as well as a more targeted intervention with apoA-I binding protein. Among others, we highlight the design of antagonists that target inflammatory receptors only in their activated form of homo- or heterodimers, when receptor dimerization occurs in pathological lipid rafts. Other therapies aim to promote raft-dependent physiological functions, such as augmenting caveolae-dependent tissue repair. The overview of this highly dynamic field will provide readers with a view on the emerging concept of targeting lipid rafts as a therapeutic strategy.




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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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Hematopoiesis is regulated by cholesterol efflux pathways and lipid rafts: connections with cardiovascular diseases [Thematic Reviews]

Lipid rafts are highly ordered regions of the plasma membrane that are enriched in cholesterol and sphingolipids and play important roles in many cells. In hematopoietic stem and progenitor cells (HSPCs), lipid rafts house receptors critical for normal hematopoiesis. Lipid rafts also can bind and sequester kinases that induce negative feedback pathways to limit proliferative cytokine receptor cycling back to the cell membrane. Modulation of lipid rafts occurs through an array of mechanisms, with optimal cholesterol efflux one of the major regulators. As such, cholesterol homeostasis also regulates hematopoiesis. Increased lipid raft content, which occurs in response to changes in cholesterol efflux in the membrane, can result in prolonged receptor occupancy in the cell membrane and enhanced signaling. In addition, certain diseases, like diabetes, may contribute to lipid raft formation and affect cholesterol retention in rafts. In this review, we explore the role of lipid raft-related mechanisms in hematopoiesis and CVD (specifically, atherosclerosis) and discuss how defective cholesterol efflux pathways in HSPCs contribute to expansion of lipid rafts, thereby promoting myelopoiesis and thrombopoiesis. We also discuss the utility of cholesterol acceptors in contributing to lipid raft regulation and disruption, and highlight the potential to manipulate these pathways for therapeutic gain in CVD as well as other disorders with aberrant hematopoiesis.




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Lipid rafts in glial cells: role in neuroinflammation and pain processing [Thematic Reviews]

Activation of microglia and astrocytes secondary to inflammatory processes contributes to the development and perpetuation of pain with a neuropathic phenotype. This pain state presents as a chronic debilitating condition and affects a large population of patients with conditions like rheumatoid arthritis and diabetes, or after surgery, trauma, or chemotherapy. Here, we review the regulation of lipid rafts in glial cells and the role they play as a key component of neuroinflammatory sensitization of central pain signaling pathways. In this context, we introduce the concept of an inflammaraft (i-raft), enlarged lipid rafts harboring activated receptors and adaptor molecules and serving as an organizing platform to initiate inflammatory signaling and the cellular response. Characteristics of the inflammaraft include increased relative abundance of lipid rafts in inflammatory cells, increased content of cholesterol per raft, and increased levels of inflammatory receptors, such as toll-like receptor (TLR)4, adaptor molecules, ion channels, and enzymes in lipid rafts. This inflammaraft motif serves an important role in the membrane assembly of protein complexes, for example, TLR4 dimerization. Operating within this framework, we demonstrate the involvement of inflammatory receptors, redox molecules, and ion channels in the inflammaraft formation and the regulation of cholesterol and sphingolipid metabolism in the inflammaraft maintenance and disruption. Strategies for targeting inflammarafts, without affecting the integrity of lipid rafts in noninflammatory cells, may lead to developing novel therapies for neuropathic pain states and other neuroinflammatory conditions.




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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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Lipid rafts as signaling hubs in cancer cell survival/death and invasion: implications in tumor progression and therapy [Thematic Reviews]

Cholesterol/sphingolipid-rich membrane domains, known as lipid rafts or membrane rafts, play a critical role in the compartmentalization of signaling pathways. Physical segregation of proteins in lipid rafts may modulate the accessibility of proteins to regulatory or effector molecules. Thus, lipid rafts serve as sorting platforms and hubs for signal transduction proteins. Cancer cells contain higher levels of intracellular cholesterol and lipid rafts than their normal non-tumorigenic counterparts. Many signal transduction processes involved in cancer development (insulin-like growth factor system and phosphatidylinositol 3-kinase-AKT) and metastasis [cluster of differentiation (CD)44] are dependent on or modulated by lipid rafts. Additional proteins playing an important role in several malignant cancers (e.g., transmembrane glycoprotein mucin 1) are also being detected in association with lipid rafts, suggesting a major role of lipid rafts in tumor progression. Conversely, lipid rafts also serve as scaffolds for the recruitment and clustering of Fas/CD95 death receptors and downstream signaling molecules leading to cell death-promoting raft platforms. The partition of death receptors and downstream signaling molecules in aggregated lipid rafts has led to the formation of the so-called cluster of apoptotic signaling molecule-enriched rafts, or CASMER, which leads to apoptosis amplification and can be pharmacologically modulated. These death-promoting rafts can be viewed as a linchpin from which apoptotic signals are launched. In this review, we discuss the involvement of lipid rafts in major signaling processes in cancer cells, including cell survival, cell death, and metastasis, and we consider the potential of lipid raft modulation as a promising target in cancer therapy.




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Lipid rafts and pathogens: the art of deception and exploitation [Thematic Reviews]

Lipid rafts, solid regions of the plasma membrane enriched in cholesterol and glycosphingolipids, are essential parts of a cell. Functionally, lipid rafts present a platform that facilitates interaction of cells with the outside world. However, the unique properties of lipid rafts required to fulfill this function at the same time make them susceptible to exploitation by pathogens. Many steps of pathogen interaction with host cells, and sometimes all steps within the entire lifecycle of various pathogens, rely on host lipid rafts. Such steps as binding of pathogens to the host cells, invasion of intracellular parasites into the cell, the intracellular dwelling of parasites, microbial assembly and exit from the host cell, and microbe transfer from one cell to another all involve lipid rafts. Interaction also includes modification of lipid rafts in host cells, inflicted by pathogens from both inside and outside the cell, through contact or remotely, to advance pathogen replication, to utilize cellular resources, and/or to mitigate immune response. Here, we provide a systematic overview of how and why pathogens interact with and exploit host lipid rafts, as well as the consequences of this interaction for the host, locally and systemically, and for the microbe. We also raise the possibility of modulation of lipid rafts as a therapeutic approach against a variety of infectious agents.




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Biology of Lipid Rafts: Introduction to the Thematic Review Series [Thematic Reviews]

Lipid rafts are organized plasma membrane microdomains, which provide a distinct level of regulation of cellular metabolism and response to extracellular stimuli, affecting a diverse range of physiologic and pathologic processes. This Thematic Review Series focuses on Biology of Lipid Rafts rather than on their composition or structure. The aim is to provide an overview of ideas on how lipid rafts are involved in regulation of different pathways and how they interact with other layers of metabolic regulation. Articles in the series will review the involvement of lipid rafts in regulation of hematopoiesis, production of extracellular vesicles, host interaction with infection, and the development and progression of cancer, neuroinflammation, and neurodegeneration, as well as the current outlook on therapeutic targeting of lipid rafts.




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Membrane domains beyond the reach of microscopy [Commentaries]




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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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Images in Lipid Research [Editorials]











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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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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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Finite-dimensional approximations to the Poincaré–Steklov operator for general elliptic boundary value problems in domains with cylindrical and periodic exits to infinity

S. A. Nazarov
Trans. Moscow Math. Soc. 80 (2020), 1-51.
Abstract, references and article information





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Candidíase – Conheça as causas, sintomas e tratamentos

O que é Candidíase? Candidíase, é uma infecção sistêmica causada pelo fungos da Candida albicans. A Candida albicans é um tipo de fungo (levedura) que vive em harmonia no organismo,…

The post Candidíase – Conheça as causas, sintomas e tratamentos appeared first on Saúde Próspera.



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S2 Ep38: Crashing iPhones, ransomware tales and human chatbots – Naked Security Podcast

Get the latest cybersecurity news, opinion and advice.




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Is Myanmar Running Out of Time?

Research Event

17 February 2020 - 1:00pm to 2:00pm

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

Event participants

Thant Myint-U, Conservationist; Author, The Hidden History of Burma: Race, Capitalism, and the Crisis of Democracy in the 21st Century
Chair: Champa Patel, Head of Asia-Pacific Programme, Chatham House

Just a few years ago the West was celebrating what appeared to be the conclusion of a quarter-century long contest between Myanmar’s democrats and a military dictatorship. Today, the country stands charged with genocide at the International Court of Justice, with Aung San Suu Kyi leading the defence. Is Myanmar a democratic transition gone awry? Or something else entirely?  

The speaker will argue that Myanmar is not the simple morality tale often portrayed. It has instead become the stage for some of the world’s most pressing challenges such as climate change, explosive inequality and rising populism, the impact of social media; and the rise of China as the next global superpower.

In this context, are 20th century democratic institutions and free-market reforms the correct remedy for a country plagued by the legacies of colonialism, decades of civil war, tyranny and a predatory economic system? The speaker will offer a prognosis for Myanmar’s future, assessing the question of whether it will become Asia’s next failed state.

This event will be held off the record.

 

Lucy Ridout

Programme Administrator, Asia-Pacific Programme
+44 (0) 207 314 2761




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Network Power in the Asia-Pacific: Making Sense of the New Regionalism and Opportunities for Cooperation

Research Event

7 February 2020 - 9:45am to 5:30pm

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

The Asia-Pacific region continues to increase in geopolitical and geoeconomic importance. The rise of China and tensions with the US are affecting bilateral relationships and traditional alliances in the region. Whether seen from the perspective of the Quad – Australia, India, Japan and the US – or the Indo-Pacific concept embraced by a wide range of countries but with no shared consensus on scope and objectives or with ASEAN who insists on the importance of its own centrality, the region is redefining and reconceptualising itself.

With a diverse range of initiatives – including the Regional Comprehensive Economic Partnership (RCEP) and Comprehensive and Progressive Agreement for Trans-Pacific Partnership (CPTPP) – there are a plethora of regional agreements and institutional groupings that add further complexity.

As the Bretton Woods architecture continues to be dominated by Western powers, China is also spearheading parallel governance initiatives such as the Asian Infrastructure Investment Bank (AIIB), the Belt and Road Initiative and the Shanghai Cooperation Organization (SCO) as a means of enhancing its geopolitical and geoeconomic influence.

This one-day conference will focus on how such networks and alliances have been built, and sustained, in the Asia-Pacific region. In order to understand how new regional initiatives might open up opportunities for new forms of international cooperation, the conference will focus on the themes of cyber-technology and innovation, sustainable development and mitigating the impacts of climate change and new infrastructure initiatives. It will assess whether there is a zero-sum conflict between competing networks and agendas or whether a common approach can be developed.

Lucy Ridout

Programme Administrator, Asia-Pacific Programme
+44 (0) 207 314 2761




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Will a Devastating Bushfire Season Change Australia’s Climate Stance?

23 January 2020

Madeleine Forster

Richard and Susan Hayden Academy Fellow, International Law Programme

Professor Tim Benton

Research Director, Emerging Risks; Director, Energy, Environment and Resources Programme
With Australians experiencing first-hand the risks of climate change, Madeleine Forster and Tim Benton examine the influencers, at home or abroad, that could push the government towards more action.

2020-01-23-FireNSW.jpg

Residents look on as flames burn through bush on 4 January 2020 in Lake Tabourie, NSW. Photo: Getty Images.

The 2019–20 fire season in Australia has been unprecedented. To date, an estimated 18 million hectares of fire has cut swathes through the bush – an area greater than that of the average European country and over five times the size of blazes in the Amazon.

This reflects previous predictions of Australian science. Since 2008 and as recently as 2018, scientific bodies have warned that climate change will exacerbate existing conditions for fires and other climatic disasters in Australia. What used to be once-in-a-generation fires now re-appear within 10–15 years with increased ferocity, over longer seasons.

In a country known for climate denial and division, debate has erupted around bushfire management and climate change. One of these is whether controlled burns are the answer to Australia’s climate-affected fire conditions.

There is no single risk reduction strategy. Controlled burning remains key, if adapted to the environment and climate

But when three out of four seasons in a year can support destructive bushfires, there are clear limits to what controlled burning and other fire management techniques can achieve. Other ‘adaptation’ measures are also likely to provoke intense debate – including bush clearance. As one Australian expert offered to highlight where Australia has got to, families should probably not go on holiday to bush and beach during the height of summer when temperatures and fire risk peaks. 

So, unless Australia is prepared to debate radical changes to where people live and how land is used, the limits to adaptation imply the need for mitigation. This means supporting ambitious global greenhouse emissions reductions targets. As research from Victoria, one fire-prone state in Australia, highlights, ‘the emissions pathway we follow is the largest determinant of change to many variables [such as temperature] beyond the next few decades.’

Can Australia become a more active global partner on emissions?

Australia accounts for just over one per cent of global emissions, so reducing domestic emissions – even though on a per capita basis they are the highest in the world – will not reduce Australia’s climate risk. Showing international leadership and supporting a powerful coalition of the willing to tackle climate change is the only way ahead. By showing a willingness to adopt climate ambition, Australia can help more constructive worldwide action, and thereby reduce its own risk exposure. 

Leading by example is a politically difficult issue for Australia. Prime Minister Scott Morrison was re-elected in May 2019 on an economic stability platform, and a promise not to imperil employment growth through climate action. Australia has contested UN estimates that it will not meet its existing modest goals for domestic emissions, by seeking to rely on carryover credits from action under the Kyoto Protocol as proof of progress.

It has also distanced itself from concerns over global supply and demand in fossil fuels. Australia remains a global supplier for fossil fuels, including coal – the nation’s coal exports accounted for $67 billion in revenues in 2019 in an expanding but changing Asian market, supplying ‘some of the cheapest electricity in the world’.

Possible influencers of change

With Australians experiencing first-hand the risks of climate change, there is already pressure to do more. Many are sceptical this will translate into domestic targets or export policies that give Australia the moral authority to ask for more action on the global stage.

Here, diverse groups who share a common interest in seeing Australia recover from the bushfires and address future climate risks could be key.

Importantly this includes rural and urban-fringe communities affected by the bushfires. They were part of Morrison’s traditional supporter-base but are angry at the government’s handling of the crisis and increasingly see how tiptoeing around emissions (including exports) has also ‘buried’ open discussion at home on climate-readiness.

Australian states could also find themselves taking a lead role. Virtually all jurisdictions have now committed to their own goals, most based on zero-carbon goals by 2050 (as has New Zealand). These can support modelling for Australia’s energy transition from coal, through gas, to market competitive renewables, while also help to ensure this reflects community expectations on jobs, electricity prices and other costs. 

Other emerging voices include the insurance and banking sectors (the Reserve Bank of Australia warned of the long-term financial stability risks of climate change before the fires) and indigenous Australians (one group of Torres Strait Islanders have filed a complaint to the UN Human Rights Committee which, if heard, will place Australia’s emissions record under the spotlight again). Their challenge now is finding a common language on what a cohesive approach to addressing climate change risk looks like. 

The international picture is mixed. The United States’ poor federal climate policy is a buffer for Australia. French President Emmanuel Macron has tried to raise the cost of inaction for Australia in current EU–Australia trade negotiations, but many large emitters in the Indo-Pacific region remain key Australian trading partners, investors and buyers of Australian coal. 

In the meantime, the United Kingdom is preparing for the meeting of parties to the Paris Agreement in Glasgow in November. A key global event following Brexit, the UK will no doubt be hoping to encourage a leadership circle with national commitments that meet global need to make the Glasgow meeting a success.

The UK public has expressed enormous sympathy for Australia in the bushfires and outrage over ‘climate denialism.’ Australia’s experience will be a cautionary tale of the effects of climate change at the meeting. Could the UK also support Australia to become a less reluctant partner in global climate action?




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What the ICJ Decision on Myanmar Means

24 January 2020

Dr Champa Patel

Director, Asia-Pacific Programme
Champa Patel on the implications of the International Court of Justice’s decision to order protection for the Rohingya.

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Rohingya refugees watch ICJ proceedings at a restaurant in a refugee camp in Cox's Bazar, Bangladesh in December. Photo: Getty Images.

The decision by the International Court of Justice (ICJ) that Myanmar should take all measures available to prevent acts of genocide against the persecuted Rohingya minority is truly ground-breaking. The case shows how small states can play an important role in upholding international law and holding other states accountable. 

The Gambia, acting with the support of the Organization of Islamic Cooperation, skilfully used Article IX of the Genocide Convention, which allows for a state party to the convention to pursue cases against another state party where it is felt there has been a dispute regarding the ‘interpretation, application or fulfilment’ of the convention.

Seventeen states have entered reservations against this specific provision but Myanmar is not one of them. It was on this basis that The Gambia was able to take its case to the ICJ. This exciting development expands the possibilities of international accountability at the state-to-state level.

But it should be noted that the current ruling is focused on provisional measures – the central case could still take years to conclude. There is still a long road ahead on the court determining whether the Myanmar authorities committed acts of genocide.

And, while the decision was unanimous and binding, the ICJ cannot enforce its ruling. Myanmar has shown itself resistant to international criticism and there is a real risk they will fail to comply.

One way forward, should Myanmar not respect the ruling, is that the UN Security Council could agree a resolution to compel action. However, it seems unlikely that China would ever vote for such a resolution, given its strong stance on non-intervention and its economic interests in the country. 




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Bangladesh: The Trade-Off Between Economic Prosperity and Human Rights

Research Event

11 March 2020 - 1:00pm to 2:00pm

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

Event participants

K. Anis Ahmed, Publisher, Dhaka Tribune and Bangla Tribune; Author of Good Night, Mr. Kissinger, Co-director, Dhaka Literary Festival
Meenakshi Ganguly, South Asia Director, Human Rights Watch
Chair: Ed Cumming, Writer, The Independent

Bangladesh's recent gains in economic and social indices, set against its record of corruption and poor civil rights, has at times been termed the ‘Bangladesh Paradox’. Yet this label is overly simplistic; the current situation proves that these trends can coexist.

The Awami League government, in power since 2009, has increased political stability, delivered unprecedented economic and social advances, and adopted a counter-terrorism strategy to stamp out extremist groups. At the same time, it is criticized for curbing civil rights and failing to hold credible elections. However, as the two previous regimes have demonstrated, the rights situation is unlikely to improve even if the Awami League were replaced.

How did worsening rights become a feature of the state irrespective of its political dispensation? An unresolved contest between political and non-political state actors may hold the key to that puzzle. The perils of the current dispensation have recently manifested in weakening economic indicators, which jeopardize the very stability and social progress for which the country has garnered much praise.

Lucy Ridout

Programme Administrator, Asia-Pacific Programme
+44 (0) 207 314 2761




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Webinar: Make or Break: China and the Geopolitical Impacts of COVID-19

Research Event

28 April 2020 - 12:00pm to 12:45pm

Event participants

Yu Jie, Senior Research Fellow on China, Asia-Pacific Programme, Chatham House
Kerry Brown, Associate Fellow, Asia-Pacific Programme, Chatham House; Professor of Chinese Studies and Director of Lau China Institute, King’s College London

The COVID-19 crisis has accelerated geopolitical tensions that, in part, have arisen from US-China tensions. At a time when the world needs strong and collective leadership to fight the coronavirus, both countries have been locked in a battle of words characterized by escalating hostility, polarizing narratives, blame and misinformation. Caught in the crossfire, many people of Chinese descent across differing countries have reported an increase in xenophobic attacks.

Middle powers such as the UK and Australia have swerved between recognition of the global collaboration needed to solve this pandemic and calls for China to be held ‘accountable’ for its initial response. Others such, as France and Japan, have been trying to foster international cooperation. 

Against this context, speakers will discuss China’s response to the crisis, including the initial delay and Beijing’s later containment strategies. How do we best assess the delay amidst all the heated rhetoric? What was the response of people within China to the measures? Does COVID-19 mark a point of no return for US-China relations? How might this impact on relations between US allies and China? And what kind of China will emerge from this current crisis?

Lucy Ridout

Programme Administrator, Asia-Pacific Programme
+44 (0) 207 314 2761




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Making Movies Come Alive

Many movie animation techniques are based on mathematics. Characters, background, and motion are all created using software that combines pixels into geometric shapes which are stored and manipulated using the mathematics of computer graphics. Software encodes features that are important to the eye, like position, motion, color, and texture, into each pixel. The software uses vectors, matrices, and polygonal approximations to curved surfaces to determine the shade of each pixel. Each frame in a computer-generated film has over two million pixels and can have over forty million polygons. The tremendous number of calculations involved makes computers necessary, but without mathematics the computers wouldn.t know what to calculate. Said one animator, ". . . it.s all controlled by math . . . all those little X,Y.s, and Z.s that you had in school - oh my gosh, suddenly they all apply." For More Information: Mathematics for Computer Graphics Applications, Michael E. Mortenson, 1999.




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Putting Music on the Map

Mathematics and music have long been closely associated. Now a recent mathematical breakthrough uses topology (a generalization of geometry) to represent musical chords as points in a space called an orbifold, which twists and folds back on itself much like a Mobius strip does. This representation makes sense musically in that sounds that are far apart in one sense yet similar in another, such as two notes that are an octave apart, are identified in the space.This latest insight provides a way to analyze any type of music. In the case of Western music, pleasing chords lie near the center of the orbifolds and pleasing melodies are paths that link nearby chords. Yet despite the new connection between music and coordinate geometry, music is still more than a connect-the-dots exercise, just as mathematics is more than addition and multiplication. For More Information: The Geometry of Musical Chords, Dmitri Tymoczko, Science, July 7, 2006.




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Making Votes Count

The outcome of elections that offer more than two alternatives but with no preference by a majority, is determined more by the voting procedure used than by the votes themselves. Mathematicians have shown that in such elections, illogical results are more likely than not. For example, the majority of this group want to go to a warm place, but the South Pole is the group.s plurality winner. So if these people choose their group.s vacation destination in the same way most elections are conducted, they will all go to the South Pole and six people will be disappointed, if not frostbitten. Elections in which only the top preference of each voter is counted are equivalent to a school choosing its best student based only on the number of A.s earned. The inequity of such a situation has led to the development of other voting methods. In one method, points are assigned to choices, just as they are to grades. Using this procedure, these people will vacation in a warm place a more desirable conclusion for the group. Mathematicians study voting methods in hopes of finding equitable procedures, so that no one is unfairly left out in the cold. For more information: Chaotic Elections: A Mathematician Looks at Voting, Donald Saari




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Hearing a Master.s Voice

The spools of wire below contain the only known live recording of the legendary folk singer Woody Guthrie. A mathematician, Kevin Short, was part of a team that used signal processing techniques associated with chaotic music compression to recapture the live performance, which was often completely unintelligible. The modern techniques employed, instead of resulting in a cold, digital output, actually retained the original concert.s warmth and depth. As a result, Short and the team received a Grammy Award for their remarkable restoration of the recording. To begin the restoration the wire had to be manually pulled through a playback device and converted to a digital format. Since the pulling speed wasn.t constant there was distortion in the sound, frequently quite considerable. Algorithms corrected for the speed variations and reconfigured the sound waves to their original shape by using a background noise with a known frequency as a "clock." This clever correction also relied on sampling the sound selectively, and reconstructing and resampling the music between samples. Mathematics did more than help recreate a performance lost for almost 60 years: These methods are used to digitize treasured tapes of audiophiles everywhere. For More Information: "The Grammy in Mathematics," Julie J. Rehmeyer, Science News Online, February 9, 2008.




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Working It Out. Math solves a mystery about the opening of "A Hard Day's Night."

The music of most hit songs is pretty well known, but sometimes there are mysteries. One question that remained unanswered for over forty years is: What instrumentation and notes make up the opening chord of the Beatles. "A Hard Day.s Night"? Mathematician Jason Brown - a big Beatles fan - recently solved the puzzle using his musical knowledge and discrete Fourier transforms, mathematical transformations that help decompose signals into their basic parts. These transformations simplify applications ranging from signal processing to multiplying large numbers, so that a researcher doesn.t have to be "working like a dog" to get an answer. Brown is also using mathematics, specifically graph theory, to discover who wrote "In My Life," which both Lennon and McCartney claimed to have written. In his graphs, chords are represented by points that are connected when one chord immediately follows another. When all songs with known authorship are diagrammed, Brown will see which collection of graphs - McCartney.s or Lennon.s - is a better fit for "In My Life." Although it may seem a bit counterintuitive to use mathematics to learn more about a revolutionary band, these analytical methods identify and uncover compositional principles inherent in some of the best Beatles. music. Thus it.s completely natural and rewarding to apply mathematics to the Fab 4 For More Information: Professor Uses Mathematics to Decode Beatles Tunes, "The Wall Street Journal", January 30, 2009..




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Matching Vital Needs - Increasing the number of live-donor kidney transplants

A person needing a kidney transplant may have a friend or relative who volunteers to be a living donor, but whose kidney is incompatible, forcing the person to wait for a transplant from a deceased donor. In the U.S. alone, thousands of people die each year without ever finding a suitable kidney. A new technique applies graph theory to groups of incompatible patient-donor pairs to create the largest possible number of paired-donation exchanges. These exchanges, in which a donor paired with Patient A gives a kidney to Patient B while a donor paired with Patient B gives to Patient A, will dramatically increase transplants from living donors. Since transplantation is less expensive than dialysis, this mathematical algorithm, in addition to saving lives, will also save hundreds of millions of dollars annually. Naturally there can be more transplants if matches along longer patient-donor cycles are considered (e.g., A.s donor to B, B.s donor to C, and C.s donor to A). The problem is that the possible number of longer cycles grows so fast hundreds of millions of A >B>C>A matches in just 5000 donor-patient pairs that to search through all the possibilities is impossible. An ingenious use of random walks and integer programming now makes searching through all three-way matches feasible, even in a database large enough to include all incompatible patient-donor pairs. For More Information: Matchmaking for Kidneys, Dana Mackenzie, SIAM News, December 2008. Image of suboptimal two-way matching (in purple) and an optimal matching (in green), courtesy of Sommer Gentry.




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Predicting Climate - Part 2

What.s in store for our climate and us? It.s an extraordinarily complex question whose answer requires physics, chemistry, earth science, and mathematics (among other subjects) along with massive computing power. Mathematicians use partial differential equations to model the movement of the atmosphere; dynamical systems to describe the feedback between land, ocean, air, and ice; and statistics to quantify the uncertainty of current projections. Although there is some discrepancy among different climate forecasts, researchers all agree on the tremendous need for people to join this effort and create new approaches to help understand our climate. It.s impossible to predict the weather even two weeks in advance, because almost identical sets of temperature, pressure, etc. can in just a few days result in drastically different weather. So how can anyone make a prediction about long-term climate? The answer is that climate is an average of weather conditions. In the same way that good predictions about the average height of 100 people can be made without knowing the height of any one person, forecasts of climate years into the future are feasible without being able to predict the conditions on a particular day. The challenge now is to gather more data and use subjects such as fluid dynamics and numerical methods to extend today.s 20-year projections forward to the next 100 years. For More Information: Mathematics of Climate Change: A New Discipline for an Uncertain Century, Dana Mackenzie, 2007.




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Predicting Climate - Part 1

What.s in store for our climate and us? It.s an extraordinarily complex question whose answer requires physics, chemistry, earth science, and mathematics (among other subjects) along with massive computing power. Mathematicians use partial differential equations to model the movement of the atmosphere; dynamical systems to describe the feedback between land, ocean, air, and ice; and statistics to quantify the uncertainty of current projections. Although there is some discrepancy among different climate forecasts, researchers all agree on the tremendous need for people to join this effort and create new approaches to help understand our climate. It.s impossible to predict the weather even two weeks in advance, because almost identical sets of temperature, pressure, etc. can in just a few days result in drastically different weather. So how can anyone make a prediction about long-term climate? The answer is that climate is an average of weather conditions. In the same way that good predictions about the average height of 100 people can be made without knowing the height of any one person, forecasts of climate years into the future are feasible without being able to predict the conditions on a particular day. The challenge now is to gather more data and use subjects such as fluid dynamics and numerical methods to extend today.s 20-year projections forward to the next 100 years. For More Information: Mathematics of Climate Change: A New Discipline for an Uncertain Century, Dana Mackenzie, 2007.




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Thinking Outside the Box Score - Math and basketball: Part 1

Muthu Alagappan explains how topology and analytics are bringing a new look to basketball.




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Making an Attitude Adjustment: Part 1

Nazareth Bedrossian talks about using math to reposition the International Space Station.




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Making Art Work

Researcher: Annalisa Crannell, Franklin & Marshall College. Annalisa Crannell on perspective in art.




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Maintaining a Balance Part 2

Researcher: Daniel Rothman, MIT. Dan Rothman talks about how math helped understand a mass extinction.




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Making the Earth Flat

Tom Patterson and Bojan Savric discuss the Equal Earth projection map that they created with Bernhard Jenny.




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Making Beautiful Mathematics

Rob Schneiderman talks about the metaphorical connections between math and music




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Unmasking Deepfakes

Hany Farid talks about fighting fake videos: "Mathematically, there's a lot of linear algebra, multivariate calculus, probability and statistics, and then a lot of techniques from pattern recognition, signal processing, and image processing."