Invitation Only Research Event

Research Event

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.

The pregnane X receptor (PXR) is a nuclear receptor that can be activated by numerous drugs and xenobiotic chemicals. PXR thereby functions as a xenobiotic sensor to coordinately regulate host responses to xenobiotics by transcriptionally regulating many genes involved in xenobiotic metabolism. We have previously reported that PXR has pro-atherogenic effects in animal models, but how PXR contributes to atherosclerosis development in different tissues or cell types remains elusive. In this study, we generated an LDL receptor-deficient mouse model with myeloid-specific PXR deficiency (PXR^MyeLDLR^–/–) to elucidate the role of macrophage PXR signaling in atherogenesis. The myeloid PXR deficiency did not affect metabolic phenotypes and plasma lipid profiles, but PXR^MyeLDLR^–/– mice had significantly decreased atherosclerosis at both aortic root and brachiocephalic arteries compared with control littermates. Interestingly, the PXR deletion did not affect macrophage adhesion and migration properties, but reduced lipid accumulation and foam cell formation in the macrophages. PXR deficiency also led to decreased expression of the scavenger receptor CD36 and impaired lipid uptake in macrophages of the PXR^MyeLDLR^–/– mice. Further, RNA-Seq analysis indicated that treatment with a prototypical PXR ligand affects the expression of many atherosclerosis-related genes in macrophages in vitro. These findings reveal a pivotal role of myeloid PXR signaling in atherosclerosis development and suggest that PXR may be a potential therapeutic target in atherosclerosis management.

Expert

Invitation Only Research Event

17 January 2020

Invitation Only Research Event

Event participants

Dr Robin Niblett CMG, Director, Chatham House  
Toshiro Mutoh, Honorary Chairman, Daiwa Institute of Research; CEO, Tokyo Organising Committee of the Olympic and Paralympic Game
José Manuel Barroso, Senior Adviser, Chatham House; President of the European Commission (2004-14); Prime Minister of Portugal (2002-04)
Akihiko Tanaka, President, National Graduate Institute for Policy Studies

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Time: 10:00 AM (Canceled/see notice), Location: E1.036 (Finance Room)

The challenges, for Hong Kong, are as much local as they are global. I know many of you are concerned about the recent social unrest here in Hong Kong, about whether it is affecting our financial market and whether there has been outflow of funds.

First of all, there's the obvious: Hong Kong is undergoing a time of unprecedented turbulence. Dissension has gripped our community for months now. That said, we are working to address and respond to those concerns, determined to find a path to peace, harmony and renewed prosperity in 2020.

We have been making progress. But there is still much to be done before we can put this testing time behind us.

Competitive advantages

What I can tell is that the advantages Hong Kong has long been recognised for are still very much with us, and they are not going anywhere anytime soon.

They begin with our enviable location, at the heart of Asia. Which means that Hong Kong is fully plugged into the round-the-clock global financial trading cycle. We provide certain and seamless connectivity with the financial hubs of Europe and North America, as well as those in the Middle East and across Asia.

Hong Kong is blessed with the dual advantages of "one country, two systems". The rule of law, an independent judiciary and an unshakable adherence to free enterprise are among Hong Kong's core values.

We offer businesses from the Mainland and all over the world - more than 9,000 at last count - a level-playing field, a competitive market, whatever their businesses, whatever their investments. Our linked exchange rate system remains solid, our currency fully convertible and capital flowing in and out freely, as enshrined in Article 112 of the Basic Law. Our capital markets are deep and liquid.

Despite our external and domestic challenges, Hong Kong's financial market remains stable. Our banking system continues to run smoothly and with ample liquidity.

The figures speak for themselves. In 2019, Hong Kong again topped the world in funds raised through IPOs - some US$40 billion worth. This is the seventh time we have come first in the past 11 years.

Our stock market's capitalisation is about US$4.9 trillion. That's more than 13 times Hong Kong's GDP.

As at end November 2019, bank deposits in both Hong Kong dollars and foreign currencies continued to increase over the same period last year, totalling US$1.8 trillion.

Our exchange rate remains stable. These and other measures reflect the integrity of Hong Kong's financial and legal system, the confidence it conveys, even as we face formidable external and domestic shocks.

In September last year, the Global Financial Centres Index once again ranked Hong Kong among the world's top three financial centres, behind only New York and bearing in on London.

Last October, the World Economic Forum's Global Competitiveness Report ranked our financial system top in the world, while the World Bank rated Hong Kong the third-easiest place to do business.

Hong Kong is still very much the largest offshore renminbi business hub in the world.

We are, as well, the premier asset and wealth management centre. Apart from exempting onshore and offshore funds from profits tax, we are considering introducing a more competitive tax arrangement to attract private equity funds to domicile in Hong Kong.  

The insurance industry is equally important. We have, after all, the highest concentration of insurers in Asia - more than 160 at the end of September. And we will enable the issuance of insurance-linked securities, expanding the insurable risks of captive insurers in Hong Kong.

On the taxes front, we already have the world's most business-friendly tax system, according to Paying Taxes 2020, a report produced by Pricewaterhouse Coopers and the World Bank. Still, we plan to provide tax relief to promote the development of marine insurance and the underwriting of specialty risks in Hong Kong.

Green finance is our policy priority going forward. Green bonds issued and arranged in Hong Kong increased over 200% to US$11 billion in 2018 as compared to the previous year.

That was followed by our inaugural government green bond issuance of US$1 billion last May. And we plan to issue more, and encourage more entities to arrange financing for their green projects right here in Hong Kong.

Fintech is another area where we strive to excel.

Looking at the big picture, the International Monetary Fund (IMF)'s latest projection of global economic growth this year has been adjusted downward to 3.4%. Growth in Asia, however, will continue to outperform the rest of the world.

The IMF forecasts the Mainland economy to grow by 5.8% in 2020, down slightly but still far and away leading most other jurisdictions.

Robust financial system

As for Hong Kong, the IMF Staff Report last month commended the resilience of our financial system and linked exchange rate, despite its slowing economy. The IMF's Hong Kong report noted, and I quote, that "robust policy frameworks and ample buffers will help the economy weather the challenges ahead".

The IMF also expressed approval for the Government's wide-ranging policies to support the economy and safeguard financial stability.

While we welcome the IMF's confidence in Hong Kong, I am prepared to roll out further relief measures as necessary.

We will also step up efforts to capitalise on emerging opportunities - not only from green finance and fintech but from the development of the Guangdong-Hong Kong-Macao Greater Bay Area and the Belt & Road Initiative, which demonstrates Hong Kong's uniqueness and irreplaceable position in the Mainland's national and economic development strategy.

Hong Kong is, and will remain, the business bridge between the Mainland and the rest of the world. Count on Hong Kong, as always, to be your partner, to help you build your business in the Mainland, throughout the Asian region and around the world. Count on Hong Kong to connect you with abundant capital and continuing opportunities.

Financial Secretary Paul Chan gave these remarks at the 13th Asian Financial Forum keynote luncheon on January 13.

Carla E. Cox
Aug 1, 2017; 30:157-160
From Research to Practice

Howard Craig Zisser
Apr 1, 2007; 20:85-89
Articles

(Arizona State University) Cun-Zheng Ning, a professor of electrical engineering in the Ira A. Fulton Schools of Engineering at Arizona State University, and collaborators from Tsinghua University in China discovered a process of physics that enables low-power nanolasers to be produced in 2D semiconductor materials. Understanding the physics behind lasers at nanoscale and how they interact with semiconductors can have major implications for high-speed communication channels for supercomputers and data centers.

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.