Weimin Chen
Proc. Amer. Math. Soc. 148 (2020), 2707-2716.
Abstract, references and article information

Mahmoud Benkhalifa
Proc. Amer. Math. Soc. 148 (2020), 2695-2706.
Abstract, references and article information

Alyson Bittner
Proc. Amer. Math. Soc. 148 (2020), 2683-2693.
Abstract, references and article information

Shi-Zhong Du
Proc. Amer. Math. Soc. 148 (2020), 2631-2643.
Abstract, references and article information

Yingxiang Hu and Shicheng Xu
Proc. Amer. Math. Soc. 148 (2020), 2609-2615.
Abstract, references and article information

Moacir Aloisio, Silas L. Carvalho and César R. de Oliveira
Proc. Amer. Math. Soc. 148 (2020), 2509-2523.
Abstract, references and article information

Quanlei Fang and Jingbo Xia
Proc. Amer. Math. Soc. 148 (2020), 2497-2507.
Abstract, references and article information

Tonie Fares and Pascal Lefèvre
Proc. Amer. Math. Soc. 148 (2020), 2487-2496.
Abstract, references and article information

Michiya Mori
Proc. Amer. Math. Soc. 148 (2020), 2477-2485.
Abstract, references and article information

Véronique Bazier-Matte and Pierre-Guy Plamondon
Proc. Amer. Math. Soc. 148 (2020), 2397-2409.
Abstract, references and article information

Joachim Kock and David I. Spivak
Proc. Amer. Math. Soc. 148 (2020), 2317-2329.
Abstract, references and article information

We are less than two weeks into the new year and already, geo-political concerns, large and alarming, dominate the news. Still, I believe the year ahead will mark a milestone for Asia. Asian economies, in terms of purchasing power parity, will become larger than the rest of the world combined for the first time since the 19th century. That represents a quantum leap from about one-third just two decades ago. Asia this year will also be home to half of the middle class of the world. That heralds enormous business opportunities for the world at large. Indeed, Asia, powered by Mainland China, has for some time been a global growth engine.

Hong Kong, with its strategic regional location, and its extensive, ever-deepening cultural and financial links with the Mainland, is China's international financial centre, contributing to the sustainable progress of the country, the region and the world.

In pursuing sustainable development, quality as well as quantity counts. Today's economies are exploring growth through innovation and technology, while seeking inclusiveness. They are, to be sure, hard-won goals given the unprecedented challenges we've faced over the past two years: the global economic slowdown, trade disputes among major economies, geopolitical uncertainties and local issues. But if we cannot direct the wind, we can surely adjust our sails, which has been what we are doing here in Hong Kong. Thanks to lessons learned and measures implemented, particularly since the Asian financial crisis, Hong Kong's financial system remains stable and remarkably successful.

Globally competitive

Our core competitiveness, and our status as one of the world's premier financial centres, continues to be internationally recognised. Last September, we again ranked third in the world in the Global Financial Centres Index, just behind New York and London. That's a compelling statement of confidence in our freely convertible currency, our world-class banking system and stock market and the professionals who power our financial sector. It's a telling reflection of our strategic geographic location and sophisticated connections to global financial markets. It's recognition, too, of the free flow of capital within, into and out of Hong Kong, as enshrined in Article 112 of the Basic Law. More than capital flows, information and people also move effortlessly in and out of Hong Kong.

People around the world are confident in our regimes. They take reassurance in our trusted and bilingual common law system, our sound financial regulatory framework, low taxes and deep connections with the Mainland and the rest of the world. It helps, too, that Hong Kong again topped the world in 2019 in funds raised through initial public offerings, taking in about US$40 billion in 2019. That marked the seventh time in the past 11 years in which Hong Kong has led the world in IPOs.

Hong Kong is also the first international financial centre to have laid down a clearly-defined and comprehensive regulatory regime for listed companies with weighted voting rights structures and additional corporate governance and disclosure requirements. It's clearly working. Hong Kong is now the second-largest fundraising venue in the world for biotech companies. And, of course, the Alibaba Group Holding's secondary listing on our stock market in late November was one of the world's biggest stock offerings of 2019. The decision by the e-commerce giant - one of the Mainland's largest e-commerce companies and Asia's most valuable listed companies - may well encourage other Mainland enterprises listed elsewhere, to expand their investor links into the Asian region, with Hong Kong as their base.

Then there's the Guangdong-Hong Kong-Macao Greater Bay Area development. With a population of 71 million and a combined GDP of US$1.6 trillion, the Greater Bay Area and its huge market potential present boundless promise for Hong Kong, particularly our financial services sector.

Innovation will drive development in the bay area. Measures will be rolled out to expand the flow of capital and people, opening up new markets and business opportunities thanks to enhanced connectivity. Among others, with the support of the Central Government, especially a Leading Group on the Greater Bay Area development chaired by the Vice Premier Han Zheng, a two-way wealth management connect scheme is being drawn up to meet the cross-boundary, wealth-management needs of residents in Hong Kong and the rest of the bay area.

Coupled with the Belt & Road Initiative, the bay area development will ensure long-term prospects for Hong Kong's economy. Through these two national policies, Hong Kong will enhance its role as the business bridge between the Mainland and the rest of the world. I'm talking here of our status as a leading fundraising centre, the world's largest offshore renminbi business hub and a premier asset and wealth management hub.

We are no less committed to Hong Kong's development as a green finance centre. In May 2019, we issued our inaugural green bond under the Government Green Bond Programme. And, with the introduction of a Green Bond Grant Scheme, which subsidises green bond issuers in obtaining certification under the Green Finance Certification Scheme, green bonds issued and arranged in Hong Kong in 2018 reached US$11 billion. A good start, I'd say, in creating financial programmes that also pay off in environmental benefits for our sustainable development.

We are hard at work as well on enabling development of our capital markets. Our open-ended fund company regime has been in operation since end-July 2018. And since last April, onshore and offshore privately offered funds can enjoy profits tax exemption under our tax law.

We're also building on our mutual recognition of funds arrangement. It now covers six economies: the Mainland, Switzerland, France, the United Kingdom, Luxembourg and the Netherlands. Such connections will strengthen our role as the world's premier offshore renminbi hub and wealth management centre.

Our connectivity with the Mainland is also enhanced through such financial schemes as Hong Kong-Shanghai Stock Connect, Hong Kong-Shenzhen Stock Connect and Bond Connect. Since its inception, in late 2014, stock connect has realised cumulative net transactions of about US$150 billion in the Mainland and over US$130 billion in Hong Kong.

We continue to diversify our fund structures. Among other things, we are working on a new regime of limited partnership for the registration of private equity funds. We are also enhancing Hong Kong's status as an international insurance and risk-management hub. And, to broaden the range of risk-management offerings in Hong Kong, we plan to enable the issuance of insurance-linked securities, including catastrophe bonds. Moreover, we will expand the scope of insurable risks by captive insurers in Hong Kong to meet the risk-management needs of multinationals.

To exemplify our commitment to technology, last year, we issued eight virtual banking licences, as well as two virtual insurer licences. These can spur financial innovation, while boosting customer experience and building financial inclusion. And our Faster Payment System, launched in 2018 to enable instant payment, now handles about 168,000 transactions, totalling more than US$307 million, a day.

Bridging East and West

We've been busy making the most of Hong Kong's manifold advantages. In creating connections between businesses, investors and financial markets, East and West, we help you excel. That is also the great strength of the Asian Financial Forum (AFF), bringing East and West together for two intensive days of the latest information and intelligence, deliberation and debate, networking opportunities and business promise.

This year's AFF is, as always, packed with panel discussions and workshops on financial policy, asset and wealth management, insurance, sustainable finance and deal-making sessions. As fintech continues to shake up the financial world, the AFF continues to expand its focus on fintech. This year, we launch the FintechHK Startup Salon, showcasing promising business ideas from fintech startups. It builds on the success of last year's Fintech Showcase, which returns with more than 60 fintech startups. And there's even more on offer this year in areas, ranging from global trade finance to environmental, social and governance, profit with purpose and succession planning for family corporations.

It gives me great pleasure, as well, to tell you that your keynote luncheon speakers today and tomorrow, respectively, are Dr Janet Yellen, formerly the Chair of the US Federal Reserve System's Board of Governors, and Prof Abhijit Banerjee, the 2019 Economics Nobel laureate. I am honoured that they come to Hong Kong and offer us their insight and their inspiration.

The forum is part of International Financial Week in Hong Kong, which brings together some 16 events covering everything from private equity and fund-raising to alternative investment and advertising strategies for financial concerns. A trip to Shenzhen is also featured this year, with visits to leading financial services and technology companies. Shenzhen, of course, is our close partner in the bay area and a global pacesetter in technology.

The Asian Financial Forum symbolises Hong Kong's wide-ranging strengths and resilience as an economy and a community. These strengths and resilience, just like our financial systems, have not been undermined despite that we have experienced considerable social unrest and challenges in recent months. Through the concerted efforts of the Government, and the people of Hong Kong, I am confident that we will bridge our divide, that we will realise the common goal of a reunited community and a flourishing economy.

Chief Executive Carrie Lam gave these remarks at the 13th Asian Financial Forum on January 13.

The Science Museum is presenting the special Unlocking the Secrets - The Science of Conservation at The Palace Museum exhibition to tie in with the 600th anniversary of the Forbidden City in 2020.

More than 100 artefacts from the Palace Museum collection are being showcased to highlight the application of science and technology in conservation.

They include bronzes, clocks, textiles, thangkas, wood furniture, lacquerware and inlaid works along with ceramics, calligraphy and hand-painted copies of ancient paintings.

The show also presents the Conservation Office’s work by showcasing intriguing restoration cases so that visitors can learn more about the work and skills of conservators as well as their mission to preserve Hong Kong’s heritage assets.

The Science Museum will launch a series of interactive family activities, including demonstrations and workshops conducted by Palace Museum conservators, guided tours featuring theatrical plays and storytelling, and visits to conservation laboratories.

Jointly presented by the Leisure & Cultural Services Department and the Palace Museum, the exhibition will run until March 18 next year.

Call 2732 3232 for enquiries.

The Immigration Department announced today that the operation of all nine Smart Identity Card Replacement Centres will be fully resumed on May 11 in light of the more stabilised epidemic situation.

The department earlier suspended the replacement of Hong Kong identity cards at the centres to avoid the increased risk of spreading COVID-19.

To arrange for people affected by the service suspension to replace their identity cards in an orderly manner, the Secretary for Security has made an amendment order to revise the replacement period for people born in 1957 to 1963 and 1970 to 1976 and the arrangement for members of the sixth term of District Councils.

Click here for the arrangements.

If the replacement of identity cards needs to be suspended again in the future to cope with a sudden turn of the epidemic situation, the amendment order also provides that if all the centres are not in service for a period of 21 working days or more from May 11 to July 27 for public health reasons, the specified period for the above people will be further extended or amended.

The amendment order will be tabled at the Legislative Council on May 13 for negative vetting.

To reduce crowd gatherings, applicants who have not made appointments previously should do so via the Internet, the department’s mobile application or the 24-hour hotline at 2121 1234.

The department also appealed to applicants to pre-fill the application form when making appointments through the Internet or mobile application.

For details click here or call 2824 6111.

(Georgia Institute of Technology) The science behind sticky gecko's feet lets gecko adhesion materials pick up about anything. But cost-effective mass production of the materials was out of reach until now. A new method of making them could usher the spread of gecko-inspired grabbers to assembly lines and homes.

Prevention of aberrant cutaneous wound repair and appropriate regeneration of an intact and functional integument require the coordinated timing of fibroblast and keratinocyte migration. Here, we identified a mechanism whereby opposing cell-specific motogenic functions of a multifunctional intracellular and extracellular protein, the receptor for hyaluronan-mediated motility (RHAMM), coordinates fibroblast and keratinocyte migration speed and ensures appropriate timing of excisional wound closure. We found that, unlike in WT mice, in Rhamm-null mice, keratinocyte migration initiates prematurely in the excisional wounds, resulting in wounds that have re-surfaced before the formation of normal granulation tissue, leading to a defective epidermal architecture. We also noted aberrant keratinocyte and fibroblast migration in the Rhamm-null mice, indicating that RHAMM suppresses keratinocyte motility but increases fibroblast motility. This cell context–dependent effect resulted from cell-specific regulation of extracellular signal-regulated kinase 1/2 (ERK1/2) activation and expression of a RHAMM target gene encoding matrix metalloprotease 9 (MMP-9). In fibroblasts, RHAMM promoted ERK1/2 activation and MMP-9 expression, whereas in keratinocytes, RHAMM suppressed these activities. In keratinocytes, loss of RHAMM function or expression promoted epidermal growth factor receptor–regulated MMP-9 expression via ERK1/2, which resulted in cleavage of the ectodomain of the RHAMM partner protein CD44 and thereby increased keratinocyte motility. These results identify RHAMM as a key factor that integrates the timing of wound repair by controlling cell migration.

Myostatin (or growth/differentiation factor 8 (GDF8)) is a member of the transforming growth factor β superfamily of growth factors and negatively regulates skeletal muscle growth. Its dysregulation is implicated in muscle wasting diseases. SRK-015 is a clinical-stage mAb that prevents extracellular proteolytic activation of pro- and latent myostatin. Here we used integrated structural and biochemical approaches to elucidate the molecular mechanism of antibody-mediated neutralization of pro-myostatin activation. The crystal structure of pro-myostatin in complex with 29H4-16 Fab, a high-affinity variant of SRK-015, at 2.79 Å resolution revealed that the antibody binds to a conformational epitope in the arm region of the prodomain distant from the proteolytic cleavage sites. This epitope is highly sequence-divergent, having only limited similarity to other closely related members of the transforming growth factor β superfamily. Hydrogen/deuterium exchange MS experiments indicated that antibody binding induces conformational changes in pro- and latent myostatin that span the arm region, the loops contiguous to the protease cleavage sites, and the latency-associated structural elements. Moreover, negative-stain EM with full-length antibodies disclosed a stable, ring-like antigen–antibody structure in which the two Fab arms of a single antibody occupy the two arm regions of the prodomain in the pro- and latent myostatin homodimers, suggesting a 1:1 (antibody:myostatin homodimer) binding stoichiometry. These results suggest that SRK-015 binding stabilizes the latent conformation and limits the accessibility of protease cleavage sites within the prodomain. These findings shed light on approaches that specifically block the extracellular activation of growth factors by targeting their precursor forms.

Inter-α-inhibitor is a proteoglycan essential for mammalian reproduction and also plays a less well-characterized role in inflammation. It comprises two homologous “heavy chains” (HC1 and HC2) covalently attached to chondroitin sulfate on the bikunin core protein. Before ovulation, HCs are transferred onto the polysaccharide hyaluronan (HA) to form covalent HC·HA complexes, thereby stabilizing an extracellular matrix around the oocyte required for fertilization. Additionally, such complexes form during inflammatory processes and mediate leukocyte adhesion in the synovial fluids of arthritis patients and protect against sepsis. Here using X-ray crystallography, we show that human HC1 has a structure similar to integrin β-chains, with a von Willebrand factor A domain containing a functional metal ion-dependent adhesion site (MIDAS) and an associated hybrid domain. A comparison of the WT protein and a variant with an impaired MIDAS (but otherwise structurally identical) by small-angle X-ray scattering and analytical ultracentrifugation revealed that HC1 self-associates in a cation-dependent manner, providing a mechanism for HC·HA cross-linking and matrix stabilization. Surprisingly, unlike integrins, HC1 interacted with RGD-containing ligands, such as fibronectin, vitronectin, and the latency-associated peptides of transforming growth factor β, in a MIDAS/cation-independent manner. However, HC1 utilizes its MIDAS motif to bind to and inhibit the cleavage of complement C3, and small-angle X-ray scattering–based modeling indicates that this occurs through the inhibition of the alternative pathway C3 convertase. These findings provide detailed structural and functional insights into HC1 as a regulator of innate immunity and further elucidate the role of HC·HA complexes in inflammation and ovulation.

β-Glucocerebrosidase (GBA) hydrolyzes glucosylceramide (GlcCer) to generate ceramide. Previously, we demonstrated that lysosomal GBA1 and nonlysosomal GBA2 possess not only GlcCer hydrolase activity, but also transglucosylation activity to transfer the glucose residue from GlcCer to cholesterol to form β-cholesterylglucoside (β-GlcChol) in vitro. β-GlcChol is a member of sterylglycosides present in diverse species. How GBA1 and GBA2 mediate β-GlcChol metabolism in the brain is unknown. Here, we purified and characterized sterylglycosides from rodent and fish brains. Although glucose is thought to be the sole carbohydrate component of sterylglycosides in vertebrates, structural analysis of rat brain sterylglycosides revealed the presence of galactosylated cholesterol (β-GalChol), in addition to β-GlcChol. Analyses of brain tissues from GBA2-deficient mice and GBA1- and/or GBA2-deficient Japanese rice fish (Oryzias latipes) revealed that GBA1 and GBA2 are responsible for β-GlcChol degradation and formation, respectively, and that both GBA1 and GBA2 are responsible for β-GalChol formation. Liquid chromatography–tandem MS revealed that β-GlcChol and β-GalChol are present throughout development from embryo to adult in the mouse brain. We found that β-GalChol expression depends on galactosylceramide (GalCer), and developmental onset of β-GalChol biosynthesis appeared to be during myelination. We also found that β-GlcChol and β-GalChol are secreted from neurons and glial cells in association with exosomes. In vitro enzyme assays confirmed that GBA1 and GBA2 have transgalactosylation activity to transfer the galactose residue from GalCer to cholesterol to form β-GalChol. This is the first report of the existence of β-GalChol in vertebrates and how β-GlcChol and β-GalChol are formed in the brain.

Cell-surface signaling (CSS) in Gram-negative bacteria involves highly conserved regulatory pathways that optimize gene expression by transducing extracellular environmental signals to the cytoplasm via inner-membrane sigma regulators. The molecular details of ferric siderophore-mediated activation of the iron import machinery through a sigma regulator are unclear. Here, we present the 1.56 Å resolution structure of the periplasmic complex of the C-terminal CSS domain (CCSSD) of PupR, the sigma regulator in the Pseudomonas capeferrum pseudobactin BN7/8 transport system, and the N-terminal signaling domain (NTSD) of PupB, an outer-membrane TonB-dependent transducer. The structure revealed that the CCSSD consists of two subdomains: a juxta-membrane subdomain, which has a novel all-β-fold, followed by a secretin/TonB, short N-terminal subdomain at the C terminus of the CCSSD, a previously unobserved topological arrangement of this domain. Using affinity pulldown assays, isothermal titration calorimetry, and thermal denaturation CD spectroscopy, we show that both subdomains are required for binding the NTSD with micromolar affinity and that NTSD binding improves CCSSD stability. Our findings prompt us to present a revised model of CSS wherein the CCSSD:NTSD complex forms prior to ferric-siderophore binding. Upon siderophore binding, conformational changes in the CCSSD enable regulated intramembrane proteolysis of the sigma regulator, ultimately resulting in transcriptional regulation.

The Mycobacterium tuberculosis virulence factor EsxA and its chaperone EsxB are secreted as a heterodimer (EsxA:B) and are crucial for mycobacterial escape from phagosomes and cytosolic translocation. Current findings support the idea that for EsxA to interact with host membranes, EsxA must dissociate from EsxB at low pH. However, the molecular mechanism by which the EsxA:B heterodimer separates is not clear. In the present study, using liposome-leakage and cytotoxicity assays, LC-MS/MS–based proteomics, and CCF-4 FRET analysis, we obtained evidence that the Nα-acetylation of the Thr-2 residue on EsxA, a post-translational modification that is present in mycobacteria but absent in Escherichia coli, is required for the EsxA:B separation. Substitutions at Thr-2 that precluded Nα-acetylation inhibited the heterodimer separation and hence prevented EsxA from interacting with the host membrane, resulting in attenuated mycobacterial cytosolic translocation and virulence. Molecular dynamics simulations revealed that at low pH, the Nα-acetylated Thr-2 makes direct and frequent “bind-and-release” contacts with EsxB, which generates a force that pulls EsxB away from EsxA. In summary, our findings provide evidence that the Nα-acetylation at Thr-2 of EsxA facilitates dissociation of the EsxA:B heterodimer required for EsxA membrane permeabilization and mycobacterial cytosolic translocation and virulence.

Lens proteins become increasingly cross-linked through nondisulfide linkages during aging and cataract formation. One mechanism that has been implicated in this cross-linking is glycation through formation of advanced glycation end products (AGEs). Here, we found an age-associated increase in stiffness in human lenses that was directly correlated with levels of protein–cross-linking AGEs. α-Crystallin in the lens binds to other proteins and prevents their denaturation and aggregation through its chaperone-like activity. Using a FRET-based assay, we examined the stability of the αA-crystallin–γD-crystallin complex for up to 12 days and observed that this complex is stable in PBS and upon incubation with human lens–epithelial cell lysate or lens homogenate. Addition of 2 mm ATP to the lysate or homogenate did not decrease the stability of the complex. We also generated complexes of human αA-crystallin or αB-crystallin with alcohol dehydrogenase or citrate synthase by applying thermal stress. Upon glycation under physiological conditions, the chaperone–client complexes underwent greater extents of cross-linking than did uncomplexed protein mixtures. LC-MS/MS analyses revealed that the levels of cross-linking AGEs were significantly higher in the glycated chaperone–client complexes than in glycated but uncomplexed protein mixtures. Mouse lenses subjected to thermal stress followed by glycation lost resilience more extensively than lenses subjected to thermal stress or glycation alone, and this loss was accompanied by higher protein cross-linking and higher cross-linking AGE levels. These results uncover a protein cross-linking mechanism in the lens and suggest that AGE-mediated cross-linking of α-crystallin–client complexes could contribute to lens aging and presbyopia.

The dextransucrase DSR-OK from the Gram-positive bacterium Oenococcus kitaharae DSM17330 produces a dextran of the highest molar mass reported to date (∼109 g/mol). In this study, we selected a recombinant form, DSR-OKΔ1, to identify molecular determinants involved in the sugar polymerization mechanism and that confer its ability to produce a very-high-molar-mass polymer. In domain V of DSR-OK, we identified seven putative sugar-binding pockets characteristic of glycoside hydrolase 70 (GH70) glucansucrases that are known to be involved in glucan binding. We investigated their role in polymer synthesis through several approaches, including monitoring of dextran synthesis, affinity assays, sugar binding pocket deletions, site-directed mutagenesis, and construction of chimeric enzymes. Substitution of only two stacking aromatic residues in two consecutive sugar-binding pockets (variant DSR-OKΔ1-Y1162A-F1228A) induced quasi-complete loss of very-high-molar-mass dextran synthesis, resulting in production of only 10–13 kg/mol polymers. Moreover, the double mutation completely switched the semiprocessive mode of DSR-OKΔ1 toward a distributive one, highlighting the strong influence of these pockets on enzyme processivity. Finally, the position of each pocket relative to the active site also appeared to be important for polymer elongation. We propose that sugar-binding pockets spatially closer to the catalytic domain play a major role in the control of processivity. A deep structural characterization, if possible with large-molar-mass sugar ligands, would allow confirming this hypothesis.

Bacterial biofilms are cellular communities that produce an adherent matrix. Exopolysaccharides are key structural components of this matrix and are required for the assembly and architecture of biofilms produced by a wide variety of microorganisms. The human bacterial pathogens Escherichia coli and Salmonella enterica produce a biofilm matrix composed primarily of the exopolysaccharide phosphoethanolamine (pEtN) cellulose. Once thought to be composed of only underivatized cellulose, the pEtN modification present in these matrices has been implicated in the overall architecture and integrity of the biofilm. However, an understanding of the mechanism underlying pEtN derivatization of the cellulose exopolysaccharide remains elusive. The bacterial cellulose synthase subunit G (BcsG) is a predicted inner membrane–localized metalloenzyme that has been proposed to catalyze the transfer of the pEtN group from membrane phospholipids to cellulose. Here we present evidence that the C-terminal domain of BcsG from E. coli (EcBcsGΔN) functions as a phosphoethanolamine transferase in vitro with substrate preference for cellulosic materials. Structural characterization of EcBcsGΔN revealed that it belongs to the alkaline phosphatase superfamily, contains a Zn2+ ion at its active center, and is structurally similar to characterized enzymes that confer colistin resistance in Gram-negative bacteria. Informed by our structural studies, we present a functional complementation experiment in E. coli AR3110, indicating that the activity of the BcsG C-terminal domain is essential for integrity of the pellicular biofilm. Furthermore, our results established a similar but distinct active-site architecture and catalytic mechanism shared between BcsG and the colistin resistance enzymes.

T-type (Cav3) Ca2+ channels are important regulators of excitability and rhythmic activity of excitable cells. Among other voltage-gated Ca2+ channels, Cav3 channels are uniquely sensitive to oxidation and zinc. Using recombinant protein expression in HEK293 cells, patch clamp electrophysiology, site-directed mutagenesis, and homology modeling, we report here that modulation of Cav3.2 by redox agents and zinc is mediated by a unique extracellular module containing a high-affinity metal-binding site formed by the extracellular IS1–IS2 and IS3–IS4 loops of domain I and a cluster of extracellular cysteines in the IS1–IS2 loop. Patch clamp recording of recombinant Cav3.2 currents revealed that two cysteine-modifying agents, sodium (2-sulfonatoethyl) methanethiosulfonate (MTSES) and N-ethylmaleimide, as well as a reactive oxygen species–producing neuropeptide, substance P (SP), inhibit Cav3.2 current to similar degrees and that this inhibition is reversed by a reducing agent and a zinc chelator. Pre-application of MTSES prevented further SP-mediated current inhibition. Substitution of the zinc-binding residue His191 in Cav3.2 reduced the channel's sensitivity to MTSES, and introduction of the corresponding histidine into Cav3.1 sensitized it to MTSES. Removal of extracellular cysteines from the IS1–IS2 loop of Cav3.2 reduced its sensitivity to MTSES and SP. We hypothesize that oxidative modification of IS1–IS2 loop cysteines induces allosteric changes in the zinc-binding site of Cav3.2 so that it becomes sensitive to ambient zinc.

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.

Kindlins are focal adhesion proteins that regulate integrin activation and outside-in signaling. The kindlin family consists of three members, kindlin-1, -2, and -3. Kindlin-2 is widely expressed in multiple cell types, except those from the hematopoietic lineage. A previous study has reported that the Drosophila Fit1 protein (an ortholog of kindlin-2) prevents abnormal spindle assembly; however, the mechanism remains unknown. Here, we show that kindlin-2 maintains spindle integrity in mitotic human cells. The human neuroblastoma SH-SY5Y cell line expresses only kindlin-2, and we found that when SH-SY5Y cells are depleted of kindlin-2, they exhibit pronounced spindle abnormalities and delayed mitosis. Of note, acetylation of α-tubulin, which maintains microtubule flexibility and stability, was diminished in the kindlin-2–depleted cells. Mechanistically, we found that kindlin-2 maintains α-tubulin acetylation by inhibiting the microtubule-associated deacetylase histone deacetylase 6 (HDAC6) via a signaling pathway involving AKT Ser/Thr kinase (AKT)/glycogen synthase kinase 3β (GSK3β) or paxillin. We also provide evidence that prolonged hypoxia down-regulates kindlin-2 expression, leading to spindle abnormalities not only in the SH-SY5Y cell line, but also cell lines derived from colon and breast tissues. The findings of our study highlight that kindlin-2 regulates mitotic spindle assembly and that this process is perturbed in cancer cells in a hypoxic environment.

Entrepreneur Ricky Chan’s information technology company has been hard at work developing a virtual reality application that enables designers and their clients to walk through different versions of their home or office without having to physically move a single piece of furniture.

From the colour of the walls to the style of fixtures and fittings, Mr Chan’s app caters to all personal tastes and design ideas.

“We have customers who are interior designers or furniture retailers. Our virtual reality application brings their sketches to life. Designers in the past needed weeks to produce sketches. Now they can make designs instantly,” he explained.

Up to 40% of the application was developed at Smart-Space 8 in Tsuen Wan, Cyberport’s first co-working space outside its main Pok Fu Lam campus.

“Cyberport provides funding that helps to lower our expenses and we can hold seminars here with a rental fee that is much lower than the market price,” Mr Chan added.
 

The 20,000 sq ft space launched last year was specifically designed with young entrepreneurs in mind and provides workshops and seminars for startups. For companies that wish to join the Smart-Space 8 community, one of its founders must be aged between 18 and 35 and the company itself should not have been in operation for longer than seven years.

Smart-Space 8 users are entitled to comprehensive entrepreneurial support and value-added services to accelerate their businesses such as the Cyberport Creative Micro Fund and Cyberport Incubation Programme.

Mr Chan, who lives in the New Territories, said the added bonus of setting up shop in Smart-Space 8 is the commute, as Cyberport in Pok Fu Lam is farther away for him and his clients.

Cyberport may be expanding beyond Pok Fu Lam, but some entrepreneurs like agriculture technology company CEO and founder Gordon Tam have opted to stay at the home campus because of the incentives available.

“The business network here is unique. There are so many startups and we encourage and learn from each other.”

Mr Tam’s company sells vegetables from an indoor farm to local supermarkets and is now exploring the overseas market. He credits the vibrant community and ecosystem at Cyberport for building up his business.

“Traditional agriculture comes with a host of problems and the efficiency of Hong Kong’s agriculture industry is relatively low. This is why we are looking into indoor agriculture. We want to grow plants in industrial buildings.”

When Mr Tam joined the Cyberport Incubation Programme, his firm was offered two years of rent reduction. But more importantly, he said, the space is a one-of-a-kind ecosystem where his team can brainstorm ideas and continue to innovate.

Other startup owners share the same sentiment. Information technology company CEO and founder Stark Chan noted that with Cyberport as a public body, it offers a lot of support and rents are more stable.

“We have been here since we first started up. My colleagues are familiar with this environment and the atmosphere is good for innovation,” Mr Chan said.

The ability to connect to a Google BigQuery database via OAuth is now available with this hot fix. Three new options have been added, REFRESH_TOKEN=, CLIENT_ID=, and CLIENT_SECRET=. You can use these options with 

The ability to connect to a Google BigQuery database via a proxy is available with this hot fix. You can use the newly added option, PROXY=, with the following methods of connection to the Google BigQuery database:

(King's College London) A study of female astronauts has assessed the risk of blood clots associated with spaceflight.The study, published in Aerospace Medicine and Human Performance, in collaboration with King's College London, the Centre for Space Medicine Baylor College of Medicine, NASA Johnson Space Centre and the International Space University, examines the potential risk factors for developing a blood clot (venous thromboembolism) in space.

(JAMA Network) This randomized clinical trial looked at the effect of a face-aging mobile app on daily sunscreen use and other skin protection among teens in Brazil. Selfies of students were altered to show UV effects on their future faces and shown to their class, accompanied by information about sun protection. Reducing UV exposure in children and adolescents is important because of the increased risk of skin cancer with cumulative UV exposure and sunburns early in life.

(American Association for the Advancement of Science) High-resolution images and video were taken by the Japanese space agency's Hayabusa2 spacecraft as it briefly landed to collect samples from Ryugu -- a nearby asteroid that orbits mostly between Earth and Mars -- allowing researchers to get an up-close look at its rocky surface, according to a new report.

(NASA/Goddard Space Flight Center) NASA has selected a new pathfinding CubeSat mission to gather data not collected since the agency flew the Dynamics Explorer in the early 1980s.

(University of York) An international team of scientists, led by researchers at the University of York, analysed the molecular remains of food left in pottery used by the first farmers who settled along the Atlantic Coast of Europe from 7,000 to 6,000 years ago.

(Max Planck Institute for the Science of Human History) What makes our species unique compared to other hominins? High profile genetic, fossil and material culture discoveries present scientists working in the Late Pleistocene with an ever-more complex picture of interactions between early hominin populations. One distinctive characteristic of Homo sapiens, however, appears to be its global distribution. Exploring how Homo sapiens colonized most of the world's continents in a relatively short period could reveal the exceptional capacities of humans relative to other hominins.

(Florida Museum of Natural History) More than a thousand years ago, people from across the Southeast regularly traveled to a small island on Florida's Gulf Coast to bond over oysters, likely as a means of coping with climate change and social upheaval.

(Perot Museum of Nature and Science) Published in PLOS ONE today, a study by an international team from the Perot Museum of Nature and Science in Dallas and Hokkaido University in Japan further explores the proliferation of the most commonly occurring duck-billed dinosaur of the ancient Arctic as the genus Edmontosaurus. The findings reinforce that the hadrosaurs -- dubbed 'caribou of the Cretaceous' -- had a geographical distribution of approximately 60 degrees of latitude, spanning the North American West from Alaska to Colorado.

(Alfred Wegener Institute, Helmholtz Centre for Polar and Marine Research) Thanks to the support of additional German research vessels, the MOSAiC expedition will continue, despite the coronavirus pandemic. The new team will start in May.

(American Association for the Advancement of Science) Ice sheet losses from Greenland and Antarctica have outpaced snow accumulation and contributed approximately 14 millimeters to sea level rise over 16 years (2003 to 2019), a new analysis of data from NASA's laser-shooting satellites has revealed.

(Oregon State University) The world's oceans play a critical role in climate regulation, mitigation and adaptation and should be integrated into comprehensive 'green new deal' proposals being promoted by elected officials and agency policymakers.

Chief Justice Patience Roggensack faced backlash for her comment, with some people calling it "elitist" to separate meatpackers from "regular folks."