Geralyn Spollett
Jan 1, 2003; 16:
Case Studies

The Government is set to revive the economy through different measures and everyone should act together to attain this goal.

Secretary for Financial Services & the Treasury Christopher Hui made the remarks today after attending a radio programme, saying the economy has been seriously affected by the epidemic.

“I think right now the immediate priority is definitely to revive the economy because after all, we have been subjected to many restrictions on all you can imagine in the past few months due to COVID-19.

“So the immediate priority is really for us to act together to revive the economy through different measures.

“And the measures that are subject to the Legislative Council’s approval as you have seen over the past few days, I think are definitely something that we want to do in order to provide a sort of foundation for our economic recovery.”

(To watch the whole media session with sign language interpretation, click here.)

Hong Kong's economy in the first quarter of 2020 contracted 8.9% over a year earlier, the largest decline on record since 1974.

The Census & Statistics Department announced the findings today as it released advance estimates on Gross Domestic Product for the first quarter.

Addressing the media today, Financial Secretary Paul Chan noted the economic recession deepened in Hong Kong in the first quarter of 2020.

“Although locally, the epidemic situation seems to be under control, but the external environment is still very challenging. Globally, the epidemic is yet to be put under complete control. That will affect our exports. That will also affect international travelling and business investments. 

“So, going forward in the second quarter, we believe that even if there is improvement, the improvement will be gradual and small.”

According to those estimates, private consumption expenditure decreased 10.2% in real terms in the first quarter from a year earlier, deteriorating from the 2.9% decline in the fourth quarter of 2019.

Government consumption expenditure grew 8.3% year-on-year, after the increase of 6.1% in the fourth quarter of 2019.

Gross domestic fixed capital formation dropped by 13.9%, compared with the decrease of 16.8% in the previous quarter.

Over the same period, total exports of goods declined 9.7% and imports of goods also fell 10.9%.

Exports of services dropped 37.8% and imports of services decreased 25.4%.

Mr Chan called on people to work together to promote economic development by consumption.

“If we are able to work together, if we can unite together - not just to fight the virus, but to stimulate consumption to promote economic development - I think the economic situation will be able to stabilise somewhat in the second quarter. 

“If the global epidemic situation improves, we will be able to come out of recession gradually towards the end of this year. 

“I will appeal to our people's support for us to roll out various measures in the Anti-epidemic Fund - round one and round two - as well as the relief packages in the 2020-21 Budget as soon as possible.

“Many of those initiatives are still yet to be implemented. Upon full implementation of those measures, I think the positive impact on the economy would be better felt by the community. We will be monitoring the situation carefully.”

The Government stands ready to roll out additional measures to support Hong Kong people and the businesses, Mr Chan added.

The Government has mechanisms to investigate complaints against civil servants impartially, Secretary for the Civil Service Patrick Nip said today.

Mr Nip made the remarks in response to media queries on recent allegations levelled against senior police officers.

He said: “There are established mechanisms to investigate every complaint in accordance with the procedures and rules. Depending on the circumstances and the case details, some are being handled by departments and bureaus. Some may be handled by the Civil Service Bureau.

“There are established mechanisms in dealing with that. Of course we would handle each and every complaint in a very serious and impartial manner.”

(To watch the full media session with sign language interpretation, click here.)

Chief Executive Carrie Lam today said the prevailing chairwoman of the Legislative Council House Committee should have the responsibility and power to deal with the matters of the committee.

Mrs Lam made the statement ahead of the Executive Council meeting this morning, noting LegCo President Andrew Leung had sought advice from outside senior counsel on how to address the delay in electing the committee’s chairman.

She said the senior counsels have observed that many of the matters raised in the House Committee’s meetings by the presiding member in the past six months have been irrelevant to the purpose of electing the committee’s chairman and vice-chairman.

“The second point that the senior counsels have observed during their very detailed scrutiny of the deliberations is that there was at least one occasion on March 13 in the House Committee meeting that gave people a very clear impression that the delaying of the election by the presiding member of the House Committee was quite deliberate and deliberate for political reasons.

“And the third thing that I observed from the senior counsels’ advice is, having regard to all these circumstances, they are of the firm view - this is the word taken from the senior counsels’ statement - that the prevailing chairwoman of the House Committee should have the responsibility and the power to deal with the business of the House Committee.”

The Chief Executive added that she expects the committee’s prevailing chairwoman Starry Lee to exercise her power.

Here are the tech companies that are planning to launch on the stock market this year

Here is some insight into the first ever blockchain advert

A group of technologists has led crowdsourcing efforts to create a single repository of information for specialists fighting the Coronavirus outbreak. Techworld speaks with founder Edward Saperia to hear more about how collaboration tools can help the efforts

The 'unicorn letter', sent by some of the best-funded private technology companies in the country, asks the chancellor to form an urgent taskforce to give them access to government-backed lending schemes during the pandemic

The Treasury has announced a new set of financial measures aimed at helping startups during the coronavirus pandemic, including a £250 Future Fund for startups with at least £250,000 in funding

The digital challenger bank is now the most switched to bank in the UK as Nationwide Building Society loses its long-held top spot

Companies with large numbers of furloughed workers are offering staff an introductory course in JavaScript coding, thanks to the European coding bootcamp, Codeworks.

The Housing Authority’s Commercial Properties Committee today approved the extension of rent concessions to over 8,300 non-domestic tenants or licensees for six months from April 1 to September 30.

The authority had earlier granted a 50% rent concession to its eligible retail and factory tenants for six months from April 1.

Under the extension, their rent concession will be increased to 75% over the same period with retrospective effect from April 1. The rent concession does not include rates and air-conditioning charges.

The authority said such further measures are to support the Government's new series of measures announced in early April to relieve the financial burden of individuals and businesses.

A total of 2,450 retail and 3,300 factory tenants will benefit from the approved increase in the rent concession.

The 75% rent concession will also be extended to cover tenants and licensees of bus kiosks and most advertising signboards, as well as car park users for the monthly parking of commercial vehicles.

About 40 tenancies for bus kiosks, 80 advertising signboards and about 2,500 car park users stand to benefit from the concession.

Tenants of premises in the authority's properties which are required to be closed under relevant regulations or the Government's directions, may also apply to the authority for a 100% rent concession for the period during which they are required to be closed.

The authority added that the approved measures will be implemented as soon as possible. For rent and licence fees already paid for the months of April and May, arrangements will be made for offsetting in the payment for subsequent months.

The committee has approved three rounds of rent concessions since last September. Together with this round, the total rent and licence fees foregone by the authority is estimated to reach more than $1 billion.

The Tour Service Coach Drivers (Mainly Serving Tourists) Support Scheme, under the second round of the Anti-epidemic Fund, is open for applications from today to June 5, the Government announced.

The scheme will provide each tour service coach driver with a one-off subsidy of $10,000 and aims to benefit about 9,300 drivers.

In addition, the Government explained that the second round of the Anti-epidemic Fund includes other tourism industry support measures. 

Applications for the Hotel Sector Support Scheme are being accepted until May 18, while the deadline to apply for the Travel Agents & Practitioners Support Scheme is June 15.

Click here for more details.

Chief Secretary Matthew Cheung today chaired the Anti-epidemic Fund Steering Committee's fifth meeting to examine the implementation progress of the host of measures launched under the fund.

The committee noted the details of over 20 second-round relief measures have been announced since the Legislative Council Finance Committee approved the $120.5 billion injection to the fund on April 18.

Other measures will be launched as soon as possible to provide timely relief to the affected sectors and individuals. 

The committee also noted that the fund has paid out over $13 billion, and many businesses and members of the public have gradually received subsidies.

Mr Cheung said the measures aim to preserve employment and assist the self-employed, provide additional relief to those sectors hard hit by the pandemic and pave the way for the post-pandemic economic recovery. 

“We will continue to process applications and disburse subsidies as soon as possible to help businesses and members of the public tackle the challenges caused by the pandemic and to support enterprises, safeguard jobs and relieve people’s burden," he stressed. 

For the Retail Sector Subsidy Scheme which provides a one-off subsidy of $80,000 to eligible retailers, about 93,000 applications were received.

The committee was pleased to note that the scheme has been disbursing subsidies progressively and over $2.7 billion in subsidies have been approved so far, involving about 33,000 applications.

The Development Bureau today briefed the Land & Development Advisory Committee on the major recommendations of the Planning & Urban Design Review for Developments at Kai Tak Runway Tip (KTRT).

Members noted the planning objectives, design principles and key study recommendations for the KTRT developments, including the existing and planned public open spaces as well as the Tourism Node site included in the 2020-21 Land Sale Programme.

They generally supported the recommendations of the KTRT study and provided comments on various aspects, such as ways to attract people to KTRT, the connectivity to and within the area, and promotion of healthy city and kid-friendly concepts.

The committee was also briefed on the proposed two-envelope tender arrangement, which refers to evaluation of both design and price proposals, for disposal of Site 3 of the New Central Harbourfront.

With a total area of 4.75 hectares, the site will comprise a commercial development in separate blocks mainly for office and retail, with a total gross floor area not exceeding 150,000 sq m, to be built alongside a spacious public open space of no less than 25,000 sq m to be opened round-the-clock.

There will be a continuous landscaped deck spanning across the site in a north-south direction, allowing visitors to walk all the way from the hinterland of the Central Business District to the harbourfront.

While noting that the two-envelope approach was rather unconventional for government land sale, members agreed that the approach would allow both quality and price considerations to be taken into account, and the setting of a reserve price would ensure reasonable protection to public revenue.

Below, Mac Hyman, Tulane University, talks about types of mathematical models--their strengths and weaknesses--the data that we currently have and what we really need, and what models can tell us about a possible second wave.

At the beginning of the video, he thanks the mathematics community for its work, and near the end says, "Our mathematical community is really playing a central role in helping to predict the spread, and help mitigate this epidemic, and prioritize our efforts. …Do not underestimate the power that mathematics can have in helping to mitigate this epidemic—-we have a role to play."

See the full set of videos on modeling COVID-19 and see media coverage of mathematics' role in modeling the pandemic.

updated April 1, 2020

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General Stations: 1 to 2 (Health Risk: Low)

Roadside Stations: 2 (Health Risk: Low)

(College of Engineering, Carnegie Mellon University) Carnegie Mellon University's Maarten de Boer and Gianluca Piazza are developing reliable, mechanical switches the size of a DNA molecule, thanks to a $2M LEAP-HI grant from the National Science Foundation.

(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.

(University of Illinois Grainger College of Engineering) Three Nick Holonyak Jr., Micro and Nanotechnology Lab (HMNTL) faculty members received NSF Rapid Response Research (RAPID) program grants, all of which aim to shorten the amount of time it takes to process a COVID-19 test with less false negatives. Current tests can take as long as five days for results to be.

(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.

(ICFO-The Institute of Photonic Sciences) ICFO researchers report on a new method to obtain high color purity 3D objects with the use of a new class of nanoparticles.

The Centre for Health Protection announced that as of 4pm today, no new COVID-19 cases have been recorded, leaving the number of confirmed cases in Hong Kong at 1,040 so far.

The centre again urged members of the public to maintain an appropriate social distance with other people in their daily lives to minimise the risk of infection.

People should go out less and avoid social activities such as having meals out or other gatherings to minimise the risk of coronavirus clusters emerging in the community.

As the COVID-19 situation remains severe and the number of cases reported around the world continues to rise, people are strongly urged to avoid all non-essential travel outside Hong Kong as well as maintain strict personal and environmental hygiene at all times.

Additionally, the Hospital Authority reported that there are currently 142 patients under isolation and that 920 patients have been discharged upon recovery.

For information and health advice on COVID-19, visit the Government's dedicated webpage.

The Centre for Health Protection announced that as of 4pm today, no new COVID-19 cases have been recorded, leaving the number of confirmed cases in Hong Kong at 1,040 so far.

The centre again urged members of the public to maintain an appropriate social distance with other people to minimise the risk of infection.

People should go out less and avoid social activities such as having meals out or other gatherings to minimise the risk of coronavirus clusters emerging in the community.

As the COVID-19 situation remains severe and the number of cases reported around the world continues to rise, people are strongly urged to avoid all non-essential travel outside Hong Kong as well as maintain strict personal and environmental hygiene at all times.

Additionally, the Hospital Authority reported that there are currently 127 patients under isolation and that 932 patients have been discharged upon recovery.

For information and health advice on COVID-19, visit the Government's dedicated webpage.

The Centre for Health Protection today announced it is investigating four additional confirmed COVID-19 cases.

The newly reported cases involve four males aged between 11 and 47. All of them travelled during the incubation period.

Epidemiological investigations and relevant contact tracing on the confirmed cases are ongoing.

The centre again urged the public to maintain an appropriate social distance from other people as much as possible to minimise the risk of infection.

People should go out less and avoid social activities such as having meals out or other gatherings to minimise the risk of outbreak clusters emerging in the community.

As the COVID-19 situation remains severe and the number of cases reported around the world continues to rise, people are strongly advised to avoid all non-essential travel outside Hong Kong as well as maintain strict personal and environmental hygiene at all times.

Additionally, the Hospital Authority reported that there are currently 120 patients under isolation and that 944 patients have been discharged upon recovery.

For information and health advice on COVID-19, visit the Government's dedicated webpage.

(To watch the full press briefing with sign language interpretation, click here.)

A recovered COVID-19 patient has tested positive for the virus again, the Hospital Authority announced today.

The authority’s Chief Manager (Quality & Standards) Dr Lau Ka-hin told a media briefing this afternoon that the patient was first admitted to Queen Mary Hospital on March 24 after having fever for a week. He subsequently tested positive for COVID-19.

He was discharged on April 16 after two consecutive negative tests for the virus.

Dr Lau said: "The patient presented to the Accident & Emergency Department of Queen Mary Hospital on May 5 because of some abdominal pain and diarrhoea.

"He was admitted to our hospital and was found to have a positive result for COVID-19 in the throat saliva, but the cycle threshold value is very high - nearly 36.

"The experts consider that this is the residual virus left in the patient’s body, which is not infective, and it is not likely to be a reinfection at this moment."

He added that the patient is in a stable condition.

The Centre for Health Protection announced that as of 4pm today, no new COVID-19 cases have been recorded, leaving the number of confirmed cases in Hong Kong at 1,044 so far.

The centre again urged members of the public to maintain an appropriate social distance with other people to minimise the risk of infection.

It said people should go out less and avoid social activities such as having meals out or other gatherings to minimise the risk of coronavirus clusters emerging in the community.

As the COVID-19 situation remains severe and the number of cases reported around the world continues to rise, people are strongly urged to avoid all non-essential travel outside Hong Kong as well as maintain strict personal and environmental hygiene.

Additionally, the Hospital Authority reported that there are currently 109 patients under isolation and that 960 patients have been discharged upon recovery.

For information and health advice on COVID-19, visit the Government's dedicated webpage.

The Centre for Health Protection announced that as of 4pm today, no new COVID-19 cases have been recorded, leaving the number of confirmed cases in Hong Kong at 1,044 so far.

The centre again urged the public to maintain an appropriate social distance with other people to minimise the risk of infection.

It said people should go out less and avoid social activities such as having meals out or other gatherings to minimise the risk of coronavirus clusters emerging in the community.

As the COVID-19 situation remains severe and the number of cases reported around the world continues to rise, people are strongly urged to avoid all non-essential travel outside Hong Kong as well as maintain strict personal and environmental hygiene.

Additionally, the Hospital Authority reported that there are currently 90 patients under isolation and that 967 patients have been discharged upon recovery.

For information and health advice on COVID-19, visit the Government's dedicated webpage.

Congratulations to the 2020 AMS Math Poetry Contest Winners in the middle school, high school, and college categories: Sabrina Little, Mackintosh Academy, Boulder, for "Outlier;" Austen Mazenko, Cherry Creek High School, for "The Number Won; and Chenyu Lin, Colorado Christian University, for "x² + y² = 1(ife)." The poems were read during Mathemati-Con at the 2020 Joint Mathematics Meetings in Denver, CO. Read the poems and learn about the contest and Math and Poetry. (Photo: (left to right) Austen Mazenko, Sabrina Little, poetry contest judge Gizem Karaali, and Chenyu Lin.

VOLUME 285 (2010) PAGES 13742–13747In Fig. 1E, passage 10, the splicing of a non-adjacent lane from the same immunoblot was not marked. This error has now been corrected and does not affect the results or conclusions of this work.jbc;295/16/5533/F1F1F1Figure 1E.

Extracytoplasmic sugar decoration of glycopolymer components of the bacterial cell wall contributes to their structural diversity. Typically, the molecular mechanism that underpins such a decoration process involves a three-component glycosylation system (TGS) represented by an undecaprenyl-phosphate (Und-P) sugar-activating glycosyltransferase (Und-P GT), a flippase, and a polytopic glycosyltransferase (PolM GT) dedicated to attaching sugar residues to a specific glycopolymer. Here, using bioinformatic analyses, CRISPR-assisted recombineering, structural analysis of cell wall–associated polysaccharides (CWPS) through MALDI-TOF MS and methylation analysis, we report on three such systems in the bacterium Lactococcus lactis. On the basis of sequence similarities, we first identified three gene pairs, csdAB, csdCD, and csdEF, each encoding an Und-P GT and a PolM GT, as potential TGS component candidates. Our experimental results show that csdAB and csdCD are involved in Glc side-chain addition on the CWPS components rhamnan and polysaccharide pellicle (PSP), respectively, whereas csdEF plays a role in galactosylation of lipoteichoic acid (LTA). We also identified a potential flippase encoded in the L. lactis genome (llnz_02975, cflA) and confirmed that it participates in the glycosylation of the three cell wall glycopolymers rhamnan, PSP, and LTA, thus indicating that its function is shared by the three TGSs. Finally, we observed that glucosylation of both rhamnan and PSP can increase resistance to bacteriophage predation and that LTA galactosylation alters L. lactis resistance to bacteriocin.

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

Telomeres are specific nucleoprotein structures that are located at the ends of linear eukaryotic chromosomes and play crucial roles in genomic stability. Telomere DNA consists of simple repeats of a short G-rich sequence: TTAGGG in mammals and TTTAGGG in most plants. In recent years, the mammalian telomeric G-rich repeats have been shown to form G-quadruplex (G4) structures, which are crucial for modulating telomere functions. Surprisingly, even though plant telomeres are essential for plant growth, development, and environmental adaptions, only few reports exist on plant telomeric G4 DNA (pTG4). Here, using bulk and single-molecule assays, including CD spectroscopy, and single-molecule FRET approaches, we comprehensively characterized the structure and dynamics of a typical plant telomeric sequence, d[GGG(TTTAGGG)3]. We found that this sequence can fold into mixed G4s in potassium, including parallel and antiparallel structures. We also directly detected intermediate dynamic transitions, including G-hairpin, parallel G-triplex, and antiparallel G-triplex structures. Moreover, we observed that pTG4 is unfolded by the AtRecQ2 helicase but not by AtRecQ3. The results of our work shed light on our understanding about the existence, topological structures, stability, intermediates, unwinding, and functions of pTG4.

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.

Hypersecretion of glucagon from pancreatic α-cells strongly contributes to diabetic hyperglycemia. Moreover, failure of α-cells to increase glucagon secretion in response to falling blood glucose concentrations compromises the defense against hypoglycemia, a common complication in diabetes therapy. However, the mechanisms underlying glucose regulation of glucagon secretion are poorly understood and likely involve both α-cell–intrinsic and intraislet paracrine signaling. Among paracrine factors, glucose-stimulated release of the GABA metabolite γ-hydroxybutyric acid (GHB) from pancreatic β-cells might mediate glucose suppression of glucagon release via GHB receptors on α-cells. However, the direct effects of GHB on α-cell signaling and glucagon release have not been investigated. Here, we found that GHB (4–10 μm) lacked effects on the cytoplasmic concentrations of the secretion-regulating messengers Ca2+ and cAMP in mouse α-cells. Glucagon secretion from perifused mouse islets was also unaffected by GHB at both 1 and 7 mm glucose. The GHB receptor agonist 3-chloropropanoic acid and the antagonist NCS-382 had no effects on glucagon secretion and did not affect stimulation of secretion induced by a drop in glucose from 7 to 1 mm. Inhibition of endogenous GHB formation with the GABA transaminase inhibitor vigabatrin also failed to influence glucagon secretion at 1 mm glucose and did not prevent the suppressive effect of 7 mm glucose. In human islets, GHB tended to stimulate glucagon secretion at 1 mm glucose, an effect mimicked by 3-chloropropanoic acid. We conclude that GHB does not mediate the inhibitory effect of glucose on glucagon secretion.

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.

The actin cytoskeleton is extremely dynamic and supports diverse cellular functions in many physiological and pathological processes, including tumorigenesis. However, the mechanisms that regulate the actin-related protein 2/3 (ARP2/3) complex and thereby promote actin polymerization and organization in cancer cells are not well-understood. We previously implicated the proline-rich 11 (PRR11) protein in lung cancer development. In this study, using immunofluorescence staining, actin polymerization assays, and siRNA-mediated gene silencing, we uncovered that cytoplasmic PRR11 is involved in F-actin polymerization and organization. We found that dysregulation of PRR11 expression results in F-actin rearrangement and nuclear instability in non-small cell lung cancer cells. Results from molecular mechanistic experiments indicated that PRR11 associates with and recruits the ARP2/3 complex, facilitates F-actin polymerization, and thereby disrupts the F-actin cytoskeleton, leading to abnormal nuclear lamina assembly and chromatin reorganization. Inhibition of the ARP2/3 complex activity abolished irregular F-actin polymerization, lamina assembly, and chromatin reorganization due to PRR11 overexpression. Notably, experiments with truncated PRR11 variants revealed that PRR11 regulates F-actin through different regions. We found that deletion of either the N or C terminus of PRR11 abrogates its effects on F-actin polymerization and nuclear instability and that deletion of amino acid residues 100–184 or 100–200 strongly induces an F-actin structure called the actin comet tail, not observed with WT PRR11. Our findings indicate that cytoplasmic PRR11 plays an essential role in regulating F-actin assembly and nuclear stability by recruiting the ARP2/3 complex in human non-small cell lung carcinoma cells.

The canonical pathway of eicosanoid production in most mammalian cells is initiated by phospholipase A2-mediated release of arachidonic acid, followed by its enzymatic oxidation resulting in a vast array of eicosanoid products. However, recent work has demonstrated that the major phospholipase in mitochondria, iPLA2γ (patatin-like phospholipase domain containing 8 (PNPLA8)), possesses sn-1 specificity, with polyunsaturated fatty acids at the sn-2 position generating polyunsaturated sn-2-acyl lysophospholipids. Through strategic chemical derivatization, chiral chromatographic separation, and multistage tandem MS, here we first demonstrate that human platelet-type 12-lipoxygenase (12-LOX) can directly catalyze the regioselective and stereospecific oxidation of 2-arachidonoyl-lysophosphatidylcholine (2-AA-LPC) and 2-arachidonoyl-lysophosphatidylethanolamine (2-AA-LPE). Next, we identified these two eicosanoid-lysophospholipids in murine myocardium and in isolated platelets. Moreover, we observed robust increases in 2-AA-LPC, 2-AA-LPE, and their downstream 12-LOX oxidation products, 12(S)-HETE-LPC and 12(S)-HETE-LPE, in calcium ionophore (A23187)-stimulated murine platelets. Mechanistically, genetic ablation of iPLA2γ markedly decreased the calcium-stimulated production of 2-AA-LPC, 2-AA-LPE, and 12-HETE-lysophospholipids in mouse platelets. Importantly, a potent and selective 12-LOX inhibitor, ML355, significantly inhibited the production of 12-HETE-LPC and 12-HETE-LPE in activated platelets. Furthermore, we found that aging is accompanied by significant changes in 12-HETE-LPC in murine serum that were also markedly attenuated by iPLA2γ genetic ablation. Collectively, these results identify previously unknown iPLA2γ-initiated signaling pathways mediated by direct 12-LOX oxidation of 2-AA-LPC and 2-AA-LPE. This oxidation generates previously unrecognized eicosanoid-lysophospholipids that may serve as biomarkers for age-related diseases and could potentially be used as targets in therapeutic interventions.