Many startups in Britain either do not intend to or cannot access the government's Coronavirus Business Interruption and Loan Scheme, and may be forced to respond with furloughs or layoffs, warns a report

A lone developer from the company that provided aerodynamic analysis for the cars in the PlayStation game Gran Turismo has applied the tooling to demonstrate the spread of germs with and without wearing a mask

While coordinated action is urgently needed, should we be racing to download everything that promises a solution?

The London-headquartered fintech startup Soldo has repurposed its spend management tools for local authorities in Italy to support its COVID-19 emergency response measures

dlberek posted a photo:

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

S. Waleed Noor and Osmar R. Severiano
Proc. Amer. Math. Soc. 148 (2020), 2469-2476.
Abstract, references and article information

Police today announced its decision to prohibit two public meetings and object to a public procession intended to be held on Hong Kong Island on May 1.

Upon risk assessment, Police said it regarded that the public meetings and procession are high-risk activities with crowd gatherings.

Police have grounds to believe that such activities do not only increase the risk of infecting participants and other people with COVID-19, but pose a serious threat to the lives and health of all citizens, jeopardising public safety and affecting the rights of others.

Police emphasised that it believed it is necessary to prohibit the public meetings and object to the public procession in accordance with the Public Order Ordinance for maintaining public order and public safety as well as protecting the rights and freedom of others.

Police reminded the public that taking part in an unauthorised assembly is a criminal offence and those found guilty could be liable to five years’ imprisonment.

During the third month of our fight against COVID-19, Hong Kong has experienced daunting challenges posed by the epidemic with no room to let down our guard.  Though we are a bit relieved to see a significant drop in the number of confirmed cases recently, the Government needs to remain alert given the volatility of the epidemic.

Developments of the epidemic

In the past month, the epidemic continued to spread rapidly in many countries around the world. The number of confirmed cases increased from 400,000 a month ago to 2.6 million today, an increase of some 600%, with over 180,000 deaths.  Many governments had little choice but to take extreme measures such as a city lockdown. During the same period, the overseas epidemic situation resulted in a large number of Hong Kong residents abroad, including students studying in the United States and Europe, particularly in the United Kingdom, to return to Hong Kong. Due to the large number of imported cases, Hong Kong’s epidemic situation, which had remained stable for a period up to mid-March, started to become severe and reached its peak at the end of March. On March 27, 28 and 29, Hong Kong recorded 65, 64 and 59 confirmed cases respectively on a single day. We were then extremely worried because if 60 new cases have to be admitted to hospital and placed in isolation each day (according to Hospital Authority statistics every confirmed case stays in hospital for 15 to 20 days on average) and if this number of new confirmed cases continued for one month then the Hospital Authority’s 1,200 or so isolation beds would be fully occupied and our hospital system would face unimaginable pressure.

Although deeply anxious, we did not lose our composure but continued to respond promptly to the developments of the epidemic taking account of expert advice. We bit the bullet and resolutely took stringent measures in response to the situation. The number of confirmed cases has dropped from the peak at end-March to single digits since April 12, with the great majority of cases being imported or their close contacts (See Graphic 1). This shows we have prevented local transmission and that Hong Kong, once again, has overcome the challenge.

Anti-epidemic efforts

Since the Government implemented stringent border control measures before end-March, including denying the entry to Hong Kong by plane of all non-Hong Kong residents arriving from overseas countries or regions from March 25, the anti-epidemic measures introduced over the past month focused on enhancing virus testing for inbound travellers and restricting social interactions to prevent the spread of the disease. However, we have not prohibited people from going out as many overseas countries have done. Most restaurants and shops have remained open.  People by and large can maintain their daily life.

Major measures implemented by the Government to respond to the developments of the epidemic in the past month are set out in the following table:  

Date

Event

March 25-26

Four chartered flights were sent over two days to bring back to Hong Kong the second batch of 558 Hong Kong residents stranded in Hubei Province.

March 25-26

The Centre for Health Protection (CHP) extended the Enhanced Laboratory Surveillance Programme and set up a temporary specimen collection centre at AsiaWorld-Expo to provide virus testing for asymptomatic inbound travellers arriving from the UK and other countries in Europe as well as the US.

March 27

The Government announced that catering premises must comply with six disease control requirements and six types of premises (ie amusement game centres, bathhouses, fitness centres, places of amusement, places of public entertainment and premises for hire for holding social gatherings) must close from 6pm on March 28; and gatherings of more than four people in a public place would be prohibited from midnight on March 29.  At the same time, the Chief Executive announced the preparation of the second round of the Anti-epidemic Fund to provide further assistance to individuals and businesses.

April 1-2

The Government announced that karaoke establishments, mahjong-tin kau establishments and nightclubs must be closed and beauty parlours, clubhouses and massage establishments must step up epidemic control measures from 6pm on April 1; and bars must close from 6pm on April 3.

April 5

Sixty-five Hong Kong residents who took the chartered flights arranged by the Hong Kong Special Administrative Region Government arrived in Hong Kong from Peru. Upon arrival, they were taken to the temporary specimen collection centre at AsiaWorld-Expo to undergo virus testing and were admitted to hospital or put under home quarantine subject to the test results.

April 8

The Government announced the closure of beauty parlours and massage establishments from midnight on April 10, and the extension of measures regulating catering businesses and scheduled premises as well as prohibiting group gatherings until April 23.

April 8

The Chief Executive announced the second round of the Anti-epidemic Fund and other related measures involving over $130 billion, including an $80 billion Employment Support Scheme. The Legislative Council Finance Committee approved the funding on April 18.

April 8

The Department of Health (DH) mandated all asymptomatic inbound travellers arriving at the Hong Kong International Airport to proceed to the temporary specimen collection centre to collect deep throat saliva samples according to instructions before undergoing compulsory quarantine at their place of accommodation. Besides, specimen collection containers will be provided to inbound travellers arriving via land boundary control points who have been to Hubei Province in the past 14 days.

April 9

The DH required all asymptomatic inbound travellers arriving on flights from the UK to stay and wait for the test results at the temporary specimen collection centre, and they can continue their quarantine at their place of accommodation only if the test result is negative. The arrangement was extended to asymptomatic inbound travellers arriving on flights from the US and other areas in Europe from April 13.

April 10

Twenty-seven Hong Kong residents who left Morocco on a chartered flight arranged by the Chinese Embassy in the Kingdom of Morocco arrived in Guangzhou. Apart from one Hong Kong resident who chose to stay in Guangzhou, all others returned to Hong Kong by prearranged coaches and were taken to AsiaWorld-Expo to undergo virus testing.

April 11

To ensure adequate quarantine facilities to cope with the development of the epidemic, the CHP will, where necessary, arrange for people under compulsory quarantine to stay at quarantine centres for the first 10 days and then continue quarantine at home for the remaining four days after virus testing.

April 19

The DH required all asymptomatic inbound travellers arriving on flights landing in the morning to stay and wait for the test results at the temporary specimen collection centre. They can continue quarantine at their place of accommodation only if the test result is negative.

April 19

With a declining number of inbound travellers, the Hospital Authority suspended the operation of the test centre at AsiaWorld-Expo from noon. Inbound travellers with symptoms will be admitted to public hospitals to undergo testing.

April 20

The DH started a trial to provide an extra specimen collection container to inbound travellers arriving at the Hong Kong International Airport for the submission of samples for another round of virus testing (on the 12th day) before the completion of home quarantine. The quarantine can be completed only if the test result is negative.

April 21

The Government announced the extension of all statutory measures to enhance social distancing for 14 days until May 7.

April 22

The DH required all asymptomatic inbound travellers arriving on flights landing in the afternoon or at night to stay and wait for virus test results at the holding centre in the Regal Oriental Hotel. They can continue quarantine at their place of accommodation only if the test result is negative. Upon implementation of the measure, all inbound travellers arriving at Hong Kong International Airport will be required to undergo testing and can return to the community only if the test result is negative.

The decision to extend various enhanced social distancing measures to early May is no doubt a further blow to the affected business sectors. The Government fully understands the disappointment and frustration of these sectors, but we dare not let down our guard as we look at the second or third wave of outbreaks around the world. In addressing the public health crisis, the Government also needs to consider the impact of the measures on the economy, livelihood and the daily lives of people.  I recall that Prof Gabriel Leung, one of the experts for the Government’s anti-epidemic work, once described the difficulty of the Government in making its decisions as a three-way tug of war (See Graphic 2).

We will continue to listen to the views of the experts and various sectors and constantly adjust the suppress and lift strategy according to the actual situation of the epidemic. The target is to achieve the optimal level of controls at all times.

Supporting individuals and businesses affected by the disease

The epidemic has lasted for more than three months and presents unprecedented challenges to our economy. Many businesses are facing pressure to close down or resort to massive staff layoffs, and many families and members of the public are facing severe hardship. According to the latest labour force statistics released by the Census & Statistics Department, the seasonally adjusted unemployment rate for January to March 2020 increased worryingly to 4.2%, the highest level in over nine years.

The Government will continue to make an all-out effort to keep our workers employed, relieve the financial burden of businesses and members of the public, and pave the way for post-epidemic economic recovery. The two rounds of the Anti-epidemic Fund and related relief measures, together with the relief package in the 2020-21 Budget announced by the Financial Secretary earlier on (yet to be approved by the LegCo), amount to $287.5 billion, representing 10% of gross domestic product. These measures are being implemented progressively to help businesses and members of the public tide over the difficult times.

Fighting the virus together

The hard-earned results of our anti-epidemic work over the past month are due to the togetherness of the community at large, the unswerving commitment of our healthcare professionals, the collaborative efforts of various government departments and the understanding of all sectors in society. I am confident that Hong Kong will come through the epidemic and the economic downturn. As long as we can hold on for some more time, we will soon see a bright tomorrow.

Chief Executive Carrie Lam issued this article entitled Three Months into Our Fight Seeing the Arrival of Dawn on April 25.

The confidence level of Hong Kong’s exporters has fallen to its lowest-ever level in the face of a triple challenge – the COVID-19 outbreak, softening global demand and lingering trade tension between the United States and Mainland...

Two short films have made it one step closer to an Oscar nomination after picking up a Light in Motion (LIM) award at the Foyle Film Festival’s closing ceremony in Brunswick Moviebowl.

The Buildings Department approved 13 building plans in February - four on Hong Kong Island, one in Kowloon and eight in the New Territories.

Of the approved plans, nine were for apartment and apartment-commercial developments, one was for commercial development, one was for factory and industrial developments, and two were for community services developments.

Consent was given for works to start on two building projects, which will provide 77,942 sq m of gross floor area for non-domestic use.

The department also issued 14 occupation permits - four on Hong Kong Island, one in Kowloon and nine in the New Territories.

Buildings certified for occupation have 149,306 sq m of gross floor area for domestic use involving 2,912 units, and 67,594 sq m for non-domestic use.

The declared cost of new buildings completed in the month was $3.7 billion.

At 1 a.m. at the Hong Kong Observatory :
Air temperature : 29 degrees Celsius
Relative Humidity : 82 per cent

To reduce social contact in light of the COVID-19 epidemic, the Primary One Central Allocation results will be posted to parents.

Announcing the move today, the Education Bureau said it will deliver door-to-door the Primary One Registration Form with Central Allocation results to parents from June 3 to 4 through Hongkong Post’s Local CourierPost service.

If no one is present to receive the item at the time of delivery, a mail collection notification card will be left for parents to collect it from the designated post office from the afternoon of the following working day.

If parents have not received the Primary One Registration Form or the notification card by June 5, they can collect the registration form at the designated Collection Centre from June 6 to 7.

The Education Bureau will send letters to parents tomorrow to notify them of the arrangements.

Parents can get updates on the latest arrangements for the release of Central Allocation results and registration through the bureau’s press releases and messages posted on its website.

Call 2891 0088 for information on Primary One admission. For further enquiries, contact the bureau's School Places Allocation Section (Primary One Admission) on 2832 7700 or 2832 7740.

Sarah S. Farabi
Feb 1, 2016; 29:10-13
From Research to Practice

Ruban Dhaliwal
Feb 1, 2014; 27:9-20
Research to Practice

Mays H. Vue
Aug 1, 2011; 24:171-177
Pharmacy and Therapeutics

Pasquale Passarella
Aug 1, 2018; 31:218-224
From Research to Practice

Deborah Hinnen
Aug 1, 2017; 30:202-210
Feature Articles

(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 winners were revealed at a glitzy party in Shoreditch on 22 February

Education secretary, Damian Hinds, wants schools across the UK to “take advantage of all of the opportunities available through Edtech” in the government's new strategy

The UK-based digital identity specialist managed to raise a bumper round during the peak of the COVID-19 pandemic, and is looking at ways to apply its technology to help combat the global crisis

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

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

In response to current challenges that colleges and universities face as a result of the spread of COVID-19, the American Mathematical Society is offering libraries and institutions additional support, in line with recommendations in the ICOLC Statement on the Global COVID-19 Pandemic and Its Impact on Library Services and Resources.

The AMS is also participating in the Copyright Clearance Center Education Continuity License program, providing access to our content for distance learning and other educational uses at no cost to the user.

We are extending grace access for content hosted on our platforms (including MathSciNet) through the end of May for our existing customers. We will re-evaluate this timing as needed.

As courses transition to online, we can provide instructors with complimentary electronic “reserve” copies of our textbooks for cases in which students do not have access to their print copies.

E-books purchased through the perpetual access model on the AMS platform are always available DRM-free with unlimited simultaneous use. In addition, we are partnering with ProQuest to allow multi-user access through mid-June to all e-books purchased on their platforms. Read ProQuest’s statement.

We are providing remote access to all our content, including MathSciNet. In normal circumstances, this remote access can be set up while on campus or while connected via institution VPN (in order to validate IP-based access). We realize many students, faculty, and researchers did not have an opportunity to initiate this access before leaving campus, so we have given instructions to our library partners on how patrons can connect to our content. Please contact your librarian for assistance.

Libraries: if you have not received instructions to share with your patrons, please email us at cust-serv@ams.org or be in touch about any other of your library’s needs.

Review all AMS Resources & Updates.

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

Roadside Stations: 2 (Health Risk: Low)

(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.

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 Innovation & Technology Bureau announced that as of 3pm today, the CuMask online registration system had received over 500,000 registrations, covering close to 1.38 million registrants in total. 

The bureau also responded to reports concerning the purpose of information collection and security of the registration system.

It noted that information provided by citizens in obtaining the masks will not be used for other purposes and that the Government will ensure the retention period of the personal data is no longer than the time required for the purposes for which the data is used.

The bureau pointed out that the registration system for masks operates on the Government's private cloud to ensure the stability and security of the system. 

In order to prevent intrusion and data leakage, multiple security measures have been put in place in compliance with the Government Information Technology Security Policy & Guidelines. 

These measures include a firewall, intrusion detection, anti-bot technology and installation of the latest anti-virus software with regular updates of virus definitions. 

The service has also passed an information security risk assessment and audit before launch.

The Privacy Commissioner for Personal Data has been consulted on the system's personal data processing arrangements. 

The system has also passed an independent third-party privacy impact assessment to ensure that the relevant service and system comply with the Personal Data (Privacy) Ordinance.

The bureau further explained that citizens need to provide their Hong Kong identity card number and date of birth for the registration system to match data with the Immigration Department’s system.

The process will be used to ascertain whether the registrant is a Hong Kong resident and check against any duplicated registrations. 

The local mobile number serves as a way to receive SMS messages on registration results and delivery, while the name and local address of the main registrant serves to verify whether the address exists and for arranging delivery. 

The bureau emphasised that the purposes of information collection have been clearly displayed on the front of the registration page for citizens to browse before registration.

Meanwhile, the bureau clarified the online rumours regarding the manufacturer of CuMask, noting that the CuMask is not manufactured by the Sun Hing Knitting Factory Limited nor Nan Fung Group.

The procurement of raw materials, coordination of production, sterilisation and packaging of the CuMask are being handled by the Hong Kong Research Institute of Textiles & Apparel, it said.

The bureau expressed regret about the rumours.

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.

More than 8,200 applications for the Anti-epidemic Support Scheme for Property Management Sector (ASPM) have been received, with over 3,850 approved, the Government announced today.

The approved applications involve subsidies of more than $140 million and will benefit around 22,000 building blocks and about 35,750 frontline property management workers.

Launched under the Anti-epidemic Fund, the ASPM provides subsidies to owners' organisations or property management companies of eligible buildings to provide hardship allowance to frontline property management workers.

It also provides the Anti-epidemic Cleansing Subsidy to owners' organisations or property management companies.

The scheme’s first phase covers private residential and composite buildings, while its second phase covers industrial and commercial buildings.

The ASPM is still open for applications and continues to disburse subsidies.

Contact the Property Management Services Authority at 3696 1156 or 3696 1166, or visit its website for details.

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.

IntroductionThe nucleolus is the central organelle within eukaryotic cells whose primary function is to generate ribosomes, the major protein producing machines within all cells. New roles for the nucleolus are continuously emerging as we explore its molecular intricacies. Despite the central and fundamental role of the nucleolus in cell biology, there has previously been no single official meeting that enables the gathering of scientists whose research converges on the nucleolus. As a result, the community of researchers who study this organelle risks fragmentation across disciplines. The Emerging Roles for the Nucleolus Symposium, which has now taken place twice on a biennial basis, first in 2017 (1) and again in 2019, therefore, represents the first of its kind. The overarching goals of this symposium are (a) to convene researchers who study the nucleolus across model systems (yeast, nematodes, fruit flies, mouse, human cell lines) and biological perspectives (structural, biophysical, molecular, cellular, pathophysiology), (b) to share and disseminate the latest research breakthroughs in nucleolar biology, (c) to promote interaction, engagement, and collaboration centered on the nucleolus across disciplines, and (d) to provide trainees and early career investigators with an organelle-specific scientific community of support.The second Emerging Roles for the Nucleolus meeting was sponsored by the American Society for Biochemistry and Molecular Biology and was held at the Stowers Institute for Medical Research in Kansas City, MO, from October 24 to October 27, 2019. It was organized by Jennifer Gerton (Stowers Institute), Francesca Duncan (Northwestern University Feinberg School of Medicine), and Craig Pikaard...

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.

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.

Lethal infections by strains of the highly-pathogenic avian influenza virus (HPAIV) H5N1 pose serious threats to both the poultry industry and public health worldwide. A lack of confirmed HPAIV epitopes recognized by cytotoxic T lymphocytes (CTLs) has hindered the utilization of CD8+ T-cell–mediated immunity and has precluded the development of effectively diversified epitope-based vaccination approaches. In particular, an HPAIV H5N1 CTL-recognized epitope based on the peptide MHC-I–β2m (pMHC-I) complex has not yet been designed. Here, screening a collection of selected peptides of several HPAIV strains against a specific pathogen-free pMHC-I (pBF2*1501), we identified a highly-conserved HPAIV H5N1 CTL epitope, named HPAIV–PA123–130. We determined the structure of the BF2*1501–PA123–130 complex at 2.1 Å resolution to elucidate the molecular mechanisms of a preferential presentation of the highly-conserved PA123–130 epitope in the chicken B15 lineage. Conformational characteristics of the PA123–130 epitope with a protruding Tyr-7 residue indicated that this epitope has great potential to be recognized by specific TCRs. Moreover, significantly increased numbers of CD8+ T cells specific for the HPAIV–PA123–130 epitope in peptide-immunized chickens indicated that a repertoire of CD8+ T cells can specifically respond to this epitope. We anticipate that the identification and structural characterization of the PA123–130 epitope reported here could enable further studies of CTL immunity against HPAIV H5N1. Such studies may aid in the development of vaccine development strategies using well-conserved internal viral antigens in chickens.