Wolfgang Dahmen, Felix Gruber and Olga Mula
Math. Comp. 89 (2020), 1605-1646.
Abstract, references and article information

Ricardo G. Durán, Enrique Otárola and Abner J. Salgado
Math. Comp. 89 (2020), 1581-1603.
Abstract, references and article information

Boris Adamczewski, Julien Cassaigne and Marion Le Gonidec
Trans. Amer. Math. Soc. 373 (2020), 3085-3115.
Abstract, references and article information

M. V. Pratsiovytyi and S. P. Ratushniak
Theor. Probability and Math. Statist. 99 (2020), 211-228.
Abstract, references and article information

N. N. Leonenko, I. Papić, A. Sikorskii and N. Šuvak
Theor. Probability and Math. Statist. 99 (2020), 137-147.
Abstract, references and article information

N. V. Krylov
St. Petersburg Math. J. 31 (2020), 509-520.
Abstract, references and article information

Phạm Tiến Sơn
Proc. Amer. Math. Soc. 148 (2020), 2739-2741.
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.

Last month, I paid a visit to Yuen Long where I met a few families at Long Shin Estate. Apart from distributing face masks and anti-epidemic supplies to them, I was also given a better understanding of the impact brought by the epidemic on their daily lives. To show our concerted support in the fight against the disease, the Department of Justice (DoJ) Staff Club organised a volunteer activity on Sunday, which I joined with my fellow colleagues in offering our help to those in need.

To echo the Government's move to stay united, the DoJ Staff Club put forth a cash contribution campaign to buy anti-epidemic supplies for donation. The staff club volunteers acquired face masks and alcohol-based handrub in different ways - some were purchased through online shopping and some were bought at medicine stores. Last Sunday, I joined the volunteers in packing the anti-epidemic supplies, supermarket cash coupons and leaflets with health information. Our volunteers took the care packs in person to a non-governmental organisation a few days ago for passing to the elderly and low-income groups.

The staff club has been participating in volunteer services now and then. Given the overwhelming response this time, I am glad to know that more volunteer activities would be organised in the future. I would definitely be joining as many as I could. Through offering our efforts to help those in need, we hope to show our care for the less privileged in society and contribute to building a caring and inclusive community.

The public services of the DoJ, like all other government departments, have gradually resumed back to normal. I inspected the Justice Place on Monday to learn more about the infection control measures in place, such as the body temperature checking arrangement, provision of hand sanitisers and sanitising mats at building entrances.

We must remain vigilant as the epidemic is still severe, and more importantly, we also need to stand in solidarity in the fight against the disease.

Secretary for Justice Teresa Cheng wrote this article and posted it on her blog on March 5.

The Government issued directions in the Gazette today to close bars and premises selling liquor for 14 days from 6pm on April 3.

The Secretary for Food & Health issued the directions in accordance with the Prevention & Control of Disease (Requirements & Directions) (Business & Premises) Regulation.

The directions include the closure of bars and pubs, as well as any part of a catering business premise or a clubhouse mainly used for the sale or supply of intoxicating liquors for consumption.

The new measures were introduced due to the emergence of 62 confirmed COVID-19 cases related to the bar and band cluster with further spread to an additional 14 cases who had not visited bars.

The Government on April 1 introduced directions on the closure of karaoke, mahjong-tin kau and nightclub establishments as well as the suspension of karaoke and mahjong-tin kau activities in catering premises and clubhouses.

It has also been reviewing the feasibility of relevant measures and will make timely adjustments according to the latest developments of the disease.

Rare artefacts from Afghanistan will be on display at the Museum of History from November 6 until February 10, 2020.

Ancient Artefacts of Afghanistan - Glistening Treasures in the Dust will display 231 artefacts, including gold and glass wares, bronze sculptures and ivory carvings unearthed from four famous archaeological sites in Afghanistan.

Highlight exhibits include a golden bowl with a bearded-bull motif unearthed in Tepe Fullol and pendants with styles that were common in the Mesopotamian and Persian Plateau regions.

The precious relics are on loan from the National Museum of Afghanistan.

The museum’s director Mohammad Rahimi said that because Afghanistan borders many countries including China, the artefacts attest to the role ancient Afghanistan played as the cultural crossroads of the Silk Road.

“Afghanistan has been given the title of the crossroads of the ancient civilisation by different scholars of the world. So we had very good relations with different civilisations in the past so that’s why we can see a lot of influences of different cultures in our objects.”

Mr Rahimi added that Afghanistan is sharing its exhibit with Hong Kong as a gesture of goodwill and friendship and with the hope of strengthening relations with China.

“We have also seen different examples of our ancient relations with China. Because of that, we want to build on our relations with China through this exhibition and we have shown that we have had very good connections in the past.”

Many of the exhibits will be equipped with interactive designs so that visitors can compare and contrast the displayed treasures with similar artefacts.

Click here for details.

The East Kowloon Cultural Centre Public Artwork Commissioning Project is inviting artists, designers and architects to create an art landscape for the centre.

Presented by the Leisure & Cultural Services Department and organised by the Art Promotion Office, the project endeavors to capture and showcase the past, present and future of East Kowloon.

The commissioned artworks will represent five themes - memory, impression, moment, dream and imagination - aiming to display the district’s changing nature, and to manifest the local community’s cultural sustainability, aspirations and dreams.

Interested participants must submit their preliminary proposal with their curriculum vitae, documentation of their previous artwork and the artistic concept of the proposed artwork.

All proposals must be delivered to the centre’s Public Art Project Management Team at G/F, 50-54 Lok Ku Road, Sheung Wan before 7pm on May 4.

Participants shortlisted by the selection panel are required to submit detailed proposals before 7pm on June 30 for the next stage of the selection process.

Up to three proposals shall be chosen by the selection panel for commissioning and installing in the centre.

With the novel coronavirus expected to further impact Hong Kong’s already slowing economy, the Hong Kong Trade Development Council (HKTDC) is working hand in hand with local small and medium-sized enterprises (SMEs) to brave the...

The Transport Department today invited tenders for operating six major licensed ferry services for outlying islands for five years from April 1, 2021.

The six routes are between Central to Cheung Chau, Inter-islands between Peng Chau, Mui Wo, Chai Ma Wan and Cheung Chau, Central to Mui Wo, Central to Peng Chau, Central to Yung Shue Wan and Central to Sok Kwu Wan.

The department said that for the purposes of maintaining financial viability of the six major routes, alleviating the burden of fare increases on passengers, enhancing service quality and promoting a green city development, the Government would continue to provide special measures to the routes.

Such measures would include launching a new Vessel Subsidy Scheme to help selected ferry operators replace the fleets of the six major routes and introduce greener vessels in phases, straddling 10 years from 2021.

Having regard to factors such as passenger demand, overall fleet requirements, flexibility in vessel deployment, operational efficiency, and after consulting the Islands District Council, the six major routes are grouped into two packages for tendering.

The first package covers Central-Cheung Chau, Peng Chau-Mui Wo-Chi Ma Wan-Cheung Chau (Inter Islands) and Central-Mui Wo routes.

The other package covers Central-Peng Chau, Central-Yung Shue Wan and Central-Sok Kwu Wan routes.

Tenderers are required to propose a fare for each fare type of each relevant route and it must not exceed the existing fare level of the corresponding route by more than 5%. Tenders should also include in their submissions fare concession proposals that will be considered in the tender evaluation.

In support of the Government's development of a smart city, tenderers should propose measures including dissemination of real-time arrival/departure time of ferry routes, number of remaining seats via mobile phone apps and opening up such data for the public’s use under data.gov.hk.

The tenders must be sealed in envelopes and placed in the Transport Department Tender Box adjacent to the reception counter of the department on the 10th floor of South Tower, West Kowloon Government Offices, 11 Hoi Ting Road, Yau Ma Tei before noon on June 30.

The cover of the tender submission should be marked with tender reference TD 382/2019 and include the subject of the tender. It should also be addressed to the Commissioner for Transport.

Tender documents will be available for collection at the Transport Department’s Ferry & Paratransit Division on the 14th Floor, South Tower, West Kowloon Government Offices, 11 Hoi Ting Road, Yau Ma Tei from April 27 during office hours.

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

The Chief Executive has reappointed Frederick Ma as Chairman of the Education University of Hong Kong (EdUHK) Council from April 25 to December 31, the Government announced today.

Secretary for Education Kevin Yeung thanked Mr Ma for accepting the reappointment, saying that under his leadership, EdUHK continues to focus on educational research, development and innovation and promoting and supporting the development of teacher education in Hong Kong by nurturing outstanding and committed educators and professionals.

Mr Ma cannot accept a three-year term up until 2023 due to personal reasons. In the meantime, the Government will identify a suitable candidate for the chairmanship of the EdUHK Council.

The Government said it will continue to spare no effort in improving workers' benefits and protection and enhance occupational safety and health in various industries at a pace commensurate with Hong Kong's overall socio-economic development.

The Government made the statement today in response to the demands of different labour groups, noting that it would take into account both employees' interests and employers' abilities to afford the benefits, despite the severe blow dealt by the COVID-19 epidemic to the local economy.

"The seasonally adjusted unemployment and underemployment rates for January to March this year have soared to their highest levels in recent years. The labour market will continue to face significant pressure in the near term.

“The Government has rolled out relief measures of unprecedented scale, including the one-off measures in the 2020-21 Budget and two rounds of measures under the Anti-epidemic Fund (AEF) totalling $287.5 billion, with a view to preserving the vitality of the economy and relieving people's financial burden.

“The Government will launch as soon as possible the Employment Support Scheme under the second round of the AEF, with a total commitment of $81 billion, to provide time-limited financial support to employers to help them retain employees who will otherwise be made redundant.”

Moreover, the Government explained that it has earmarked $6 billion to create around 30,000 time-limited jobs in the public and private sectors in the coming two years for people with different skills and academic qualifications.

It emphasised that the Labour Department will raise the ceiling of on-the-job training allowance payable to employers under the Employment Programme for the Elderly & Middle-aged, the Youth Employment & Training Programme and the Work Orientation & Placement Scheme in the second half of this year.

It will also launch a pilot scheme to encourage eligible participants of these programmes to undergo and complete the training by offering a retention allowance.

On improvements to other labour benefits, the Government pointed out that it is working at full steam on the preparatory work to abolish the arrangement of 'offsetting' severance payments and long service payments with employers' mandatory contributions under the Mandatory Provident Fund System.

It stressed that it will strive to introduce the enabling bill into the Legislative Council by the end of this year, aiming to secure its passage by 2022.

Meanwhile, the Government introduced the Employment (Amendment) Bill 2019 into LegCo on January 8 this year. The bill, which proposes to extend statutory maternity leave by four weeks, is now being handled by the LegCo Panel on Manpower.

The Chief Executive announced on January 14 this year 10 new initiatives on improving people's livelihood, one of which is to increase progressively the number of statutory holidays so that it will be on par with that of general holidays.

The Government stated that it will work out the relevant proposal, invite the Labour Advisory Board to discuss, and will facilitate and support its work.

The Minimum Wage Commission is conducting a new round of review on the Statutory Minimum Wage rate and will submit a report on its recommendation to the Chief Executive in Council by end-October.

The Government added that it attaches great importance to employees' occupational safety and health.

It said the Labour Department has been adjusting its strategies of inspection and enforcement, publicity and promotion, education and training according to the occupational safety and health risk levels of different industries as well as taking sufficient precautionary measures to prevent accidents by driving employers and employees to work together.

The Hong Kong Special Administrative Region Government has rejected allegations made by certain officials and politicians in the United States, United Kingdom and European Parliament relating to an April 18 arrest operation and other security matters.

In a statement today, the Hong Kong SAR Government said such allegations were totally unfounded and amounted to a serious intervention in Hong Kong's affairs.

The SAR Government strongly disagreed with the grossly irresponsible remarks and expressed deep regret about them.

It pointed out that since its return to the Motherland, the HKSAR has maintained stability and prosperity under the principle of "one country, two systems", exercising "Hong Kong people administering Hong Kong" and a high degree of autonomy in strict accordance with the Basic Law (BL).   

"The Central Government has time and again reiterated that it will unswervingly implement the policy of one country, two systems' and make sure that it is fully applied in Hong Kong without being bent or distorted. 

“How to implement the policy in the HKSAR - an inalienable part of the People's Republic of China (BL Article 1) and a local administrative region of the People's Republic of China which shall enjoy a high degree of autonomy and come directly under the Central People's Government (BL Article 12) - are entirely internal affairs of the People's Republic of China.

“No other state has the right to intervene, directly or indirectly, in those internal affairs.”

The statement noted Hong Kong people enjoy extensive rights and freedoms which are enshrined in the Basic Law. Basic Law Article 4 states that the HKSAR shall safeguard the rights and freedoms of the residents and of other persons in the region in accordance with law. 

“In addition, human rights and freedoms in Hong Kong are fully protected by the Hong Kong Bill of Rights Ordinance and other legislation, and underpinned by an independent judiciary."

The SAR Government said it always respects and protects human rights and freedoms. Any allegation that there has been an erosion in freedoms enjoyed by Hong Kong people is unfounded.

However, these rights are not absolute. As pointed out by the Chief Justice of the Court of Final Appeal at the Ceremonial Opening of the Legal Year 2020: "It is important to understand that the enjoyment of these rights has limits so as not to affect adversely to an unacceptable level the enjoyment by other members of their community of their rights and liberties."

There are clear limits in the law as to the exercise of these rights. When the law is broken, action will be taken in accordance with the criminal justice system.

"We therefore take great exception to comments made by officials and politicians in foreign countries concerning the recent arrests and prosecution of a number of persons for organising and participating in unauthorised assemblies in Hong Kong. 

“The allegation by some that those arrests amounted to an attack on Hong Kong's freedoms and a breach of the BL is absurd and can hardly stand the test of any law-abiding jurisdiction," the statement emphasised.

It also pointed out that Basic Law Article 63 provides that "The Department of Justice of the Hong Kong Special Administrative Region shall control criminal prosecutions, free from any interference." 

Prosecutors have always been discharging this constitutional duty independently and professionally, without fear or favour. Prosecutorial decisions are based on an objective assessment of all admissible evidence and applicable laws, made strictly in accordance with the Prosecution Code which is available to the public.

Cases will not be handled any differently owing to the political beliefs or background of the persons involved.

When law enforcement agencies have completed their investigation, they would seek legal advice from the Department of Justice. The prosecutors would carefully consider the investigation reports and relevant materials submitted. A prosecution would only be commenced if the prosecutor is satisfied that there is sufficient admissible evidence to support a reasonable prospect of conviction.

In short, the well-established procedures of Hong Kong's criminal justice system include the independent investigations by law enforcement agencies, the independent prosecutorial decisions based on the objective assessment of evidence, applicable laws and in accordance with the Prosecution Code, and finally, open trials by an independent judiciary. 

"The guarantee of judicial independence is explicitly set out in the BL and the quality of the judgments of our courts contributes to the much respected judiciary and rule of law in the HKSAR.

"We therefore note with abhorrence certain overseas politicians' request that the HKSAR Government should drop the charges against the arrested individuals. If we were to accede or to be seen to yield to such unreasonable demands, we would not only be unfair and unprofessional but would also act in violation of the spirit of the rule of law – a core value in Hong Kong," the statement added.

The SAR Government remains steadfast to uphold the rule of law. The latest Rule of Law Index 2020 released by the World Justice Project, in which Hong Kong maintains its ranking as No. 5 in the East Asia and Pacific Region and No. 16 globally, several places ahead of the United States, has clearly affirmed Hong Kong's commitment.

On legislating for Basic Law Article 23, the statement said, "The HKSAR Government has the constitutional duty to ensure that the necessary legislation is in place to safeguard national security.

“Having laws in place to protect national security is common in many jurisdictions, and we do not see how any defence of sovereignty and security by a jurisdiction would impact on its local and overseas investment. 

“Coincidentally, it is relevant to note security issues arising from the social unrest last year were part of the causes affecting Hong Kong's score under 'Investment Freedom' according to the US-based Heritage Foundation 2020 Index of Economic Freedom."

As regards enquiries about the role of the Hong Kong & Macao Affairs Office of the State Council (HKMAO) and the Liaison Office of the Central People's Government (LOCPG) in the HKSAR, they represent the Central People's Government to which the HKSAR comes directly under pertaining to Basic Law Article 12. 

These offices have the power and responsibility over the proper and full implementation of the Basic Law and "one country, two systems" in Hong Kong.

It is therefore clearly legitimate for the HKMAO and LOCPG to recently express their concerns over the prolonged paralysis of the Legislative Council House Committee, thereby hindering LegCo's performance of its legislative functions under the Basic Law.

"Any suggestion that those legitimate remarks by the HKMAO and the LOCPG amount to interference only illustrates an ignorance of the constitutional order of the HKSAR and its relationship with the Central Authorities," the SAR Government added.

Police today said it is highly concerned about recent criminal offences involving police officers and that a number of these officers have been arrested.

Among them, officers in connection with serious offences have been or will be interdicted.

The force said it is furious and disappointed about the officers who are suspected of having breached the law and that the incidents have impaired public confidence in Police.

Police attach the utmost importance to the discipline and integrity of officers.

All officers, irrespective of their ranks, must abide by the law at all times.

Police management has zero tolerance towards any acts that breach the law or discipline by police officers, it added.

The force also said it attaches great importance to the integrity of its officers.

The Complaints & Internal Investigations Branch formulated the Integrated Integrity Management Framework to promote integrity and honesty among officers as well as to regulate their discipline and conduct.

To avoid similar incidents, Police said its management is reviewing the force’s internal management strategy.

Police reiterated that no bad element in the force can be tolerated.

If an officer is suspected of having breached the law or committed a breach of discipline, Police will conduct an investigation according to the established mechanism and take appropriate actions.

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.

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.

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.

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.

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.

Purinergic signaling by extracellular ATP regulates a variety of cellular events and is implicated in both normal physiology and pathophysiology. Several molecules have been associated with the release of ATP and other small molecules, but their precise contributions have been difficult to assess because of their complexity and heterogeneity. Here, we report on the results of a gain-of-function screen for modulators of hypotonicity-induced ATP release using HEK-293 cells and murine cerebellar granule neurons, along with bioluminescence, calcium FLIPR, and short hairpin RNA–based gene-silencing assays. This screen utilized the most extensive genome-wide ORF collection to date, covering 90% of human, nonredundant, protein-encoding genes. We identified two ABCG1 (ABC subfamily G member 1) variants, which regulate cellular cholesterol, as modulators of hypotonicity-induced ATP release. We found that cholesterol levels control volume-regulated anion channel–dependent ATP release. These findings reveal novel mechanisms for the regulation of ATP release and volume-regulated anion channel activity and provide critical links among cellular status, cholesterol, and purinergic signaling.

Fatty acid transport protein 2 (FATP2) is highly expressed in the liver, small intestine, and kidney, where it functions in both the transport of exogenous long-chain fatty acids and the activation of very-long-chain fatty acids. Here, using a murine model, we investigated the phenotypic impacts of deleting FATP2, followed by a transcriptomic analysis using unbiased RNA-Seq to identify concomitant changes in the liver transcriptome. WT and FATP2-null (Fatp2−/−) mice (5 weeks) were maintained on a standard chow diet for 6 weeks. The Fatp2−/− mice had reduced weight gain, lowered serum triglyceride, and increased serum cholesterol levels and attenuated dietary fatty acid absorption. Transcriptomic analysis of the liver revealed 258 differentially expressed genes in male Fatp2−/− mice and a total of 91 in female Fatp2−/− mice. These genes mapped to the following gene ontology categories: fatty acid degradation, peroxisome biogenesis, fatty acid synthesis, and retinol and arachidonic acid metabolism. Targeted RT-quantitative PCR verified the altered expression of selected genes. Of note, most of the genes with increased expression were known to be regulated by peroxisome proliferator–activated receptor α (PPARα), suggesting that FATP2 activity is linked to a PPARα-specific proximal ligand. Targeted metabolomic experiments in the Fatp2−/− liver revealed increases of total C16:0, C16:1, and C18:1 fatty acids; increases in lipoxin A4 and prostaglandin J2; and a decrease in 20-hydroxyeicosatetraenoic acid. We conclude that the expression of FATP2 in the liver broadly affects the metabolic landscape through PPARα, indicating that FATP2 provides an important role in liver lipid metabolism through its transport or activation activities.

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.

Type 2 diabetes mellitus (T2DM) is characterized by impaired glucose-stimulated insulin secretion and increased peripheral insulin resistance. Unremitting endoplasmic reticulum (ER) stress can lead to beta-cell apoptosis and has been linked to type 2 diabetes. Although many studies have attempted to link ER stress and T2DM, the specific effects of ER stress on beta-cell function remain incompletely understood. To determine the interrelationship between ER stress and beta-cell function, here we treated insulin-secreting INS-1(832/13) cells or isolated mouse islets with the ER stress–inducer tunicamycin (TM). TM induced ER stress as expected, as evidenced by activation of the unfolded protein response. Beta cells treated with TM also exhibited concomitant alterations in their electrical activity and cytosolic free Ca2+ oscillations. As ER stress is known to reduce ER Ca2+ levels, we tested the hypothesis that the observed increase in Ca2+ oscillations occurred because of reduced ER Ca2+ levels and, in turn, increased store-operated Ca2+ entry. TM-induced cytosolic Ca2+ and membrane electrical oscillations were acutely inhibited by YM58483, which blocks store-operated Ca2+ channels. Significantly, TM-treated cells secreted increased insulin under conditions normally associated with only minimal release, e.g. 5 mm glucose, and YM58483 blocked this secretion. Taken together, these results support a critical role for ER Ca2+ depletion–activated Ca2+ current in mediating Ca2+-induced insulin secretion in response to ER stress.