The Financial Secretary just delivered the latest Budget on Wednesday. The Department of Justice would foster the policy initiatives relating to "Diversified Economy" and continue our ongoing works. The Inclusive Dispute Avoidance & Resolution Office (IDAR Office, email: idar@doj.gov.hk), which was set up in January last year, is to better co-ordinate and implement initiatives in the areas of dispute avoidance and resolution, thereby further consolidating our position as an international legal and dispute resolution services centre in the Asia-Pacific region.

The Department of Justice has always been actively striving for the presence of international dispute resolution bodies in Hong Kong in order to meet the upsurge in demand for legal and dispute resolution services arising from the Belt & Road Initiative and the Greater Bay Area Plan. Their presence in Hong Kong would also enhance our status as a leading centre for international legal and dispute resolution services. With the support of the Central People's Government, we are now exploring the possibility for the Asian-African Legal Consultative Organization (AALCO) to establish a regional centre for international commercial arbitration in Hong Kong.

Last year, the inter-sessional meetings of the Judgments Project of the Hague Conference on Private International Law were successfully concluded in Hong Kong. This invaluable experience has reinforced our determination in looking for decision-making meetings of international and intergovernmental organisations to be held in Hong Kong, including hosting the 59th Annual Session of AALCO and an intersessional meeting of UNCITRAL's Working Group III this year. High ranking government officials and legal experts from member states would take part in these meetings to discuss matters such as maritime law and cyber space law.

In addition, we are committed to strengthening Hong Kong's status as a regional capacity building centre which seeks to enhance legal infrastructure in the neighbouring regions and facilitate cross-border mobility and business activities. For instance, the Department of Justice organised the Investment Law & Investor-State Mediator Training Course for two consecutive years since 2018. World-renowned trainers were invited to share with the participants their experience in international investment law and investor-state mediation. We would be stepping up our efforts in organising capacity building courses in dispute resolution.

At the same time, the Department of Justice has reached an agreement with the Hague Academy of International Law, one of the world's leading academic institutes on international law, to support them in organising law courses in Hong Kong regularly in collaboration with the Asian Academy of International Law from this year. We anticipate this cooperation would provide Hong Kong and the neighbouring regions with high quality training for legal professionals, which helps further raise our international profile.

Looking ahead, colleagues in the Department of Justice would keep pursuing co-operation or partnership agreements with other jurisdictions and international organisations and host important events in Hong Kong, with a view to raising the international profile of Hong Kong in deal-making and dispute resolution through overseas capacity building and promotional activities.

Secretary for Justice Teresa Cheng wrote this article and posted it on her blog on March 1.

The Hong Kong Museum of Art will reopen on November 30 with 11 new exhibitions, after major expansion and renovation.

Ordinary to Extraordinary: Stories of the Museum, an exhibition of gems from the museum's collection, will showcase exceptional works curated from its four core collections - Chinese Antiquities, Chinese Painting & Calligraphy, China Trade Art, and Modern & Hong Kong Art.

Museum of Art Director Maria Mok said that by sharing the fascinating stories behind these works, the exhibition will help visitors discover little-known anecdotes about the museum throughout the 57 years since its founding.

The exhibition From Dung Basket to Dining Cart: 100th Anniversary of the Birth of Wu Guanzhong will showcase more than 100 of the artist’s paintings to not only honour his contributions to Chinese art, but also pay tribute to his artistic pursuits spanning over half a century.

The development of Hong Kong art has been a unique local experience.

The Hong Kong Experience‧Hong Kong Experiment exhibition makes use of the museum's collection accumulated over half a century to capture all these different experiences and experiments, portraying the development of Hong Kong art.

The museum has been closed since August 2015 for renovations to increase exhibition space and upgrade its facilities.

After the expansion, its total exhibition area will increase from about 7,000 to 10,000 sq m and the number of galleries will increase from seven to 12.

Click here to reserve admission time slots.

The Space Museum will present Turtle Odyssey 3D between January 1 and April 30 where audiences can join sea turtle Bunji for a remarkable adventure and meet an astonishing range of strange and fascinating creatures, including breaching whales, manta rays and clownfish.

Bunji's journey starts from the moment her fragile egg cracks open below the warm sand of an Australian beach.

Having traversed thousands of kilometres of open oceans, she returns after decades with mysterious precision back to the very beach where she was born to lay eggs and start the next generation.

Her journey reminds the audience of how interconnected all creatures are, moving them to cherish these beautiful and vulnerable sea turtles even more.

The 41-minute show will be screened daily at 2.40pm and 6.10pm. An additional show at 11.10am will be available on Sundays and public holidays.

Tickets are available at the Space Museum Box Office and URBTIX. The museum is closed on Tuesdays except public holidays.

Click here for details.

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.

The Government will launch a series of measures to retain and create jobs to prevent massive layoffs amid record levels of unemployment and underemployment for the first three months of the year.

The seasonally adjusted unemployment and underemployment rates have soared recently due to the severe blow dealt by the COVID-19 epidemic to Hong Kong’s economy.

With reference to the practice of some overseas governments in providing wage subsidies to employers and following the funding approval by the Legislative Council Finance Committee, the Government will launch the $81 billion Employment Support Scheme (ESS) as soon as possible.

The scheme will provide time-limited financial support to employers to retain workers who will inevitably be made redundant due to the downturn in business.

The provision of subsidies for employers, together with other relief measures and loan arrangements under the Anti-epidemic Fund and the 2020-21 Budget will help businesses stay afloat and retain jobs to prepare for a quick recovery once the epidemic is over.

Except for the Government, statutory bodies and government-funded organisations whose employees' salaries are not affected by the epidemic, employers who have been making Mandatory Provident Fund (MPF) contributions or have set up Occupational Retirement Schemes will be eligible for the ESS.

Employers joining the scheme have to provide an undertaking not to implement redundancies during the subsidy period and spend all wage subsidies from the Government in paying wages to their employees.

Wage subsidies provided under the ESS are calculated based on 50% of wages in a specified month subject to a wage cap of $18,000 per month for six months.

Payment will be made in two tranches, with the first payout no later than the end of June to subsidise employers to pay employees' wages from June to August.

After approval of the application, the number of employees on payroll shall not be less than the number of employees in March and the wage subsidies applied by employers must be used fully for employees' wages.

Under the ESS, self-employed people who have contributed to the MPF from January 1, 2019 to March 31 will be granted a one-off subsidy of $7,500.

The scheme is expected to benefit over 260,000 employers who have been making MPF contributions or have set up Occupational Retirement Schemes for 1.7 million employees, and about 215,000 self-employed people.

Employers and employees in the catering, construction and transport sectors that are not covered by the MPF will be taken care of by sector-specific schemes.

Regarding job creation, the Government has earmarked $6 billion to create about 30,000 time-limited jobs in public and private sectors in the coming two years for people of different skills and academic qualifications.

This is in addition to more than 10,000 civil service job openings for replacing retirees and filling new posts to be created in the 2020-21 Estimates, and about 5,000 short-term interns for young people.

In the second half of the year, the Labour Department will raise the ceiling of the 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 to further encourage employers to hire seniors, youngsters and the disabled.

The department plans to launch a pilot scheme in the second half of the year to encourage these people to undergo and complete on-the-job training under the above-mentioned employment programmes through the provision of a retention allowance.

A time-limited unemployment support scheme will be launched through the Comprehensive Social Security Assistance Scheme at the same time to provide timely and basic financial support to the unemployed who may not be covered by the ESS.

To maintain Hong Kong's economic vibrancy and relieve the financial burden of the public under the epidemic, the Government has introduced the largest package of relief measures to date, including the one-off relief measures in the Budget costing $120 billion and two rounds of measures under the Anti-epidemic Fund totalling $287.5 billion.

This accounts for about 10% of Hong Kong's gross domestic product, the Government added.

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.

Secretary for the Civil Service Patrick Nip today visited the Inland Revenue Department and the Labour Department to inspect the resumption of public services.

The Government had earlier announced that public services will be resumed under a phased approach.

Counter services of most government departments have returned to normal.

Mr Nip first visited the Inland Revenue Department in Revenue Tower and was briefed on counter services at the Central Enquiry Counter, the Business Registration Office and the Stamp Office.

He learnt that the department has implemented various infection control and crowd management measures, such as a ticketing system, to safeguard the health of colleagues and the public.

Later Mr Nip visited the Hong Kong East Job Centre and a recruitment centre for the catering and retail industries and was briefed on the resumption of normal services at the Labour Department's job and recruitment centres.

He said: “While maintaining a high degree of vigilance and adopting all necessary precautionary measures, the Government gradually resumed public services today in a smooth and orderly manner.

“Various infection control measures have been put in place at government buildings and offices. These include checking the body temperature of persons at entrances, providing alcohol-based hand sanitiser and enhancing the cleaning of public facilities.

“The Government will closely monitor the situation to determine when to embark on full resumption of normal business.”

All the details on Uber's biggest announcements as well as updates on the controversial company's trials and tribulations

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 virtual-based office hours is to connect female founders with early-stage VC investors who will provide business advice and investments

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

Roadside Stations: 2 (Health Risk: Low)

(University of Montreal) A chemistry professor at Université de Montréal has developed a new test using gold nanoparticles to establish the flavour profile of maple syrup and help producers evaluate its quality.

(University of Southampton) Scientists have published highly detailed images of lab-grown neurons using Extreme Ultraviolet radiation that could aid the analysis of neurodegenerative diseases.

(Dartmouth College) Annual award supports the research and teaching careers of talented young faculty in the chemical sciences.

(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 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 Government urged District Councillors to focus on livelihood issues and discuss matters rationally, adding that it will continue to co-operate with the District Council under the principles of mutual respect, observation of order and rational discussion.

The Government issued the statement after a number of Central & Western District Council members today entered the office area of the Central & Western District Office without consent.

The statement noted that the members shouted loudly and knocked on the door of the office.

Despite repeated responses and an appeal from the District Office staff, the members still refused to leave.

The statement added that the members stayed in the District Office for a long time, seriously affecting its operation.

The Government expressed regret over their acts.

Premises can still operate other licensed businesses which are not required to be suspended if they were operating more than one licensed business before the closure, the Food & Health Bureau said today.

The bureau made the statement in response to media enquiries on some anti-epidemic measures which were relaxed from today.

The statement noted that in accordance with the Prevention & Control of Disease (Requirements & Directions) (Business & Premises) Regulation, the Secretary for Food & Health has issued directions by notices in the Gazette that certain scheduled premises, namely karaoke establishments, clubs or nightclubs, party rooms and bathhouses, should remain closed until May 21.

These scheduled premises may still operate other licensed businesses if the operators have implemented all measures to effectively stop or avoid operation of businesses and offering services which are required to be suspended.

For example, premises originally operated as karaoke establishments and catering businesses can continue their catering business in accordance with the relevant directions if all karaoke operation and services are suspended.

The directions state that facilities, installations and equipment for karaoke activities are closed or properly sealed off and notices are posted in prominent locations at the entrances clearly indicating that only catering services but no karaoke services are provided in the premises.

Other scheduled premises operating more than one licensed business can adopt similar measures to operate other licensed businesses which are not required to be suspended, the bureau added.

Emily Riehl, Johns Hopkins University, received the university's $250,000 President's Frontier Award, whose purpose is to nurture individuals at Johns Hopkins University who are breaking new ground and poised to become leaders in their field. Riehl studies category theory and says that "I just thought the proofs were the most beautiful of any of the other areas I've encountered. ... It was sort of love at first sight and I am lucky to be able to do what I love." The award is considered a "$250,000 investment in doing more of what she loves."

Also see and hear this coverage: "Johns Hopkins Mathematician from B-N [Bloomington-Normal, IL] Breaks Barriers and Wins Research Grant, by Jolie Sherman, WGLT, February 27, 2020.

Neoantimycins are anticancer compounds of 15-membered ring antimycin-type depsipeptides. They are biosynthesized by a hybrid multimodular protein complex of nonribosomal peptide synthetase (NRPS) and polyketide synthase (PKS), typically from the starting precursor 3-formamidosalicylate. Examining fermentation extracts of Streptomyces conglobatus, here we discovered four new neoantimycin analogs, unantimycins B–E, in which 3-formamidosalicylates are replaced by an unusual 3-hydroxybenzoate (3-HBA) moiety. Unantimycins B–E exhibited levels of anticancer activities similar to those of the chemotherapeutic drug cisplatin in human lung cancer, colorectal cancer, and melanoma cells. Notably, they mostly displayed no significant toxicity toward noncancerous cells, unlike the serious toxicities generally reported for antimycin-type natural products. Using site-directed mutagenesis and heterologous expression, we found that unantimycin productions are correlated with the activity of a chorismatase homolog, the nat-hyg5 gene, from a type I PKS gene cluster. Biochemical analysis confirmed that the catalytic activity of Nat-hyg5 generates 3-HBA from chorismate. Finally, we achieved selective production of unantimycins B and C by engineering a chassis host. On the basis of these findings, we propose that unantimycin biosynthesis is directed by the neoantimycin-producing NRPS–PKS complex and initiated with the starter unit of 3-HBA. The elucidation of the biosynthetic unantimycin pathway reported here paves the way to improve the yield of these compounds for evaluation in oncotherapeutic applications.

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.

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.

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

Treatment of patients with chronic lymphocytic leukemia (CLL) with inhibitors of Bruton's tyrosine kinase (BTK), such as ibrutinib, is limited by primary or secondary resistance to this drug. Examinations of CLL patients with late relapses while on ibrutinib, which inhibits BTK's catalytic activity, revealed several mutations in BTK, most frequently resulting in the C481S substitution, and disclosed many mutations in PLCG2, encoding phospholipase C-γ2 (PLCγ2). The PLCγ2 variants typically do not exhibit constitutive activity in cell-free systems, leading to the suggestion that in intact cells they are hypersensitive to Rac family small GTPases or to the upstream kinases spleen-associated tyrosine kinase (SYK) and Lck/Yes-related novel tyrosine kinase (LYN). The sensitivity of the PLCγ2 variants to BTK itself has remained unknown. Here, using genetically-modified DT40 B lymphocytes, along with various biochemical assays, including analysis of PLCγ2-mediated inositol phosphate formation, inositol phospholipid assessments, fluorescence recovery after photobleaching (FRAP) static laser microscopy, and determination of intracellular calcium ([Ca2+]i), we show that various CLL-specific PLCγ2 variants such as PLCγ2S707Y are hyper-responsive to activated BTK, even in the absence of BTK's catalytic activity and independently of enhanced PLCγ2 phospholipid substrate supply. At high levels of B-cell receptor (BCR) activation, which may occur in individual CLL patients, catalytically-inactive BTK restored the ability of the BCR to mediate increases in [Ca2+]i. Because catalytically-inactive BTK is insensitive to active-site BTK inhibitors, the mechanism involving the noncatalytic BTK uncovered here may contribute to preexisting reduced sensitivity or even primary resistance of CLL to these drugs.

Protein phosphatase 2A (PP2A) is a large enzyme family responsible for most cellular Ser/Thr dephosphorylation events. PP2A substrate specificity, localization, and regulation by second messengers rely on more than a dozen regulatory subunits (including B/R2, B'/R5, and B″/R3), which form the PP2A heterotrimeric holoenzyme by associating with a dimer comprising scaffolding (A) and catalytic (C) subunits. Because of partial redundancy and high endogenous expression of PP2A holoenzymes, traditional approaches of overexpressing, knocking down, or knocking out PP2A regulatory subunits have yielded only limited insights into their biological roles and substrates. To this end, here we sought to reduce the complexity of cellular PP2A holoenzymes. We used tetracycline-inducible expression of pairs of scaffolding and regulatory subunits with complementary charge-reversal substitutions in their interaction interfaces. For each of the three regulatory subunit families, we engineered A/B charge–swap variants that could bind to one another, but not to endogenous A and B subunits. Because endogenous Aα was targeted by a co-induced shRNA, endogenous B subunits were rapidly degraded, resulting in expression of predominantly a single PP2A heterotrimer composed of the A/B charge–swap pair and the endogenous catalytic subunit. Using B'δ/PPP2R5D, we show that PP2A complexity reduction, but not PP2A overexpression, reveals a role of this holoenzyme in suppression of extracellular signal–regulated kinase signaling and protein kinase A substrate dephosphorylation. When combined with global phosphoproteomics, the PP2A/B'δ reduction approach identified consensus dephosphorylation motifs in its substrates and suggested that residues surrounding the phosphorylation site play roles in PP2A substrate specificity.

Bacterial products such as lipopolysaccharides (or endotoxin) cause systemic inflammation, resulting in a substantial global health burden. The onset, progression, and resolution of the inflammatory response to endotoxin are usually tightly controlled to avoid chronic inflammation. Members of the NF-κB family of transcription factors are key drivers of inflammation that activate sets of genes in response to inflammatory signals. Such responses are typically short-lived and can be suppressed by proteins that act post-translationally, such as the SOCS (suppressor of cytokine signaling) family. Less is known about direct transcriptional regulation of these responses, however. Here, using a combination of in vitro approaches and in vivo animal models, we show that endotoxin treatment induced expression of the well-characterized transcriptional repressor Krüppel-like factor 3 (KLF3), which, in turn, directly repressed the expression of the NF-κB family member RELA/p65. We also observed that KLF3-deficient mice were hypersensitive to endotoxin and exhibited elevated levels of circulating Ly6C+ monocytes and macrophage-derived inflammatory cytokines. These findings reveal that KLF3 is a fundamental suppressor that operates as a feedback inhibitor of RELA/p65 and may be important in facilitating the resolution of inflammation.

Prominins (proms) are transmembrane glycoproteins conserved throughout the animal kingdom. They are associated with plasma membrane protrusions, such as primary cilia, as well as extracellular vesicles derived thereof. Primary cilia host numerous signaling pathways affected in diseases known as ciliopathies. Human PROM1 (CD133) is detected in both somatic and cancer stem cells and is also expressed in terminally differentiated epithelial and photoreceptor cells. Genetic mutations in the PROM1 gene result in retinal degeneration by impairing the proper formation of the outer segment of photoreceptors, a modified cilium. Here, we investigated the impact of proms on two distinct examples of ciliogenesis. First, we demonstrate that the overexpression of a dominant-negative mutant variant of human PROM1 (i.e. mutation Y819F/Y828F) significantly decreases ciliary length in Madin–Darby canine kidney cells. These results contrast strongly to the previously observed enhancing effect of WT PROM1 on ciliary length. Mechanistically, the mutation impeded the interaction of PROM1 with ADP-ribosylation factor–like protein 13B, a key regulator of ciliary length. Second, we observed that in vivo knockdown of prom3 in zebrafish alters the number and length of monocilia in the Kupffer's vesicle, resulting in molecular and anatomical defects in the left-right asymmetry. These distinct loss-of-function approaches in two biological systems reveal that prom proteins are critical for the integrity and function of cilia. Our data provide new insights into ciliogenesis and might be of particular interest for investigations of the etiologies of ciliopathies.

Heat shock factor 1 (HSF1) regulates cellular adaptation to challenges such as heat shock and oxidative and proteotoxic stresses. We have recently reported a previously unappreciated role for HSF1 in the regulation of energy metabolism in fat tissues; however, whether HSF1 is differentially expressed in adipose depots and how its levels are regulated in fat tissues remain unclear. Here, we show that HSF1 levels are higher in brown and subcutaneous fat tissues than in those in the visceral depot and that HSF1 is more abundant in differentiated, thermogenic adipocytes. Gene expression experiments indicated that HSF1 is transcriptionally regulated in fat by agents that modulate cAMP levels, by cold exposure, and by pharmacological stimulation of β-adrenergic signaling. An in silico promoter analysis helped identify a putative response element for activating transcription factor 3 (ATF3) at −258 to −250 base pairs from the HSF1 transcriptional start site, and electrophoretic mobility shift and ChIP assays confirmed ATF3 binding to this sequence. Furthermore, functional assays disclosed that ATF3 is necessary and sufficient for HSF1 regulation. Detailed gene expression analysis revealed that ATF3 is one of the most highly induced ATFs in thermogenic tissues of mice exposed to cold temperatures or treated with the β-adrenergic receptor agonist CL316,243 and that its expression is induced by modulators of cAMP levels in isolated adipocytes. To the best of our knowledge, our results show for the first time that HSF1 is transcriptionally controlled by ATF3 in response to classic stimuli that promote heat generation in thermogenic tissues.

Nucleoside analogues are a valuable experimental tool. Incorporation of these molecules into newly synthesized DNA (i.e. pulse-labeling) is used to monitor cell proliferation or to isolate nascent DNA. Some of the most common nucleoside analogues used for pulse-labeling of DNA in cells are the deoxypyrimidine analogues 5-ethynyl-2'-deoxyuridine (EdU) and 5-ethynyl-2'-deoxycytidine (EdC). Click chemistry enables conjugation of an azide molecule tagged with a fluorescent dye or biotin to the alkyne of the analog, which can then be used to detect incorporation of EdU and EdC into DNA. The use of EdC is often recommended because of the potential cytotoxicity associated with EdU during longer incubations. Here, by comparing the relative incorporation efficiencies of EdU and EdC during short 30-min pulses, we demonstrate significantly lower incorporation of EdC than of EdU in noninfected human fibroblast cells or in cells infected with either human cytomegalovirus or Kaposi's sarcoma-associated herpesvirus. Interestingly, cells infected with herpes simplex virus type-1 (HSV-1) incorporated EdC and EdU at similar levels during short pulses. Of note, exogenous expression of HSV-1 thymidine kinase increased the incorporation efficiency of EdC. These results highlight the limitations when using substituted pyrimidine analogues in pulse-labeling and suggest that EdU is the preferable nucleoside analogue for short pulse-labeling experiments, resulting in increased recovery and sensitivity for downstream applications. This is an important discovery that may help to better characterize the biochemical properties of different nucleoside analogues with a given kinase, ultimately leading to significant differences in labeling efficiency of nascent DNA.

(Geological Society of America) The annual meeting of The Geological Society of America's North-Central Section, originally scheduled to take place in Duluth, Minnesota, will be held virtually on May 18-19, 2020, with technical sessions in the morning and student programming in the afternoon. The online meeting is open and available to everyone for free. No registration is required.

(University of Cambridge) Parents should not feel pressured to make their young children undertake structured learning or achieve specific tasks, particularly during lockdown. A new study of children under the age of two has found that parents who take a more flexible approach to their child's learning can - for children who were easy babies - minimise behavioural problems during toddlerhood.

(Elsevier) Children looking for health information online could end up more prone to obesity. A new study in the Journal of Nutrition Education and Behavior, published by Elsevier, shows a lack of digital health literacy can lead children to misinterpret portions, adopt recommendations intended for adults, or take guidance from noncredible sources.

The Hong Kong Special Administrative Region Government today welcomed the promulgation of the Meteorological Development Plan for the Guangdong-Hong Kong-Macao Greater Bay Area (2020-2035) by the China Meteorological Administration.

In a statement, the Hong Kong SAR Government said the promulgation of the plan would further strengthen meteorological co-operation among Guangdong, Hong Kong and Macau in areas such as data sharing, scientific research and innovation, and training of meteorological personnel.

Such co-operation would in turn enhance the meteorological services in the three places, it added.

The relevant co-operation initiatives will benefit the Hong Kong Observatory (HKO) in its development of fine-scale meteorological monitoring, warning and forecasting services, and will further enhance Hong Kong's capability in forecasting extreme weather events, the statement said, adding the HKO will take forward the initiatives in collaboration with the relevant authorities in Guangdong and Macau.

The full text of the meteorological plan is available on the China Meteorological Administration's website. It can also be accessed via the Hong Kong SAR Government's Greater Bay Area and HKO websites.

Residents may have seen a distinctive white car, fitted with advanced imaging and sensory gadgetry, on its journey to create the next generation of Hong Kong maps.

As it travels up and down the city’s streets, it records the three-dimensional shapes of buildings ranging from the iconic Convention & Exhibition Centre to the Customs Headquarters Building, and even primary school campuses.

The vehicle, dubbed the Mobile Mapping System, is one of the latest technologies used by the Lands Department to survey the city.

Five pieces of equipment work in concert to collect detailed information for the 3D City Map - a core component of the digital infrastructure underpinning Hong Kong’s smart city development.

A high-resolution camera on top of the vehicle captures 360-degree images and a 3D laser scanner collects spatial measurements. An inertial navigation system and a global navigation satellite system receiver provide precise positioning.

Lands Department Assistant Land Surveyor Charlie Hung said one of the biggest advantages of this system is its ability to quickly and efficiently acquire data, which can be used to enrich 3D models and enhance existing maps.

“We can enhance the attributed information of our basic map. For example, the lamppost number, the building name or the street number.”

Drones are also used to map the city, she added. However, air surveying may not be suitable for collecting data from ground level. This is where the Mobile Mapping System vehicle comes into play.

Better data

The 3D City Map is part of the 3D Digital Map Development, which aims to contribute to an innovative, sustainable and smart Hong Kong.

Compared with traditional maps, the 3D City Map can provide more accurate and abundantly better spatial data.

The map will cover the entire city by 2023, serving as a handy tool for analysis and planning, according to Lands Department Land Surveyor Ben Fan.

He said: “Based on the 3D digital map, we can develop various kinds of applications such as land administration, environmental assessment, town planning and also transport and engineering studies.”

The latest transport infrastructures such as the Hong Kong-Zhuhai-Macao Bridge, the Central-Wan Chai Bypass and the Heung Yuen Wai Highway have also been scanned.

In the next stage of the 3D Digital Map Development, the department will create the 3D Indoor Map. As a start, data from 150 buildings in Kowloon East will be collected first before extending to other buildings in the city.

The last stage 3D models of objects such as trees and lampposts for city modelling will be produced.

SAS Visual Analytics can be configured to send a notification to specific users when report objects contain data that meets certain criteria. This SAS note contains frequently asked questions about setting up alerts.

The SAS Stored Process Server does not create a detailed log file by default. However, you can create a detailed SAS Stored Process Server log file (that will contain information about all of the code that was executed) by using this approach. AUTO

Problems might occur when using SAS Enterprise Guide with dual monitors. For example, it might appear there is a performance problem with the query builder or other task, or it might appear that code or a task is hung, or

(Wiley) A recent Psycho-Oncology analysis of published studies found that few cancer survivors received financial information support from healthcare facilities during their initial treatment, even though cancer-related financial toxicity has multiple impacts on survivors' health and quality of life.