Banks and financial institutions taking part in providing mortgage loans for the Housing Authority Subsidised Sale Flats Scheme (SSFS) may offer a mortgage principal moratorium plan to the scheme’s mortgagors.

The authority today wrote to these institutions to confirm and agree that such a plan is applicable for SSFS flats.

Principal repayment may be deferred for a maximum 12-month period and the mortgage loan repayment period may be extended correspondingly by a maximum of 12 months.

The principal moratorium period may commence by December 31 this year at the latest.

The arrangement is applicable to the Home Ownership Scheme, the Private Sector Participation Scheme, the Buy or Rent Option Scheme, the Tenants Purchase Scheme and the Green Form Subsidised Home Ownership Scheme in the primary market and under the Secondary Market Scheme.

To encourage participating financial institutions to provide mortgage loans and better mortgage terms for SSFS flat purchasers, the authority provides a mortgage default guarantee for them.

It undertakes to meet the shortfall in repayment in the event of default by the borrowers under specified circumstances during the guarantee period.

Due to the requirements in the guarantee deed on the mortgage loan period and the monthly instalment amount, participating financial institutions may not be able to offer a mortgage principal moratorium plan to SSFS flat owners.

In light of the economic downturn arising from the COVID-19 outbreak, the authority confirmed today that a mortgage principal moratorium plan is applicable for SSFS flats.

The move will encourage participating financial institutions to offer such a plan to SSFS flat owners, reducing their burden of mortgage repayment.

Applications for the $1.3 billion in subsidies earmarked for registered owners of goods vehicles and green minibus operators under the Anti-epidemic Fund opened today, the Transport Department announced.

A one-off non-accountable subsidy of $10,000 will be provided to each registered goods vehicle owner for each goods vehicle.

From today until September 30, registered owners of goods vehicles who have received the department's letters must use the registration PIN provided in the letters for submission of registrations through GovHK.

After successful completion of registration, the subsidy will be disbursed to the designated local bank account provided in the registration through autopay in about two to three weeks.

Cross-boundary goods vehicle drivers who conduct nucleic acid tests in Hong Kong can apply for the subsidy on an accountable basis, with the maximum amount being $350 per test.

A one-off non-accountable subsidy of $30,000 per green minibus will be provided to each holder of a Passenger Service Licence-Public Light Bus (Scheduled) Service who has been approved to operate a relevant green minibus route package.

The department briefed the green minibus trade today on the subsidy arrangement and application details with the distribution of the application forms.

Green minibus operators are required to send the completed application forms to the department by post on or before September 30.

After the department has verified their submissions, the subsidy will be disbursed through autopay in about one month.

To assist the transport trades to cope with operational demands in the prevailing economic environment, the Government has rolled out the fuel subsidy and one-off subsidy measures under the first round of the Anti-epidemic Fund progressively.

As of mid-April, the department has received applications for subsidies from three franchised bus companies, 10 franchised and licensed ferry operators, Hong Kong Tramways Limited, registrations from 1,700 registered owners of non-franchised public buses, school private light buses and hire cars. Over $100 million of the subsidies have been disbursed.

Click here for details.

The tender for a Mong Kok site has been awarded on a 50-year land grant at a premium of $467.18 million, the Lands Department announced today.

Kowloon Inland Lot No. 11240 at the junction of Soy Street and Shanghai Street was awarded to Worth Forever, a subsidiary of Bring Bright.

It has a site area of about 625.5 sq m with a minimum gross floor area of 3,751.75 sq m.

The maximum gross floor area for private residential purposes is 4,691.25 sq m.

The maximum gross floor area for non-industrial purposes is computed according to the relevant special condition in the conditions of sale.

Carla E. Cox
Aug 1, 2017; 30:157-160
From Research to Practice

Betsy B. Dokken
Jul 1, 2007; 20:166-170
Articles

Brenna Cholerton
Nov 1, 2016; 29:210-219
From Research to Practice

Priscilla Hollander
Jul 1, 2007; 20:159-165
Articles

Ryan A. Ristau
Nov 1, 2013; 26:211-215
From Research to Practice

John Zrebiec
Oct 1, 2006; 19:212-215
Clinical Decision Making

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

Janet L. Kelly
Aug 1, 2014; 27:218-223
Pharmacy and Therapeutics

Betsy B. Dokken
Jul 1, 2008; 21:160-165
From Research to Practice/Cardiovascular Disease and Diabetes

Guillermo E. Umpierrez
Jan 1, 2002; 15:
Articles

Property management companies and owners’ organisations which have successfully applied for an anti-epidemic support scheme were reminded today to disburse the hardship allowance to frontline workers as soon as practicable upon receiving the subsidies.

The Home Affairs Department said the workers concerned shall acknowledge receipt of the allowance using the prescribed forms.

The property management companies or owners’ organisations shall submit a report on the allowance’s overall payment to the Property Management Services Authority within three months of receiving the subsidies.

The department and/or the authority will conduct a random review and check to ensure that the frontline property management workers have received the allowance.

As of today, more than 8,160 applications have been received for the Anti-epidemic Support Scheme for Property Management Sector under the Anti-epidemic Fund.

About 2,850 applications have been approved, involving more than $100 million in subsidies and benefitting more than 17,500 building blocks and about 25,500 frontline workers.

Call 3696 1156 or 3696 1166 for enquiries.

The Commerce & Economic Development Bureau today announced that the subsidy quota for three mask production lines have been reassigned.

Three production lines, previously approved under the Local Mask Production Subsidy Scheme, have withdrawn from the scheme, the Government said.

The subsidy quota concerned has been allocated to SDL Skin (Asia), Safeguard HK and SwissTech.

SDL Skin (Asia) has been approved for obtaining a subsidy for a second production line and is expected to supply an average of 1.6 million masks every month to the Government. The production line may receive a subsidy of up to $1 million.

Safeguard HK has been approved for obtaining a subsidy for one production line and is expected to supply an average of 500,000 masks to the Government every month. The production line may receive up to $2 million.

SwissTech has been approved for obtaining a subsidy for one production line and is expected to supply an average of 2 million masks every month to the Government and produce a further 1 million masks on average monthly for the local market.

The production line may receive up to $3 million.

It is estimated that when all 20 subsidised lines under the scheme are in full production, they will collectively supply 33.85 million masks to the Government and a further 7.15 million to the local market monthly.

The companies which withdrew from the scheme were CareHK and Shang Manufactory.

The Government did not sign agreements with or make disbursements to these firms.

The Food & Environmental Hygiene Department announced that applications for the Catering Business (Social Distancing) Subsidy Scheme, under the second round of the Anti-epidemic Fund, will start from May 5.

The department said the scheme, which is estimated to benefit 16,000 catering outlets and their employees, will provide financial relief measures to the catering businesses which have been hard hit by the COVID-19 epidemic and social distancing measures.

It will provide subsidies ranging from $250,000 to $2,200,000 to eligible licence holders of general restaurants, light refreshment restaurants, marine restaurants and factory canteens in operation according to the floor area of the premises as specified on the licence.

The primary goal of the scheme is to support the payment of employees' salaries during a six-month period following application approval.

To provide immediate relief to the catering sector, the subsidy will be dished out upfront, in two tranches.

To avoid abuse, applicants should undertake that there will be no redundancy of staff for three months on receipt of the first tranche of subsidy and another three months on receipt of the second tranche.

They should also undertake that not less than 80% of the subsidies for respective months would be used to pay salaries of staff working at the premises.

Applicants should submit within a specified period a certificate issued by a Certified Public Accountant (practising) on its total staff salaries and total number of salaried staff for each of the months covered by the subsidy.

They should also submit a certificate issued by a CPA on its total staff salaries and total number of staff working at the premises for the month of March this year.

To avoid double benefits, applicants should declare that they have not and will not submit any application under the Employment Support Scheme.

Each catering outlet directed to close its licensed premises under the Prevention & Control of Disease (Requirements & Directions) (Business & Premises) Regulation, including karaoke establishments, nightclubs and bars or pubs, is eligible for a further one-off subsidy of $50,000.

Applications should be submitted to the department's District Environmental Hygiene Offices in person or by mail. Food licence holders can also submit their applications through the website.

The deadline for application is June 5.

Upon receipt of the completed application form and supporting documents and after verification, the disbursement of the first tranche of subsidies can generally be made in two to three weeks by crossed cheques to the corresponding licensed food premises.

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.”

GitHub is holding its annual 'Universe' conference in San Francisco this week.

The coach and rail journey app has launched a new AI voice app for automated disruption alerts

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

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

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

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

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

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

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

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

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

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

Secretary for Innovation & Technology Alfred Sit today met representatives of the Hong Kong Science & Technology Parks Corporation (HKSTPC) and research and development centres (R&D) specialising in innovations winning recognition worldwide.

While touring the Hong Kong Science Park, Mr Sit visited the Hong Kong Applied Science & Technology Research Institute, the Logistics & Supply Chain MultiTech R&D Centre, the Nano & Advanced Materials Institute and HKSTPC.

He met representatives of HKSTPC start-ups that specialise in healthcare technology, artificial intelligence, chips, material science and vehicle safety technology. Some start-ups have participated in the StayHomeSafe mobile app.

Mr Sit noted that Science Park is a breeding ground for local innovation and technology that shows tremendous strength.

He emphasised that with the concerted efforts of the HKSTPC and all R&D centres, batches of R&D talent have been nurtured, with their innovations winning recognition worldwide.

Their work has also helped consolidate Hong Kong's R&D strengths, promote applied R&D and foster commercialisation of R&D results, he added.

On the application of technology solutions in fighting the COVID-19 pandemic, the secretary pointed out that the electronic wristbands and StayHomeSafe mobile app used for home quarantine arrangements, the NASK Nanofiber Smart Mask supplied to the Hospital Authority and the CuMask are all R&D achievements from Science Park.

Mr Sit said he hoped that with the collaborative efforts of the HKSTPC and R&D centres, the I&T development in Hong Kong will be further promoted, driving economic development and improving people's livelihood.

Secretary for Financial Services & the Treasury Christopher Hui today visited the Companies Registry (CR) to inspect its operation.

Mr Hui visited the New Companies Section, the Public Search Section and the Document Management Section at the registry and spoke with staff there to learn about their work conditions and the services that they provide.

He said: “The COVID-19 pandemic has dealt a heavy blow to Hong Kong's overall economy.

“To help enterprises cope with their operating pressure amid the economic downturn, the Financial Secretary announced in the 2020-21 Budget the waiver of registration fees for annual returns, except for late delivery, charged by the CR for two years.

“And with a view to encouraging the wider use of the CR's electronic services, we also propose to reduce the fees payable in relation to the incorporation of companies, including registration of non-Hong Kong companies, through electronic means by 10%."

The Companies (Fees) (Amendment) Regulation 2020 gazetted today will be tabled at the Legislative Council for negative vetting on May 13 for the waiver and reduction to take effect from October 1.

The waiver of registration fees for annual returns will benefit about 1.4 million companies.

Mr Hui added that he was pleased that the CR has been providing electronic services for filing of documents and company searches.

He appealed to the department to adopt wider use of technology, adding that a business-friendly environment is needed more than ever in the process of economic recovery.

Mr Hui also expressed gratitude to CR staff for their dedication in providing public services amid the pandemic.

The CuMasks have undergone strict testing and certification processes before the product will be distributed to help people combat the COVID-19 virus, Secretary for Innovation & Technology Alfred Sit said today.

Mr Sit’s remarks came amid public concerns over the safety of the free reusable face masks that the Government plans to distribute to all Hong Kong citizens.

Addressing reporters after attending a radio programme this morning, Mr Sit said: “The product has gone through a very comprehensive and clear testing and certification process.

“The product can fully comply with the American Society for Testing & Materials (ASTM) F2100 Level 1 requirement, so that the product can fully meet the need of protecting our people from COVID-19.

“I have to emphasise that this whole process must be done by proper laboratories and that’s what we have done.”

Mr Sit noted that a dedicated website on the CuMask has been set up that contains information on the testing reports of the masks.

“For those people who may not have a complete understanding about our product, they may go to our website so that they can see the reports and certificates.

“I fully hope this product can help our people to combat COVID-19.That’s what we would like to do."

(Arizona State University) Cun-Zheng Ning, a professor of electrical engineering in the Ira A. Fulton Schools of Engineering at Arizona State University, and collaborators from Tsinghua University in China discovered a process of physics that enables low-power nanolasers to be produced in 2D semiconductor materials. Understanding the physics behind lasers at nanoscale and how they interact with semiconductors can have major implications for high-speed communication channels for supercomputers and data centers.

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

(Johannes Gutenberg Universitaet Mainz) Scientists at Johannes Gutenberg University Mainz (JGU) and the Helmholtz Institute Mainz (HIM) in Germany have presented a non-contact method for detecting the state of charge and any defects in lithium-ion batteries.

(Lancaster University) Lancaster University's Dr Samuli Autti has been awarded a Young Scientist Prize 2020 by the International Union of Pure and Applied Physics. The prestigious prize, awarded only once every three years, was made by the Low Temperature Commission of the IUPAP.

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.

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

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

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

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

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

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

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

He added that the patient is in a stable condition.

Secretary for Home Affairs Caspar Tsui visited the Physical Fitness Association of Hong Kong, China today to inspect its work in implementing the Fitness Centre Subsidy Scheme launched under the second phase of the Anti-epidemic Fund.

Mr Tsui said the scheme aims to provide a one-off subsidy of $100,000 to fitness centres to tide businesses over financial difficulties arising from anti-epidemic measures.

He thanked the association for handling the scheme’s applications.

Mr Tsui also expressed gratitude to the fitness industry for complying with the Government’s preventive measures, including suspension of business, in the fight against the virus.

Given the stabilising epidemic situation, the Government has conducted a health risk assessment and will allow premises, including fitness centres, to resume operations, Mr Tsui said, adding that he hopes the fitness industry will soon regain vitality.

The Home Affairs Bureau commissioned the association to assist in implementing the scheme, which opened for applications on May 4.

As of May 7, the association received 397 applications, of which more than half of them have been initially found to be eligible, involving subsidies of about $20 million.

The application period for the scheme will end on June 3.

Call 2302 9089 or send an email for enquiries.

"Artist uses snow as canvas for massive geometrical designs," by Thomas Peipert, AP, January 16, 2020.

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.

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

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.

Previous studies have shown that sphingosine kinase interacting protein (SKIP) inhibits sphingosine kinase (SK) function in fibroblasts. SK phosphorylates sphingosine producing the potent signaling molecule sphingosine-1-phosphate (S1P). SKIP gene (SPHKAP) expression is silenced by hypermethylation of its promoter in acute myeloid leukemia (AML). However, why SKIP activity is silenced in primary AML cells is unclear. Here, we investigated the consequences of SKIP down-regulation in AML primary cells and the effects of SKIP re-expression in leukemic cell lines. Using targeted ultra-HPLC-tandem MS (UPLC-MS/MS), we measured sphingolipids (including S1P and ceramides) in AML and control cells. Primary AML cells had significantly lower SK activity and intracellular S1P concentrations than control cells, and SKIP-transfected leukemia cell lines exhibited increased SK activity. These findings show that SKIP re-expression enhances SK activity in leukemia cells. Furthermore, other bioactive sphingolipids such as ceramide were also down-regulated in primary AML cells. Of note, SKIP re-expression in leukemia cells increased ceramide levels 2-fold, inactivated the key signaling protein extracellular signal-regulated kinase, and increased apoptosis following serum deprivation or chemotherapy. These results indicate that SKIP down-regulation in AML reduces SK activity and ceramide levels, an effect that ultimately inhibits apoptosis in leukemia cells. The findings of our study contrast with previous results indicating that SKIP inhibits SK function in fibroblasts and therefore challenge the notion that SKIP always inhibits SK activity.

Prostate cancer (PCa) cells heavily rely on an active androgen receptor (AR) pathway for their survival. Enzalutamide (MDV3100) is a second-generation antiandrogenic drug that was approved by the Food and Drug Administration in 2012 to treat patients with castration-resistant prostate cancer (CRPC). However, emergence of resistance against this drug is inevitable, and it has been a major challenge to develop interventions that help manage enzalutamide-resistant CRPC. Erythropoietin-producing human hepatocellular (Eph) receptors are targeted by ephrin protein ligands and have a broad range of functions. Increasing evidence indicates that this signaling pathway plays an important role in tumorigenesis. Overexpression of EPH receptor B4 (EPHB4) has been observed in multiple types of cancer, being closely associated with proliferation, invasion, and metastasis of tumors. Here, using RNA-Seq analyses of clinical and preclinical samples, along with several biochemical and molecular methods, we report that enzalutamide-resistant PCa requires an active EPHB4 pathway that supports drug resistance of this tumor type. Using a small kinase inhibitor and RNAi-based gene silencing to disrupt EPHB4 activity, we found that these disruptions re-sensitize enzalutamide-resistant PCa to the drug both in vitro and in vivo. Mechanistically, we found that EPHB4 stimulates the AR by inducing proto-oncogene c-Myc (c-Myc) expression. Taken together, these results provide critical insight into the mechanism of enzalutamide resistance in PCa, potentially offering a therapeutic avenue for enhancing the efficacy of enzalutamide to better manage this common malignancy.

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

Haploinsufficiency of Meis homeobox 2 (MEIS2), encoding a transcriptional regulator, is associated with human cleft palate, and Meis2 inactivation leads to abnormal palate development in mice, implicating MEIS2 functions in palate development. However, its functional mechanisms remain unknown. Here we observed widespread MEIS2 expression in the developing palate in mice. Wnt1Cre-mediated Meis2 inactivation in cranial neural crest cells led to a secondary palate cleft. Importantly, about half of the Wnt1Cre;Meis2f/f mice exhibited a submucous cleft, providing a model for studying palatal bone formation and patterning. Consistent with complete absence of palatal bones, the results from integrative analyses of MEIS2 by ChIP sequencing, RNA-Seq, and an assay for transposase-accessible chromatin sequencing identified key osteogenic genes regulated directly by MEIS2, indicating that it plays a fundamental role in palatal osteogenesis. De novo motif analysis uncovered that the MEIS2-bound regions are highly enriched in binding motifs for several key osteogenic transcription factors, particularly short stature homeobox 2 (SHOX2). Comparative ChIP sequencing analyses revealed genome-wide co-occupancy of MEIS2 and SHOX2 in addition to their colocalization in the developing palate and physical interaction, suggesting that SHOX2 and MEIS2 functionally interact. However, although SHOX2 was required for proper palatal bone formation and was a direct downstream target of MEIS2, Shox2 overexpression failed to rescue the palatal bone defects in a Meis2-mutant background. These results, together with the fact that Meis2 expression is associated with high osteogenic potential and required for chromatin accessibility of osteogenic genes, support a vital function of MEIS2 in setting up a ground state for palatal osteogenesis.

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