The proptech startup wanted to democratise investment in prime real estate projects through crowdfunding, but government regulations have limited its reach to high net worth individuals

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

Cătălin I. Cârstea, Gen Nakamura and Lauri Oksanen
Trans. Amer. Math. Soc. 373 (2020), 3423-3443.
Abstract, references and article information

R. E. Maĭboroda, G. V. Navara and O. V. Sugakova
Theor. Probability and Math. Statist. 99 (2020), 169-188.
Abstract, references and article information

A. G. Kukush and O. O. Chernova
Theor. Probability and Math. Statist. 99 (2020), 125-135.
Abstract, references and article information

Yu. V. Kozachenko and I. V. Rozora
Theor. Probability and Math. Statist. 99 (2020), 113-124.
Abstract, references and article information

A. V. Ivanov and I. K. Matsak
Theor. Probability and Math. Statist. 99 (2020), 91-99.
Abstract, references and article information

D. V. Gusak and E. V. Karnaukh
Theor. Probability and Math. Statist. 99 (2020), 77-89.
Abstract, references and article information

S. V. Bodnarchuk and O. M. Kulyk
Theor. Probability and Math. Statist. 99 (2020), 53-65.
Abstract, references and article information

C. Tintarev
St. Petersburg Math. J. 31 (2020), 421-434.
Abstract, references and article information

You don't need a backer to start a business. Here's how to start a business from scratch.

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.

To counter our adverse economic conditions, I have unveiled four sets of relief measures since last August. Totalling some $25 billion, the funds are focused on supporting businesses and lightening the burden weighing on the people of Hong Kong.

Meanwhile, we will continue to reach out to the community. Through wide-ranging dialogue communication and the pursuit of policies that address the deep-seated issues at the heart of our divide, I am hopeful that together we will find a path to peace and prosperity.

From an economic perspective, there is reason for optimism. I am heartened by the confidence private equity investors have shown in us. In the third quarter of 2019, some 560 private equity companies here managed US$153 billion.

We have nearly 50 more private equity (PE) firms based here when compared with the previous quarter. Among the world's top 10 PE fund managers, nine have a presence here in Hong Kong. That, ladies and gentlemen, underlines Hong Kong's formidable strengths in the Asian PE market. In that we trail only Mainland.

By channelling capital into corporations and startups in the innovation and technology field, PE and VC (venture capital) funds may well become as important as banks and IPO markets one day.

This Government is determined to help unlock the vast potential of the asset and wealth management business, because we believe you are critical to ensuring Hong Kong's status as one of the world's leading financial centres.

Fund-service centre 

That is why we have been stepping up efforts to sharpen Hong Kong's competitive edge on asset and wealth management through a multi-pronged approach including: (a) diversifying our fund structures and streamlining the licensing process to encourage fund formation; (b) adopting a more user-friendly approach to attract family offices; (c) providing a more facilitative tax environment for funds; and (d) expanding our fund distribution network through deepening our mutual access arrangements with other major financial markets.

On fund structure, the long-awaited, limited-partnership fund regime is close to reality, thanks in part to your favourable feedback. Indeed, we are now developing the necessary legislation. Because of the current filibustering at the Legislative Council, the tabling of the legislation got a little delayed, but it remains our top policy priority for the rest of this year to put this forward.

We are confident that the new regime will attract PE and VC funds, and we count on your support for that. With the new regime in place, we aim to bring in as many offshore funds as possible onshore to Hong Kong. We are well positioned to capture the opportunity arising from what happened on the international front over tax base erosion. This is mutually beneficial to Hong Kong as a fund hub and also the PE industry at large as you search for a new home for the funds you manage.

PE and VC funds, whether onshore or offshore, have enjoyed a profits tax exemption since last April. A tax-exempt fund can invest in local and overseas private companies. Hong Kong, by now, has a tax regime at fund level that is competitive and caters to the needs of the PE industry. I fully understand that resolving the tax issues at fund level is not enough in itself. It is of even greater importance to tackle head-on the tax arrangement for investment managers. This is a hard nut to crack, but one that I am determined to look into and come up with solutions that will strengthen Hong Kong's position as a leading fund hub with one of the most competitive tax arrangements for investment managers in the PE industry.

The significance of the limited partnership fund regime in completing Hong Kong's fund manufacturing infrastructure is underpinned by its precursor - the open-ended fund company regime. Since its operation in July 2018, a number of open-ended fund companies have sprouted. The SFC (Securities & Futures Commission) is also looking into how to make the regime more business-friendly to facilitate the take-up.

In short, the Government and our regulators are committed to developing Hong Kong into a full-fledged fund-service centre.

We are equally intent on expanding our fund-distribution network. We continue to expand our Mutual Recognition of Funds arrangements. Last year, Luxembourg and the Netherlands joined existing partners, the Mainland, Switzerland, France and the United Kingdom. More international partnerships will follow.

Family offices
Hong Kong is also an ideal location for the establishment of family offices, and we are boosting our promotional efforts in this regard.

The Hong Kong Monetary Authority and InvestHK will provide comprehensive services to attract family offices to Hong Kong. The SFC has also recently issued licensing guidance for PE firms and family offices. This will enhance clarity and would help address the industry's concerns.

Without a steady flow of talented professionals, of course, we will not be able to cash in on all the opportunities there for us. That is why the Government's Pilot Programme to Enhance Talent Training for the Asset & Wealth Management Sector has been supporting the industry since 2016.

I encourage you to offer exposure, opportunity and jobs for our youth. To give them a stake in the society through the programme.

Business bridge 

Zooming out a bit, the Government will continue to boost Hong Kong's singular advantage as the business and financial bridge between international markets and investors and their counterparts on the Mainland.

To that end, we continue to emphasise the established channels - our Stock Connects, Bond Connect and the Mutual Recognition of Funds arrangements. We will also strengthen our position as the global offshore Renminbi business hub.

Then there is the Guangdong-Hong Kong-Macao Greater Bay Area Development, and the extraordinary opportunity that it presents to Hong Kong.

With a GDP in excess of US$1.6 trillion and more than 70 million prosperous consumers, the Greater Bay Area presents vast potential for the asset and wealth management sector. For each and every one of you. The establishment of a Greater Bay Area wealth-management connect scheme, which was, as you know, recently announced, will go a long way towards realising that promise.

Our regulators are working out the details with their counterparts on the Mainland, and we will keep you posted and we are determined to push that forward as soon as possible. 

Financial Secretary Paul Chan gave these remarks at the Asia Private Equity Forum 2020 on January 15.

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.

On April 4, 1990, the Basic Law of the Hong Kong Special Administrative Region of the People’s Republic of China was adopted by the Seventh National People’s Congress (NPC) of the People’s Republic of China (PRC). The Basic Law enshrines the basic policies of the PRC regarding the Hong Kong Special Administrative Region (HKSAR) and provides a solid constitutional basis for the implementation of “one country, two systems”. Looking back, we must not forget the purpose and mission of the Basic Law.

The Basic Law clearly states that Hong Kong has been part of the territory of China since ancient times and is an inalienable part of the PRC. It is a Special Administrative Region enjoying a high degree of autonomy under the Central People’s Government. Upholding national unity and territorial integrity, maintaining the prosperity and stability of Hong Kong, and taking account of history and realities, the “one country, two systems” principle was put forth by Mr Deng Xiaoping as a way to preserve the characteristics and strengths of Hong Kong as much as possible and to enable Hong Kong citizens to maintain their way of life.

In the 22 years since her return to the motherland, Hong Kong has weathered different challenges and, on the whole, the implementation of “one country, two systems” has been successful. Leveraging on our strengths in free market economy, rule of law, independent judiciary and the free flow of information and with our country’s strong support, Hong Kong has developed into an international financial, trade and transportation centre and attracted more than 9,000 overseas and Mainland companies to establish offices here, with many of them making Hong Kong as their regional headquarters in Asia-Pacific.

International financial centre

Article 109 of the Basic Law confirms Hong Kong’s status as an international financial centre and stipulates that the Government of the Hong Kong Special Administrative Region shall provide an appropriate economic and legal environment for the maintenance of such status. Specifically, under the Basic Law:

- The Hong Kong dollar is the legal tender of the HKSAR and the linked exchange rate system has been maintained. With the strong support of the Central Government, Hong Kong has been able to maintain financial stability even during turbulent times. Riding on our country’s reform and opening up, Hong Kong has also developed into the world’s largest offshore renminbi centre.

 - The free flow of capital is protected and has attracted a large number of foreign direct investment and companies using Hong Kong as an ideal platform for initial public offerings and fundraising. Over the past 10 years, Hong Kong has topped the annual global IPO rankings six times.

- Hong Kong maintains a simple and low tax system, which is key to Hong Kong’s success as an international financial, trading and business centre. The Hong Kong Special Administrative Region Government is free to implement tax measures according to policy needs under its independent tax system. Since I took office, I have put in place initiatives such as the two-tier profits tax system and tax deduction for research and development expenditure to enhance Hong Kong’s competitiveness.

Rule of law and independent judiciary

The Basic Law preserves and guarantees Hong Kong’s long-established and trusted common law system and allows the HKSAR to enjoy independent judicial power, including that of final adjudication. The rule of law and an independent judiciary, which are held dearly by Hong Kong people, are constitutionally protected. The Basic Law stipulates that judges shall be appointed by the Chief Executive on the recommendation of an independent commission; for the appointment of judges of the Court of Final Appeal (CFA) and the Chief Judge of the High Court, the Chief Executive shall obtain the endorsement of the Legislative Council and report such appointment to the Standing Committee of the NPC for the record. Last month, I accepted the recommendation of the Judicial Officers Recommendation Commission to appoint the Honourable Justice Andrew Cheung, Permanent Judge of the CFA, to succeed The Honourable Chief Justice Geoffrey Ma who will retire next year.

The Basic Law also allows the CFA to draw on the experience of judges from other common law jurisdictions. Currently, 15 eminent judges from the United Kingdom, Australia and Canada are sitting on the CFA as non-permanent judges. Their participation shows that our rule of law and independent judiciary are well recognised.

Rights and freedoms of residents

The fundamental rights and freedoms of Hong Kong residents are fully protected by the Basic Law. Under Chapter 3, Hong Kong residents shall have freedom of speech, of the press and of publication; freedom of association, of assembly, of procession and of demonstration; freedom of the person; freedom of communication; freedom of religious belief; freedom of choice of occupation; freedom to engage in academic research, literary and artistic creation, and other cultural activities; freedom of marriage and so forth. However, as pointed out by our courts in their judgments, freedom is not absolute; one should respect the rights and freedoms of other people and be subject to law when exercising such freedoms.

Developing external affairs

Hong Kong has always been a bridge between the East and the West. The Basic Law allows the HKSAR to maintain and develop relations with foreign states and regions and relevant international organisations in the appropriate fields, including economic, trade, financial and monetary, shipping, communications, tourism, cultural and sports fields on its own, using the name Hong Kong, China. The HKSAR has participated in the World Trade Organization, the World Meteorological Organization, the Asia-Pacific Economic Cooperation and many others in the name Hong Kong, China and has entered into hundreds of bilateral agreements with other countries, including Free Trade Agreements, Investment Promotion & Protection Agreements and Comprehensive Double Taxation Agreements. Hong Kong athletes can also represent Hong Kong in international competitions.

The implementation of “one country, two systems” fully demonstrates that it is the best institutional arrangement to maintain Hong Kong’s long-term prosperity and stability. As a pioneering initiative, its application entails an evolving process and we have to effectively and fully apply this principle in order to maintain the prosperity and stability of Hong Kong, to meet the aspirations of our citizens and to meet the fundamental interests of our country. I encourage all Hong Kong citizens to learn more about the Basic Law, including the institutional safeguards, and the rights and duties of Hong Kong residents. In so doing, we should consider how best we can continue to leverage on Hong Kong’s advantages, allowing Hong Kong to advance with the country and enabling every Hong Kong resident to realise their goal.

Chief Executive Carrie Lam wrote this op-ed entitled The Basic Law - Best Safeguard for the Prosperity & Stability of Hong Kong on April 4.

The banking sector today launched a scheme to alleviate the cashflow pressure faced by corporate customers in light of the economic challenges brought about by the COVID-19 outbreak.

Jointly announced by the Monetary Authority and the Banking Sector SME Lending Coordination Mechanism, the Pre-approved Principal Payment Holiday Scheme is estimated to cover more than 80% of all corporate borrowers in Hong Kong.

All corporate customers that have an annual sales turnover of $800 million or less and with no outstanding loan payments overdue for more than 30 days are eligible for the scheme.

Eligible customers’ loan principal payments due within a six-month period between May 1 and October 31 this year will be pre-approved for deferment.

The loans’ principal payments, including revolving facilities, will generally be deferred by six months, whereas trade facilities, given their short-term nature, will be deferred by three months.

The scheme does not cover syndicated loans or loans used for financing purchases of shares or other financial assets.

Banks will begin informing eligible customers of the pre-approval under the scheme as soon as practicable. Eligible customers do not need to apply. They only need to contact the bank within 14 days of the bank’s notice to confirm the detailed arrangements.

The authority has issued a circular requesting all banks to participate in the scheme and has received support from all 11 major lenders in the co-ordination mechanism.

It will monitor the scheme’s operation and maintain close dialogue with banks.

Start-up Express, a development programme launched by the Hong Kong Trade Development Council (HKTDC) in 2018, is returning for its third edition to help local start-ups build connections, explore markets, seek partners and enhance...

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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.

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

The 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.

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.

"Driverless cars, robot butlers and reusable rockets--if the big inventions of the past decade and the artificial intelligence developed to create them have taught us anything, it's that maths is undeniably cool. And if you’re still not convinced, chances are you’ve never had it explained to you via a live experiment with a pigeon before. Temporary pigeon handler and queen of making numbers fun is Dr Hannah Fry, the host of this year's annual Royal Institution Christmas Lectures." Learn more in "Christmas Lectures presenter Dr Hannah Fry on pigeons, AI and the awesome power of maths," by Rachael Pells, inews, December 23, 2019.

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.

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.

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.

Aldehyde oxidases (AOXs) are a small group of enzymes belonging to the larger family of molybdo-flavoenzymes, along with the well-characterized xanthine oxidoreductase. The two major types of reactions that are catalyzed by AOXs are the hydroxylation of heterocycles and the oxidation of aldehydes to their corresponding carboxylic acids. Different animal species have different complements of AOX genes. The two extremes are represented in humans and rodents; whereas the human genome contains a single active gene (AOX1), those of rodents, such as mice, are endowed with four genes (Aox1-4), clustering on the same chromosome, each encoding a functionally distinct AOX enzyme. It still remains enigmatic why some species have numerous AOX enzymes, whereas others harbor only one functional enzyme. At present, little is known about the physiological relevance of AOX enzymes in humans and their additional forms in other mammals. These enzymes are expressed in the liver and play an important role in the metabolisms of drugs and other xenobiotics. In this review, we discuss the expression, tissue-specific roles, and substrate specificities of the different mammalian AOX enzymes and highlight insights into their physiological roles.

For successful infection of their hosts, pathogenic bacteria recognize host-derived signals that induce the expression of virulence factors in a spatiotemporal manner. The fulminating food-borne pathogen Vibrio vulnificus produces a cytolysin/hemolysin protein encoded by the vvhBA operon, which is a virulence factor preferentially expressed upon exposure to murine blood and macrophages. The Fe-S cluster containing transcriptional regulator IscR activates the vvhBA operon in response to nitrosative stress and iron starvation, during which the cellular IscR protein level increases. Here, electrophoretic mobility shift and DNase I protection assays revealed that IscR directly binds downstream of the vvhBA promoter PvvhBA, which is unusual for a positive regulator. We found that in addition to IscR, the transcriptional regulator HlyU activates vvhBA transcription by directly binding upstream of PvvhBA, whereas the histone-like nucleoid-structuring protein (H-NS) represses vvhBA by extensively binding to both downstream and upstream regions of its promoter. Of note, the binding sites of IscR and HlyU overlapped with those of H-NS. We further substantiated that IscR and HlyU outcompete H-NS for binding to the PvvhBA regulatory region, resulting in the release of H-NS repression and vvhBA induction. We conclude that concurrent antirepression by IscR and HlyU at regions both downstream and upstream of PvvhBA provides V. vulnificus with the means of integrating host-derived signal(s) such as nitrosative stress and iron starvation for precise regulation of vvhBA transcription, thereby enabling successful host infection.

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.