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

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

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

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

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

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

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

Developments of the epidemic

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

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

Anti-epidemic efforts

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

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

Date

Event

March 25-26

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

March 25-26

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

March 27

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

April 1-2

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

April 5

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

April 8

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

April 8

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

April 8

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

April 9

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

April 10

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

April 11

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

April 19

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

April 19

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

April 20

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

April 21

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

April 22

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

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

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

Supporting individuals and businesses affected by the disease

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

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

Fighting the virus together

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

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

Ensemble SU from Korea will stage a concert at Sha Tin Town Hall in December.

The quintet breaks boundaries by merging both traditional Korean musical instruments with Western instruments to bring music to life.

The world touring group plays works ranging from Arirang Rhapsody to Bohemian Rhapsody and from Bul-no-ha to the jazz classic Take Five.

The concert will be held at 8pm on December 6 and tickets are available at URBTIX.

Click here for details.

An extraordinary strings crossover performance by erhu master Xu Ke and the Tokyo String Quintet will be held in December.

Heralded as the Paganini of the erhu world, Mr Xu is currently a guest professor at the Shanghai Conservatory of Music and the Senzoku Gakuen College of Music in Japan.

Presented by the Leisure & Cultural Services Department as part of the Music Delight Series, the concert will be held at Tsuen Wan Town Hall on December 14.

Tickets are available at URBTIX.

Click here for details.

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

Guest of Honour at Film Mayo launch on 1st December

Sarah Tomasello
Jan 1, 2008; 21:19-25
Articles

Nancy J. D'Hondt
Oct 1, 2008; 21:255-261
Articles

Jennal L. Johnson
Jul 1, 2006; 19:148-153
Articles

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

Geralyn Spollett
Jan 1, 2003; 16:
Case Studies

The Government is set to revive the economy through different measures and everyone should act together to attain this goal.

Secretary for Financial Services & the Treasury Christopher Hui made the remarks today after attending a radio programme, saying the economy has been seriously affected by the epidemic.

“I think right now the immediate priority is definitely to revive the economy because after all, we have been subjected to many restrictions on all you can imagine in the past few months due to COVID-19.

“So the immediate priority is really for us to act together to revive the economy through different measures.

“And the measures that are subject to the Legislative Council’s approval as you have seen over the past few days, I think are definitely something that we want to do in order to provide a sort of foundation for our economic recovery.”

(To watch the whole media session with sign language interpretation, click here.)

Hong Kong's economy in the first quarter of 2020 contracted 8.9% over a year earlier, the largest decline on record since 1974.

The Census & Statistics Department announced the findings today as it released advance estimates on Gross Domestic Product for the first quarter.

Addressing the media today, Financial Secretary Paul Chan noted the economic recession deepened in Hong Kong in the first quarter of 2020.

“Although locally, the epidemic situation seems to be under control, but the external environment is still very challenging. Globally, the epidemic is yet to be put under complete control. That will affect our exports. That will also affect international travelling and business investments. 

“So, going forward in the second quarter, we believe that even if there is improvement, the improvement will be gradual and small.”

According to those estimates, private consumption expenditure decreased 10.2% in real terms in the first quarter from a year earlier, deteriorating from the 2.9% decline in the fourth quarter of 2019.

Government consumption expenditure grew 8.3% year-on-year, after the increase of 6.1% in the fourth quarter of 2019.

Gross domestic fixed capital formation dropped by 13.9%, compared with the decrease of 16.8% in the previous quarter.

Over the same period, total exports of goods declined 9.7% and imports of goods also fell 10.9%.

Exports of services dropped 37.8% and imports of services decreased 25.4%.

Mr Chan called on people to work together to promote economic development by consumption.

“If we are able to work together, if we can unite together - not just to fight the virus, but to stimulate consumption to promote economic development - I think the economic situation will be able to stabilise somewhat in the second quarter. 

“If the global epidemic situation improves, we will be able to come out of recession gradually towards the end of this year. 

“I will appeal to our people's support for us to roll out various measures in the Anti-epidemic Fund - round one and round two - as well as the relief packages in the 2020-21 Budget as soon as possible.

“Many of those initiatives are still yet to be implemented. Upon full implementation of those measures, I think the positive impact on the economy would be better felt by the community. We will be monitoring the situation carefully.”

The Government stands ready to roll out additional measures to support Hong Kong people and the businesses, Mr Chan added.

The 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

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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.

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Review all AMS Resources & Updates.

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

Roadside Stations: 2 (Health Risk: Low)

(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.

Congratulations to the 2020 AMS Math Poetry Contest Winners in the middle school, high school, and college categories: Sabrina Little, Mackintosh Academy, Boulder, for "Outlier;" Austen Mazenko, Cherry Creek High School, for "The Number Won; and Chenyu Lin, Colorado Christian University, for "x² + y² = 1(ife)." The poems were read during Mathemati-Con at the 2020 Joint Mathematics Meetings in Denver, CO. Read the poems and learn about the contest and Math and Poetry. (Photo: (left to right) Austen Mazenko, Sabrina Little, poetry contest judge Gizem Karaali, and Chenyu Lin.

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.

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.

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

Heme-regulatory motifs (HRMs) are present in many proteins that are involved in diverse biological functions. The C-terminal tail region of human heme oxygenase-2 (HO2) contains two HRMs whose cysteine residues form a disulfide bond; when reduced, these cysteines are available to bind Fe3+-heme. Heme binding to the HRMs occurs independently of the HO2 catalytic active site in the core of the protein, where heme binds with high affinity and is degraded to biliverdin. Here, we describe the reversible, protein-mediated transfer of heme between the HRMs and the HO2 core. Using hydrogen-deuterium exchange (HDX)-MS to monitor the dynamics of HO2 with and without Fe3+-heme bound to the HRMs and to the core, we detected conformational changes in the catalytic core only in one state of the catalytic cycle—when Fe3+-heme is bound to the HRMs and the core is in the apo state. These conformational changes were consistent with transfer of heme between binding sites. Indeed, we observed that HRM-bound Fe3+-heme is transferred to the apo-core either upon independent expression of the core and of a construct spanning the HRM-containing tail or after a single turnover of heme at the core. Moreover, we observed transfer of heme from the core to the HRMs and equilibration of heme between the core and HRMs. We therefore propose an Fe3+-heme transfer model in which HRM-bound heme is readily transferred to the catalytic site for degradation to facilitate turnover but can also equilibrate between the sites to maintain heme homeostasis.

Cell-surface signaling (CSS) in Gram-negative bacteria involves highly conserved regulatory pathways that optimize gene expression by transducing extracellular environmental signals to the cytoplasm via inner-membrane sigma regulators. The molecular details of ferric siderophore-mediated activation of the iron import machinery through a sigma regulator are unclear. Here, we present the 1.56 Å resolution structure of the periplasmic complex of the C-terminal CSS domain (CCSSD) of PupR, the sigma regulator in the Pseudomonas capeferrum pseudobactin BN7/8 transport system, and the N-terminal signaling domain (NTSD) of PupB, an outer-membrane TonB-dependent transducer. The structure revealed that the CCSSD consists of two subdomains: a juxta-membrane subdomain, which has a novel all-β-fold, followed by a secretin/TonB, short N-terminal subdomain at the C terminus of the CCSSD, a previously unobserved topological arrangement of this domain. Using affinity pulldown assays, isothermal titration calorimetry, and thermal denaturation CD spectroscopy, we show that both subdomains are required for binding the NTSD with micromolar affinity and that NTSD binding improves CCSSD stability. Our findings prompt us to present a revised model of CSS wherein the CCSSD:NTSD complex forms prior to ferric-siderophore binding. Upon siderophore binding, conformational changes in the CCSSD enable regulated intramembrane proteolysis of the sigma regulator, ultimately resulting in transcriptional regulation.

Accumulating evidence suggests that brown adipose tissue (BAT) is a potential therapeutic target for managing obesity and related diseases. PGAM family member 5, mitochondrial serine/threonine protein phosphatase (PGAM5), is a protein phosphatase that resides in the mitochondria and regulates many biological processes, including cell death, mitophagy, and immune responses. Because BAT is a mitochondria-rich tissue, we have hypothesized that PGAM5 has a physiological function in BAT. We previously reported that PGAM5-knockout (KO) mice are resistant to severe metabolic stress. Importantly, lipid accumulation is suppressed in PGAM5-KO BAT, even under unstressed conditions, raising the possibility that PGAM5 deficiency stimulates lipid consumption. However, the mechanism underlying this observation is undetermined. Here, using an array of biochemical approaches, including quantitative RT-PCR, immunoblotting, and oxygen consumption assays, we show that PGAM5 negatively regulates energy expenditure in brown adipocytes. We found that PGAM5-KO brown adipocytes have an enhanced oxygen consumption rate and increased expression of uncoupling protein 1 (UCP1), a protein that increases energy consumption in the mitochondria. Mechanistically, we found that PGAM5 phosphatase activity and intramembrane cleavage are required for suppression of UCP1 activity. Furthermore, utilizing a genome-wide siRNA screen in HeLa cells to search for regulators of PGAM5 cleavage, we identified a set of candidate genes, including phosphatidylserine decarboxylase (PISD), which catalyzes the formation of phosphatidylethanolamine at the mitochondrial membrane. Taken together, these results indicate that PGAM5 suppresses mitochondrial energy expenditure by down-regulating UCP1 expression in brown adipocytes and that its phosphatase activity and intramembrane cleavage are required for UCP1 suppression.

NAD+ is a central metabolite participating in core metabolic redox reactions. The prokaryotic NAD synthetase enzyme NadE catalyzes the last step of NAD+ biosynthesis, converting nicotinic acid adenine dinucleotide (NaAD) to NAD+. Some members of the NadE family use l-glutamine as a nitrogen donor and are named NadEGln. Previous gene neighborhood analysis has indicated that the bacterial nadE gene is frequently clustered with the gene encoding the regulatory signal transduction protein PII, suggesting a functional relationship between these proteins in response to the nutritional status and the carbon/nitrogen ratio of the bacterial cell. Here, using affinity chromatography, bioinformatics analyses, NAD synthetase activity, and biolayer interferometry assays, we show that PII and NadEGln physically interact in vitro, that this complex relieves NadEGln negative feedback inhibition by NAD+. This mechanism is conserved in distantly related bacteria. Of note, the PII protein allosteric effector and cellular nitrogen level indicator 2-oxoglutarate (2-OG) inhibited the formation of the PII-NadEGln complex within a physiological range. These results indicate an interplay between the levels of ATP, ADP, 2-OG, PII-sensed glutamine, and NAD+, representing a metabolic hub that may balance the levels of core nitrogen and carbon metabolites. Our findings support the notion that PII proteins act as a dissociable regulatory subunit of NadEGln, thereby enabling the control of NAD+ biosynthesis according to the nutritional status of the bacterial cell.

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.

Kindlins are focal adhesion proteins that regulate integrin activation and outside-in signaling. The kindlin family consists of three members, kindlin-1, -2, and -3. Kindlin-2 is widely expressed in multiple cell types, except those from the hematopoietic lineage. A previous study has reported that the Drosophila Fit1 protein (an ortholog of kindlin-2) prevents abnormal spindle assembly; however, the mechanism remains unknown. Here, we show that kindlin-2 maintains spindle integrity in mitotic human cells. The human neuroblastoma SH-SY5Y cell line expresses only kindlin-2, and we found that when SH-SY5Y cells are depleted of kindlin-2, they exhibit pronounced spindle abnormalities and delayed mitosis. Of note, acetylation of α-tubulin, which maintains microtubule flexibility and stability, was diminished in the kindlin-2–depleted cells. Mechanistically, we found that kindlin-2 maintains α-tubulin acetylation by inhibiting the microtubule-associated deacetylase histone deacetylase 6 (HDAC6) via a signaling pathway involving AKT Ser/Thr kinase (AKT)/glycogen synthase kinase 3β (GSK3β) or paxillin. We also provide evidence that prolonged hypoxia down-regulates kindlin-2 expression, leading to spindle abnormalities not only in the SH-SY5Y cell line, but also cell lines derived from colon and breast tissues. The findings of our study highlight that kindlin-2 regulates mitotic spindle assembly and that this process is perturbed in cancer cells in a hypoxic environment.

The action mechanisms revealed by the biochemical and structural analyses of replicative and translesion synthesis (TLS) DNA polymerases (Pols) are retained in their cellular roles. In this regard, DNA polymerase θ differs from other Pols in that whereas purified Polθ misincorporates an A opposite 1,N6-ethenodeoxyadenosine (ϵdA) using an abasic-like mode, Polθ performs predominantly error-free TLS in human cells. To test the hypothesis that Polθ adopts a different mechanism for replicating through ϵdA in human cells than in the purified Pol, here we analyze the effects of mutations in the two highly conserved tyrosine residues, Tyr-2387 and Tyr-2391, in the Polθ active site. Our findings that these residues are indispensable for TLS by the purified Pol but are not required in human cells, as well as other findings, provide strong evidence that the Polθ active site is reconfigured in human cells to stabilize ϵdA in the syn conformation for Hoogsteen base pairing with the correct nucleotide. The evidence that a DNA polymerase can configure its active site entirely differently in human cells than in the purified Pol establishes a new paradigm for DNA polymerase function.

(Florida Atlantic University) Despite PPE use, reports show that many health care workers contracted COVID-19. A novel training technique reinforces the importance of using proper procedures to put on and take off PPE when caring for patients during the pandemic. Researchers vividly demonstrate how aerosol-generating procedures can lead to exposure of the contagion with improper PPE use. The most common error made by the health care workers was contaminating the face or forearms during PPE removal.

Various government departments, together with volunteers today conducted a shoreline clean-up along the remote rocky beach in Kung Pui Wan, Tap Mun to remove two tonnes of refuse.

The Environmental Protection Department, the Food & Environmental Hygiene Department (FEHD) and the Marine Department participated in the operation.

The Inter-departmental Working Group on Marine Environmental Management said the beach, facing the windy and wavy sea, is not easily accessible by working vessels and the rough terrain connecting the rocky beach also increases the difficulty of routine cleaning work.

FEHD cleaners along with the volunteers packed the refuse and delivered it on foot to a nearby pier for temporary storage. FEHD staff then took the refuse to the Marine Department's collection vessel in batches for onward delivery to a rubbish collection point for centralised handling.

To minimise the risk of spreading COVID-19, the operation was carried out in groups of no more than four participants each. They maintained an appropriate distance from each other and paid heed to personal protection, including wearing masks.

The working group thanked the volunteers for taking part and called on the public to keep the countryside and shoreline clean during outings.

For information on clean shorelines, visit the Clean Shorelines facebook and Instagram pages.