The relationship wellness app is seeing a significant uptick in interest as couples are locked down together during the COVID-19 pandemic

Changfeng Gui, Kelei Wang and Jucheng Wei
Trans. Amer. Math. Soc. 373 (2020), 3649-3668.
Abstract, references and article information

Jungang Li, Guozhen Lu and Qiaohua Yang
Trans. Amer. Math. Soc. 373 (2020), 3483-3513.
Abstract, references and article information

Jordi Pau and Antti Perälä
Trans. Amer. Math. Soc. 373 (2020), 3031-3062.
Abstract, references and article information

Cédric Arhancet
Proc. Amer. Math. Soc. 148 (2020), 2551-2563.
Abstract, references and article information

Daniel Carando, Santiago Muro and Daniela M. Vieira
Proc. Amer. Math. Soc. 148 (2020), 2447-2457.
Abstract, references and article information

Why did the undergraduates cross the road? Extra credit. In concept as well as in practice, I have never understood extra credit. As someone who was home-schooled by a former Catholic high-school principal, “extra credit” was never a part of … Continue reading →

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

Recipients of the Individual-based Work Incentive Transport Subsidy (I-WITS) will receive a one-off extra allowance after the passage of the Appropriation Bill 2020, the Government announced today.

The extra allowance was proposed in the 2020-21 Budget and would be disbursed one month after the bill’s passage at the earliest.

Eligible recipients are those whose I-WITS applications were made in the applicable period - from the first day of the month in which the bill is passed to the date of the bill’s passage, and six calendar months before that month.

New applicants or previous I-WITS recipients who have yet to submit applications in the applicable period should do so on or before the date of the bill’s passage to be eligible for the extra allowance.

The extra allowance will be the average monthly amount of approved months payable to the applicants in their I-WITS applications which were most recently submitted in the applicable period and eventually approved.

Click here for details.

To reduce social contact in light of the COVID-19 epidemic, the Primary One Central Allocation results will be posted to parents.

Announcing the move today, the Education Bureau said it will deliver door-to-door the Primary One Registration Form with Central Allocation results to parents from June 3 to 4 through Hongkong Post’s Local CourierPost service.

If no one is present to receive the item at the time of delivery, a mail collection notification card will be left for parents to collect it from the designated post office from the afternoon of the following working day.

If parents have not received the Primary One Registration Form or the notification card by June 5, they can collect the registration form at the designated Collection Centre from June 6 to 7.

The Education Bureau will send letters to parents tomorrow to notify them of the arrangements.

Parents can get updates on the latest arrangements for the release of Central Allocation results and registration through the bureau’s press releases and messages posted on its website.

Call 2891 0088 for information on Primary One admission. For further enquiries, contact the bureau's School Places Allocation Section (Primary One Admission) on 2832 7700 or 2832 7740.

Janine Freeman
Jul 1, 2004; 17:137-140
Nutrition FYI

Some 60,000 workers of over 340 contractors received the first round of allowance under the Anti-epidemic Fund, the Government said today.

The Government explained that it has been making use of the fund to provide allowances to eligible cleansing and security workers engaged by service contractors of the Government and Housing Authority.

Front-line cleansing workers, toilet attendants and security workers employed by the service contractors can receive a monthly allowance of $1,000 for a period of no fewer than four months throughout the epidemic period.

The first round of funding amounted to some $60 million.

Eligible workers who performed duties in March have received the $1,000 allowance applicable to that month.

Arrangements were made for the April allowance to be issued concurrently with the salary of that month.

Front-line workers are not required to submit any application for the allowance.

The departments and the Housing Authority entered into agreements with their contractors to ensure the transfer of the allowance to eligible workers. 

The Government said the allowance aims to provide financial support to cleansing and security staff engaged by service contractors in anti-epidemic efforts, and gives recognition for their committed services at this critical juncture.

The value of total retail sales in March, provisionally estimated at $23 billion, fell 42% compared with the same month in 2019, the Census & Statistics Department announced today.

After netting out the effect of price changes over the same period, the volume of total retail sales decreased 43.8% year-on-year.

The value of sales of food, alcoholic drinks and tobacco decreased 21.2%.

This was followed by commodities in department stores (-42.7% in value); other consumer goods, not elsewhere classified (-29.1%); electrical goods and other consumer durable goods, not elsewhere classified (-39.6%); jewellery, watches and clocks, and valuable gifts (-75.2%); medicines and cosmetics (-63.8%); wearing apparel (-67.2%); motor vehicles and parts (-19.8%); fuels (-8%); furniture and fixtures (-14.4%); books, newspapers, stationery and gifts (-48.4%); Chinese drugs and herbs (-51.7%); footwear, allied products and other clothing accessories (-60.6%); and optical shops (-46.6%).

The value of sales of commodities in supermarkets increased 16.1% for the period.

The Government said retail sales continued to plummet in March as the COVID‑19 pandemic and resulting anti-epidemic measures brought inbound tourism to a standstill and seriously disrupted consumption-related activities.

For the first quarter as a whole, the volume of retail sales fell 36.9% year-on-year, the largest decline for a single quarter on record.

Noting that the business environment for retail trade will remain very difficult in the near term amid the deep economic recession and sharp deterioration in the labour market, the Government said it will closely monitor the developments.

The Government has mechanisms to investigate complaints against civil servants impartially, Secretary for the Civil Service Patrick Nip said today.

Mr Nip made the remarks in response to media queries on recent allegations levelled against senior police officers.

He said: “There are established mechanisms to investigate every complaint in accordance with the procedures and rules. Depending on the circumstances and the case details, some are being handled by departments and bureaus. Some may be handled by the Civil Service Bureau.

“There are established mechanisms in dealing with that. Of course we would handle each and every complaint in a very serious and impartial manner.”

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

Chief Executive Carrie Lam today said law enforcement agencies are investigating cases where police officers are suspected of breaching property rules and will give a full account to society.

Speaking to reporters before the Executive Council meeting this morning, Mrs Lam said nobody is above the law.

“The law will be applied in the same manner regardless of the status, the background, the political affiliation of that particular person.

“As far as I am concerned, as the Chief Executive of Hong Kong and also as an individual, no law-breaking behaviour is acceptable. But it is not for me to stand here to judge each and every case because every case or every complaint has to be investigated and analysed by the law enforcement agencies.

“I am sure that they will do it as diligently as possible and will give a full account to society, especially given the recent concerns.”

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.

Extracytoplasmic sugar decoration of glycopolymer components of the bacterial cell wall contributes to their structural diversity. Typically, the molecular mechanism that underpins such a decoration process involves a three-component glycosylation system (TGS) represented by an undecaprenyl-phosphate (Und-P) sugar-activating glycosyltransferase (Und-P GT), a flippase, and a polytopic glycosyltransferase (PolM GT) dedicated to attaching sugar residues to a specific glycopolymer. Here, using bioinformatic analyses, CRISPR-assisted recombineering, structural analysis of cell wall–associated polysaccharides (CWPS) through MALDI-TOF MS and methylation analysis, we report on three such systems in the bacterium Lactococcus lactis. On the basis of sequence similarities, we first identified three gene pairs, csdAB, csdCD, and csdEF, each encoding an Und-P GT and a PolM GT, as potential TGS component candidates. Our experimental results show that csdAB and csdCD are involved in Glc side-chain addition on the CWPS components rhamnan and polysaccharide pellicle (PSP), respectively, whereas csdEF plays a role in galactosylation of lipoteichoic acid (LTA). We also identified a potential flippase encoded in the L. lactis genome (llnz_02975, cflA) and confirmed that it participates in the glycosylation of the three cell wall glycopolymers rhamnan, PSP, and LTA, thus indicating that its function is shared by the three TGSs. Finally, we observed that glucosylation of both rhamnan and PSP can increase resistance to bacteriophage predation and that LTA galactosylation alters L. lactis resistance to bacteriocin.

β-1,3-d-Glucan is a ubiquitous glucose polymer produced by plants, bacteria, and most fungi. It has been used as a diagnostic tool in patients with invasive mycoses via a highly-sensitive reagent consisting of the blood coagulation system of horseshoe crab. However, no method is currently available for measuring β-1,6-glucan, another primary β-glucan structure of fungal polysaccharides. Herein, we describe the development of an economical and highly-sensitive and specific assay for β-1,6-glucan using a modified recombinant endo-β-1,6-glucanase having diminished glucan hydrolase activity. The purified β-1,6-glucanase derivative bound to the β-1,6-glucan pustulan with a KD of 16.4 nm. We validated the specificity of this β-1,6-glucan probe by demonstrating its ability to detect cell wall β-1,6-glucan from both yeast and hyphal forms of the opportunistic fungal pathogen Candida albicans, without any detectable binding to glucan lacking the long β-1,6-glucan branch. We developed a sandwich ELISA-like assay with a low limit of quantification for pustulan (1.5 pg/ml), and we successfully employed this assay in the quantification of extracellular β-1,6-glucan released by >250 patient-derived strains of different Candida species (including Candida auris) in culture supernatant in vitro. We also used this assay to measure β-1,6-glucan in vivo in the serum and in several organs in a mouse model of systemic candidiasis. Our work describes a reliable method for β-1,6-glucan detection, which may prove useful for the diagnosis of invasive fungal infections.

The actin cytoskeleton is extremely dynamic and supports diverse cellular functions in many physiological and pathological processes, including tumorigenesis. However, the mechanisms that regulate the actin-related protein 2/3 (ARP2/3) complex and thereby promote actin polymerization and organization in cancer cells are not well-understood. We previously implicated the proline-rich 11 (PRR11) protein in lung cancer development. In this study, using immunofluorescence staining, actin polymerization assays, and siRNA-mediated gene silencing, we uncovered that cytoplasmic PRR11 is involved in F-actin polymerization and organization. We found that dysregulation of PRR11 expression results in F-actin rearrangement and nuclear instability in non-small cell lung cancer cells. Results from molecular mechanistic experiments indicated that PRR11 associates with and recruits the ARP2/3 complex, facilitates F-actin polymerization, and thereby disrupts the F-actin cytoskeleton, leading to abnormal nuclear lamina assembly and chromatin reorganization. Inhibition of the ARP2/3 complex activity abolished irregular F-actin polymerization, lamina assembly, and chromatin reorganization due to PRR11 overexpression. Notably, experiments with truncated PRR11 variants revealed that PRR11 regulates F-actin through different regions. We found that deletion of either the N or C terminus of PRR11 abrogates its effects on F-actin polymerization and nuclear instability and that deletion of amino acid residues 100–184 or 100–200 strongly induces an F-actin structure called the actin comet tail, not observed with WT PRR11. Our findings indicate that cytoplasmic PRR11 plays an essential role in regulating F-actin assembly and nuclear stability by recruiting the ARP2/3 complex in human non-small cell lung carcinoma cells.

Lens proteins become increasingly cross-linked through nondisulfide linkages during aging and cataract formation. One mechanism that has been implicated in this cross-linking is glycation through formation of advanced glycation end products (AGEs). Here, we found an age-associated increase in stiffness in human lenses that was directly correlated with levels of protein–cross-linking AGEs. α-Crystallin in the lens binds to other proteins and prevents their denaturation and aggregation through its chaperone-like activity. Using a FRET-based assay, we examined the stability of the αA-crystallin–γD-crystallin complex for up to 12 days and observed that this complex is stable in PBS and upon incubation with human lens–epithelial cell lysate or lens homogenate. Addition of 2 mm ATP to the lysate or homogenate did not decrease the stability of the complex. We also generated complexes of human αA-crystallin or αB-crystallin with alcohol dehydrogenase or citrate synthase by applying thermal stress. Upon glycation under physiological conditions, the chaperone–client complexes underwent greater extents of cross-linking than did uncomplexed protein mixtures. LC-MS/MS analyses revealed that the levels of cross-linking AGEs were significantly higher in the glycated chaperone–client complexes than in glycated but uncomplexed protein mixtures. Mouse lenses subjected to thermal stress followed by glycation lost resilience more extensively than lenses subjected to thermal stress or glycation alone, and this loss was accompanied by higher protein cross-linking and higher cross-linking AGE levels. These results uncover a protein cross-linking mechanism in the lens and suggest that AGE-mediated cross-linking of α-crystallin–client complexes could contribute to lens aging and presbyopia.

In bacteria, the restart of stalled DNA replication forks requires the DNA helicase PriA. PriA can recognize and remodel abandoned DNA replication forks, unwind DNA in the 3'-to-5' direction, and facilitate the loading of the helicase DnaB onto the DNA to restart replication. Single-stranded DNA–binding protein (SSB) is typically present at the abandoned forks, but it is unclear how SSB and PriA interact, although it has been shown that the two proteins interact both physically and functionally. Here, we used atomic force microscopy to visualize the interaction of PriA with DNA substrates with or without SSB. These experiments were done in the absence of ATP to delineate the substrate recognition pattern of PriA before its ATP-catalyzed DNA-unwinding reaction. These analyses revealed that in the absence of SSB, PriA binds preferentially to a fork substrate with a gap in the leading strand. Such a preference has not been observed for 5'- and 3'-tailed duplexes, suggesting that it is the fork structure that plays an essential role in PriA's selection of DNA substrates. Furthermore, we found that in the absence of SSB, PriA binds exclusively to the fork regions of the DNA substrates. In contrast, fork-bound SSB loads PriA onto the duplex DNA arms of forks, suggesting a remodeling of PriA by SSB. We also demonstrate that the remodeling of PriA requires a functional C-terminal domain of SSB. In summary, our atomic force microscopy analyses reveal key details in the interactions between PriA and stalled DNA replication forks with or without SSB.

Antibodies are widely used as cancer therapeutics, but their current use is limited by the low number of antigens restricted to cancer cells. A receptor tyrosine kinase, receptor tyrosine kinase-like orphan receptor 2 (ROR2), is normally expressed only during embryogenesis and is tightly down-regulated in postnatal healthy tissues. However, it is up-regulated in a diverse set of hematologic and solid malignancies, thus ROR2 represents a candidate antigen for antibody-based cancer therapy. Here we describe the affinity maturation and humanization of a rabbit mAb that binds human and mouse ROR2 but not human ROR1 or other human cell-surface antigens. Co-crystallization of the parental rabbit mAb in complex with the human ROR2 kringle domain (hROR2-Kr) guided affinity maturation by heavy-chain complementarity-determining region 3 (HCDR3)-focused mutagenesis and selection. The affinity-matured rabbit mAb was then humanized by complementarity-determining region (CDR) grafting and framework fine tuning and again co-crystallized with hROR2-Kr. We show that the affinity-matured and humanized mAb retains strong affinity and specificity to ROR2 and, following conversion to a T cell–engaging bispecific antibody, has potent cytotoxicity toward ROR2-expressing cells. We anticipate that this humanized affinity-matured mAb will find application for antibody-based cancer therapy of ROR2-expressing neoplasms.

Barttin is the accessory subunit of the human ClC-K chloride channels, which are expressed in both the kidney and inner ear. Barttin promotes trafficking of the complex it forms with ClC-K to the plasma membrane and is involved in activating this channel. Barttin undergoes post-translational palmitoylation that is essential for its functions, but the enzyme(s) catalyzing this post-translational modification is unknown. Here, we identified zinc finger DHHC-type containing 7 (DHHC7) protein as an important barttin palmitoyl acyltransferase, whose depletion affected barttin palmitoylation and ClC-K-barttin channel activation. We investigated the functional role of barttin palmitoylation in vivo in Zdhhc7−/− mice. Although palmitoylation of barttin in kidneys of Zdhhc7−/− animals was significantly decreased, it did not pathologically alter kidney structure and functions under physiological conditions. However, when Zdhhc7−/− mice were fed a low-salt diet, they developed hyponatremia and mild metabolic alkalosis, symptoms characteristic of human Bartter syndrome (BS) type IV. Of note, we also observed decreased palmitoylation of the disease-causing R8L barttin variant associated with human BS type IV. Our results indicate that dysregulated DHHC7-mediated barttin palmitoylation appears to play an important role in chloride channel dysfunction in certain BS variants, suggesting that targeting DHHC7 activity may offer a potential therapeutic strategy for reducing hypertension.

The rapid emergence and dissemination of methicillin-resistant Staphylococcus aureus (MRSA) strains poses a major threat to public health. MRSA possesses an arsenal of secreted host-damaging virulence factors that mediate pathogenicity and blunt immune defenses. Panton–Valentine leukocidin (PVL) and α-toxin are exotoxins that create lytic pores in the host cell membrane. They are recognized as being important for the development of invasive MRSA infections and are thus potential targets for antivirulence therapies. Here, we report the high-resolution X-ray crystal structures of both PVL and α-toxin in their soluble, monomeric, and oligomeric membrane-inserted pore states in complex with n-tetradecylphosphocholine (C14PC). The structures revealed two evolutionarily conserved phosphatidylcholine-binding mechanisms and their roles in modulating host cell attachment, oligomer assembly, and membrane perforation. Moreover, we demonstrate that the soluble C14PC compound protects primary human immune cells in vitro against cytolysis by PVL and α-toxin and hence may serve as the basis for the development of an antivirulence agent for managing MRSA infections.

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

(Arizona State University) Gary Moore, assistant professor in ASU's School of Molecular Sciences and the Biodesign Institute's Center for Applied Structural Discovery has just been named one of 14 young faculty nationwide to be honored with a 2020 Camille Dreyfus Teacher-Scholar Award by the Camille and Henry Dreyfus Foundation.

People living in units 13 and 14 of the top six floors of Heng Tai House in Fu Heng Estate, Tai Po need to be quarantined as a precaution.

Hong Kong University Chair of Infectious Disease Prof Yuen Kwok-yung made the statement at a media briefing today after an expert team conducted initial epidemiological investigations in the building to find the cause of a new COVID-19 infection.

The new case announced this afternoon involves a 59-year-old man who lives on the 34th floor of the building.

Prof Yuen said: “There is a possibility that when the patients on the 32nd floor are defecating - we know now that the fecal material actually contains the virus - while they’re defecating the fecal material goes into the sewer system.

“There is a vent of air that comes through the venting pipe, which goes to the top floor and maybe aerosolised in the air and then the droplets try to settle but, while at the same time, when there’s a light wind blowing, in which the air current going over the rooftop carries the particles back into the top floors.

“And of course, the 34th floor is the top floor. That is the most dangerous, followed by the 33rd and 32nd floors.”

Prof Yuen added he is uncertain if the venting pipe will continue to produce more infected aerosolised particles.

“So it is just a precautionary measure that we must remove the residents from the top six floors in units 13 and 14 for a period of time.”

For information and health advice on COVID-19, visit the Government's dedicated webpage.

(Memorial Sloan Kettering Cancer Center) Scientists at the Sloan Kettering Institute have solved the puzzle of how small chromosomes ensure that they aren't skipped over during meiosis, the process that makes sperm and egg.

(JAMA Network) The considerations and challenges affecting the palliative care specialty and delivery of palliative care in the COVID-19 era, as well as potential solutions, are discussed in this Viewpoint.