The dextransucrase DSR-OK from the Gram-positive bacterium Oenococcus kitaharae DSM17330 produces a dextran of the highest molar mass reported to date (∼109 g/mol). In this study, we selected a recombinant form, DSR-OKΔ1, to identify molecular determinants involved in the sugar polymerization mechanism and that confer its ability to produce a very-high-molar-mass polymer. In domain V of DSR-OK, we identified seven putative sugar-binding pockets characteristic of glycoside hydrolase 70 (GH70) glucansucrases that are known to be involved in glucan binding. We investigated their role in polymer synthesis through several approaches, including monitoring of dextran synthesis, affinity assays, sugar binding pocket deletions, site-directed mutagenesis, and construction of chimeric enzymes. Substitution of only two stacking aromatic residues in two consecutive sugar-binding pockets (variant DSR-OKΔ1-Y1162A-F1228A) induced quasi-complete loss of very-high-molar-mass dextran synthesis, resulting in production of only 10–13 kg/mol polymers. Moreover, the double mutation completely switched the semiprocessive mode of DSR-OKΔ1 toward a distributive one, highlighting the strong influence of these pockets on enzyme processivity. Finally, the position of each pocket relative to the active site also appeared to be important for polymer elongation. We propose that sugar-binding pockets spatially closer to the catalytic domain play a major role in the control of processivity. A deep structural characterization, if possible with large-molar-mass sugar ligands, would allow confirming this hypothesis.

Heterotrimeric G proteins mediate a variety of signaling processes by coupling G protein–coupled receptors to intracellular effector molecules. In Drosophila, the Gαq gene encodes several Gαq splice variants, with the Gαq1 isoform protein playing a major role in fly phototransduction. However, Gαq1 null mutant flies still exhibit a residual light response, indicating that other Gαq splice variants or additional Gq α subunits are involved in phototransduction. Here, we isolated a mutant fly with no detectable light responses, decreased rhodopsin (Rh) levels, and rapid retinal degeneration. Using electrophysiological and genetic studies, biochemical assays, immunoblotting, real-time RT-PCR, and EM analysis, we found that mutations in the Gαq gene disrupt light responses and demonstrate that the Gαq3 isoform protein is responsible for the residual light response in Gαq1 null mutants. Moreover, we report that Gαq3 mediates rhodopsin synthesis. Depletion of all Gαq splice variants led to rapid light-dependent retinal degeneration, due to the formation stable Rh1-arrestin 2 (Arr2) complexes. Our findings clarify essential roles of several different Gαq splice variants in phototransduction and retinal integrity in Drosophila and reveal that Gαq3 functions in rhodopsin synthesis.

The protein-tyrosine phosphatase SHP2 is an allosteric enzyme critical for cellular events downstream of growth factor receptors. Mutations in the SHP2 gene have been linked to many different types of human diseases, including developmental disorders, leukemia, and solid tumors. Unlike most SHP2-activating mutations, the T507K substitution in SHP2 is unique in that it exhibits oncogenic Ras-like transforming activity. However, the biochemical basis of how the SHP2/T507K variant elicits transformation remains unclear. By combining kinetic and biophysical methods, X-ray crystallography, and molecular modeling, as well as using cell biology approaches, here we uncovered that the T507K substitution alters both SHP2 substrate specificity and its allosteric regulatory mechanism. We found that although SHP2/T507K exists in the closed, autoinhibited conformation similar to the WT enzyme, the interactions between its N-SH2 and protein-tyrosine phosphatase domains are weakened such that SHP2/T507K possesses a higher affinity for the scaffolding protein Grb2-associated binding protein 1 (Gab1). We also discovered that the T507K substitution alters the structure of the SHP2 active site, resulting in a change in SHP2 substrate preference for Sprouty1, a known negative regulator of Ras signaling and a potential tumor suppressor. Our results suggest that SHP2/T507K's shift in substrate specificity coupled with its preferential association of SHP2/T507K with Gab1 enable the mutant SHP2 to more efficiently dephosphorylate Sprouty1 at pTyr-53. This dephosphorylation hyperactivates Ras signaling, which is likely responsible for SHP2/T507K's Ras-like transforming activity.

T-type (Cav3) Ca2+ channels are important regulators of excitability and rhythmic activity of excitable cells. Among other voltage-gated Ca2+ channels, Cav3 channels are uniquely sensitive to oxidation and zinc. Using recombinant protein expression in HEK293 cells, patch clamp electrophysiology, site-directed mutagenesis, and homology modeling, we report here that modulation of Cav3.2 by redox agents and zinc is mediated by a unique extracellular module containing a high-affinity metal-binding site formed by the extracellular IS1–IS2 and IS3–IS4 loops of domain I and a cluster of extracellular cysteines in the IS1–IS2 loop. Patch clamp recording of recombinant Cav3.2 currents revealed that two cysteine-modifying agents, sodium (2-sulfonatoethyl) methanethiosulfonate (MTSES) and N-ethylmaleimide, as well as a reactive oxygen species–producing neuropeptide, substance P (SP), inhibit Cav3.2 current to similar degrees and that this inhibition is reversed by a reducing agent and a zinc chelator. Pre-application of MTSES prevented further SP-mediated current inhibition. Substitution of the zinc-binding residue His191 in Cav3.2 reduced the channel's sensitivity to MTSES, and introduction of the corresponding histidine into Cav3.1 sensitized it to MTSES. Removal of extracellular cysteines from the IS1–IS2 loop of Cav3.2 reduced its sensitivity to MTSES and SP. We hypothesize that oxidative modification of IS1–IS2 loop cysteines induces allosteric changes in the zinc-binding site of Cav3.2 so that it becomes sensitive to ambient zinc.

S-Palmitoylation is a reversible post-translational lipid modification that dynamically regulates protein functions. Voltage-gated sodium channels are subjected to S-palmitoylation and exhibit altered functions in different S-palmitoylation states. Our aim was to investigate whether and how S-palmitoylation regulates Nav1.6 channel function and to identify S-palmitoylation sites that can potentially be pharmacologically targeted. Acyl-biotin exchange assay showed that Nav1.6 is modified by S-palmitoylation in the mouse brain and in a Nav1.6 stable HEK 293 cell line. Using whole-cell voltage clamp, we discovered that enhancing S-palmitoylation with palmitic acid increases Nav1.6 current, whereas blocking S-palmitoylation with 2-bromopalmitate reduces Nav1.6 current and shifts the steady-state inactivation in the hyperpolarizing direction. Three S-palmitoylation sites (Cys1169, Cys1170, and Cys1978) were identified. These sites differentially modulate distinct Nav1.6 properties. Interestingly, Cys1978 is exclusive to Nav1.6 among all Nav isoforms and is evolutionally conserved in Nav1.6 among most species. Cys1978 S-palmitoylation regulates current amplitude uniquely in Nav1.6. Furthermore, we showed that eliminating S-palmitoylation at specific sites alters Nav1.6-mediated excitability in dorsal root ganglion neurons. Therefore, our study reveals S-palmitoylation as a potential isoform-specific mechanism to modulate Nav activity and neuronal excitability in physiological and diseased conditions.

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.

Bacterial type VII secretion systems secrete a wide range of extracellular proteins that play important roles in bacterial viability and in interactions of pathogenic mycobacteria with their hosts. Mycobacterial type VII secretion systems consist of five subtypes, ESX-1–5, and have four substrate classes, namely, Esx, PE, PPE, and Esp proteins. At least some of these substrates are secreted as heterodimers. Each ESX system mediates the secretion of a specific set of Esx, PE, and PPE proteins, raising the question of how these substrates are recognized in a system-specific fashion. For the PE/PPE heterodimers, it has been shown that they interact with their cognate EspG chaperone and that this chaperone determines the designated secretion pathway. However, both structural and pulldown analyses have suggested that EspG cannot interact with the Esx proteins. Therefore, the determining factor for system specificity of the Esx proteins remains unknown. Here, we investigated the secretion specificity of the ESX-1 substrate pair EsxB_1/EsxA_1 in Mycobacterium marinum. Although this substrate pair was hardly secreted when homologously expressed, it was secreted when co-expressed together with the PE35/PPE68_1 pair, indicating that this pair could stimulate secretion of the EsxB_1/EsxA_1 pair. Surprisingly, co-expression of EsxB_1/EsxA_1 with a modified PE35/PPE68_1 version that carried the EspG5 chaperone-binding domain, previously shown to redirect this substrate pair to the ESX-5 system, also resulted in redirection and co-secretion of the Esx pair via ESX-5. Our results suggest a secretion model in which PE35/PPE68_1 determines the system-specific secretion of EsxB_1/EsxA_1.

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.

We previously reported that overexpression of cytochrome P450 family 24 subfamily A member 1 (CYP24A1) increases lung cancer cell proliferation by activating RAS signaling and that CYP24A1 knockdown inhibits tumor growth. However, the mechanism of CYP24A1-mediated cancer cell proliferation remains unclear. Here, we conducted cell synchronization and biochemical experiments in lung adenocarcinoma cells, revealing a link between CYP24A1 and anaphase-promoting complex (APC), a key cell cycle regulator. We demonstrate that CYP24A1 expression is cell cycle–dependent; it was higher in the G2-M phase and diminished upon G1 entry. CYP24A1 has a functional destruction box (D-box) motif that allows binding with two APC adaptors, CDC20-homologue 1 (CDH1) and cell division cycle 20 (CDC20). Unlike other APC substrates, however, CYP24A1 acted as a pseudo-substrate, inhibiting CDH1 activity and promoting mitotic progression. Conversely, overexpression of a CYP24A1 D-box mutant compromised CDH1 binding, allowing CDH1 hyperactivation, thereby hastening degradation of its substrates cyclin B1 and CDC20, and accumulation of the CDC20 substrate p21, prolonging mitotic exit. These activities also occurred with a CYP24A1 isoform 2 lacking the catalytic cysteine (Cys-462), suggesting that CYP24A1's oncogenic potential is independent of its catalytic activity. CYP24A1 degradation reduced clonogenic survival of mutant KRAS-driven lung cancer cells, and calcitriol treatment increased CYP24A1 levels and tumor burden in Lsl-KRASG12D mice. These results disclose a catalytic activity-independent growth-promoting role of CYP24A1 in mutant KRAS-driven lung cancer. This suggests that CYP24A1 could be therapeutically targeted in lung cancers in which its expression is high.

Fatty acid esters of hydroxy fatty acids (FAHFAs) are a newly discovered class of signaling lipids with anti-inflammatory and anti-diabetic properties. However, the endogenous regulation of FAHFAs remains a pressing but unanswered question. Here, using MS-based FAHFA hydrolysis assays, LC-MS–based lipidomics analyses, and activity-based protein profiling, we found that androgen-induced gene 1 (AIG1) and androgen-dependent TFPI-regulating protein (ADTRP), two threonine hydrolases, control FAHFA levels in vivo in both genetic and pharmacologic mouse models. Tissues from mice lacking ADTRP (Adtrp-KO), or both AIG1 and ADTRP (DKO) had higher concentrations of FAHFAs particularly isomers with the ester bond at the 9th carbon due to decreased FAHFA hydrolysis activity. The levels of other lipid classes were unaltered indicating that AIG1 and ADTRP specifically hydrolyze FAHFAs. Complementing these genetic studies, we also identified a dual AIG1/ADTRP inhibitor, ABD-110207, which is active in vivo. Acute treatment of WT mice with ABD-110207 resulted in elevated FAHFA levels, further supporting the notion that AIG1 and ADTRP activity control endogenous FAHFA levels. However, loss of AIG1/ADTRP did not mimic the changes associated with pharmacologically administered FAHFAs on extent of upregulation of FAHFA levels, glucose tolerance, or insulin sensitivity in mice, indicating that therapeutic strategies should weigh more on FAHFA administration. Together, these findings identify AIG1 and ADTRP as the first endogenous FAHFA hydrolases identified and provide critical genetic and chemical tools for further characterization of these enzymes and endogenous FAHFAs to unravel their physiological functions and roles in health and disease.

The cellular energy sensor AMP-activated protein kinase (AMPK) is a metabolic regulator that mediates adaptation to nutritional variations to maintain a proper energy balance in cells. We show here that suckling-weaning and fasting-refeeding transitions in rodents are associated with changes in AMPK activation and the cellular energy state in the liver. These nutritional transitions were characterized by a metabolic switch from lipid to glucose utilization, orchestrated by modifications in glucose levels and the glucagon/insulin ratio in the bloodstream. We therefore investigated the respective roles of glucose and pancreatic hormones on AMPK activation in mouse primary hepatocytes. We found that glucose starvation transiently activates AMPK, whereas changes in glucagon and insulin levels had no impact on AMPK. Challenge of hepatocytes with metformin-induced metabolic stress strengthened both AMPK activation and cellular energy depletion under limited-glucose conditions, whereas neither glucagon nor insulin altered AMPK activation. Although both insulin and glucagon induced AMPKα phosphorylation at its Ser485/491 residue, they did not affect its activity. Finally, the decrease in cellular ATP levels in response to an energy stress was additionally exacerbated under fasting conditions and by AMPK deficiency in hepatocytes, revealing metabolic inflexibility and emphasizing the importance of AMPK for maintaining hepatic energy charge. Our results suggest that nutritional changes (i.e. glucose availability), rather than the related hormonal changes (i.e. the glucagon/insulin ratio), sensitize AMPK activation to the energetic stress induced by the dietary transition during fasting. This effect is critical for preserving the cellular energy state in the liver.

Hong Kong Observatory Director Cheng Cho-ming today said he expects four to seven tropical cyclones to hit Hong Kong this year.

Presenting the weather outlook at a press briefing in the afternoon, Mr Cheng also said the overall mean temperature for the year will be higher than normal.

“The way that we produce our temperature forecast is based on a couple of things. One is based on the worldwide climate model - what they forecast for this year - and also based on some objective indicators.

“Based on all these indicators we expect that the overall mean temperature this year will be above normal, and very likely, will have a high chance of reaching the top 10 positions.”

Reviewing last year’s weather, Mr Cheng noted Hong Kong experienced its second warmest winter since records began, with a mean temperature of 18.7 degrees Celsius.

There was only one day when the temperature fell below 12 degrees Celsius.

Additionally, Mr Cheng said the new Hong Kong Hiking Trail Weather Service webpage has been launched to provide weather information services to people taking part in outdoor activities.

He added the Observatory also collaborated with the Agriculture, Fisheries & Conservation Department to provide weather information at popular hiking hotspots via QR codes.

The Government today said the first batch of subsidies amounting to $5.6 million under two relief measures for recyclers has been disbursed, while $5.6 million in subsidies had been approved under a management sector support scheme.

The two Recycling Fund measures aim to help the recycling industry cope with the current economic situation and recent operational difficulties arising from the COVID-19 epidemic.

The Advisory Committee on Recycling Fund announced in mid-March to reserve $100 million to launch the One-off Recycling Industry Anti-epidemic Scheme.

The scheme provides timely financial support to help with recyclers’ operational costs for six months. The funding limit for each recycler is $20,000 per month from January 1 to June 30, or $120,000 in total maximum subsidy.

The committee has also allocated additional funds to extend the earlier-launched One-off Rental Support Scheme for another six months, providing a total funding of $200 million to fight the virus and help the recycling industry ride out the difficult times.

The rental support scheme, which benefits street-corner recycling shops and recycling sites, originally ran from October to March. It has been extended for six months until September this year, totalling 12 months.

The monthly rental subsidy for each recycler is capped at $25,000, setting the maximum total rental subsidy at $300,000.

Separately, the Anti-epidemic Support Scheme for Property Management Sector has approved 205 applications involving around $5.6 million in subsidies to benefit more than 1,500 building blocks.

The relevant property management companies and owners’ organisations will receive notifications for subsidy disbursement shortly.

The list of properties for which applications have been approved is available online.

Briefing sessions were held earlier to introduce the scheme to the property management sector and owners’ organisations.

Non-residential and residential electricity accounts are benefitting from government relief measures, the Environmental Bureau announced today.

Under the measures, nearly 90% of non-residential electricity bills obtained a 75% subsidy for electricity charges in March, while 40% of residential electricity accounts enjoyed zero electricity charges in the first quarter of the year.

The Government announced about $2.3 billion in provisions last December to provide an electricity charge subsidy to each eligible non-residential electricity account holder to cover 75% of their monthly electricity charges for four months, subject to a monthly cap of $5,000.

The Budget further provided $2.9 billion to extend the subsidy period to eight months.

According to the bills issued by the two power companies in March, 360,000 non-residential bills obtained a 75% subsidy. This is close to 90% of the total eligible non-residential tariff bills.

To balance the impact on people's livelihood of the recent transition to cleaner electricity generating systems in Hong Kong, the bureau implemented the electricity charges relief scheme in January 2019.

A monthly electricity charge relief of $50 has been granted to each eligible residential electricity account for 60 months.

To help the public cope with the challenging economic environment, the Government implemented a new round of one-off electricity charge subsidy schemes in January.

A subsidy of $160 will be credited to each residential electricity account from January to November, while $240 will be credited in December.

From early this year, over 2.7 million households have been benefitting from both the electricity charges relief measures and the electricity charges subsidy. The bills of the two power companies indicated that 40% of residential electricity accounts, representing 1 million households, enjoyed zero electricity charges.

The bureau called on the community to cherish environmental resources, including saving energy and electricity to mitigate climate change and improve air quality.

The traditionally blue-collar neighbourhood of Sham Shui Po is home to a kaleidoscopic collection of landmarks, streets and shops.

Participants of the Sham Shui Po Ensemble project explored the area and told its story through video and music production.

One of the project’s creative productions, the short film Collage created by Cobe Yau and her team, documented the daily lives of the area’s residents.

Ms Yau said Sham Shui Po’s diversity inspired her team to combine footage of residents’ daily activities, such as the unloading of meat and vegetables in wet markets and hawkers selling their wares.

“We hope our viewers can realise that although there are some street sleepers and it may be a bit grimy in some parts of Sham Shui Po, there are also many interesting aspects that make this community stand out.”

Creative journeys

Sham Shui Po Ensemble is under the Community Record Company, an 18-month community-based programme which also showcases two other unique locales.

Last year, participants explored Sai Ying Pun under the West Side Re-Discovery project. Sham Shui Po Ensemble was launched in April and concluded in late July, while the Wander in To Kwa Wan project began this month.

Local documentary maker Wong Siu-pong, the Community Curator of the Sham Shui Po project, hopes participants are able to explore the community without bias.

“Apart from the basics of film production, I did not teach them a lot of filmmaking skills. I hope they learn to be humble when making a documentary.

“A lot of the time, we read the news to learn about a community. I hope they can discover these places without prejudice, this is important.”

Project participants were also able to paint a picture of the community with music.

Warren Luk joined the project’s music stream and wrote the song Rich on Life with his team.

“People always have preconceived ideas of Sham Shui Po. But when you walk through the neighbourhood, you can find lots of quirky and interesting landmarks.

“When you observe the interactions between residents there, you can see that although their lives may be tough, they are enjoying themselves a lot. It is very inspiring.”

The Community Record Company programme is organised by non-governmental organisation MaD Institute and sponsored by the Home Affairs Bureau’s Arts Capacity Development Funding Scheme, which seeks to strengthen Hong Kong’s cultural software and build up the arts sector.

Application details for the next funding exercise will be available in November.

A 53-year-old building on Fa Yuen Street near Prince Edward, like most of the buildings in Yau Tsim Mong District, was in poor condition two years ago. Walls, both inside and out, were worn down, staircases were broken, and with electrical installation panels exposed on the outside. 

But with the help of various subsidy schemes launched by the Government and Urban Renewal Authority, older buildings are being given a new lease of life. The schemes include Operation Building Bright 2.0 (OBB 2.0), the Fire Safety Improvement Works Subsidy Scheme (FSWS) and the Lift Modernisation Subsidy Scheme (LIMSS).
 

Helping hand

Octogenarian owner-occupiers Leung Ting-lam and Chu Lai-chun have lived in this building on Fa Yuen Street for more than two decades. They welcome the improvements, which include a new metal gate and lift.

“Modernising the lift was done so quickly. It only took a few months and that was the most satisfying part,” said Mr Leung. Ms Chu agreed that the lift no longer breaks down so regularly.

It cost $800,000 just to modernise the lift. Add to that the other repair and maintenance works, and the total cost exceeded $3 million. Those who own a flat had to shoulder tens of thousands of dollars in the 10-storey building containing 19 units.

For seniors on a fixed income, it is not easy to cover the full cost of repair works. With the government subsidies, they no longer have to worry about the financial burden of upgrading their buildings on their own.

Popular services

The lift modernisation work under the LIMSS is assisted by the Electrical & Mechanical Services Department. The department’s Assistant Director Raymond Poon said the subsidy can cover up to 60% of the total cost of the works - plus a consultation fee - with a cap of $500,000 per lift for eligible buildings.

For elderly owner-occupiers, they can receive the full cost of relevant works capped at $50,000 per domestic unit.

Up until August 1, the department received around 1,171 applications for the scheme involving nearly 5,000 lifts in the first round of applications. This far exceeded the quota of 1,400 lifts set for the round, a response Mr Poon described as overwhelming.

Apart from the LIMSS, owner-occupiers can also apply for OBB 2.0 and other schemes to cover maintenance costs.

In one 58-year-old Hung Hom building, residents had to spend more than $800,000 to paint the common areas, replace above-ground drainage pipework and other structural upgrades.

The building’s owners’ corporation has applied for several funding schemes to get some financial relief, including OBB 2.0. Under this scheme, elderly recipients can receive the full cost of the work, subject to a cap of $50,000. Other owner-occupiers can receive 80%, capped at $40,000.

As of August, the owners or owners’ corporations of 479 Category One buildings were prepared to carry out the prescribed inspection and repair works for the common areas of their buildings under OBB 2.0. They can do so on a voluntary basis to comply with the Mandatory Building Inspection Scheme (MBIS) statutory notices.

These buildings are in 13 districts. Among them, Yau Tsim Mong has the largest number of applications, followed by Kowloon City and Sham Shui Po.

More help ahead

In the future, another $3 billion will be injected into OBB 2.0. This means a total of $6 billion will be used to benefit 5,000 buildings.

Development Bureau Principal Assistant Secretary Jasmine Choi said they have received feedback from the community which hopes the operation will eventually allow younger buildings to join the rehabilitation schemes.

Upon review, buildings between 40 and 49 years old with an outstanding MBIS statutory notice not yet complied with will be accepted in the next round of applications.

Apart from these younger structures, OBB 2.0 will also accept buildings aged 50 and older, even if they do not have an outstanding notice.

The ability to connect to a Google BigQuery database via OAuth is now available with this hot fix. Three new options have been added, REFRESH_TOKEN=, CLIENT_ID=, and CLIENT_SECRET=. You can use these options with 

The ability to connect to a Google BigQuery database via a proxy is available with this hot fix. You can use the newly added option, PROXY=, with the following methods of connection to the Google BigQuery database:

(Impact Journals LLC) Volume 11, Issue 18 of @Oncotarget Clinical implications of chromatin accessibility assessed by ATAC-seq profiling in human cancers especially in a large patient cohort is largely unknown.

(Center for Genomic Regulation) An analysis of 13,000 tumours highlights two previously overlooked genes as potential new therapeutic targets for cancer treatment. Researchers also identify potential new therapeutic targets for male infertility. Both findings are the result of the most comprehensive evolutionary analysis of RNA modification proteins to date, published today in the journal Genome Biology.

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

(Luxembourg Institute of Health) Scientists at the Department of Infection and Immunity of the Luxembourg Institute of Health (LIH) revealed a novel mechanism through which the immune system controls autoimmunity and cancer. In the special focus of the researchers were regulatory T cells -- a type of white blood cells that act as a brake on the immune system.

(University of Houston) A University of Houston biomedical researcher is developing a new device to treat babies with blood disorders, because current technology is designed for adults. The ability to perform lifesaving leukapheresis safely and effectively in these most vulnerable pediatric patients will significantly increase their access to highly effective cell-based therapies.

Every summer, rainstorms occur in Hong Kong occasionally, leading to loss of property or even casualties.

(George Mason University) The team's work supports evidence-based decision making, informed by models, to rethink and facilitate hospital operations during the pandemic.

(The Institute of Medical Science, The University of Tokyo) Understanding the principles of cancer evolution is important in designing a therapeutic strategy. A research group at The Institute of Medical Science, The University of Tokyo (IMSUT) announced a new simulation model that describes various modes of cancer evolution in a unified manner.

(Keck School of Medicine of USC) A new USC study suggests that temporarily suppressing the body's immune system during the early stages of COVID-19 could help a patient avoid severe symptoms. That's because the research shows that an interaction between the body's two main lines of defense may be causing the immune system to go into overdrive in some patients.

(SCALE Nanotech) ESA-backed researchers demonstrate the laser-propulsion of graphene sails in microgravity. The light sails use a scalable micro-membrane design that minimizes their mass and hence increases their thrust upon light irradiation. To demonstrate the new sail concept, the scientists gained access to ZARM Drop Tower. There, the sail prototypes were set in vacuum and microgravity, and 1W-lasers caused their acceleration up to 1 m/s2.

(Universitat Autonoma de Barcelona) More than 500 researchers from all around the world will gather virtually tomorrow Wednesday May 6 at the Institute of Environmental Science and Technology of the Universitat Autònoma de Barcelona (ICTA-UAB) to discuss and propose how society should adopt more sustainable and low-carbon forms of lifestyle that contribute to mitigating climate change.

(Molecular Biology and Evolution (Oxford University Press)) In a new paper, Dang Liu, Mark Stoneking and colleagues have analyzed newly generated genome-wide SNP data for the Kinh and 21 additional ethnic groups in Vietnam, encompassing all five major language families in MSEA, along with previously published data from nearby populations and ancient samples.

(PLOS) The ancient cemetery of Mözs-Icsei d?l? in present-day Hungary holds clues to a unique community formation during the beginnings of Europe's Migration Period, according to a study published April 29, 2020 in the open-access journal PLOS ONE by Corina Knipper from the Curt-Engelhorn-Center for Archaeometry, Germany, István Koncz, Tivadar Vida from the Eötvös Loránd University, Budapest, Hungary and colleagues.

(American Society of Agronomy) Study shows which desert soils better recover from disturbance.

(Arizona State University) Hydrogen is an essential commodity with over 60 million tons produced globally every year. However over 95 percent of it is made by steam reformation of fossil fuels, a process that is energy intensive and produces carbon dioxide. If we could replace even a part of that with algal biohydrogen that is made via light and water, it would have a substantial impact.

(University of Tennessee Institute of Agriculture) David Mercker, an Extension forestry specialist with the University of Tennessee Department of Forestry, Wildlife and Fisheries, has been named 2020 Extension Forester of the Year by the Forest Landowners Association (FLA). FLA is a national organization that promotes and protects the interests of private forest landowners and bestows this award annually as determined by its board of directors.

(American Association for the Advancement of Science) Microplastic particles entering the sea surface were thought to settle to the seafloor directly below them, but now, a new study reveals that slow-moving currents near the bottom of the ocean direct the flow of plastics, creating microplastic hotpots in sediments of the deep sea.

Chief Justice Patience Roggensack faced backlash for her comment, with some people calling it "elitist" to separate meatpackers from "regular folks."

As part of the College's move to remote learning, 143 first-year students are taking a series of virtual field courses to investigate biodiversity.

(American Geriatrics Society) The American Geriatrics Society (AGS) today announced that Ellen Flaherty, PhD, APRN, AGSF, an assistant professor at the Dartmouth Geisel School of Medicine and director of the Dartmouth Centers for Health & Aging, will deliver the society's prestigious Henderson State-of-the-Art Lecture. Dr. Flaherty will deliver her talk, Leveraging the Potential of Interprofessional Teams in Primary Care Practice, at the AGS 2021 Annual Scientific Meeting (#AGS21) in Chicago, Ill. (May 12-15, 2021).

(American Geriatrics Society) The American Geriatrics Society (AGS) will this year honor past AGS President Todd Semla, PharmD, MS, AGSF, with the prestigious Nascher/Manning Award, given biannually at the AGS Annual Scientific Meeting (#AGS21, to be held next year May 13-15 in Chicago, Ill., following the cancellation of the AGS 2020 Annual Scientific Meeting due to COVID-19).

(University of Surrey) A new research study, investigating how service robots in hotels could help redefine leadership and boost the hospitality industry, has taken on new significance in the light of the seismic impact of the Covid-19 outbreak on tourism and business travel. The study by academics at The University of Surrey and MODUL University Vienna focuses on how HR experts perceive service robots and their impact on leadership and HR management in the hotel industry.