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CBD Notification SCBD/OES/EM/DC/88726 (2020-025): Registration and Credentials for Fifteenth meeting of the Conference of the Parties to the Convention on Biological Diversity (COP 15), Tenth meeting of the Conference of the Parties serving as the meeting




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CBD Notification SCBD/SSSF/AS/SBG/JSH/AER/88592 (2020-026): Postponement of the Global Taxonomy Initiative Forum - Berlin, Germany, 7-9 April 2020




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CBD Notification SCBD/IMS/JMF/NP/CR/IH/88710 (2020-027): Final Call for Nominations for the MIDORI Prize for Biodiversity 2020




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CBD Notification SCBD/NPU/DC/WY/BG/RKi/88737 (2020-028): Peer review of a study related to Article 10 of the Nagoya Protocol




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CBD News: Statement by Ms. Elizabeth Maruma Mrema, Acting Executive Secretary of the Convention on Biological Diversity, at the opening of the Subregional Exchange for the Caribbean on the Restoration of Forests and Other Ecosystems, 9-13 March 2020




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CBD Notification SCBD/OES/EM/DC/88792 (2020-029): Update regarding COVID-19 and upcoming CBD meetings




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CBD Notification SCBD/SSSF/AS/SBG/JSH/VA/JM/AER/88592 (2020-031): Postponement of the Global Taxonomy Initiative Forum and selected participants




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CBD Notification SCBD/NPU/DC/WY/BG/RKi/88737 (2020-030): Extension of deadline: Peer review of a study related to Article 10 of the Nagoya Protocol




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CBD Notification SCBD/OES/EM/DC/88792 (2020-033): Dates and venue: Twenty-fourth Meeting of the Subsidiary Body on Scientific, Technical and Technological Advice (SBSTTA 24), 17 to 22 August 2020, and Third Meeting of the Subsidiary Body on Implementation




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CBD News: Two meetings of the UN Convention on Biological Diversity's (CBD) permanent subsidiary bodies originally scheduled for May 2020 and then rescheduled for August/September 2020 will now take place in August 2020.




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CBD Notification SCBD/OES/EM/DC/IS/88838 (2020-034): Summit on Biodiversity




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CBD Notification SCBD/OES/DAIN/MB/FD/88610 (2020-035): Logo for the International Day for Biological Diversity 2020: "Our solutions are in nature"




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CBD Notification SCBD/SSSF/AS/BB/ML/GD/88853 (2020-036): Launching of the UNEP Strategy for Private Sector Engagement




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Best tech podcasts 2020




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Health & Human Services - 9/9/2020

Time: 9:00 AM, Location: Senate Chamber




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Finance - 6/2/2020

Time: 10:00 AM (Canceled/see notice), Location: E1.036 (Finance Room)




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Art museum to reopen on Nov 30

The Hong Kong Museum of Art will reopen on November 30 with 11 new exhibitions, after major expansion and renovation.

 

Ordinary to Extraordinary: Stories of the Museum, an exhibition of gems from the museum's collection, will showcase exceptional works curated from its four core collections - Chinese Antiquities, Chinese Painting & Calligraphy, China Trade Art, and Modern & Hong Kong Art.

 

Museum of Art Director Maria Mok said that by sharing the fascinating stories behind these works, the exhibition will help visitors discover little-known anecdotes about the museum throughout the 57 years since its founding.

 

The exhibition From Dung Basket to Dining Cart: 100th Anniversary of the Birth of Wu Guanzhong will showcase more than 100 of the artist’s paintings to not only honour his contributions to Chinese art, but also pay tribute to his artistic pursuits spanning over half a century.

 

The development of Hong Kong art has been a unique local experience.

 

The Hong Kong Experience‧Hong Kong Experiment exhibition makes use of the museum's collection accumulated over half a century to capture all these different experiences and experiments, portraying the development of Hong Kong art.

 

The museum has been closed since August 2015 for renovations to increase exhibition space and upgrade its facilities.

 

After the expansion, its total exhibition area will increase from about 7,000 to 10,000 sq m and the number of galleries will increase from seven to 12.

 

Click here to reserve admission time slots.




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20 Questions–Job Interview, or First Date?

We are now in the peak of job season. Depending upon your branch, applications may have been due as early as October 1. Big deadlines are November 1, November 15, and December 1.  Still, you should basically be done applying now—see … Continue reading




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Foyle Film Festival Announces Winners of 2014 Festival

Two short films have made it one step closer to an Oscar nomination after picking up a Light in Motion (LIM) award at the Foyle Film Festival’s closing ceremony in Brunswick Moviebowl.




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Bulletin updated at 01:02 HKT 10/05/2020

At 1 a.m. at the Hong Kong Observatory :
Air temperature : 29 degrees Celsius
Relative Humidity : 82 per cent

The air temperatures at other places were:
Hong Kong Observatory29 degrees ;
King's Park28 degrees ;
Wong Chuk Hang28 degrees ;
Ta Kwu Ling26 degrees ;
Lau Fau Shan28 degrees ;
Tai Po28 degrees ;
Sha Tin29 degrees ;
Tuen Mun27 degrees ;
Tseung Kwan O28 degrees ;
Sai Kung28 degrees ;
Cheung Chau26 degrees ;
Chek Lap Kok29 degrees ;
Tsing Yi27 degrees ;
Shek Kong28 degrees ;
Tsuen Wan Ho Koon27 degrees ;
Tsuen Wan Shing Mun Valley27 degrees ;
Hong Kong Park28 degrees ;
Shau Kei Wan28 degrees ;
Kowloon City28 degrees ;
Happy Valley28 degrees ;
Wong Tai Sin29 degrees ;
Stanley27 degrees ;
Kwun Tong28 degrees ;
Sham Shui Po28 degrees ;
Kai Tak Runway Park28 degrees ;
Yuen Long Park28 degrees ;
Tai Mei Tuk28 degrees .




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Hypertension Management in Diabetes: 2018 Update

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




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60k workers received allowance

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.




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Techworld unveils the techies 2018 winners

The winners were revealed at a glitzy party in Shoreditch on 22 February




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UK government launches £10 million Edtech strategy

Education secretary, Damian Hinds, wants schools across the UK to “take advantage of all of the opportunities available through Edtech” in the government's new strategy




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How Onfido raised $100 million at the peak of a pandemic

The UK-based digital identity specialist managed to raise a bumper round during the peak of the COVID-19 pandemic, and is looking at ways to apply its technology to help combat the global crisis




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2020 National Academy of Sciences Elections

17 individuals in the mathematical sciences are among the 126 new members and foreign associates elected to the National Academy of Sciences (NAS) in 2020.

Members: Ivet Bahar, University of Pittsburgh School of Medicine; Abhijit Banerjee, Massachusetts Institute of Technology; Gerard Ben Arous, Courant Institute of Mathematical Sciences, New York University; Bonnie Berger, Massachusetts Institute of Technology; Laura G. DeMarco, Northwestern University; Ronald Fagin, IBM Almaden Research Center; Katherine Freese, The University of Texas at Austin; Dennis Gaitsgory, Harvard University; Robert L. Griess, University of Michigan, Ann Arbor; Jacob Lurie, Institute for Advanced Study; Terence T. Hwa, University of California, San Diego; Wilfried Schmid, Harvard University; Jeffrey D. Ullman, Stanford University; Lai-Sang Young, Courant Institute of Mathematical Sciences, New York University; and Ofer Zeitouni, Weizmann Institute of Science; Foreign Associates: Yoav Benjamini, Tel Aviv University (Israel) and Jürg Fröhlich, ETH Zurich (Switzerland). Berger, DeMarco, Griess, Schmid, and Zeitouni are members of the AMS and Fellows of the AMS. Fagin is a member of the AMS.

The NAS recognizes achievement in science by election to membership, and—along with the National Academy of Engineering and the National Academy of Medicine—provides science, engineering, and health policy advice to the federal government and other organizations. See the full list of this year's honorees. (Image courtesy of the National Academy of Sciences.)




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Math in the Media - May 2020:John Conway, "magical mathematician", Topological analysis of zebrafish, teaching online...




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2020 Mathematical Art Exhibition gallery on AMS Mathematical Imagery




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Hershberger Named 2020 AMS Mass Media Fellow

The AMS is pleased to announce that Scott Hershberger has been chosen as the 2020 AMS Mass Media Fellow. Scott studied mathematics and physics at Washington University in St. Louis and will graduate in May 2020. He will be working at Scientific American this summer.

The Mass Media Science and Engineering Fellows program is organized by the American Association for the Advancement of Science (AAAS). This program is designed to improve public understanding of science and technology by placing advanced undergraduate, graduate and postgraduate science, mathematics and engineering students in media outlets nationwide. The fellows work for ten weeks over the summer as reporters, researchers, and production assistants alongside media professionals to sharpen their communication skills and increase their understanding of the editorial process by which events and ideas become news.

Now in its 45th year, this fellowship program has placed more than 700 fellows in media organizations nationwide as they research, write, and report today’s headlines. The program is designed to report science-related issues in the media in easy-to-understand ways so as to improve public understanding and appreciation for science and technology.

For more information on the AMS Mass Media Fellowship, visit the website.




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European Congress of Mathematics: Krakow, July 2-7, 2012

Rafal Latala, University of Warsaw, Andrzei Rucinski, Adam Mickiewicz University, Pawel Strzelecki, University of Warsaw, Jacek Swiatkowski, University of Wroclaw, and Dariusz Wrzosek and Piotr Zakrzewski, University of Warsaw, Editors - A publication of the European Mathematical Society, 2013, 824 pp., Hardcover, ISBN-13: 978-3-03719-120-0, List: US$128, All AMS Members: US$102.40, EMSEMC/2012

The European Congress of Mathematics, held every four years, has become a well-established major international mathematical event. Following those in...




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HKSAR Air Quality Health Index at : Sun, 10 May 2020 01:30:00 +0800 Current Condition :

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

Roadside Stations: 2 (Health Risk: Low)




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$140m approved for support scheme

More than 8,200 applications for the Anti-epidemic Support Scheme for Property Management Sector (ASPM) have been received, with over 3,850 approved, the Government announced today.

      

The approved applications involve subsidies of more than $140 million and will benefit around 22,000 building blocks and about 35,750 frontline property management workers.

 

Launched under the Anti-epidemic Fund, the ASPM provides subsidies to owners' organisations or property management companies of eligible buildings to provide hardship allowance to frontline property management workers.

 

It also provides the Anti-epidemic Cleansing Subsidy to owners' organisations or property management companies.

 

The scheme’s first phase covers private residential and composite buildings, while its second phase covers industrial and commercial buildings.

 

The ASPM is still open for applications and continues to disburse subsidies.

 

Contact the Property Management Services Authority at 3696 1156 or 3696 1166, or visit its website for details.




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2020 Mathematical Art Exhibition Awards

The 2020 Mathematical Art Exhibition Awards were made at the Joint Mathematics Meetings last week "for aesthetically pleasing works that combine mathematics and art." The chosen works were selected from the exhibition of juried works in various media by over 90 mathematicians and artists from around the world.

"Suspended Helical Stair," by Mark Donohue (California College of the Arts, San Francisco, CA), was awarded Best textile, sculpture, or other medium. "A unique cable system to suspend a stair was developed in collaboration with a leading structural engineer. The suspended cables form a double helicoid nested within an ascending spiral hyperboloid to create the necessary points of support for the gravity loads and lateral bracing for the seismic loads. Each concrete stair tread was designed as an independent element that is strung together with the stairs above and below it to form a single spiral stair when the steel cables that run through them are post tensioned. The entire stair tread and suspension cable system can be understood as a play of ruled surfaces with each part related to the other through their shared geometric lineage." The work is string and plywood,45 x 23 x 23 cm, 2018.

2018

"A Unit Domino," by Douglas McKenna (Mathemaesthetics, Inc., Boulder, CO), was awarded Best photograph, painting, or print. "This piece is based upon an artist-discovered "half-domino" space-filling curve. The drawing comprises some half-million connected line segments, arranged in two perfectly recursive levels of double-spiral pairs, slowly changing color, in a single, over-one-mile-long self-avoiding path from lower left to lower right (the lower right square that sticks out is an integral part of its self-negative structure). The limiting curve covers a self-similar gasket tile with an infinitely long, almost-everywhere linear border. With an upside-down copy of itself, two such gaskets of unit area exactly cover a 1x2 domino, without overlap. The artist's app/eBook "Hilbert Curves" for iPad/iPhone explains how he discovered these beautiful constructions." The work is a glicée print,106 x 66 cm, 2015.

"Computational Wings," by David Bachman (Pitzer College, Claremont, CA), received Honorable Mention. "The body of this dragonfly is taken from a photograph, while the wings were computationally generated. A variety of algorithms were used to create them. First, a set of points were randomly populated across each wing and moved by a circle packing algorithm, where the radius of each circle was inversely proportional to the distance from the body. Next, those points were used to create a Voronoi diagram. Main veins were located by a shortest walk algorithm through the edges of this diagram, and those veins were given a variable thickness according to the distance travelled as you traverse them outward from the body." The work is laser etched acrylic, 23 x 35 x 3 cm, 2019.

(Click on the thumbnails to see larger versions of the images.)

The Mathematical Art Exhibition Award "for aesthetically pleasing works that combine mathematics and art" was established in 2008 through an endowment provided to the American Mathematical Society by an anonymous donor who wishes to acknowledge those whose works demonstrate the beauty and elegance of mathematics expressed in a visual art form. The awards are $400 for Best photograph, painting, or print; $400 for Best textile, sculpture, or other medium; and $200 for Honorable Mention. The Mathematical Art Exhibition of juried works in various media is held at the annual Joint Mathematics Meetings of the American Mathematical Society (AMS) and Mathematical Association of America (MAA). a gallery of works in the 2020 exhibition will be on AMS Mathematical Imagery.

Find out more about the Mathematical Art Exhibition Award and see past recipients.

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***

The American Mathematical Society is dedicated to advancing research and connecting the diverse global mathematical community through our publications, meetings and conferences, MathSciNet, professional services, advocacy, and awareness programs.




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2020 AMS Math Poetry Contest winners

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.




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Emerging Roles for the Nucleolus 2019 [Meeting Report]

IntroductionThe nucleolus is the central organelle within eukaryotic cells whose primary function is to generate ribosomes, the major protein producing machines within all cells. New roles for the nucleolus are continuously emerging as we explore its molecular intricacies. Despite the central and fundamental role of the nucleolus in cell biology, there has previously been no single official meeting that enables the gathering of scientists whose research converges on the nucleolus. As a result, the community of researchers who study this organelle risks fragmentation across disciplines. The Emerging Roles for the Nucleolus Symposium, which has now taken place twice on a biennial basis, first in 2017 (1) and again in 2019, therefore, represents the first of its kind. The overarching goals of this symposium are (a) to convene researchers who study the nucleolus across model systems (yeast, nematodes, fruit flies, mouse, human cell lines) and biological perspectives (structural, biophysical, molecular, cellular, pathophysiology), (b) to share and disseminate the latest research breakthroughs in nucleolar biology, (c) to promote interaction, engagement, and collaboration centered on the nucleolus across disciplines, and (d) to provide trainees and early career investigators with an organelle-specific scientific community of support.The second Emerging Roles for the Nucleolus meeting was sponsored by the American Society for Biochemistry and Molecular Biology and was held at the Stowers Institute for Medical Research in Kansas City, MO, from October 24 to October 27, 2019. It was organized by Jennifer Gerton (Stowers Institute), Francesca Duncan (Northwestern University Feinberg School of Medicine), and Craig Pikaard...




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Structural basis of specific inhibition of extracellular activation of pro- or latent myostatin by the monoclonal antibody SRK-015 [Molecular Biophysics]

Myostatin (or growth/differentiation factor 8 (GDF8)) is a member of the transforming growth factor β superfamily of growth factors and negatively regulates skeletal muscle growth. Its dysregulation is implicated in muscle wasting diseases. SRK-015 is a clinical-stage mAb that prevents extracellular proteolytic activation of pro- and latent myostatin. Here we used integrated structural and biochemical approaches to elucidate the molecular mechanism of antibody-mediated neutralization of pro-myostatin activation. The crystal structure of pro-myostatin in complex with 29H4-16 Fab, a high-affinity variant of SRK-015, at 2.79 Å resolution revealed that the antibody binds to a conformational epitope in the arm region of the prodomain distant from the proteolytic cleavage sites. This epitope is highly sequence-divergent, having only limited similarity to other closely related members of the transforming growth factor β superfamily. Hydrogen/deuterium exchange MS experiments indicated that antibody binding induces conformational changes in pro- and latent myostatin that span the arm region, the loops contiguous to the protease cleavage sites, and the latency-associated structural elements. Moreover, negative-stain EM with full-length antibodies disclosed a stable, ring-like antigen–antibody structure in which the two Fab arms of a single antibody occupy the two arm regions of the prodomain in the pro- and latent myostatin homodimers, suggesting a 1:1 (antibody:myostatin homodimer) binding stoichiometry. These results suggest that SRK-015 binding stabilizes the latent conformation and limits the accessibility of protease cleavage sites within the prodomain. These findings shed light on approaches that specifically block the extracellular activation of growth factors by targeting their precursor forms.




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Structures of the MHC-I molecule BF2*1501 disclose the preferred presentation of an H5N1 virus-derived epitope [Protein Structure and Folding]

Lethal infections by strains of the highly-pathogenic avian influenza virus (HPAIV) H5N1 pose serious threats to both the poultry industry and public health worldwide. A lack of confirmed HPAIV epitopes recognized by cytotoxic T lymphocytes (CTLs) has hindered the utilization of CD8+ T-cell–mediated immunity and has precluded the development of effectively diversified epitope-based vaccination approaches. In particular, an HPAIV H5N1 CTL-recognized epitope based on the peptide MHC-I–β2m (pMHC-I) complex has not yet been designed. Here, screening a collection of selected peptides of several HPAIV strains against a specific pathogen-free pMHC-I (pBF2*1501), we identified a highly-conserved HPAIV H5N1 CTL epitope, named HPAIV–PA123–130. We determined the structure of the BF2*1501–PA123–130 complex at 2.1 Å resolution to elucidate the molecular mechanisms of a preferential presentation of the highly-conserved PA123–130 epitope in the chicken B15 lineage. Conformational characteristics of the PA123–130 epitope with a protruding Tyr-7 residue indicated that this epitope has great potential to be recognized by specific TCRs. Moreover, significantly increased numbers of CD8+ T cells specific for the HPAIV–PA123–130 epitope in peptide-immunized chickens indicated that a repertoire of CD8+ T cells can specifically respond to this epitope. We anticipate that the identification and structural characterization of the PA123–130 epitope reported here could enable further studies of CTL immunity against HPAIV H5N1. Such studies may aid in the development of vaccine development strategies using well-conserved internal viral antigens in chickens.




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Structure of an ancestral mammalian family 1B1 cytochrome P450 with increased thermostability [Enzymology]

Mammalian cytochrome P450 enzymes often metabolize many pharmaceuticals and other xenobiotics, a feature that is valuable in a biotechnology setting. However, extant P450 enzymes are typically relatively unstable, with T50 values of ∼30–40 °C. Reconstructed ancestral cytochrome P450 enzymes tend to have variable substrate selectivity compared with related extant forms, but they also have higher thermostability and therefore may be excellent tools for commercial biosynthesis of important intermediates, final drug molecules, or drug metabolites. The mammalian ancestor of the cytochrome P450 1B subfamily was herein characterized structurally and functionally, revealing differences from the extant human CYP1B1 in ligand binding, metabolism, and potential molecular contributors to its thermostability. Whereas extant human CYP1B1 has one molecule of α-naphthoflavone in a closed active site, we observed that subtle amino acid substitutions outside the active site in the ancestor CYP1B enzyme yielded an open active site with four ligand copies. A structure of the ancestor with 17β-estradiol revealed only one molecule in the active site, which still had the same open conformation. Detailed comparisons between the extant and ancestor forms revealed increases in electrostatic and aromatic interactions between distinct secondary structure elements in the ancestral forms that may contribute to their thermostability. To the best of our knowledge, this represents the first structural evaluation of a reconstructed ancestral cytochrome P450, revealing key features that appear to contribute to its thermostability.




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Mechanistic insights explain the transforming potential of the T507K substitution in the protein-tyrosine phosphatase SHP2 [Signal Transduction]

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.




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The hibernating 100S complex is a target of ribosome-recycling factor and elongation factor G in Staphylococcus aureus [Protein Synthesis and Degradation]

The formation of translationally inactive 70S dimers (called 100S ribosomes) by hibernation-promoting factor is a widespread survival strategy among bacteria. Ribosome dimerization is thought to be reversible, with the dissociation of the 100S complexes enabling ribosome recycling for participation in new rounds of translation. The precise pathway of 100S ribosome recycling has been unclear. We previously found that the heat-shock GTPase HflX in the human pathogen Staphylococcus aureus is a minor disassembly factor. Cells lacking hflX do not accumulate 100S ribosomes unless they are subjected to heat exposure, suggesting the existence of an alternative pathway during nonstressed conditions. Here, we provide biochemical and genetic evidence that two essential translation factors, ribosome-recycling factor (RRF) and GTPase elongation factor G (EF-G), synergistically split 100S ribosomes in a GTP-dependent but tRNA translocation-independent manner. We found that although HflX and the RRF/EF-G pair are functionally interchangeable, HflX is expressed at low levels and is dispensable under normal growth conditions. The bacterial RRF/EF-G pair was previously known to target only the post-termination 70S complexes; our results reveal a new role in the reversal of ribosome hibernation that is intimately linked to bacterial pathogenesis, persister formation, stress responses, and ribosome integrity.




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COQ11 deletion mitigates respiratory deficiency caused by mutations in the gene encoding the coenzyme Q chaperone protein Coq10 [Lipids]

Coenzyme Q (Qn) is a vital lipid component of the electron transport chain that functions in cellular energy metabolism and as a membrane antioxidant. In the yeast Saccharomyces cerevisiae, coq1–coq9 deletion mutants are respiratory-incompetent, sensitive to lipid peroxidation stress, and unable to synthesize Q6. The yeast coq10 deletion mutant is also respiratory-deficient and sensitive to lipid peroxidation, yet it continues to produce Q6 at an impaired rate. Thus, Coq10 is required for the function of Q6 in respiration and as an antioxidant and is believed to chaperone Q6 from its site of synthesis to the respiratory complexes. In several fungi, Coq10 is encoded as a fusion polypeptide with Coq11, a recently identified protein of unknown function required for efficient Q6 biosynthesis. Because “fused” proteins are often involved in similar biochemical pathways, here we examined the putative functional relationship between Coq10 and Coq11 in yeast. We used plate growth and Seahorse assays and LC-MS/MS analysis to show that COQ11 deletion rescues respiratory deficiency, sensitivity to lipid peroxidation, and decreased Q6 biosynthesis of the coq10Δ mutant. Additionally, immunoblotting indicated that yeast coq11Δ mutants accumulate increased amounts of certain Coq polypeptides and display a stabilized CoQ synthome. These effects suggest that Coq11 modulates Q6 biosynthesis and that its absence increases mitochondrial Q6 content in the coq10Δcoq11Δ double mutant. This augmented mitochondrial Q6 content counteracts the respiratory deficiency and lipid peroxidation sensitivity phenotypes of the coq10Δ mutant. This study further clarifies the intricate connection between Q6 biosynthesis, trafficking, and function in mitochondrial metabolism.




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The cytochrome P450 enzyme CYP24A1 increases proliferation of mutant KRAS-dependent lung adenocarcinoma independent of its catalytic activity [Cell Biology]

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.




0

Government announces Study Subsidy Scheme for Designated Professions/Sectors for 2020/21 cohort - sub-degree programmes




0

Life Planning Education Conference 2019 held today




0

HKEAA submits 2019 Territory-wide System Assessment Report




0

Speech by SED at opening ceremony of Learning and Teaching Expo 2019




0

Subsidy amount for Non-means-tested Subsidy Scheme for Self-financing Undergraduate Studies in Hong Kong in 2020/21 academic year announced




0

First School Allocation Exercise 2020 invites applications for five kindergarten premises in public housing estates




0

EDB announces arrangements for provision of Student Grant in 2019/20 school year




0

Application deadline extended for First School Allocation Exercise 2020 for allocation of five new estate kindergarten premises