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From Strings to Mirrors




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HKTDC to launch Spring Virtual Expo and Guided SME Support

The COVID-19 pandemic has impacted business activity and supply chains across the globe, with numerous trade fairs and events around the world being postponed or cancelled, depriving many enterprises of business and marketing...




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Start-up Express returns for third edition

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




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HKTDC to host Summer Virtual Expo

The pilot month-long Spring Virtual Expo, organised by the Hong Kong Trade Development Council (HKTDC) on its online marketplace hktdc.com Sourcing, concluded successfully on 30 April. It drew 1.4 million online buyers from around the...




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Irish Projects Set for Les Arcs Co-Production Village

The Les Arcs Co-Production village, running December 13-16 within the Les Arcs European Film Festival (Dec 13-20), will present 25 projects in development and a further 10 works-in-progress. Several of the projects chosen for this year’s event are Irish films and films with Irish producers’ backing.




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Interview with Director Pat O’ Connor

Guest of Honour at Film Mayo launch on 1st December




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EdUHK council chair reappointed

The Chief Executive has reappointed Frederick Ma as Chairman of the Education University of Hong Kong (EdUHK) Council from April 25 to December 31, the Government announced today.

 

Secretary for Education Kevin Yeung thanked Mr Ma for accepting the reappointment, saying that under his leadership, EdUHK continues to focus on educational research, development and innovation and promoting and supporting the development of teacher education in Hong Kong by nurturing outstanding and committed educators and professionals.

 

Mr Ma cannot accept a three-year term up until 2023 due to personal reasons. In the meantime, the Government will identify a suitable candidate for the chairmanship of the EdUHK Council.




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Case Study: Cognitive Impairment, Depression, and Severe Hypoglycemia

John Zrebiec
Oct 1, 2006; 19:212-215
Clinical Decision Making




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Patrick Nip visits IRD, Labour Dep't

Secretary for the Civil Service Patrick Nip today visited the Inland Revenue Department and the Labour Department to inspect the resumption of public services.

 

The Government had earlier announced that public services will be resumed under a phased approach.

 

Counter services of most government departments have returned to normal.

 

Mr Nip first visited the Inland Revenue Department in Revenue Tower and was briefed on counter services at the Central Enquiry Counter, the Business Registration Office and the Stamp Office.

 

He learnt that the department has implemented various infection control and crowd management measures, such as a ticketing system, to safeguard the health of colleagues and the public.

 

Later Mr Nip visited the Hong Kong East Job Centre and a recruitment centre for the catering and retail industries and was briefed on the resumption of normal services at the Labour Department's job and recruitment centres.

 

He said: “While maintaining a high degree of vigilance and adopting all necessary precautionary measures, the Government gradually resumed public services today in a smooth and orderly manner.

 

“Various infection control measures have been put in place at government buildings and offices. These include checking the body temperature of persons at entrances, providing alcohol-based hand sanitiser and enhancing the cleaning of public facilities.

 

“The Government will closely monitor the situation to determine when to embark on full resumption of normal business.”




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Technologists lead crowdsourced Coronavirus Tech Handbook response

A group of technologists has led crowdsourcing efforts to create a single repository of information for specialists fighting the Coronavirus outbreak. Techworld speaks with founder Edward Saperia to hear more about how collaboration tools can help the efforts




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Tech Nation launches virtual 'Office Hours' event for female founders

The virtual-based office hours is to connect female founders with early-stage VC investors who will provide business advice and investments




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Karin Melnick receives Birman Fellowship

Karin Melnick of the University of Maryland, College Park, has been awarded the AMS Joan and Joseph Birman Fellowship for Women Scholars for the 2020–2021 academic year.

Melnick’s research is on differential-geometric aspects of rigidity. This work comprises global and local results relating the automorphisms of a differential-geometric structure with the geometric and topological properties of the space. Melnick also works in smooth dynamics, in which an invariant differential-geometric structure plays an important role in the proof of rigidity theorems. Melnick is a leader in research on the Lorentzian Lichnerowicz conjecture, a statement about conformal transformations of compact Lorentzian manifolds. Together with collaborators, she has developed new techniques in the setting of Cartan connections that have facilitated progress on this problem, as well as many results for other differential-geometric structures and general parabolic Cartan geometries.  

Brief Biography of Karin Melnick:

Melnick received her PhD at the University of Chicago in 2006 under the direction of Benson Farb. With an NSF Postdoctoral Research Fellowship, she went to Yale University as a Gibbs Assistant Professor. She received a Junior Research Fellowship from the Erwin Schrödinger Institute in the spring of 2009 and that fall began at the University of Maryland, where she is now an associate professor. Previously, Melnick has been awarded an AMS Centennial Fellowship and an NSF CAREER grant. She divides her time between the U.S. and Germany with her partner and their young child, and is very grateful for the flexibility provided by the Birman Fellowship and the opportunities it provides to advance her research and career goals.  

About the Fellowship:

Established in 2017, the AMS Joan and Joseph Birman Fellowship for Women Scholars seeks to give exceptionally talented women extra research support during their mid-career years. The primary selection criterion for the Birman Fellowship, which carries a stipend of US$50,000, is the excellence of the candidate’s research. Read an interview with Joan Birman about her decision to create the Fellowship with the goal of "helping more women mathematicians to develop their creative voices." See more information about the Fellowship.

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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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One-Dimensional General Forest Fire Processes

Xavier Bressaud, Universite Paul Sabatier, and Nicolas Fournier, Universite Paris-Est - A publication of the Societe Mathematique de France, 2013, 138 pp., Softcover, ISBN-13: 978-2-85629-765-0, List: US$48, All AMS Members: US$38.40, SMFMEM/132

The authors consider the one-dimensional generalized forest fire process: at each site of (mathbb{Z}), seeds and matches fall according to i.i.d....




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Transformations Birationnelles de Petit Degre

Dominique Cerveau, Universite de Rennes 1, and Julie Deserti, Universite Paris 7 - A publication of the Societe Mathematique de France, 2013, 223 pp., Softcover, ISBN-13: 978-2-85629-770-4, List: US$108, All AMS Members: US$86.40, COSP/19

Since the end of the 19th century, we have known that each birational map of the complex projective plane is the product of a finite number of...




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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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Dartmouth's Katherine Mirica wins National Teacher-Scholar Honor

(Dartmouth College) Annual award supports the research and teaching careers of talented young faculty in the chemical sciences.




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Bank of REU/Grad Fair Questions




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The transcriptional regulator IscR integrates host-derived nitrosative stress and iron starvation in activation of the vvhBA operon in Vibrio vulnificus [Gene Regulation]

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




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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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Correction: A dual druggable genome-wide siRNA and compound library screening approach identifies modulators of parkin recruitment to mitochondria. [Additions and Corrections]

VOLUME 295 (2020) PAGES 3285–3300An incorrect graph was used in Fig. 5C. This error has now been corrected. Additionally, some of the statistics reported in the legend and text referring to Fig. 5C were incorrect. The F statistics for Fig. 5C should state Fken(3,16) = 7.454, p < 0.01; FCCCP(1,16) = 102.9, p < 0.0001; Finteraction(3,16) = 7.480, p < 0.01. This correction does not affect the results or conclusions of this work.jbc;295/17/5835/F5F1F5Figure 5C.




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X-ray structures of catalytic intermediates of cytochrome c oxidase provide insights into its O2 activation and unidirectional proton-pump mechanisms [Molecular Biophysics]

Cytochrome c oxidase (CcO) reduces O2 to water, coupled with a proton-pumping process. The structure of the O2-reduction site of CcO contains two reducing equivalents, Fea32+ and CuB1+, and suggests that a peroxide-bound state (Fea33+–O−–O−–CuB2+) rather than an O2-bound state (Fea32+–O2) is the initial catalytic intermediate. Unexpectedly, however, resonance Raman spectroscopy results have shown that the initial intermediate is Fea32+–O2, whereas Fea33+–O−–O−–CuB2+ is undetectable. Based on X-ray structures of static noncatalytic CcO forms and mutation analyses for bovine CcO, a proton-pumping mechanism has been proposed. It involves a proton-conducting pathway (the H-pathway) comprising a tandem hydrogen-bond network and a water channel located between the N- and P-side surfaces. However, a system for unidirectional proton-transport has not been experimentally identified. Here, an essentially identical X-ray structure for the two catalytic intermediates (P and F) of bovine CcO was determined at 1.8 Å resolution. A 1.70 Å Fe–O distance of the ferryl center could best be described as Fea34+ = O2−, not as Fea34+–OH−. The distance suggests an ∼800-cm−1 Raman stretching band. We found an interstitial water molecule that could trigger a rapid proton-coupled electron transfer from tyrosine-OH to the slowly forming Fea33+–O−–O−–CuB2+ state, preventing its detection, consistent with the unexpected Raman results. The H-pathway structures of both intermediates indicated that during proton-pumping from the hydrogen-bond network to the P-side, a transmembrane helix closes the water channel connecting the N-side with the hydrogen-bond network, facilitating unidirectional proton-pumping during the P-to-F transition.




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N{alpha}-Acetylation of the virulence factor EsxA is required for mycobacterial cytosolic translocation and virulence [Molecular Bases of Disease]

The Mycobacterium tuberculosis virulence factor EsxA and its chaperone EsxB are secreted as a heterodimer (EsxA:B) and are crucial for mycobacterial escape from phagosomes and cytosolic translocation. Current findings support the idea that for EsxA to interact with host membranes, EsxA must dissociate from EsxB at low pH. However, the molecular mechanism by which the EsxA:B heterodimer separates is not clear. In the present study, using liposome-leakage and cytotoxicity assays, LC-MS/MS–based proteomics, and CCF-4 FRET analysis, we obtained evidence that the Nα-acetylation of the Thr-2 residue on EsxA, a post-translational modification that is present in mycobacteria but absent in Escherichia coli, is required for the EsxA:B separation. Substitutions at Thr-2 that precluded Nα-acetylation inhibited the heterodimer separation and hence prevented EsxA from interacting with the host membrane, resulting in attenuated mycobacterial cytosolic translocation and virulence. Molecular dynamics simulations revealed that at low pH, the Nα-acetylated Thr-2 makes direct and frequent “bind-and-release” contacts with EsxB, which generates a force that pulls EsxB away from EsxA. In summary, our findings provide evidence that the Nα-acetylation at Thr-2 of EsxA facilitates dissociation of the EsxA:B heterodimer required for EsxA membrane permeabilization and mycobacterial cytosolic translocation and virulence.




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Withdrawal: miR-21-mediated radioresistance occurs via promoting repair of DNA double strand breaks. [Withdrawals/Retractions]

VOLUME 292 (2017) PAGES 3531–3540This article has been withdrawn by Shuofeng Hu, Xiaomin Ying, Xiangming Zhang, and Ya Wang. Baocheng Hu, Xiang Wang, Ping Wang, Jian Wang, and Hongyan Wang could not be reached. In Fig. 1C, the DAPI and merged images for the no IR control were switched. The DNA-PKcs and actin immunoblots on the left appear to have been spliced. In Fig. 4C, the DNA-PKcs immunoblot appears to have been spliced. In Fig. 4D, lanes 1 and 5; lanes 2, 6, and 8; and lanes 3 and 7 of the DNA-PKcs immunoblot are the same. In the p-DNA-PKcs immunoblot, lanes 1 and 8, lanes 2 and 6, and lanes 3 and 7 are the same. In the CRY2 immunoblot, lanes 5 and 7 are the same. In the CDC25A immunoblot, lanes 3 and 8 are the same. In the GSK3B immunoblot, lanes 1 and 5 and lanes 3 and 7 are the same. Also in the GSK3B immunoblot, the upper GSK3B bands in lanes 6 and 8 are the same. Lanes 4 and 8 of the cyclin D1 immunoblot are the same. In Fig. 5A, the CDC25A immunoblot appears to have been spliced. Also in Fig. 5A, lanes 2–4 and lanes 6–8 of the CDC25A immunoblot are the same. Lanes 4–6 and 7–9 of the actin immunoblot are the same. In Fig. 5C, lane 1 of the CDC25A immunoblot was reused in lane 5, and lanes 3 and 4 were reused in lanes 7 and 8. In the...




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Withdrawal: Distinct roles of Ape1 protein, an enzyme involved in DNA repair, in high or low linear energy transfer ionizing radiation-induced cell killing. [Withdrawals/Retractions]

VOLUME 289 (2014) PAGES 30635–30644This article has been withdrawn by Guangnan Chen, Dongkyoo Park, Francis A. Cucinotta, David S. Yu, Xingming Deng, William S. Dynan, Paul W. Doetsch, and Ya Wang. Hongyan Wang, Xiang Wang, Xiangming Zhang, and Xiaobing Tang could not be reached. The last two lanes of the actin immunoblot in Fig. 1A were reused in the last two lanes of the actin immunoblot in Fig. 1C. In Fig. 2A, the γ-H2AX and the merge with DAPI images for no IR treatment do not match. In Fig. 3A, lanes 3 and 4 of the γ-H2AX immunoblot were reused in lanes 7 and 8, and lanes 5 and 6 of the H2A immunoblot were reused in lanes 7 and 8. In Fig. 3B, lanes 5 and 6 of the H2A immunoblot were reused in lanes 7 and 8. In Fig. 3C, lanes 5 and 6 of the γ-H2AX immunoblot were reused in lanes 7 and 8. Additionally, lanes 1 and 2 of the H2A immunoblot were reused in lanes 3 and 4. In Fig. 3D, lanes 1 and 2 of the Mre11 immunoblot from lysates were reused in lanes 4 and 5. In the γ-H2AX immunoblot, lane 3 was reused in lane 7, and lane 4 was reused in lanes 6 and 8. Also in the H2A immunoblot, lanes 1 and 2 were reused in lanes 3 and 4. In Fig. 4B, lanes 2 and 6 of the Mre11 immunoblot from Ogg1−/− cells are the same. In the Ape1...




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Certain ortho-hydroxylated brominated ethers are promiscuous kinase inhibitors that impair neuronal signaling and neurodevelopmental processes [Cell Biology]

The developing nervous system is remarkably sensitive to environmental signals, including disruptive toxins, such as polybrominated diphenyl ethers (PBDEs). PBDEs are an environmentally pervasive class of brominated flame retardants whose neurodevelopmental toxicity mechanisms remain largely unclear. Using dissociated cortical neurons from embryonic Rattus norvegicus, we found here that chronic exposure to 6-OH–BDE-47, one of the most prevalent hydroxylated PBDE metabolites, suppresses both spontaneous and evoked neuronal electrical activity. On the basis of our previous work on mitogen-activated protein kinase (MAPK)/extracellular signal-related kinase (ERK) (MEK) biology and our observation that 6-OH–BDE-47 is structurally similar to kinase inhibitors, we hypothesized that certain hydroxylated PBDEs mediate neurotoxicity, at least in part, by impairing the MEK–ERK axis of MAPK signal transduction. We tested this hypothesis on three experimental platforms: 1) in silico, where modeling ligand–protein docking suggested that 6-OH–BDE-47 is a promiscuous ATP-competitive kinase inhibitor; 2) in vitro in dissociated neurons, where 6-OH–BDE-47 and another specific hydroxylated BDE metabolite similarly impaired phosphorylation of MEK/ERK1/2 and activity-induced transcription of a neuronal immediate early gene; and 3) in vivo in Drosophila melanogaster, where developmental exposures to 6-OH–BDE-47 and a MAPK inhibitor resulted in offspring displaying similarly increased frequency of mushroom-body β–lobe midline crossing, a metric of axonal guidance. Taken together, our results support that certain ortho-hydroxylated PBDE metabolites are promiscuous kinase inhibitors and can cause disruptions of critical neurodevelopmental processes, including neuronal electrical activity, pre-synaptic functions, MEK–ERK signaling, and axonal guidance.




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MtrP, a putative methyltransferase in Corynebacteria, is required for optimal membrane transport of trehalose mycolates [Lipids]

Pathogenic bacteria of the genera Mycobacterium and Corynebacterium cause severe human diseases such as tuberculosis (Mycobacterium tuberculosis) and diphtheria (Corynebacterium diphtheriae). The cells of these species are surrounded by protective cell walls rich in long-chain mycolic acids. These fatty acids are conjugated to the disaccharide trehalose on the cytoplasmic side of the bacterial cell membrane. They are then transported across the membrane to the periplasm where they act as donors for other reactions. We have previously shown that transient acetylation of the glycolipid trehalose monohydroxycorynomycolate (hTMCM) enables its efficient transport to the periplasm in Corynebacterium glutamicum and that acetylation is mediated by the membrane protein TmaT. Here, we show that a putative methyltransferase, encoded at the same genetic locus as TmaT, is also required for optimal hTMCM transport. Deletion of the C. glutamicum gene NCgl2764 (Rv0224c in M. tuberculosis) abolished acetyltrehalose monocorynomycolate (AcTMCM) synthesis, leading to accumulation of hTMCM in the inner membrane and delaying its conversion to trehalose dihydroxycorynomycolate (h2TDCM). Complementation with NCgl2764 normalized turnover of hTMCM to h2TDCM. In contrast, complementation with NCgl2764 derivatives mutated at residues essential for methyltransferase activity failed to rectify the defect, suggesting that NCgl2764/Rv0224c encodes a methyltransferase, designated here as MtrP. Comprehensive analyses of the individual mtrP and tmaT mutants and of a double mutant revealed strikingly similar changes across several lipid classes compared with WT bacteria. These findings indicate that both MtrP and TmaT have nonredundant roles in regulating AcTMCM synthesis, revealing additional complexity in the regulation of trehalose mycolate transport in the Corynebacterineae.




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Impact of 1,N6-ethenoadenosine, a damaged ribonucleotide in DNA, on translesion synthesis and repair [Enzymology]

Incorporation of ribonucleotides into DNA can severely diminish genome integrity. However, how ribonucleotides instigate DNA damage is poorly understood. In DNA, they can promote replication stress and genomic instability and have been implicated in several diseases. We report here the impact of the ribonucleotide rATP and of its naturally occurring damaged analog 1,N6-ethenoadenosine (1,N6-ϵrA) on translesion synthesis (TLS), mediated by human DNA polymerase η (hpol η), and on RNase H2–mediated incision. Mass spectral analysis revealed that 1,N6-ϵrA in DNA generates extensive frameshifts during TLS, which can lead to genomic instability. Moreover, steady-state kinetic analysis of the TLS process indicated that deoxypurines (i.e. dATP and dGTP) are inserted predominantly opposite 1,N6-ϵrA. We also show that hpol η acts as a reverse transcriptase in the presence of damaged ribonucleotide 1,N6-ϵrA but has poor RNA primer extension activities. Steady-state kinetic analysis of reverse transcription and RNA primer extension showed that hpol η favors the addition of dATP and dGTP opposite 1,N6-ϵrA. We also found that RNase H2 recognizes 1,N6-ϵrA but has limited incision activity across from this lesion, which can lead to the persistence of this detrimental DNA adduct. We conclude that the damaged and unrepaired ribonucleotide 1,N6-ϵrA in DNA exhibits mutagenic potential and can also alter the reading frame in an mRNA transcript because 1,N6-ϵrA is incompletely incised by RNase H2.




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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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Modification of a PE/PPE substrate pair reroutes an Esx substrate pair from the mycobacterial ESX-1 type VII secretion system to the ESX-5 system [Molecular Bases of Disease]

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.




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Structure-based discovery of a small-molecule inhibitor of methicillin-resistant Staphylococcus aureus virulence [Molecular Biophysics]

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.




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5-Ethynyl-2'-deoxycytidine and 5-ethynyl-2'-deoxyuridine are differentially incorporated in cells infected with HSV-1, HCMV, and KSHV viruses [Microbiology]

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.




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Chairman of Council of Lingnan University departs early




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Appointment of Chairman of Council of Lingnan University




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




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EDB's response to Ombudsman's direct investigation report




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




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The first local case of dengue fever in 2020




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Re-appointment of Chairman of Council of Education University of Hong Kong




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Application for Exemption from the Language Proficiency Requirement is to close on 29 May 2020




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Could a polio vaccine stop the coronavirus pandemic? (video)

(American Chemical Society) The COVID-19 pandemic has scientists considering a few less-conventional options while vaccines against SARS-CoV-2 are being developed. One option might be the oral polio vaccine. We chatted with one of the researchers proposing the idea -- Robert Gallo, M.D. -- to understand why a vaccine that hasn't been used in the U.S. for two decades might provide short-term protection against this new coronavirus: https://youtu.be/Wqw4aX4c33c.




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GSA's North-Central Section Meeting goes virtual

(Geological Society of America) The annual meeting of The Geological Society of America's North-Central Section, originally scheduled to take place in Duluth, Minnesota, will be held virtually on May 18-19, 2020, with technical sessions in the morning and student programming in the afternoon. The online meeting is open and available to everyone for free. No registration is required.




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HK airport’s fresh approach

In March, Hong Kong International Airport (HKIA) became the first in the world to be certified as an International Air Transport Association (IATA) Center of Excellence for Perishable Logistics (CEIV Fresh) Partner Airport.

 

Two of the airport’s cargo terminal operators, Hong Kong Air Cargo Terminals Limited (HACTL) and Cathay Pacific Services Limited (CPSL) have achieved IATA CEIV Fresh Certification, while Cathay Pacific recently became the world’s first airline to be certified.

 

IATA created the Centre of Excellence for Independent Validators (CEIV) to help organisations involved in the air cargo supply chain achieve handling excellence.

 

The certification underscores the speed, consistency and efficiency of all HKIA stakeholders when it comes to the treatment and transportation of perishable products.

 

It also helps to ensure food safety, and reduce food wastage and loss along the supply chain.

 

Quality benchmark

Hong Kong Air Cargo Terminals Limited Chief Executive Wilson Kwong said the main value of the accreditation is that it provides a universally recognised standard.

 

“It gives assurance to the various stakeholders that we have, and we are adhering to the highest possible standards.”

 

Both accredited cargo terminal operators HACTL and CPSL have set up perishable cargo handling areas with truck docks next to the apron.

 

As soon as the perishable goods are unloaded from the aircraft, they are immediately transported to the handling area.

 

The clearance and sampling checks have been streamlined to minimise the time taken to unload the goods. There are cold rooms set at tailored temperatures for various kinds of perishable cargo.

 

Their staff training and handling process have also been assessed and certified for their compliance with the global industry standards.

 

Cathay Pacific Services Limited Chief Executive Officer Jenny Lam noted that one of the challenges in meeting the certification standard is training its 2,000 employees in handling and storing perishable goods.

 

“They first have to identify what types of perishables they are, such as are they flowers, are they fruits, are they meat, so that they know how to segregate the storage.

 

“Secondly, they gain knowledge about certain fruits that cannot be put close to each other such as bananas and apples.”

 

Growth opportunities

In 2018, the airport handled about 380,000 tonnes of perishable cargo - a rise of 12% on 2017, with perishables accounting for about 8% of total air cargo volume.

 

Airport Authority Commercial Executive Director Cissy Chan explained that temperature-controlled air freight is one of the fastest growing segments in the air cargo market.

 

She believes with the new certification, the airport is well-placed to capture the increasing growth opportunities in the market for fresh and perishable goods.

 

“With the opening of the Hong Kong-Zhuhai-Macao Bridge, the transport time between the airport and the Greater Bay Area, notably the western part of the Pearl River Delta, will be further cut down.

 

“So this will put us in an even better position to become the transhipment hub for these perishables for the entire bay area.”

 

Extra backing

To support the growing demand for perishables, the Airport Authority has provided additional cool dollies, so there are now more than 30 for use by the whole airport community. It is also building apron shelters to protect the perishables from ambient weather elements.

 

Cathay Pacific Cargo Service Delivery General Manager Frosti Lau said they would work closely with the authority and its cargo terminal to see what new investments are required to handle the increasing demand.




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HK Airport sets green standard

The Airport Authority expanded the scope of its food waste recycling programme in 2011 to cover Hong Kong International Airport business partners, including restaurants and lounges operating in terminal buildings, as well as airline catering companies, hotels and cargo terminals.

 

In 2017-18, over 2,000 tonnes of food waste from 17 airport business partners were collected for recycling.

 

Rainie Ho, the supervisor of one participating restaurant, said staff make every effort to collect food waste on a constant basis.

 

“We have three bins of recycled food waste, including eggs, toast, bread, chicken, meat, pork bones, tea and coffee every day.”

 

Ms Ho gave kudos to the Airport Authority for making the process simple.

 

“The Airport Authority provides us with garbage bags every month. We explain to our staff that the red bags are for food waste, while the black ones are for general rubbish. This makes it easier for them to remember and handle.”

 

Airport Authority Assistant General Manager (Sustainability) Mike Kilburn is the facilitator of the food waste recycling programme. He hoped to encourage more business partners to join by making the scheme as trouble-free as possible.

 

“This is an example of an easy, useful and free programme because the contractor comes to collect from each company and the contractor provides a clean rubbish bin for the food waste, they take the food waste away, they wash the bin and then they bring it back clean.

 

“And it is useful because the food waste is not just sent to the landfill, but it is turned into fish meal so it goes back into the food chain because the fish meal is fed to the fish and the people can eat the fish, so it is a very complete system.”

 

Surplus food collection

In addition to food waste recycling, the authority promotes the Food Rescue Programme in co-operation with a local non-governmental organisation called Food Angel.

 

In 2013, the authority helped Food Angel to purchase a refrigerated truck and covered the cost of collecting surplus food from business partners on the airport island.

 

By 2014, a central storage room was set up in the terminal building to collect even more surplus food from catering outlets.

 

By proving it can reduce its environmental impact by working closely with the entire airport community, the authority was recognised at the 2018 Hong Kong Awards for Environmental Excellence where it won the Gold Award for the Public & Community Services Sector.

 

Future prep

In 2018, the authority launched a voluntary municipal solid waste charging pilot scheme to achieve waste reduction.

 

It has assisted more than 200 tenants with measuring their waste generation and calculating what it would cost to dump it in the future.

 

Another participating restaurant manager Alfred Lau explained that the pilot scheme helps restaurants gear up for the polluter-pays principle.

 

“A mock monthly invoice was issued to us, showing the quantity of waste disposed and the estimated disposal charge. Now we understand that by reducing our waste, we will pay less in the end.”

 

Mr Lau believes the pilot scheme encourages eateries to alter their disposal behaviour by recycling as much food waste as possible.

 

“Our disposed waste amount fell sharply once we learnt useful ways to recycle. Our restaurant is located in the restricted area of the airport where drinks are not allowed to be brought inside. So many passengers buy bottled drinks and create a large amount of plastic waste. Just by recycling plastic bottles, our waste decreased significantly.”

 

The authority said it is proud to be the driving force behind waste reduction.

 

“We make it easy for them because we do all the organisation, we make it useful because they can help them to prepare, and it is free for them to join the programme. This is very important for us because as the Airport Authority, our job is to create a concept that other people can follow and if you address those three criteria, you make it very hard for them to say no to you. We take away their reasons to say no, so it is easy for them to join our scheme,” said Mr Kilburn.

 

The Hong Kong Awards for Environmental Excellence is led by the Environmental Campaign Committee alongside the Environmental Protection Department and in conjunction with nine organisations. The objective is to reduce Hong Kong’s environmental impact by promoting environmental management.

 

The Airport Authority’s current target is to reduce, recycle and recover 50% of all its waste by 2021.




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How to Make Sound Decisions with Limited Data During the Coronavirus Pandemic

Thursday, April 2, 2020 - 13:00

Coronavirus presents an unprecedented predicament: Everyday, leaders must make momentous decisions with life or death consequences for many—but there is a dearth of data. Oded Netzer is a Columbia Business School professor and Data Science Institute affiliate who builds statistical and econometric models to measure consumer behavior that help business leaders make data-driven decisions. Here, he discusses how leaders from all fields can make sound decisions with scarce data to guide them.




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Research from Columbia Business School Suggests Hypersensitivity to Coronavirus News Is Driving Market Reactions – and Vice Versa

Friday, April 10, 2020 - 22:45

NEW YORK – On March 11th, the Dow Jones Industrial Average plunged 1,485 points, ending the longest bull-market run in history, and sending the market into nosedive the likes of which has not been witnessed since the Great Recession. While it could take years to fully understand all of the factors that led to this recent crash, a consensus has emerged that fear of an economic downturn brought on by the coronavirus has played a large role.




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Cool Met Stuff, composition of air, main gases, climate change, global warming, carbon dioxide concentration, fraction, atmosphere

Do you know which main gases are contained in the composition of air? Under climate change and global warming, carbon dioxide ...




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Vitamin D linked to low virus death rate -- Study

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Recent Australian wildfires made worse by logging

(University of Queensland) Logging of native forests increases the risk and severity of fire and likely had a profound effect on the recent, catastrophic Australian bushfires, according to new research.In the wake of the country's worst forest fires in recorded history, University of Queensland researchers have been part of an international collaboration, investigating Australia's historical and contemporary land-use.




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New book shows how ancient Greek writing helps us understand today's environmental crises

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Considering how many firms can meet pollutant standards can spur green tech development

(Carnegie Mellon University) A new study developed a model of regulation in which the probability of a stricter standard being enacted increased with the proportion of firms in an industry that could meet the standard. The study found that regulations that consider the proportion of firms that can meet the new standard can motivate the development of a new green technology more effectively than regulations that do not consider this factor.