ine <strong>UPDATED:</strong> Access MathSciNet and other AMS content during COVID-19 closures By www.ams.org Published On :: Thu, 19 Mar 2020 00:00:00 EST updated April 1, 2020 In response to current challenges that colleges and universities face as a result of the spread of COVID-19, the American Mathematical Society is offering libraries and institutions additional support, in line with recommendations in the ICOLC Statement on the Global COVID-19 Pandemic and Its Impact on Library Services and Resources. The AMS is also participating in the Copyright Clearance Center Education Continuity License program, providing access to our content for distance learning and other educational uses at no cost to the user. We are extending grace access for content hosted on our platforms (including MathSciNet) through the end of May for our existing customers. We will re-evaluate this timing as needed. As courses transition to online, we can provide instructors with complimentary electronic “reserve” copies of our textbooks for cases in which students do not have access to their print copies. E-books purchased through the perpetual access model on the AMS platform are always available DRM-free with unlimited simultaneous use. In addition, we are partnering with ProQuest to allow multi-user access through mid-June to all e-books purchased on their platforms. Read ProQuest’s statement. We are providing remote access to all our content, including MathSciNet. In normal circumstances, this remote access can be set up while on campus or while connected via institution VPN (in order to validate IP-based access). We realize many students, faculty, and researchers did not have an opportunity to initiate this access before leaving campus, so we have given instructions to our library partners on how patrons can connect to our content. Please contact your librarian for assistance. Libraries: if you have not received instructions to share with your patrons, please email us at cust-serv@ams.org or be in touch about any other of your library’s needs. Review all AMS Resources & Updates. Full Article
ine Nonlinear Stability of Ekman Boundary Layers in Rotating Stratified Fluids By www.ams.org Published On :: Hajime Koba, Waseda University - AMS, 2014, 127 pp., Softcover, ISBN-13: 978-0-8218-9133-9, List: US$79, All AMS Members: US$63.20, MEMO/228/1073 A stationary solution of the rotating Navier-Stokes equations with a boundary condition is called an Ekman boundary layer. This book constructs... Full Article
ine Semiclassical Standing Waves with Clustering Peaks for Nonlinear Schrodinger Equations By www.ams.org Published On :: Jaeyoung Byeon, KAIST, and Kazunaga Tanaka, Waseda University - AMS, 2013, 89 pp., Softcover, ISBN-13: 978-0-8218-9163-6, List: US$71, All AMS Members: US$56.80, MEMO/229/1076 The authors study the following singularly perturbed problem: (-epsilon^2Delta u+V(x)u = f(u)) in (mathbf{R}^N). Their main result is the... Full Article
ine Dartmouth's Katherine Mirica wins National Teacher-Scholar Honor By www.eurekalert.org Published On :: Tue, 05 May 2020 00:00:00 EDT (Dartmouth College) Annual award supports the research and teaching careers of talented young faculty in the chemical sciences. Full Article
ine Hospital discharge criteria explained By www.news.gov.hk Published On :: Thu, 07 May 2020 00:00:00 +0800 (To watch the full press briefing with sign language interpretation, click here.) The Centre for Health Protection today said recovered COVID-19 patients or those who did not have any symptoms may be discharged from hospital 10 days after the onset of symptoms or a positive test result. Its Communicable Disease Branch Head Dr Chuang Shuk-kwan told a press briefing that the revised discharge criteria was based on the latest scientific evidence. “Our Scientific Committee on Emerging & Zoonotic Diseases met yesterday and examined the latest scientific evidence on whether the virus will be viable from a patient. “And the available evidence showed that this virus is usually not detected after 10 days since the onset of symptoms of patients. Some patients may have persistent positive PCR (polymerase chain reaction) for a long period of time.” Dr Chuang noted that patients still had to meet the criteria of having two clinical specimens test negative, or testing positive for the SARS-CoV-2 antibody to be discharged. “We have revised the discharge criteria to include the patient who (must have) been staying in the hospital for at least 10 days after the onset of symptoms. So this is the additional criteria, in addition to the previous criteria of two consecutive negative specimens. “We added another criteria (which is) in case a patient has stayed in the hospital for a long time, more than 10 days since the onset of symptoms, but he or she has persistent positive PCR despite the Ct (cycle threshold) value being very high, they can check their serology, the antibody. So if the antibody turns positive, usually it is after 10 days, then he or she can be discharged. “So this is based on the latest scientific evidence.” Full Article
ine Repression of sphingosine kinase (SK)-interacting protein (SKIP) in acute myeloid leukemia diminishes SK activity and its re-expression restores SK function [Molecular Bases of Disease] By www.jbc.org Published On :: 2020-04-17T00:06:05-07:00 Previous studies have shown that sphingosine kinase interacting protein (SKIP) inhibits sphingosine kinase (SK) function in fibroblasts. SK phosphorylates sphingosine producing the potent signaling molecule sphingosine-1-phosphate (S1P). SKIP gene (SPHKAP) expression is silenced by hypermethylation of its promoter in acute myeloid leukemia (AML). However, why SKIP activity is silenced in primary AML cells is unclear. Here, we investigated the consequences of SKIP down-regulation in AML primary cells and the effects of SKIP re-expression in leukemic cell lines. Using targeted ultra-HPLC-tandem MS (UPLC-MS/MS), we measured sphingolipids (including S1P and ceramides) in AML and control cells. Primary AML cells had significantly lower SK activity and intracellular S1P concentrations than control cells, and SKIP-transfected leukemia cell lines exhibited increased SK activity. These findings show that SKIP re-expression enhances SK activity in leukemia cells. Furthermore, other bioactive sphingolipids such as ceramide were also down-regulated in primary AML cells. Of note, SKIP re-expression in leukemia cells increased ceramide levels 2-fold, inactivated the key signaling protein extracellular signal-regulated kinase, and increased apoptosis following serum deprivation or chemotherapy. These results indicate that SKIP down-regulation in AML reduces SK activity and ceramide levels, an effect that ultimately inhibits apoptosis in leukemia cells. The findings of our study contrast with previous results indicating that SKIP inhibits SK function in fibroblasts and therefore challenge the notion that SKIP always inhibits SK activity. Full Article
ine Proline-rich 11 (PRR11) drives F-actin assembly by recruiting the actin-related protein 2/3 complex in human non-small cell lung carcinoma [DNA and Chromosomes] By www.jbc.org Published On :: 2020-04-17T00:06:05-07:00 The actin cytoskeleton is extremely dynamic and supports diverse cellular functions in many physiological and pathological processes, including tumorigenesis. However, the mechanisms that regulate the actin-related protein 2/3 (ARP2/3) complex and thereby promote actin polymerization and organization in cancer cells are not well-understood. We previously implicated the proline-rich 11 (PRR11) protein in lung cancer development. In this study, using immunofluorescence staining, actin polymerization assays, and siRNA-mediated gene silencing, we uncovered that cytoplasmic PRR11 is involved in F-actin polymerization and organization. We found that dysregulation of PRR11 expression results in F-actin rearrangement and nuclear instability in non-small cell lung cancer cells. Results from molecular mechanistic experiments indicated that PRR11 associates with and recruits the ARP2/3 complex, facilitates F-actin polymerization, and thereby disrupts the F-actin cytoskeleton, leading to abnormal nuclear lamina assembly and chromatin reorganization. Inhibition of the ARP2/3 complex activity abolished irregular F-actin polymerization, lamina assembly, and chromatin reorganization due to PRR11 overexpression. Notably, experiments with truncated PRR11 variants revealed that PRR11 regulates F-actin through different regions. We found that deletion of either the N or C terminus of PRR11 abrogates its effects on F-actin polymerization and nuclear instability and that deletion of amino acid residues 100–184 or 100–200 strongly induces an F-actin structure called the actin comet tail, not observed with WT PRR11. Our findings indicate that cytoplasmic PRR11 plays an essential role in regulating F-actin assembly and nuclear stability by recruiting the ARP2/3 complex in human non-small cell lung carcinoma cells. Full Article
ine Substrate recognition and ATPase activity of the E. coli cysteine/cystine ABC transporter YecSC-FliY [Microbiology] By www.jbc.org Published On :: 2020-04-17T00:06:05-07:00 Sulfur is essential for biological processes such as amino acid biogenesis, iron–sulfur cluster formation, and redox homeostasis. To acquire sulfur-containing compounds from the environment, bacteria have evolved high-affinity uptake systems, predominant among which is the ABC transporter family. Theses membrane-embedded enzymes use the energy of ATP hydrolysis for transmembrane transport of a wide range of biomolecules against concentration gradients. Three distinct bacterial ABC import systems of sulfur-containing compounds have been identified, but the molecular details of their transport mechanism remain poorly characterized. Here we provide results from a biochemical analysis of the purified Escherichia coli YecSC-FliY cysteine/cystine import system. We found that the substrate-binding protein FliY binds l-cystine, l-cysteine, and d-cysteine with micromolar affinities. However, binding of the l- and d-enantiomers induced different conformational changes of FliY, where the l- enantiomer–substrate-binding protein complex interacted more efficiently with the YecSC transporter. YecSC had low basal ATPase activity that was moderately stimulated by apo FliY, more strongly by d-cysteine–bound FliY, and maximally by l-cysteine– or l-cystine–bound FliY. However, at high FliY concentrations, YecSC reached maximal ATPase rates independent of the presence or nature of the substrate. These results suggest that FliY exists in a conformational equilibrium between an open, unliganded form that does not bind to the YecSC transporter and closed, unliganded and closed, liganded forms that bind this transporter with variable affinities but equally stimulate its ATPase activity. These findings differ from previous observations for similar ABC transporters, highlighting the extent of mechanistic diversity in this large protein family. Full Article
ine Dopamine transporter trafficking and Rit2 GTPase: Mechanism of action and in vivo impact [Neurobiology] By www.jbc.org Published On :: 2020-04-17T00:06:05-07:00 Following its evoked release, dopamine (DA) signaling is rapidly terminated by presynaptic reuptake, mediated by the cocaine-sensitive DA transporter (DAT). DAT surface availability is dynamically regulated by endocytic trafficking, and direct protein kinase C (PKC) activation acutely diminishes DAT surface expression by accelerating DAT internalization. Previous cell line studies demonstrated that PKC-stimulated DAT endocytosis requires both Ack1 inactivation, which releases a DAT-specific endocytic brake, and the neuronal GTPase, Rit2, which binds DAT. However, it is unknown whether Rit2 is required for PKC-stimulated DAT endocytosis in DAergic terminals or whether there are region- and/or sex-dependent differences in PKC-stimulated DAT trafficking. Moreover, the mechanisms by which Rit2 controls PKC-stimulated DAT endocytosis are unknown. Here, we directly examined these important questions. Ex vivo studies revealed that PKC activation acutely decreased DAT surface expression selectively in ventral, but not dorsal, striatum. AAV-mediated, conditional Rit2 knockdown in DAergic neurons impacted baseline DAT surface:intracellular distribution in DAergic terminals from female ventral, but not dorsal, striatum. Further, Rit2 was required for PKC-stimulated DAT internalization in both male and female ventral striatum. FRET and surface pulldown studies in cell lines revealed that PKC activation drives DAT-Rit2 surface dissociation and that the DAT N terminus is required for both PKC-mediated DAT-Rit2 dissociation and DAT internalization. Finally, we found that Rit2 and Ack1 independently converge on DAT to facilitate PKC-stimulated DAT endocytosis. Together, our data provide greater insight into mechanisms that mediate PKC-regulated DAT internalization and reveal unexpected region-specific differences in PKC-stimulated DAT trafficking in bona fide DAergic terminals. Full Article
ine Structural and mutational analyses of the bifunctional arginine dihydrolase and ornithine cyclodeaminase AgrE from the cyanobacterium Anabaena [Enzymology] By www.jbc.org Published On :: 2020-04-24T06:08:45-07:00 In cyanobacteria, metabolic pathways that use the nitrogen-rich amino acid arginine play a pivotal role in nitrogen storage and mobilization. The N-terminal domains of two recently identified bacterial enzymes: ArgZ from Synechocystis and AgrE from Anabaena, have been found to contain an arginine dihydrolase. This enzyme provides catabolic activity that converts arginine to ornithine, resulting in concomitant release of CO2 and ammonia. In Synechocystis, the ArgZ-mediated ornithine–ammonia cycle plays a central role in nitrogen storage and remobilization. The C-terminal domain of AgrE contains an ornithine cyclodeaminase responsible for the formation of proline from ornithine and ammonia production, indicating that AgrE is a bifunctional enzyme catalyzing two sequential reactions in arginine catabolism. Here, the crystal structures of AgrE in three different ligation states revealed that it has a tetrameric conformation, possesses a binding site for the arginine dihydrolase substrate l-arginine and product l-ornithine, and contains a binding site for the coenzyme NAD(H) required for ornithine cyclodeaminase activity. Structure–function analyses indicated that the structure and catalytic mechanism of arginine dihydrolase in AgrE are highly homologous with those of a known bacterial arginine hydrolase. We found that in addition to other active-site residues, Asn-71 is essential for AgrE's dihydrolase activity. Further analysis suggested the presence of a passage for substrate channeling between the two distinct AgrE active sites, which are situated ∼45 Å apart. These results provide structural and functional insights into the bifunctional arginine dihydrolase–ornithine cyclodeaminase enzyme AgrE required for arginine catabolism in Anabaena. Full Article
ine Noncatalytic Bruton's tyrosine kinase activates PLC{gamma}2 variants mediating ibrutinib resistance in human chronic lymphocytic leukemia cells [Membrane Biology] By www.jbc.org Published On :: 2020-04-24T06:08:45-07:00 Treatment of patients with chronic lymphocytic leukemia (CLL) with inhibitors of Bruton's tyrosine kinase (BTK), such as ibrutinib, is limited by primary or secondary resistance to this drug. Examinations of CLL patients with late relapses while on ibrutinib, which inhibits BTK's catalytic activity, revealed several mutations in BTK, most frequently resulting in the C481S substitution, and disclosed many mutations in PLCG2, encoding phospholipase C-γ2 (PLCγ2). The PLCγ2 variants typically do not exhibit constitutive activity in cell-free systems, leading to the suggestion that in intact cells they are hypersensitive to Rac family small GTPases or to the upstream kinases spleen-associated tyrosine kinase (SYK) and Lck/Yes-related novel tyrosine kinase (LYN). The sensitivity of the PLCγ2 variants to BTK itself has remained unknown. Here, using genetically-modified DT40 B lymphocytes, along with various biochemical assays, including analysis of PLCγ2-mediated inositol phosphate formation, inositol phospholipid assessments, fluorescence recovery after photobleaching (FRAP) static laser microscopy, and determination of intracellular calcium ([Ca2+]i), we show that various CLL-specific PLCγ2 variants such as PLCγ2S707Y are hyper-responsive to activated BTK, even in the absence of BTK's catalytic activity and independently of enhanced PLCγ2 phospholipid substrate supply. At high levels of B-cell receptor (BCR) activation, which may occur in individual CLL patients, catalytically-inactive BTK restored the ability of the BCR to mediate increases in [Ca2+]i. Because catalytically-inactive BTK is insensitive to active-site BTK inhibitors, the mechanism involving the noncatalytic BTK uncovered here may contribute to preexisting reduced sensitivity or even primary resistance of CLL to these drugs. Full Article
ine Detailed analyses of the crucial functions of Zn transporter proteins in alkaline phosphatase activation [Enzymology] By www.jbc.org Published On :: 2020-04-24T06:08:45-07:00 Numerous zinc ectoenzymes are metalated by zinc and activated in the compartments of the early secretory pathway before reaching their destination. Zn transporter (ZNT) proteins located in these compartments are essential for ectoenzyme activation. We have previously reported that ZNT proteins, specifically ZNT5–ZNT6 heterodimers and ZNT7 homodimers, play critical roles in the activation of zinc ectoenzymes, such as alkaline phosphatases (ALPs), by mobilizing cytosolic zinc into these compartments. However, this process remains incompletely understood. Here, using genetically-engineered chicken DT40 cells, we first determined that Zrt/Irt-like protein (ZIP) transporters that are localized to the compartments of the early secretory pathway play only a minor role in the ALP activation process. These transporters included ZIP7, ZIP9, and ZIP13, performing pivotal functions in maintaining cellular homeostasis by effluxing zinc out of the compartments. Next, using purified ALP proteins, we showed that zinc metalation on ALP produced in DT40 cells lacking ZNT5–ZNT6 heterodimers and ZNT7 homodimers is impaired. Finally, by genetically disrupting both ZNT5 and ZNT7 in human HAP1 cells, we directly demonstrated that the tissue-nonspecific ALP-activating functions of both ZNT complexes are conserved in human cells. Furthermore, using mutant HAP1 cells, we uncovered a previously-unrecognized and unique spatial regulation of ZNT5–ZNT6 heterodimer formation, wherein ZNT5 recruits ZNT6 to the Golgi apparatus to form the heterodimeric complex. These findings fill in major gaps in our understanding of the molecular mechanisms underlying zinc ectoenzyme activation in the compartments of the early secretory pathway. Full Article
ine 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] By www.jbc.org Published On :: 2020-05-01T00:06:09-07:00 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... Full Article
ine The Escherichia coli cellulose synthase subunit G (BcsG) is a Zn2+-dependent phosphoethanolamine transferase [Glycobiology and Extracellular Matrices] By www.jbc.org Published On :: 2020-05-01T00:06:09-07:00 Bacterial biofilms are cellular communities that produce an adherent matrix. Exopolysaccharides are key structural components of this matrix and are required for the assembly and architecture of biofilms produced by a wide variety of microorganisms. The human bacterial pathogens Escherichia coli and Salmonella enterica produce a biofilm matrix composed primarily of the exopolysaccharide phosphoethanolamine (pEtN) cellulose. Once thought to be composed of only underivatized cellulose, the pEtN modification present in these matrices has been implicated in the overall architecture and integrity of the biofilm. However, an understanding of the mechanism underlying pEtN derivatization of the cellulose exopolysaccharide remains elusive. The bacterial cellulose synthase subunit G (BcsG) is a predicted inner membrane–localized metalloenzyme that has been proposed to catalyze the transfer of the pEtN group from membrane phospholipids to cellulose. Here we present evidence that the C-terminal domain of BcsG from E. coli (EcBcsGΔN) functions as a phosphoethanolamine transferase in vitro with substrate preference for cellulosic materials. Structural characterization of EcBcsGΔN revealed that it belongs to the alkaline phosphatase superfamily, contains a Zn2+ ion at its active center, and is structurally similar to characterized enzymes that confer colistin resistance in Gram-negative bacteria. Informed by our structural studies, we present a functional complementation experiment in E. coli AR3110, indicating that the activity of the BcsG C-terminal domain is essential for integrity of the pellicular biofilm. Furthermore, our results established a similar but distinct active-site architecture and catalytic mechanism shared between BcsG and the colistin resistance enzymes. Full Article
ine Mechanistic insights explain the transforming potential of the T507K substitution in the protein-tyrosine phosphatase SHP2 [Signal Transduction] By www.jbc.org Published On :: 2020-05-01T00:06:09-07:00 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. Full Article
ine Delineating an extracellular redox-sensitive module in T-type Ca2+ channels [Membrane Biology] By www.jbc.org Published On :: 2020-05-01T00:06:09-07:00 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. Full Article
ine Impact of 1,N6-ethenoadenosine, a damaged ribonucleotide in DNA, on translesion synthesis and repair [Enzymology] By www.jbc.org Published On :: 2020-05-01T00:06:09-07:00 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. Full Article
ine 5-Ethynyl-2'-deoxycytidine and 5-ethynyl-2'-deoxyuridine are differentially incorporated in cells infected with HSV-1, HCMV, and KSHV viruses [Microbiology] By www.jbc.org Published On :: 2020-05-01T00:06:09-07:00 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. Full Article
ine Profiles of kindergartens posted online By www.info.gov.hk Published On :: Wed, 09 Oct 2019 15:09:58 Full Article
ine Application deadline extended for First School Allocation Exercise 2020 for allocation of five new estate kindergarten premises By www.info.gov.hk Published On :: Thu, 30 Jan 2020 17:58:19 Full Article
ine LSU Health study suggests nicotine exposure alone leads to pulmonary hypertension By www.eurekalert.org Published On :: Fri, 01 May 2020 00:00:00 EDT (Louisiana State University Health Sciences Center) A study conducted at LSU Health New Orleans has shown for the first time that chronic exposure to inhaled nicotine alone increases blood pressure in both the body's general circulation and in the lungs that can lead to pulmonary hypertension. The study also found that nicotine-induced pulmonary hypertension is accompanied by changes in the size, shape and function (remodeling) of the blood vessels in the lung and the right lower chamber of the heart. Full Article
ine Could a polio vaccine stop the coronavirus pandemic? (video) By www.eurekalert.org Published On :: Mon, 04 May 2020 00:00:00 EDT (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. Full Article
ine New guidelines for treating the sickest COVID-19 patients By www.eurekalert.org Published On :: Mon, 04 May 2020 00:00:00 EDT (University of Houston) A new set of recommendations for health care workers on the front lines, to help them make decisions on how to treat the most critical COVID-19 patients, those with severe lung or heart failure, has been published. Full Article
ine 'Terrible twos' not inevitable: With engaged parenting, happy babies can become happy toddlers By www.eurekalert.org Published On :: Wed, 06 May 2020 00:00:00 EDT (University of Cambridge) Parents should not feel pressured to make their young children undertake structured learning or achieve specific tasks, particularly during lockdown. A new study of children under the age of two has found that parents who take a more flexible approach to their child's learning can - for children who were easy babies - minimise behavioural problems during toddlerhood. Full Article
ine Children don't know how to get proper nutrition information online By www.eurekalert.org Published On :: Wed, 06 May 2020 00:00:00 EDT (Elsevier) Children looking for health information online could end up more prone to obesity. A new study in the Journal of Nutrition Education and Behavior, published by Elsevier, shows a lack of digital health literacy can lead children to misinterpret portions, adopt recommendations intended for adults, or take guidance from noncredible sources. Full Article
ine COVID-19 dog case explained By www.news.gov.hk Published On :: Wed, 04 Mar 2020 00:00:00 +0800 A pet dog repeatedly tested weak positive for the COVID-19 virus, indicating a low-level of infection with the virus, the Agriculture, Fisheries & Conservation Department said today. The department first collected test samples from the dog on February 26. It detected low levels of COVID-19 virus from its nasal and oral cavity samples on February 27. The dog also tested weak positive for the virus when the department repeated the test on February 28 and March 2. Experts from Hong Kong University’s School of Public Health, City University’s College of Veterinary Medicine & Life Sciences and the World Organisation for Animal Health have been consulted, and unanimously agreed that these results suggest that the dog has a low-level of infection and it is likely to be a case of human-to-animal transmission, the department noted. The dog has not shown any signs of disease related to COVID-19. It is currently under quarantine at the animal keeping facility at the Hong Kong Port of Hong Kong-Zhuhai-Macao Bridge. The department will closely monitor the dog and repeat the test later. To ensure public and animal health, the department strongly advises that mammalian pets from households with COVID-19 infected people, or close contacts of infected individuals, should be put under quarantine in the department’s facilities. The department emphasised that there is currently no evidence that pets can be a source of infection of COVID-19 and under no circumstances should people abandon their pets. Full Article
ine Shoreline clean-up conducted By www.news.gov.hk Published On :: Mon, 27 Apr 2020 00:00:00 +0800 Various government departments, together with volunteers today conducted a shoreline clean-up along the remote rocky beach in Kung Pui Wan, Tap Mun to remove two tonnes of refuse. The Environmental Protection Department, the Food & Environmental Hygiene Department (FEHD) and the Marine Department participated in the operation. The Inter-departmental Working Group on Marine Environmental Management said the beach, facing the windy and wavy sea, is not easily accessible by working vessels and the rough terrain connecting the rocky beach also increases the difficulty of routine cleaning work. FEHD cleaners along with the volunteers packed the refuse and delivered it on foot to a nearby pier for temporary storage. FEHD staff then took the refuse to the Marine Department's collection vessel in batches for onward delivery to a rubbish collection point for centralised handling. To minimise the risk of spreading COVID-19, the operation was carried out in groups of no more than four participants each. They maintained an appropriate distance from each other and paid heed to personal protection, including wearing masks. The working group thanked the volunteers for taking part and called on the public to keep the countryside and shoreline clean during outings. For information on clean shorelines, visit the Clean Shorelines facebook and Instagram pages. Full Article
ine About the cover: The Fine–Petrović Polygons and the Newton–Puiseux Method for Algebraic Ordinary Differential Equations By www.ams.org Published On :: Fri, 13 Mar 2020 16:19 EDT Vladimir Dragović and Irina Goryuchkina Bull. Amer. Math. Soc. 57 (2020), 293-299. Abstract, references and article information Full Article
ine Balancing Act: Consumers Are Willing to Sacrifice Privacy to See Fewer Digital Ads, According to New Columbia Business School Research By www8.gsb.columbia.edu Published On :: Mon, 17 Feb 2020 18:01:28 +0000 Business Economics and Public Policy Marketing Media and Technology Tuesday, February 4, 2020 - 12:45 NEW YORK – In the era of online surveillance, consumers continually express concerns about how their digital footprint is being tracked and their privacy compromised. Full Article
ine Researchers Answer a Diversity Puzzle: Why Chinese Americans but not Indian Americans are Underrepresented in Leadership Positions By www8.gsb.columbia.edu Published On :: Thu, 20 Feb 2020 16:26:43 +0000 Leadership Thursday, February 20, 2020 - 11:15 New studies identify the boundary and causes of the “Bamboo Ceiling” Full Article
ine Same Old Tune: Columbia Business School Research Shows Bias Against Women in the Music Industry By www8.gsb.columbia.edu Published On :: Fri, 28 Feb 2020 21:54:41 +0000 Leadership Operations Thursday, February 27, 2020 - 16:45 NEW YORK – In 2018, the Grammy Awards faced criticism when male artists swept the most prestigious music awards – prompting Recording Academy president Neil Portnow to say the solution is for women to “step up.” But the truth is women artists have been stepping up for decades, according to research from Columbia Business School’s Professor of Business Michael Mauskapf and Associate Professor of Organizational Behavior Noah Askin. Full Article
ine Research from Columbia Business School Suggests Hypersensitivity to Coronavirus News Is Driving Market Reactions – and Vice Versa By www8.gsb.columbia.edu Published On :: Fri, 03 Apr 2020 02:46:58 +0000 Business Economics and Public Policy Capital Markets and Investments Healthcare Media and Technology 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. Full Article
ine New Research from Columbia Business School Shows Radical Changes in Household Spending Habits During COVID-19 Epidemic By www8.gsb.columbia.edu Published On :: Tue, 28 Apr 2020 18:37:51 +0000 Business Economics and Public Policy Operations Risk Management Tuesday, April 28, 2020 - 14:30 Study provides first real-time view into household consumption during outbreak in U.S., showing an initial sharp increase in key categories, followed by a sharp decrease in overall spending Full Article
ine Lockdown Losses: Lack of Government Transparency during COVID-19 Pandemic Holds Back Businesses from Taking Risks, Making Financial Decisions By www8.gsb.columbia.edu Published On :: Wed, 29 Apr 2020 18:19:09 +0000 Business Economics and Public Policy Operations Risk Management Strategy Thursday, April 30, 2020 - 14:15 NEW YORK – Since the coronavirus outbreak began, states across the U.S. have implemented stay-at-home orders, disrupting businesses and causing many to shut down. In addition, almost half of U.S. states from New York to Oregon have extended their lockdown orders beyond the original end date. These extensions of lockdown policy, while clearly beneficial to address public health concerns, can damage the economy beyond their immediate impact on business closures and layoffs. Full Article
ine New Research: Entrepreneurship, New Business Creation are Critical to COVID-19 Economic Recovery By www8.gsb.columbia.edu Published On :: Tue, 05 May 2020 13:02:07 +0000 Business Economics and Public Policy Entrepreneurship Tuesday, May 5, 2020 - 09:00 Working Paper from Columbia Business School Emphasizes the Need to Accelerate New Businesses, Not Just Protect Existing Ones, to Restore the U.S. Economy Full Article
ine Germline genomic profiles of children, young adults with solid tumors to inform managementand treatment By www.eurekalert.org Published On :: Tue, 05 May 2020 00:00:00 EDT (Cleveland Clinic) A new Cleveland Clinic study demonstrates the importance of genetics evaluation and genetic testing for children, adolescents and young adults with solid tumor cancers. The study was published today in Nature Communications. Full Article
ine Online Video Course, Public Course, Weather Observation By www.hko.gov.hk Published On :: The "Online Video Course on Weather Observation" will explain concisely the basic weather observation methods and techniques, such... Full Article I
ine Civil engineering Professor Sharon Di wins NSF CAREER Award By www.eurekalert.org Published On :: Thu, 30 Apr 2020 00:00:00 EDT (Columbia University School of Engineering and Applied Science) Sharon Di, assistant professor of civil engineering and engineering mechanics, has won a National Science Foundation CAREER Award for her work in the nascent field of autonomous vehicles and shared mobility transportation, areas rapidly being transformed by emerging communications and sensing technologies. Full Article
ine Hidden symmetry found in chemical kinetic equations By www.eurekalert.org Published On :: Fri, 01 May 2020 00:00:00 EDT (Rice University) Rice University researchers have discovered a hidden symmetry in the chemical kinetic equations scientists have long used to model and study many of the chemical processes essential for life. Full Article
ine AI tool speeds up search for COVID-19 treatments and vaccines By www.eurekalert.org Published On :: Mon, 04 May 2020 00:00:00 EDT (Northwestern University) Northwestern University researchers are using artificial intelligence (AI) to speed up the search for COVID-19 treatments and vaccines. The AI-powered tool makes it possible to prioritize resources for the most promising studies -- and ignore research that is unlikely to yield benefits. Full Article
ine UBC researchers establish new timeline for ancient magnetic field on Mars By www.eurekalert.org Published On :: Fri, 01 May 2020 00:00:00 EDT (University of British Columbia) Mars had a global magnetic field much earlier -- and much later -- than previously known. Analysis of new satellite data found clear evidence of a magnetic field coming from a lava flow that formed less than 3.7 billion years ago, half a billion years after many people thought the Martian dynamo had ceased. The researchers also detected low-intensity magnetic fields over the Borealis Basin, believed to be one of the oldest features on Mars. Full Article
ine New study examines which galaxies are best for intelligent life By www.eurekalert.org Published On :: Fri, 01 May 2020 00:00:00 EDT (University of Arkansas) Giant elliptical galaxies are not as likely as disk-shaped galaxies, such as our own Milky Way, to be cradles of technological civilizations, according to a recent paper by a University of Arkansas astrophysicist. Full Article
ine Evidence of Late Pleistocene human colonization of isolated islands beyond Wallace's Line By www.eurekalert.org Published On :: Wed, 29 Apr 2020 00:00:00 EDT (Max Planck Institute for the Science of Human History) What makes our species unique compared to other hominins? High profile genetic, fossil and material culture discoveries present scientists working in the Late Pleistocene with an ever-more complex picture of interactions between early hominin populations. One distinctive characteristic of Homo sapiens, however, appears to be its global distribution. Exploring how Homo sapiens colonized most of the world's continents in a relatively short period could reveal the exceptional capacities of humans relative to other hominins. Full Article
ine New freeze-resistant trichinella species discovered in wolverines By www.eurekalert.org Published On :: Wed, 06 May 2020 00:00:00 EDT (US Department of Agriculture - Agricultural Research Service) A new freeze-resistant Trichinella species has been discovered in wolverines by Agricultural Research Service scientists and their colleagues. Trichinella are parasites that cause the disease trichinosis (formally referred to as trichinellosis), which people can get by eating raw or undercooked meat from infected animals. Full Article
ine Mats made from nanofibers linked to a red wine chemical could help prevent oxidation By www.eurekalert.org Published On :: Wed, 06 May 2020 00:00:00 EDT (Texas A&M University) Spoiling foods, souring wine and worsening wounds have a common culprit -- a process called oxidation. Although the ill effects of these chemical reactions can be curtailed by antioxidants, creating a sturdy platform capable of providing prolonged antioxidant activity is an ongoing challenge. Full Article
ine NIST helps expand genome sequencing of marine mammals By www.eurekalert.org Published On :: Thu, 07 May 2020 00:00:00 EDT (National Institute of Standards and Technology (NIST)) Researchers will soon have access to the full genomic sequences for 23 marine mammal species preserved by the National Institute of Standards and Technology (NIST), thanks to an ongoing collaboration between NIST and a scientific consortium called the DNA Zoo. Full Article
ine Using AI to map marine environments By www.eurekalert.org Published On :: Wed, 06 May 2020 00:00:00 EDT (University of Bath) Researchers at the University of Bath have developed an AI model that can automatically classify underwater environments directly from sonar measurements. Full Article
ine Ukraine must drain corruption swamp, Saakashvili says in latest comeback By news.yahoo.com Published On :: Fri, 08 May 2020 12:41:07 -0400 Mikheil Saakashvili, the former president of Georgia, vowed on Friday to help his new boss, Ukrainian President Volodymyr Zelenskiy, clean out a political "swamp" of oligarchs' interests that he said were preventing Ukraine prospering. Twice president of Georgia, Saakashvili had a brief but stormy spell in Ukrainian politics five years ago under Zelenskiy's predecessor Petro Poroshenko in which he once clambered onto a roof to avoid law enforcement. Full Article
ine Frontier Airlines becomes first U.S. airline to announce passenger temperature checks By news.yahoo.com Published On :: Thu, 07 May 2020 18:36:43 -0400 The budget carrier will begin conducting temperature checks via touchless thermometers on June 1. Passengers have to start wearing masks Friday. Full Article
ine Navy nominee: Service is in rough waters, cites leadership By news.yahoo.com Published On :: Thu, 07 May 2020 13:40:04 -0400 The U.S. Navy is in “rough waters” and suffering from leadership failures, the diplomat tapped to be the next Navy secretary told a Senate committee Thursday. Kenneth J. Braithwaite, the ambassador to Norway and a retired Navy rear admiral, faced repeated questions about recent crises that have rocked the service, including the firing of an aircraft carrier captain who urged faster action to fight a coronavirus outbreak on his ship and the subsequent resignation of the acting secretary who fired him. Braithwaite said that Navy culture has been tarnished and trust in the service's leaders has broken down. Full Article