at Classification and Identification of Lie Algebras By www.ams.org Published On :: Libor Snobl, Czech Technical University, and Pavel Winternitz, Centre de Recherches Mathematiques, and Universite de Montreal - AMS | CRM, 2014, 306 pp., Hardcover, ISBN-13: 978-0-8218-4355-0, List: US$124, All AMS Members: US$99.20, CRMM/33 The purpose of this book is to serve as a tool for researchers and practitioners who apply Lie algebras and Lie groups to solve problems arising in... Full Article
at Ring Theory and Its Applications By www.ams.org Published On :: Dinh Van Huynh, S. K. Jain, and Sergio R. Lopez-Permouth, Ohio University, and S. Tariq Rizvi and Cosmin S. Roman, Ohio State University, Editors - AMS, 2014, 311 pp., Softcover, ISBN-13: 978-0-8218-8797-4, List: US$113, All AMS Members: US$90.40, CONM/609 This volume contains the proceedings of the Ring Theory Session in honor of T. Y. Lam's 70th birthday, at the 31st Ohio State-Denison Mathematics... Full Article
at Perspectives in Representation Theory By www.ams.org Published On :: Pavel Etingof, Massachusetts Institute of Technology, Mikhail Khovanov, Columbia University, and Alistair Savage, University of Ottawa, Editors - AMS, 2014, 370 pp., Softcover, ISBN-13: 978-0-8218-9170-4, List: US$126, All AMS Members: US$100.80, CONM/610 This volume contains the proceedings of the conference Perspectives in Representation Theory, held from May 12-17, 2012, at Yale University, in honor... Full Article
at Harmonic Analysis and Partial Differential Equations By www.ams.org Published On :: Patricio Cifuentes and Jose Garcia-Cuerva, Universidad Autonoma de Madrid, Gustavo Garrigos, Universidad de Murcia, Eugenio Hernandez, Universidad Autonoma de Madrid, Jose Maria Martell, Javier Parcet, and Keith M. Rogers, Consejo Superior de Investigaciones Cientificas, and Alberto Ruiz, Fernando Soria, and Ana Vargas, Universidad Autonoma de Madrid, Editors - AMS, 2014, 178 pp., Softcover, ISBN-13: 978-0-8218-9433-0, List: US$78, All AMS Members: US$62.40, CONM/612 This volume contains the Proceedings of the 9th International Conference on Harmonic Analysis and Partial Differential Equations, held June 11-15,... Full Article
at Near Soliton Evolution for Equivariant Schrodinger Maps in Two Spatial Dimensions By www.ams.org Published On :: Ioan Bejenaru, University of California, San Diego, and Daniel Tataru, University of California, Berkeley - AMS, 2014, 108 pp., Softcover, ISBN-13: 978-0-8218-9215-2, List: US$76, All AMS Members: US$60.80, MEMO/228/1069 The authors consider the Schrödinger Map equation in (2+1) dimensions, with values into (mathbb{S}^2). This admits a lowest energy steady... Full Article
at Large Deviations for Additive Functionals of Markov Chains By www.ams.org Published On :: Alejandro D. de Acosta and Peter Ney - AMS, 2014, 108 pp., Softcover, ISBN-13: 978-0-8218-9089-9, List: US$76, All AMS Members: US$60.80, MEMO/228/1070 For a Markov chain ({X_j}) with general state space (S) and ({f:S ightarrowmathbf{R}^d}), the large deviation principle for... Full Article
at Relative Equilibria in the 3-Dimensional Curved (n)-Body Problem By www.ams.org Published On :: Florin Diacu, University of Victoria - AMS, 2014, 80 pp., Softcover, ISBN-13: 978-0-8218-9136-0, List: US$71, All AMS Members: US$56.80, MEMO/228/1071 The author considers the (3)-dimensional gravitational (n)-body problem, (nge 2), in spaces of constant Gaussian curvature (kappa e 0), i.e.... Full Article
at Spectra of Symmetrized Shuffling Operators By www.ams.org Published On :: Victor Reiner, University of Minnesota, Franco Saliola, Universite du Quebec a Montreal, and Volkmar Welker, Philipps-Universitaet Marburg - AMS, 2014, 109 pp., Softcover, ISBN-13: 978-0-8218-9095-0, List: US$76, All AMS Members: US$60.80, MEMO/228/1072 For a finite real reflection group (W) and a (W)-orbit (mathcal{O}) of flats in its reflection arrangement--or equivalently a conjugacy class of... Full Article
at 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
at Classical Mechanics with Calculus of Variations and Optimal Control: An Intuitive Introduction By www.ams.org Published On :: Mark Levi, Pennsylvania State University - AMS, 2014, 299 pp., Softcover, ISBN-13: 978-0-8218-9138-4, List: US$42, All AMS Members: US$33.60, STML/69 It is hard to imagine a more original and insightful approach to classical mechanics. Most physicists would regard this as a well-worn and settled... Full Article
at Group Theory, Combinatorics, and Computing By www.ams.org Published On :: Robert Fitzgerald Morse, University of Evansville, Daniela Nikolova-Popova, Florida Atlantic University, and Sarah Witherspoon, Texas A & M University, Editors - AMS, 2014, 187 pp., Softcover, ISBN-13: 978-0-8218-9435-4, List: US$78, All AMS Members: US$62.40, CONM/611 This volume contains the proceedings of the International Conference on Group Theory, Combinatorics and Computing held from October 3-8, 2012, in Boca... Full Article
at Pearls from a Lost City: The Lvov School of Mathematics By www.ams.org Published On :: Roman Duda, University of Wroclaw - Translated by Daniel Davies - AMS, 2014, approx. 216 pp., Hardcover, ISBN-13: 978-1-4704-1076-6, List: US$39, All AMS Members: US$31.20, HMATH/40 The fame of the Polish school at Lvov rests with the diverse and fundamental contributions of Polish mathematicians working there during the interwar... Full Article
at Global and Local Regularity of Fourier Integral Operators on Weighted and Unweighted Spaces By www.ams.org Published On :: David Dos Santos Ferreira, Universite Paris 13, and Wolfgang Staubach, Uppsala University - AMS, 2013, 65 pp., Softcover, ISBN-13: 978-0-8218-9119-3, List: US$63, All AMS Members: US$50.40, MEMO/229/1074 The authors investigate the global continuity on (L^p) spaces with (pin [1,infty]) of Fourier integral operators with smooth and rough amplitudes... Full Article
at Operator-Valued Measures, Dilations, and the Theory of Frames By www.ams.org Published On :: Deguang Han, University of Central Florida, David R. Larson, Texas A&M University, Bei Liu, Tianjin University of Technology, and Rui Liu, Nankai University - AMS, 2013, 84 pp., Softcover, ISBN-13: 978-0-8218-9172-8, List: US$65, All AMS Members: US$52, MEMO/229/1075 The authors develop elements of a general dilation theory for operator-valued measures. Hilbert space operator-valued measures are closely related to... Full Article
at 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
at HKSAR Air Quality Health Index at : Sun, 10 May 2020 01:30:00 +0800 Current Condition : By www.aqhi.gov.hk Published On :: General Stations: 1 to 2 (Health Risk: Low)Roadside Stations: 2 (Health Risk: Low) Full Article
at Water-splitting module a source of perpetual energy By www.eurekalert.org Published On :: Mon, 04 May 2020 00:00:00 EDT (Rice University) Rice University researchers have integrated high-efficiency solar cells and electrode catalysts into an efficient, low-cost device that splits water to produce hydrogen fuel. Full Article
at Brazilian and Indian scientists produce crystal with many potential applications By www.eurekalert.org Published On :: Mon, 04 May 2020 00:00:00 EDT (Fundação de Amparo à Pesquisa do Estado de São Paulo) Thanks to its magnetic properties, the material -- zinc-doped manganese chromite -- can be used in a range of products, from gas sensors to data storage devices. Full Article
at 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
at Filtering out toxic chromium from water By www.eurekalert.org Published On :: Wed, 06 May 2020 00:00:00 EDT (Ecole Polytechnique Fédérale de Lausanne) EPFL chemists have developed sponges to capture various target substances, like gold, mercury and lead, dissolved in solution. The sponges are actually porous crystals called metal organic frameworks, and now one exists for capturing toxic hexavalent chromium from water. Full Article
at Real-time visualization of solid-phase ion migration By www.eurekalert.org Published On :: Wed, 06 May 2020 00:00:00 EDT (University of Science and Technology of China) Researchers from University of science and technology of China has shed new lights on the topic of solid-phase ion migration. Researchers demonstrated a unique in-situ strategy for visualizing the dynamic solid-phase ion migration between nanostructures with nanogap at the atomic scale. The research article entitled "Real-Time Visualization of Solid-Phase Ion Migration Kinetics on Nanowire Monolayer" was published in Journal of the American Chemical Society on April 29th. Full Article
at Research found a new way to make functional materials based on polymers of metal clusters By www.eurekalert.org Published On :: Wed, 06 May 2020 00:00:00 EDT (University of Jyväskylä - Jyväskylän yliopisto) Researchers at the universities of Jyvaskyla and Xiamen discovered a novel way to make functional macroscopic crystalline materials out of nanometer-size 34-atom silver-gold intermetallic clusters. The cluster material has a highly anisotropic electrical conductivity, being a semiconductor in one direction and an electrical insulator in other directions. The research was published in Nature Communications on May 6, 2020. Full Article
at Surfaces that grip like gecko feet could be easily mass-produced By www.eurekalert.org Published On :: Wed, 06 May 2020 00:00:00 EDT (Georgia Institute of Technology) The science behind sticky gecko's feet lets gecko adhesion materials pick up about anything. But cost-effective mass production of the materials was out of reach until now. A new method of making them could usher the spread of gecko-inspired grabbers to assembly lines and homes. Full Article
at New simple method for measuring the state of lithium-ion batteries By www.eurekalert.org Published On :: Thu, 07 May 2020 00:00:00 EDT (Johannes Gutenberg Universitaet Mainz) Scientists at Johannes Gutenberg University Mainz (JGU) and the Helmholtz Institute Mainz (HIM) in Germany have presented a non-contact method for detecting the state of charge and any defects in lithium-ion batteries. Full Article
at CE explains relaxation of measures By www.news.gov.hk Published On :: Tue, 05 May 2020 00:00:00 +0800 (To watch the full press conference with sign language interpretation, click here.) The relaxation of anti-epidemic measures is a step in the right direction, Chief Executive Carrie Lam said today. Mrs Lam made the statement at a press conference this afternoon. She said the Government will relax the requirement limiting group gatherings in public places to a maximum of four people. Starting from Friday, up to eight people can gather in public places. "So raising the number from four to eight for the catering business and also for the prohibition against group gatherings under Cap 599G is not an exact science, but this is a step in the right direction of relaxation. "Maybe in another 14 days’ time we will raise the number of eight to 10, to 12, to 15 and so on." Regarding bars and pubs, Mrs Lam said these venues will be able to reopen but the Government will put in place requirements to prevent physical interactions. "We have decided that perhaps to strike a pragmatic balance is to allow them to reopen for business but to put in far more stringent requirements." Such requirements include no live music, band performances or dancing in bar premises. "That would be another way to keep the social distance and prevent as much as possible physical interactions." Click here for the latest measures. Full Article
at Class resumption date set By www.news.gov.hk Published On :: Tue, 05 May 2020 00:00:00 +0800 (To watch the full press conference with sign language interpretation, click here.) Secretary for Education Kevin Yeung today said the Government is confident that classes can resume on May 27. Mr Yeung made the statement at a press conference this afternoon. He said: “We are not announcing class resumption right away. We are giving advance notice of about three weeks for all the stakeholders to get prepared for the school resumption.” The Government will continue to monitor the situation during this period and adjust the school resumption plan if necessary, he added. "At this stage we are still pretty confident that we should be able to resume classes on May 27." Full Article
at Gov't calls for rational discussion By www.news.gov.hk Published On :: Wed, 06 May 2020 00:00:00 +0800 The Government urged District Councillors to focus on livelihood issues and discuss matters rationally, adding that it will continue to co-operate with the District Council under the principles of mutual respect, observation of order and rational discussion. The Government issued the statement after a number of Central & Western District Council members today entered the office area of the Central & Western District Office without consent. The statement noted that the members shouted loudly and knocked on the door of the office. Despite repeated responses and an appeal from the District Office staff, the members still refused to leave. The statement added that the members stayed in the District Office for a long time, seriously affecting its operation. The Government expressed regret over their acts. Full Article
at COVID-19 patient tests positive again 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.) A recovered COVID-19 patient has tested positive for the virus again, the Hospital Authority announced today. The authority’s Chief Manager (Quality & Standards) Dr Lau Ka-hin told a media briefing this afternoon that the patient was first admitted to Queen Mary Hospital on March 24 after having fever for a week. He subsequently tested positive for COVID-19. He was discharged on April 16 after two consecutive negative tests for the virus. Dr Lau said: "The patient presented to the Accident & Emergency Department of Queen Mary Hospital on May 5 because of some abdominal pain and diarrhoea. "He was admitted to our hospital and was found to have a positive result for COVID-19 in the throat saliva, but the cycle threshold value is very high - nearly 36. "The experts consider that this is the residual virus left in the patient’s body, which is not infective, and it is not likely to be a reinfection at this moment." He added that the patient is in a stable condition. Full Article
at Caspar Tsui visits sports association By www.news.gov.hk Published On :: Fri, 08 May 2020 00:00:00 +0800 Secretary for Home Affairs Caspar Tsui visited the Physical Fitness Association of Hong Kong, China today to inspect its work in implementing the Fitness Centre Subsidy Scheme launched under the second phase of the Anti-epidemic Fund. Mr Tsui said the scheme aims to provide a one-off subsidy of $100,000 to fitness centres to tide businesses over financial difficulties arising from anti-epidemic measures. He thanked the association for handling the scheme’s applications. Mr Tsui also expressed gratitude to the fitness industry for complying with the Government’s preventive measures, including suspension of business, in the fight against the virus. Given the stabilising epidemic situation, the Government has conducted a health risk assessment and will allow premises, including fitness centres, to resume operations, Mr Tsui said, adding that he hopes the fitness industry will soon regain vitality. The Home Affairs Bureau commissioned the association to assist in implementing the scheme, which opened for applications on May 4. As of May 7, the association received 397 applications, of which more than half of them have been initially found to be eligible, involving subsidies of about $20 million. The application period for the scheme will end on June 3. Call 2302 9089 or send an email for enquiries. Full Article
at Interview with mathematician and book author Kit Yates By www.ams.org Published On :: Mon, 23 Dec 2019 00:00:00 EST "In his new book--The Math of Life & Death: 7 Mathematical Principles that Shape Our Lives--mathematician Kit Yates makes complex mathematical concepts easily accessible to anyone, and which can improve decision making in an increasingly quantitative society. In this Q&A, Yates discusses why math is relevant to everyday life." See "Mathematician Kit Yates on Anti Vaxxer Movement, Air Travel Germs and Samoa's Measles Outbreak," by Meredith Wold Schizer, Newsweek, December 23, 2019. Full Article
at Math Students + Habitat for Humanity build homes By www.ams.org Published On :: Tue, 24 Dec 2019 00:00:00 EST Students in a math class at Columbine High School in Colorado used geometry to work with Habitat for Humanity to build homes for those in need. See the video segment at "Students Build Houses For Families In Need...In Math Class," by Shaun Boyd, CBS4 Denver TV, December 23, 2019. Full Article
at Mathematics from arts? By www.ams.orghttps Published On :: Fri, 27 Dec 2019 00:00:00 EST Full Article
at Quanta hosts a new podcast series on mathematics By www.ams.org Published On :: Tue, 21 Jan 2020 00:00:00 EST "[W]hen the editors at Quanta Magazine invited me to host a podcast for them, I jumped at the chance...Through this podcast, I've been learning about the inner lives of some of the most intriguing mathematicians and scientists working today. [I]n every case, I wanted to know what makes them tick. I wanted to know why they do what they do, what they’ve discovered, and why it matters to them and to the world." Read "Why I'm Hosting The Joy of x Podcast," by Steven Strogatz, Quanta Magazine, January 14, 2020. Full Article
at Mathematician Emily Riehl earns President's Frontier Award By www.ams.org Published On :: Tue, 21 Jan 2020 00:00:00 EST Emily Riehl, Johns Hopkins University, received the university's $250,000 President's Frontier Award, whose purpose is to nurture individuals at Johns Hopkins University who are breaking new ground and poised to become leaders in their field. Riehl studies category theory and says that "I just thought the proofs were the most beautiful of any of the other areas I've encountered. ... It was sort of love at first sight and I am lucky to be able to do what I love." The award is considered a "$250,000 investment in doing more of what she loves." Also see and hear this coverage: "Johns Hopkins Mathematician from B-N [Bloomington-Normal, IL] Breaks Barriers and Wins Research Grant, by Jolie Sherman, WGLT, February 27, 2020. Full Article
at 2020 Mathematical Art Exhibition Awards By www.ams.org Published On :: Thu, 23 Jan 2020 00:00:00 EST The 2020 Mathematical Art Exhibition Awards were made at the Joint Mathematics Meetings last week "for aesthetically pleasing works that combine mathematics and art." The chosen works were selected from the exhibition of juried works in various media by over 90 mathematicians and artists from around the world. "Suspended Helical Stair," by Mark Donohue (California College of the Arts, San Francisco, CA), was awarded Best textile, sculpture, or other medium. "A unique cable system to suspend a stair was developed in collaboration with a leading structural engineer. The suspended cables form a double helicoid nested within an ascending spiral hyperboloid to create the necessary points of support for the gravity loads and lateral bracing for the seismic loads. Each concrete stair tread was designed as an independent element that is strung together with the stairs above and below it to form a single spiral stair when the steel cables that run through them are post tensioned. The entire stair tread and suspension cable system can be understood as a play of ruled surfaces with each part related to the other through their shared geometric lineage." The work is string and plywood,45 x 23 x 23 cm, 2018. 2018 "A Unit Domino," by Douglas McKenna (Mathemaesthetics, Inc., Boulder, CO), was awarded Best photograph, painting, or print. "This piece is based upon an artist-discovered "half-domino" space-filling curve. The drawing comprises some half-million connected line segments, arranged in two perfectly recursive levels of double-spiral pairs, slowly changing color, in a single, over-one-mile-long self-avoiding path from lower left to lower right (the lower right square that sticks out is an integral part of its self-negative structure). The limiting curve covers a self-similar gasket tile with an infinitely long, almost-everywhere linear border. With an upside-down copy of itself, two such gaskets of unit area exactly cover a 1x2 domino, without overlap. The artist's app/eBook "Hilbert Curves" for iPad/iPhone explains how he discovered these beautiful constructions." The work is a glicée print,106 x 66 cm, 2015. "Computational Wings," by David Bachman (Pitzer College, Claremont, CA), received Honorable Mention. "The body of this dragonfly is taken from a photograph, while the wings were computationally generated. A variety of algorithms were used to create them. First, a set of points were randomly populated across each wing and moved by a circle packing algorithm, where the radius of each circle was inversely proportional to the distance from the body. Next, those points were used to create a Voronoi diagram. Main veins were located by a shortest walk algorithm through the edges of this diagram, and those veins were given a variable thickness according to the distance travelled as you traverse them outward from the body." The work is laser etched acrylic, 23 x 35 x 3 cm, 2019. (Click on the thumbnails to see larger versions of the images.) The Mathematical Art Exhibition Award "for aesthetically pleasing works that combine mathematics and art" was established in 2008 through an endowment provided to the American Mathematical Society by an anonymous donor who wishes to acknowledge those whose works demonstrate the beauty and elegance of mathematics expressed in a visual art form. The awards are $400 for Best photograph, painting, or print; $400 for Best textile, sculpture, or other medium; and $200 for Honorable Mention. The Mathematical Art Exhibition of juried works in various media is held at the annual Joint Mathematics Meetings of the American Mathematical Society (AMS) and Mathematical Association of America (MAA). a gallery of works in the 2020 exhibition will be on AMS Mathematical Imagery. Find out more about the Mathematical Art Exhibition Award and see past recipients. [% ams_include('pao-contact') %] *** 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. Full Article
at 2020 AMS Math Poetry Contest winners By www.ams.org Published On :: Mon, 27 Jan 2020 00:00:00 EST Congratulations to the 2020 AMS Math Poetry Contest Winners in the middle school, high school, and college categories: Sabrina Little, Mackintosh Academy, Boulder, for "Outlier;" Austen Mazenko, Cherry Creek High School, for "The Number Won; and Chenyu Lin, Colorado Christian University, for "x2 + y2 = 1(ife)." The poems were read during Mathemati-Con at the 2020 Joint Mathematics Meetings in Denver, CO. Read the poems and learn about the contest and Math and Poetry. (Photo: (left to right) Austen Mazenko, Sabrina Little, poetry contest judge Gizem Karaali, and Chenyu Lin. Full Article
at Three distinct glycosylation pathways are involved in the decoration of Lactococcus lactis cell wall glycopolymers [Microbiology] By www.jbc.org Published On :: 2020-04-17T00:06:05-07:00 Extracytoplasmic sugar decoration of glycopolymer components of the bacterial cell wall contributes to their structural diversity. Typically, the molecular mechanism that underpins such a decoration process involves a three-component glycosylation system (TGS) represented by an undecaprenyl-phosphate (Und-P) sugar-activating glycosyltransferase (Und-P GT), a flippase, and a polytopic glycosyltransferase (PolM GT) dedicated to attaching sugar residues to a specific glycopolymer. Here, using bioinformatic analyses, CRISPR-assisted recombineering, structural analysis of cell wall–associated polysaccharides (CWPS) through MALDI-TOF MS and methylation analysis, we report on three such systems in the bacterium Lactococcus lactis. On the basis of sequence similarities, we first identified three gene pairs, csdAB, csdCD, and csdEF, each encoding an Und-P GT and a PolM GT, as potential TGS component candidates. Our experimental results show that csdAB and csdCD are involved in Glc side-chain addition on the CWPS components rhamnan and polysaccharide pellicle (PSP), respectively, whereas csdEF plays a role in galactosylation of lipoteichoic acid (LTA). We also identified a potential flippase encoded in the L. lactis genome (llnz_02975, cflA) and confirmed that it participates in the glycosylation of the three cell wall glycopolymers rhamnan, PSP, and LTA, thus indicating that its function is shared by the three TGSs. Finally, we observed that glucosylation of both rhamnan and PSP can increase resistance to bacteriophage predation and that LTA galactosylation alters L. lactis resistance to bacteriocin. Full Article
at Biosynthesis of depsipeptides with a 3-hydroxybenzoate moiety and selective anticancer activities involves a chorismatase [Metabolism] By www.jbc.org Published On :: 2020-04-17T00:06:05-07:00 Neoantimycins are anticancer compounds of 15-membered ring antimycin-type depsipeptides. They are biosynthesized by a hybrid multimodular protein complex of nonribosomal peptide synthetase (NRPS) and polyketide synthase (PKS), typically from the starting precursor 3-formamidosalicylate. Examining fermentation extracts of Streptomyces conglobatus, here we discovered four new neoantimycin analogs, unantimycins B–E, in which 3-formamidosalicylates are replaced by an unusual 3-hydroxybenzoate (3-HBA) moiety. Unantimycins B–E exhibited levels of anticancer activities similar to those of the chemotherapeutic drug cisplatin in human lung cancer, colorectal cancer, and melanoma cells. Notably, they mostly displayed no significant toxicity toward noncancerous cells, unlike the serious toxicities generally reported for antimycin-type natural products. Using site-directed mutagenesis and heterologous expression, we found that unantimycin productions are correlated with the activity of a chorismatase homolog, the nat-hyg5 gene, from a type I PKS gene cluster. Biochemical analysis confirmed that the catalytic activity of Nat-hyg5 generates 3-HBA from chorismate. Finally, we achieved selective production of unantimycins B and C by engineering a chassis host. On the basis of these findings, we propose that unantimycin biosynthesis is directed by the neoantimycin-producing NRPS–PKS complex and initiated with the starter unit of 3-HBA. The elucidation of the biosynthetic unantimycin pathway reported here paves the way to improve the yield of these compounds for evaluation in oncotherapeutic applications. Full Article
at The FKH domain in FOXP3 mRNA frequently contains mutations in hepatocellular carcinoma that influence the subcellular localization and functions of FOXP3 [Molecular Bases of Disease] By www.jbc.org Published On :: 2020-04-17T00:06:05-07:00 The transcription factor forkhead box P3 (FOXP3) is a biomarker for regulatory T cells and can also be expressed in cancer cells, but its function in cancer appears to be divergent. The role of hepatocyte-expressed FOXP3 in hepatocellular carcinoma (HCC) is unknown. Here, we collected tumor samples and clinical information from 115 HCC patients and used five human cancer cell lines. We examined FOXP3 mRNA sequences for mutations, used a luciferase assay to assess promoter activities of FOXP3's target genes, and employed mouse tumor models to confirm in vitro results. We detected mutations in the FKH domain of FOXP3 mRNAs in 33% of the HCC tumor tissues, but in none of the adjacent nontumor tissues. None of the mutations occurred at high frequency, indicating that they occurred randomly. Notably, the mutations were not detected in the corresponding regions of FOXP3 genomic DNA, and many of them resulted in amino acid substitutions in the FKH region, altering FOXP3's subcellular localization. FOXP3 delocalization from the nucleus to the cytoplasm caused loss of transcriptional regulation of its target genes, inactivated its tumor-inhibitory capability, and changed cellular responses to histone deacetylase (HDAC) inhibitors. More complex FKH mutations appeared to be associated with worse prognosis in HCC patients. We conclude that mutations in the FKH domain of FOXP3 mRNA frequently occur in HCC and that these mutations are caused by errors in transcription and are not derived from genomic DNA mutations. Our results suggest that transcriptional mutagenesis of FOXP3 plays a role in HCC. Full Article
at A comprehensive evaluation of a typical plant telomeric G-quadruplex (G4) DNA reveals the dynamics of G4 formation, rearrangement, and unfolding [Plant Biology] By www.jbc.org Published On :: 2020-04-17T00:06:05-07:00 Telomeres are specific nucleoprotein structures that are located at the ends of linear eukaryotic chromosomes and play crucial roles in genomic stability. Telomere DNA consists of simple repeats of a short G-rich sequence: TTAGGG in mammals and TTTAGGG in most plants. In recent years, the mammalian telomeric G-rich repeats have been shown to form G-quadruplex (G4) structures, which are crucial for modulating telomere functions. Surprisingly, even though plant telomeres are essential for plant growth, development, and environmental adaptions, only few reports exist on plant telomeric G4 DNA (pTG4). Here, using bulk and single-molecule assays, including CD spectroscopy, and single-molecule FRET approaches, we comprehensively characterized the structure and dynamics of a typical plant telomeric sequence, d[GGG(TTTAGGG)3]. We found that this sequence can fold into mixed G4s in potassium, including parallel and antiparallel structures. We also directly detected intermediate dynamic transitions, including G-hairpin, parallel G-triplex, and antiparallel G-triplex structures. Moreover, we observed that pTG4 is unfolded by the AtRecQ2 helicase but not by AtRecQ3. The results of our work shed light on our understanding about the existence, topological structures, stability, intermediates, unwinding, and functions of pTG4. Full Article
at The transcriptional regulator MEIS2 sets up the ground state for palatal osteogenesis in mice [Gene Regulation] By www.jbc.org Published On :: 2020-04-17T00:06:05-07:00 Haploinsufficiency of Meis homeobox 2 (MEIS2), encoding a transcriptional regulator, is associated with human cleft palate, and Meis2 inactivation leads to abnormal palate development in mice, implicating MEIS2 functions in palate development. However, its functional mechanisms remain unknown. Here we observed widespread MEIS2 expression in the developing palate in mice. Wnt1Cre-mediated Meis2 inactivation in cranial neural crest cells led to a secondary palate cleft. Importantly, about half of the Wnt1Cre;Meis2f/f mice exhibited a submucous cleft, providing a model for studying palatal bone formation and patterning. Consistent with complete absence of palatal bones, the results from integrative analyses of MEIS2 by ChIP sequencing, RNA-Seq, and an assay for transposase-accessible chromatin sequencing identified key osteogenic genes regulated directly by MEIS2, indicating that it plays a fundamental role in palatal osteogenesis. De novo motif analysis uncovered that the MEIS2-bound regions are highly enriched in binding motifs for several key osteogenic transcription factors, particularly short stature homeobox 2 (SHOX2). Comparative ChIP sequencing analyses revealed genome-wide co-occupancy of MEIS2 and SHOX2 in addition to their colocalization in the developing palate and physical interaction, suggesting that SHOX2 and MEIS2 functionally interact. However, although SHOX2 was required for proper palatal bone formation and was a direct downstream target of MEIS2, Shox2 overexpression failed to rescue the palatal bone defects in a Meis2-mutant background. These results, together with the fact that Meis2 expression is associated with high osteogenic potential and required for chromatin accessibility of osteogenic genes, support a vital function of MEIS2 in setting up a ground state for palatal osteogenesis. Full Article
at Cell-specific expression of the transcriptional regulator RHAMM provides a timing mechanism that controls appropriate wound re-epithelialization [Glycobiology and Extracellular Matrices] By www.jbc.org Published On :: 2020-04-17T00:06:05-07:00 Prevention of aberrant cutaneous wound repair and appropriate regeneration of an intact and functional integument require the coordinated timing of fibroblast and keratinocyte migration. Here, we identified a mechanism whereby opposing cell-specific motogenic functions of a multifunctional intracellular and extracellular protein, the receptor for hyaluronan-mediated motility (RHAMM), coordinates fibroblast and keratinocyte migration speed and ensures appropriate timing of excisional wound closure. We found that, unlike in WT mice, in Rhamm-null mice, keratinocyte migration initiates prematurely in the excisional wounds, resulting in wounds that have re-surfaced before the formation of normal granulation tissue, leading to a defective epidermal architecture. We also noted aberrant keratinocyte and fibroblast migration in the Rhamm-null mice, indicating that RHAMM suppresses keratinocyte motility but increases fibroblast motility. This cell context–dependent effect resulted from cell-specific regulation of extracellular signal-regulated kinase 1/2 (ERK1/2) activation and expression of a RHAMM target gene encoding matrix metalloprotease 9 (MMP-9). In fibroblasts, RHAMM promoted ERK1/2 activation and MMP-9 expression, whereas in keratinocytes, RHAMM suppressed these activities. In keratinocytes, loss of RHAMM function or expression promoted epidermal growth factor receptor–regulated MMP-9 expression via ERK1/2, which resulted in cleavage of the ectodomain of the RHAMM partner protein CD44 and thereby increased keratinocyte motility. These results identify RHAMM as a key factor that integrates the timing of wound repair by controlling cell migration. Full Article
at {gamma}-Hydroxybutyrate does not mediate glucose inhibition of glucagon secretion [Signal Transduction] By www.jbc.org Published On :: 2020-04-17T00:06:05-07:00 Hypersecretion of glucagon from pancreatic α-cells strongly contributes to diabetic hyperglycemia. Moreover, failure of α-cells to increase glucagon secretion in response to falling blood glucose concentrations compromises the defense against hypoglycemia, a common complication in diabetes therapy. However, the mechanisms underlying glucose regulation of glucagon secretion are poorly understood and likely involve both α-cell–intrinsic and intraislet paracrine signaling. Among paracrine factors, glucose-stimulated release of the GABA metabolite γ-hydroxybutyric acid (GHB) from pancreatic β-cells might mediate glucose suppression of glucagon release via GHB receptors on α-cells. However, the direct effects of GHB on α-cell signaling and glucagon release have not been investigated. Here, we found that GHB (4–10 μm) lacked effects on the cytoplasmic concentrations of the secretion-regulating messengers Ca2+ and cAMP in mouse α-cells. Glucagon secretion from perifused mouse islets was also unaffected by GHB at both 1 and 7 mm glucose. The GHB receptor agonist 3-chloropropanoic acid and the antagonist NCS-382 had no effects on glucagon secretion and did not affect stimulation of secretion induced by a drop in glucose from 7 to 1 mm. Inhibition of endogenous GHB formation with the GABA transaminase inhibitor vigabatrin also failed to influence glucagon secretion at 1 mm glucose and did not prevent the suppressive effect of 7 mm glucose. In human islets, GHB tended to stimulate glucagon secretion at 1 mm glucose, an effect mimicked by 3-chloropropanoic acid. We conclude that GHB does not mediate the inhibitory effect of glucose on glucagon secretion. Full Article
at Structural basis of specific inhibition of extracellular activation of pro- or latent myostatin by the monoclonal antibody SRK-015 [Molecular Biophysics] By www.jbc.org Published On :: 2020-04-17T00:06:05-07:00 Myostatin (or growth/differentiation factor 8 (GDF8)) is a member of the transforming growth factor β superfamily of growth factors and negatively regulates skeletal muscle growth. Its dysregulation is implicated in muscle wasting diseases. SRK-015 is a clinical-stage mAb that prevents extracellular proteolytic activation of pro- and latent myostatin. Here we used integrated structural and biochemical approaches to elucidate the molecular mechanism of antibody-mediated neutralization of pro-myostatin activation. The crystal structure of pro-myostatin in complex with 29H4-16 Fab, a high-affinity variant of SRK-015, at 2.79 Å resolution revealed that the antibody binds to a conformational epitope in the arm region of the prodomain distant from the proteolytic cleavage sites. This epitope is highly sequence-divergent, having only limited similarity to other closely related members of the transforming growth factor β superfamily. Hydrogen/deuterium exchange MS experiments indicated that antibody binding induces conformational changes in pro- and latent myostatin that span the arm region, the loops contiguous to the protease cleavage sites, and the latency-associated structural elements. Moreover, negative-stain EM with full-length antibodies disclosed a stable, ring-like antigen–antibody structure in which the two Fab arms of a single antibody occupy the two arm regions of the prodomain in the pro- and latent myostatin homodimers, suggesting a 1:1 (antibody:myostatin homodimer) binding stoichiometry. These results suggest that SRK-015 binding stabilizes the latent conformation and limits the accessibility of protease cleavage sites within the prodomain. These findings shed light on approaches that specifically block the extracellular activation of growth factors by targeting their precursor forms. Full Article
at Biochemical and structural insights into how amino acids regulate pyruvate kinase muscle isoform 2 [Enzymology] By www.jbc.org Published On :: 2020-04-17T00:06:05-07:00 Pyruvate kinase muscle isoform 2 (PKM2) is a key glycolytic enzyme involved in ATP generation and critical for cancer metabolism. PKM2 is expressed in many human cancers and is regulated by complex mechanisms that promote tumor growth and proliferation. Therefore, it is considered an attractive therapeutic target for modulating tumor metabolism. Various stimuli allosterically regulate PKM2 by cycling it between highly active and less active states. Several small molecules activate PKM2 by binding to its intersubunit interface. Serine and cysteine serve as an activator and inhibitor of PKM2, respectively, by binding to its amino acid (AA)-binding pocket, which therefore represents a potential druggable site. Despite binding similarly to PKM2, how cysteine and serine differentially regulate this enzyme remains elusive. Using kinetic analyses, fluorescence binding, X-ray crystallography, and gel filtration experiments with asparagine, aspartate, and valine as PKM2 ligands, we examined whether the differences in the side-chain polarity of these AAs trigger distinct allosteric responses in PKM2. We found that Asn (polar) and Asp (charged) activate PKM2 and that Val (hydrophobic) inhibits it. The results also indicate that both Asn and Asp can restore the activity of Val-inhibited PKM2. AA-bound crystal structures of PKM2 displayed distinctive interactions within the binding pocket, causing unique allosteric effects in the enzyme. These structure-function analyses of AA-mediated PKM2 regulation shed light on the chemical requirements in the development of mechanism-based small-molecule modulators targeting the AA-binding pocket of PKM2 and provide broader insights into the regulatory mechanisms of complex allosteric enzymes. Full Article
at Evolution, expression, and substrate specificities of aldehyde oxidase enzymes in eukaryotes [Enzymology] By www.jbc.org Published On :: 2020-04-17T00:06:05-07:00 Aldehyde oxidases (AOXs) are a small group of enzymes belonging to the larger family of molybdo-flavoenzymes, along with the well-characterized xanthine oxidoreductase. The two major types of reactions that are catalyzed by AOXs are the hydroxylation of heterocycles and the oxidation of aldehydes to their corresponding carboxylic acids. Different animal species have different complements of AOX genes. The two extremes are represented in humans and rodents; whereas the human genome contains a single active gene (AOX1), those of rodents, such as mice, are endowed with four genes (Aox1-4), clustering on the same chromosome, each encoding a functionally distinct AOX enzyme. It still remains enigmatic why some species have numerous AOX enzymes, whereas others harbor only one functional enzyme. At present, little is known about the physiological relevance of AOX enzymes in humans and their additional forms in other mammals. These enzymes are expressed in the liver and play an important role in the metabolisms of drugs and other xenobiotics. In this review, we discuss the expression, tissue-specific roles, and substrate specificities of the different mammalian AOX enzymes and highlight insights into their physiological roles. Full Article
at The transcriptional regulator IscR integrates host-derived nitrosative stress and iron starvation in activation of the vvhBA operon in Vibrio vulnificus [Gene Regulation] By www.jbc.org Published On :: 2020-04-17T00:06:05-07:00 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. Full Article
at 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
at A peroxisome deficiency-induced reductive cytosol state up-regulates the brain-derived neurotrophic factor pathway [Metabolism] By www.jbc.org Published On :: 2020-04-17T00:06:05-07:00 The peroxisome is a subcellular organelle that functions in essential metabolic pathways, including biosynthesis of plasmalogens, fatty acid β-oxidation of very-long-chain fatty acids, and degradation of hydrogen peroxide. Peroxisome biogenesis disorders (PBDs) manifest as severe dysfunction in multiple organs, including the central nervous system (CNS), but the pathogenic mechanisms in PBDs are largely unknown. Because CNS integrity is coordinately established and maintained by neural cell interactions, we here investigated whether cell-cell communication is impaired and responsible for the neurological defects associated with PBDs. Results from a noncontact co-culture system consisting of primary hippocampal neurons with glial cells revealed that a peroxisome-deficient astrocytic cell line secretes increased levels of brain-derived neurotrophic factor (BDNF), resulting in axonal branching of the neurons. Of note, the BDNF expression in astrocytes was not affected by defects in plasmalogen biosynthesis and peroxisomal fatty acid β-oxidation in the astrocytes. Instead, we found that cytosolic reductive states caused by a mislocalized catalase in the peroxisome-deficient cells induce the elevation in BDNF secretion. Our results suggest that peroxisome deficiency dysregulates neuronal axogenesis by causing a cytosolic reductive state in astrocytes. We conclude that astrocytic peroxisomes regulate BDNF expression and thereby support neuronal integrity and function. Full Article
at 12-LOX catalyzes the oxidation of 2-arachidonoyl-lysolipids in platelets generating eicosanoid-lysolipids that are attenuated by iPLA2{gamma} knockout [Signal Transduction] By www.jbc.org Published On :: 2020-04-17T00:06:05-07:00 The canonical pathway of eicosanoid production in most mammalian cells is initiated by phospholipase A2-mediated release of arachidonic acid, followed by its enzymatic oxidation resulting in a vast array of eicosanoid products. However, recent work has demonstrated that the major phospholipase in mitochondria, iPLA2γ (patatin-like phospholipase domain containing 8 (PNPLA8)), possesses sn-1 specificity, with polyunsaturated fatty acids at the sn-2 position generating polyunsaturated sn-2-acyl lysophospholipids. Through strategic chemical derivatization, chiral chromatographic separation, and multistage tandem MS, here we first demonstrate that human platelet-type 12-lipoxygenase (12-LOX) can directly catalyze the regioselective and stereospecific oxidation of 2-arachidonoyl-lysophosphatidylcholine (2-AA-LPC) and 2-arachidonoyl-lysophosphatidylethanolamine (2-AA-LPE). Next, we identified these two eicosanoid-lysophospholipids in murine myocardium and in isolated platelets. Moreover, we observed robust increases in 2-AA-LPC, 2-AA-LPE, and their downstream 12-LOX oxidation products, 12(S)-HETE-LPC and 12(S)-HETE-LPE, in calcium ionophore (A23187)-stimulated murine platelets. Mechanistically, genetic ablation of iPLA2γ markedly decreased the calcium-stimulated production of 2-AA-LPC, 2-AA-LPE, and 12-HETE-lysophospholipids in mouse platelets. Importantly, a potent and selective 12-LOX inhibitor, ML355, significantly inhibited the production of 12-HETE-LPC and 12-HETE-LPE in activated platelets. Furthermore, we found that aging is accompanied by significant changes in 12-HETE-LPC in murine serum that were also markedly attenuated by iPLA2γ genetic ablation. Collectively, these results identify previously unknown iPLA2γ-initiated signaling pathways mediated by direct 12-LOX oxidation of 2-AA-LPC and 2-AA-LPE. This oxidation generates previously unrecognized eicosanoid-lysophospholipids that may serve as biomarkers for age-related diseases and could potentially be used as targets in therapeutic interventions. Full Article