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"Mathematics and the Family Tree of Sars-Cov-2," the May Feature Column by Bill Casselman




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




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2020 Mathematical Art Exhibition gallery on AMS Mathematical Imagery




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Perturbation de la Dynamique de Diffeomorphismes en Topologie (C^{1})

Sylvain Crovisier, University of Paris-Sud - A publication of the Societe Mathematique de France, 2013, 164 pp., Softcover, ISBN-13: 978-2-85629-764-3, List: US$67, All AMS Members: US$53.60, AST/354

This memoir deals with the dynamics of diffeomorphisms of compact manifolds. For the study of generic properties or for the construction of examples,...




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Persistence of Stratifications of Normally Expanded Laminations

Pierre Berger, Universite Paris 13 - A publication of the Societe Mathematique de France, 2013, 113 pp., Softcover, ISBN-13: 978-2-85629-767-4, List: US$45, All AMS Members: US$36, SMFMEM/134

This manuscript complements the Hirsch-Pugh-Shub (HPS) theory on persistence of normally hyperbolic laminations and implies several structural...




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Microlocalization of Subanalytic Sheaves

Luca Prelli, Universita degli Studi di Padova - A publication of the Societe Mathematique de France, 2013, 101 pp., Softcover, ISBN-13: 978-2-85629-768-1, List: US$45, All AMS Members: US$36, SMFMEM/135

The author defines the specialization and microlocalization functors for subanalytic sheaves. Applying these tools to the sheaves of tempered and...




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

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

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




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Metric Spaces, Convexity and Nonpositive Curvature: Second Edition

Athanase Papadopoulos, Universite de Strasbourg - A publication of the European Mathematical Society, 2013, 320 pp., Softcover, ISBN-13: 978-3-03719-132-3, List: US$58, All AMS Members: US$46.40, EMSILMTP/6.R

This book is about metric spaces of nonpositive curvature in the sense of Busemann, that is, metric spaces whose distance function satisfies a...




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Advances in Representation Theory of Algebras

David J. Benson, University of Aberdeen, Henning Krause, University of Bielefeld, and Andrzej Skowronski, Nicolaus Copernicus University, Editors - A publication of the European Mathematical Society, 2013, 378 pp., Hardcover, ISBN-13: 978-3-03719-125-5, List: US$98, Institutional Member: US$78.40, All Individuals: US$78.40, EMSSCR/9

This volume presents a collection of articles devoted to representations of algebras and related topics. Dististinguished experts in this field...




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Capacity Theory with Local Rationality: The Strong Fekete-Szego Theorem on Curves

Robert Rumely, University of Georgia - AMS, 2013, 437 pp., Hardcover, ISBN-13: 978-1-4704-0980-7, List: US$119, All AMS Members: US$95.20, SURV/193

This book is devoted to the proof of a deep theorem in arithmetic geometry, the Fekete-Szegö theorem with local rationality conditions. The...




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Hodge Theory, Complex Geometry, and Representation Theory

Robert S. Doran, Greg Friedman, and Scott Nollet, Texas Christian University, Editors - AMS, 2014, approx. 318 pp., Softcover, ISBN-13: 978-0-8218-9415-6, List: US$113, All AMS Members: US$90.40, CONM/608

This volume contains the proceedings of an NSF/Conference Board of the Mathematical Sciences (CBMS) regional conference on Hodge theory, complex...




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Ring Theory and Its Applications

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...




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Perspectives in Representation Theory

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...




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Harmonic Analysis and Partial Differential Equations

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,...




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Relative Equilibria in the 3-Dimensional Curved (n)-Body Problem

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....




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Spectra of Symmetrized Shuffling Operators

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...




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Nonlinear Stability of Ekman Boundary Layers in Rotating Stratified Fluids

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...




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Group Theory, Combinatorics, and Computing

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...




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Topology and Field Theories

Stephan Stolz, University of Notre Dame, Editor - AMS, 2014, 176 pp., Softcover, ISBN-13: 978-1-4704-1015-5, List: US$78, All AMS Members: US$62.40, CONM/613

This book is a collection of expository articles based on four lecture series presented during the 2012 Notre Dame Summer School in Topology and Field...




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The Joys of Haar Measure

Joe Diestel, Kent State University, and Angela Spalsbury, Youngstown State University - AMS, 2013, 320 pp., Hardcover, ISBN-13: 978-1-4704-0935-7, List: US$65, All AMS Members: US$52, GSM/150

From the earliest days of measure theory, invariant measures have held the interests of geometers and analysts alike, with the Haar measure playing an...




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Geometry of Isotropic Convex Bodies

Silouanos Brazitikos and Apostolos Giannopoulos, University of Athens, Petros Valettas, Texas A & M University, and Beatrice-Helen Vritsiou, University of Athens - AMS, 2014, 594 pp., Hardcover, ISBN-13: 978-1-4704-1456-6, List: US$134, All AMS Members: US$107.20, SURV/196

The study of high-dimensional convex bodies from a geometric and analytic point of view, with an emphasis on the dependence of various parameters on...




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Pearls from a Lost City: The Lvov School of Mathematics

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...




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Really Big Numbers

Richard Evan Schwartz, Brown University - AMS, 2014, 192 pp., Softcover, ISBN-13: 978-1-4704-1425-2, List: US$25, All AMS Members: US$20, MBK/84

A superb, beautifully illustrated book for kids -- and those of us still children at heart -- that takes you up (and up, and up,and up, and up, and...




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Global and Local Regularity of Fourier Integral Operators on Weighted and Unweighted Spaces

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...




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Operator-Valued Measures, Dilations, and the Theory of Frames

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...




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Cohomology for Quantum Groups via the Geometry of the Nullcone

Christopher P. Bendel, University of Wisconsin-Stout, Daniel K. Nakano, University of Georgia, Brian J. Parshall, University of Virginia, and Cornelius Pillen, University of South Alabama - AMS, 2013, 93 pp., Softcover, ISBN-13: 978-0-8218-9175-9, List: US$71, All AMS Members: US$56.80, MEMO/229/1077

Let (zeta) be a complex (ell)th root of unity for an odd integer (ell>1). For any complex simple Lie algebra (mathfrak g), let...




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

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

Roadside Stations: 2 (Health Risk: Low)




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Water-splitting module a source of perpetual energy

(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.




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Brazilian and Indian scientists produce crystal with many potential applications

(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.




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An artificial 'tongue' of gold to taste maple syrup

(University of Montreal) A chemistry professor at Université de Montréal has developed a new test using gold nanoparticles to establish the flavour profile of maple syrup and help producers evaluate its quality.




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Extreme ultraviolet imaging displays potential to enhance study of Alzheimer's disease

(University of Southampton) Scientists have published highly detailed images of lab-grown neurons using Extreme Ultraviolet radiation that could aid the analysis of neurodegenerative diseases.




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Research found a new way to make functional materials based on polymers of metal clusters

(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.




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Three NSF RAPID grants to develop quicker test for COVID-19 for Holonyak Lab faculty

(University of Illinois Grainger College of Engineering) Three Nick Holonyak Jr., Micro and Nanotechnology Lab (HMNTL) faculty members received NSF Rapid Response Research (RAPID) program grants, all of which aim to shorten the amount of time it takes to process a COVID-19 test with less false negatives. Current tests can take as long as five days for results to be.




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Surfaces that grip like gecko feet could be easily mass-produced

(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.




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High color purity 3D printing

(ICFO-The Institute of Photonic Sciences) ICFO researchers report on a new method to obtain high color purity 3D objects with the use of a new class of nanoparticles.




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Young Scientist prize for Lancaster physicist

(Lancaster University) Lancaster University's Dr Samuli Autti has been awarded a Young Scientist Prize 2020 by the International Union of Pure and Applied Physics. The prestigious prize, awarded only once every three years, was made by the Low Temperature Commission of the IUPAP.





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Masks for the needy ensured

(To watch the full press conference with sign language interpretation, click here.)

 

Chief Executive Carrie Lam today said that Hong Kong’s needy and disadvantaged will receive masks as part of the Government’s new mask distribution programme.

 

Mrs Lam made the announcement during a press conference this afternoon and explained that millions of donated masks will also be distributed to those in need.

 

“I have outlined six measures to distribute masks freely to the people of Hong Kong, and of course in so doing, we will take special account of the disadvantaged, the elderly and street sleepers. 

 

“So apart from being a member of the Hong Kong population, they will receive reusable masks. They will receive disposable masks. We have this mask distribution program together with a large number of non-governmental organisations, charity groups and self-help groups.

 

“So we will continue to work with them to distribute another three million masks, which were donated to us.”

 

Mrs Lam emphasised that should there be a shortage of masks set aside for the needy, the Government will use its own supply to cover the shortfall.

 

“I am announcing that if we run out of donated masks, but there is still a need from this disadvantaged groups, we will use the government masks - the masks that we procured which are supposed to be for our own use - and share these with the needy groups in society.

 

“That's a way to ensure that, in a public health situation that we are now in, the needs of the disadvantaged groups will be fully taken care of.”

 

In addition to distributing donated masks, the Government announced other measures on mask supplies that include handing out single-use and reusable masks to all Hong Kong residents and students in need.

 

Such measures also call for increasing the supply of masks to staff of elderly homes and cleaning workers employed by the Government's outsourced service contractors, as well as providing masks to private medical practitioners.




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Interview with mathematician and book author Kit Yates

"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.




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Math Students + Habitat for Humanity build homes

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.




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Hannah Fry to show strengths and weaknesses of algorithms

"Driverless cars, robot butlers and reusable rockets--if the big inventions of the past decade and the artificial intelligence developed to create them have taught us anything, it's that maths is undeniably cool. And if you’re still not convinced, chances are you’ve never had it explained to you via a live experiment with a pigeon before. Temporary pigeon handler and queen of making numbers fun is Dr Hannah Fry, the host of this year's annual Royal Institution Christmas Lectures." Learn more in "Christmas Lectures presenter Dr Hannah Fry on pigeons, AI and the awesome power of maths," by Rachael Pells, inews, December 23, 2019.





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Mathematician Emily Riehl earns President's Frontier Award

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.




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2020 AMS Math Poetry Contest winners

Congratulations to the 2020 AMS Math Poetry Contest Winners in the middle school, high school, and college categories: Sabrina Little, Mackintosh Academy, Boulder, for "Outlier;" Austen Mazenko, Cherry Creek High School, for "The Number Won; and Chenyu Lin, Colorado Christian University, for "x2 + y2 = 1(ife)." The poems were read during Mathemati-Con at the 2020 Joint Mathematics Meetings in Denver, CO. Read the poems and learn about the contest and Math and Poetry. (Photo: (left to right) Austen Mazenko, Sabrina Little, poetry contest judge Gizem Karaali, and Chenyu Lin.




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Wish you were here: Meetings, no meetings, meeting reports [Editorial]

We've all been saying it: These are unprecedented times. The impacts of the COVID-19 pandemic are incredibly wide-ranging and affect all facets of life. One that is hitting the scientific community very hard is the cancellation of meetings, large and small. While we are well-versed in connecting with colleagues and collaborators across a variety of online platforms, these do not replace the immensely gratifying aspects of attending meetings in person: the pleasure of catching up with old friends and making new ones, the insights gained from having real-time conversations with others working on the same topic but with different expertise and perspectives, and the stimulating new scientific ideas we carry home. We have all been feeling the disappointment as we learn that one meeting after another is forced to cancel, from the vibrant ASBMB annual meeting to summer conferences of all types.Another loss from the appropriate but painful decision to cancel the ASBMB annual meeting was the chance to hear from our Herbert Tabor Early Career Investigator Awardees, who represent the best science published in JBC in the preceding year. This year, the competition was particularly fierce. We hope and anticipate that we will be able to hear from the winners at next year's ASBMB annual meeting. But in the meantime, we want to raise a toast to Wenchao Zhao, Yue Yang, Manisha Dagar, Febin Varghese, and Ayumi Nagashima-Kasahara as our 2020 winners. We've captured their award-winning 2019 papers (1–5) on the JBC website (6), and extended profiles of the...




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Three distinct glycosylation pathways are involved in the decoration of Lactococcus lactis cell wall glycopolymers [Microbiology]

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.




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Biosynthesis of depsipeptides with a 3-hydroxybenzoate moiety and selective anticancer activities involves a chorismatase [Metabolism]

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.




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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]

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.




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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]

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.




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Inhibition of the erythropoietin-producing receptor EPHB4 antagonizes androgen receptor overexpression and reduces enzalutamide resistance [Molecular Bases of Disease]

Prostate cancer (PCa) cells heavily rely on an active androgen receptor (AR) pathway for their survival. Enzalutamide (MDV3100) is a second-generation antiandrogenic drug that was approved by the Food and Drug Administration in 2012 to treat patients with castration-resistant prostate cancer (CRPC). However, emergence of resistance against this drug is inevitable, and it has been a major challenge to develop interventions that help manage enzalutamide-resistant CRPC. Erythropoietin-producing human hepatocellular (Eph) receptors are targeted by ephrin protein ligands and have a broad range of functions. Increasing evidence indicates that this signaling pathway plays an important role in tumorigenesis. Overexpression of EPH receptor B4 (EPHB4) has been observed in multiple types of cancer, being closely associated with proliferation, invasion, and metastasis of tumors. Here, using RNA-Seq analyses of clinical and preclinical samples, along with several biochemical and molecular methods, we report that enzalutamide-resistant PCa requires an active EPHB4 pathway that supports drug resistance of this tumor type. Using a small kinase inhibitor and RNAi-based gene silencing to disrupt EPHB4 activity, we found that these disruptions re-sensitize enzalutamide-resistant PCa to the drug both in vitro and in vivo. Mechanistically, we found that EPHB4 stimulates the AR by inducing proto-oncogene c-Myc (c-Myc) expression. Taken together, these results provide critical insight into the mechanism of enzalutamide resistance in PCa, potentially offering a therapeutic avenue for enhancing the efficacy of enzalutamide to better manage this common malignancy.