Aldo-keto reductases (AKRs) are NADPH/NADP+-dependent oxidoreductase enzymes that metabolize an aldehyde/ketone to the corresponding alcohol. AKR4C14 from rice exhibits a much higher efficiency in metabolizing malondialdehyde (MDA) than do the Arabidopsis enzymes AKR4C8 and AKR4C9, despite sharing greater than 60% amino-acid sequence identity. This study confirms the role of rice AKR4C14 in the detoxification of methylglyoxal and MDA, and demonstrates that the endogenous contents of both aldehydes in transgenic Arabidopsis ectopically expressing AKR4C14 are significantly lower than their levels in the wild type. The apo structure of indica rice AKR4C14 was also determined in the absence of the cofactor, revealing the stabilized open conformation. This is the first crystal structure in AKR subfamily 4C from rice to be observed in the apo form (without bound NADP+). The refined AKR4C14 structure reveals a stabilized open conformation of loop B, suggesting the initial phase prior to cofactor binding. Based on the X-ray crystal structure, the substrate- and cofactor-binding pockets of AKR4C14 are formed by loops A, B, C and β1α1. Moreover, the residues Ser211 and Asn220 on loop B are proposed as the hinge residues that are responsible for conformational alteration while the cofactor binds. The open conformation of loop B is proposed to involve Phe216 pointing out from the cofactor-binding site and the opening of the safety belt. Structural comparison with other AKRs in subfamily 4C emphasizes the role of the substrate-channel wall, consisting of Trp24, Trp115, Tyr206, Phe216, Leu291 and Phe295, in substrate discrimination. In particular, Leu291 could contribute greatly to substrate selectivity, explaining the preference of AKR4C14 for its straight-chain aldehyde substrate.

The bond-valence method has been used for valence calculations of FeMo/V cofactors in FeMo/V proteins using 51 crystallographic data sets of FeMo/V proteins from the Protein Data Bank. The calculations show molybdenum(III) to be present in MoFe7S9C(Cys)(HHis)[R-(H)homocit] (where H4homocit is homocitric acid, HCys is cysteine and HHis is histidine) in FeMo cofactors, while vanadium(III) with a more reduced iron complement is obtained for FeV cofactors. Using an error analysis of the calculated valences, it was found that in FeMo cofactors Fe1, Fe6 and Fe7 can be unambiguously assigned as iron(III), while Fe2, Fe3, Fe4 and Fe5 show different degrees of mixed valences for the individual Fe atoms. For the FeV cofactors in PDB entry 5n6y, Fe4, Fe5 and Fe6 correspond to iron(II), iron(II) and iron(III), respectively, while Fe1, Fe2, Fe3 and Fe7 exhibit strongly mixed valences. Special situations such as CO-bound and selenium-substituted FeMo cofactors and O(N)H-bridged FeV cofactors are also discussed and suggest rearrangement of the electron configuration on the substitution of the bridging S atoms.

Despite the importance of seasonally dry forests, little is known of their ecology. Now, a new book The Ecology and Conservation of Seasonally Dry Forests in Asia, published by Smithsonian Institution Scholarly Press, explores these unique ecosystems, its animals, plants, and the people that inhabit them.

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Imke K. Mandemaker, Di Zhou, Serena T. Bruens, Dick H. Dekkers, Pernette J. Verschure, Raghu R. Edupuganti, Eran Meshorer, Jeroen A. Demmers, and Jurgen A. Marteijn

Many chromatin remodeling and modifying proteins are involved in the DNA damage response by stimulating repair or inducing DNA damage signaling. Interestingly, here we identified that down regulation of the H1-interacting protein SET results in increased resistance to a wide variety of DNA damaging agents. We found that this increased resistance is not the result of an inhibitory effect of SET on DNA repair, but rather the consequence of a suppressed apoptotic response to DNA damage. We further provide evidence that the histone chaperone SET is responsible for the eviction of H1 from chromatin. Knock down of H1 in SET-depleted cells resulted in re-sensitization of cells to DNA damage, suggesting that the increased DNA damage resistance in SET-depleted cells is the result of enhanced retention of H1 on chromatin. Finally, clonogenic survival assays show that SET and p53 are epistatic in attenuating DNA damage-induced cell death. Altogether, our data show a role for SET in the DNA damage response as a regulator of cell survival following genotoxic stress.

Eric Peterman, Mindaugas Valius, and Rytis Prekeris

During mitotic cell division, the actomyosin cytoskeleton undergoes several dynamic changes that play key roles in progression through mitosis. While the regulators of cytokinetic ring formation and contraction are well-established, proteins that regulate cortical stability during anaphase and telophase have been understudied. Here, we describe a role for CLIC4 in regulating actin and actin-regulators at the cortex and cytokinetic cleavage furrow during cytokinesis. We first describe CLIC4 as a new component of the cytokinetic cleavage furrow that is required for successful completion of mitotic cell division. We also demonstrate that CLIC4 regulates the remodeling of sub-plasma membrane actomyosin network within the furrow by recruiting MST4 kinase and regulating ezrin phosphorylation. This work identifies and characterizes new molecular players involved in regulating cortex stiffness and blebbing during late stages of cytokinetic furrowing.

Liza Botros MD., Manon C. A. Pronk PhD., Jenny Juschten MD., John Liddle, Sofia K. S. H. Morsing, Jaap D. van Buul PhD., Robert H. Bates, Pieter R. Tuinman MD. PhD., Jan S. M. van Bezu, Stephan Huveneers PhD., Harm Jan Bogaard MD. PhD., Victor W. M. van Hinsbergh PhD., Peter L. Hordijk PhD., and Jurjan Aman MD. PhD.

Aims: Endothelial barrier dysfunction leads to edema and vascular leak, carrying high morbidity and mortality. Previously, Abl kinase inhibition was shown to protect against vascular leak. Using the distinct inhibitory profiles of clinically available Abl kinase inhibitors, we aimed to provide a mechanistic basis for novel treatment strategies against vascular leakage syndromes.

Methods & Results: Bosutinib most potently protected against inflammation-induced endothelial barrier disruption. In vivo, bosutinib prevented LPS-induced alveolar protein extravasation in an acute lung injury mice model. Mechanistically, Mitogen-activated Protein 4 Kinase 4 (MAP4K4) was identified as important novel mediator of endothelial permeability, which signals via ezrin, radixin and moesin proteins to increase turnover of integrin-based focal adhesions. The combined inhibition of MAP4K4 and Arg by bosutinib preserved adherens junction integrity and reduced turnover of focal adhesions, which synergistically act to stabilize the endothelial barrier during inflammation.

Conclusion: MAP4K4 was identified as important regulator of endothelial barrier integrity, increasing focal adhesion turnover and disruption of cell-cell junctions during inflammation. Inhibiting both Arg and MAP4K4, the clinically available drug bosutinib may form a viable strategy against vascular leakage syndromes.

Olivia R. Grafinger, Genya Gorshtein, Tyler Stirling, Megan I. Brasher, and Marc G. Coppolino

Malignant cancer cells can invade extracellular matrix (ECM) through the formation of F-actin-rich subcellular structures termed invadopodia. ECM degradation at invadopodia is mediated by matrix metalloproteinases (MMPs), and recent findings indicate that membrane-anchored membrane type 1-matrix metalloproteinase (MT1-MMP) has a primary role in this process. Maintenance of an invasive phenotype is dependent on internalization of MT1-MMP from the plasma membrane and its recycling to sites of ECM remodeling. Internalization of MT1-MMP is dependent on its phosphorylation, and here we examine the role of β1 integrin-mediated signaling in this process. Activation of β1 integrin using the antibody P4G11 induced phosphorylation and internalization of MT1-MMP and resulted in increased cellular invasiveness and invadopodium formation in vitro. We also observed phosphorylation of Src and epidermal growth factor receptor (EGFR) and an increase in their association in response to β1 integrin activation, and determined that Src and EGFR promote phosphorylation of MT1-MMP on Thr⁵⁶⁷. These results suggest that MT1-MMP phosphorylation is regulated by a β1 integrin-Src-EGFR signaling pathway that promotes recycling of MT1-MMP to sites of invadopodia formation during cancer cell invasion.

Miniature camels and horses, a rhinoceros and a giant bear-dog are among fossils unearthed in the recent excavations of the Panama Canal expansion project. These […]

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Scientists from the Smithsonian and the University of Rhode Island have found unsuspected linkages between the oxidation state of iron in volcanic rocks and variations […]

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In the battle against invasive species, giant commercial ships are on the front lines. But even when they follow the rules, one of their best […]

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Appendices B4 and B5 of Cayron [Acta Cryst. (2019), A75, 411–437] contain equations involving the point group and the metric tensor in which the equality symbol should be substituted by the inclusion symbol.

The transformations from the primitive cells of the centered Bravais lattices to the corresponding centered cells have conventionally been listed as three-by-three matrices that transform three-space lattice vectors. Using those three-by-three matrices when working in the six-dimensional space of lattices represented as Selling scalars as used in Delone (Delaunay) reduction, one could transform to the three-space representation, apply the three-by-three matrices and then back-transform to the six-space representation, but it is much simpler to have the equivalent six-by-six matrices and apply them directly. The general form of the transformation from the three-space matrix to the corresponding matrix operating on Selling scalars (expressed in space S6) is derived, and the particular S6matrices for the centered Delone types are listed. (Note: in his later publications, Boris Delaunay used the Russian version of his surname, Delone.)

George Smith, a marine biologist at the Smithsonian Environmental Research Center, explains his work of finding ways to prevent invasive species from being released in Baltimore Harbor in the ballast water of large ships.

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The Crab Nebula is one of the most studied objects in the night sky. First observed by Chinese astronomers in 1054 A.D., and possibly others, this supernova remnant and its neutron star have become favorite targets for amateur and professional astronomers alike. The Chandra X-Ray Observatory is operated for NASA by the Smithsonian Astrophysical Observatory in Cambridge, Mass.

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When animal care staff at the Smithsonian's National Zoo need to know when to breed their pandas or when to expect a cub they turn to the Endocrine (Hormones) Research Lab at the Zoo's Front Royal, Va. facility.

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Invasive plant species are threatening native species across the globe. Learn how scientists at the Smithsonian Tropical Research Center in Panama are trying to fight one species of grass in Panama that is wreaking havoc on the country's tropical biodiversity.

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The post After a bulldozer unearthed five statues in Ain Ghazal, Jordan in 1984, Smithsonian conservators carefully restore these otherworldy figures appeared first on Smithsonian Insider.

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As enjoyable as scientific work can be, says entomologist Dave Roubik, its greatest satisfactions are often long delayed. He gives the best example from his career: a seventeen-year study that finally helped to change our understanding of the notorious "killer bees."

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Mark Torchin, a marine ecologist at the Smithsonian Tropical Research Institute (STRI) in Panama, talks about how he studies the parasites of invasive marine animals such as snails. Much of his research focuses on biological invasions and the dynamics between the host, the parasites and the surrounding ecosystem.

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On June 7 the Sun unleashed an spectacular solar flare with a substantial coronal mass ejection. A large cloud of plasma mushroomed up, and while some parts fell back into the Sun, most rushed off into space. The first two segments of this video are seen through the Atmospheric Imaging Assembly aboard NASA's Solar Dynamics Observatory. The AIA was developed by Smithsonian scientists.

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A short history of the Harvard-Smithsonian Center for Astrophysics

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Animal care staff at the Smithsonian Conservation Biology Institute in Front Royal, Virginia, are hand-rearing the pair of clouded leopard cubs born on March 28, increasing the chances that the cubs will be more successful at breeding later in their life.

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What's possibly the most calming yet nerve-racking job in the world? Come behind the scenes of the Smithsonian's Freer Gallery of Art to find out!

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School's nearly back in session, but the seven young lions at the Smithsonian's National Zoo have been working hard through the summer months!

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The post The amazing story of adaptation and survival in our species, Homo sapiens. appeared first on Smithsonian Insider.

The post Smithsonian conservators open 2001 Jim Thorpe Wheaties Box from the Smithsonian’s National Museum of the American Indian appeared first on Smithsonian Insider.

This film is from the collections of the Human Studies Film Archives, Smithsonian Institution. Clip from silent film, Beautiful Japan (1917-18), by travel-lecturer Benjamin Brodsky. Benten Festival is celebrated on Shiraishi Island. Benten (Benzaiten) is the Goddess of the Sea and one of the Seven Lucky Gods of Japan.

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Silent black & white archival film clip from "Japan: Promotional and Theatrical Footage, ca. 1927". The full film, which is 17 minutes long, includes segments from what are believed to be a theatrical film, a promotional film and, possibly, amateur film - all of unknown origin.

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The post What will invasive round goby fish do to Great Lakes streams? Join SERC post doc Matt Kornis and find out. appeared first on Smithsonian Insider.

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The post Kepler 11: A Six-Planet Sonata by Alex Parker, postdoctoral researcher at the Harvard–Smithsonian Center for Astrophysics appeared first on Smithsonian Insider.

Most earthworms in U.S. soils aren’t native–and they are threatening America’s forests. Smithsonian ecologist Melissa McCormick explains how earthworms can be good for gardens and […]

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If a supernova vaporized Earth’s ozone layer, what would happen to life in the ocean? Smithsonian biologist Pat Neale shows how UV rays could harm […]

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This shell-less gastropod was found during the Marine Larvae course at the Smithsonian Tropical Research Institute’s Bocas del Toro Research Station. It was so unusual […]

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Seven red panda cubs were born at the Smithsonian Conservation Biology Institute! The cubs were born to mothers Nutmeg, Regan and Leo Mei. Keepers are […]

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This is a short film showing the process of the detail paint work on the conservation of the original U.S.S. Enterprise studio model. The detail […]

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Oct. 4, 2016—The Smithsonian Conservation Biology Institute welcomed an Eld’s deer fawn Oct. 2 around 4:30 p.m. Both the fawn and her mom Sienna appear […]

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Aukeran is a professional dance troupe from Basque country founded in 1997 by Edu Muruamendiaraz. The beautiful and graceful professional dancers have backgrounds in both […]

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National Air and Space Museum Curator John Anderson describes major flight innovations made possible by the Full Scale Tunnel, built in 1931 at the National […]

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At age 19, athlete Amy Purdy had both legs amputated below the knee due to a sudden illness that culminated in septic shock. Two years […]

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The circus is coming to the Smithsonian! The Big Top went up on the National Mall this week in preparation for the 2017 Smithsonian Folklife […]

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For more than twenty years, Vaquero, a monumental sculpture by Luis Jiménez, has greeted visitors as they enter the Smithsonian American Art Museum. Art conservator […]

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 Blues singer and pianist Marcia Ball performs “Louella” at the 2008 Smithsonian Folklife Festival.      

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