With a non-stop babble of hums, grunts and shrill squeals as they argue over fish and defend their territories, the Amazon’s giant otters are one […]

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Smithsonian scientists have joined NASA and other organizations this summer to do something incredible: launch a spacecraft, the Parker Solar Probe, into space and have […]

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l-Hydroxyproline (l-Hyp) is a nonstandard amino acid that is present in certain proteins, in some antibiotics and in the cell-wall components of plants. l-Hyp is the product of the post-translational modification of protein prolines by prolyl hydroxylase enzymes, and the isomers trans-3-hydroxy-l-proline (T3LHyp) and trans-4-hydroxy-l-proline (T4LHyp) are major components of mammalian collagen. T4LHyp follows two distinct degradation pathways in bacteria and mammals, while T3LHyp is metabolized by a two-step metabolic pathway that is conserved in bacteria and mammals, which involves a T3LHyp dehydratase and a Δ1-pyrroline-2-carboxylate (Pyr2C) reductase. In order to shed light on the structure and catalysis of the enzyme involved in the second step of the T3LHyp degradation pathway, the crystal structure of Pyr2C reductase from the archaeon Thermococcus litoralis DSM 5473 complexed with NADH and l-proline is presented. The model allows the mapping of the residues involved in cofactor and product binding and represents a valid model for rationalizing the catalysis of Pyr2C reductases.

The biological processes related to protein homeostasis in Mycobacterium tuberculosis, the etiologic agent of tuberculosis, have recently been established as critical pathways for therapeutic intervention. Proteins of particular interest are ClpC1 and the ClpC1–ClpP1–ClpP2 proteasome complex. The structure of the potent antituberculosis macrocyclic depsipeptide ecumicin complexed with the N-terminal domain of ClpC1 (ClpC1-NTD) is presented here. Crystals of the ClpC1-NTD–ecumicin complex were monoclinic (unit-cell parameters a = 80.0, b = 130.0, c = 112.0 Å, β = 90.07°; space group P21; 12 complexes per asymmetric unit) and diffracted to 2.5 Å resolution. The structure was solved by molecular replacement using the self-rotation function to resolve space-group ambiguities. The new structure of the ecumicin complex showed a unique 1:2 (target:ligand) stoichiometry exploiting the intramolecular dyad in the α-helical fold of the target N-terminal domain. The structure of the ecumicin complex unveiled extensive interactions in the uniquely extended N-terminus, a critical binding site for the known cyclopeptide complexes. This structure, in comparison with the previously reported rufomycin I complex, revealed unique features that could be relevant for understanding the mechanism of action of these potential antituberculosis drug leads. Comparison of the ecumicin complex and the ClpC1-NTD-L92S/L96P double-mutant structure with the available structures of rufomycin I and cyclomarin A complexes revealed a range of conformational changes available to this small N-terminal helical domain and the minor helical alterations involved in the antibiotic-resistance mechanism. The different modes of binding and structural alterations could be related to distinct modes of action.

Mycoplasma hyopneumoniae is a prokaryotic pathogen that colonizes the respiratory ciliated epithelial cells in swine. Infected animals suffer respiratory lesions, causing major economic losses in the porcine industry. Characterization of the immunodominant membrane-associated proteins from M. hyopneumoniae may be instrumental in the development of new therapeutic approaches. Here, the crystal structure of P46, one of the main surface-antigen proteins, from M. hyopneumoniae is presented and shows N- and C-terminal α/β domains connected by a hinge. The structures solved in this work include a ligand-free open form of P46 (3.1 Å resolution) and two ligand-bound structures of P46 with maltose (2.5 Å resolution) and xylose (3.5 Å resolution) in open and closed conformations, respectively. The ligand-binding site is buried in the cleft between the domains at the hinge region. The two domains of P46 can rotate with respect to each other, giving open or closed alternative conformations. In agreement with this structural information, sequence analyses show similarities to substrate-binding members of the ABC transporter superfamily, with P46 facing the extracellular side as a functional subunit. In the structure with xylose, P46 was also bound to a high-affinity (Kd = 29 nM) Fab fragment from a monoclonal antibody, allowing the characterization of a structural epitope in P46 that exclusively involves residues from the C-terminal domain. The Fab structure in the complex with P46 shows only small conformational rearrangements in the six complementarity-determining regions (CDRs) with respect to the unbound Fab (the structure of which is also determined in this work at 1.95 Å resolution). The structural information that is now available should contribute to a better understanding of sugar nutrient intake by M. hyopneumoniae. This information will also allow the design of protocols and strategies for the generation of new vaccines against this important swine pathogen.

As command module pilot for the Apollo 15 mission to the moon in 1971, Al Worden spent six days orbiting the moon, including three days completely alone, the most isolated human in existence. In Falling to Earth, Worden tells for the first time the full story around the dramatic events that shook NASA and ended his spaceflight career.

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Christian Renz, Veronique Albanese, Vera Tröster, Thomas K. Albert, Olivier Santt, Susan C. Jacobs, Anton Khmelinskii, Sebastien Leon, and Helle D. Ulrich

Polyubiquitin chains linked via lysine (K) 63 play an important role in endocytosis and membrane trafficking. Their primary source is the ubiquitin protein ligase (E3) Rsp5/NEDD4, which acts as a key regulator of membrane protein sorting. The heterodimeric ubiquitin-conjugating enzyme (E2), Ubc13-Mms2, catalyses K63-specific polyubiquitylation in genome maintenance and inflammatory signalling. In budding yeast, the only ubiquitin protein ligase (E3) known to cooperate with Ubc13-Mms2 so far is a nuclear RING finger protein, Rad5, involved in the replication of damaged DNA. We now report a contribution of Ubc13-Mms2 to the sorting of membrane proteins to the yeast vacuole via the multivesicular body (MVB) pathway. In this context, Ubc13-Mms2 cooperates with Pib1, a FYVE-RING finger protein associated with internal membranes. Moreover, we identified a family of membrane-associated FYVE-(type)-RING finger proteins as cognate E3s for Ubc13-Mms2 in several species, and genetic analysis indicates that the contribution of Ubc13-Mms2 to membrane trafficking in budding yeast goes beyond its cooperation with Pib1. Thus, our results widely implicate Ubc13-Mms2 as an Rsp5-independent source of K63-linked polyubiquitin chains in the regulation of membrane protein sorting.

Hem Sapkota, Jonathan D. Wren, and Gary J. Gorbsky

Centrosomes focus microtubules to promote mitotic spindle bipolarity, a critical requirement for balanced chromosome segregation. Comprehensive understanding of centrosome function and regulation requires a complete inventory of components. While many centrosome components have been identified, others may yet remain undiscovered. We have used a bioinformatics approach, based on "guilt by association" expression to identify novel mitotic components among the large group of predicted human proteins that have yet to be functionally characterized. Here we identify Chondrosarcoma-Associated Gene 1 (CSAG1) in maintaining centrosome integrity during mitosis. Depletion of CSAG1 disrupts centrosomes and leads to multipolar spindles more effectively in cells with compromised p53 function. Thus, CSAG1 may reflect a class of "mitotic addiction" genes whose expression is more essential in transformed cells.

Björn Eismann, Teresa G. Krieger, Jürgen Beneke, Ruben Bulkescher, Lukas Adam, Holger Erfle, Carl Herrmann, Roland Eils, and Christian Conrad

3D cell cultures enable the in vitro study of dynamic biological processes such as the cell cycle, but their use in high-throughput screens remains impractical with conventional fluorescent microscopy. Here, we present a screening workflow for the automated evaluation of mitotic phenotypes in 3D cell cultures by light-sheet microscopy. After sample preparation by a liquid handling robot, cell spheroids are imaged for 24 hours in toto with a dual-view inverted selective plane illumination microscope (diSPIM) with a much improved signal-to-noise ratio, higher imaging speed, isotropic resolution and reduced light exposure compared to a spinning disc confocal microscope. A dedicated high-content image processing pipeline implements convolutional neural network based phenotype classification. We illustrate the potential of our approach by siRNA knock-down and epigenetic modification of 28 mitotic target genes for assessing their phenotypic role in mitosis. By rendering light-sheet microscopy operational for high-throughput screening applications, this workflow enables target gene characterization or drug candidate evaluation in tissue-like 3D cell culture models.

Julian Chollet, Alexander Dünkler, Anne Bäuerle, Laura Vivero-Pol, Medhanie A. Mulaw, Thomas Gronemeyer, and Nils Johnsson

Yeast cells select the position of their new bud at the beginning of each cell cycle. The recruitment of the septins to this prospective bud site is one of the critical events in a complex assembly pathway that culminates in the outgrowth of a new daughter cell. Hereby, the septin-rods follow the high concentration of Cdc42_GTP that is generated by the focused localization of its GEF Cdc24. We show that shortly before budding Cdc24 not only activates Cdc42 but also transiently interacts with Cdc11, the septin subunit that caps both ends of the septin rods. Mutations in Cdc24 reducing the affinity to Cdc11 impair septin recruitment and decrease the stability of the polarity patch. The interaction between septins and Cdc24 thus reinforces bud assembly at sites where septin structures are formed. Once the septins polymerize into the ring, Cdc24 is found at the cortex of the bud and directs its further outgrowth from this position.

The Hope Diamond’s red glow has long been considered a unique property of that stone. Most blue diamonds produce a bluish-white phosphorescence if exposed to ultraviolet light. The few other diamonds known to emit red phosphorescence were commonly assumed to have been from the even larger original stone from which the Hope was cut.

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Smithsonian Institution Libraries has recently acquired a rare first edition of Darwin's Geological Observations on the Volcanic Islands, Visited During the Voyage of the H.M.S. Beagle.

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The prehistoric Xenicibis used its wings like two clubs hinged at the wrist joint in order to swing at and attack one another.

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Left to themselves, coastal wetlands can adapt to sea-level rise. But humans could be sabotaging some of their best defenses, according to a review paper […]

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Odile Madden knows a lot about plastic. A materials scientist with the Smithsonian Museum Conservation Institute, she has spent the past eight years studying plastics […]

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On Monday, Aug. 21, beginning shortly after 9 a.m. Pacific Time, the sky will darken across North America as the moon’s orbit carries it between […]

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Under the anomalous transmission condition in the Bragg mode, X-ray interference fringes were observed between two beams with different hyperbolic trajectories in a very weakly bent plane-parallel perfect crystal with negative strain gradient. The origin of the fringes was analysed based on the dynamical theory of diffraction for a distorted crystal. In the reflected beam from the entrance surface, the interference fringes were observed between once- and twice-reflected beams from the back surface. In the transmitted beam from the back surface, the interference fringes were observed between the direct beam and once-reflected beam from the entrance surface. In the emitted beam from the lateral surface, the interference fringes were observed between the beams after different numbers of reflections in the crystal. The multiply reflected beams were formed by a combined result of long propagation length along the beam direction with large divergence of the refracted beams when the strain gradient was negative. The period of these interference fringes was sensitive to very weak strain, of the order of 10−7.

Chip Clark came to the Smithsonian's National Museum of Natural History in 1973, with a degree in biology and an interest in photography. He has been a photographer on staff ever since, documenting thousands of specimens and exhibits, and accompanying scientists on research trips around the world. He died June 12, 2010. This video interview was made by Lauren Dare, an intern with the Smithsonian Institution Archives, on May 27, 2010, as part of an oral history project for the National Museum of Natural History's Centennial (2010-2011). To learn more about Chip Clark, see his page on the Centennial website-- www.mnh.si.edu/onehundredyears/profiles/Chip_Clark.html -- where you also can find more videos and stories about the people and the work of the NMNH.

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Jim Zimbelman, planetary geologist in the Center for Earth and Planetary Studies at the Smithsonian’s National Air and Space Museum, shares his three favorite images from the exhibition "Beyond: Visions of Our Solar System.” On view at the Air and Space Museum through May 2, 2011, the exhibition by artist Michael Benson combines art, science, photography and exploration to unveil the diverse landscapes found on the planets in our Solar System.

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The post Learn about the ash that comes from volcanoes with Dr. Liz Cottrell, a geologist from the National Museum of Natural History appeared first on Smithsonian Insider.

The post With the recent hatching of two Cuban crocodiles, the National Zoo just got a little snappier! appeared first on Smithsonian Insider.

The nation’s top bird science and conservation groups have come together to publish The State of the Birds 2014—the most comprehensive review of long-term trend […]

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Cooper Hewitt, Smithsonian Design Museum, the only museum in the U.S. devoted exclusively to design, reopens after a 3-year makeover with 60 percent more exhibition […]

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The Smithsonian Deep Reef Observation Project (DROP) captures a new species of deep-reef fish, the Godzilla goby, using the Curasub submersible. The lead scientist on […]

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Gwen Ifill sat down with Lonnie Bunch, the director of the Smithsonian Museum of African American History and Culture, which is due to open this […]

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Meet Nick Pyenson, one of our paleontologists at the National Museum of Natural History. His job as a time traveler is to make discoveries about […]

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Meet Amy Homma, the Director of Digital Learning at Art Lab+. Learn how Smithsonian’s Hirshhorn Museum and Sculpture Garden has created a dynamic program to […]

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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 Emeco Alfi Chair is on view as part of ‘Making | Breaking New Arrivals,’ at Cooper Hewitt, Smithsonian Design Museum May–October, 2017. To learn […]

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The storage and flux of terrestrial carbon (C) is one of the most uncertain components of the global C budget and detailed quantification of forest […]

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New results from a massive study at the Smithsonian Tropical Research Institute show that interactions among community members play an important role in determining which organisms thrive.

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For the first time researchers from the Smithsonian, South Dakota State University and the University of Nebraska described the immature stages of the switchgrass moth, first collected in Denver in 1910.

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Recently a team of scientists working at the Smithsonian’s Tropical Research Institute in Panama, decided to try and learn for the first time just which body parts the gliding ant C. atratus uses to steer as they glide.

The post Gliding ants steer with hind legs as they fly backwards, scientists learn appeared first on Smithsonian Insider.

The scientists staked out dozens of the gingers night and day while the plants flowered, but no long-proboscid pollinator ever appeared. Climate change, they surmised, was responsible for the loss of this highly specialized and now, perhaps forever unknown insect.

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The post Community ecologist Sunshine Van Bael explains her work in Panama with leafcutting ants appeared first on Smithsonian Insider.

The chief appeal of The Anatomy of Palms is some 800 color photographs that document the extent of palm anatomical diversity.

The post With 800 color photographs, new book takes a fascinating look inside palms appeared first on Smithsonian Insider.

The Smithsonian Environmental Research Center has created NEMESIS--National Estuarine and Marine Exotic Species Information System--an online public database that provides key information about the non-native marine species throughout the United States.

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Despite many laws to protect it, a new survey reveals wild ginseng in Maryland is on the decline.

The post Wild ginseng in steep decline in Maryland, survey reveals: Q&A with Smithsonian botanist Christopher Puttock appeared first on Smithsonian Insider.

Scientific inspiration springs from many sources. In the case of Smithsonian botanist David Kenfack, ant bites were the inspiration for a recent paper he co-authored […]

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