A social media celebrity was born last week when the bright lights and camera of NOAA’s remotely operated vehicle Deep Discoverer zoomed in on a […]

The post Ghost octopod shows how little we know about deep-sea life appeared first on Smithsonian Insider.

Pop quiz! Name the first five dinosaurs that come to mind. Chances are good that one you named was Tyrannosaurs rex, a popular favorite perhaps best […]

The post New horse-sized tyrannosaur with big brain reveals how “T. rex” became top predator appeared first on Smithsonian Insider.

It is rare but not entirely uncommon to see a manatee swimming in the Atlantic waters of Maryland and Virginia. This one was dead, however, […]

The post In face of mass extinctions, Smithsonian’s Global Genome Initiative quietly saves world’s DNA appeared first on Smithsonian Insider.

Ten years ago, cownose rays in the Atlantic got a bad rap when this species (Rhinoptera bonasus) was accused of excessively eating up scallops in […]

The post Cownose Rays Aquitted: Not Guilty of Decimating Chesapeake Oysters appeared first on Smithsonian Insider.

Seven fossil teeth exposed by the Panama Canal expansion project are the first evidence of a monkey on the North American continent before the Isthmus […]

The post First North American Monkey Fossils Found in Panama Canal Excavation appeared first on Smithsonian Insider.

When is a blue bird not blue? The answer to this question is always. There actually is no such thing as a blue bird. To find […]

The post When Is a Blue Bird Not Blue? appeared first on Smithsonian Insider.

Earlier this year scientists presented evidence for Planet Nine, a Neptune-mass planet in an elliptical orbit 10 times farther from our Sun than Pluto. Since […]

The post Planet 9: A world that should not exist appeared first on Smithsonian Insider.

Astronomers announced today that they have found the organic molecule methyl alcohol, or methanol, in the TW Hydrae protoplanetary disk. This is the first such […]

The post Methanol reveals comets forming in distant solar system appeared first on Smithsonian Insider.

Thanks to a recent reassessment of specimens preserved in jars of alcohol at the Smithsonian’s National Museum of Natural History, New Hampshire is now on […]

The post Discovery in Smithsonian collection broadens understanding of rare North American leech appeared first on Smithsonian Insider.

Space: the final frontier. These are the voyages of the Starship Enterprise…and you know the rest, probably even if you’re not a huge fan of […]

The post Five things only a conservator would know about the USS Enterprise appeared first on Smithsonian Insider.

 The distant planet GJ 1132b intrigued astronomers when it was discovered last year. Located just 39 light-years from Earth, it might have an atmosphere despite […]

The post Venus-like Exoplanet Might Have Oxygen Atmosphere, But Not Life appeared first on Smithsonian Insider.

Keith Gagnon, a 9-year-old fascinated by birds, talks about the importance of bird conservation and why birds really matter. Step outside your house in the […]

The post Why Birds Really Matter: Keith Gagnon appeared first on Smithsonian Insider.

Like many predators, the fringe-lipped bat primarily uses its hearing to find its prey, but with human-generated noise on the rise, scientists are examining how […]

The post Bats Use Second Sense to Hunt Prey in Noisy Environments appeared first on Smithsonian Insider.

Perhaps puppies cuddling in the snow makes winter’s bite not so unpleasant? In one of his most charming designs, Japanese artist Isoda Koryūsai (1735–1790) depicted […]

The post Snow puppies appeared first on Smithsonian Insider.

The 11 farthest known stars in our galaxy are located about 300,000 light-years from Earth, well outside the Milky Way’s spiral disk. New research by […]

The post Farthest Milky Way stars might be ripped from another galaxy appeared first on Smithsonian Insider.

Fast radio bursts (FRBs) are brief spurts of radio emission, lasting just one-thousandth of a second, whose origins are mysterious. Fewer than two dozen have […]

The post Astronomers propose cell phone search for galactic radio bursts appeared first on Smithsonian Insider.

For more than 60 years, researchers have tried to successfully cryopreserve (or freeze) the embryo of zebrafish, a species that is an important medical model […]

The post Gold nanotechnology and lasers used to successfully freeze fish embryos appeared first on Smithsonian Insider.

The next time you swat a fly ponder this: inside its belly is the DNA of whatever it ate before landing on your picnic dinner—roadkill, […]

The post Innovation: Belly gunk from flies used to survey forest animals appeared first on Smithsonian Insider.

Three former scientists from the Smithsonian’s National Zoological Park–Ellen Lamirande, Don Nichols, and Allan Pessier–were honored at the sixth annual Golden Goose Award ceremony at […]

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This animation shows how binary neutron stars warp space-time to create gravitational waves, then collide and explode into a visible kilonova, which can be detected […]

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A bat specimen collected in France at the end of World War I, since housed in the collections of the Smithsonian’s National Museum of Natural […]

The post DNA on 100-year-old bat from France may help fight deadly fungus in North America appeared first on Smithsonian Insider.

The next generation of the Sloan Digital Sky Survey (SDSS-V), directed by Juna Kollmeier of the Carnegie Institution for Science, will move forward with mapping […]

The post Next generation astronomical survey to map the entire sky appeared first on Smithsonian Insider.

“Somber” is the adjective Smithsonian beetle expert Terry Erwin uses to describe the insects he collects on the forest floor in Peru and Ecuador. “They […]

The post Meet the newest New World canopy beetle species. ‘Gazillions’ await discovery. appeared first on Smithsonian Insider.

There are currently more than 3,500 confirmed known exoplanets thanks to the remarkable sensitivity of the Kepler spacecraft and to technological advances in space and […]

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Poaching wasn’t the largest conservation concern for Asian elephants, an endangered species, until satellite tracking stunned researchers. Scientists at the Smithsonian Conservation Biology Institute (SCBI) […]

The post Poachers are killing endangered Asian elephants for their skin and meat, not their tusks appeared first on Smithsonian Insider.

When a natural disaster strikes, it devastates lives and homes, and can even destroy a culture’s identity and history. After a disaster, humanitarian response is […]

The post Protecting Puerto Rico’s heritage from another disaster appeared first on Smithsonian Insider.

Death-associated protein kinase 1 (DAPK1) is a serine/threonine protein kinase that regulates apoptosis and autophagy. DAPK1 is considered to be a therapeutic target for amyloid-β deposition, endometrial adenocarcinomas and acute ischemic stroke. Here, the potent inhibitory activity of the natural anthraquinone purpurin against DAPK1 phosphorylation is shown. Thermodynamic analysis revealed that while the binding affinity of purpurin is similar to that of CPR005231, which is a DAPK1 inhibitor with an imidazopyridazine moiety, the binding of purpurin was more enthalpically favorable. In addition, the inhibition potencies were correlated with the enthalpic changes but not with the binding affinities. Crystallographic analysis of the DAPK1–purpurin complex revealed that the formation of a hydrogen-bond network is likely to contribute to the favorable enthalpic changes and that stabilization of the glycine-rich loop may cause less favorable entropic changes. The present findings indicate that purpurin may be a good lead compound for the discovery of inhibitors of DAPK1, and the observation of enthalpic changes could provide important clues for drug development.

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.

The new book Subsistence Economies of Indigenous North American Societies provides a comprehensive and in-depth documentation of how Native American societies met the challenges of […]

The post New book: “The Subsistence Economies of Indigenous North American Societies: A Handbook” appeared first on Smithsonian Insider.

In the first volume of the Secret Smithsonian Adventures graphic-novel series from Smithsonian Books, The Wrong Wrights, four middle-school kids visit the Smithsonian’s National Air […]

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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.

Yung-An Huang, Chih-Hsuan Hsu, Ho-Chieh Chiu, Pei-Yu Hsi, Chris T. Ho, Wei-Lun Lo, and Eric Hwang

Microtubule (MT) is the most abundant cytoskeleton in neurons and controls multiple facets of their development. While the MT-organizing center (MTOC) in mitotic cells is typically located at the centrosome, MTOC in neurons switches to non-centrosomal sites. A handful of cellular components have been shown to promote non-centrosomal MT (ncMT) formation in neurons, yet the regulation mechanism remains unknown. Here we demonstrate that the small GTPase Ran is a key regulator of ncMTs in neurons. Using an optogenetic tool that enables light-induced local production of RanGTP, we demonstrate that RanGTP promotes ncMT plus-end growth along the neurite. Additionally, we discovered that actin waves drive the anterograde transport of RanGTP. Pharmacological disruption of actin waves abolishes the enrichment of RanGTP and reduces growing ncMT plus-ends at the neurite tip. These observations identify a novel regulation mechanism of ncMTs and pinpoint an indirect connection between the actin and MT cytoskeletons in neurons.

Kasun Buddika, Ishara S. Ariyapala, Mary A. Hazuga, Derek Riffert, and Nicholas S. Sokol

Stressed cells downregulate translation initiation and assemble membrane-less foci termed stress granules (SGs). Extensively characterized in cultured cells, the existence of such structures in stressed adult stem cell pools remain poorly characterized. Here we report that Drosophila orthologs of mammalian SG components AGO1, ATX2, CAPRIN, eIF4E, FMRP, G3BP, LIN-28, PABP, and TIAR are enriched in adult intestinal progenitor cells where they accumulate in small cytoplasmic messenger ribonucleoprotein complexes (mRNPs). Treatment with sodium arsenite or rapamycin reorganized these mRNPs into large cytoplasmic granules. Formation of these intestinal progenitor stress granules (IPSGs) depended on polysome disassembly, led to translational downregulation, and was reversible. While canonical SG nucleators ATX2 and G3BP were sufficient for IPSG formation in the absence of stress, neither of them, nor TIAR, either individually or collectively, were required for stress-induced IPSG formation. This work therefore finds that IPSGs do not assemble via a canonical mechanism, raising the possibility that other stem cell populations employ a similar stress-response mechanism.

Aline A. Alves, Heloisa B. Gabriel, Maria J. R. Bezerra, Wanderley de Souza, Sue Vaughan, Narcisa L. Cunha-e-Silva, and Jack D. Sunter

Eukaryotic flagella are complex microtubule based organelles and in many organisms there are extra-axonemal structures present, including the outer dense fibres of mammalian sperm and the paraflagellar rod (PFR) of trypanosomes. Flagellum assembly is a complex process occurring across three main compartments, the cytoplasm, the transition fibre-transition zone, and the flagellum. It begins with translation of protein components, followed by their sorting and trafficking into the flagellum, transport to the assembly site and then incorporation. Flagella are formed from over 500 proteins; the principles governing axonemal component assembly are relatively clear. However, the coordination and sites of extra-axonemal structure assembly processes are less clear.

We have discovered two cytoplasmic proteins in T. brucei that are required for PFR formation, PFR assembly factors 1 and 2. Deletion of either PFR-AF1 or PFR-AF2 dramatically disrupted PFR formation and caused a reduction in the amount of major PFR proteins. The presence of cytoplasmic factors required for PFR formation aligns with the concept of processes occurring across multiple compartments to facilitate axoneme assembly and this is likely a common theme for extra-axonemal structure assembly.

Victor J. F. Kitano, Yoko Ohyama, Chiyomi Hayashida, Junta Ito, Mari Okayasu, Takuya Sato, Toru Ogasawara, Maki Tsujita, Akemi Kakino, Jun Shimada, Tatsuya Sawamura, and Yoshiyuki Hakeda

Osteoporosis is associated with vessel diseases attributed to hyperlipidemia, and bone resorption by multinucleated osteoclasts is related to lipid metabolism. In this study, we generated low-density lipoprotein receptor (LDLR)/lectin-like oxidized LDL receptor-1 (LOX-1) double knockout (dKO) mice. We found that, like LDLR single KO (sKO), LDLR/LOX-1 dKO impaired cell-cell fusion of osteoclast-like cells (OCLs). LDLR/LOX-1 dKO and LDLR sKO preosteoclasts exhibited decreased uptake of LDL. The cell surface cholesterol levels of both LDLR/LOX-1 dKO and LDLR sKO osteoclasts were lower than the levels of wild-type OCLs. Additionally, the amount of phosphatidylethanolamine (PE) on the cell surface was attenuated in LDLR/LOX-1 dKO and LDLR sKO pre-OCLs, while the PE distribution in wild-type OCLs was concentrated on the filopodia in contact with neighboring cells. Abrogation of the ATP binding cassette G1 (ABCG1) transporter, which transfers PE to the cell surface, caused decreased PE translocation to the cell surface and subsequent cell-cell fusion. The findings of this study indicate the involvement of a novel cascade (LDLR~ABCG1~PE translocation to cell surface~cell-cell fusion) in multinucleation of OCLs.

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.

Olga Kopach, Noemi Esteras, Selina Wray, Dmitri A. Rusakov, and Andrey Y. Abramov

Frontotemporal dementia and parkinsonism (FTDP-17) caused by the 10+16 splice-site mutation in the MAPT provides an established platform to model tau-related dementia in vitro. Human iPSC-derived neurons have been shown to recapitulate the neurodevelopmental profile of tau pathology during in vitro corticogenesis as in the adult human brain. However, the neurophysiological phenotype of these cells has remained unknown, leaving unanswered questions over the functional relevance and the gnostic power of this disease model. Here we used electrophysiology to explore the membrane properties and intrinsic excitability of the generated neurons to find that human cells mature by ~150 days of neurogenesis to become compatible with matured cortical neurons. In earlier FTDP-17, neurons, however, exhibited a depolarized resting membrane potential associated with increased resistance and reduced voltage-gated Na⁺- and K⁺-channel-mediated conductance. The Na_v1.6 protein was reduced in FTDP-17. These led to a reduced cell capability of induced firing and changed action potential waveform in FTDP-17. The revealed neuropathology may thus contribute to the clinicopathological profile of the disease. This sheds new light on the significance of human models of dementia in vitro.

Karolina Losenkova, Mariachiara Zuccarini, Marika Karikoski, Juha Laurila, Detlev Boison, Sirpa Jalkanen, and Gennady G. Yegutkin

Extracellular adenosine mediates diverse anti-inflammatory, angiogenic and vasoactive effects and becomes an important therapeutic target for cancer, which has been translated into clinical trials. This study was designed to comprehensively assess adenosine metabolism in prostate and breast cancer cells. We identified cellular adenosine turnover as a complex cascade, comprised of (a) the ectoenzymatic breakdown of ATP via sequential nucleotide pyrophosphatase/phosphodiesterase-1, ecto-5’-nucleotidase/CD73 and adenosine deaminase reactions, and ATP re-synthesis through counteracting adenylate kinase and nucleoside diphosphokinase; (b) the uptake of nucleotide-derived adenosine via equilibrative nucleoside transporters; and (c) the intracellular adenosine phosphorylation into ATP by adenosine kinase and other nucleotide kinases. The exposure of cancer cells to 1% O₂ for 24 hours triggered ~2-fold up-regulation of CD73, without affecting nucleoside transporters, adenosine kinase activity and cellular ATP content. The ability of adenosine to inhibit the tumor-initiating potential of breast cancer cells via receptor-independent mechanism was confirmed in vivo using a xenograft mouse model. The existence of redundant pathways controlling extracellular and intracellular adenosine provides a sufficient justification for reexamination of the current concepts of cellular purine homeostasis and signaling in cancer.

Stephen Kershaw, David J. Morgan, James Boyd, David G. Spiller, Gareth Kitchen, Egor Zindy, Mudassar Iqbal, Magnus Rattray, Chris M. Sanderson, Andrew Brass, Claus Jorgensen, Tracy Hussell, Laura C. Matthews, and David W. Ray

Glucocorticoids (GCs) act through the glucocorticoid receptor (GR) to regulate immunity, energy metabolism, and tissue repair. Upon ligand binding, activated GR mediates cellular effects by regulating gene expression, but some GR effects can occur rapidly without new transcription. We show GCs rapidly inhibit cell migration, in response to both GR agonist and antagonist ligand binding. The inhibitory effect on migration is prevented by GR knockdown with siRNA, confirming GR specificity, but not by actinomycin D treatment, suggesting a non-transcriptional mechanism. We identified a rapid onset increase in microtubule polymerisation following glucocorticoid treatment, identifying cytoskeletal stabilisation as the likely mechanism of action. HDAC6 overexpression, but not knockdown of αTAT1, rescued the GC effect, implicating HDAC6 as the GR effector. Consistent with this hypothesis, ligand-dependent cytoplasmic interaction between GR and HDAC6 was demonstrated by quantitative imaging. Taken together, we propose that activated GR inhibits HDAC6 function and thereby increases the stability of the microtubule network to reduce cell motility. We therefore report a novel, non-transcriptional mechanism whereby GCs impair cell motility through inhibition of HDAC6 and rapid reorganization of the cell architecture.

The Smithsonian’s National Museum of Natural History recently acquired four remarkable gemstones and jewelry pieces for the Smithsonian’s National Gem Collection in celebration of the 100th anniversary of the museum.

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The Smithsonian Research Online program recently surpassed the mark of 10,000 publications in the Digital Repository. This collection of digital publications by Smithsonian staff represents a broad review of research done by researchers at the Institution.

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Richard Wunderman is managing editor of the Bulletin of the Global Volcanism Network and a geologist in the Division of Mineral Sciences at the Smithsonian’s […]

The post Q&A: Smithsonian volcanologist Richard Wunderman answers questions about the Aug. 23, East Coast earthquake appeared first on Smithsonian Insider.

Restless volcano. This Feb. 10 satellite radar image shows the summit of Alaska’s Cleveland Volcano and a new lava dome within the volcano’s summit crater […]

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According to the weekly report of the Smithsonian’s Global Volcanism Program, gas-and-ash plumes rose nearly one mile above the crater of Mexico’s Popocatépetl volcano from […]

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