For the first time, astronomers have detected around a burgeoning solar system a sprawling cloud of water vapor that’s cold enough to form comets, which could eventually deliver oceans to dry planets.

The post Frigid water cloud may be source of water delivered to dry planets by comets appeared first on Smithsonian Insider.

Smithsonian Secretary Wayne Clough, left, talks with Carlos Jaramillo, scientist at the Smithsonian Tropical Research Institute in Panama, at a research site near the Panama […]

The post Wayne Clough & Carlos Jaramillo, at a research site near the Panama Canal. appeared first on Smithsonian Insider.

Observations by the NASA/ESA Hubble Space Telescope have come up with a new class of planet, a waterworld enshrouded by a thick, steamy atmosphere. It’s smaller than Uranus but larger than Earth.

The post Waterworld enshrouded by a thick, steamy atmosphere is new class of planet appeared first on Smithsonian Insider.

The fastest wind ever discovered blowing off a disk around a stellar-mass black hole has been observed by a team of astronomers using NASA’s Chandra X-ray Observatory.

The post Chandra X-ray Observatory clocks stellar wind at 20 million mph appeared first on Smithsonian Insider.

Paleontologists studying an extreme short-term global warming event have discovered direct evidence about how mammals respond to rising temperatures. In a study that appeared recently […]

The post Evolution of earliest horses driven by climate change appeared first on Smithsonian Insider.

A recent decline in Ovenbirds (Seiurus aurocapilla), a ground-nesting migratory songbird, in forests in the northern Midwest United States is being linked by scientists to a seemingly unlikely culprit: earthworms.

The post Earthworms to blame for decline of Ovenbirds in northern Midwest forests, study reveals appeared first on Smithsonian Insider.

The Sun’s Active Region 1429 has been shooting off flares and coronal mass ejections since it rotated into Earth’s view on March 2, 2012. Two X-class flares have been released overnight, an X1.3 and an X5.4.

The post X-Class flares released by the Sun, March 6, captured by Atmospheric Imaging Assembly appeared first on Smithsonian Insider.

One problem in unraveling the mystery of quasars is that many (perhaps most) quasar nuclei seem to be surrounded by a torus of obscuring dust that makes them difficult to study.

The post The origins of a torus in a galactic nucleus appeared first on Smithsonian Insider.

This composite image from the Chandra X-ray Observatory (operated for NASA by the Smithsonian Astrophysical Observatory) shows the distribution of dark matter, galaxies, and hot […]

The post Chandra image of the core of the merging galaxy cluster Abell 520 appeared first on Smithsonian Insider.

16,000 square kilometers of giant panda habitat will likely be lost by the year 2080

The post Panda habitat to be lost, shifted by climate change appeared first on Smithsonian Insider.

The only explanation for such symmetry across these vast distances, explains Smithsonian anthropologist Dennis Stanford, is that the method of creating the points was handed down from person to person.

The post 3-D imaging adds remarkable new understanding of North America’s mysterious Clovis people appeared first on Smithsonian Insider.

The specimen’s skull measures 24 centimeters, roughly the size of a regulation NFL football. The shell which was recovered nearby – and is believed to belong to the same species – measures 172 centimeters, or about 5 feet 7 inches, long.

The post Giant prehistoric turtle from Colombia chomped everything in sight–including crocodiles! appeared first on Smithsonian Insider.

Imagine a gas giant planet spanning three times more sky than the Moon looming over the molten landscape of a lava world. This alien vista exists in the newly discovered two-planet system of Kepler-36.

The post Close encounters between planetary systems of Kepler-36 stun astrophysicists appeared first on Smithsonian Insider.

Scientists determine there is more to the shape and length of bird bills than just how they “get the worm.”

The post New study determines bill size in birds varies according to climate appeared first on Smithsonian Insider.

Justin Touchon, post-doctoral fellow at the Smithsonian Tropical Research Institute, discovered that climate change in Panama may be altering frogs’ course of evolution.

The post Climate change may alter amphibian evolution appeared first on Smithsonian Insider.

The newest additions at the Reptile Discovery Center at the Smithsonian’s National Zoo are eight tentacled snakes, born Oct. 21 to parents that have not produced viable […]

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Cheeseburgers. Ice cream. French fries. These are a few of the culprits, doctors warn us, responsible for atherosclerosis, a disease commonly known as hardening of […]

The post Ancient mummies reveal atherosclerosis is very likely just a part of aging appeared first on Smithsonian Insider.

All stars begin their lives in groups. Most stars, including our Sun, are born in small, benign groups that quickly fall apart. Others form in […]

The post First transiting planets in a star cluster discovered appeared first on Smithsonian Insider.

For the first time since exoplanets, or planets around stars other than the sun, were discovered almost 20 years ago, X-ray observations have detected an […]

The post NASA’s Chandra sees eclipsing planet in X-rays for first time appeared first on Smithsonian Insider.

A groundbreaking study by Harvard University’s Harvard Forest and the Smithsonian Conservation Biology Institute reveals that, if left unchecked, recent trends in the loss of […]

The post Sprawl threatens water quality, climate protection, and land conservation in Massachusetts appeared first on Smithsonian Insider.

W49A might be one of the best-kept secrets in our galaxy. This star-forming region shines 100 times brighter than the Orion nebula, but is so […]

The post SMA reveals giant star cluster in the making appeared first on Smithsonian Insider.

Paddling the remote oxbow lakes and bayous of the White River National Wildlife Refuge in Arkansas, the team of scientists was seeking proof of a […]

The post Nest discovery turns back the clock to days of Daniel Boone and Colonial America appeared first on Smithsonian Insider.

A new species of mite discovered recently in Ohio is so tiny that it lives in the space between particles in sandy, impoverished soils. Despite […]

The post New dragon-like mite found in Ohio is gentle, reclusive appeared first on Smithsonian Insider.

A new study of gamma-ray light from the center of our galaxy makes the strongest case to date that some of this emission may arise […]

The post Fermi data offer clues to dark matter appeared first on Smithsonian Insider.

The galaxy known as M87 has a fastball that would be the envy of any baseball pitcher. It has thrown an entire star cluster toward […]

The post Star cluster thrown out of its galaxy appeared first on Smithsonian Insider.

The clouded leopard, a native of Southeast Asia, is among the most charismatic, secretive and least understood cat species in the world. In 2002, the […]

The post Clouded leopards, from crisis to success: Q&A with Janine Brown appeared first on Smithsonian Insider.

The Smithsonian’s National Air and Space Museum has acquired a large collection from the Sir Arthur C. Clarke Trust. The collection consists of 87 cubic […]

The post Arthur C. Clarke papers come to Air and Space Museum Archives appeared first on Smithsonian Insider.

Skygazers at northern latitudes are familiar with the W-shaped star pattern of Cassiopeia the Queen. This circumpolar constellation is visible year-round near the North Star. […]

The post CASSIOPEIA’S HIDDEN GEM: THE CLOSEST ROCKY, TRANSITING PLANET appeared first on Smithsonian Insider.

Since researchers began surveys in the 1980s, coral reefs in the Caribbean have undergone widespread change following bleaching and disease epidemics that have reduced the […]

The post Study reveals Agriculture and Fishing Cause Coral Reef Decline appeared first on Smithsonian Insider.

Tucked away on the lower levels of the Smithsonian’s National Museum of Natural History and National Museum of American History are some of science’s most […]

The post Smithsonian Libraries’ rare texts include early superstars of science appeared first on Smithsonian Insider.

Globular star clusters are extraordinary in almost every way. They’re densely packed, holding a million stars in a ball only about 100 light-years across on […]

The post Globular Clusters Could Nurture Interstellar Civilizations appeared first on Smithsonian Insider.

For the past 50 years, the number of wood thrush (Hylocichla mustelina) that breed in the United States has decreased more than 60 percent. However, […]

The post Smithsonian Scientists Solve Puzzle of Dramatic Wood Thrush Decline appeared first on Smithsonian Insider.

The planet’s last stronghold of wild cheetahs (Acinonyx jubatus) is losing genetic diversity at an alarming rate according to a new study from the Smithsonian […]

The post Smithsonian Study reveals Decline of Genetic Diversity in Wild Cheetahs appeared first on Smithsonian Insider.

Amid efforts to restore native oyster populations on the West Coast, how are oysters expected to fare under climate change in the decades and centuries […]

The post Climate Change May Benefit Native Oysters, but There’s a Catch appeared first on Smithsonian Insider.

Crustaceans that thrive in the vastness of the open ocean have no place to hide from their predators. Consequently, many creatures that live at depths […]

The post Tiny ocean crustaceans wear invisibility cloak of living bacteria appeared first on Smithsonian Insider.

When the heat and humidity of the Washington, D.C. summer sends its residents scrambling for air conditioning and iced coffee, the animal care specialists at […]

The post How do National Zoo animals beat the heat? Bloodsicles and other frozen delicacies appeared first on Smithsonian Insider.

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.

Supplying archaeological and oceanographic evidence, this book persuasively links Clovis technology with the culture of the Solutrean people who occupied France and Spain more than 20,000 years ago.

The post New Book: “Across Atlantic Ice : The Origin of America’s Clovis Culture” appeared first on Smithsonian Insider.

This Secret Smithsonian Adventures series follows four middle schoolers as they foil events by two dastardly doers who try to dangerously change the true course […]

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Yinlong Song, Yikan Zhang, Ying Pan, Jianfeng He, Yan Wang, Wei Chen, Jing Guo, Haiteng Deng, Yi Xue, Xianyang Fang, and Xin Liang

Microtubules dynamics is regulated by the plus end-tracking proteins (+TIPs) in cells. End binding protein 1 (EB1) acts as a master regulator in +TIPs networks by targeting microtubule growing ends and recruiting other factors. However, the molecular mechanism of how EB1 binds to microtubule ends with a high affinity remains to be an open question. Using single-molecule imaging, we show that the end-binding kinetics of EB1 changes along with the polymerizing and hydrolysis rate of tubulin dimers, confirming the binding of EB1 to GTP/GDP-Pi tubulin at microtubule growing ends. The affinity of wild-type EB1 to these sites is higher than monomeric EB1 mutants, suggesting that two CH domains in the dimer contribute to the end-binding. Introducing phosphomimicking mutations into the linker domain of EB1 weakens the end-binding affinity and confers a more curved conformation to EB1 dimer without compromising dimerization, suggesting that the overall architecture of EB1 is important for the end-binding affinity. Taken together, our results provide insights into understanding how the high-affinity end-binding of EB1 can be achieved and how this activity may be regulated in cells.

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.

Scott J. Neal, Qingxiang Zhou, and Francesca Pignoni

The specification of organs, tissues and cell types results from cell fate restrictions enacted by nuclear transcription factors under the control of conserved signaling pathways. The progenitor epithelium of the Drosophila compound eye, the eye imaginal disc, is a premier model for the study of such processes. Early in development, apposing cells of the eye disc are established as either retinal progenitors or support cells of the peripodial epithelium (PE), in a process whose genetic and mechanistic determinants are poorly understood. We have identified Protein Phosphatase 2A (PP2A), and specifically a STRIPAK-PP2A complex that includes the scaffolding and substrate-specificity components Cka, Strip and SLMAP, as a critical player in the retina-PE fate choice. We show that these factors suppress ectopic retina formation in the presumptive PE and do so via the Hippo signaling axis. STRIPAK-PP2A negatively regulates Hpo kinase, and consequently its substrate Wts, to release the transcriptional co-activator Yki into the nucleus. Thus, a modular higher-order PP2A complex refines the activity of this general phosphatase to act in a precise specification of cell fate.

Archan Chakraborty, Wei-Cheng Lin, Yu-Tsun Lin, Kuang-Jing Huang, Pei-Yu Wang, Yi-Feng Chang, Hsiang-Iu Wang, Kung-Ting Ma, Chun-Yen Wang, Xuan-Rong Huang, Yen-Hsien Lee, Bi-Chang Chen, Ya-Ju Hsieh, Kun-Yi Chien, Tzu-Yang Lin, Ji-Long Liu, Li-Ying Sung, Jau-Song Yu, Yu-Sun Chang, and Li-Mei Pai

Under metabolic stress, cellular components can assemble into distinct membraneless organelles for adaptation. One such example is cytidine 5'-triphosphate synthase (CTPS), which forms filamentous structures under glutamine deprivation. We have previously demonstrated that histidine (His)-mediated methylation regulates the formation of CTPS filaments to suppress enzymatic activity and preserve the CTPS protein under Gln deprivation, which promotes cancer cell growth after stress alleviation. However, it remains unclear where and how these enigmatic structures are assembled. Using CTPS-APEX2-mediated in vivo proximity labeling, we found that SNAP29 regulates the spatiotemporal filament assembly of CTPS along the cytokeratin network in a keratin 8 (KRT8)-dependent manner. Knockdown of synaptosome-associated protein 29 (SNAP29) interfered with assembly and relaxed the filament-induced suppression of CTPS enzymatic activity. Furthermore, APEX2 proximity labeling of keratin 18 (KRT18) revealed a spatiotemporal association of SNAP29 with cytokeratin in response to stress. Super-resolution imaging suggests that during CTPS filament formation, SNAP29 interacts with CTPS along the cytokeratin network. This study links the cytokeratin network to the regulation of metabolism by compartmentalization of metabolic enzymes during nutrient deprivation.

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.

Laura O'Regan, Giancarlo Barone, Rozita Adib, Chang Gok Woo, Hui Jeong Jeong, Emily L. Richardson, Mark W. Richards, Patricia A.J. Muller, Spencer J. Collis, Dean A. Fennell, Jene Choi, Richard Bayliss, and Andrew M. Fry

EML4-ALK is an oncogenic fusion present in ~5% non-small cell lung cancers. However, alternative breakpoints in the EML4 gene lead to distinct variants with different patient outcomes. Here, we show in cell models that EML4-ALK variant 3 (V3), which is linked to accelerated metastatic spread, causes microtubule stabilization, formation of extended cytoplasmic protrusions and increased cell migration. It also recruits the NEK9 and NEK7 kinase to microtubules via the N-terminal EML4 microtubule-binding region. Overexpression of wild-type EML4 as well as constitutive activation of NEK9 also perturb cell morphology and accelerate migration in a microtubule-dependent manner that requires the downstream kinase NEK7 but not ALK activity. Strikingly, elevated NEK9 expression is associated with reduced progression-free survival in EML4-ALK patients. Hence, we propose that EML4-ALK V3 promotes microtubule stabilization through NEK9 and NEK7 leading to increased cell migration. This represents a novel actionable pathway that could drive metastatic disease progression in EML4-ALK lung cancer.

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.

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.