Imagine a place where ice cream never drips. Ice cream lovers, how far would you be willing to go to avoid that heartbreaking moment where […]

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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 […]

The post A solar probe is on its way to touch the sun. The Smithsonian built the tool that will measure the sun without melting 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.

When many people think of the Chesapeake Bay, one of the first creatures that comes to mind is the iconic blue crab. But parts of […]

The post Smithsonian scientists become shark detectives to track species in the Chesapeake Bay 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.

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.

The number of new X-ray crystallography-based submissions to the Protein Data Bank appears to be at the beginning of a decline, perhaps signalling an end to the era of the dominance of X-ray crystallography within structural biology. This letter, from the viewpoint of a young structural biologist, applies the Copernican method to the life expectancy of crystallography and asks whether the technique is still the mainstay of structural biology. A study of the rate of Protein Data Bank depositions allows a more nuanced analysis of the fortunes of macromolecular X-ray crystallography and shows that cryo-electron microscopy might now be outcompeting crystallography for new labour and talent, perhaps heralding a change in the landscape of the field.

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.

Benjamin Ziman, Peter Karabinis, Paul Barghouth, and Nestor J. Oviedo

Nutrient availability upon feeding leads to an increase in body size in the planarian Schmidtea mediterranea. However, it remains unclear how food consumption integrates with cell division at the organismal level. Here we show that Sirtuins is evolutionarily conserved in planarians and specifically demonstrate that Sirtuin-1 (Smed-Sirt-1) regulates organismal growth by impairing both feeding behavior and intestinal morphology. Disruption of Smed-Sirt-1 with either RNAi or pharmacological treatment leads to reduced animal growth. Conversely, enhancement of Smed-Sirt-1 with resveratrol accelerates growth. Differences in growth rates were associated with changes in the amount of time to locate food and overall consumption. Furthermore, Smed-Sirt-1(RNAi) animals displayed reduced cell death and increased stem cell proliferation accompanied by impaired expression of intestinal lineage progenitors and reduced branching of the gut. Altogether, our findings indicate Sirtuin-1 is a crucial metabolic hub capable of controlling animal behavior, tissue renewal and morphogenesis of the adult intestine.

Tara L. Mastro, Vishnu P. Tripathi, and Susan L. Forsburg

Translesion synthesis polymerases (TLSPs) are non-essential error-prone enzymes that ensure cell survival by facilitating DNA replication in the presence of DNA damage. In addition to their role in bypassing lesions, TLSPs have been implicated in meiotic double strand break repair in several systems. Here we examine the joint contribution of four TLS polymerases to meiotic progression in the fission yeast S. pombe. We observed the dramatic loss of spore viability in fission yeast lacking all four TLSPs which is accompanied by disruptions in chromosome segregation during meiosis I and II. Rec8 cohesin dynamics are altered in the absence of the TLSPs. These data suggest that the TLSPs contribute to multiple aspects of meiotic chromosome dynamics.

The geologic faults responsible for the rise of the eastern Andes mountains in Colombia became active 25 million years ago—18 million years before the previously accepted start date for the Andes’ rise.

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Formed some 250,000 years ago when the Nile River pushed through a low channel near Wadi Tushka, it flooded the eastern Sahara, creating a lake that at its highest level covered more than 42,000 square miles.

The post Ancient megalake discovered beneath Sahara Desert appeared first on Smithsonian Insider.

During a press conference Friday, July 22 at the Smithsonian's National Air and Space Museum, NASA announced that Gale Crater will be the landing site for the Mars Science Laboratory. Scheduled to launch in late 2011 and arrive at Mars in August 2012, the Mars Science Laboratory is a rover that will assess the planet’s “habitability”—if it ever was, or is today, an environment able to support microbial life.

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The humble salamander may provide evidence to support a controversial claim that North and South America were joined together much earlier than previously thought. The […]

The post Salamander DNA reveals evidence of older land connection between Central and South America appeared first on Smithsonian Insider.

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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What was happening (geologically speaking) on Earth way back when it was a mere babe and being showered with meteorites? Until a time machine is […]

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Oysters are keystone organisms in estuaries around the world, influencing water quality, constructing habitat and providing food for humans and wildlife. Yet their populations in […]

The post Ancient Native-American methods may be key to sustainable oyster harvests appeared first on Smithsonian Insider.

Great white sharks, killer whales, sea lions, even polar bears—the ocean is full of giant predators. But one of the ocean’s worst enemies is not […]

The post Beautiful plastic sculptures tell ugly story of human garbage in the ocean appeared first on Smithsonian Insider.

Could the universe’s earliest stars have formed planets, and if so, what might they have looked like? That was the question Harvard-Smithsonian Center for Astrophysics […]

The post Diamonds are a planet’s best friend? In the early universe, perhaps appeared first on Smithsonian Insider.

Antarctica is home to fewer insect species than anywhere else on earth. But it wasn’t always that way. A geologist digging in bluffs on Antarctica’s […]

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To the Hopewell Culture, ancient Native Americans who sought out the exotic from near and far, metal was a rare and precious resource. Copper, found […]

The post Ancient Native American beads traced to otherworldy source: an iron meteorite appeared first on Smithsonian Insider.

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.

The use of strongly bent crystals in spectrometers for pulses of a hard X-ray free-electron laser is explored theoretically. Diffraction is calculated in both dynamical and kinematical theories. It is shown that diffraction can be treated kinematically when the bending radius is small compared with the critical radius given by the ratio of the Bragg-case extinction length for the actual reflection to the Darwin width of this reflection. As a result, the spectral resolution is limited by the crystal thickness, rather than the extinction length, and can become better than the resolution of a planar dynamically diffracting crystal. As an example, it is demonstrated that spectra of the 12 keV pulses can be resolved in the 440 reflection from a 20 µm-thick diamond crystal bent to a radius of 10 cm.

A crystallographic indexing algorithm, pinkIndexer, is presented for the analysis of snapshot diffraction patterns. It can be used in a variety of contexts including measurements made with a monochromatic radiation source, a polychromatic source or with radiation of very short wavelength. As such, the algorithm is particularly suited to automated data processing for two emerging measurement techniques for macromolecular structure determination: serial pink-beam X-ray crystallography and serial electron crystallography, which until now lacked reliable programs for analyzing many individual diffraction patterns from crystals of uncorrelated orientation. The algorithm requires approximate knowledge of the unit-cell parameters of the crystal, but not the wavelengths associated with each Bragg spot. The use of pinkIndexer is demonstrated by obtaining 1005 lattices from a published pink-beam serial crystallography data set that had previously yielded 140 indexed lattices. Additionally, in tests on experimental serial crystallography diffraction data recorded with quasi-monochromatic X-rays and with electrons the algorithm indexed more patterns than other programs tested.

In this study, the atomic structure of the ternary icosahedral ZnMgTm quasicrystal (QC) is investigated by means of single-crystal X-ray diffraction. The structure is found to be a member of the Bergman QC family, frequently found in Zn–Mg–rare-earth systems. The ab initio structure solution was obtained by the use of the Superflip software. The infinite structure model was founded on the atomic decoration of two golden rhombohedra, with an edge length of 21.7 Å, constituting the Ammann–Kramer–Neri tiling. The refined structure converged well with the experimental diffraction diagram, with the crystallographic R factor equal to 9.8%. The Bergman clusters were found to be bonded by four possible linkages. Only two linkages, b and c, are detected in approximant crystals and are employed to model the icosahedral QCs in the cluster approach known for the CdYb Tsai-type QC. Additional short b and a linkages are found in this study. Short interatomic distances are not generated by those linkages due to the systematic absence of atoms and the formation of split atomic positions. The presence of four linkages allows the structure to be pictured as a complete covering by rhombic triacontahedral clusters and consequently there is no need to define the interstitial part of the structure (i.e. that outside the cluster). The 6D embedding of the solved structure is discussed for the final verification of the model.

Entangled embedded periodic nets and crystal frameworks are defined, along with their dimension type, homogeneity type, adjacency depth and periodic isotopy type. Periodic isotopy classifications are obtained for various families of embedded nets with small quotient graphs. The 25 periodic isotopy classes of depth-1 embedded nets with a single-vertex quotient graph are enumerated. Additionally, a classification is given of embeddings of n-fold copies of pcu with all connected components in a parallel orientation and n vertices in a repeat unit, as well as demonstrations of their maximal symmetry periodic isotopes. The methodology of linear graph knots on the flat 3-torus [0,1)3 is introduced. These graph knots, with linear edges, are spatial embeddings of the labelled quotient graphs of an embedded net which are associated with its periodicity bases.

A new approach is presented to obtain candidate structures from atomic pair distribution function (PDF) data in a highly automated way. It fetches, from web-based structural databases, all the structures meeting the experimenter's search criteria and performs structure refinements on them without human intervention. It supports both X-ray and neutron PDFs. Tests on various material systems show the effectiveness and robustness of the algorithm in finding the correct atomic crystal structure. It works on crystalline and nanocrystalline materials including complex oxide nanoparticles and nanowires, low-symmetry and locally distorted structures, and complicated doped and magnetic materials. This approach could greatly reduce the traditional structure searching work and enable the possibility of high-throughput real-time auto-analysis PDF experiments in the future.

Black holes sound wildly complicated. After all, there are all sorts of bizarre things going on: intense gravity, the warping of the fabric of space, the distortion of time itself. But when it comes to describing black holes, it comes down to just two numbers: the mass of the black hole and its spin. That’s right. Everything you physically need to describe a black hole is found in just these two numbers.

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John Ososky, preparator in the Osteology Laboratory at the Smithsonian's National Museum of Natural History in Washington, D.C., explains how skeletons of animal specimens are prepared for exhibtion and for study—with the assistance of nearly 1 million flesh-eating beetles.

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Bruce Campbell, of the Center for Earth and Planetary Studies at the Smithsonian's National Air and Space Museum, is at the National Radio Astronomy Observatory in Green Bank, W. Va., to make a radar map of the Moon.

The post Smithsonian geophysicist Bruce Campbell explains his work of making a detailed radar map of the Moon appeared first on Smithsonian Insider.

Keeper Tracey Barnes talks about Billie Jean, an Andean bear, and her two new cubs at the Smithsonian's National Zoo.

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The three male cheetahs that left the Zoo's D.C. campus in 2009 returned in November and are now on exhibit. The five-and-a-half-year-old brothers―Draco, Granger, and Zabini, named after characters in the Harry Potter stories―have been living at the Zoo's Smithsonian Conservation Biology Institute's Cheetah Science Facility in Front Royal, Virginia.

The post The three male cheetahs that left the National Zoo’s D.C. campus in 2009 returned in November and are now on exhibit appeared first on Smithsonian Insider.

The post Many years of research are celebrated in the December 2010 birth of two cheetah cubs at the Smithsonian Conservation Biology Institute appeared first on Smithsonian Insider.

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 Invasive Caribbean lionfish under scrutiny by Smithsonian Tropical Research Institute intern appeared first on Smithsonian Insider.

Which is more important for a career as a scientist, good grades in math or a strong sense of adventure? Hear what Smithsonian geologist Liz Cottrell has to say as she recounts her own school years and the steps that led to a career she can't imagine ever giving up.

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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."

The post Long-term killer bee study in tropics yields unexpected discovery: invasive killer bees are good for the native bees appeared first on Smithsonian Insider.

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!

The post Zen and the art of fine art conservation: Behind the scenes in the Freer Gallery’s art conservation lab appeared first on Smithsonian Insider.

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!

The post Lion cub summer school: Instead of learning their ABCs, the National Zoo’s lion cubs are learning behaviors that will help animal care staff evaluate their health. appeared first on Smithsonian Insider.

Members of the Human Origins Program team at the Smithsonian's National Museum of Natural History describe why they love their job.

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The post Pam Wintle, senior film archivist, describes the moving image collection of the Human Studies Film Archives appeared first on Smithsonian Insider.

The post Conrad Labandiera, Smithsonian palentologist, studies fossils to learn how insects got along before flowering plants arrived appeared first on Smithsonian Insider.