“The Smithsonian Institution”―When most people hear the name, museums, scientific research, even Dorothy’s ruby slippers and the Wright brothers’ plane come to mind. But many […]

The post James Smithson, the scientist who started the Smithsonian appeared first on Smithsonian Insider.

Through sheer coincidence, two Smithsonian researchers at the National Zoological Park have discovered that 18 percent of the white-tailed deer population in the Eastern United […]

The post Smithsonian study reveals white-tailed deer in eastern U.S. are infected with a malaria parasite appeared first on Smithsonian Insider.

Einstein’s general theory of relativity predicts the emission of gravitational waves by massive celestial bodies moving though space-time. For the past century gravitational waves have […]

The post Astronomers complete First Search for Visible Light Associated with Gravitational Waves 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.

Washington, D.C. is a city of symbols. The rites, rituals, and places that define Washington capture the aspirations of our nation and its citizens. Just […]

The post Trusted Sources: Why Museums and Libraries Are More Relevant Than Ever appeared first on Smithsonian Insider.

Four years after conservationists relocated 570 desert tortoises (Gopherus agassizii) in California from a threatened habitat to a new nearby location, the tortoises outwardly appeared […]

The post Smithsonian Study shows relocated desert tortoises reproduce at lower rate appeared first on Smithsonian Insider.

Finding clean ways to store water is a challenge that humans have faced for millennia. In a new paper in Environmental Health, anthropologist Sabrina Sholts […]

The post Study shows ancient California Indians risked toxins from bitumen-coated bottles appeared first on Smithsonian Insider.

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 […]

The post Astronomers see light show associated with gravitational waves appeared first on Smithsonian Insider.

“Probably no genus of birds in the American avifauna has received the amount of attention that has been bestowed upon the turkeys…there has been no […]

The post Happy Thanksgiving! Here are 25 fun turkey-related objects in Smithsonian collections! appeared first on Smithsonian Insider.

Some of Hong Kong’s most disturbed and pristine marine environments were the recent focus of an intense 10-day MarineGEO survey of living organisms by a […]

The post MarineGEO survey conducted in Hong Kong appeared first on Smithsonian Insider.

Very early on, cockroach moms found out maternal care gave their offspring a better chance at survival. The cockroach parenting method—which includes feeding, guarding and […]

The post Helicopter cockroach moms have protected their young for millions of years 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.

Leucocyte common antigen-related protein (LAR) is a post-synaptic type I transmembrane receptor protein that is important for neuronal functionality and is genetically coupled to neuronal disorders such as attention deficit hyperactivity disorder (ADHD). To understand the molecular function of LAR, structural and biochemical studies of protein fragments derived from the ectodomain of human LAR have been performed. The crystal structure of a fragment encompassing the first four FNIII domains (LARFN1–4) showed a characteristic L shape. SAXS data suggested limited flexibility within LARFN1–4, while rigid-body refinement of the SAXS data using the X-ray-derived atomic model showed a smaller angle between the domains defining the L shape compared with the crystal structure. The capabilities of the individual LAR fragments to interact with heparin was examined using microscale thermophoresis and heparin-affinity chromatography. The results showed that the three N-terminal immunoglobulin domains (LARIg1–3) and the four C-terminal FNIII domains (LARFN5–8) both bound heparin, while LARFN1–4 did not. The low-molecular-weight heparin drug Innohep induced a shift in hydrodynamic volume as assessed by size-exclusion chromatography of LARIg1–3 and LARFN5–8, while the chemically defined pentameric heparin drug Arixtra did not. Together, the presented results suggest the presence of an additional heparin-binding site in human LAR.

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.

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.

Osiris Martinez-Guzman, Mathilda M. Willoughby, Arushi Saini, Jonathan V. Dietz, Iryna Bohovych, Amy E. Medlock, Oleh Khalimonchuk, and Amit R. Reddi

Heme is a cofactor and signaling molecule that is essential for much of aerobic life. All heme-dependent processes in eukaryotes require that heme is trafficked from its site of synthesis in the mitochondria to hemoproteins located throughout the cell. However, the mechanisms governing the mobilization of heme out of the mitochondria, and the spatio-temporal dynamics of these processes, are poorly understood. Herein, using genetically encoded fluorescent heme sensors, we developed a live cell assay to monitor heme distribution dynamics between the mitochondrial inner-membrane, where heme is synthesized, and the mitochondrial matrix, cytosol, and nucleus. Surprisingly, heme trafficking to the nucleus is ~25% faster than to the cytosol or mitochondrial matrix, which are nearly identical, potentially supporting a role for heme as a mitochondrial-nuclear retrograde signal. Moreover, we discovered that the heme synthetic enzyme, 5-aminolevulinic acid synthase (ALAS), and GTPases in control of the mitochondrial dynamics machinery, Mgm1 and Dnm1, and ER contact sites, Gem1, regulate the flow of heme between the mitochondria and nucleus. Overall, our results indicate that there are parallel pathways for the distribution of bioavailable heme.

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.

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.

Samantha-Su Z. Taylor, Nicole L. Jacobsen, Tasha K. Pontifex, Paul Langlais, and Janis M. Burt

Connexin 37 (Cx37) expression profoundly suppresses proliferation of rat insulinoma (Rin) cells in a manner dependent on gap junction channel (GJCh) functionality and the presence and phosphorylation status of its carboxyl-terminus (CT). In Rin cells growth arrested by induced Cx37 expression, serine 319 (S319) is frequently phosphorylated. Preventing phosphorylation at this site (alanine substitution; S319A) relieved Cx37 of its growth suppressive effect whereas mimicking phosphorylation at this site (aspartate substitution; S319D) enhanced Cx37's growth suppressive properties. Like Cx37-WT, -S319D GJChs and hemichannels (HChs) preferred the closed state, rarely opening fully, and gated slowly. In contrast, Cx37-S319A channels preferred open states, opened fully, and gated rapidly. These data indicate that phosphorylation-dependent conformational differences in Cx37 protein and channel function underlie Cx37-induced growth arrest vs. growth permissive phenotypes. That the closed state of -WT and Cx37-S319D GJChs and HChs favors growth arrest suggests that rather than specific permeants mediating cell cycle arrest, the closed conformation instead supports interaction of Cx37 with growth regulatory proteins that result in growth arrest.

Isabella Guardamagna, Elisabetta Bassi, Monica Savio, Paola Perucca, Ornella Cazzalini, Ennio Prosperi, and Lucia A. Stivala

Assessing DNA repair is an important endpoint to study the DNA damage response for investigating the biochemical mechanisms of this process and the efficacy of chemotherapy, which often uses DNA damaging compounds. Numerous in vitro methods to biochemically characterize DNA repair mechanisms have been developed so far. However, they show some limitations mainly due to the lack of chromatin organization. Here we describe a functional cell-free system to study DNA repair synthesis in vitro, using G1-phase nuclei isolated from human cells treated with different genotoxic agents. Upon incubation in the correspondent damage-activated cytosolic extracts, containing biotin-16-dUTP, nuclei are able to initiate DNA repair synthesis. The use of specific DNA synthesis inhibitors markedly decreased biotinylated dUTP incorporation, indicating the specificity of the repair response. Exogenously added human recombinant PCNA protein, but not the sensors of UV-DNA damage DDB2 or DDB1, stimulated UVC induced dUTP incorporation. In contrast, a DDB2^PCNA- mutant protein, unable to associate with PCNA, interfered with DNA repair synthesis. Given its responsiveness to different type of DNA lesions, this system offers an additional tool to study DNA repair mechanisms.

More than 500 carats of rough diamonds were recently donated to the Department of Mineral Sciences of the Smithsonian’s Natural History Museum by Jewlers Mutual Insurance Co. of Neenah, Wis.

The post 500 carats of rough diamonds donated to Natural History Museum appeared first on Smithsonian Insider.

A full 94 percent of the dead zones in the world’s oceans lie in regions expected to warm at least 2 degrees Celsius by the […]

The post Climate change expected to expand majority of ocean dead zones appeared first on Smithsonian Insider.

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.

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.

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.

It takes a Tlingit artist up to 2,000 hours, or 83 days, to weave just one ceremonial robe. Not surprisingly, this art form is practiced by a dedicated few including Tlingit artists Teri Rofkar and Shelly Laws of Alaska. In their presentation for the Smithsonian Spotlight series hosted by the Arctic Studies Center at the Anchorage Museum, Rofkar and Laws discuss the methods and cultural significance of robes, spruce root baskets and more.
For more information, go to http://www.mnh.si.edu/arctic/html/alaska.htm

The post The artistry of Tlingit weaving is practiced by a dedicated few including artists Teri Rofkar and Shelly Laws of Alaska appeared first on Smithsonian Insider.

The post The Space Shuttle Discovery, mounted atop a 747 jet, is delivered to the Smithsonian on April 17, 2012 appeared first on Smithsonian Insider.

The post Short video featuring the fieldwork of Smithsonian scientists created in 2000, posted by the Smithsonian Archives appeared first on Smithsonian Insider.

The post Samuel P. Langley, Secretary of the Smithsonian, and his development of the ill-fated Aerodrome A appeared first on Smithsonian Insider.

Last October Smithsonian Folkways released “The Brothers Nazaroff: The Happy Prince,” a boisterous, high-energy tribute to cult Yiddish troubadour Nathan “Prince” Nazaroff, who recorded the […]

The post Animated Music Video: “Ich A Mazeldicker Yid” by The Brothers Nazaroff appeared first on Smithsonian Insider.

Yesterday may have been a holiday on paper, but if you were navigating LA's major freeways, there was no sign people had the day off.

Steve Julian: Business analyst Mark Lacter, is this more evidence that Southern California traffic getting worse?

Mark Lacter: Steve, L.A. continues to be the most clogged-up city in the U.S. - according to something called the TomTom Traffic Index - with commuters caught up in delays, on average, 35 percent of the time.  Or, to put it another way, L.A. commuters are in congestion up to 40 minutes of each hour they're driving.  The worst time of the week to commute is Thursday night; that's when there's congestion more than 80 percent of the time.  Monday morning commutes are the lightest.

Julian: After L.A., where should you not live if congestion bugs you?

Lacter: The next worst cities in the U.S. are San Francisco, Honolulu, Seattle, and San Jose.  Now, the Census Bureau comes up with its own commuting surveys, and if you compare the most recent numbers with those back in 2000, you'll see that things aren't all that different.  Matter of fact, the percentage of commuters driving alone to work actually increased a little over the last decade to 72 percent, while the percentage of those carpooling has declined.

Julian: What about public transit?

Lacter: Well, the numbers are up slightly from 2000, but only to 7.3 percent of all commuters.  So, even assuming that the number inches up in the next couple of years when the Expo Line extends into Santa Monica, it's still a smallish piece of the pie.  And, since many of the other public transit projects being planned are decades away from being completed, those numbers might not change much.  One other thing, Steve: less than 1 percent of all L.A. commuters bike to work, which would throw cold water on the idea that biking in L.A. is becoming a popular way of getting to the office.

Julian: People just prefer commuting by car…

Lacter: It remains the most convenient way of getting around - despite the congestion.  New car sales are up 14 percent through the first nine months of the year in Southern California.  Add to that are generally affordable gas prices (they've been especially low in the last few weeks).  In other parts of the world, congestion is considered a good thing because it means that the economy is doing well.  Which explains that while L.A. is the most congested city in the U.S., it doesn't rank among the 10 around the world.  On that front, Moscow is tops, followed by Istanbul, and Rio de Janeiro.

Julian: What about driverless cars?

Lacter: Well, these vehicles hold the most promise for reducing accidents, lowering travel times, and improving fuel economy - and you don't have to give up your car.  Actually, a lot of the technology is already in place - that includes stuff like radar-based cruise control, and devices that keep you at a safe distance from the car in front of you.  The trick, of course, is taking these individual capabilities and integrating them into an entirely driverless car.  Several car companies say they could be ready to start selling by 2020, with Google saying that its car could be ready even sooner.

Julian: Is that realistic?

Lacter: Who knows?  But even if the dates can be met - and that's a big if, considering how complex these systems are - legislatures will have to determine, among other things, whether vehicles can be fully autonomous (meaning that you can curl up and take a nap while the computer is driving by itself).  Or, whether they will only be semi-autonomous, which would be like an airline crew using automatic pilot, but always prepared to take over the controls.

Julian: Is that a liability issue?

Lacter: Yes - if something does go wrong, who will get the blame?  The owner of the vehicle?  The carmaker?  The suppliers of the car companies?  These questions might take years to get resolved in the courts - and even then, it could be years before the percentage of these vehicles on the road is large enough to truly have an impact.  But, considering that most commuters aren't willing to give up their cars, this would seem to be the most exciting, most desirable idea.  One day.

Mark Lacter writes for Los Angeles Magazine and pens the business blog at LA Observed.com.

This content is from Southern California Public Radio. View the original story at SCPR.org.

using Irfanview & UnFREEz

Latinus 9333 is the Latin translation of the so-called Tacuinum sanitatis, a medieval handbook on wellness written in Arabic by the 11th-century physician ibn Butlan. It deals with factors influencing human health: from the air, the environment and food, to physical exercise and sexual activity.

The post Medieval book is important resource for how plants were once collected, treated and used appeared first on Smithsonian Insider.

Obsessive in his collecting and emotionally invested in contributing to science and perpetuating knowledge, Palmer lived the adventurous yet nomadic life of a collector.

The post Remarkable ethnobotany collections of Edward Palmer highlighted in new Smithsonian Website appeared first on Smithsonian Insider.

Non-native plant species pose a significant threat to the natural ecosystems of the United States. Many of these invasive plants are escapees from gardens and […]

The post Escape of the invasives: Top six invasive plant species in the United States appeared first on Smithsonian Insider.

For the first time, a new public database will link genetic data with records of where and when the samples it was taken from were […]

The post A first: New website reveals origin of genetic samples and date collected appeared first on Smithsonian Insider.

The title complex, Cu(L)2 or [Cu(C15HF10O2)2], comprising one copper ion and two fully fluorinated ligands (L−), was crystallized with 3,4-ethyl­ene­dioxy­thio­phene (EDOT, C6H6O2S) as a guest mol­ecule to give in a di­chloro­methane solution a unique co-crystal, Cu(L)2·3C6H6O2S.

Simulink might produce an incorrect sorted order for a model that meets all of the following conditions:

• The model contains blocks from the SoC Blockset
• The Signal logging option is selected in the model configuration set
• Signals using asynchronous sample time are configured for logging

If you try to open a text file with UTF-16 or UTF-32 encoding, the Import Tool displays a warning message stating that the encoding is not supported.  If you continue to load the file anyways, it is opened with UTF-8 encoding, and the file may not be displayed or imported as expected.This bug exists in the following release(s):
R2020a

This bug has a workaround

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