Model quality assessment programs estimate the quality of protein models and can be used to estimate local error in protein models. ProQ3D is the most recent and most accurate version of our software. Here, it is demonstrated that it is possible to use local error estimates to substantially increase the quality of the models for molecular replacement (MR). Adjusting the B factors using ProQ3D improved the log-likelihood gain (LLG) score by over 50% on average, resulting in significantly more successful models in MR compared with not using error estimates. On a data set of 431 homology models to address difficult MR targets, models with error estimates from ProQ3D received an LLG of >50 for almost half of the models 209/431 (48.5%), compared with 175/431 (40.6%) for the previous version, ProQ2, and only 74/431 (17.2%) for models with no error estimates, clearly demonstrating the added value of using error estimates to enable MR for more targets. ProQ3D is available from http://proq3.bioinfo.se/ both as a server and as a standalone download.

In processing X-ray diffraction data, the intensities obtained from integration of the diffraction images must be corrected for experimental effects in order to place all intensities on a common scale both within and between data collections. Scaling corrects for effects such as changes in sample illumination, absorption and, to some extent, global radiation damage that cause the measured intensities of symmetry-equivalent observations to differ throughout a data set. This necessarily requires a prior evaluation of the point-group symmetry of the crystal. This paper describes and evaluates the scaling algorithms implemented within the DIALS data-processing package and demonstrates the effectiveness and key features of the implementation on example macromolecular crystallographic rotation data. In particular, the scaling algorithms enable new workflows for the scaling of multi-crystal or multi-sweep data sets, providing the analysis required to support current trends towards collecting data from ever-smaller samples. In addition, the implementation of a free-set validation method is discussed, which allows the quantification of the suitability of scaling-model and algorithm choices.

This paper discusses the full structural solution of the hybrid perovskite formamidinium lead tribromide (FAPbBr3) and its temperature-dependent phase transitions in the range from 3 K to 300 K using neutron powder diffraction and synchrotron X-ray diffraction. Special emphasis is put on the influence of deuteration on formamidinium, its position in the unit cell and disordering in comparison to fully hydrogenated FAPbBr3. The temperature-dependent measurements show that deuteration critically influences the crystal structures, i.e. results in partially-ordered temperature-dependent structural modifications in which two symmetry-independent molecule positions with additional dislocation of the molecular centre atom and molecular angle inclinations are present.

Small-angle scattering tensor tomography (SASTT) is a recently developed technique able to tomographically reconstruct the 3D reciprocal space from voxels within a bulk volume. SASTT extends the concept of X-ray computed tomography, which typically reconstructs scalar values, by reconstructing a tensor per voxel, which represents the local nanostructure 3D organization. In this study, the nanostructure orientation in a human trabecular-bone sample obtained by SASTT was validated by sectioning the sample and using 3D scanning small-angle X-ray scattering (3D sSAXS) to measure and analyze the orientation from single voxels within each thin section. Besides the presence of cutting artefacts from the slicing process, the nanostructure orientations obtained with the two independent methods were in good agreement, as quantified with the absolute value of the dot product calculated between the nanostructure main orientations obtained in each voxel. The average dot product per voxel over the full sample containing over 10 000 voxels was 0.84, and in six slices, in which fewer cutting artefacts were observed, the dot product increased to 0.91. In addition, SAXS tensor tomography not only yields orientation information but can also reconstruct the full 3D reciprocal-space map. It is shown that the measured anisotropic scattering for individual voxels was reproduced from the SASTT reconstruction in each voxel of the 3D sample. The scattering curves along different 3D directions are validated with data from single voxels, demonstrating SASTT's potential for a separate analysis of nanostructure orientation and structural information from the angle-dependent intensity distribution.

Double-sided Fresnel zone plates are diffractive lenses used for high-resolution hard X-ray microscopy. The double-sided structures have significantly higher aspect ratios compared with single-sided components and hence enable more efficient imaging. The zone plates discussed in this paper are fabricated on each side of a thin support membrane, and the alignment of the zone plates with respect to each other is critical. Here, a simple and reliable way of quantifying misalignments by recording efficiency maps and measuring the absolute diffraction efficiency of the zone plates as a function of tilting angle in two directions is presented. The measurements are performed in a setup based on a tungsten-anode microfocus X-ray tube, providing an X-ray energy of 8.4 keV through differential measurements with a Cu and an Ni filter. This study investigates the sources of the misalignments and concludes that they can be avoided by decreasing the structure heights on both sides of the membrane and by pre-programming size differences between the front- and back-side zone plates.

Serial crystallography is a powerful technique in structure determination using many small crystals at X-ray free-electron laser or synchrotron radiation facilities. The large diffraction data volumes require high-throughput software to preprocess the raw images for subsequent analysis. ClickX is a program designated for serial crystallography data preprocessing, capable of rapid data sorting for online feedback and peak-finding refinement by parameter optimization. The graphical user interface (GUI) provides convenient access to various operations such as pattern visualization, statistics plotting and parameter tuning. A batch job module is implemented to facilitate large-data-volume processing. A two-step geometry calibration for single-panel detectors is also integrated into the GUI, where the beam center and detector tilting angles are optimized using an ellipse center shifting method first, then all six parameters, including the photon energy and detector distance, are refined together using a residual minimization method. Implemented in Python, ClickX has good portability and extensibility, so that it can be installed, configured and used on any computing platform that provides a Python interface or common data file format. ClickX has been tested in online analysis at the Pohang Accelerator Laboratory X-ray Free-Electron Laser, Korea, and the Linac Coherent Light Source, USA. It has also been applied in post-experimental data analysis. The source code is available via https://github.com/LiuLab-CSRC/ClickX under a GNU General Public License.

Bone crystallite chemistry and structure change during bone maturation. However, these properties of bone can also be affected by limited uptake of the chemical constituents of the mineral by the animal. This makes probing the effect of bone-mineralization-related diseases a complicated task. Here it is shown that the combination of vibrational spectroscopy with two-dimensional X-ray diffraction can provide unparalleled information on the changes in bone chemistry and structure associated with different bone pathologies (phosphate deficiency) and/or health conditions (pregnancy, lactation). Using a synergistic analytical approach, it was possible to trace the effect that changes in the remodelling regime have on the bone mineral chemistry and structure in normal and mineral-deficient (hypophosphatemic) mice. The results indicate that hypophosphatemic mice have increased bone remodelling, increased carbonate content and decreased crystallinity of the bone mineral, as well as increased misalignment of crystallites within the bone tissue. Pregnant and lactating mice that are normal and hypophosphatemic showed changes in the chemistry and misalignment of the apatite crystals that can be related to changes in remodelling rates associated with different calcium demand during pregnancy and lactation.

DatView is a new graphical user interface (GUI) for plotting parameters to explore correlations, identify outliers and export subsets of data. It was designed to simplify and expedite analysis of very large unmerged serial femtosecond crystallography (SFX) data sets composed of indexing results from hundreds of thousands of microcrystal diffraction patterns. However, DatView works with any tabulated data, offering its functionality to many applications outside serial crystallography. In DatView's user-friendly GUI, selections are drawn onto plots and synchronized across all other plots, so correlations between multiple parameters in large multi-parameter data sets can be rapidly identified. It also includes an item viewer for displaying images in the current selection alongside the associated metadata. For serial crystallography data processed by indexamajig from CrystFEL [White, Kirian, Martin, Aquila, Nass, Barty & Chapman (2012). J. Appl. Cryst. 45, 335–341], DatView generates a table of parameters and metadata from stream files and, optionally, the associated HDF5 files. By combining the functionality of several commonly needed tools for SFX in a single GUI that operates on tabulated data, the time needed to load and calculate statistics from large data sets is reduced. This paper describes how DatView facilitates (i) efficient feedback during data collection by examining trends in time, sample position or any parameter, (ii) determination of optimal indexing and integration parameters via the comparison mode, (iii) identification of systematic errors in unmerged SFX data sets, and (iv) sorting and highly flexible data filtering (plot selections, Boolean filters and more), including direct export of subset CrystFEL stream files for further processing.

The program Mercury, developed at the Cambridge Crystallographic Data Centre, was originally designed primarily as a crystal structure visualization tool. Over the years the fields and scientific communities of chemical crystallography and crystal engineering have developed to require more advanced structural analysis software. Mercury has evolved alongside these scientific communities and is now a powerful analysis, design and prediction platform which goes a lot further than simple structure visualization.

Knowledge of the appearance of texture components and fibres in pole figures, in inverse pole figures and in Euler space is fundamental for texture analysis. For cubic crystal systems, such as steels, an extensive literature exists and, for example, the book by Matthies, Vinel & Helming [Standard Distributions in Texture Analysis: Maps for the Case of Cubic Orthorhomic Symmetry, (1987), Akademie-Verlag Berlin] provides an atlas to identify texture components. For lower crystal symmetries, however, equivalent comprehensive overviews that can serve as guidance for the interpretation of experimental textures do not exist. This paper closes this gap by providing a set of scripts for the MTEX package [Bachmann, Hielscher & Schaeben (2010). Solid State Phenom. 160, 63–68] that allow the texture practitioner to compile such an atlas for a given material system, thus aiding orientation distribution function analysis also for non-cubic systems.

SVAT4 is a computer program for interactive visualization of three-dimensional crystal structures. A wide range of functions are available for structural analysis.

Cytisine, a natural product with high affinity for clinically relevant nicotinic acetylcholine receptors (nAChRs), is used as a smoking-cessation agent. The compound displays an excellent clinical profile and hence there is an interest in derivatives that may be further improved or find use in the treatment of other conditions. Here, the binding of a cytisine derivative modified by the addition of a 3-(hydroxypropyl) moiety (ligand 4) to Aplysia californica acetylcholine-binding protein (AcAChBP), a surrogate for nAChR orthosteric binding sites, was investigated. Isothermal titration calorimetry revealed that the favorable binding of cytisine and its derivative to AcAChBP is driven by the enthalpic contribution, which dominates an unfavorable entropic component. Although ligand 4 had a less unfavorable entropic contribution compared with cytisine, the affinity for AcAChBP was significantly diminished owing to the magnitude of the reduction in the enthalpic component. The high-resolution crystal structure of the AcAChBP–4 complex indicated close similarities in the protein–ligand interactions involving the parts of 4 common to cytisine. The point of difference, the 3-(hydroxypropyl) substituent, appears to influence the conformation of the Met133 side chain and helps to form an ordered solvent structure at the edge of the orthosteric binding site.

Immunoglobulin E (IgE) plays a central role in the allergic response, in which cross-linking of allergen by Fc∊RI-bound IgE triggers mast cell and basophil degranulation and the release of inflammatory mediators. The high-affinity interaction between IgE and Fc∊RI is a long-standing target for therapeutic intervention in allergic disease. Omalizumab is a clinically approved anti-IgE monoclonal antibody that binds to free IgE, also with high affinity, preventing its interaction with Fc∊RI. All attempts to crystallize the pre-formed complex between the omalizumab Fab and the Fc region of IgE (IgE-Fc), to understand the structural basis for its mechanism of action, surprisingly failed. Instead, the Fab alone selectively crystallized in different crystal forms, but their structures revealed intermolecular Fab/Fab interactions that were clearly strong enough to disrupt the Fab/IgE-Fc complexes. Some of these interactions were common to other Fab crystal structures. Mutations were therefore designed to disrupt two recurring packing interactions observed in the omalizumab Fab crystal structures without interfering with the ability of the omalizumab Fab to recognize IgE-Fc; this led to the successful crystallization and subsequent structure determination of the Fab/IgE-Fc complex. The mutagenesis strategy adopted to achieve this result is applicable to other intractable Fab/antigen complexes or systems in which Fabs are used as crystallization chaperones.

A recent study of dog bones excavated from archaeological sites on the Channel Islands of California has cast new light on the past ecology of the islands and the impact that domestic dogs--brought to the islands by Native Americans more than 6,000 years ago—may have once had on the islands’ animals and ecosystems.

The post Dog bones reveal ecological history of California’s Channel Islands appeared first on Smithsonian Insider.

Now that astronomers are finding rocky worlds orbiting distant stars, they're asking the next logical questions: Do any of those worlds have volcanoes? And if so, could we detect them? Work by theorists at the Harvard-Smithsonian Center for Astrophysics suggests that the answer to the latter is a qualified "Yes."

The post Can we spot volcanoes on alien worlds? Astronomers say yes appeared first on Smithsonian Insider.

This 'hot Jupiter', now named Qatar-1b, adds to the growing list of alien planets orbiting distant stars, or exoplanets. Its discovery demonstrates the power of science to cross political boundaries and increase ties between nations.

The post International team discovers alien planet that’s Jupiter-sized appeared first on Smithsonian Insider.


They found that the molars of fruit-eating species had sharp outer edges that likely allow them to pierce tough fruit skin and pulp... By contrast, the molars of insect-eating species were less complex, possibly because of their smoother shearing surfaces.

The post From chewing tough insects to soft fruit, bat teeth are highly specialized appeared first on Smithsonian Insider.

Evidence for a diversified sea-based economy among North American inhabitants dating from 12,200 to 11,400 years ago is emerging from three sites on California's Channel Islands.

The post New archaeological evidence reveals California’s Channel Islands as North America’s earliest seafaring economy appeared first on Smithsonian Insider.

The Smithsonian’s National Zoo has a new addition: Rocky, a male whooping crane (Grus americana). This is the first time the Zoo has exhibited this species in 88 years.

The post Whooping crane will help teach visitors and scientists alike appeared first on Smithsonian Insider.

A new study by a team of scientists from the Smithsonian’s National Museum of Natural History, the National University of Singapore and the Slovenian Academy of Sciences and Arts have unlocked the secret to mate binding in orb web spiders, and revealed just how it calms the cannibalistic female spider.

The post Suitor’s gentle massage soothes aggressive, cannibalistic female spiders, researchers find appeared first on Smithsonian Insider.

The snakes are not only eating the area’s birds, but also the birds’ eggs straight from the nest.

The post Invasive pythons in Florida now stealing bird eggs straight from the nest appeared first on Smithsonian Insider.

In celebration of the annual spring appearance of the Easter bunny on Sunday, April 8, Smithsonian Science offers these five facts from the book "Rabbits: The Animal Answer Guide"

The post 5 rabbit realities appeared first on Smithsonian Insider.

New research by a team of astronomers found that planets smaller than Neptune are located around a wide variety of stars, including those with fewer heavy elements than the Sun.

The post Alien Earths may have formed in Universe earlier than expected appeared first on Smithsonian Insider.

Astronomers have discovered that one well-known elliptical galaxy has a split personality. Centaurus A is hiding a gassy spiral in its center.

The post Split-personality elliptical galaxy holds a hidden spiral appeared first on Smithsonian Insider.

The western long-beaked echidna, one of the world's five egg-laying species of mammal, became extinct in Australia thousands of years ago…or did it?

The post Scientists discover long-beaked echidna may not be a thing of the past in Australia appeared first on Smithsonian Insider.

Douglas Owsley, the division head for physical anthropology at the Smithsonian’s National Museum of Natural History, presented today a forensic analysis of 17th-century human remains […]

The post Forensic analysis of 17th-century human remains at Jamestown, Va., reveals evidence of survival cannibalism appeared first on Smithsonian Insider.

Microbes that live in rice paddies, northern peat bogs and other previously unexpected environments are among the bacteria that can generate highly toxic methylmercury, researchers […]

The post Toxic methylmercury-producing microbes more widespread than realized 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.

Out in Montana’s Big Sky Country Dale Greenwalt spends his summers seeking the incredibly tiny and fragile. Armed with a putty knife honed razor-sharp on […]

The post Quality of insect fossils from Montana’s Flathead River astounds scientists appeared first on Smithsonian Insider.

Move over Matrix, astronomers have done you one better. They have created the first realistic virtual universe using a computer simulation called “Illustris.” Illustris can […]

The post Astronomers create first realistic virtual universe appeared first on Smithsonian Insider.

Humanity is on the threshold of being able to detect signs of alien life on other worlds. By studying exoplanet atmospheres, we can look for […]

The post Finding ET by searching for alien air pollution appeared first on Smithsonian Insider.

California’s Channel Islands are located dozens of miles west of the state’s coast and surrounded by Pacific waters, yet they too are experiencing the same […]

The post Drought slows wildlife reproduction on California’s Channel Islands appeared first on Smithsonian Insider.

New fossils found in Northeastern China have revealed a remarkable evolutionary coincidence: an extinct group of insects known as Kalligrammatid lacewings (Order Neuroptera) share an […]

The post Remarkable butterfly look-alike lived 50 million years before butterflies appeared appeared first on Smithsonian Insider.

There’s something exciting and strange about having an idea. It can come suddenly. Unexpectedly. Randomly. Intensely. Ideas can uninvitingly appear full-forced and bright—like the cliché […]

The post Making the Smithsonian’s New “Sidedoor” podcast series a reality appeared first on Smithsonian Insider.

In 1935, 101 cane toads from Hawaii were set loose in Australia to help control beetles that were decimating the Australian sugar crop. But instead […]

The post Discovery: Australia’s invasive cane toads modify their bodies to conquer new territory faster appeared first on Smithsonian Insider.

The search for extraterrestrial intelligence has looked for many different signs of alien life, from radio broadcasts to laser flashes, without success. However, newly published […]

The post Could Fast Radio Bursts Be Powering Alien Probes? 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.

A new project using data from NASA’s Chandra X-ray Observatory and other telescopes allows people to navigate through real data of the remains of an […]

The post A new stellar X-ray “reality” show debuts appeared first on Smithsonian Insider.

Animal species can become endangered, but what about languages? Around 80 percent of the world’s population speaks just 20 percent of its 7,000 languages. That […]

The post Why languages become endangered, and how we can keep them alive appeared first on Smithsonian Insider.

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

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.

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.

Kristina Drizyte-Miller, Jing Chen, Hong Cao, Micah B. Schott, and Mark A. McNiven

Epithelial cells such as liver-resident hepatocytes rely heavily on the Rab family of small GTPases to perform membrane trafficking events that dictate cell physiology and metabolism. Not surprisingly, disruption of several Rabs can manifest in metabolic diseases or cancer. Rab32 is expressed in many secretory epithelial cells but its role in cellular metabolism is virtually unknown. In this study, we find that Rab32 associates with lysosomes and regulates proliferation and cell size of Hep3B hepatoma and HeLa cells. Specifically, we identify that Rab32 supports mTORC1 signaling under basal and amino acid stimulated conditions. Consistent with inhibited mTORC1, an increase in nuclear TFEB localization and lysosome biogenesis is also observed in Rab32-depleted cells. Finally, we find that Rab32 interacts with mTOR kinase and that loss of Rab32 reduces the association of mTOR and mTORC1 pathway proteins with lysosomes, suggesting that Rab32 regulates lysosomal mTOR trafficking. In summary, these findings suggest that Rab32 functions as a novel regulator of cellular metabolism through supporting mTORC1 signaling.

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.

Juan Martin D'Ambrosio, Veronique Albanese, Nicolas-Frederic Lipp, Lucile Fleuriot, Delphine Debayle, Guillaume Drin, and Alenka Copic

Osh6 and Osh7 are lipid transfer proteins (LTPs) that move phosphatidylserine (PS) from the endoplasmic reticulum (ER) to the plasma membrane (PM). High PS level at the PM is key for many cellular functions. Intriguingly, Osh6/7 localize to ER-PM contact sites, although they lack membrane-targeting motifs, in contrast to multidomain LTPs that both bridge membranes and convey lipids. We show that Osh6 localization to contact sites depends on its interaction with the cytosolic tail of the ER-PM tether Ist2, a homologue of TMEM16 proteins. We identify a motif in the Ist2 tail, conserved in yeasts, as the Osh6-binding region, and we map an Ist2-binding surface on Osh6. Mutations in the Ist2 tail phenocopy osh6 osh7 deletion: they decrease cellular PS levels, and block PS transport to the PM. Our study unveils an unexpected partnership between a TMEM16-like protein and a soluble LTP, which together mediate lipid transport at contact sites.

Sanjeev Chavan Nayak and Vegesna Radha

C3G (RapGEF1) plays a role in cell differentiation and is essential for early embryonic development in mice. In this study, we identify C3G as a centrosomal protein colocalizing with cenexin at the mother centriole in interphase cells. C3G interacts through its catalytic domain with cenexin, and they show interdependence for localization to the centrosome. C3G depletion caused a decrease in cellular cenexin levels. Centrosomal localization is lost as myocytes differentiate to form myotubes. Stable clone of cells depleted of C3G by CRISPR/Cas9 showed the presence of supernumerary centrioles. Overexpression of C3G, or a catalytically active deletion construct inhibited centrosome duplication. Cilia length is longer in C3G knockout cells, and the phenotype could be reverted upon reintroduction of C3G or its catalytic domain. Association of C3G with the basal body is dynamic, decreasing upon serum starvation, and increasing upon reentry into the cell cycle. C3G inhibits cilia formation and length dependent on its catalytic activity. We conclude that C3G inhibits centrosome duplication and maintains ciliary homeostasis, properties that may be important for its role in embryonic development.

The pendant took Grand Prize in the National Saul Bell Design Competition in 2008 and features a beautiful 3.76-ct pink tourmaline from Nigeria.

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George Smith, a marine biologist at the Smithsonian Environmental Research Center, explains his work of finding ways to prevent invasive species from being released in Baltimore Harbor in the ballast water of large ships.

The post Preventing ballast-water invasions of alien species appeared first on Smithsonian Insider.

The state's online registration for Covered California has been up for a couple of weeks, and reaction has been mixed.

Steve Julian: Business analyst, Mark Lacter, what's your take on how well Californians are getting into the Affordable Care Act?

Mark Lacter: It's hard to get a good read, Steve, because it's hard to measure the success of what is really a new marketplace.  If you're basing it on the number of unique visitors coming to the Covered California website, well, then the program clearly has attracted lots of interest - they had almost a million visitors during the first week of eligibility.  But, maybe a better measure would be the number of people whose applications actually have been received by the insurance companies that are going to handle the claims.  If that's your measuring stick, then the numbers have been far smaller so far.  Now, it's worth pointing out that California - and particularly L.A. County - have a higher percentage of households without insurance than other parts of the nation, and so you'd expect there to be lots of interest.

Julian: So the question, then, is how many folks turn into actual policyholders paying actual premiums each month.

Lacter: The truth is nobody knows, which is why state officials want to sign up as many people as possible in the early going when the program is getting so much attention.  This is especially true for younger and healthier people who are needed to help offset the cost of caring for older and sicker people.

Julian: And, that's also why any computer glitch can be such a headache...

Lacter: That's right.  Covered California did run into problems in the early going, but everybody agrees that things are going much better than the federal website, which is the default site used by folks in states that don't have their own program to oversee the health care laws.  That federal site has been an utter disaster.  So, by comparison, California is ahead of the game.

Julian: It's a work in progress, even here.

Lacter: Very much so.  The California website still doesn't have a way for enrollees to find out which doctors and hospitals are included in each health plan.  And, that's a big deal because  insurance companies are limiting the options available as a way of keeping premiums low.  So, it's possible that the doctor you had been using for your individual insurance plan will not be on the list of doctors that can be used for one of the cheaper plans.  Of course, for someone who doesn't have any health coverage, none of that is likely to matter.

Julian: And then, there's the continued threat of a U.S. default...

Lacter: You know, Steve, this is like watching the beginning of a bad traffic accident in slow motion - and we're all pretty helpless to do anything about it.  And, so are the financial markets, which are moving back and forth not based on what's going on with the economy or with any industry, but on the latest press conference out of Washington.  One thing we do know is that if the nation does go into quote-unquote default - and we're not even sure what that might mean - but if Wall Street and somehow declares this a major crisis, it's going to be bad.

Julian: Who gets hit?

Lacter: It'll impact anyone who has a retirement account, any business wanting to borrow money, and potentially it's going to impact the budgeting of the state.  You know, one of the things we were reminded of during the Great Recession was how reliant California has been on higher-income individuals who make a lot of their money through the stock market and other investments.  So, when those folks do well - as they have been over the last year - the state coffers will do well.  And when they don't, as was the case in 2008 and 2009, the state takes a huge hit because there's not enough tax dollars coming in.  Gov. Brown and others have tried to lessen the reliance on those top tiers - so far without success.

Julian: And the state's budget situation is so much better than it was a year or two ago.

Lacter: That's the real pity.  And, even if the House and Senate reach a temporary agreement on the debt ceiling, it's just a matter of weeks or months before another deadline crops up - and more uncertainty for the financial markets.  I guess Chick Hearn would have called this nervous time.

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.