ration Lockdown has cut Britain's vibrations, seismologists find - The Guardian By www.theguardian.com Published On :: Mon, 06 Apr 2020 19:15:48 GMT Lockdown has cut Britain's vibrations, seismologists find The Guardian Full Article
ration European lockdown a boon to seismologists checking Earth's vibrations - E&T Magazine By eandt.theiet.org Published On :: Fri, 24 Apr 2020 07:00:00 GMT European lockdown a boon to seismologists checking Earth's vibrations E&T Magazine Full Article
ration Dehydration synthesis and crystal structure of terbium oxychloride, TbOCl By scripts.iucr.org Published On :: 2020-04-03 Terbium oxychloride, TbOCl, was synthesized via the simple heat-treatment of TbCl3·6H2O and its structure was determined by refinement against X-ray powder diffraction data. TbOCl crystallizes with the matlockite (PbFCl) structure in the tetragonal space group P4/nmm and is composed of alternating (001) layers of (TbO)n and n Cl−. The unit-cell parameters, unit-cell volume, and density were compared to the literature data of other isostructural rare-earth oxychlorides in the same space group and showed good agreement when compared to the calculated trendlines. Full Article text
ration Structure of a push–pull olefin prepared by ynamine hydroboration with a borandiol ester By scripts.iucr.org Published On :: 2020-04-21 N-[(Z)-2-(2H-1,3,2-Benzodioxaborol-2-yl)-2-phenylethenyl]-N-(propan-2-yl)aniline, C23H22BNO2, contains a C=C bond that is conjugated with a donor and an acceptor group. An analysis that included similar push–pull olefins revealed that bond lengths in their B—C=C—N core units correlate with the perceived acceptor and donor strength of the groups. The two phenyl groups in the molecule are rotated with respect to the plane that contains the BCCN atoms, and are close enough for significant π-stacking. Definite characterization of the title compound demonstrates, for the first time in a reliable way, that hydroboration of ynamines with borandiol esters is feasible. Compared to olefin hydroboration with borane, the ynamine substrate is activated enough to undergo reaction with the less active hydroboration reagent catecholborane. Full Article text
ration Equatorial aberration of powder diffraction data collected with an Si strip X-ray detector by a continuous-scan integration method By scripts.iucr.org Published On :: 2020-05-05 Exact and approximate mathematical formulas of equatorial aberration for powder diffraction data collected with an Si strip X-ray detector in continuous-scan integration mode are presented. An approximate formula is applied to treat the experimental data measured with a commercial powder diffractometer. Full Article text
ration A cryo-EM grid preparation device for time-resolved structural studies By scripts.iucr.org Published On :: 2019-09-05 Structural biology generally provides static snapshots of protein conformations that can provide information on the functional mechanisms of biological systems. Time-resolved structural biology provides a means to visualize, at near-atomic resolution, the dynamic conformational changes that macromolecules undergo as they function. X-ray free-electron-laser technology has provided a powerful tool to study enzyme mechanisms at atomic resolution, typically in the femtosecond to picosecond timeframe. Complementary to this, recent advances in the resolution obtainable by electron microscopy and the broad range of samples that can be studied make it ideally suited to time-resolved approaches in the microsecond to millisecond timeframe to study large loop and domain motions in biomolecules. Here we describe a cryo-EM grid preparation device that permits rapid mixing, voltage-assisted spraying and vitrification of samples. It is shown that the device produces grids of sufficient ice quality to enable data collection from single grids that results in a sub-4 Å reconstruction. Rapid mixing can be achieved by blot-and-spray or mix-and-spray approaches with a delay of ∼10 ms, providing greater temporal resolution than previously reported mix-and-spray approaches. Full Article text
ration CryoEM at 100 keV: a demonstration and prospects By scripts.iucr.org Published On :: 2019-10-11 100 kV is investigated as the operating voltage for single-particle electron cryomicroscopy (cryoEM). Reducing the electron energy from the current standard of 300 or 200 keV offers both cost savings and potentially improved imaging. The latter follows from recent measurements of radiation damage to biological specimens by high-energy electrons, which show that at lower energies there is an increased amount of information available per unit damage. For frozen hydrated specimens around 300 Å in thickness, the predicted optimal electron energy for imaging is 100 keV. Currently available electron cryomicroscopes in the 100–120 keV range are not optimized for cryoEM as they lack both the spatially coherent illumination needed for the high defocus used in cryoEM and imaging detectors optimized for 100 keV electrons. To demonstrate the potential of imaging at 100 kV, the voltage of a standard, commercial 200 kV field-emission gun (FEG) microscope was reduced to 100 kV and a side-entry cryoholder was used. As high-efficiency, large-area cameras are not currently available for 100 keV electrons, a commercial hybrid pixel camera designed for X-ray detection was attached to the camera chamber and was used for low-dose data collection. Using this configuration, five single-particle specimens were imaged: hepatitis B virus capsid, bacterial 70S ribosome, catalase, DNA protection during starvation protein and haemoglobin, ranging in size from 4.5 MDa to 64 kDa with corresponding diameters from 320 to 72 Å. These five data sets were used to reconstruct 3D structures with resolutions between 8.4 and 3.4 Å. Based on this work, the practical advantages and current technological limitations to single-particle cryoEM at 100 keV are considered. These results are also discussed in the context of future microscope development towards the goal of rapid, simple and widely available structure determination of any purified biological specimen. Full Article text
ration Throughput and resolution with a next-generation direct electron detector By scripts.iucr.org Published On :: 2019-10-24 Direct electron detectors (DEDs) have revolutionized cryo-electron microscopy (cryo-EM) by facilitating the correction of beam-induced motion and radiation damage, and also by providing high-resolution image capture. A new-generation DED, the DE64, has been developed by Direct Electron that has good performance in both integrating and counting modes. The camera has been characterized in both modes in terms of image quality, throughput and resolution of cryo-EM reconstructions. The modulation transfer function, noise power spectrum and detective quantum efficiency (DQE) were determined for both modes, as well as the number of images per unit time. Although the DQE for counting mode was superior to that for integrating mode, the data-collection throughput for this mode was more than ten times slower. Since throughput and resolution are related in single-particle cryo-EM, data for apoferritin were collected and reconstructed using integrating mode, integrating mode in conjunction with a Volta phase plate (VPP) and counting mode. Only the counting-mode data resulted in a better than 3 Å resolution reconstruction with similar numbers of particles, and this increased performance could not be compensated for by the increased throughput of integrating mode or by the increased low-frequency contrast of integrating mode with the VPP. These data show that the superior image quality provided by counting mode is more important for high-resolution cryo-EM reconstructions than the superior throughput of integrating mode. Full Article text
ration The resolution revolution in cryoEM requires high-quality sample preparation: a rapid pipeline to a high-resolution map of yeast fatty acid synthase By scripts.iucr.org Published On :: 2020-01-25 Single-particle electron cryo-microscopy (cryoEM) has undergone a `resolution revolution' that makes it possible to characterize megadalton (MDa) complexes at atomic resolution without crystals. To fully exploit the new opportunities in molecular microscopy, new procedures for the cloning, expression and purification of macromolecular complexes need to be explored. Macromolecular assemblies are often unstable, and invasive construct design or inadequate purification conditions and sample-preparation methods can result in disassembly or denaturation. The structure of the 2.6 MDa yeast fatty acid synthase (FAS) has been studied by electron microscopy since the 1960s. Here, a new, streamlined protocol for the rapid production of purified yeast FAS for structure determination by high-resolution cryoEM is reported. Together with a companion protocol for preparing cryoEM specimens on a hydrophilized graphene layer, the new protocol yielded a 3.1 Å resolution map of yeast FAS from 15 000 automatically picked particles within a day. The high map quality enabled a complete atomic model of an intact fungal FAS to be built. Full Article text
ration Estimation of high-order aberrations and anisotropic magnification from cryo-EM data sets in RELION-3.1 By scripts.iucr.org Published On :: 2020-02-11 Methods are presented that detect three types of aberrations in single-particle cryo-EM data sets: symmetrical and antisymmetrical optical aberrations and magnification anisotropy. Because these methods only depend on the availability of a preliminary 3D reconstruction from the data, they can be used to correct for these aberrations for any given cryo-EM data set, a posteriori. Using five publicly available data sets, it is shown that considering these aberrations improves the resolution of the 3D reconstruction when these effects are present. The methods are implemented in version 3.1 of the open-source software package RELION. Full Article text
ration High-resolution cryo-EM reconstructions in the presence of substantial aberrations By scripts.iucr.org Published On :: 2020-03-26 Here, an analysis is performed of how uncorrected antisymmetric aberrations, such as coma and trefoil, affect cryo-EM single-particle reconstruction (SPR) results, and an analytical formula quantifying information loss owing to their presence is inferred that explains why Fourier-shell coefficient-based statistics may report significantly overestimated resolution if these aberrations are not fully corrected. The analysis is validated with reference-based aberration refinement for two cryo-EM SPR data sets acquired with a 200 kV microscope in the presence of coma exceeding 40 µm, and 2.3 and 2.7 Å reconstructions for 144 and 173 kDa particles, respectively, were obtained. The results provide a description of an efficient approach for assessing information loss in cryo-EM SPR data acquired in the presence of higher order aberrations, and address inconsistent guidelines regarding the level of aberrations that is acceptable in cryo-EM SPR experiments. Full Article text
ration Biochemical and structural explorations of α-hydroxyacid oxidases reveal a four-electron oxidative decarboxylation reaction By scripts.iucr.org Published On :: 2019-07-30 p-Hydroxymandelate oxidase (Hmo) is a flavin mononucleotide (FMN)-dependent enzyme that oxidizes mandelate to benzoylformate. How the FMN-dependent oxidation is executed by Hmo remains unclear at the molecular level. A continuum of snapshots from crystal structures of Hmo and its mutants in complex with physiological/nonphysiological substrates, products and inhibitors provides a rationale for its substrate enantioselectivity/promiscuity, its active-site geometry/reactivity and its direct hydride-transfer mechanism. A single mutant, Y128F, that extends the two-electron oxidation reaction to a four-electron oxidative decarboxylation reaction was unexpectedly observed. Biochemical and structural approaches, including biochemistry, kinetics, stable isotope labeling and X-ray crystallography, were exploited to reach these conclusions and provide additional insights. Full Article text
ration Controlled dehydration, structural flexibility and gadolinium MRI contrast compound binding in the human plasma glycoprotein afamin By scripts.iucr.org Published On :: 2019-11-19 Afamin, which is a human blood plasma glycoprotein, a putative multifunctional transporter of hydrophobic molecules and a marker for metabolic syndrome, poses multiple challenges for crystallographic structure determination, both practically and in analysis of the models. Several hundred crystals were analysed, and an unusual variability in cell volume and difficulty in solving the structure despite an ∼34% sequence identity with nonglycosylated human serum albumin indicated that the molecule exhibits variable and context-sensitive packing, despite the simplified glycosylation in insect cell-expressed recombinant afamin. Controlled dehydration of the crystals was able to stabilize the orthorhombic crystal form, reducing the number of molecules in the asymmetric unit from the monoclinic form and changing the conformational state of the protein. An iterative strategy using fully automatic experiments available on MASSIF-1 was used to quickly determine the optimal protocol to achieve the phase transition, which should be readily applicable to many types of sample. The study also highlights the drawback of using a single crystallographic structure model for computational modelling purposes given that the conformational state of the binding sites and the electron density in the binding site, which is likely to result from PEGs, greatly varies between models. This also holds for the analysis of nonspecific low-affinity ligands, where often a variety of fragments with similar uncertainty can be modelled, inviting interpretative bias. As a promiscuous transporter, afamin also seems to bind gadoteridol, a magnetic resonance imaging contrast compound, in at least two sites. One pair of gadoteridol molecules is located near the human albumin Sudlow site, and a second gadoteridol molecule is located at an intermolecular site in proximity to domain IA. The data from the co-crystals support modern metrics of data quality in the context of the information that can be gleaned from data sets that would be abandoned on classical measures. Full Article text
ration Shake-it-off: a simple ultrasonic cryo-EM specimen-preparation device By scripts.iucr.org Published On :: 2019-11-22 Although microscopes and image-analysis software for electron cryomicroscopy (cryo-EM) have improved dramatically in recent years, specimen-preparation methods have lagged behind. Most strategies still rely on blotting microscope grids with paper to produce a thin film of solution suitable for vitrification. This approach loses more than 99.9% of the applied sample and requires several seconds, leading to problematic air–water interface interactions for macromolecules in the resulting thin film of solution and complicating time-resolved studies. Recently developed self-wicking EM grids allow the use of small volumes of sample, with nanowires on the grid bars removing excess solution to produce a thin film within tens of milliseconds from sample application to freezing. Here, a simple cryo-EM specimen-preparation device that uses components from an ultrasonic humidifier to transfer protein solution onto a self-wicking EM grid is presented. The device is controlled by a Raspberry Pi single-board computer and all components are either widely available or can be manufactured by online services, allowing the device to be constructed in laboratories that specialize in cryo-EM rather than instrument design. The simple open-source design permits the straightforward customization of the instrument for specialized experiments. Full Article text
ration ALEPH: a network-oriented approach for the generation of fragment-based libraries and for structure interpretation By scripts.iucr.org Published On :: 2020-02-26 The analysis of large structural databases reveals general features and relationships among proteins, providing useful insight. A different approach is required to characterize ubiquitous secondary-structure elements, where flexibility is essential in order to capture small local differences. The ALEPH software is optimized for the analysis and the extraction of small protein folds by relying on their geometry rather than on their sequence. The annotation of the structural variability of a given fold provides valuable information for fragment-based molecular-replacement methods, in which testing alternative model hypotheses can succeed in solving difficult structures when no homology models are available or are successful. ARCIMBOLDO_BORGES combines the use of composite secondary-structure elements as a search model with density modification and tracing to reveal the rest of the structure when both steps are successful. This phasing method relies on general fold libraries describing variations around a given pattern of β-sheets and helices extracted using ALEPH. The program introduces characteristic vectors defined from the main-chain atoms as a way to describe the geometrical properties of the structure. ALEPH encodes structural properties in a graph network, the exploration of which allows secondary-structure annotation, decomposition of a structure into small compact folds, generation of libraries of models representing a variation of a given fold and finally superposition of these folds onto a target structure. These functions are available through a graphical interface designed to interactively show the results of structure manipulation, annotation, fold decomposition, clustering and library generation. ALEPH can produce pictures of the graphs, structures and folds for publication purposes. Full Article text
ration The influence of deuteration on the crystal structure of hybrid halide perovskites: a temperature-dependent neutron diffraction study of FAPbBr3 By scripts.iucr.org Published On :: 2020-03-20 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. Full Article text
ration Saturation and self-absorption effects in the angle-dependent 2p3d resonant inelastic X-ray scattering spectra of Co3+ By journals.iucr.org Published On :: It is shown that the 2p3d resonant inelastic X-ray scattering intensity is distorted by saturation and self-absorption effects, i.e. by incident-energy-dependent saturation and by emission-energy-dependent self-absorption. Full Article text
ration Correlative vibrational spectroscopy and 2D X-ray diffraction to probe the mineralization of bone in phosphate-deficient mice By scripts.iucr.org Published On :: 2019-08-23 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. Full Article text
ration POWGEN: rebuild of a third-generation powder diffractometer at the Spallation Neutron Source By scripts.iucr.org Published On :: 2019-10-01 The neutron powder diffractometer POWGEN at the Spallation Neutron Source has recently (2017–2018) undergone an upgrade which resulted in an increased detector complement along with a full overhaul of the structural design of the instrument. The current instrument has a solid angular coverage of 1.2 steradians and maintains the original third-generation concept, providing a single-histogram data set over a wide d-spacing range and high resolution to access large unit cells, detailed structural refinements and in situ/operando measurements. Full Article text
ration Successful sample preparation for serial crystallography experiments By scripts.iucr.org Published On :: 2019-11-14 Serial crystallography, at both synchrotron and X-ray free-electron laser light sources, is becoming increasingly popular. However, the tools in the majority of crystallization laboratories are focused on producing large single crystals by vapour diffusion that fit the cryo-cooled paradigm of modern synchrotron crystallography. This paper presents several case studies and some ideas and strategies on how to perform the conversion from a single crystal grown by vapour diffusion to the many thousands of micro-crystals required for modern serial crystallography grown by batch crystallization. These case studies aim to show (i) how vapour diffusion conditions can be converted into batch by optimizing the length of time crystals take to appear; (ii) how an understanding of the crystallization phase diagram can act as a guide when designing batch crystallization protocols; and (iii) an accessible methodology when attempting to scale batch conditions to larger volumes. These methods are needed to minimize the sample preparation gap between standard rotation crystallography and dedicated serial laboratories, ultimately making serial crystallography more accessible to all crystallographers. Full Article text
ration A study of the strain distribution by scanning X-ray diffraction on GaP/Si for III–V monolithic integration on silicon By journals.iucr.org Published On :: The distribution of plastic relaxation defects is studied using a nondestructive sub-micrometre X-ray diffraction scanning technique. Full Article text
ration Equatorial aberration of powder diffraction data collected with an Si strip X-ray detector by a continuous-scan integration method By journals.iucr.org Published On :: Exact and approximate formulas for equatorial aberration of a continuous-scan Si strip detector are compared. Full Article text
ration Researchers discover treefrog embryos can evaluate different features of vibrations By insider.si.edu Published On :: Wed, 16 Dec 2009 16:16:58 +0000 Recently, researchers from Boston University and the Smithsonian Tropical Research Institute in Panama have been taking a closer look at the vibrations that red-eyed treefrog embryos use as cues to trigger early hatching. They discovered that treefrog embryos can evaluate different features of vibrations. The post Researchers discover treefrog embryos can evaluate different features of vibrations appeared first on Smithsonian Insider. Full Article Research News Science & Nature amphibian frogs Tropical Research Institute
ration Environmental Research Center to help with Chesapeake Bay seagrass restoration By insider.si.edu Published On :: Wed, 22 Dec 2010 15:33:41 +0000 A research team from The Smithsonian Environmental Research Center and Virginia's Old Dominion University will be awarded $110,999 to develop a tool to help seagrass restorers predict which places will be the best for planting seagrasses, the Virginia Sea Grant has announced. The post Environmental Research Center to help with Chesapeake Bay seagrass restoration appeared first on Smithsonian Insider. Full Article Animals Marine Science Research News Science & Nature biodiversity Chesapeake Bay climate change conservation biology Smithsonian Environmental Research Center
ration New genetic evidence confirms coyote migration route to Virginia and hybridization with wolves By insider.si.edu Published On :: Wed, 26 Oct 2011 12:37:08 +0000 In a new study researchers from the Smithsonian Conservation Biology Institute’s Center for Conservation and Evolutionary Genetics used DNA from coyote scat (feces) to trace the route that led some of the animals to colonize in Northern Virginia. The post New genetic evidence confirms coyote migration route to Virginia and hybridization with wolves appeared first on Smithsonian Insider. Full Article Animals Science & Nature conservation biology endangered species invasive species mammals Smithsonian's National Zoo
ration Vampire Squid Illustration By insider.si.edu Published On :: Wed, 31 Oct 2012 13:27:42 +0000 Vampire Squid Illustration, 1889 This Smithsonian Snapshot celebrates the Halloween season with this 1889 scientific illustration of a vampire squid from Smithsonian Libraries. Its jet-black […] The post Vampire Squid Illustration appeared first on Smithsonian Insider. Full Article Animals Art Snapshot visual arts
ration Illustration from American game fishes, their habits, habitat, and peculiarities By insider.si.edu Published On :: Wed, 02 Jan 2013 16:24:55 +0000 Frontispiece illustration of “flies” from the 1882 book American game fishes, their habits, habitat, and peculiarities; how, when, and where to angle for them, featuring […] The post Illustration from American game fishes, their habits, habitat, and peculiarities appeared first on Smithsonian Insider. Full Article Marine Science Research News Science & Nature Spotlight conservation biology fishes National Museum of Natural History
ration New project to unlock migration mysteries from air By insider.si.edu Published On :: Fri, 06 Dec 2013 15:55:45 +0000 Unlocking the mysteries of animal migration through precise, near real-time tracking can solve major conservation challenges and transform wildlife science worldwide. For the past year, […] The post New project to unlock migration mysteries from air appeared first on Smithsonian Insider. Full Article Animals Research News Science & Nature aeronautics aviation biodiversity birds climate change conservation conservation biology endangered species extinction mammals Migratory Bird Center migratory birds new species Smithsonian's National Zoo
ration Interstellar exploration – five planets where humans may (or may not) be able to live someday By insider.si.edu Published On :: Mon, 10 Nov 2014 17:54:43 +0000 Unless you live under a lunar rock, you’ve probably heard about or seen director Christopher Nolan’s latest blockbuster “Interstellar.” Starring Anne Hathaway and Matthew McConaughey, […] The post Interstellar exploration – five planets where humans may (or may not) be able to live someday appeared first on Smithsonian Insider. Full Article Research News Science & Nature Space planets
ration Panama shatters raptor migration record By insider.si.edu Published On :: Wed, 12 Nov 2014 13:40:28 +0000 More than two million migrating raptors passed over Panama City on Sunday, Nov. 2, doubling the previous record of almost 900,000 tallied in a single […] The post Panama shatters raptor migration record appeared first on Smithsonian Insider. Full Article Animals Research News Science & Nature birds migratory birds
ration Warming temperatures may mean more monarch generations in some areas of North America By insider.si.edu Published On :: Wed, 19 Aug 2015 16:25:22 +0000 Warming temperatures may mean more generations of monarch butterflies in North America during summer months, say scientists who recently finished experiments with monarch caterpillars and […] The post Warming temperatures may mean more monarch generations in some areas of North America appeared first on Smithsonian Insider. Full Article Animals Research News Science & Nature climate change
ration Two invasive species have Hawaiian reunion after 80-year separation By insider.si.edu Published On :: Mon, 30 Jan 2017 13:20:25 +0000 Fat, toxic and nocturnal, cane toads (Rhinella marina) are abundant today in Hawaii, even though they are South American natives. Released on the Hawaiian Islands […] The post Two invasive species have Hawaiian reunion after 80-year separation appeared first on Smithsonian Insider. Full Article Animals Research News Science & Nature invasive species reptiles Smithsonian Tropical Research Institute
ration Next generation astronomical survey to map the entire sky By insider.si.edu Published On :: Mon, 27 Nov 2017 18:23:08 +0000 The next generation of the Sloan Digital Sky Survey (SDSS-V), directed by Juna Kollmeier of the Carnegie Institution for Science, will move forward with mapping […] The post Next generation astronomical survey to map the entire sky appeared first on Smithsonian Insider. Full Article Science & Nature Space Center for Astrophysics | Harvard & Smithsonian Smithsonian Astrophysical Observatory
ration GBT Detection Unlocks Exploration of ‘Aromatic’ Interstellar Chemistry By insider.si.edu Published On :: Thu, 11 Jan 2018 14:30:53 +0000 Astronomers had a mystery on their hands. No matter where they looked, from inside the Milky Way to distant galaxies, they observed a puzzling glow […] The post GBT Detection Unlocks Exploration of ‘Aromatic’ Interstellar Chemistry appeared first on Smithsonian Insider. Full Article Science & Nature Space Smithsonian Astrophysical Observatory
ration EML4-ALK V3 oncogenic fusion proteins promote microtubule stabilization and accelerated migration through NEK9 and NEK7 [RESEARCH ARTICLE] By jcs.biologists.org Published On :: 2020-03-17T03:51:28-07:00 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. FryEML4-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. Full Article
ration Maturation and phenotype of pathophysiological neuronal excitability of human cells in tau-related dementia [RESEARCH ARTICLE] By jcs.biologists.org Published On :: 2020-04-16T06:39:33-07:00 Olga Kopach, Noemi Esteras, Selina Wray, Dmitri A. Rusakov, and Andrey Y. AbramovFrontotemporal 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 Nav1.6 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. Full Article
ration En bloc TGN recruitment of Aspergillus TRAPPII reveals TRAPP maturation as unlikely to drive RAB1-to-RAB11 transition [RESEARCH ARTICLE] By jcs.biologists.org Published On :: 2020-04-23T01:49:49-07:00 M. Pinar and M. A. PenalvaTRAnsport Protein Particle (TRAPP) complexes regulate membrane traffic. TRAPPII and TRAPPIII share a core hetero-heptamer, also denoted TRAPPI. In fungi TRAPPIII and TRAPPII mediate GDP exchange on RAB1 and RAB11, respectively, regulating traffic across the Golgi, with TRAPPIII also activating RAB1 in autophagosomes. Our finding that Aspergillus nidulans TRAPPII can be assembled by addition of a TRAPPII-specific subcomplex onto core TRAPP prompted us to investigate the possibility that TRAPPI/TRAPPIII already residing in the Golgi matures into TRAPPII to determine a RAB1-to-RAB11 conversion as Golgi cisternae progress from early Golgi to TGN identity. By time-resolved microscopy we determine that the TRAPPII reporter Trs120/TRAPPC9 is recruited to existing TGN cisternae slightly before RAB11 arrives, and resides for~45 sec on them before cisternae tear off into RAB11 secretory carriers. Notably, the core TRAPP reporter Bet3/TRAPPC3 was not detectable in early Golgi cisternae, being instead recruited to TGN cisternae simultaneously with Trs120/TRAPPC9, indicating en bloc recruitment of TRAPPII to the Golgi and arguing strongly against the TRAPP maturation model. Full Article
ration Tetrahymena Poc5 is a transient basal body component that is important for basal body maturation [RESEARCH ARTICLE] By jcs.biologists.org Published On :: 2020-04-29T02:35:34-07:00 Westley Heydeck, Brian A. Bayless, Alexander J. Stemm-Wolf, Eileen T. O'Toole, Amy S. Fabritius, Courtney Ozzello, Marina Nguyen, and Mark WineyBasal bodies (BBs) are microtubule-based organelles that template and stabilize cilia at the cell surface. Centrins ubiquitously associate with BBs and function in BB assembly, maturation, and stability. Human POC5 (hPOC5) is a highly conserved centrin-binding protein that binds centrins through Sfi1p-like repeats and is required for building full-length, mature centrioles. Here, we use the BB-rich cytoskeleton of Tetrahymena thermophila to characterize Poc5 BB functions. Tetrahymena Poc5 (TtPoc5) uniquely incorporates into assembling BBs and is then removed from mature BBs prior to ciliogenesis. Complete genomic knockout of TtPOC5 leads to a significantly increased production of BBs yet a markedly reduced ciliary density, both of which are rescued by reintroduction of TtPoc5. A second Tetrahymena POC5-like gene, SFR1, is similarly implicated in modulating BB production. When TtPOC5 and SFR1 are co-deleted, cell viability is compromised, and levels of BB overproduction are exacerbated. Overproduced BBs display defective transition zone formation and a diminished capacity for ciliogenesis. This study uncovers a requirement for Poc5 in building mature BBs, providing a possible functional link between hPOC5 mutations and impaired cilia. Full Article
ration Glucocorticoids rapidly inhibit cell migration through a novel, non-transcriptional HDAC6 pathway [RESEARCH ARTICLE] By jcs.biologists.org Published On :: 2020-05-07T00:45:50-07:00 Stephen Kershaw, David J. Morgan, James Boyd, David G. Spiller, Gareth Kitchen, Egor Zindy, Mudassar Iqbal, Magnus Rattray, Chris M. Sanderson, Andrew Brass, Claus Jorgensen, Tracy Hussell, Laura C. Matthews, and David W. RayGlucocorticoids (GCs) act through the glucocorticoid receptor (GR) to regulate immunity, energy metabolism, and tissue repair. Upon ligand binding, activated GR mediates cellular effects by regulating gene expression, but some GR effects can occur rapidly without new transcription. We show GCs rapidly inhibit cell migration, in response to both GR agonist and antagonist ligand binding. The inhibitory effect on migration is prevented by GR knockdown with siRNA, confirming GR specificity, but not by actinomycin D treatment, suggesting a non-transcriptional mechanism. We identified a rapid onset increase in microtubule polymerisation following glucocorticoid treatment, identifying cytoskeletal stabilisation as the likely mechanism of action. HDAC6 overexpression, but not knockdown of αTAT1, rescued the GC effect, implicating HDAC6 as the GR effector. Consistent with this hypothesis, ligand-dependent cytoplasmic interaction between GR and HDAC6 was demonstrated by quantitative imaging. Taken together, we propose that activated GR inhibits HDAC6 function and thereby increases the stability of the microtubule network to reduce cell motility. We therefore report a novel, non-transcriptional mechanism whereby GCs impair cell motility through inhibition of HDAC6 and rapid reorganization of the cell architecture. Full Article
ration PBS Newshour takes a look at the new National Air and Space Museum exhibition “NASA | ART: 50 Years of Exploration” By insider.si.edu Published On :: Sun, 05 Jun 2011 09:34:15 +0000 This new PBS Newshour video takes a look at a new exhibit at the Air and Space Museum celebrating NASA's space art program. The post PBS Newshour takes a look at the new National Air and Space Museum exhibition “NASA | ART: 50 Years of Exploration” appeared first on Smithsonian Insider. Full Article History & Culture Science & Nature Space Video astronomy astrophysics exhibitions National Air and Space Museum
ration Restoration of the Ohkay Owingeh Tribe’s historic pueblo By insider.si.edu Published On :: Tue, 03 Jan 2017 19:41:29 +0000 Ohkay Owingeh from Adventure Pictures on Vimeo. Currently featured in the exhibition “By the People” at the Cooper Hewitt, Smithsonian Design Museum in New York City […] The post Restoration of the Ohkay Owingeh Tribe’s historic pueblo appeared first on Smithsonian Insider. Full Article Anthropology History & Culture Science & Nature Video Cooper Hewitt
ration Adding 750,000 dots to The Obliteration Room By insider.si.edu Published On :: Mon, 15 May 2017 18:45:59 +0000 Time-lapse captured at the Hirshhorn Museum of Yayoi Kusama’s The Obliteration Room, on view in “Yayoi Kusama: Infinity Mirrors.” In Yayoi Kusama’s “The Obliteration Room,” […] The post Adding 750,000 dots to The Obliteration Room appeared first on Smithsonian Insider. Full Article Art History & Culture Video Hirshhorn Museum and Sculpture Garden
ration Flight Operations on the USS Eisenhower By insider.si.edu Published On :: Wed, 09 Aug 2017 12:30:34 +0000 Timelapse video of Flight operations aboard the USS Dwight D. Eisenhower brought to you by the Smithsonian’s National Air and Space Museum. The post Flight Operations on the USS Eisenhower appeared first on Smithsonian Insider. Full Article History & Culture Video National Air and Space Museum
ration Frederick Walpole illustrations recovered By insider.si.edu Published On :: Wed, 21 Dec 2011 16:01:49 +0000 Lodgepole pine drawn in 1898 by U.S. National Herbarium illustrator Frederick Andrew Walpole. The post Frederick Walpole illustrations recovered appeared first on Smithsonian Insider. Full Article Plants Spotlight National Museum of Natural History
ration Nonlinear optical organic–inorganic crystals: synthesis, structural analysis and verification of harmonic generation in tri-(o-chloroanilinium nitrate) By scripts.iucr.org Published On :: 2019-01-01 The structural and nonlinear optical properties of a new anilinium hybrid crystal of chemical formula (C6H7NCl+·NO3−)3 have been investigated. The crystal structure was determined from single-crystal X-ray diffraction measurements performed at a temperature of 100 K which show that the compound crystallizes in a noncentrosymmetric space group (Pna21). The structural analysis was coupled with Hirshfeld surface analysis to evaluate the contribution of the different intermolecular interactions to the formation of supramolecular assemblies in the solid state that exhibit nonlinear optical features. This analysis reveals that the studied compound is characterized by a three-dimensional network of hydrogen bonds and the main contributions are provided by the O...H, C...H, H...H and Cl...H interactions, which alone represent ∼85% of the total contributions to the Hirshfeld surfaces. It is noteworthy that the halogen...H contributions are quite comparable with those of the H...H contacts. The nonlinear optical properties were investigated by nonlinear diffuse femtosecond-pulse reflectometry and the obtained results were compared with those of the reference material LiNbO3. The hybrid crystals exhibit notable second (SHG) and third (THG) harmonic generation which confirms its polarity is generated by the different intermolecular interactions. These measurements also highlight that the THG signal of the new anilinium compound normalized to its SHG counterpart is more pronounced than for LiNbO3. Full Article text
ration Simulink - Incorrect Code Generation: In a model containing blocks from the SoC Blockset and asynchronous sample time, the sorted order might be incorrect By in.mathworks.com Published On :: Fri, 08 May 2020 14:04:15 +0000 Simulink might produce an incorrect sorted order for a model that meets all of the following conditions:The model contains blocks from the SoC BlocksetThe Signal logging option is selected in the model configuration setSignals using asynchronous sample time are configured for loggingAs a result, Simulink might produce incorrect results in Normal, Accelerator, and Rapid Accelerator simulation modes as well as in generated code.This bug exists in the following release(s): R2020a Interested in Upgrading? Full Article
ration Simulink - Signal Editor prematurely indicates that a save operation is complete By in.mathworks.com Published On :: Fri, 08 May 2020 15:26:15 +0000 When the Signal Editor is saving data, the indicator that the save is occurring does not appear. You might notice a delay when saving large data files.This bug exists in the following release(s): R2020a Interested in Upgrading? Full Article
ration Lamellipodin tunes cell migration by stabilizing protrusions and promoting adhesion formation By jcs.biologists.org Published On :: 2020-04-09 Georgi DimchevApr 9, 2020; 133:jcs239020-jcs239020Articles Full Article
ration ADAMTS-1 and syndecan-4 intersect in the regulation of cell migration and angiogenesis By jcs.biologists.org Published On :: 2020-04-08 Jordi LambertApr 8, 2020; 133:jcs235762-jcs235762Articles Full Article
ration Next generation operating system? By www.bleepingcomputer.com Published On :: 2019-07-11T05:51:38-05:00 Full Article