Archives, Room Use Only - HE336.E94 O74 1858

Archives, Room Use Only - HE7631.S75 1946

Archives, Room Use Only - TK5451.S33 1876

Archives, Room Use Only - TK5627.J46 1862

Archives, Room Use Only - HE7045.C46 1952

Special CorrespondentHyderabad

Awareness through music

Surge in number of returnees without registration

The aviation sector has been hit hard due to the suspension of all commercial passenger flights during the coronavirus-induced lockdown in the country

Being able to visualize biology at the molecular level is essential for our understanding of the world. A structural biology approach reveals the molecular basis of disease processes and can guide the design of new drugs as well as aid in the optimization of existing medicines. However, due to the lack of a synchrotron light source, adequate infrastructure, skilled persons and incentives for scientists in addition to limited financial support, the majority of countries across the African continent do not conduct structural biology research. Nevertheless, with technological advances such as robotic protein crystallization and remote data collection capabilities offered by many synchrotron light sources, X-ray crystallography is now potentially accessible to Africa-based scientists. This leap in technology led to the establishment in 2017 of BioStruct-Africa, a non-profit organization (Swedish corporate ID: 802509-6689) whose core aim is capacity building for African students and researchers in the field of structural biology with a focus on prevalent diseases in the African continent. The team is mainly composed of, but not limited to, a group of structural biologists from the African diaspora. The members of BioStruct-Africa have taken up the mantle to serve as a catalyst in order to facilitate the information and technology transfer to those with the greatest desire and need within Africa. BioStruct-Africa achieves this by organizing workshops onsite at our partner universities and institutions based in Africa, followed by post-hoc online mentoring of participants to ensure sustainable capacity building. The workshops provide a theoretical background on protein crystallography, hands-on practical experience in protein crystallization, crystal harvesting and cryo-cooling, live remote data collection on a synchrotron beamline, but most importantly the links to drive further collaboration through research. Capacity building for Africa-based researchers in structural biology is crucial to win the fight against the neglected tropical diseases, e.g. ascariasis, hookworm, trichuriasis, lymphatic filariasis, active trachoma, loiasis, yellow fever, leprosy, rabies, sleeping sickness, onchocerciasis, schistosomiasis, etc., that constitute significant health, social and economic burdens to the continent. BioStruct-Africa aims to build local and national expertise that will have direct benefits for healthcare within the continent.

Geologists discover hundreds of buried valleys throughout Britain  Press and Journal

The X-chromosome-linked inhibitor of apoptosis protein (XIAP) is a multidomain protein whose main function is to block apoptosis by caspase inhibition. XIAP is also involved in other signalling pathways, including NF-κB activation and copper homeostasis. XIAP is overexpressed in tumours, potentiating cell survival and resistance to chemotherapeutics, and has therefore become an important target for the treatment of malignancy. Despite the fact that the structure of each single domain is known, the conformation of the full-length protein has never been determined. Here, the first structural model of the full-length XIAP dimer, determined by an integrated approach using nuclear magnetic resonance, small-angle X-ray scattering and electron paramagnetic resonance data, is presented. It is shown that XIAP adopts a compact and relatively rigid conformation, implying that the spatial arrangement of its domains must be taken into account when studying the interactions with its physiological partners and in developing effective inhibitors.

High-throughput X-ray crystal structures of protein–ligand complexes are critical to pharmaceutical drug development. However, cryocooling of crystals and X-ray radiation damage may distort the observed ligand binding. Serial femtosecond crystallography (SFX) using X-ray free-electron lasers (XFELs) can produce radiation-damage-free room-temperature structures. Ligand-binding studies using SFX have received only modest attention, partly owing to limited beamtime availability and the large quantity of sample that is required per structure determination. Here, a high-throughput approach to determine room-temperature damage-free structures with excellent sample and time efficiency is demonstrated, allowing complexes to be characterized rapidly and without prohibitive sample requirements. This yields high-quality difference density maps allowing unambiguous ligand placement. Crucially, it is demonstrated that ligands similar in size or smaller than those used in fragment-based drug design may be clearly identified in data sets obtained from <1000 diffraction images. This efficiency in both sample and XFEL beamtime opens the door to true high-throughput screening of protein–ligand complexes using SFX.

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.

The phase problem remains a major barrier to overcome in protein structure solution by X-ray crystallography. In recent years, new molecular-replacement approaches using ab initio models and ideal secondary-structure components have greatly contributed to the solution of novel structures in the absence of clear homologues in the PDB or experimental phasing information. This has been particularly successful for highly α-helical structures, and especially coiled-coils, in which the relatively rigid α-helices provide very useful molecular-replacement fragments. This has been seen within the program AMPLE, which uses clustered and truncated ensembles of numerous ab initio models in structure solution, and is already accomplished for α-helical and coiled-coil structures. Here, an expansion in the scope of coiled-coil structure solution by AMPLE is reported, which has been achieved through general improvements in the pipeline, the removal of tNCS correction in molecular replacement and two improved methods for ab initio modelling. Of the latter improvements, enforcing the modelling of elongated helices overcame the bias towards globular folds and provided a rapid method (equivalent to the time requirements of the existing modelling procedures in AMPLE) for enhanced solution. Further, the modelling of two-, three- and four-helical oligomeric coiled-coils, and the use of full/partial oligomers in molecular replacement, provided additional success in difficult and lower resolution cases. Together, these approaches have enabled the solution of a number of parallel/antiparallel dimeric, trimeric and tetrameric coiled-coils at resolutions as low as 3.3 Å, and have thus overcome previous limitations in AMPLE and provided a new functionality in coiled-coil structure solution at lower resolutions. These new approaches have been incorporated into a new release of AMPLE in which automated elongated monomer and oligomer modelling may be activated by selecting `coiled-coil' mode.

Microcrystal delivery methods are pivotal in the use of serial femtosecond crystallography (SFX) to resolve the macromolecular structures of proteins. Here, the development of a novel technique and instruments for efficiently delivering microcrystals for SFX are presented. The new method, which relies on a one-dimensional fixed-target system that includes a microcrystal container, consumes an extremely low amount of sample compared with conventional two-dimensional fixed-target techniques at ambient temperature. This novel system can deliver soluble microcrystals without highly viscous carrier media and, moreover, can be used as a microcrystal growth device for SFX. Diffraction data collection utilizing this advanced technique along with a real-time visual servo scan system has been successfully demonstrated for the structure determination of proteinase K microcrystals at 1.85 Å resolution.

Single-crystalline-like thin films composed of crystallographically aligned grains are a new prototype of 2D materials developed recently for low-cost and high-performance flexible electronics as well as second-generation high-temperature superconductors. In this work, significant texture improvement in single-crystalline-like materials is achieved through growth of a 330 nm-thick silver layer.

Ba excess in LaBaGaO4 triggers ionic conductivity together with structural disorder. A direct correlation is found between the density functional theory model energy and the pair distribution function fit residual.

Finding this stellar relic wasn’t easy. It is 60,000 times dimmer than the faintest star visible to the unaided eye. The team also had to distinguish it from many surrounding stars that aren’t so old. Just like an archaeological dig, the hunt succeeded through a combination of patience and clever use of technology.

The post Ancient star discovered through patience and clever use of technology appeared first on Smithsonian Insider.

Snowflake Study through Photomicrography, 1890 Wilson A. Bentley became fascinated with the crystalline structure of individual snowflakes on his parent’s Vermont farm. By adapting a […]

The post Snowflake Study through Photomicrography, 1890 appeared first on Smithsonian Insider.

Humanity's most complex ground-based astronomy observatory, the Atacama Large Millimeter/submillimeter Array (ALMA), has officially opened for astronomers at its 16,500-foot high desert plateau in northern Chile.

The post Center for Astrophysics project gets first look through new ALMA telescope appeared first on Smithsonian Insider.

For centuries, cultures around the world have used masks in ritual dances and festivals to represent traditional characters. This copper mask, found in the Smithsonian’s […]

The post Mexican Masks: Tales Through Dance appeared first on Smithsonian Insider.

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.

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. Ray

Glucocorticoids (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.

We’ve seen a serious series of super moons this summer and the show’s not over yet. Mark your calendars: the next one will light up […]

The post Cutting through the dust: Radar shows moon’s true face for first time appeared first on Smithsonian Insider.

This work studies the elastic scattering behavior of electron vortices when propagating through amorphous samples. A formulation of the multislice approach in cylindrical coordinates is used to theoretically investigate the redistribution of intensity between different angular momentum components due to scattering. To corroborate and elaborate on our theoretical results, extensive numerical simulations are performed on three model systems (Si3N4, Fe0.8B0.2, Pt) for a wide variety of experimental parameters to quantify the purity of the vortices, the net angular momentum transfer, and the variability of the results with respect to the random relative position between the electron beam and the scattering atoms. These results will help scientists to further improve the creation of electron vortices and enhance applications involving them.

On June 7 the Sun unleashed an spectacular solar flare with a substantial coronal mass ejection. A large cloud of plasma mushroomed up, and while some parts fell back into the Sun, most rushed off into space. The first two segments of this video are seen through the Atmospheric Imaging Assembly aboard NASA's Solar Dynamics Observatory. The AIA was developed by Smithsonian scientists.

The post Spectacular June 7 solar flare seen through the Atmospheric Imaging Assembly aboard Solar Dynamics Observatory appeared first on Smithsonian Insider.

As the host of PBS’s “Scientific American Frontiers,” Alan Alda has interviewed scientists, physicists, neuroscientists, and academics. Forging a connection with these guests through freewheeling […]

The post Alan Alda: Relating Through Improvisation appeared first on Smithsonian Insider.

A single breakthrough discovery for managing citrus greening in Florida in the future is unlikely, says a new report by the National Academies of Sciences, Engineering, and Medicine.

A new report from the National Academies of Sciences, Engineering, and Medicine identifies the most promising scientific breakthroughs that are possible to achieve in the next decade to increase the U.S. food and agriculture system’s sustainability, competitiveness, and resilience.

A new report from the National Academies of Sciences, Engineering, and Medicine highlights the dynamic process of learning throughout the life span and identifies frontiers in which more research is needed to pursue an even deeper understanding of human learning.

A new report from the National Academies of Sciences, Engineering, and Medicine recommends changes in the way that the U.S. Department of Energy manages science and technology (S&T) development in order to accelerate the cleanup of radioactive waste and contaminated soil, groundwater, and facilities at U.S. nuclear weapons sites.

Circus of Books storefront.; Credit: Netflix/Circus Of Books (2020)

Rachel Mason had, to a certain extent, the normal upbringing you’d imagine a family of five with small business owner parents would have. But in her documentary, ‘Circus of Books’, she pulls the curtain on the double-life her parents led as modest business owners and pillars of the LGBTQ community.

Karen and Barry Mason established West Hollywood’s Circus of Books on Santa Monica Boulevard in the 1980s. What seemed like an unassuming bookstore was actually a gay porn shop that became an institution in the LGBTQ community during a time when homosexuality was still largely unaccepted. The store was far from being a “bookstore with a circus theme”. The Los Angeles-based shop was the central hub for gay pornography around the country, once one of the main distributors for adult films. 

While the store was becoming a home for gay culture and pride, the Masons largely kept their business a secret from colleagues, friends, family, even their own children. It’s a central conflict that Rachel Mason explores throughout the film as the daughter of two shop owners caught between the pressures of maintaining a traditional family image and making a living as gay pornography distributors.

Today on FilmWeek, we’re joined by ‘Circus of Books’ director Rachel Mason for a conversation on her documentary and the experience of creating a film with her parents and their secret as the subject.

‘Circus Of Books’ is currently streaming on Netflix. For more on the film from LAist’s Mike Roe, click here.

Guest:

Rachel Mason, director of the Netflix documentary ‘Circus of Books’ and daughter of Circus of Books owners Karen and Barry Mason; she tweets @RachelMasonArt

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

The world’s marine ecosystems are at risk of sudden and damaging changes. The authors of a recent study say that co-ordinated management of the many drivers of marine changes, such as overfishing and pollution, is needed across international, national and local scales to help avoid the ‘regime shifts’ that affect ecosystem services and human wellbeing.

Campaigns which remind individuals of the environmentally-friendly actions they already perform may motivate them to even more pro-environmental behaviours, new research suggests. If people identify themselves as environmentally-friendly, they are more likely to carry out green actions, even in the absence of any incentive.

A team of researchers from Florida State University, Johns Hopkins University and the National Institutes of Health has found existing drug compounds that can both stop Zika from replicating in the body and from damaging the crucial fetal brain cells that lead to birth defects in newborns.

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Concrete and asphalt's environmental impact could be reduced by over a third through changes to manufacturing processes and the use of alternative raw materials, according to research. A scenario study based on life cycle analysis has indicated that using alternative types of cement in concrete and producing asphalt at lower temperatures could substantially improve the green credentials of these two common building materials.

Eco-innovations which help prevent the production of waste are explored in a recent German study. It considers the drivers and barriers to the uptake of material efficiency measures in businesses, green procurement and product leasing schemes.

A study has evaluated three types of media campaign conducted by a large UK supermarket to encourage shoppers to reduce their food waste. These used social media, an e-newsletter and a print/digital magazine, respectively. Although they all appeared to lead to reductions in food waste to some extent, similar behavioural changes were also seen for customers who had not participated in any of the campaigns.

The cost of a Mediterranean marine protected area (MPA) network could be cut by over two thirds if countries surrounding the Sea collaborate in its creation. This is the conclusion of a study that explored how the Convention on Biological Diversity’s goals to protect wildlife through MPAs could be met cost-efficiently.

Preliminary findings from a mass participation study have indicated a link between weather conditions - specifically rain and lack of sunshine - and chronic pain.

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Tracing products through the supply chain is a key feature for all businesses and industries; this is currently possible via automated identification systems that link a product to a database to track its progress, and through information-tracing (‘infotracing’) systems that keep accessible records of this progress. A study now introduces blockchain technology as a way to electronically trace timber as it travels from the forest to final product, using an infotracing system based on open source and Radio Frequency Identification (RFID) technology that retains records in a secure, decentralised, distributed ledger.