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.

Recent developments have resulted in electron cryo-microscopy (cryo-EM) becoming a useful tool for the structure determination of biological macromolecules. For samples containing inherent flexibility, heterogeneity or preferred orientation, the collection of extensive cryo-EM data using several conditions and microscopes is often required. In such a scenario, merging cryo-EM data sets is advantageous because it allows improved three-dimensional reconstructions to be obtained. Since data sets are not always collected with the same pixel size, merging data can be challenging. Here, two methods to combine cryo-EM data are described. Both involve the calculation of a rescaling factor from independent data sets. The effects of errors in the scaling factor on the results of data merging are also estimated. The methods described here provide a guideline for cryo-EM users who wish to combine data sets from the same type of microscope and detector.

As part of the Virus-X Consortium that aims to identify and characterize novel proteins and enzymes from bacteriophages and archaeal viruses, the genes of the putative lytic proteins XepA from Bacillus subtilis prophage PBSX and YomS from prophage SPβ were cloned and the proteins were subsequently produced and functionally characterized. In order to elucidate the role and the molecular mechanism of XepA and YomS, the crystal structures of these proteins were solved at resolutions of 1.9 and 1.3 Å, respectively. XepA consists of two antiparallel β-sandwich domains connected by a 30-amino-acid linker region. A pentamer of this protein adopts a unique dumbbell-shaped architecture consisting of two discs and a central tunnel. YomS (12.9 kDa per monomer), which is less than half the size of XepA (30.3 kDa), shows homology to the C-terminal part of XepA and exhibits a similar pentameric disc arrangement. Each β-sandwich entity resembles the fold of typical cytoplasmic membrane-binding C2 domains. Only XepA exhibits distinct cytotoxic activity in vivo, suggesting that the N-terminal pentameric domain is essential for this biological activity. The biological and structural data presented here suggest that XepA disrupts the proton motive force of the cytoplasmatic membrane, thus supporting cell lysis.

Cryo-electron microscopy (cryo-EM) has rapidly expanded with the introduction of direct electron detectors, improved image-processing software and automated image acquisition. Its recent adoption by industry, particularly in structure-based drug design, creates new requirements in terms of reliability, reproducibility and throughput. In 2016, Thermo Fisher Scientific (then FEI) partnered with the Medical Research Council Laboratory of Molecular Biology, the University of Cambridge Nanoscience Centre and five pharmaceutical companies [Astex Pharmaceuticals, AstraZeneca, GSK, Sosei Heptares and Union Chimique Belge (UCB)] to form the Cambridge Pharmaceutical Cryo-EM Consortium to share the risks of exploring cryo-EM for early-stage drug discovery. The Consortium expanded with a second Themo Scientific Krios Cryo-EM at the University of Cambridge Department of Materials Science and Metallurgy. Several Consortium members have set up in-house facilities, and a full service cryo-EM facility with Krios and Glacios has been created with the Electron Bio-Imaging Centre for Industry (eBIC for Industry) at Diamond Light Source (DLS), UK. This paper will cover the lessons learned during the setting up of these facilities, including two Consortium Krios microscopes and preparation laboratories, several Glacios microscopes at Consortium member sites, and a Krios and Glacios at eBIC for Industry, regarding site evaluation and selection for high-resolution cryo-EM microscopes, the installation process, scheduling, the operation and maintenance of the microscopes and preparation laboratories, and image processing.

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.

Crystallographic textures, as they develop for example during cold forming, can have a significant influence on the mechanical properties of metals, such as plastic anisotropy. Textures are typically characterized by a non-uniform distribution of crystallographic orientations that can be measured by diffraction experiments like electron backscatter diffraction (EBSD). Such experimental data usually contain a large number of data points, which must be significantly reduced to be used for numerical modeling. However, the challenge in such data reduction is to preserve the important characteristics of the experimental data, while reducing the volume and preserving the computational efficiency of the numerical model. For example, in micromechanical modeling, representative volume elements (RVEs) of the real microstructure are generated and the mechanical properties of these RVEs are studied by the crystal plasticity finite element method. In this work, a new method is developed for extracting a reduced set of orientations from EBSD data containing a large number of orientations. This approach is based on the established integer approximation method and it minimizes its shortcomings. Furthermore, the L1 norm is applied as an error function; this is commonly used in texture analysis for quantitative assessment of the degree of approximation and can be used to control the convergence behavior. The method is tested on four experimental data sets to demonstrate its capabilities. This new method for the purposeful reduction of a set of orientations into equally weighted orientations is not only suitable for numerical simulation but also shows improvement in results in comparison with other available methods.

Last week, the Kepler team and CfA astronomers announced the discovery of a system of six transiting planets around one Sun-like star. The previous record holder for the number of transiting planets was three.

The post Six orbiting planets sets record for Sun-like stars say Kepler, Smithsonian astronmers appeared first on Smithsonian Insider.

A new study of marmosets, small South American monkeys, indicates that obesity may begin very early in life and suggests that marmosets may be a helpful model for obesity in humans.

The post Is obesity predestined at infancy? Marmoset study may help scientists find out. appeared first on Smithsonian Insider.

The new Sant Director of the National Museum of Natural History, Kirk Johnson, had only been on the job for 26 days when he got […]

The post Female “spidernaut” settles into new home at Smithsonian’s Insect Zoo appeared first on Smithsonian Insider.

Marmosets on track for obesity appeared to be more efficient in their feeding behavior. “Although all animals consumed the same amount of liquid, the ones […]

The post Obese marmosets are more developmentally advanced as infants, study shows 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.

Two worlds orbiting a distant star are about to become a snack of cosmic proportions. Astronomers have announced that the planets Kepler-56b and Kepler-56c will […]

The post Star set to swallow two planets appeared first on Smithsonian Insider.

A few images of comet 67P/Churyumov-Gerasimenko just sent back by the European spaceship Rosetta appear to be a snowboarder’s dream: pristine slopes covered in powder. […]

The post Comet probe set to answer ancient question of life on earth appeared first on Smithsonian Insider.

Imke K. Mandemaker, Di Zhou, Serena T. Bruens, Dick H. Dekkers, Pernette J. Verschure, Raghu R. Edupuganti, Eran Meshorer, Jeroen A. Demmers, and Jurgen A. Marteijn

Many chromatin remodeling and modifying proteins are involved in the DNA damage response by stimulating repair or inducing DNA damage signaling. Interestingly, here we identified that down regulation of the H1-interacting protein SET results in increased resistance to a wide variety of DNA damaging agents. We found that this increased resistance is not the result of an inhibitory effect of SET on DNA repair, but rather the consequence of a suppressed apoptotic response to DNA damage. We further provide evidence that the histone chaperone SET is responsible for the eviction of H1 from chromatin. Knock down of H1 in SET-depleted cells resulted in re-sensitization of cells to DNA damage, suggesting that the increased DNA damage resistance in SET-depleted cells is the result of enhanced retention of H1 on chromatin. Finally, clonogenic survival assays show that SET and p53 are epistatic in attenuating DNA damage-induced cell death. Altogether, our data show a role for SET in the DNA damage response as a regulator of cell survival following genotoxic stress.

Bipasha Dey and Richa Rikhy

Cell shape morphogenesis from spherical to polygonal occurs in epithelial cell formation in metazoan embryogenesis. In syncytial Drosophila embryos, the plasma membrane incompletely surrounds each nucleus and is organized as a polygonal epithelial-like array. Each cortical syncytial division cycle shows circular to polygonal plasma membrane transition along with furrow extension between adjacent nuclei from interphase to metaphase. In this study, we assess the relative contribution of DE-cadherin and Myosin II at the furrow for polygonal shape transition. We show that polygonality initiates during each cortical syncytial division cycle when the furrow extends from 4.75 to 5.75 µm. Polygon plasma membrane organization correlates with increased junctional tension, increased DE-cadherin and decreased Myosin II mobility. DE-cadherin regulates furrow length and polygonality. Decreased Myosin II activity allows for polygonality to occur at a lower length than controls. Increased Myosin II activity leads to loss of lateral furrow formation and complete disruption of polygonal shape transition. Our studies show that DE-cadherin-Myosin II balance regulates an optimal lateral membrane length during each syncytial cycle for polygonal shape transition.

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

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

(The Paypers) Financial institutions (FIs) working in digital assets have been required by US regulatory bodies to pay attention to their anti-money laundering and...

(The Paypers) The European Banking...

The US Federal Reserve has created a new group to advise on its planned faster payments service, the FedNow...

Source: Knox Henderson for Streetwise Reports   05/07/2020

A quick update since FansUnite Entertainment Inc. (FANS:CSE) went live on Tuesday, May 5, because big things are happening in the industry, thus showing there is an enormous appetite for this kind of technology especially now, as we (very slowly) emerge out of this COVID pandemic.

On the sports front, Germany announced that its Bundesliga soccer will resume games in May, yet with tight restrictions and no fans. This is followed by the Turkish soccer league, which plans to resume playing on June 12. The Ultimate Fighting Championship (UFC), with a huge draw to the masses—the UFC 246 prelims averaged 1.767 million viewers on ESPN—will return at VyStar Veterans Memorial Arena in Jacksonville, Fla., on May 9, again featuring no live fans. So as more sports emerge in our "new reality," where will those fans be? Online, of course! In a fanless sports environment we're going to see a lot of online engagement no matter what sport or activity that may be. That's going to spawn even more online attention, which will likely hold firm even after we emerge from our home quarantine.

The industry is rapidly consolidating. On Tuesday we alluded to The Stars Group Inc. (formerly Amaya), which, according to Bloomberg, "saw record revenue in its first quarter as COVID-19 led to an increase in online activity starting in March. Indeed TSGI.T has had a great run from $18 mid-March to a high of $40 on May 1 after it confirmed shareholder approval of a friendly takeover by UK based Flutter Entertainment plc. (LSE:FLTR.L - News). The two create a £10 billion (US$12 billion) giant, according to Racing Post, and combine for more than 13 million customers, US$4.6 billion in revenue and US$1.7 billion in EBITDA.

Investors are getting on board

In our previous note we referred to DraftKings (NASDAQ:DKNG), which launched as recently as April 23, in the thick of this stay-at-home pandemic. After completing a merger with Diamond Eagle, a special purpose acquisition company, and back-end technology provider SBTech, its stock soared. DraftKings' stock jumped 14% in its first day of trading before closing up 10.38% at $19.35. The company was also able to add another half a billion dollars on the balance sheet at a time when it's not easy to raise money. That company currently has a $17 billion market capitalization.

Meanwhile there's been a noticeable correlation of trading activity in the industry from mid-March to the end of April:

• Prior to the merger with Canadian The Stars Group, Dublin, Ireland-based Flutter, trading as OTC:PDYPY in the U.S., had a good run of its own. Since mid-March it doubled from $31 to $64 by the end of April, despite any global sport-killing pandemic.

• UK-based GVC Holdings PLC (LSE:GVC) gained 23% in the last month, from $611 to $750, reaching a US$4.3 billion market capitalization.

• After falling from February highs of $30, Scientific Games (NASDAQ:SGMS) more than tripled from a $4 low mid-march to $13 by the end of April to again reach a $1 billion market valuation.

• Penn National Gaming (NASDAQ:PENN), now at a US$1.8 billion market capitalization, has a chart that mirrors SGMS. After February highs of $38, PENN rebounded through the COVID crisis. It also more than tripled from a low of $4.50 mid-March to a $17.80 high by the end of April.

• Score Media and Gaming (SCR.V,) with a market capitalization of $185 million, during that same period, ran from $0.32 to $0.42 mid-march to April 29, gaining 31%

• (are you starting to a pattern here?)

On the regulatory front, Colorado, became the next state to legalize sports bargaining following New Jersey, Nevada, Delaware and Pennsylvania. The state is poised to generate $6 billion in annual wagers and an estimated $400 million in revenue once the industry matures, according to Dustin Gouker, chief analyst for PlayColorado.com. According to the Denver Post, Colorado fans will have their pick of 17 digital sportsbooks currently licensed to operate in the state.

FansUnite Is at a Small-Cap Entry Point with Tremendous Upside.

It is in this environment that FansUnite launched on the Canadian Securities Exchange on May 5. "We are just getting started," said CEO Darius Eghdami. "We've bought a great asset in McBookie and will be continuing to focus on M&A." McBookie, the company's first acquisition, is a white-label sportsbook in the UK, focusing on the Scottish market. It offers 200,000 members active in sports and virtual games, and boasts over $100 million turnover cumulatively the last three years. "We want to be active in finding that next 'McBookie' operating in a niche market, looking at Esports assets and also creative ways to get into the U.S. market. "

After a financing at $0.35, the now-trading company rests slightly above that as a relatively new and unknown entity—so far—which is why now is great opportunity participate in a smaller scale, yet leveraged, consolidation play. "We have a great opportunity to use our stock as currency, and then grow and scale companies through our team and resources," says Eghdami.

"We also have great investors and support, a very experienced board and management team and a clear vision of how we want to be that next gaming giant. The path has been shown by other Canadian gaming companies such as Amaya, and we want to follow that path and execute on our vision."

It's an ambitious plan: a CA$25 million market-cap company, $2 million in the bank, with a consolidation plan to attack a $1 trillion online industry. Yet FansUnite comes out of the gate with strong financial backing led by board member Shafin Diamond, CEO of Victory Square since 2015, a venture builder that builds start-ups in web, mobile, gaming, AI and AR/VR. Diamond has launched 40 start-ups in 24 countries, employed more than 350 people, and has generated over $100 million in annual revenues.

Eghdami says the immediate plan is to strengthen its UK presence with McBookie and focus on M&A activity, while continuing to develop its software platform.

The games are just beginning.

Knox Henderson is a journalist and capital markets communications consultant. He has advised for a broad range of small cap companies in the resource, life sciences and technology sectors for more than 25 years.

Disclosure:
1) 1) Knox Henderson: I, or members of my immediate household or family, own shares of the following companies mentioned in this article: None. I personally am, or members of my immediate household or family are, paid by the following companies mentioned in this article: FansUnite Entertainment Inc. My company has a financial relationship with the following companies mentioned in this article: None. I determined which companies would be included in this article based on my research and understanding of the sector.
2) The following companies mentioned in this article are billboard sponsors of Streetwise Reports: None. Click here for important disclosures about sponsor fees. As of the date of this article, an affiliate of Streetwise Reports has a consulting relationship with FansUnite. Please click here for more information. The information provided above is for informational purposes only and is not a recommendation to buy or sell any security.
3) Statements and opinions expressed are the opinions of the author and not of Streetwise Reports or its officers. The author is wholly responsible for the validity of the statements. The author was not paid by Streetwise Reports for this article. Streetwise Reports was not paid by the author to publish or syndicate this article. Streetwise Reports requires contributing authors to disclose any shareholdings in, or economic relationships with, companies that they write about. Streetwise Reports relies upon the authors to accurately provide this information and Streetwise Reports has no means of verifying its accuracy.
4) This article does not constitute investment advice. Each reader is encouraged to consult with his or her individual financial professional and any action a reader takes as a result of information presented here is his or her own responsibility. By opening this page, each reader accepts and agrees to Streetwise Reports' terms of use and full legal disclaimer. This article is not a solicitation for investment. Streetwise Reports does not render general or specific investment advice and the information on Streetwise Reports should not be considered a recommendation to buy or sell any security. Streetwise Reports does not endorse or recommend the business, products, services or securities of any company mentioned on Streetwise Reports.
5) From time to time, Streetwise Reports and its directors, officers, employees or members of their families, as well as persons interviewed for articles and interviews on the site, may have a long or short position in securities mentioned. Directors, officers, employees or members of their immediate families are prohibited from making purchases and/or sales of those securities in the open market or otherwise from the time of the interview or the decision to write an article until three business days after the publication of the interview or article. The foregoing prohibition does not apply to articles that in substance only restate previously published company releases. As of the date of this article, officers and/or employees of Streetwise Reports LLC (including members of their household) own securities of FansUnite, a company mentioned in this article.

( Companies Mentioned: FANS:CSE, )

Darkly colored, carotene-rich fruits and vegetables -- such as carrots, sweet potatoes, and broccoli -- provide the body with half as much vitamin A as previously thought.

The vast majority of healthy people adequately meet their daily hydration needs by letting thirst be their guide, says the newest report on nutrient recommendations from the Institute of Medicine of the National Academies.

The role of guns in U.S. society is a subject of intense policy debate and disagreement.

Each year, tens of millions of Americans, young and old, choose to learn about science in informal ways -- by visiting museums and aquariums, attending after-school programs, pursuing personal hobbies, and watching TV documentaries, for example.

Most Americans and Canadians up to age 70 need no more than 600 international units (IUs) of vitamin D per day to maintain health, and those 71 and older may need as much as 800 IUs, says a new report from the Institute of Medicine.

The analysis used by federal agencies to set standards for fuel economy and greenhouse gas emissions for new U.S. light-duty vehicles -- passenger cars and light trucks -- from 2017 to 2025 was thorough and of high caliber overall, says a new report from the National Research Council.