Major city in state of Washington, United States; county seat of King County, Washington

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Virginia Mason Franciscan Health
May 11, 2021
/PRNewswire/ -- Virginia Mason Franciscan Health hospitals are ranked among the top in the nation for patient experience and patient safety by Healthgrades,...
Rodney Holt for Mayor
May 10, 2021
/PRNewswire/ -- Mayoral Candidate Rodney Holt Hopes to Create Economic Harmony with the release of his new song, Praise God Everyday. The song Praise God...
DHI Group, Inc.
May 6, 2021
/PRNewswire/ -- Tech hiring surged in the first quarter, as optimism for a swift economic recovery drove tech job postings up 28% nationwide, according to the...
InterDent Service Corporation
May 5, 2021
/PRNewswire/ -- Gentle Dental, a full service dental provider with nearly 165 locations nationwide, is relocating it's Ballard, Washington location on May 6,...
May 4, 2021
ABC News
America's normal temperature is now a degree hotter than just 20 years ago
May 4, 2021
America's new normal temperature is a degree hotter than it was just two decades ago. Scientists have long talked about climate change -- hotter temperatures...
Seth Borenstein
May 4, 2021
America's new normal temperature is a degree hotter than it was just two decades ago.
Alaska Airlines
April 28, 2021
/PRNewswire/ -- Alaska Airlines' "Our Commitment" aircraft took to the skies in partnership with UNCF (United Negro College Fund), a symbol of the airline's...
Julia Hotz
April 28, 2021
MIT Technology Review
Seattle gave residents $100 in a bid to make the city's campaign contributions more representative of its electorate. Now, the program is spreading.
The Linux Foundation
April 28, 2021
/PRNewswire/ -- The Linux Foundation, the nonprofit organization enabling mass innovation through open source, announced today that Open Source Summit +...
S&P Dow Jones Indices
April 27, 2021
/PRNewswire/ -- S&P Dow Jones Indices (S&P DJI) today released the latest results for the S&P CoreLogic Case-Shiller Indices, the leading measure of U.S. home...
Simon Cohen
April 26, 2021
Digital Trends
Apple Music is bringing more local flavor to its charts feature with a new City Charts section. It captures the daily top 25 tracks for more than 100 cities.
Adriana Nunez
April 22, 2021
Business Insider
Amazon is bringing Amazon One to Whole Foods stores in Seattle and plans to roll out the system in more Whole Foods locations throughout the area.
Grist Creative
April 21, 2021
With global energy demand expected to increase by as much as 58 percent in the next three decades, the urgency to transition away from burning fossil fuels to power buildings and vehicles is growing. Over the past few years, calls for turning to electricity as a power source have grown louder and more persistent. The [...]
Krystin Arneson
April 21, 2021
Business Insider
These spa-inspired Airbnbs feel like a five-star hotel with private pools, soaking tubs, outdoor showers, on-demand spa services, and more.
Chris Isidore, CNN Business
April 21, 2021
Amazon will let customers at some Whole Foods stores pay with simple wave of their hands.
April 13, 2021
/PRNewswire/ -- After eight months of consistent slowdowns, rent growth in the nation's largest housing markets saw its first uptick in March, rising 1.1%...
Apoorva Mandavilli
April 13, 2021
Even before the pandemic, many female scientists felt unsupported in their fields. Now, some are hitting a breaking point.
Divine, R., Dang, H. V., Ueda, G., Fallas, J. A., Vulovic, I., Sheffler, W., Saini, S., Zhao, Y. T., Raj, I. X., Morawski, P. A., Jennewein, M. F., Homad, L. J., Wan, Y.-H., Tooley, M. R., Seeger, F., Etemadi, A., Fahning, M. L., Lazarovits, J., Roederer, A., Walls, A. C., Stewart, L., Mazloomi, M., King, N. P., Campbell, D. J., McGuire, A. T., Stamatatos, L., Ruohola-Baker, H., Mathieu, J., Veesler, D., Baker, D.
April 2, 2021
Antibodies are broadly used in therapies and as research tools because they can be generated against a wide range of targets. Efficacy can often be increased by clustering antibodies in multivalent assemblies. Divine et al. designed antibody nanocages from two components: One is an antibody-binding homo-oligomic protein and the other is the antibody itself. Computationally designed proteins drive the assembly of antibody nanocages in a range of architectures, allowing control of the symmetry and the antibody valency. The multivalent display enhances antibody-dependent signaling, and nanocages displaying antibodies against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein effectively neutralize pseudovirus. Science , this issue p. [eabd9994][1] ### INTRODUCTION Antibodies that bind tightly to targets of interest play central roles in biological research and medicine. Clusters of antibodies, typically generated by fusing antibodies to polymers or genetically linking antibody fragments together, can enhance signaling. Currently lacking are approaches for making antibody assemblies with a range of precisely specified architectures and valencies. ### RATIONALE We set out to computationally design proteins that assemble antibodies into precise architectures with different valencies and symmetries. We developed an approach to designing proteins that position antibodies or Fc-fusions on the twofold symmetry axes of regular dihedral and polyhedral architectures. We hypothesized that such designs could robustly drive arbitrary antibodies into homogeneous and structurally well-defined nanocages and that such assemblies could have pronounced effects on cell signaling. ### RESULTS Antibody cage (AbC)-forming designs were created by rigidly fusing antibody constant domain-binding modules to cyclic oligomers through helical spacer domains such that the symmetry axes of the dimeric antibody and cyclic oligomer are at orientations that generate different dihedral or polyhedral (e.g., tetrahedral, octahedral, or icosahedral) architectures. The junction regions between the connected building blocks were optimized to fold to the designed structures. Synthetic genes encoding the designs were expressed in bacterial cultures; of 48 structurally characterized designs, eight assemblies matched the design models. Successful designs encompass D2 dihedral (three designs), T32 tetrahedral (two designs), O42 octahedral (one design), and I52 icosahedral (two designs) architectures; these contain 2, 6, 12, or 30 antibodies, respectively. We investigated the effects of AbCs on cell signaling. AbCs formed with a death receptor-targeting antibody induced apoptosis of tumor cell lines that were unaffected by the soluble antibody or the native ligand. Angiopoietin pathway signaling, CD40 signaling, and T cell proliferation were all enhanced by assembling Fc-fusions or antibodies in AbCs. AbC formation also enhanced in vitro viral neutralization of a severe acute respiratory syndrome coronavirus 2 pseudovirus. ### CONCLUSION We have designed multiple antibody cage-forming proteins that precisely cluster any protein A-binding antibody into nanocages with controlled valency and geometry. AbCs can be formed with 2, 6, 12, or 30 antibodies simply by mixing the antibody with the corresponding designed protein, without the need for any covalent modification of the antibody. Incorporating receptor binding or virus-neutralizing antibodies into AbCs enhanced their biological activity across a range of cell systems. We expect that our rapid and robust approach for assembling antibodies into homogeneous and ordered nanocages without the need for covalent modification will have broad utility in research and medicine. ![Figure][2] Designed proteins assemble antibodies into large symmetric architectures. Designed antibody-clustering proteins (light gray) assemble antibodies (purple) into diverse nanocage architectures (top). Antibody nanocages enhance cell signaling compared with free antibodies (bottom). IMAGE: IAN HAYDON, INSTITUTE FOR PROTEIN DESIGN Multivalent display of receptor-engaging antibodies or ligands can enhance their activity. Instead of achieving multivalency by attachment to preexisting scaffolds, here we unite form and function by the computational design of nanocages in which one structural component is an antibody or Fc-ligand fusion and the second is a designed antibody-binding homo-oligomer that drives nanocage assembly. Structures of eight nanocages determined by electron microscopy spanning dihedral, tetrahedral, octahedral, and icosahedral architectures with 2, 6, 12, and 30 antibodies per nanocage, respectively, closely match the corresponding computational models. Antibody nanocages targeting cell surface receptors enhance signaling compared with free antibodies or Fc-fusions in death receptor 5 (DR5)-mediated apoptosis, angiopoietin-1 receptor (Tie2)-mediated angiogenesis, CD40 activation, and T cell proliferation. Nanocage assembly also increases severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pseudovirus neutralization by α-SARS-CoV-2 monoclonal antibodies and Fc-angiotensin-converting enzyme 2 (ACE2) fusion proteins. [1]: /lookup/doi/10.1126/science.abd9994 [2]: pending:yes
The Associated Press
April 5, 2021
-- Against the odds, Melissa McCarthy and her husband, filmmaker Ben Falcone, have managed to put out two movies during the pandemic. Last November came HBO ...
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