Introduction: An Unsettled Time from \u3cem\u3eAmerican Political Development and the Trump Presidency\u3c/em\u3e

As the words of his inaugural address echoed across a rain- soaked National Mall, Donald Trump cut a hole in time. His presidency, he said, marked a breaking point in American politics. No longer would a “small group” of elites reap the benefits of government while “forgotten Americans” bore the cost. “Now,” Trump suggested, “we are only looking to the future.” Even so, the speech telegraphed a dystopian pre sent; the United States had become a landscape of rusted- out factories, cities teeming with crime, and national borders defenseless against terrorist threats. Gone was the promised land that Trump’s predecessors foretold in their inaugural speeches, the “city on a hill” that America was destined to be. Trump identified few, if any, sources of political possibility. America would be “made great again” not through providence, but by Trump himself: “I will fight for you with every breath in my body— and I will never, ever let you down.” Rather than binding the nation through conciliation and compromise, Trump promised nationalism: “The bedrock of our politics,” he said, “will be a total allegiance to the United States of America.” He labeled his foreign policy with a phrase burdened with an isolationist and anti- Semitic history: “America First.” ..

Ribosome-associated vesicles: A dynamic subcompartment of the endoplasmic reticulum in secretory cells

The endoplasmic reticulum (ER) is a highly dynamic network of membranes. Here, we combine live-cell microscopy with in situ cryo–electron tomography to directly visualize ER dynamics in several secretory cell types including pancreatic β-cells and neurons under near-native conditions. Using these imaging approaches, we identify a novel, mobile form of ER, ribosome-associated vesicles (RAVs), found primarily in the cell periphery, which is conserved across different cell types and species. We show that RAVs exist as distinct, highly dynamic structures separate from the intact ER reticular architecture that interact with mitochondria via direct intermembrane contacts. These findings describe a new ER subcompartment within cells

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

The seams of the state: Infrastructure and intergovernmental relations in American state building

Institutional change in the American federal system, especially the shift from the early decentralized state to the current strong central state, is generally explained by appealing to exogenous shocks. Traditionally, American state building theories have relied on war or economic transformations to explain the growth of the federal government. In contrast to these theories, I argue that political centralization is actually the result of endogenous forces that are inherent in American federalism. Local policy failures combine with interstate competition to drive sub-national policy concerns to Congress, thereby transforming previously parochial concerns into federal issues. Thus, the national state finds itself in new policy areas primarily because of bottom-top pressure. To expand this idea, I examine American rail development during the antebellum period. My analysis begins by analyzing state rail promotion and coordination efforts. While these initial state-level programs provided a fairly complete rail system, local failures harmed the overall efficiency of the national rail system. These local shortcomings led Congressional representatives from states with poorly functioning rail systems to press for national intervention. However, Congressional involvement altered American rail development, as external interests began to shape local railroads to reflect national concerns. Yet, despite this intrusion, local political actors continued to shape their parochial rail plans. Hence, while federalism encouraged national intervention, the separation of powers within a federal system still allowed local political actors leeway over rail planning. While the analysis primarily emphasizes how federalism has shaped American state building, the findings also underscore the importance of political geography in state building. State building requires the manipulation of space, and spatial organization can exert a long-term and profound impact on political development. By examining both federalism and space, significant light is shed on how the American political development process

Ribosome-associated Vesicles: A Dynamic Subcompartment of the Endoplasmic Reticulum in Secretory Cells

The endoplasmic reticulum (ER) is a highly dynamic network of membranes. Here, we combine live-cell microscopy with in situ cryo-electron tomography to directly visualize ER dynamics in several secretory cell types including pancreatic β-cells and neurons under near-native conditions. Using these imaging approaches, we identify a novel, mobile form of ER, ribosome-associated vesicles (RAVs), found primarily in the cell periphery, which is conserved across different cell types and species. We show that RAVs exist as distinct, highly dynamic structures separate from the intact ER reticular architecture that interact with mitochondria via direct intermembrane contacts. These findings describe a new ER subcompartment within cells.Support for this study was provided by the L. V. Gerstner Jr., Scholars Program (to Z.F.), the Leon Levy Foundation (to Z.F.), the John F. and Nancy A. Emmerling Fund of the Pittsburgh Foundation (to Z.F.), the Department of Defense PR141292 (to Z.F.), NIH K08DA031241 (to Z.F.), NSF MCB-1408986 (to S.A.M.), the National Science Foundation Graduate Research Fellowship (to N.H.T.), NIH K01AG045335 (to E.A.G.), NIH 1S10RR019003 (to S.C.W.), NIH 1S10RR025488 (to S.C.W.), NIH 1S10RR016236 (to S.C.W.), NIH F30NS093798 (to S.E.S.), NIH R56AG058593 (to Z.P.W.), the Howard Hughes Medical Institute (to P.W., N.H.T., J.F., and G.J.J.), NIH GM29169 (to J.F.), NIH GM122588 (to G.J.J.), NIH AI150464 (to G.J.J.), the Israel Science Foundation Grant 1285/14 (to S.G.W.), the European Research Council under the European Union’s Seventh Framework Programme (grant number 310649) (to D.F.), MINECO AIC-A-2011-0638 (to J.M.C.), the Spanish Ministry of Economy and Competitiveness grant BIO2016-76400-R AEI/FEDER, UE (to J.M.C.), and Comunidad Autónoma de Madrid grant S2017/BMD-3817 (to J.M.C.). Some of the cryo-ET was performed in the Beckman Institute Resource Center for Transmission EM at Caltech. Additional work was also performed at the Simons Electron Microscopy Center and National Resource for Automated Molecular Microscopy located at the New York Structural Biology Center, supported by grants from the Simons Foundation (349247), NYSTAR, and the NIH National Institute of General Medical Sciences (GM103310) with added support from NIH S10 RR029300-01. CSTET data acquisition was partially supported by the Irving and Cherna Moskowitz Center for Nano and Bio-Nano Imaging at the Weizmann Institute of Science. Some of the live confocal images were collected and processed in the Confocal and Specialized Microscopy Shared Resource of the Herbert Irving Comprehensive Cancer Center at Columbia University and supported by NIH P30 CA013696. Part of the cryo-EM image processing was conducted as an Instruct-ERIC collaboration project PD1222 at the Instruct Image Processing CenterPeer reviewe