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The causative agent of the coronavirus disease 2019 (COVID-19) pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has infected millions and killed hundreds of thousands of people worldwide, highlighting an urgent need to develop antiviral therapies. Here we present a quantitative mass spectrometry-based phosphoproteomics survey of SARS-CoV-2 infection in Vero E6 cells, revealing dramatic rewiring of phosphorylation on host and viral proteins. SARS-CoV-2 infection promoted casein kinase II (CK2) and p38 MAPK activation, production of diverse cytokines, and shutdown of mitotic kinases, resulting in cell cycle arrest. Infection also stimulated a marked induction of CK2-containing filopodial protrusions possessing budding viral particles. Eighty-seven drugs and compounds were identified by mapping global phosphorylation profiles to dysregulated kinases and pathways. We found pharmacologic inhibition of the p38, CK2, CDK, AXL, and PIKFYVE kinases to possess antiviral efficacy, representing potential COVID-19 therapies.

I present a 2-stage theory in which emerging market firms first compete domestically based on traditional competitive advantages. Once they achieve a threshold stage, then they go overseas and are able to succeed based on company and industry characteristics, as well as emerging market characteristics. I expect to see that factors enabling firms to get to the threshold stage will include: brand value, low-cost production, experience/age, company size, possibly membership in a business group, and international sales (but not technology). Then I would expect that factors enabling firms to succeed internationally should depend on the industrial sector and the target market, as well as demonstrating emerging market idiosyncrasies such as ability to deal with high uncertainty in government policies and economic conditions as well as flexibility in dealing with business conditions. Most analyses of emerging market MNEs focus only on the last set of factors that are common to emerging markets. Key Words: emerging market multinationals; emerging markets; competitiveness; global strategy; competitive advantages. Thanks to Abhyuday Singhal for excellent research assistance on this project. I., I. Introduction A number of authors have written about the successes of emerging market companies in going international and in competing in overseas markets over the past 50 years. The [...]

International business in the past century has largely been the domain of large multinational enterprises and banks, as well as small exporting and importing companies. The scope of international business activity has grown in recent years, and today there are many State-owned companies involved in international business activities, as well as financial investors rather than only industrial or commercial companies undertaking foreign direct investment (FDI). Government policy toward international business has largely been supportive since the 1990s, while concerns have arisen particularly in regard to the activities of State-owned enterprises and also the activities of non-traditional investors such as investment funds. To achieve the greatest benefits from FDI and trade, governments need to understand which companies are making the key decisions in global value chains and to collaborate in rule-setting and in guiding companies to pursue desirable activities and to limit non-business goal-seeking. Keywords: foreign direct investment, cross-border M&A, multinational enterprises, global value chains, state-owned enterprises JEL classification codes: F21, F23, F42, G34, 1. Introduction At the 2021 World Investment Forum sponsored by UNCTAD (https:// worldInvestmentforum.unctad.org/7th-world-investment-forum/), In sessions co-sponsored by the Academy of International Business, the issue of non-traditional ownership of international business [...]

Precise segregation of chromosomes during mitosis requires assembly of a bipolar mitotic spindle followed by correct attachment of microtubules to the kinetochores. This highly spatiotemporally organized process is controlled by various mitotic kinases and molecular motors. We have recently shown that Casein Kinase 1 (CK1) promotes timely progression through mitosis by phosphorylating FAM110A leading to its enrichment at spindle poles. However, the mechanism by which FAM110A exerts its function in mitosis is unknown. Using structure prediction and a set of deletion mutants, we mapped here the interaction of the N-and C-terminal domains of FAM110A with actin and tubulin, respectively. Next, we found that the FAM110A-Δ40-61 mutant deficient in actin binding failed to rescue defects in chromosomal alignment caused by depletion of endogenous FAM110A. Depletion of FAM110A impaired assembly of F-actin in the proximity of spindle poles and was rescued by expression of the wild-type FAM110A, but not the FAM110A-Δ40-61 mutant. Purified FAM110A promoted binding of F-actin to microtubules as well as bundling of actin filaments in vitro. Finally, we found that the inhibition of CK1 impaired spindle actin formation and delayed progression through mitosis. We propose that CK1 and FAM110A promote timely progression through mitosis by mediating the interaction between spindle microtubules and filamentous actin to ensure proper mitotic spindle formation. [ABSTRACT FROM AUTHOR]

Actin is well known for its cytoskeletal functions, where it helps to control and maintain cell shape and architecture, as well as regulating cell migration and intracellular cargo transport, among others. However, actin is also prevalent in the nucleus, where genome-regulating roles have been described, including it being part of chromatin-remodeling complexes. More recently, with the help of advances in microscopy techniques and specialized imaging probes, direct visualization of nuclear actin filament dynamics has helped elucidate new roles for nuclear actin, such as in cell cycle regulation, DNA replication and repair, chromatin organization and transcriptional condensate formation. In this Cell Science at a Glance article, we summarize the known signaling events driving the dynamic assembly of actin into filaments of various structures within the nuclear compartment for essential genome functions. Additionally, we highlight the physiological role of nuclear F-actin in meiosis and early embryonic development. [ABSTRACT FROM AUTHOR]

Innovation is a key competitive advantage for companies in the 21st century. R&D and other innovative work was traditionally carried out by MNEs in their home countries, although it spread to some affiliates in other developed countries in the late 20th century, and to some emerging markets more recently. This paper analyzes the assignment of innovative activity, particularly R&D, by MNEs to their affiliates in emerging markets. Using both aggregate data produced by government organizations and company-specific interviews and published commentaries, we find that MNEs assign more responsibility for R&D and innovation to affiliates in emerging markets that have larger markets, lower human resource costs, greater overall R&D activity and to some extent greater activity of the company in question. China and India are huge exceptions to the rule that MNEs tend to assign only development work to emerging market affiliates: they are increasingly assigning core R&D to these two large countries. Corporate strategy can be adjusted to take advantage of low-cost R&D capabilities, particularly in these large markets, and to pull innovations from those affiliates throughout the rest of the firm. Public policy to attract R&D by MNEs should look at offering companies better access to sizable markets, offering incentives for R&D activity and building up R&D activity in the local economy, by companies and government alike. Keywords: emerging markets, innovation, MNEs, new technology, R&D, 1. Introduction Innovation is one of the most important competitive advantages of the 21st century (Rubera and Kirca 2012; Pisano 2015; Grosse 2015; Chatzoglou and Chatzoudes 2018). Countries as well [...]