Gene Expression Profiles of the NCI-60 Human Tumor Cell Lines Define Molecular Interaction Networks Governing Cell Migration Processes

Although there is extensive information on gene expression and molecular interactions in various cell types, integrating those data in a functionally coherent manner remains challenging. This study explores the premise that genes whose expression at the mRNA level is correlated over diverse cell lines are likely to function together in a network of molecular interactions. We previously derived expression-correlated gene clusters from the database of the NCI-60 human tumor cell lines and associated each cluster with function categories of the Gene Ontology (GO) database. From a cluster rich in genes associated with GO categories related to cell migration, we extracted 15 genes that were highly cross-correlated; prominent among them were RRAS, AXL, ADAM9, FN14, and integrin-beta1. We then used those 15 genes as bait to identify other correlated genes in the NCI-60 database. A survey of current literature disclosed, not only that many of the expression-correlated genes engaged in molecular interactions related to migration, invasion, and metastasis, but that highly cross-correlated subsets of those genes engaged in specific cell migration processes. We assembled this information in molecular interaction maps (MIMs) that depict networks governing 3 cell migration processes: degradation of extracellular matrix, production of transient focal complexes at the leading edge of the cell, and retraction of the rear part of the cell. Also depicted are interactions controlling the release and effects of calcium ions, which may regulate migration in a spaciotemporal manner in the cell. The MIMs and associated text comprise a detailed and integrated summary of what is currently known or surmised about the role of the expression cross-correlated genes in molecular networks governing those processes

SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion

The B.1.617.2 (Delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in the state of Maharashtra in late 2020 and spread throughout India, outcompeting pre-existing lineages including B.1.617.1 (Kappa) and B.1.1.7 (Alpha)1. In vitro, B.1.617.2 is sixfold less sensitive to serum neutralizing antibodies from recovered individuals, and eightfold less sensitive to vaccine-elicited antibodies, compared with wild-type Wuhan-1 bearing D614G. Serum neutralizing titres against B.1.617.2 were lower in ChAdOx1 vaccinees than in BNT162b2 vaccinees. B.1.617.2 spike pseudotyped viruses exhibited compromised sensitivity to monoclonal antibodies to the receptor-binding domain and the amino-terminal domain. B.1.617.2 demonstrated higher replication efficiency than B.1.1.7 in both airway organoid and human airway epithelial systems, associated with B.1.617.2 spike being in a predominantly cleaved state compared with B.1.1.7 spike. The B.1.617.2 spike protein was able to mediate highly efficient syncytium formation that was less sensitive to inhibition by neutralizing antibody, compared with that of wild-type spike. We also observed that B.1.617.2 had higher replication and spike-mediated entry than B.1.617.1, potentially explaining the B.1.617.2 dominance. In an analysis of more than 130 SARS-CoV-2-infected health care workers across three centres in India during a period of mixed lineage circulation, we observed reduced ChAdOx1 vaccine effectiveness against B.1.617.2 relative to non-B.1.617.2, with the caveat of possible residual confounding. Compromised vaccine efficacy against the highly fit and immune-evasive B.1.617.2 Delta variant warrants continued infection control measures in the post-vaccination era

Critique of Urban Violence: Bismarckian Transformations in Managua, Nicaragua

Urban contexts are widely conceived as inherently violent due to their putatively disorderly nature. Such a conception of violence effectively conceives it as singular and fundamentally destructive, neither of which necessarily hold universally true. Drawing on Benjamin’s ‘Critique of Violence’ and the life history of Bismarck, a former gang member turned drug dealer turned property entrepreneur living in a poor neighbourhood in Managua, Nicaragua, this article highlights how different forms of urban violence interrelate with each other over time, and how they shape an individual’s urban experience and environment. In doing so, it underscores how urban violence is not a singular phenomenon, how it intertwines with a range of urban social processes, and how it is often socially constitutive rather than destructive. Seen from this perspective, the key question to ask is less to what extent violence is a hallmark of urban contexts but rather how different articulations of violence emerge in cities, and why it is that they can play such contrasting roles in the constitution of urban life

Educational Reform for Immigrant Youth in Japan

Transnational migration is seldom associated with Japan even though Japan has been dependent on immigrants for several generations. The research presented in this article explores a reform effort viewed as radical within the Japanese context that took place in a metropolitan school known for having one of the largest number of immigrant students in Japan, most of whom hail from Latin America, Southeast Asia, and China. While many of these “Newcomers” are of Japanese ancestry, absence from the homeland for two to four generations has left them without the cultural and linguistic skills to navigate the nuances of Japanese society. As a result, schools, which have never had to respond to the needs of immigrant youth, find themselves at a loss as to how to integrate young people whose parents have been drawn back from the Japanese diaspora through government policies designed to assuage the labor shortage of the 1980s and 1990s. Over the course of 5 months of ethnographic field work in the community in which this school is located the author offers insights gleaned from extensive time spent with social workers, translators, government workers, teachers, staff, students, parents, and community liaison volunteers, all of whom shared their frustrations and challenges with the education of immigrant youth within the context and constraints of Japanese schools