The ordinary city trap

The paper is a critique of a critique, it explains why the most salient and influential critiques of the neo-Marxist world city and global city concepts, made by those arguing to further postcolonialize urban studies through such suppositions that all cities are ‘ordinary’, are misguided. First, it is explained how the charges of economism and ethnocentrism against the world city and global city concepts are ignoratio elenchi: they do not even begin to address or critique their neo-Marxist argument that, across the difference and diversity of the world’s cities, a few major cities have the necessary economic specialization and therefore extraordinary function of commanding and controlling neoliberal globalization. Second, the error made by advocates of ordinary cities of supposing that world-systems analysis and the world city concept are forms of developmentalism is understood as the source for a wider postcolonial mistake of conflating the neo-Marxist world city and global city literatures with the very neoliberal practices toward urban development that they have long attempted to disclose and counter. Finally, the charges against the world city and global city concepts as paradigmatic, peripheralizing, and normative are also rebutted, not only to highlight how those critiques are consequentialist and dependent on the respective charges of economism, ethnocentrism, and developmentalism having veracity, but to demonstrate how an acceptance of the ordinary cities argument for an idiographic, provincial, nominalist, and comparative approach to urban studies, as an alternative to the two neo-Marxist concepts, is only to fall into the trap of making the mistake of confusing evidence of absence for absence of evidence

Racial Segregation, Income Inequality, and Mortality in US Metropolitan Areas

Evidence of the association between income inequality and mortality has been mixed. Studies indicate that growing income inequalities reflect inequalities between, rather than within, racial groups. Racial segregation may play a role. We examine the role of racial segregation on the relationship between income inequality and mortality in a cross-section of US metropolitan areas. Metropolitan areas were included if they had a population of at least 100,000 and were at least 10% black (N = 107). Deaths for the time period 1991–1999 were used to calculate age-adjusted all-cause mortality rates for each metropolitan statistical area (MSA) using direct age-adjustment techniques. Multivariate least squares regression was used to examine associations for the total sample and for blacks and whites separately. Income inequality was associated with lower mortality rates among whites and higher mortality rates among blacks. There was a significant interaction between income inequality and racial segregation. A significant graded inverse income inequality/mortality association was found for MSAs with higher versus lower levels of black–white racial segregation. Effects were stronger among whites than among blacks. A positive income inequality/mortality association was found in MSAs with higher versus lower levels of Hispanic–white segregation. Uncertainty regarding the income inequality/mortality association found in previous studies may be related to the omission of important variables such as racial segregation that modify associations differently between groups. Research is needed to further elucidate the risk and protective effects of racial segregation across groups

How does the built environment affect teenagers (aged 13–14) physical activity and fitness? A cross-sectional analysis of the ACTIVE Project

Built environments have been cited as important facilitators of activity and research using geographic information systems (GIS) has emerged as a novel approach in exploring environmental determinants. The Active Children Through Individual Vouchers Evaluation Project used GIS to conduct a cross-sectional analysis of how teenager's (aged 13-14) environments impacted on their amount of activity and influences fitness. The ACTIVE Project recruited 270 participants aged 13-14 (year 9) from 7 secondary schools in south Wales, UK. Demographic data and objective measures of accelerometery and fitness were collected from each participant between September and December 2016. Objective data was mapped in a GIS alongside datasets relating to activity provision, active travel routes, public transport stops, main roads and natural resources. This study shows that fitness and physical activity are not correlated. Teenagers who had higher levels of activity also had higher levels of sedentary time/inactivity. Teenagers showed higher amounts of moderate-to-vigorous physical activity if their homes were closer to public transport. However, they were also more active if their schools were further away from public transport and natural resources. Teenagers were fitter if schools were closer to natural resources. Sedentary behaviour, fitness and activity do not cluster in the same teenagers. Policymakers/planning committees need to consider this when designing teenage friendly environments. Access to public transport, active travel, green space and activities that teenagers want, and need could make a significant difference to teenage health

Activation-Induced Cytidine Deaminase Deficiency Causes Organ-Specific Autoimmune Disease

Activation-induced cytidine deaminase (AID) expressed by germinal center B cells is a central regulator of somatic hypermutation (SHM) and class switch recombination (CSR). Humans with AID mutations develop not only the autosomal recessive form of hyper-IgM syndrome (HIGM2) associated with B cell hyperplasia, but also autoimmune disorders by unknown mechanisms. We report here that AID−/− mice spontaneously develop tertiary lymphoid organs (TLOs) in non-lymphoid tissues including the stomach at around 6 months of age. At a later stage, AID−/− mice develop a severe gastritis characterized by loss of gastric glands and epithelial hyperplasia. The disease development was not attenuated even under germ-free (GF) conditions. Gastric autoantigen -specific serum IgM was elevated in AID−/− mice, and the serum levels correlated with the gastritis pathological score. Adoptive transfer experiments suggest that autoimmune CD4+ T cells mediate gastritis development as terminal effector cells. These results suggest that abnormal B-cell expansion due to AID deficiency can drive B-cell autoimmunity, and in turn promote TLO formation, which ultimately leads to the propagation of organ-specific autoimmune effector CD4+ T cells. Thus, AID plays an important role in the containment of autoimmune diseases by negative regulation of autoreactive B cells

A Novel Adaptive Method for the Analysis of Next-Generation Sequencing Data to Detect Complex Trait Associations with Rare Variants Due to Gene Main Effects and Interactions

There is solid evidence that rare variants contribute to complex disease etiology. Next-generation sequencing technologies make it possible to uncover rare variants within candidate genes, exomes, and genomes. Working in a novel framework, the kernel-based adaptive cluster (KBAC) was developed to perform powerful gene/locus based rare variant association testing. The KBAC combines variant classification and association testing in a coherent framework. Covariates can also be incorporated in the analysis to control for potential confounders including age, sex, and population substructure. To evaluate the power of KBAC: 1) variant data was simulated using rigorous population genetic models for both Europeans and Africans, with parameters estimated from sequence data, and 2) phenotypes were generated using models motivated by complex diseases including breast cancer and Hirschsprung's disease. It is demonstrated that the KBAC has superior power compared to other rare variant analysis methods, such as the combined multivariate and collapsing and weight sum statistic. In the presence of variant misclassification and gene interaction, association testing using KBAC is particularly advantageous. The KBAC method was also applied to test for associations, using sequence data from the Dallas Heart Study, between energy metabolism traits and rare variants in ANGPTL 3,4,5 and 6 genes. A number of novel associations were identified, including the associations of high density lipoprotein and very low density lipoprotein with ANGPTL4. The KBAC method is implemented in a user-friendly R package

Variation in helper effort among cooperatively breeding bird species is consistent with Hamilton's Rule.

Investment by helpers in cooperative breeding systems is extremely variable among species, but this variation is currently unexplained. Inclusive fitness theory predicts that, all else being equal, cooperative investment should correlate positively with the relatedness of helpers to the recipients of their care. We test this prediction in a comparative analysis of helper investment in 36 cooperatively breeding bird species. We show that species-specific helper contributions to cooperative brood care increase as the mean relatedness between helpers and recipients increases. Helper contributions are also related to the sex ratio of helpers, but neither group size nor the proportion of nests with helpers influence helper effort. Our findings support the hypothesis that variation in helping behaviour among cooperatively breeding birds is consistent with Hamilton's rule, indicating a key role for kin selection in the evolution of cooperative investment in social birds

The places parents go: understanding the breadth, scope, and experiences of activity spaces for parents

The final publication is available at Springer via https://doi.org/10.1007/s10708-015-9690-yNeighborhood environments are related to parenting behaviors, which in turn have a life-long effect on children’s health and well-being. Activity spaces, which measure individual routine patterns of movement, may be helpful in assessing how physical and social environments shape parenting. In this study we use qualitative data and GIS mapping from four California cities to examine parental activity spaces. Parents described a number of factors that shape their activity spaces including caregiving status, the age of their children, and income. Parental activity spaces also varied between times (weekends vs. weekdays) and places (adult-only vs. child-specific places). Knowing how to best capture and study parental activity spaces could identify mechanisms by which environmental factors influence parenting behaviors and child health

Identifying lineage effects when controlling for population structure improves power in bacterial association studies

Bacteria pose unique challenges for genome-wide association studies because of strong structuring into distinct strains and substantial linkage disequilibrium across the genome1,2. Although methods developed for human studies can correct for strain structure3,4, this risks considerable loss-of-power because genetic differences between strains often contribute substantial phenotypic variability5. Here, we propose a new method that captures lineage-level associations even when locus-specific associations cannot be fine-mapped. We demonstrate its ability to detect genes and genetic variants underlying resistance to 17 antimicrobials in 3,144 isolates from four taxonomically diverse clonal and recombining bacteria: Mycobacterium tuberculosis, Staphylococcus aureus, Escherichia coli and Klebsiella pneumoniae. Strong selection, recombination and penetrance confer high power to recover known antimicrobial resistance mechanisms and reveal a candidate association between the outer membrane porin nmpC and cefazolin resistance in E. coli. Hence, our method pinpoints locus-specific effects where possible and boosts power by detecting lineage-level differences when fine-mapping is intractable

An Evolutionary Framework for Association Testing in Resequencing Studies

Sequencing technologies are becoming cheap enough to apply to large numbers of study participants and promise to provide new insights into human phenotypes by bringing to light rare and previously unknown genetic variants. We develop a new framework for the analysis of sequence data that incorporates all of the major features of previously proposed approaches, including those focused on allele counts and allele burden, but is both more general and more powerful. We harness population genetic theory to provide prior information on effect sizes and to create a pooling strategy for information from rare variants. Our method, EMMPAT (Evolutionary Mixed Model for Pooled Association Testing), generates a single test per gene (substantially reducing multiple testing concerns), facilitates graphical summaries, and improves the interpretation of results by allowing calculation of attributable variance. Simulations show that, relative to previously used approaches, our method increases the power to detect genes that affect phenotype when natural selection has kept alleles with large effect sizes rare. We demonstrate our approach on a population-based re-sequencing study of association between serum triglycerides and variation in ANGPTL4

Relief of Preintegration Inhibition and Characterization of Additional Blocks for HIV Replication in Primary Mouse T Cells

Development of a small animal model to study HIV replication and pathogenesis has been hampered by the failure of the virus to replicate in non-primate cells. Most studies aimed at achieving replication in murine cells have been limited to fibroblast cell lines, but generating an appropriate model requires overcoming blocks to viral replication in primary T cells. We have studied HIV-1 replication in CD4+ T cells from human CD4/ CCR5/Cyclin T1 transgenic mice. Expression of hCD4 and hCCR5 in mouse CD4+ T cells enabled efficient entry of R5 strain HIV-1. In mouse T cells, HIV-1 underwent reverse transcription and nuclear import as efficiently as in human T cells. In contrast, chromosomal integration of HIV-1 proviral DNA was inefficient in activated mouse T cells. This process was greatly enhanced by providing a secondary T cell receptor (TCR) signal after HIV-1 infection, especially between 12 to 24 h post infection. This effect was specific for primary mouse T cells. The pathways involved in HIV replication appear to be PKCθ−, CARMA1-, and WASp-independent. Treatment with Cyclosporin A (CsA) further relieved the pre-integration block. However, transcription of HIV-1 RNA was still reduced in mouse CD4+ T cells despite expression of the hCyclin T1 transgene. Additional post-transcriptional defects were observed at the levels of Gag expression, Gag processing, Gag release and virus infectivity. Together, these post-integration defects resulted in a dramatically reduced yield of infectious virus (300–500 fold) after a single cycle of HIV-1 replication. This study implies the existence of host factors, in addition to those already identified, that are critical for HIV-1 replication in mouse cells. This study also highlights the differences between primary T cells and cell lines regarding pre-integration steps in the HIV-1 replication cycle