Repetition and difference: Lefebvre, Le Corbusier and modernity's (im)moral landscape: a commentary

This article engages with the relationship between social theory, architectural theory and material culture. The article is a reply to an article in a previous volume of the journal in question (Smith, M. (2001) ‘Repetition and difference: Lefebvre, Le Corbusier and modernity’s (im)moral landscape’, Ethics, Place and Environment, 4(1), 31-34) and, consequently, is also a direct engagement with another academic's scholarship. It represents a critique of their work as well as a recasting of their ideas, arguing that the matter in question went beyond interpretative issues to a direct critique of another author's scholarship on both Le Corbusier and Lefebvre. A reply to my article from the author of the original article was carried in a later issue of the journal (Smith, M. (2002) ‘Ethical Difference(s): a Response to Maycroft on Le Corbusier and Lefebvre’, Ethics, Place and Environment, 5(3), 260-269)

Association of Transcription Factor 4 (TCF4) variants with schizophrenia and intellectual disability

Genome wide association studies (GWAS) have revolutionized the study of complex diseases and have uncovered common genetic variants associated with an increased risk for major psychiatric disorders. A recently published schizophrenia GWAS replicated earlier findings implicating common variants in Transcription factor 4 (TCF4) as susceptibility loci for schizophrenia. By contrast, loss of function TCF4 mutations, although rare, cause Pitt-Hopkins syndrome (PTHS); a disorder characterized by intellectual disability (ID), developmental delay and behavioral abnormalities. TCF4 mutations have also been described in individuals with ID and non-syndromic neurodevelopmental disorders. TCF4 is a member of the basic helix-loop-helix (bHLH) family of transcription factors that regulate gene expression at E-box-containing promoters and enhancers. Accordingly, TCF4 has an important role during brain development and can interact with a wide array of transcriptional regulators including some proneural factors. TCF4 may, therefore, participate in the transcriptional networks that regulate the maintenance and differentiation of distinct cell types during brain development. Here, we review the role of TCF4 variants in the context of several distinct brain disorders associated with impaired cognition

A blood atlas of COVID-19 defines hallmarks of disease severity and specificity.

Treatment of severe COVID-19 is currently limited by clinical heterogeneity and incomplete description of specific immune biomarkers. We present here a comprehensive multi-omic blood atlas for patients with varying COVID-19 severity in an integrated comparison with influenza and sepsis patients versus healthy volunteers. We identify immune signatures and correlates of host response. Hallmarks of disease severity involved cells, their inflammatory mediators and networks, including progenitor cells and specific myeloid and lymphocyte subsets, features of the immune repertoire, acute phase response, metabolism, and coagulation. Persisting immune activation involving AP-1/p38MAPK was a specific feature of COVID-19. The plasma proteome enabled sub-phenotyping into patient clusters, predictive of severity and outcome. Systems-based integrative analyses including tensor and matrix decomposition of all modalities revealed feature groupings linked with severity and specificity compared to influenza and sepsis. Our approach and blood atlas will support future drug development, clinical trial design, and personalized medicine approaches for COVID-19

A new halogen bonding 1,2-iodo-triazolium-triazole benzene motif for anion recognition

The synthesis of a series of halogen bonding (XB) acyclic anion receptors based on a novel 1,2-iodo-triazolium-triazole benzene motif is reported. A combination of one- and two-dimensional 1H and 19F NMR spectroscopic techniques elucidate key conformational effects associated with the incorporation of ortho-substituted iodo-triazole based XB donors. 1H NMR anion titration experiments highlight the anion recognition potency of a mono-cationic XB iodo-triazolium-triazole benzene receptor, remarkably forming stronger halide complexes in comparison to a dicationic hydrogen bonding (HB) bis-proto-triazolium receptor analogue. X-ray crystal structure analysis provide insights into halide binding induced conformational changes and coordination modes, revealing the unique electronic and steric consequences associated with multidentate XB donor arrays