“Als wel the lord as the schepherde, He broghte hem alle in good accord”: Harmonious Materialism in the Confessio Amantis

Using R. F. Yeager\u27s analysis of the figure Arion as a starting point, this article argues that in the Confessio Amantis, John Gower shifts his impulse toward social correction from direct estates satire to a more subtle approach encoding his social critique in the love stories of the Confessio. Examples of this approach include a variety of tales from Book 5, and the Apollonius of Tyre story in Book 8. Details of the poem\u27s ending and later works like In Praise of Peace indicate that Gower still retained an interest in direct critique of social problems

Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.Peer reviewe

Process Development and cGMP Manufacturing of a Recombinant Ricin Vaccine: an Effective and Stable Recombinant Ricin A-Chain Vaccine—RVE\u3ci\u3ec\u3c/i\u3eTM

Ricin is a potent toxin and a potential bioterrorism weapon with no specific countermeasures or vaccines available. The holotoxin is composed of two polypeptide chains linked by a single disulfide bond: the A-chain (RTA), which is an N-glycosidase enzyme, and the B-chain (RTB), a lectin polypeptide that binds galactosyl moieties on the surface of the mammalian target cells. Previously (McHugh et al.), a recombinant truncated form of RTA (rRTA1-33/ 44-198 protein, herein denoted RVEaTM) expressed in Escherichia coli using a codon-optimized gene was shown to be non-toxic, stable, and protective against a ricin challenge in mice. Here, we describe the process development and scale-up at the 12 L fermentation scale, and the current Good Manufacturing Practice (cGMP)-compliant production of RVEcTM at the 40 L scale. The average yield of the final purified bulk RVEcTM is approximately 16 g/kg of wet cell weight or 1.2 g/L of fermentation broth. The RVEcTM was \u3e99% pure by three HPLC methods and SDS-PAGE. The intact mass and peptide mapping analysis of RVEcTM confirmed the identity of the product and is consistent with the absence of posttranslational modifications. Potency assays demonstrated that RVEcTM was immunoprotective against lethal ricin challenge and elicited neutralizing anti-ricin antibodies in 95–100% of the vaccinated mice