La emblemática jesuítica en El Criticón

The author abstract is posted here. For access to the full text of the article please follow publisher's link. Copyright is held by the publisher.While the impact of the humanistic emblem tradition as embodied by Andrea Alciati’s work in Baltasar Gracián’s three-part novel El Criticón (1651, 1653 and 1657) is well documented, the allegorical novel’s relationship with the Jesuit emblem tradition has not been considered in detail. This essay explores the relationship between the emblem tradition of the Society of Jesus as developed in the Imago primi saeculi Societatis Iesu a Prouincia Flandro-Belgica eiusdem Societatis repraesentata (1640) and El Criticón. In engaging with the Jesuit emblem tradition, Gracián makes secular interpretations of established Jesuit imagery. Not only does this intertextual relationship enrich the interpretation of El Criticón, but also explains the Jesuit hierarchy’s negative reaction to the novel

Don Quijote on the Plains: Harnessing Enthusiasm for the "Quijote" at the Undergraduate Level

This is the published version. Copyright 2005 Johns Hopkins University Press.Teaching Miguel de Cervantes's "El ingenioso hidalgo don Quijote de la Mancha" in the undergraduate classroom can pose a myriad of linguistic and contextual challenges for students distanced from the text by the space of four hundred years. This paper details teaching strategies that incorporate linguistic activities, film, references to visual culture, and discussion to encourage deep learning on the part of undergraduate readers of Cervantes's classic novel

An Overview of the Pre-suppression Society of Jesus in Spain

In An Overview of the Pre-suppression Society of Jesus in Spain, Patricia W. Manning offers a survey of the Society of Jesus in Spain from its origins in Ignatius of Loyola’s early preaching to the aftereffects of its expulsion. Rather than nurture the nascent order, Loyola’s homeland was often ambivalent. His pre-Jesuit freelance sermonizing prompted investigations. The young Society confronted indifference and interference from the Spanish monarchy and outright opposition from other religious orders. This essay outlines the order’s ministerial and pedagogical activities, its relationship with women and with royal institutions, including the Spanish Inquisition, and Spanish members’ roles in theological debates concerning casuistry, free will, and the immaculate conception. It also considers the impact of Jesuits’ non-religious writings. Readership: Readers interested in the Society of Jesus, textual production by Jesuits, the Society’s ties to women, early modern theological polemics, and early modern Spain, including undergraduate and graduate students

Present Dogs, Absent Witches: Illustration and Interpretation of ‘El coloquio de los perros’

The author abstract is posted here. For access to the full text of the article please follow publisher's link. Copyright is held by the publisher.Aunque los grabados que acompañan a los textos impresos de las Novelas ejemplares suelen representar los desenlaces de las novelas, las imágenes de “El coloquio de los perros” rompen con esta tendencia visual. Este trabajo analiza diez y ocho grabados de “El coloquio de los perros” publicados en los Países Bajos, Suiza, Francia y España. De estas imágenes, diez y seis representan a los perros en lugar de visualizar a Cañizares porque la representación de la bruja legitimaría la explicación que ella ofrece de las habilidades oratorias de Cipión y Berganza. Después de examinar el entorno social e histórico de la producción de estos grabados y la representación visual de las brujas, el trabajo concluye que la imagen de los perros desautoriza la narrativa de la bruja. Trece de las diez y seis viñetas ilustran a los interlocutorios caninos en el hospital. Esta situación de Cipión y Berganza como productos de la fiebre sifilítica de Campuzano tranquiliza al lector perturbado por la presentación de la sociedad en la novela

Gene Regulatory Networks from Multifactorial Perturbations Using Graphical Lasso: Application to the DREAM4 Challenge

A major challenge in the field of systems biology consists of predicting gene regulatory networks based on different training data. Within the DREAM4 initiative, we took part in the multifactorial sub-challenge that aimed to predict gene regulatory networks of size 100 from training data consisting of steady-state levels obtained after applying multifactorial perturbations to the original in silico network

Using Sequence Similarity Networks for Visualization of Relationships Across Diverse Protein Superfamilies

The dramatic increase in heterogeneous types of biological data—in particular, the abundance of new protein sequences—requires fast and user-friendly methods for organizing this information in a way that enables functional inference. The most widely used strategy to link sequence or structure to function, homology-based function prediction, relies on the fundamental assumption that sequence or structural similarity implies functional similarity. New tools that extend this approach are still urgently needed to associate sequence data with biological information in ways that accommodate the real complexity of the problem, while being accessible to experimental as well as computational biologists. To address this, we have examined the application of sequence similarity networks for visualizing functional trends across protein superfamilies from the context of sequence similarity. Using three large groups of homologous proteins of varying types of structural and functional diversity—GPCRs and kinases from humans, and the crotonase superfamily of enzymes—we show that overlaying networks with orthogonal information is a powerful approach for observing functional themes and revealing outliers. In comparison to other primary methods, networks provide both a good representation of group-wise sequence similarity relationships and a strong visual and quantitative correlation with phylogenetic trees, while enabling analysis and visualization of much larger sets of sequences than trees or multiple sequence alignments can easily accommodate. We also define important limitations and caveats in the application of these networks. As a broadly accessible and effective tool for the exploration of protein superfamilies, sequence similarity networks show great potential for generating testable hypotheses about protein structure-function relationships

Genome-Wide Gene-Environment Study Identifies Glutamate Receptor Gene GRIN2A as a Parkinson's Disease Modifier Gene via Interaction with Coffee

Our aim was to identify genes that influence the inverse association of coffee with the risk of developing Parkinson's disease (PD). We used genome-wide genotype data and lifetime caffeinated-coffee-consumption data on 1,458 persons with PD and 931 without PD from the NeuroGenetics Research Consortium (NGRC), and we performed a genome-wide association and interaction study (GWAIS), testing each SNP's main-effect plus its interaction with coffee, adjusting for sex, age, and two principal components. We then stratified subjects as heavy or light coffee-drinkers and performed genome-wide association study (GWAS) in each group. We replicated the most significant SNP. Finally, we imputed the NGRC dataset, increasing genomic coverage to examine the region of interest in detail. The primary analyses (GWAIS, GWAS, Replication) were performed using genotyped data. In GWAIS, the most significant signal came from rs4998386 and the neighboring SNPs in GRIN2A. GRIN2A encodes an NMDA-glutamate-receptor subunit and regulates excitatory neurotransmission in the brain. Achieving P2df = 10−6, GRIN2A surpassed all known PD susceptibility genes in significance in the GWAIS. In stratified GWAS, the GRIN2A signal was present in heavy coffee-drinkers (OR = 0.43; P = 6×10−7) but not in light coffee-drinkers. The a priori Replication hypothesis that “Among heavy coffee-drinkers, rs4998386_T carriers have lower PD risk than rs4998386_CC carriers” was confirmed: ORReplication = 0.59, PReplication = 10−3; ORPooled = 0.51, PPooled = 7×10−8. Compared to light coffee-drinkers with rs4998386_CC genotype, heavy coffee-drinkers with rs4998386_CC genotype had 18% lower risk (P = 3×10−3), whereas heavy coffee-drinkers with rs4998386_TC genotype had 59% lower risk (P = 6×10−13). Imputation revealed a block of SNPs that achieved P2df<5×10−8 in GWAIS, and OR = 0.41, P = 3×10−8 in heavy coffee-drinkers. This study is proof of concept that inclusion of environmental factors can help identify genes that are missed in GWAS. Both adenosine antagonists (caffeine-like) and glutamate antagonists (GRIN2A-related) are being tested in clinical trials for treatment of PD. GRIN2A may be a useful pharmacogenetic marker for subdividing individuals in clinical trials to determine which medications might work best for which patients

A Framework For Detecting Noncoding Rare-Variant associations of Large-Scale Whole-Genome Sequencing Studies

Large-scale whole-genome sequencing studies have enabled analysis of noncoding rare-variant (RV) associations with complex human diseases and traits. Variant-set analysis is a powerful approach to study RV association. However, existing methods have limited ability in analyzing the noncoding genome. We propose a computationally efficient and robust noncoding RV association detection framework, STAARpipeline, to automatically annotate a whole-genome sequencing study and perform flexible noncoding RV association analysis, including gene-centric analysis and fixed window-based and dynamic window-based non-gene-centric analysis by incorporating variant functional annotations. In gene-centric analysis, STAARpipeline uses STAAR to group noncoding variants based on functional categories of genes and incorporate multiple functional annotations. In non-gene-centric analysis, STAARpipeline uses SCANG-STAAR to incorporate dynamic window sizes and multiple functional annotations. We apply STAARpipeline to identify noncoding RV sets associated with four lipid traits in 21,015 discovery samples from the Trans-Omics for Precision Medicine (TOPMed) program and replicate several of them in an additional 9,123 toPMed samples. We also analyze five non-lipid toPMed traits

Type 2 Diabetes Modifies the association of Cad Genomic Risk Variants With Subclinical atherosclerosis

BACKGROUND: Individuals with type 2 diabetes (T2D) have an increased risk of coronary artery disease (CAD), but questions remain about the underlying pathology. Identifying which CAD loci are modified by T2D in the development of subclinical atherosclerosis (coronary artery calcification [CAC], carotid intima-media thickness, or carotid plaque) may improve our understanding of the mechanisms leading to the increased CAD in T2D. METHODS: We compared the common and rare variant associations of known CAD loci from the literature on CAC, carotid intima-media thickness, and carotid plaque in up to 29 670 participants, including up to 24 157 normoglycemic controls and 5513 T2D cases leveraging whole-genome sequencing data from the Trans-Omics for Precision Medicine program. We included first-order T2D interaction terms in each model to determine whether CAD loci were modified by T2D. The genetic main and interaction effects were assessed using a joint test to determine whether a CAD variant, or gene-based rare variant set, was associated with the respective subclinical atherosclerosis measures and then further determined whether these loci had a significant interaction test. RESULTS: Using a Bonferroni-corrected significance threshold of CONCLUSIONS: These results highlight T2D as an important modifier of rare variant associations in CAD loci with CAC

Multi-ancestry sleep-by-SNP interaction analysis in 126,926 individuals reveals lipid loci stratified by sleep duration.

Both short and long sleep are associated with an adverse lipid profile, likely through different biological pathways. To elucidate the biology of sleep-associated adverse lipid profile, we conduct multi-ancestry genome-wide sleep-SNP interaction analyses on three lipid traits (HDL-c, LDL-c and triglycerides). In the total study sample (discovery + replication) of 126,926 individuals from 5 different ancestry groups, when considering either long or short total sleep time interactions in joint analyses, we identify 49 previously unreported lipid loci, and 10 additional previously unreported lipid loci in a restricted sample of European-ancestry cohorts. In addition, we identify new gene-sleep interactions for known lipid loci such as LPL and PCSK9. The previously unreported lipid loci have a modest explained variance in lipid levels: most notable, gene-short-sleep interactions explain 4.25% of the variance in triglyceride level. Collectively, these findings contribute to our understanding of the biological mechanisms involved in sleep-associated adverse lipid profiles