\u3cem\u3e Tacito predicatore\u3c/em\u3e: The Annunciation Chapel at the Madonna dei Monti in Rome

Trent could not have been clearer. Images were permitted in churches to instruct the faithful and confirm their faith. And bishops should approve only those commissions and depictions that would serve such purposes. Late in 1563, the council\u27s twenty-fifth and final session explicitly advised that stories of the mysteries of our redemption . . . in paintings and other representations enable visitors to reflect on articles of the faith challenged at that time by Protestants less well disposed to the use of images. Trent, to be sure, issued guidelines. Nudity was frowned on. Ambiguity ought to be avoided. Scriptural stories should be presented simply, as they had been told. The council aimed to answer reformers\u27 complaints and to counter Reformation iconoclasm. Prelates in attendance echoed Pope Gregory I\u27s sanction of images—his characterization of art as scripture for the illiterate—while instructing artists on their religious obligations. And no bishop took the council\u27s decrees on images more seriously than did Gabriele Paleotti, who attended the last session before returning to his see of Bologna

PhyloMarker—A Tool for Mining Phylogenetic Markers Through Genome Comparison: Application of the Mouse Lemur (Genus Microcebus) Phylogeny

Molecular phylogeny is a fundamental tool to understanding the evolution of all life forms. One common issue faced by molecular phylogeny is the lack of sufficient molecular markers. Here, we present PhyloMarker, a phylogenomic tool designed to find nuclear gene markers for the inference of phylogeny through multiple genome comparison. Around 800 candidate markers were identified by PhyloMarker through comparison of partial genomes of Microcebus and Otolemur. In experimental tests of 20 randomly selected markers, nine markers were successfully amplified by PCR and directly sequenced in all 17 nominal Microcebus species. Phylogenetic analyses of the sequence data obtained for 17 taxa and nine markers confirmed the distinct lineage inferred from previous mtDNA data. PhyloMarker has also been used by other projects including the herons (Ardeidae, Aves) phylogeny and the Wood mice (Muridae, Mammalia) phylogeny. All source code and sample data are made available at http://bioinfo-srv1.awh.unomaha.edu/phylomarker/

Heterogeneity of magnitude, allergen immunodominance, and cytokine polarization of cockroach allergen-specific T cell responses in allergic sensitized children.

Background: Characterization of allergic responses to cockroach (CR), a common aeroallergen associated with asthma, has focused mainly on IgE reactivity, but little is known about T cell responses, particularly in children. We conducted a functional evaluation of CR allergen-specific T cell reactivity in a cohort of CR allergic children with asthma. Methods: Peripheral blood mononuclear cells (PBMCs) were obtained from 71 children, with mild-to-moderate asthma who were enrolled in a CR immunotherapy (IT) clinical trial, prior to treatment initiation. PBMC were stimulated with peptide pools derived from 11 CR allergens, and CD4+ T cell responses assessed by intracellular cytokine staining. Results: Highly heterogeneous responses in T cell reactivity were observed among participants, both in terms of the magnitude of cytokine response and allergen immunodominance. Reactivity against Bla g 9 and Bla g 5 was most frequent. The phenotype of the T cell response was dominated by IL-4 production and a Th2 polarized profile in 54.9% of participants, but IFNγ production and Th1 polarization was observed in 25.3% of the participants. The numbers of regulatory CD4+ T cells were also highly variable and the magnitude of effector responses and Th2 polarization were positively correlated with serum IgE levels specific to a clinical CR extract. Conclusions: Our results demonstrate that in children with mild-to-moderate asthma, CR-specific T cell responses display a wide range of magnitude, allergen dominance, and polarization. These results will enable examination of whether any of the variables measured are affected by IT and/or are predictive of clinical outcomes

African-specific alleles modify risk for asthma at the 17q12-q21 locus in African Americans

BACKGROUND: Asthma is the most common chronic disease in children, occurring at higher frequencies and with more severe disease in children with African ancestry. METHODS: We tested for association with haplotypes at the most replicated and significant childhood-onset asthma locus at 17q12-q21 and asthma in European American and African American children. Following this, we used whole-genome sequencing data from 1060 African American and 100 European American individuals to identify novel variants on a high-risk African American-specific haplotype. We characterized these variants in silico using gene expression and ATAC-seq data from airway epithelial cells, functional annotations from ENCODE, and promoter capture (pc)Hi-C maps in airway epithelial cells. Candidate causal variants were then assessed for correlation with asthma-associated phenotypes in African American children and adults. RESULTS: Our studies revealed nine novel African-specific common variants, enriched on a high-risk asthma haplotype, which regulated the expression of GSDMA in airway epithelial cells and were associated with features of severe asthma. Using ENCODE annotations, ATAC-seq, and pcHi-C, we narrowed the associations to two candidate causal variants that are associated with features of T2 low severe asthma. CONCLUSIONS: Previously unknown genetic variation at the 17q12-21 childhood-onset asthma locus contributes to asthma severity in individuals with African ancestries. We suggest that many other population-specific variants that have not been discovered in GWAS contribute to the genetic risk for asthma and other common diseases

De Novo and Rare Inherited Copy-Number Variations in the Hemiplegic Form of Cerebral Palsy

PurposeHemiplegia is a subtype of cerebral palsy (CP) in which one side of the body is affected. Our earlier study of unselected children with CP demonstrated de novo and clinically relevant rare inherited genomic copy-number variations (CNVs) in 9.6% of participants. Here, we examined the prevalence and types of CNVs specifically in hemiplegic CP.MethodsWe genotyped 97 unrelated probands with hemiplegic CP and their parents. We compared their CNVs to those of 10,851 population controls, in order to identify rare CNVs

Ovarian cancer immunotherapy: opportunities, progresses and challenges

Due to the low survival rates from invasive ovarian cancer, new effective treatment modalities are urgently needed. Compelling evidence indicates that the immune response against ovarian cancer may play an important role in controlling this disease. We herein summarize multiple immune-based strategies that have been proposed and tested for potential therapeutic benefit against advanced stage ovarian cancer. We will examine the evidence for the premise that an effective therapeutic vaccine against ovarian cancer is useful not only for inducing remission of the disease but also for preventing disease relapse. We will also highlight the questions and challenges in the development of ovarian cancer vaccines, and critically discuss the limitations of some of the existing immunotherapeutic strategies. Finally, we will summarize our own experience on the use of patient-specific tumor-derived heat shock protein-peptide complex for the treatment of advanced ovarian cancer

Tetracosahexaenoylethanolamide, a novel -acylethanolamide, is elevated in ischemia and increases neuronal output.

-acylethanolamines (NAEs) are endogenous lipid-signaling molecules derived from fatty acids that regulate numerous biological functions, including in the brain. Interestingly, NAEs are elevated in the absence of fatty acid amide hydrolase (FAAH) and following CO-induced ischemia/hypercapnia, suggesting a neuroprotective response. Tetracosahexaenoic acid (THA) is a product and precursor to DHA; however, the NAE product, tetracosahexaenoylethanolamide (THEA), has never been reported. Presently, THEA was chemically synthesized as an authentic standard to confirm THEA presence in biological tissues. Whole brains were collected and analyzed for unesterified THA, total THA, and THEA in wild-type and FAAH-KO mice that were euthanized by either head-focused microwave fixation, CO + microwave, or CO only. PPAR activity by transient transfection assay and ex vivo neuronal output in medium spiny neurons (MSNs) of the nucleus accumbens by patch clamp electrophysiology were determined following THEA exposure. THEA in the wild-type mice was nearly doubled ( 0.05) transcriptional activity of PPARs relative to control, but 100 nM of THEA increased ( < 0.001) neuronal output in MSNs of the nucleus accumbens. Here were identify a novel NAE, THEA, in the brain that is elevated upon ischemia/hypercapnia and by KO of the FAAH enzyme. While THEA did not activate PPAR, it augmented the excitability of MSNs in the nucleus accumbens. Overall, our results suggest that THEA is a novel NAE that is produced in the brain upon ischemia/hypercapnia and regulates neuronal excitation