This close synchronic analysis of Exodus 1-2 looks at how the pericope's structure, language, focalization and management of information form its conception and judgement of its events and ...characters. A coherence of concerns is detectable in Exodus 1-2 with allusions to Genesis and the later chapters of Exodus. One chapter is assigned to each of seven narrative unities and deals in various ways with its narrative problems. The resulting eclectic choice of analytical tools includes the study of Proppian structural functions, repetition, public rhetoric, narrative speeds, order and symbolism.
This close synchronic analysis of Exodus 1-2 looks at how the pericope's structure, language, focalization and management of information form its conception and judgement of its events and ...characters. A coherence of concerns is detectable in Exodus 1-2 with allusions to Genesis and the later chapters of Exodus. One chapter is assigned to each of seven narrative unities and deals in various ways with its narrative problems. The resulting eclectic choice of analytical tools includes the study of Proppian structural functions, repetition, public rhetoric, narrative speeds, order and symbolism.
Life is mostly composed of the elements carbon, hydrogen, nitrogen, oxygen, sulfur, and phosphorus. Although these six elements make up nucleic acids, proteins, and lipids and thus the bulk of living ...matter, it is theoretically possible that some other elements in the periodic table could serve the same functions. Here, we describe a bacterium, strain GFAJ-1 of the Halomonadaceae, isolated from Mono Lake, California, that is able to substitute arsenic for phosphorus to sustain its growth. Our data show evidence for arsenate in macromolecules that normally contain phosphate, most notably nucleic acids and proteins. Exchange of one of the major bio-elements may have profound evolutionary and geochemical importance.
A metaphor is implied when one speaks of a person of “culture”, a “cultivated” person. The word “culture” here derives from agriculture, the tilling and planting of the soil to yield a harvest of ...nourishing things.
Culture in this broad sense means simply, as Jacques Barzun defines it, “the interests and abilities acquired by taking thought.” Any thoughtful person is potentially a person of culture. Culture is not bookish or remote, not the province of the idle, the rich or the overeducated. On the contrary, it is essential to a meaningful life.
The Church clearly has a mission in the world of culture in the broad sense of ‘taking thought’ about things that matter. But such discussion often neglects the fact that most adult Mass-goers commonly relate to the Church through their parish. Since parish life is how most people experience the Church, one can legitimately ask what it is about parishes that touches culture. In what way do they carry on as communities, not only of the heart and spirit, but also of the mind?
How do laity work in the world, as
Gaudium et Spes
mandated them? How do parish priests “interpret the signs of the times” as the
Directory on the Ministry and Life of Priests
directs? Paul VI said throughout
Evangelii Nuntiandi
that we must pay attention to the culture in which we immerse ourselves and not react to it passively but creatively. How, at the broadest level?
Whatever the activity of the parish, whatever the spirituality of the laity and priests there, Scripture is a part of their experience.
Extensive genomic characterization of human cancers presents the problem of inference from genomic abnormalities to cancer phenotypes. To address this problem, we analysed proteomes of colon and ...rectal tumours characterized previously by The Cancer Genome Atlas (TCGA) and perform integrated proteogenomic analyses. Somatic variants displayed reduced protein abundance compared to germline variants. Messenger RNA transcript abundance did not reliably predict protein abundance differences between tumours. Proteomics identified five proteomic subtypes in the TCGA cohort, two of which overlapped with the TCGA 'microsatellite instability/CpG island methylation phenotype' transcriptomic subtype, but had distinct mutation, methylation and protein expression patterns associated with different clinical outcomes. Although copy number alterations showed strong cis- and trans-effects on mRNA abundance, relatively few of these extend to the protein level. Thus, proteomics data enabled prioritization of candidate driver genes. The chromosome 20q amplicon was associated with the largest global changes at both mRNA and protein levels; proteomics data highlighted potential 20q candidates, including HNF4A (hepatocyte nuclear factor 4, alpha), TOMM34 (translocase of outer mitochondrial membrane 34) and SRC (SRC proto-oncogene, non-receptor tyrosine kinase). Integrated proteogenomic analysis provides functional context to interpret genomic abnormalities and affords a new paradigm for understanding cancer biology.
We use both large and small animal models in our pre-clinical evaluation of gene transfer agents (GTAs) for cystic fibrosis (CF) gene therapy. Here, we report the use of a large animal model to ...assess three non-viral GTAs: 25 kDa-branched polyethyleneimine (PEI), the cationic liposome (GL67A) and compacted DNA nanoparticle formulated with polyethylene glycol-substituted lysine 30-mer. GTAs complexed with plasmids expressing human cystic fibrosis transmembrane conductance regulator (CFTR) complementary DNA were administered to the sheep lung (n=8 per group) by aerosol. All GTAs gave evidence of gene transfer and expression 1 day after treatment. Vector-derived mRNA was expressed in lung tissues, including epithelial cell-enriched bronchial brushing samples, with median group values reaching 1-10% of endogenous CFTR mRNA levels. GL67A gave the highest levels of expression. Human CFTR protein was detected in small airway epithelial cells in some animals treated with GL67A (two out of eight) and PEI (one out of eight). Bronchoalveolar lavage neutrophilia, lung histology and elevated serum haptoglobin levels indicated that gene delivery was associated with mild local and systemic inflammation. Our conclusion was that GL67A was the best non-viral GTA currently available for aerosol delivery to the sheep lung, led to the selection of GL67A as our lead GTA for clinical trials in CF patients.
To characterize patient-derived xenografts (PDXs) for functional studies, we made whole-genome comparisons with originating breast cancers representative of the major intrinsic subtypes. Structural ...and copy number aberrations were found to be retained with high fidelity. However, at the single-nucleotide level, variable numbers of PDX-specific somatic events were documented, although they were only rarely functionally significant. Variant allele frequencies were often preserved in the PDXs, demonstrating that clonal representation can be transplantable. Estrogen-receptor-positive PDXs were associated with ESR1 ligand-binding-domain mutations, gene amplification, or an ESR1/YAP1 translocation. These events produced different endocrine-therapy-response phenotypes in human, cell line, and PDX endocrine-response studies. Hence, deeply sequenced PDX models are an important resource for the search for genome-forward treatment options and capture endocrine-drug-resistance etiologies that are not observed in standard cell lines. The originating tumor genome provides a benchmark for assessing genetic drift and clonal representation after transplantation.
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•Genome-wide structural variants are highly preserved in breast cancer PDX models•PDXs harbor rarely functionally significant single-nucleotide variants•PDXs harbor ESR1 mutations and translocations associated with endocrine therapy resistance•ESR1 gene amplification in PDX correlated with paradoxical estradiol-induced regression
In this study, Ellis and colleagues compare whole-tumor genomes from drug-resistant breast cancers with paired xenografts. Genomic fidelity upon transplantation was high for structural variants but variable at the single-nucleotide level. Therefore, tumor and xenograft whole-genome comparisons critically assess genetic drift and clonal representation. Additional analysis revealed ESR1 mutations, amplification, and translocations associated with endocrine resistance in lumenal xenografts. Sequenced patient-derived xenografts are an important resource for functional genomics and capture treatment-resistance etiologies that are not observed in standard cell lines.
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