Symbiotic modeling: Linguistic Anthropology and the promise of chiasmus

Reflexive observations and observations of reflexivity: such agendas are by now standard practice in anthropology. Dynamic feedback loops between self and other, cause and effect, represented and representamen may no longer seem surprising; but, in spite of our enhanced awareness, little deliberate attention is devoted to modeling or grounding such phenomena. Attending to both linguistic and extra-linguistic modalities of chiasmus (the X figure), a group of anthropologists has recently embraced this challenge. Applied to contemporary problems in linguistic anthropology, chiasmus functions to highlight and enhance relationships of interdependence or symbiosis between contraries, including anthropology’s four fields, the nature of human being and facets of being human

Comprehensive Molecular Portraits of Invasive Lobular Breast Cancer

Invasive lobular carcinoma (ILC) is the second most prevalent histologic subtype of invasive breast cancer. Here, we comprehensively profiled 817 breast tumors, including 127 ILC, 490 ductal (IDC), and 88 mixed IDC/ILC. Besides E-cadherin loss, the best known ILC genetic hallmark, we identified mutations targeting PTEN, TBX3 and FOXA1 as ILC enriched features. PTEN loss associated with increased AKT phosphorylation, which was highest in ILC among all breast cancer subtypes. Spatially clustered FOXA1 mutations correlated with increased FOXA1 expression and activity. Conversely, GATA3 mutations and high expression characterized Luminal A IDC, suggesting differential modulation of ER activity in ILC and IDC. Proliferation and immune-related signatures determined three ILC transcriptional subtypes associated with survival differences. Mixed IDC/ILC cases were molecularly classified as ILC-like and IDC-like revealing no true hybrid features. This multidimensional molecular atlas sheds new light on the genetic bases of ILC and provides potential clinical options

Metafísica y retórica

The renaissance of rhetoric in the 20th century has influenced philosophy as well. Nevertheless, the rhetorical turn in modern philosophy leads to a new Sophistics which deconstructs metaphysics and its texts. On the contrary my article argues in favour of a new positive perspective of integration of philosophy and rhetoric. Parting from the discovery of the hidden rhetoric at the beginning of the history of metaphysics and developing a typology and a topology of speculative discourse. Finally, I arque against (post)modern Sophystics and for the possibility of a rhetorically illustrated metaphysics

Transcriptome characterization of matched primary breast and brain metastatic tumors to detect novel actionable targets.

Background: Breast cancer brain metastases (BrMs) are defined by complex adaptations to both adjuvant treatment regimens and the brain microenvironment. Consequences of these alterations remain poorly understood, as does their potential for clinical targeting. We utilized genome-wide molecular profiling to identify therapeutic targets acquired in metastatic disease.Methods: Gene expression profiling of 21 patient-matched primary breast tumors and their associated brain metastases was performed by TrueSeq RNA-sequencing to determine clinically actionable BrM target genes. Identified targets were functionally validated using small molecule inhibitors in a cohort of resected BrM ex vivo explants (n = 4) and in a patient-derived xenograft (PDX) model of BrM. All statistical tests were two-sided.Results: Considerable shifts in breast cancer cell-specific gene expression profiles were observed (1314 genes upregulated in BrM; 1702 genes downregulated in BrM; DESeq; fold change > 1.5, Padj Conclusions: RNA-seq profiling of longitudinally collected specimens uncovered recurrent gene expression acquisitions in metastatic tumors, distinct from matched primary tumors. Critically, we identify aberrations in key oncogenic pathways and provide functional evidence for their suitability as therapeutic targets. Altogether, this study establishes recurrent, acquired vulnerabilities in BrM that warrant immediate clinical investigation and suggests paired specimen expression profiling as a compelling and underutilized strategy to identify targetable dependencies in advanced cancers.</p