The clonal and mutational evolution spectrum of primary triple-negative breast cancers

Primary triple-negative breast cancers (TNBCs), a tumour type defined by lack of oestrogen receptor, progesterone receptor and ERBB2 gene amplification, represent approximately 16% of all breast cancers. Here we show in 104 TNBC cases that at the time of diagnosis these cancers exhibit a wide and continuous spectrum of genomic evolution, with some having only a handful of coding somatic aberrations in a few pathways, whereas others contain hundreds of coding somatic mutations. High-throughput RNA sequencing (RNA-seq) revealed that only approximately 36% of mutations are expressed. Using deep re-sequencing measurements of allelic abundance for 2,414 somatic mutations, we determine for the first time-to our knowledge-in an epithelial tumour subtype, the relative abundance of clonal frequencies among cases representative of the population. We show that TNBCs vary widely in their clonal frequencies at the time of diagnosis, with the basal subtype of TNBC showing more variation than non-basal TNBC. Although p53 (also known as TP53), PIK3CA and PTEN somatic mutations seem to be clonally dominant compared to other genes, in some tumours their clonal frequencies are incompatible with founder status. Mutations in cytoskeletal, cell shape and motility proteins occurred at lower clonal frequencies, suggesting that they occurred later during tumour progression. Taken together, our results show that understanding the biology and therapeutic responses of patients with TNBC will require the determination of individual tumour clonal genotypes.     

IgG as the main immobilization factor in rabbit antiserum againstEntamoeba

Résumé Les antisérums de lapin utilisées contre les trophozoïtes de l'Entamboeba histolytica, E. moshkovskii etE. invadens furent fractionnés par la cellulose DEAE et le Sephadex G-200. Les essais d'immobilisation avec ces antisérums fractionnés montrent que la fraction IgG est la plus active à cet effet. En usant les fractions actives, des essais démontrent l'existence d'une réaction croisée entreE. invadens etE. histolytica.

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S.E.A. is grateful for a Research Grant from the Wellcome Trust.     

The uptake and rate of clearance of125I γG globulin in lampreys (Lampetra fluviatilis)

Zusammenfassung Lampreten wurden mit menschlichem¹²⁵I-markierten,-Globulin injiziert, und die Aufnahme und Abgabe des Antigens wurden untersucht. Der Ort der Aufnahme des Antigens wurde autoradiographisch bestimmt.     

Heat-shock protein 60 translocates to the surface of apoptotic cells and differentiated megakaryocytes and stimulates phagocytosis

Heat-shock protein 60 (Hsp60) is a highly conserved stress protein which has chaperone functions in prokaryotes and mammalian cells. Hsp60 is associated with the mitochondria and the plasma membrane through phosphorylation by protein kinase A, and is incorporated into lipid membranes as a protein-folding chaperone. Its diverse intracellular chaperone functions include the secretion of proteins where it maintains the conformation of precursors and facilitates their translocation through the plasma membrane. We report here that Hsp60 is concentrated in apoptotic membrane blebs and translocates to the surface of cells undergoing apoptosis. Hsp60 is also enriched in platelets derived from terminally differentiated megakaryocytes and expressed at the surface of senescent platelets. Furthermore, the exposure of monocytic U937 cells to Hsp60 enhanced their phagocytic activity. Our results suggests that externalized Hsp60 in apoptotic cells and senescent platelets influences events subsequent to apoptosis, such as the clearance of apoptotic cells by phagocytes.     

Revisiting Galison’s ‘Aufbau/Bauhaus’ in light of Neurath’s philosophical projects

In his article entitled ‘Aufbau/Bauhaus’ and related work, Peter Galison explores the connections between the Vienna Circle and the Dessau Bauhaus. Historically, these groups were related, with members of each group familiar with the ideas of the other. Galison argues that their projects are related as well, through shared political views and methodological approach. The two main figures that connect the Vienna Circle to the Bauhaus—and the figures upon which Galison focuses—are Rudolf Carnap and Otto Neurath. Yet, in our view, the connections that Galison develops do not properly capture the common themes between the Bauhaus and Neurath’s philosophical projects. In this paper, we will examine a few of the historical connections between the Dessau Bauhaus and the Vienna Circle, as well as the philosophical connections that Galison draws between these two groups. By examining in greater depth Neurath’s philosophical commitments, we aim to demonstrate that some of these philosophical connections fail to resonate with Neurath’s projects. And, finally, we develop different connections between Neurath’s projects and the Bauhaus. In our view, these new connections between Neurath and the Dessau Bauhaus are both substantive and philosophically interesting.