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.     

Anatomy,reach and classification of the parasitoid complex of a common British moth,Anthophila fabriciana (L.) (Choreutidae)

The small plurivoltine moth Anthophila fabriciana is widespread and often abundant in Britain wherever its main larval foodplant, stinging nettle, occurs. It overwinters as a larva (first generation) then has one or more partly overlapping summer broods (notionally second generation). A total of 5017 larvae were collected and reared from widely distributed populations in Britain, and the resulting 2167 host mortalities due to parasitoids were assessed. Small collections of pupae were also made. Altogether 25 parasitoid species, including secondary parasitoids, were found. Larval parasitism was heaviest in the second generation. In each generation there was a dominant parasitoid that was absent from the other. Summary information on the developmental biology and host range (expressed quantitatively and resulting from very broad rearing programmes) for each parasitoid is given. They are classed as ‘absolute specialists’, ‘taxon oligospecialists’, ‘niche oligospecialists’, ‘niche generalists’, ‘casuals’ and ‘strays’. Both kinds of oligospecialists can be ‘paraspecialists’ if only one potential host occurs locally. Although constructing a quantitative food web is not appropriate, providing both source web and sink web data in quantitative form enables the parasitoid complex to be understood in the wider context of the ecosystem, necessary for both biodiversity and nature conservation interests. In Appendix 1, parasitoids reared from other European Choreutidae are listed quantitatively.     

Synthesis and cytokinin activity of the 3-, 7- and 9-methyl derivatives of zeatin

Zusammenfassung Die 3-, 7- und 9-Monomethylderivative des Cytokinins Zeatin wurden hergestellt und ihre Aktivität in der Karottenwurzel nachgewiesen. Die Ergebnisse zeigen, dass die Nukleotidderivative nicht not-wendige Stufen im Wirkungsmechanismus darstellen.     

Phosphorylated derivatives of the cytokinins,zeatin and its 9-β-d-ribofuranoside,naturally occurring adenine and adenosine derivatives with plant cell-division promoting activity

Zusammenfassung Zeatin-ribosid-5-phosphat wurde einerseits durch Umsetzung von 6-Chlorpurin-ribotid mit trans-4-Amino-2-methylbuten-(2)-ol-(1) und andererseits durch Behandlung von Isopropyliden-zeatin-ribosid mit Pyrophosphorylchlorid hergestellt. Die Phosphorylierung des Isopropylidenderivats in Pyridin ergab ein Allylpyridiniumderivat, dessen Struktur spektroskopisch und durch Abbau bewiesen wurde.