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.     

Alkaline phosphatase binds to collagen; a hypothesis on the mechanism of extravesicular mineralization in epiphyseal cartilage

Affinity chromatography on Sepharose 4B-collagen gels was used to test the affinity of alkaline phosphatase for collagen. Results indicate that alkaline phosphatase of preosseous cartilage binds to collagen probably by electrostatic interactions, this interaction is inhibited by proteoglycan subunits. These results suggest that, in vivo, the formation of a collagen-alkaline phosphatase complex may be a step of the process leading to cartilage calcification.     

Geminus and the concept of mean motion in Greco-Latin astronomy

Conclusion Geminus account of lunar motion in chapter 18 of hisIntroductio astronomiae is, in our view, an important contribution to Greco-Latin astronomy because, in attempting to reconstruct arithmetically (the parameters of) the Moon's motion in longitude, he undermines the task astronomers had hitherto set for themselves. This undermining of a commonly acknowledged view of the purpose of astronomy is articulated in a whole new set of questions concerning the nature and place of both observation and mathematical reasoning in the science of the heavens. Yet, one must not overlook the fact thatGeminus reconstruction also indicates resources for addressing these questions. Of these resources, the most powerful proved to be the idea that irregular motion could be quantified as a systematic departure from a mean motion, and the idea that observational data could be organized and structured by means of genetic arithmetical reconstructions.But, since we limit our attention to extant treatises and decline to speculate about works or parts of works that have not survived, we must say that it would takePtolemy to discern the new direction for astronomy thatGeminus opened up and to pursue it. In part, this involved straightening out the conflated conception of mean motion in chapter 18 — the qua arithmetic mean daily displacement can only be anapparent lunar motion in longitude and not one the Moonreally makes, but the same need not be true of the qua periodic mean daily displacement — and determining its proper relation to real and apparent planetary motion. Indeed,Ptolemy's genius lay, we think, in seeing that even though, in assimilating Babylonian astronomy, earlier and contemporary Greco-Latin writers betrayed a confused, inconsistent, and unsophisticated grasp of the proper role of arithmetic, geometry, and observation in astronomical argument [seeBowen 1994], the solution lay in a mathematical reconstruction of the observed celestial motions, in which mean motion played an essential role.     

Effect of in vivo irradiation of the rat on the taurine concentration of the heart

Summary The taurine concentration in the heart of the rat (moles/g of tissue) was not modified during 10 days after an in vivo irradiation of 900 R.     

Linking climate change to lemming cycles

The population cycles of rodents at northern latitudes have puzzled people for centuries, and their impact is manifest throughout the alpine ecosystem. Climate change is known to be able to drive animal population dynamics between stable and cyclic phases, and has been suggested to cause the recent changes in cyclic dynamics of rodents and their predators. But although predator-rodent interactions are commonly argued to be the cause of the Fennoscandian rodent cycles, the role of the environment in the modulation of such dynamics is often poorly understood in natural systems. Hence, quantitative links between climate-driven processes and rodent dynamics have so far been lacking. Here we show that winter weather and snow conditions, together with density dependence in the net population growth rate, account for the observed population dynamics of the rodent community dominated by lemmings (Lemmus lemmus) in an alpine Norwegian core habitat between 1970 and 1997, and predict the observed absence of rodent peak years after 1994. These local rodent dynamics are coherent with alpine bird dynamics both locally and over all of southern Norway, consistent with the influence of large-scale fluctuations in winter conditions. The relationship between commonly available meteorological data and snow conditions indicates that changes in temperature and humidity, and thus conditions in the subnivean space, seem to markedly affect the dynamics of alpine rodents and their linked groups. The pattern of less regular rodent peaks, and corresponding changes in the overall dynamics of the alpine ecosystem, thus seems likely to prevail over a growing area under projected climate change.