A screen of the complete protein kinase gene family identifies diverse patterns of somatic mutations in human breast cancer

We examined the coding sequence of 518 protein kinases, approximately 1.3 Mb of DNA per sample, in 25 breast cancers. In many tumors, we detected no somatic mutations. But a few had numerous somatic mutations with distinctive patterns indicative of either a mutator phenotype or a past exposure.     

Lung cancer: intragenic ERBB2 kinase mutations in tumours

The protein-kinase family is the most frequently mutated gene family found in human cancer and faulty kinase enzymes are being investigated as promising targets for the design of antitumour therapies. We have sequenced the gene encoding the transmembrane protein tyrosine kinase ERBB2 (also known as HER2 or Neu) from 120 primary lung tumours and identified 4% that have mutations within the kinase domain; in the adenocarcinoma subtype of lung cancer, 10% of cases had mutations. ERBB2 inhibitors, which have so far proved to be ineffective in treating lung cancer, should now be clinically re-evaluated in the specific subset of patients with lung cancer whose tumours carry ERBB2 mutations.     

Evidence for substantial fine-scale variation in recombination rates across the human genome

Characterizing fine-scale variation in human recombination rates is important, both to deepen understanding of the recombination process and to aid the design of disease association studies. Current genetic maps show that rates vary on a megabase scale, but studying finer-scale variation using pedigrees is difficult. Sperm-typing experiments have characterized regions where crossovers cluster into 1-2-kb hot spots, but technical difficulties limit the number of studies. An alternative is to use population variation to infer fine-scale characteristics of the recombination process. Several surveys reported 'block-like' patterns of diversity, which may reflect fine-scale recombination rate variation, but limitations of available methods made this impossible to assess. Here, we applied a new statistical method, which overcomes these limitations, to infer patterns of fine-scale recombination rate variation in 74 genes. We found extensive rate variation both within and among genes. In particular, recombination hot spots are a common feature of the human genome: 47% (35 of 74) of genes showed substantive evidence for a hot spot, and many more showed evidence for some rate variation. No primary sequence characteristics are consistently associated with precise hot-spot location, although G+C content and nucleotide diversity are correlated with local recombination rate.     

The effect of temperature variation on spontaneous potential production from explants of brain tissue in culture

Zusammenfassung Bei zwei verschiedenen Explantaten von Telencephalogewebe 14tägiger Hühnchenembryonen ergab sich als Temperaturabhängigkeit der Aktionspotentiale: Frequenz und Amplitudenabnahme bei sinkender, Zunahme bei steigender Temperatur bis zwischen 37 und 42,5°C. Weitere Temperatursteigerung bringt die Potentiale nach stetiger Verkleinerung bei 47°C schliesslich zum Verschwinden.

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This research was supported by a grant from the Office of Naval Research, U.S. Navy Contract NONR 1598(04).     

Towards the clarity limit in optical fibre

An important scientific and technological goal in the field of optical communications is the achievement of the clarity limit in optical fibres--that is, ensuring that the SiO2 glass from which fibres are made is as transparent as possible. The clarity of the wavelength transmission window (and the width of that window) in existing fibres is already sufficient to form the basis of a world-wide optical communication system, yet it is still limited by contamination of the fibre by water. Here we measure the spatial distribution of water in the glass rods from which optical fibres are drawn and explain the distribution quantitatively with a mathematical model of diffusion in a medium with essentially perfect cylindrical symmetry. Our analysis shows that the water enters from the outside of the rod and diffuses into the molten, flowing glass much faster than is expected from extrapolation of low-temperature measurements. Our elucidation of the physics underlying the contamination process has already led to the fabrication of dry fibres, which have a clarified and broadened communications window. The improved operational range of wavelengths should yield applications for new lasers, optical amplifiers and detectors, and should substantially increase the information-carrying capacity of optical communications systems.     

Colorectal carcinomas in mice lacking the catalytic subunit of PI(3)Kgamma

Phosphoinositide-3-OH kinases (PI(3)Ks) constitute a family of evolutionarily conserved lipid kinases that regulate a vast array of fundamental cellular responses, including proliferation, transformation, differentiation and protection from apoptosis. PI(3)K-mediated activation of the cell survival kinase PKB/Akt, and negative regulation of PI(3)K signalling by the tumour suppressor PTEN (refs 3, 4) are key regulatory events in tumorigenesis. Thus, a model has arisen that PI(3)Ks promote development of cancers. Here we report that genetic inactivation of the p110gamma catalytic subunit of PI(3)Kgamma (ref. 8) leads to development of invasive colorectal adenocarcinomas in mice. In humans, p110gamma protein expression is lost in primary colorectal adenocarcinomas from patients and in colon cancer cell lines. Overexpression of wild-type or kinase-dead p110gamma in human colon cancer cells with mutations of the tumour suppressors APC and p53, or the oncogenes beta-catenin and Ki-ras, suppressed tumorigenesis. Thus, loss of p110gamma in mice leads to spontaneous, malignant epithelial tumours in the colorectum and p110gamma can block the growth of human colon cancer cells.     

Towards a Feminist-Systems Theory

This paper provides the findings of a study to locate the similarity and/or differences between two epistemologies: critical systems thinking and cultural ecofeminism. Selected texts from authors in each field were coded and compared using the Constant comparative analysis, grounded theory method. The analysis revealed a multitude of similarities across a range of concepts, including systems thinking language; challenges to positivist science, reason and instrumentalism; ethics and morality and praxis. The analysis also revealed several emergent principles for working towards a feminist systems theory of practice.     

Systemic Intervention Practice at an Australian Aboriginal and Torres Strait Islander Alcohol and Other Drugs Treatment Centre

The purpose of this article is to describe the use of systemic intervention research methodology at an Indigenous-specific Australian drug and alcohol ‘therapeutic community’ rehabilitation setting. Systemic intervention is a three step methodological framework belonging to the systems thinking discipline. Practitioners must be mindful of the boundaries of the systems with which they are working; the need to select appropriate theoretical and methodological approaches to the context of the research, and undertake interventions towards sustainable and desirable change. Three participatory methods are detailed to highlight the importance and value of reflective practice. The three methods ranged from consultative through to collegial levels of participant engagement. Systemic intervention is a useful methodology in the context of indigenous health research and could be a valued approach in other research contexts that are explicit in their intent to help close the gap on Indigenous health disadvantage.