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.     

Two types of response patterns from cat retinal ganglion cells to moving stimuli

Résumé Deux Types de réponses apparaissent dans des cellules ganglionnaires du chat soumises à des stimuli mobiles. Ils correspondent aux unités répondant de façon transitoire ou durable et proviennent d'une différence dans la disposition spatiale du centre et de la périphérie du champ récepteur.

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This investigation was supported by a Public Health Research Grant No. EY00376 from the National Eye Institute, National Institutes of Health, Bethesda, Md.     

Effect of spermine on the kinetics of estradiol hydroxylation by rat liver microsomes

Résumé L'addition de spermine au microsomes du foie de rats femelles modifie leK _m du système enzymatique qui transforme 1'estradiol en 2-hydroxyestradiol et aussi en des produits aqueux. La nouvelle valeur resemble à celle qu'ont trouve avec des rats mâles, mais leV _max de la réaction reste inchangé. L'action de la spermine dans ce système est discutée.     

A transmembrane protein required for acetylcholine receptor clustering in Caenorhabditis elegans

Clustering neurotransmitter receptors at the synapse is crucial for efficient neurotransmission. Here we identify a Caenorhabditis elegans locus, lev-10, required for postsynaptic aggregation of ionotropic acetylcholine receptors (AChRs). lev-10 mutants were identified on the basis of weak resistance to the anthelminthic drug levamisole, a nematode-specific cholinergic agonist that activates AChRs present at neuromuscular junctions (NMJs) resulting in muscle hypercontraction and death at high concentrations. In lev-10 mutants, the density of levamisole-sensitive AChRs at NMJs is markedly reduced, yet the number of functional AChRs present at the muscle cell surface remains unchanged. LEV-10 is a transmembrane protein localized to cholinergic NMJs and required in body-wall muscles for AChR clustering. We also show that the LEV-10 extracellular region, containing five predicted CUB domains and one LDLa domain, is sufficient to rescue AChR aggregation in lev-10 mutants. This suggests a mechanism for AChR clustering that relies on extracellular protein-protein interactions. Such a mechanism is likely to be evolutionarily conserved because CUB/LDL transmembrane proteins similar to LEV-10, but lacking any assigned function, are expressed in the mammalian nervous system and might be used to cluster ionotropic receptors in vertebrates.     

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.     

Monoamine oxidase activities in human brain microvessels

Summary Microvessels can be easily isolated from human brain samples obtained at autopsy. Human frontal cortex MAO type A and B activities are similar in microvessel and microvessel-free preparations. In microvessels, enzyme activities and the ratio of MAO type A to type B vary among the areas studied and could selectively regulate the passage of certain amines through the blood vessel wall.Acknowledgment. The technical assistance of N. Gentile and the financial support by NIMH grant MH31156 is gratefully acknowledged.     

‘The Deepest and Most Rewarding Hole Ever Drilled’: Ice Cores and the Cold War in Greenland

The recovery of the Camp Century deep ice core in 1966 – the first ice core to reach all the way through a polar ice sheet to bedrock – marked a shift from an era of United States military dominated glaciological research in Greenland to an era of climate oriented research on the island. This paper aims to provide an understanding of this shift. I show that the Camp Century ice core was at the heart of a complex blend of environmental, military and scientific interests. By deconstructing these interests, I ultimately show that the island of Greenland underwent two reimaginings during the early Cold War. First, the island was reimagined as part of the US Cold War military sphere: driven by the need to secure the North American continent, the US established a hegemonic military colonization of Greenland. In the second reimagining of the island, environmental geography led the way: the scientific results of the Camp Century ice core and political concern about climatic change converged in the early 1970s to build Greenland into a unique location for pursuing research on climate questions. This paper adds to the literature by contextualizing the Camp Century ice core at the interface between the history of science, environmental history and Cold War history, and thereby illuminating Greenland as a dual geopolitical entity and environmental space. By highlighting the interaction of climatic change, geophysical sciences and national security narratives, it responds to recent historiographic calls to unite a set of narratives which, too often, talk past one another.     

Population density, biomass, and age-class structure of an invasive clam Corbicula fluminea in rivers of the lower San Joaquin River watershed

Corbicula fluminea is well known as an invasive filter-feeding freshwater bivalve with a variety of effects on ecosystem processes. However, C. fluminea has been relatively unstudied in the rivers of the western United States. In June 2003, we sampled C. fluminea at 16 sites in the San Joaquin River watershed of California, which was invaded by C. fluminea in the 1940s. Corbicula fluminea was common in 2 tributaries to the San Joaquin River, reaching densities of 200 clams ? m –2 , but was rare in the San Joaquin River. Biomass followed a similar pattern. Clams of the same age were shorter in the San Joaquin River than in the tributaries. Distribution of clams was different in the 2 tributaries, but the causes of the difference are unknown. The low density and biomass of clams in the San Joaquin River was likely due to stressful habitat or to water quality, because food was abundant. The success of C. fluminea invasions and subsequent effects on trophic processes likely depends on multiple factors. As C. fluminea continues to expand its range around the world, questions regarding invasion success and effects on ecosystems will become important in a wide array of environmental settings.