A new probe for the diagnosis of myotonic muscular dystrophy

Myotonic muscular dystrophy (DM) is the most common muscular dystrophy, affecting adults as well as children. It is inherited as an autosomal dominant trait and is characterized by variable expressivity and late age-of-onset. Linkage studies have established the locus on chromosome 19. In order to identify tightly linked probes for diagnosis as well as to define in detail the DM gene region, chromosome 19 libraries were constructed and screened for restriction fragment length polymorphisms tightly linked to DM. A genomic clone, LDR152 (D19S19), was isolated that is tightly linked to DM; recombination fraction = 0.0 (95% confidence limits 0.0-0.03); lod score, 15.4.     

Formation of a nematic fluid at high fields in Sr3Ru2O7

In principle, a complex assembly of strongly interacting electrons can self-organize into a wide variety of collective states, but relatively few such states have been identified in practice. We report that, in the close vicinity of a metamagnetic quantum critical point, high-purity strontium ruthenate Sr3Ru2O7 possesses a large magnetoresistive anisotropy, consistent with the existence of an electronic nematic fluid. We discuss a striking phenomenological similarity between our observations and those made in high-purity two-dimensional electron fluids in gallium arsenide devices.     

MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling

The epidermal growth factor receptor (EGFR) kinase inhibitors gefitinib and erlotinib are effective treatments for lung cancers with EGFR activating mutations, but these tumors invariably develop drug resistance. Here, we describe a gefitinib-sensitive lung cancer cell line that developed resistance to gefitinib as a result of focal amplification of the MET proto-oncogene. inhibition of MET signaling in these cells restored their sensitivity to gefitinib. MET amplification was detected in 4 of 18 (22%) lung cancer specimens that had developed resistance to gefitinib or erlotinib. We find that amplification of MET causes gefitinib resistance by driving ERBB3 (HER3)-dependent activation of PI3K, a pathway thought to be specific to EGFR/ERBB family receptors. Thus, we propose that MET amplification may promote drug resistance in other ERBB-driven cancers as well.     

Electrons in finite-sized water cavities: hydration dynamics observed in real time

We directly observed the hydration dynamics of an excess electron in the finite-sized water clusters of (H2O)n- with n = 15, 20, 25, 30, and 35. We initiated the solvent motion by exciting the hydrated electron in the cluster. By resolving the binding energy of the excess electron in real time with femtosecond resolution, we captured the ultrafast dynamics of the electron in the presolvated ("wet") and hydrated states and obtained, as a function of cluster size, the subsequent relaxation times. The solvation time (300 femtoseconds) after the internal conversion [140 femtoseconds for (H2O)35-] was similar to that of bulk water, indicating the dominant role of the local water structure in the dynamics of hydration. In contrast, the relaxation in other nuclear coordinates was on a much longer time scale (2 to 10 picoseconds) and depended critically on cluster size.     

Impact of anthropogenic CO2 on the CaCO3 system in the oceans

Rising atmospheric carbon dioxide (CO2) concentrations over the past two centuries have led to greater CO2 uptake by the oceans. This acidification process has changed the saturation state of the oceans with respect to calcium carbonate (CaCO3) particles. Here we estimate the in situ CaCO3 dissolution rates for the global oceans from total alkalinity and chlorofluorocarbon data, and we also discuss the future impacts of anthropogenic CO2 on CaCO3 shell-forming species. CaCO3 dissolution rates, ranging from 0.003 to 1.2 micromoles per kilogram per year, are observed beginning near the aragonite saturation horizon. The total water column CaCO3 dissolution rate for the global oceans is approximately 0.5 +/- 0.2 petagrams of CaCO3-C per year, which is approximately 45 to 65% of the export production of CaCO3.     

Isotopic evidence for massive oxidation of organic matter following the great oxidation event

The stable isotope record of marine carbon indicates that the Proterozoic Eon began and ended with extreme fluctuations in the carbon cycle. In both the Paleoproterozoic [2500 to 1600 million years ago (Ma)] and Neoproterozoic (1000 to 542 Ma), extended intervals of anomalously high carbon isotope ratios (δ(13)C) indicate high rates of organic matter burial and release of oxygen to the atmosphere; in the Neoproterozoic, the high δ(13)C interval was punctuated by abrupt swings to low δ(13)C, indicating massive oxidation of organic matter. We report a Paleoproterozoic negative δ(13)C excursion that is similar in magnitude and apparent duration to the Neoproterozoic anomaly. This Shunga-Francevillian anomaly may reflect intense oxidative weathering of rocks as the result of the initial establishment of an oxygen-rich atmosphere.