Imaging of Titan from the Cassini spacecraft

Titan, the largest moon of Saturn, is the only satellite in the Solar System with a substantial atmosphere. The atmosphere is poorly understood and obscures the surface, leading to intense speculation about Titan's nature. Here we present observations of Titan from the imaging science experiment onboard the Cassini spacecraft that address some of these issues. The images reveal intricate surface albedo features that suggest aeolian, tectonic and fluvial processes; they also show a few circular features that could be impact structures. These observations imply that substantial surface modification has occurred over Titan's history. We have not directly detected liquids on the surface to date. Convective clouds are found to be common near the south pole, and the motion of mid-latitude clouds consistently indicates eastward winds, from which we infer that the troposphere is rotating faster than the surface. A detached haze at an altitude of 500 km is 150-200 km higher than that observed by Voyager, and more tenuous haze layers are also resolved.     

Whole-genome analysis informs breast cancer response to aromatase inhibition

To correlate the variable clinical features of oestrogen-receptor-positive breast cancer with somatic alterations, we studied pretreatment tumour biopsies accrued from patients in two studies of neoadjuvant aromatase inhibitor therapy by massively parallel sequencing and analysis. Eighteen significantly mutated genes were identified, including five genes (RUNX1, CBFB, MYH9, MLL3 and SF3B1) previously linked to haematopoietic disorders. Mutant MAP3K1 was associated with luminal A status, low-grade histology and low proliferation rates, whereas mutant TP53 was associated with the opposite pattern. Moreover, mutant GATA3 correlated with suppression of proliferation upon aromatase inhibitor treatment. Pathway analysis demonstrated that mutations in MAP2K4, a MAP3K1 substrate, produced similar perturbations as MAP3K1 loss. Distinct phenotypes in oestrogen-receptor-positive breast cancer are associated with specific patterns of somatic mutations that map into cellular pathways linked to tumour biology, but most recurrent mutations are relatively infrequent. Prospective clinical trials based on these findings will require comprehensive genome sequencing.     

Isolation of rare circulating tumour cells in cancer patients by microchip technology

Viable tumour-derived epithelial cells (circulating tumour cells or CTCs) have been identified in peripheral blood from cancer patients and are probably the origin of intractable metastatic disease. Although extremely rare, CTCs represent a potential alternative to invasive biopsies as a source of tumour tissue for the detection, characterization and monitoring of non-haematologic cancers. The ability to identify, isolate, propagate and molecularly characterize CTC subpopulations could further the discovery of cancer stem cell biomarkers and expand the understanding of the biology of metastasis. Current strategies for isolating CTCs are limited to complex analytic approaches that generate very low yield and purity. Here we describe the development of a unique microfluidic platform (the 'CTC-chip') capable of efficient and selective separation of viable CTCs from peripheral whole blood samples, mediated by the interaction of target CTCs with antibody (EpCAM)-coated microposts under precisely controlled laminar flow conditions, and without requisite pre-labelling or processing of samples. The CTC-chip successfully identified CTCs in the peripheral blood of patients with metastatic lung, prostate, pancreatic, breast and colon cancer in 115 of 116 (99%) samples, with a range of 5-1,281 CTCs per ml and approximately 50% purity. In addition, CTCs were isolated in 7/7 patients with early-stage prostate cancer. Given the high sensitivity and specificity of the CTC-chip, we tested its potential utility in monitoring response to anti-cancer therapy. In a small cohort of patients with metastatic cancer undergoing systemic treatment, temporal changes in CTC numbers correlated reasonably well with the clinical course of disease as measured by standard radiographic methods. Thus, the CTC-chip provides a new and effective tool for accurate identification and measurement of CTCs in patients with cancer. It has broad implications in advancing both cancer biology research and clinical cancer management, including the detection, diagnosis and monitoring of cancer.     

Biodiversity (Communications arising): suspect evidence of transgenic contamination

Quist and Chapela claim that transgenic DNA constructs have been introgressed into a traditional maize variety in Mexico, and furthermore suggest that these constructs have been reassorted and introduced into different genomic backgrounds. However, we show here that their evidence for such introgression is based on the artefactual results of a flawed assay; in addition, the authors misinterpret a key reference to explain their results, concluding that reassortment of integrated transgenic DNA occurs during transformation or recombination.     

Sperm competition: motility and the midpiece in primates

In animals with multiple-partner mating systems, the gametes of two or more males must compete to fertilize a given set of ova. Here we show that the volume of the midpiece in individual sperm is significantly greater in primate species in which the females mate with multiple partners, and in which males have larger testes in relation to their body weight, than in those species that mate with only one partner and have relatively small testes. Our results indicate that sexual selection by sperm competition has influenced the evolution of a specific component of male-gamete morphology, the volume of the sperm midpiece.     

Redistribution of energy available for ocean mixing by long-range propagation of internal waves

Ocean mixing, which affects pollutant dispersal, marine productivity and global climate, largely results from the breaking of internal gravity waves--disturbances propagating along the ocean's internal stratification. A global map of internal-wave dissipation would be useful in improving climate models, but would require knowledge of the sources of internal gravity waves and their propagation. Towards this goal, I present here computations of horizontal internal-wave propagation from 60 historical moorings and relate them to the source terms of internal waves as computed previously. Analysis of the two most energetic frequency ranges--near-inertial frequencies and semidiurnal tidal frequencies--reveals that the fluxes in both frequency bands are of the order of 1 kW x m(-1) (that is, 15-50% of the energy input) and are directed away from their respective source regions. However, the energy flux due to near-inertial waves is stronger in winter, whereas the tidal fluxes are uniform throughout the year. Both varieties of internal waves can thus significantly affect the space-time distribution of energy available for global mixing.     

A periodicity of approximately 1 hour in X-ray emission from the active galaxy RE J1034+396

Active galactic nuclei and quasars are thought to be scaled-up versions of Galactic black hole binaries, powered by accretion onto supermassive black holes with masses of 10(6)-10(9) M[symbol: see text], as opposed to the approximately 10 M [symbol: see text] in binaries (here M [symbol: see text] is the solar mass). One example of the similarities between these two types of systems is the characteristic rapid X-ray variability seen from the accretion flow. The power spectrum of this variability in black hole binaries consists of a broad noise with multiple quasi-periodic oscillations superimposed on it. Although the broad noise component has been observed in many active galactic nuclei, there have hitherto been no significant detections of quasi-periodic oscillations. Here we report the discovery of an approximately 1-hour X-ray periodicity in a bright active galaxy, RE J1034+396. The signal is highly statistically significant (at the 5.6 sigma level) and very coherent, with quality factor Q > 16. The X-ray modulation arises from the direct vicinity of the black hole.     

Free choice activates a decision circuit between frontal and parietal cortex

We often face alternatives that we are free to choose between. Planning movements to select an alternative involves several areas in frontal and parietal cortex that are anatomically connected into long-range circuits. These areas must coordinate their activity to select a common movement goal, but how neural circuits make decisions remains poorly understood. Here we simultaneously record from the dorsal premotor area (PMd) in frontal cortex and the parietal reach region (PRR) in parietal cortex to investigate neural circuit mechanisms for decision making. We find that correlations in spike and local field potential (LFP) activity between these areas are greater when monkeys are freely making choices than when they are following instructions. We propose that a decision circuit featuring a sub-population of cells in frontal and parietal cortex may exchange information to coordinate activity between these areas. Cells participating in this decision circuit may influence movement choices by providing a common bias to the selection of movement goals.