An integrated semiconductor device enabling non-optical genome sequencing

The seminal importance of DNA sequencing to the life sciences, biotechnology and medicine has driven the search for more scalable and lower-cost solutions. Here we describe a DNA sequencing technology in which scalable, low-cost semiconductor manufacturing techniques are used to make an integrated circuit able to directly perform non-optical DNA sequencing of genomes. Sequence data are obtained by directly sensing the ions produced by template-directed DNA polymerase synthesis using all-natural nucleotides on this massively parallel semiconductor-sensing device or ion chip. The ion chip contains ion-sensitive, field-effect transistor-based sensors in perfect register with 1.2 million wells, which provide confinement and allow parallel, simultaneous detection of independent sequencing reactions. Use of the most widely used technology for constructing integrated circuits, the complementary metal-oxide semiconductor (CMOS) process, allows for low-cost, large-scale production and scaling of the device to higher densities and larger array sizes. We show the performance of the system by sequencing three bacterial genomes, its robustness and scalability by producing ion chips with up to 10 times as many sensors and sequencing a human genome.     

Gravity modes as a way to distinguish between hydrogen- and helium-burning red giant stars

Red giants are evolved stars that have exhausted the supply of hydrogen in their cores and instead burn hydrogen in a surrounding shell. Once a red giant is sufficiently evolved, the helium in the core also undergoes fusion. Outstanding issues in our understanding of red giants include uncertainties in the amount of mass lost at the surface before helium ignition and the amount of internal mixing from rotation and other processes. Progress is hampered by our inability to distinguish between red giants burning helium in the core and those still only burning hydrogen in a shell. Asteroseismology offers a way forward, being a powerful tool for probing the internal structures of stars using their natural oscillation frequencies. Here we report observations of gravity-mode period spacings in red giants that permit a distinction between evolutionary stages to be made. We use high-precision photometry obtained by the Kepler spacecraft over more than a year to measure oscillations in several hundred red giants. We find many stars whose dipole modes show sequences with approximately regular period spacings. These stars fall into two clear groups, allowing us to distinguish unambiguously between hydrogen-shell-burning stars (period spacing mostly ～ 50 seconds) and those that are also burning helium (period spacing ～ 100 to 300 seconds).     

An actively accreting massive black hole in the dwarf starburst galaxy Henize 2-10

Supermassive black holes are now thought to lie at the heart of every giant galaxy with a spheroidal component, including our own Milky Way. The birth and growth of the first 'seed' black holes in the earlier Universe, however, is observationally unconstrained and we are only beginning to piece together a scenario for their subsequent evolution. Here we report that the nearby dwarf starburst galaxy Henize?2-10 (refs 5 and 6) contains a compact radio source at the dynamical centre of the galaxy that is spatially coincident with a hard X-ray source. From these observations, we conclude that Henize?2-10 harbours an actively accreting central black hole with a mass of approximately one million solar masses. This nearby dwarf galaxy, simultaneously hosting a massive black hole and an extreme burst of star formation, is analogous in many ways to galaxies in the infant Universe during the early stages of black-hole growth and galaxy mass assembly. Our results confirm that nearby star-forming dwarf galaxies can indeed form massive black holes, and that by implication so can their primordial counterparts. Moreover, the lack of a substantial spheroidal component in Henize?2-10 indicates that supermassive black-hole growth may precede the build-up of galaxy spheroids.     

Decoherence in crystals of quantum molecular magnets

Quantum decoherence is a central concept in physics. Applications such as quantum information processing depend on understanding it; there are even fundamental theories proposed that go beyond quantum mechanics, in which the breakdown of quantum theory would appear as an 'intrinsic' decoherence, mimicking the more familiar environmental decoherence processes. Such applications cannot be optimized, and such theories cannot be tested, until we have a firm handle on ordinary environmental decoherence processes. Here we show that the theory for insulating electronic spin systems can make accurate and testable predictions for environmental decoherence in molecular-based quantum magnets. Experiments on molecular magnets have successfully demonstrated quantum-coherent phenomena but the decoherence processes that ultimately limit such behaviour were not well constrained. For molecular magnets, theory predicts three principal contributions to environmental decoherence: from phonons, from nuclear spins and from intermolecular dipolar interactions. We use high magnetic fields on single crystals of Fe(8) molecular magnets (in which the Fe ions are surrounded by organic ligands) to suppress dipolar and nuclear-spin decoherence. In these high-field experiments, we find that the decoherence time varies strongly as a function of temperature and magnetic field. The theoretical predictions are fully verified experimentally, and there are no other visible decoherence sources. In these high fields, we obtain a maximum decoherence quality-factor of 1.49?×?10(6); our investigation suggests that the environmental decoherence time can be extended up to about 500 microseconds, with a decoherence quality factor of ～6?×?10(7), by optimizing the temperature, magnetic field and nuclear isotopic concentrations.     

Primitive agriculture in a social amoeba

Agriculture has been a large part of the ecological success of humans. A handful of animals, notably the fungus-growing ants, termites and ambrosia beetles, have advanced agriculture that involves dispersal and seeding of food propagules, cultivation of the crop and sustainable harvesting. More primitive examples, which could be called husbandry because they involve fewer adaptations, include marine snails farming intertidal fungi and damselfish farming algae. Recent work has shown that microorganisms are surprisingly like animals in having sophisticated behaviours such as cooperation, communication and recognition, as well as many kinds of symbiosis. Here we show that the social amoeba Dictyostelium discoideum has a primitive farming symbiosis that includes dispersal and prudent harvesting of the crop. About one-third of wild-collected clones engage in husbandry of bacteria. Instead of consuming all bacteria in their patch, they stop feeding early and incorporate bacteria into their fruiting bodies. They then carry bacteria during spore dispersal and can seed a new food crop, which is a major advantage if edible bacteria are lacking at the new site. However, if they arrive at sites already containing appropriate bacteria, the costs of early feeding cessation are not compensated for, which may account for the dichotomous nature of this farming symbiosis. The striking convergent evolution between bacterial husbandry in social amoebas and fungus farming in social insects makes sense because multigenerational benefits of farming go to already established kin groups.     

The circadian molecular clock creates epidermal stem cell heterogeneity

Murine epidermal stem cells undergo alternate cycles of dormancy and activation, fuelling tissue renewal. However, only a subset of stem cells becomes active during each round of morphogenesis, indicating that stem cells coexist in heterogeneous responsive states. Using a circadian-clock reporter-mouse model, here we show that the dormant hair-follicle stem cell niche contains coexisting populations of cells at opposite phases of the clock, which are differentially predisposed to respond to homeostatic cues. The core clock protein Bmal1 modulates the expression of stem cell regulatory genes in an oscillatory manner, to create populations that are either predisposed, or less prone, to activation. Disrupting this clock equilibrium, through deletion of Bmal1 (also known as Arntl) or Per1/2, resulted in a progressive accumulation or depletion of dormant stem cells, respectively. Stem cell arrhythmia also led to premature epidermal ageing, and a reduction in the development of squamous tumours. Our results indicate that the circadian clock fine-tunes the temporal behaviour of epidermal stem cells, and that its perturbation affects homeostasis and the predisposition to tumorigenesis.