The Change of Winds
As the combined effects of Antarctic stratospheric ozone depletion and climate warming have forced the westerly surface winds in the Southern Hemisphere to shift toward the pole, mixing between the upper ocean and deeper waters has also changed. Waugh et al. (p. 568) now show that water originating at the surface at subtropical latitudes is mixing into the deeper ocean at a higher rate than 20 years ago, while the reverse is true for those originating at higher latitudes. The summer westerly winds that blow in the Southern Hemisphere have shifted toward the South Pole over the past several decades, but why? Lee and Feldstein (p. 563) show that greenhouse gas forcing and ozone depletion impart different signatures to wind patterns and conclude that ozone depletion has been responsible for more than half of the observed shift.
Exploiting Carbon Nanotubes
Individual defect-free carbon nanotubes can have exceptional mechanical, thermal, and electrical properties, which has led to speculation on a wide range of potential applications. However, challenges in growing large quantities of pure nanotubes, and for some applications tubes of only one type, have limited their widespread use. De Volder et al. (p. 535) review the efforts that have been made to scale up carbon nanotube production and discuss a number of applications where enhanced materials have made use of carbon nanotubes.
The Third Way
Because organic carbon contains a larger fraction of the light isotope 12C than inorganic carbonate, variations in the carbon isotopic record of sedimentary rocks are thought to represent changes in the amount of organic carbon buried as sediments (and thus removed from the rest of the carbon cycle). Schrag et al. (p. 540; see the Perspective by Canfield and Kump) suggest that historically a third component was important: authigenic carbonate. Authigenic carbonate is not produced in any appreciable quantity today, but was much more abundant when the level of atmospheric oxygen was low.
Not Just Wasting
Malnutrition is well known in Malawi, including a severe form—kwashiorkor—in which children do not simply waste away, they also suffer edema, liver damage, skin ulceration, and anorexia. Smith et al. (p. 548; see the Perspective by Relman) investigated the microbiota of pairs of twins in Malawian villages and found notable differences in the composition of the gut microbiota in children with kwashiorkor. In these children, a bacterial species related to Desulfovibrio, which has been associated with bowel disease and inflammation, was noticeable. When the fecal flora from either the healthy or the sick twin was transplanted into groups of germ-free mice, the mice that received the kwashiorkor sample started to lose weight, like their human counterpart.
Nanoscale NMR with Diamond Defects
Although nuclear magnetic resonance (NMR) methods can be used for spatial imaging, the low sensitivity of detectors limits the minimum sample size. Two reports now describe the use of near-surface nitrogen-vacancy (NV) defects in diamond for detecting nanotesla magnetic fields from very small volumes of material (see the Perspective by Hemmer). The spin of the defect can be detected by changes in its fluorescence, which allows proton NMR of organic samples only a few nanometers thick on the diamond surface. Mamin et al. (p. 557) used a combination of electron spin echoes and pulsed NMR manipulation of the proton spins to detect the very weak fields. Staudacher et al. (p. 561) measured statistical polarization of a population of about 104 spins near the NV center with a dynamical decoupling method.
The Power of the Collective
Sensing the environment is generally considered to require significant cognitive sampling and comparison, not to mention time. However, species that do not necessarily have the cognitive ability, or the time, have also proven to be quite adept at sensing and evaluating their environment. Berdahl et al. (p. 574) show that in shiners, a species of schooling fish, mere attraction to, and movement toward, neighboring individuals allows the group to track preferred darkness in a variable-light environment.
Bacteriophages are responsible for much of bacterial evolution, both by imposing selection for resistance to infection and by horizontal gene transfer of host genes to new bacteria. However, we know surprisingly little about the initiation of phage infection. Hu et al. (p. 576, published online 10 January) used high-throughput cryo-electron tomography and sub-volume analysis to examine Escherichia coli minicells infected with both wild-type and mutant T7 bacteriophages. High-resolution views of phage structures at different stages of infection reveal the de novo formation of an extended tail by the ejection of internal head proteins, in order to form the channel for DNA transport into the cytoplasm.
Dissecting Microtubule Stability
Microtubule-stabilizing agents (MSAs), like taxol, inhibit cell division and are widely used in cancer chemotherapy. Prota et al. (p. 587, published online 3 January) present structural data on the molecular mechanism of action of antimitotic drugs. Tubulin structures in complex with the MSAs zampanolide and epothilone A, revealed a general mechanism for how MSAs promote microtubule assembly and stability by affecting lateral tubulin interactions.
Solid tumors are composed of functionally diverse tumor cells. The prevailing view is that this "intratumoral heterogeneity" arises from the accumulation of mutations during tumor growth, resulting in multiple genetically defined subclones of cells that respond in different ways to selective pressures such as chemotherapy. Kreso et al. (p. 543, published online 13 December; see the Perspective by Marusyk and Polyak) simultaneously monitored the genetic profiles and growth behavior of human colorectal cancer cells that were serially passaged in mice. Individual tumor cells within a uniform genetic lineage displayed extensive variation in survival, growth dynamics, and response to a chemotherapeutic drug. Thus, additional diversity-generating mechanisms such as epigenetic regulation or microenvironmental variability appear to operate within a genetic clone, endowing a subset of tumor cells with robust survival potential, especially during stress.
Linking Mass and Time
The precision of atomic clocks is based on the transitions between two well-defined energy levels—the frequency of oscillation. We know from relativity that mass and energy are equivalent and from quantum mechanics that energy relates to frequency. Therefore, the ticking of a clock can be related, in principle, to the mass of a particle. The oscillation frequency of a particle is known as its Compton frequency and, because of the high frequency involved and stability of atoms, it has been argued that a clock linking mass and time would offer very high precision. Ordinarily, the Compton frequency is extremely high and not accessible to direct excitation. Lan et al. (p. 554, published online 10 January; see the Perspective by Debs et al.) demonstrate the operation of a Compton clock exploiting a related parameter, the phase accumulation rate of cold cesium atoms. Using an atom interferometer and an optical frequency comb to bring the Compton frequency into an experimentally accessible regime, mass and time could be directly linked.
Chloroplast Translocon Revealed
Protein translocation across biological membranes requires supramolecular complexes, called translocons. Chloroplasts require translocons in their double-envelope membranes to import thousands of nucleus-encoded proteins synthesized in the cytosol. However, the identity of the translocon at the inner envelope of the chloroplast (TIC) has long been a matter of debate; two proteins, Tic20 and Tic110, have been proposed to be central to protein translocation across the inner envelope membrane. Using transgenic Arabidopsis plants expressing a tagged form of Tic20, Kikuchi et al. (p. 571) report the isolation of a 1-megadalton complex composed of Tic56, Tic100, and Tic214 involved in protein translocation across the inner envelope. Thorough in vitro biochemical and in vivo genetic experimentation suggest that the isolated translocon contains both nuclear- and organellar-encoded components. Tic110 was not part of the isolated translocon.
Cells in Transit(ion)
Epithelial-mesenchymal transition (EMT) is a developmental program that converts adherent epithelial cells to a migratory mesenchymal state. This cell-fate change has been linked to tumor metastasis in preclinical models. To investigate whether EMT occurs in human cancer, Yu et al. (p. 580) isolated circulating tumor cells (CTCs) from breast cancer patients and analyzed their expression of epithelial and mesenchymal markers by RNA–in situ hybridization and RNA sequencing. Biphenotypic cells expressing both types of markers were rare in primary breast tumors but were enriched among CTCs, as were cells expressing only mesenchymal markers. Serial blood samples from one patient revealed that CTCs in the mesenchymal state declined in number when the patient responded to therapy but rebounded when the disease began to progress—a pattern repeated when a different therapy was administered. Thus, EMT may facilitate tumor cell dissemination in humans.
Much is known about various factors (transcription and epigenetic factors) involved in gene transcription, but it is difficult to predict expression at a quantitative level. Neuert et al. (p. 584) developed an integrated experimental and computational procedure to capture, predict, and understand the temporal dynamics of signal-activated gene regulation at single-molecule and single-cell resolution. The approach explores models of varying complexity and uses cross-validation analyses to estimate when models are too simple to be accurate or too complex to be precise. These approaches identify and validate a model that describes and predicts the quantitative messenger RNA dynamics of three genes activated by mitogen-activated protein kinase signaling during cellular stress in yeast.
Protein ubiquitination is a widespread mechanism for cellular regulation, and new regulators are valuable research tools and may help to generate therapeutic small molecules. Ernst et al. (p. 590, published online 3 January) used known crystal structures to roughly define the interaction domain between a ubiquitin-specific protease and a ubiquitinated substrate and then screened ubiquitin variants with changes in these residues to find variants that acted as potent and specific regulators that could modify ubiquitin pathway regulation in cells.