Editing the Genome
The ciliate Oxytricha trifallax has an unusual genome with the coding regions of genes (the exons) scattered through the genome. The exons are then somehow knitted together following transcription prior to their translation into proteins. As part of this process Oxytricha eliminates all transposable elements, stripping the genome down to 5% of the original germline DNA during development. Nowacki et al. (p. 935, published online 16 April) show that germline-limited transposases appear to be important for these large-scale DNA rearrangements.
Synaptic Tag Tagged
Input-dependent synaptic plasticity is critical for the reproducible activation of a specific neuronal assembly encoding a particular memory. The synaptic tagging hypothesis, which suggests how input specificity is maintained in late-phase synaptic plasticity, attempts to explain the persistence of long-term memory. However, it has been difficult to identify proteins that behave as the hypothesis predicts. Okada et al. (p. 904) investigated if the regulated spine entry of a late-phase-related somatically synthesized plasticity-related protein, Vesl-1S, works as a synaptic tag. Vesl-1S protein was carried from the soma to every dendrite and recruited into spines by synaptic activation in an input-specific manner. Spine entry was protein-synthesis independent, was NMDA receptor dependent, and had a persistent lifetime of activation. These results provide long-sought evidence for the input-specific capturing of a plasticity-related protein as postulated by the synaptic tagging hypothesis.
Collapse and Rise
The West Antarctic Ice Sheet (WAIS) is thought to be inherently unstable and susceptible to rapid collapse if it reaches a certain warming threshold. Although such an event is considered unlikely, to predict the consequences of collapse it is important to know how much sea level would rise in such a case. The WAIS is thought to contain enough ice to raise sea level by 5 to 7 meters were it to collapse. Bamber et al. (p. 901, see the cover; see the Perspective by Ivins) have reassessed that number, on the basis of better data on the geometry of the WAIS, and conclude that its sudden collapse would raise sea level by about 3.2 meters, on average, with large and important regional variations. Although this is only about half as much as previously thought, its impact on coastal areas would still be devastating.
Tales of Talin, Kindlin, and Integrin
The integrins are receptors on the surface of animal cells that mediate attachment to the extracellular matrix. Integrins also act as signaling molecules, activating signaling pathways when they bind to their ligands in the matrix. Furthermore, integrins can communicate signals from the inside to the outside of the cell when signals within the cell alter the affinity of integrins for their extracellular ligands. Moser et al. (p. 895) review recent advances in understanding the roles of the proteins talin and kindlin in such bidirectional signaling and how they influence the function of integrins in health and disease.
Microscopists have recently achieved fluorescence imaging at subwavelength resolution by focusing one beam of light in a halo around another beam, thereby quenching the glow of fluorescent dyes in all but the very center of the illuminated spot. Three studies have now adapted this approach to photolithography (see the Perspective by Perry). Andrew et al. (p. 917, published online 9 April) coated a photo-resist with molecules that, upon absorbing the ultraviolet etching beam, isomerized to a transparent layer but returned to the initially opaque form upon absorption of visible light. Applying an interference pattern with ultraviolet peaks superimposed on visible nodes restricted etching to narrow regions in the center of these nodes, yielding lines of subwavelength width. Scott et al. (p. 913, published online 9 April) used a central beam to activate polymerization initiators, while using a halo-shaped surrounding beam to trigger inhibitors that would halt polymerization. Li et al. (p. 910, published online 9 April) found that use of a different initiator molecule allowed both beams to share the same wavelength (800 nanometers), with a relatively weak quenching beam lagging a highly intense initiating beam slightly in time. Both the latter techniques produced three-dimensional features honed to subwavelength dimensions.
Global Analysis of Titan
In its orbit around Saturn, the Cassini spacecraft passes regularly by the planet's largest moon, Titan. Using a radar instrument to peer through the moon's thick atmosphere, Zebker et al. (p. 921, published online 2 April) developed a global model of Titan. Titan is slightly oblate, so that its poles have lower elevations than the equator, which may explain why the moon's hydrocarbon lakes are located at high latitudes.
Identifying Abortive Initiation
During transcription initiation in vitro, the RNA polymerase enzyme typically engages in cycles of synthesis and release of short RNA transcripts (“abortive initiation”) before breaking interactions with promoter DNA and beginning transcription elongation. Using hybridization methods developed to detect microRNAs, Goldman et al. (p. 927) directly detected products of abortive initiation in bacterial cells in vivo. Abortive initiation increased when interactions between RNA polymerase and the promoter were strengthened or when transcription was prevented. Thus, products of abortive initiation may help to regulate gene expression.
Regulating Oocyte Maturation
Understanding exactly how ovarian follicles mature to generate fertile eggs is key to many aspects of fertility treatment. When the pituitary surge of luteinizing hormone (LH) binds to its receptor on granulosa cells of preovulatory follicles, a cascade of signaling events triggers granulosa cells to become luteal cells and the oocyte to resume meiosis. Fan et al. (p. 938; see the Perspective by Duggavathi and Murphy), using the mouse as a model system, targeted disruption of the kinases ERK1 and ERK2 selectively in granulosa cells. The kinases were essential in vivo mediators of LH induction of ovulation and luteinization.
Migration and Asymmetry
Although vertebrates show asymmetry in internal body organization, the earliest steps toward establishing different anatomies on the left and right sides are not conserved. How this is achieved in birds has been especially confusing. Gros et al. (p. 941, published online 9 April) show that in chicks some of the earliest left-right asymmetric domains of gene expression, including those of Sonic hedgehog (Shh) and Fibroblast growth factor 8 (Fgf8), are produced passively. Genes are activated in bilateral cell populations, followed by rearrangements that shuffle Shh-expressing cells.
Stop-Go Axon Crossing
Developing axons may or may not cross the body's midline according to a balance between repulsive and attractive guidance factors. As an axon first approaches the midline, a repressive receptor encoded by the comm gene is inactivated by relocation within the cell. After the axon crosses the midline, the repressive receptor is reactivated, keeping the axon from crossing back. Yang et al. (p. 944, published online 26 March; see the Perspective by Kidd) now show that in Drosophila the comm gene is regulated by the attractive receptor known as Frazzled. The Frazzled protein thus functions in two ways: It initiates attraction in response to a ligand and it activates transcription of the comm gene, keeping the repressive signal out of the action.
The Path Not Taken
People readily recognize that unchosen actions have consequences and adjust their behavior accordingly. The ability to recognize fictive outcomes is thought to be a necessary component of regret, and disruptions in this ability may cause anxiety and problem gambling. Do animals engage in this same process? Hayden et al. (p. 948) provided monkeys with information about what rewards unchosen options would have given. The monkeys' behavior depended strongly on these fictive outcomes. Responses of single neurons in the anterior cingulate cortex, which monitors outcomes of rewarding decisions and guides subsequent changes in behavior, were recorded while monkeys performed the task. Nearly half the neurons in the sample responded to both experienced and fictive outcomes. Thus, the anterior cingulate cortex does not simply monitor the consequences of actions, but represents outcomes in a more abstract manner that incorporates both real and fictive information.
Memories of fearful associations, such as hearing a tone before receiving a low-voltage shock, are labile when they are retrieved, such that the association can be extinguished or reconsolidated. Monfils et al. (p. 951, published online 2 April) demonstrate that applying a standard extinction treatment (sounding the tone multiple times in the absence of any shocks) within a window of time during which reconsolidation would normally occur has the effect of overwriting the original memory. Rats treated in this fashion display much lower levels of renewal (fear induced by sounding the tone once by itself), reinstatement (fear induced by giving the shock once by itself), and spontaneous recovery.
Resolving Landau Levels in Graphene
The charge carriers in a two-dimensional conductor, when placed in a magnetic field, can develop an additional set of quantized energy levels. These Landau levels correspond to the carriers now moving in cyclotron orbits. In graphene, which consists of single-atom-thick sheets of graphite, an unusual set of Landau levels with nonequal energy spacing can develop in graphene layers that have undergone symmetry breaking caused by rotation between adjacent layers. Miller et al. (p. 924) used scanning tunneling microscopy at cryogenic temperatures to map out Landau levels in graphene grown on silicon carbide with high energy and momentum resolution, including the characteristic level in graphene that can occur at zero energy.
Methylation of cytosine bases, 5-methylcytosine (5mC), in DNA plays an important regulatory role in mammalian genomes. Methylation patterns are often inherited across generations, but they can also be dynamic, suggesting that active DNA demethylation pathways exist. One such pathway, best characterized in plants, involves the removal of the 5mC base, and its replacement by C, via a DNA repair mechanism. Kriaucionis and Heintz (p. 929, published online 16 April) now show that, as well as 5mC in mammalian genomes, there are also significant amounts of 5-hydroxymethylcytosine (5hmC) in DNA of Purkinje neurons, which have large nuclei with apparently very little heterochromatin. Tahiliani et al. (p. 930, published online 16 April) find that the protein TET1 is capable of converting 5mC into 5hmC both in vitro and in vivo. 5-Hydroxymethylcytosine is also present in embryonic stem cells, and levels of 5hmC and TET1 show correlated variation during cell differentiation.