- Cancer
Out-RANKing osteosarcoma
- Yevgeniya Nusinovich
Colored scanning electron micrograph of an osteosarcoma cancer cell
PHOTO: STEVE GSCHMEISSNER/SCIENCE SOURCE
Osteosarcoma, the most common primary bone cancer, can be difficult to treat, especially in patients with metastatic disease. Chen et al. developed genetically engineered mouse models of osteosarcoma and used them to demonstrate that receptor activator of nuclear factor κB ligand (RANKL) signaling contributes to the progression of this disease. Furthermore, denosumab, an antibody against RANKL already used in patients with other bone diseases, inhibited osteosarcoma in mouse models and so is a viable candidate for future testing in human patients.
Sci. Transl. Med. 7, 317ra197 (2015).
- Cancer Immunotherapy
Low mutation rate okay for T cells
- Kristen L. Mueller
Cancers that tend to have high numbers of mutations, such as melanoma and smoking-induced lung cancer, respond well to immunotherapies, whereas those with fewer mutations, such as pancreatic cancer, do not. Tran et al. searched for tumor mutation–reactive T cells in 10 patients with metastatic gastrointestinal cancers, which have relatively low mutation burdens, and discovered that 9 out of 10 harbored such cells. T cells from one patient recognized a mutation common to many types of cancers. Engineering T cells to express this particular mutation-reactive T cell receptor may extend adoptive cell immunotherapy to a larger pool of patients than previously anticipated.
Science, this issue p. 1387
- Aging
Aging: All in the head—and the gut
- L. Bryan Ray
The effects of hypoxia and caloric restriction, both of which extend life span in Caenorhabditis elegans, converge on the activation of an enzyme in cells of the intestine. Leiser et al. show that the life-extending effects of hypoxia begin in neurons with transcriptional activation by hypoxia-inducible factor–1 and increased serotonergic signaling. These effects lead to increased production of flavin-containing monooxygenase-2 (FMO-2) in the intestine, which increased longevity. Finding the relevant targets of FMO-2, which also accumulates in mammals under conditions that promote longevity, may elucidate further mechanisms that promote healthy aging.
Science, this issue p. 1375
- Ice Sheets
Shrinking shelf and faster flow
- H. Jesse Smith
Greenland's ice flows over the varied underlying terrain near the coast
PHOTO: NASA/GSFC/JEFFERSON BECK
Zachariæ Isstrøm, a large glacier in northeast Greenland, began a rapid retreat after detaching from a stabilizing sill in the late 1990s. Mouginot et al. report that between 2002 and 2014, the area covered by the glacier's ice shelf shrank by 95%; since 1999, the glacier's flow rate has nearly doubled; and its acceleration increased threefold in the fall of 2012. These dramatic changes appear to be the result of a combination of warmer air and ocean temperatures and the topography of the ocean floor at the head of the glacier. Rising sea levels should continue to destabilize the marine portion of Zachariæ Isstrøm for decades.
Science, this issue p. 1357
- Social Behavior
From faithfulness to spatial memory
- Sacha Vignieri
Natural selection shapes traits to be as adaptive as possible for a given environment. Okhovat et al. show that such varying selection also shapes variation in social behavior and the brain (see the Perspective by Robinson). Variation in male fidelity among monogamous prairie voles reflects differences in the expression, regulation, and epigenetic status of a vasopressin receptor that functions in spatial memory. Thus, the trade-offs males face between fidelity and infidelity may promote heritable variation that is important for spatial memory and maintain variation in their levels of fidelity.
- Cancer
Growing blood vessels in gliomas
- Wei Wong
Aggressive gliomas have a high density of abnormal blood vessels that enables tumor growth and damages the brain. Zhang et al. analyzed patient data and correlated increased levels of a secreted factor called pleiotrophin with more aggressive grades of glioma and decreased survival. When implanted in mice, glioma cells that released pleiotrophin formed larger tumors with more blood vessels. Mice developed smaller gliomas and survived longer when treated with inhibitors of ALK, a receptor for pleiotrophin.
Sci. Signal. 8, ra125 (2015).
- Geophysics
A mysterious mid-mantle slowdown
- Brent Grocholski
The viscosity of Earth's deep interior plays a key role in mediating plate tectonics. Rudolph et al. combined several geophysical data sets to model the viscosity of the mantle. Mantle viscosity abruptly increases below 1000 km. The increase could explain the stalling of subducting slabs and the deflections of hot upwelling plumes around this depth. Although the viscosity increase explains some recent unexpected observations, the origin of the jump itself remains a mystery.
Science, this issue p. 1349
- Superconductivity
Locking the spins in a superconductor
- Jelena Stajic
In Cooper pairs—pairs of electrons responsible for the exotic properties of superconductors—the two electrons' spins typically point in opposite directions. A strong-enough external magnetic field will destroy superconductivity by making the spins point in the same direction. Lu et al. observed a two-dimensional superconducting state in the material MoS2 that was surprisingly immune to a magnetic field applied in the plane of the sample (see the Perspective by Suderow). The band structure of MoS2 and its spin-orbit coupling conspired to create an effective magnetic field that reinforced the electron pairing, with spins aligned perpendicular to the sample.
- Cognitive Science
Handwritten characters drawn by a model
- Gilbert Chin
Not only do children learn effortlessly, they do so quickly and with a remarkable ability to use what they have learned as the raw material for creating new stuff. Lake et al. describe a computational model that learns in a similar fashion and does so better than current deep learning algorithms. The model classifies, parses, and recreates handwritten characters, and can generate new letters of the alphabet that look “right” as judged by Turing-like tests of the model's output in comparison to what real humans produce.
Science, this issue p. 1332
- Microbiome
The ocean microbial system
- Caroline Ash
The vast translucent oceans are teeming with microscopic life that drives significant life processes and elemental cycling on Earth. Yet how climate change will affect the functioning of this microbiome is not well understood. Moran reviews progress and the transformative discoveries made recently in marine microbiology that have led environmental, plant, animal, and even human microbiome research.
Science, this issue p. 10.1126/science.aac8455
- Protein Structure
The principles of protein assembly
- Valda Vinson
A knowledge of protein structure greatly enhances our understanding of protein function. In many cases, function depends on oligomerization. Ahnert et al. used mass spectrometry data together with a large-scale analysis of structures of protein complexes to examine the fundamental steps of protein assembly. Systematically combining assembly steps revealed a large set of quaternary topologies that were organized into a periodic table. Based on this table, the authors accurately predicted the expected frequencies of quaternary structure topologies.
Science, this issue p. 10.1126/science.aaa2245
- Physical Chemistry
Shaking out details of transition states
- Jake Yeston
Chemists liken reaction energetics to a landscape with hills and valleys. In this context, the transition state represents the highest barrier that reagents must pass over en route to forming products. Baraban et al. introduce a framework for extracting details about the transition state of rearrangement reactions directly from vibrational spectral data. They identified a characteristic pattern in the spacing between vibrational energy levels near the transition state, which revealed its energy as well as the specific motions involved in surmounting the barrier.
Science, this issue p. 1338
- Signal Processing
Detecting a transient needle in a haystack
- Ian S. Osborne
Discriminating signals within a noisy environment is an issue crucial to many disciplines, from observational astronomy to secure communication and imaging. If the signal is periodic, then averaging over many measurements can help enhance the signal-to-noise ratio. However, for signals that present as a single transient event, the detection capability has been limited. Ataie et al. developed a detector that can lift that limitation by combining signal cloning with frequency combs and signal-processing techniques (see the Perspective by Vasilyev). Their detector could detect signals buried within noise that would otherwise be undetectable.
- Surface Science
Sticking hydrogen atoms to surfaces
- Phil Szuromi
The simplest case of adsorption at a surface—that of a hydrogen atom—is actually quite complicated. This is because it is not clear how this light atom can transfer enough momentum to the heavy surface that it can slow down and stick. Bünermann et al. prepared highly energetically controlled hydrogen atoms (see the Perspective by Brune). On a gold surface, inelastic collisions occurred during adsorption, but not when an insulating layer of xenon atoms was used.
- Neuronal Dynamics
In vivo imaging of neuronal voltage spikes
- Peter Stern
Neuroscientists have long sought tools that allow optical imaging of individual neurons' membrane voltage dynamics in awake behaving animals. Gong et al. genetically engineered a protein voltage indicator that can report action potentials with <1-ms precision and orders of magnitude lower spike detection error rates than were previously possible. They were thus able to record action potentials and membrane voltage dynamics in the brains of awake mice and fruit flies.
Science, this issue p. 1361
- Research Investment
Tracking the knowledge economy
- Barbara R. Jasny
Although the U.S investment in scientific research can be documented readily, its output is harder to track. Zolas et al. combined data obtained from eight universities on their doctorate recipients with data from business registries and the U.S. Census Bureau. This allowed them to link Ph.D. recipients to all their subsequent employers. Doctoral recipients tended to stay in academia or join large companies with high salaries. Roughly 20% stayed in the state in which they received their degree. In the year after receiving a Ph.D., mathematicians and computer scientists received the highest salaries, and biologists received the lowest.
Science, this issue p. 1367
- Signal Transduction
Altering timing perturbs cell signaling
- L. Bryan Ray
Biological regulatory systems have been optimized by evolution to accommodate environmental variation. Yet these systems may also have fragile aspects that can be exposed by variation in the timing of signaling events. Mitchell et al. studied the properties of the yeast signaling system that allows cells to adapt to changing osmotic conditions. The same properties also made the system sensitive to hyperactivation and the consequent inhibition of cell growth if exposed to oscillations in osmotic conditions with a particular frequency. The identification of similar fragility in other regulatory pathways might prove useful in the development of therapeutic strategies against diseases in which signaling is perturbed, such as cancer and diabetes.
Science, this issue p. 1379
- Transcription
“Please release me, let me go.”
- Guy Riddihough
RNA polymerase II (Pol II) is the principal protein complex required for gene transcription in metazoan cells. Many genes have a “paused” Pol II near their promoters, waiting to be released so they can start messenger RNA synthesis. Yu et al. show that Pol II–associated factor 1 (PAF1) plays a central role in regulating the activation of these paused Pol II complexes. The positive transcription elongation factor b helps recruit PAF1 to the paused Pol II. This facilitates the phosphorylation of Pol II on its C-terminal domain, freeing it to start transcription in earnest.
Science, this issue p. 1383
- Vitamin C Research
Getting all stressed out by vitamin C
- Paula A. Kiberstis
Few experimental cancer therapies have incited as much debate as vitamin C. Yet the mechanistic effect of vitamin C on cancer cells is still poorly understood. Yun et al. studied human colorectal cancer cells with KRAS or BRAF mutations and found that they “handle” vitamin C in a different way than other cells, ultimately to their detriment (see the Perspective by Reczek and Chandel). Because a certain receptor is up-regulated in the mutant cells, they take up the oxidized form of vitamin C (dehydroascorbate). This leads to oxidative stress, inactivation of a glycolytic enzyme required by the mutant cells for growth, and finally cell death. Whether the selective toxicity of vitamin C to these mutant cells can be exploited therapeutically remains unclear.
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