Snail2 is an essential mediator of Twist1-induced epithelial mesenchymal transition and metastasis.

To metastasize, carcinoma cells must attenuate cell-cell adhesion to disseminate into distant organs. A group of transcription factors, including Twist1, Snail1, Snail2, ZEB1, and ZEB2, have been shown to induce epithelial mesenchymal transition (EMT), thus promoting tumor dissemination. However, it is unknown whether these transcription factors function independently or coordinately to activate the EMT program. Here we report that direct induction of Snail2 is essential for Twist1 to induce EMT. Snail2 knockdown completely blocks the ability of Twist1 to suppress E-cadherin transcription. Twist1 binds to an evolutionarily conserved E-box on the proximate Snail2 promoter to induce its transcription. Snail2 induction is essential for Twist1-induced cell invasion and distant metastasis in mice. In human breast tumors, the expression of Twist1 and Snail2 is highly correlated. Together, our results show that Twist1 needs to induce Snail2 to suppress the epithelial branch of the EMT program and that Twist1 and Snail2 act together to promote EMT and tumor metastasis.

Mantle shear-wave velocity structure beneath the Hawaiian hot spot.

Defining the mantle structure that lies beneath hot spots is important for revealing their depth of origin. Three-dimensional images of shear-wave velocity beneath the Hawaiian Islands, obtained from a network of sea-floor and land seismometers, show an upper-mantle low-velocity anomaly that is elongated in the direction of the island chain and surrounded by a parabola-shaped high-velocity anomaly. Low velocities continue downward to the mantle transition zone between 410 and 660 kilometers depth, a result that is in agreement with prior observations of transition-zone thinning. The inclusion of SKS observations extends the resolution downward to a depth of 1500 kilometers and reveals a several-hundred-kilometer-wide region of low velocities beneath and southeast of Hawaii. These images suggest that the Hawaiian hot spot is the result of an upwelling high-temperature plume from the lower mantle.

Magmatically triggered slow slip at Kilauea Volcano, Hawaii.

We demonstrate that a recent dike intrusion probably triggered a slow fault-slip event (SSE) on Kilauea volcano's mobile south flank. Our analysis combined models of Advanced Land Observing Satellite interferometric dike-intrusion displacement maps with continuous Global Positioning System (GPS) displacement vectors to show that deformation nearly identical to four previous SSEs at Kilauea occurred at far-field sites shortly after the intrusion. We model stress changes because of both secular deformation and the intrusion and find that both would increase the Coulomb failure stress on possible SSE slip surfaces by roughly the same amount. These results, in concert with the observation that none of the previous SSEs at Kilauea was directly preceded by intrusions but rather occurred during times of normal background deformation, suggest that both extrinsic (intrusion-triggering) and intrinsic (secular fault creep) fault processes can lead to SSEs.

Empirical evidence for the effect of airline travel on inter-regional influenza spread in the United States.

BACKGROUND: The influence of air travel on influenza spread has been the subject of numerous investigations using simulation, but very little empirical evidence has been provided. Understanding the role of airline travel in large-scale influenza spread is especially important given the mounting threat of an influenza pandemic. Several recent simulation studies have concluded that air travel restrictions may not have a significant impact on the course of a pandemic. Here, we assess, with empirical data, the role of airline volume on the yearly inter-regional spread of influenza in the United States. METHODS AND FINDINGS: We measured rate of inter-regional spread and timing of influenza in the United States for nine seasons, from 1996 to 2005 using weekly influenza and pneumonia mortality from the Centers for Disease Control and Prevention. Seasonality was characterized by band-pass filtering. We found that domestic airline travel volume in November (mostly surrounding the Thanksgiving holiday) predicts the rate of influenza spread (r(2) = 0.60; p = 0.014). We also found that international airline travel influences the timing of influenza mortality (r(2) = 0.59; p = 0.016). The flight ban in the US after the terrorist attack on September 11, 2001, and the subsequent depression of the air travel market, provided a natural experiment for the evaluation of flight restrictions; the decrease in air travel was associated with a delayed and prolonged influenza season. CONCLUSIONS: We provide the first empirical evidence for the role of airline travel in long-range dissemination of influenza. Our results suggest an important influence of international air travel on the timing of influenza introduction, as well as an influence of domestic air travel on the rate of inter-regional influenza spread in the US. Pandemic preparedness strategies should account for a possible benefit of airline travel restrictions on influenza spread.

Systematic survey reveals general applicability of "guilt-by-association" within gene coexpression networks.

BACKGROUND: Biological processes are carried out by coordinated modules of interacting molecules. As clustering methods demonstrate that genes with similar expression display increased likelihood of being associated with a common functional module, networks of coexpressed genes provide one framework for assigning gene function. This has informed the guilt-by-association (GBA) heuristic, widely invoked in functional genomics. Yet although the idea of GBA is accepted, the breadth of GBA applicability is uncertain. RESULTS: We developed methods to systematically explore the breadth of GBA across a large and varied corpus of expression data to answer the following question: To what extent is the GBA heuristic broadly applicable to the transcriptome and conversely how broadly is GBA captured by a priori knowledge represented in the Gene Ontology (GO)? Our study provides an investigation of the functional organization of five coexpression networks using data from three mammalian organisms. Our method calculates a probabilistic score between each gene and each Gene Ontology category that reflects coexpression enrichment of a GO module. For each GO category we use Receiver Operating Curves to assess whether these probabilistic scores reflect GBA. This methodology applied to five different coexpression networks demonstrates that the signature of guilt-by-association is ubiquitous and reproducible and that the GBA heuristic is broadly applicable across the population of nine hundred Gene Ontology categories. We also demonstrate the existence of highly reproducible patterns of coexpression between some pairs of GO categories. CONCLUSION: We conclude that GBA has universal value and that transcriptional control may be more modular than previously realized. Our analyses also suggest that methodologies combining coexpression measurements across multiple genes in a biologically-defined module can aid in characterizing gene function or in characterizing whether pairs of functions operate together.

Mantle fault zone beneath Kilauea Volcano, Hawaii.

Relocations and focal mechanism analyses of deep earthquakes (>/=13 kilometers) at Kilauea volcano demonstrate that seismicity is focused on an active fault zone at 30-kilometer depth, with seaward slip on a low-angle plane, and other smaller, distinct fault zones. The earthquakes we have analyzed predominantly reflect tectonic faulting in the brittle lithosphere rather than magma movement associated with volcanic activity. The tectonic earthquakes may be induced on preexisting faults by stresses of magmatic origin, although background stresses from volcano loading and lithospheric flexure may also contribute.