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<jats:p>Successful embryogenesis requires proper sorting and compartmentalization of different cell types. Mechanical interactions between cells help govern these processes. In the past, physics-based theories have guided in vitro studies of cell sorting and tissue surface tension. Recent experiments have challenged this approach, indicating that adhesive molecules also act as signaling molecules that initiate local reorganization of actomyosin and demonstrating that cells at the boundary of a colony of initially identical cells become “mechanically polarized.” Extending physical models to account for mechanical polarization helps solve a long-standing paradox about magnitudes of tissue surface tensions and potentially explains discrepancies between recent in vivo and in vitro cell-sorting experiments. New experiments are needed to further explore the connection between mechanical polarization and tissue boundary formation in vivo.</jats:p>

<jats:p>During development, cells undergo a unidirectional course of differentiation that progressively decreases the number of cell types they can potentially become. Stem cells, however, keep their potential to both proliferate and differentiate. A very important issue then is to understand the characteristics that distinguish stem cells from other cell types and allow them to conduct stable proliferation and differentiation. Here, we review relevant dynamical-systems approaches to describe the state transition between stem and differentiated cells, with an emphasis on fluctuating and oscillatory gene expression levels, as these represent the specific properties of stem cells. Relevance between recent experimental results and dynamical-systems descriptions of stem cell differentiation is also discussed.</jats:p>

<jats:p>Animal bodies and the embryos that generate them exhibit an assortment of stereotypic morphological motifs that first appeared more than half a billion years ago. During development, cells arrange themselves into tissues with interior cavities and multiple layers with immiscible boundaries, containing patterned arrangements of cell types. These tissues go on to elongate, fold, segment, and form appendages. Their motifs are similar to the outcomes of physical processes generic to condensed, chemically excitable, viscoelastic materials, although the embryonic mechanisms that generate them are typically much more complex. I propose that the origins of animal development lay in the mobilization of physical organizational effects that resulted when certain gene products of single-celled ancestors came to operate on the spatial scale of multicellular aggregates.</jats:p>

<jats:p>Tumor genome sequencing reveals the molecular basis of a patient’s unexpected and dramatic response to a cancer drug.</jats:p>

<jats:title>Ancient Genomics</jats:title> <jats:p> The Denisovans were archaic humans closely related to Neandertals, whose populations overlapped with the ancestors of modern-day humans. Using a single-stranded library preparation method, <jats:bold> Meyer <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" page="222" related-article-type="in-this-issue" vol="338" xlink:href="10.1126/science.1224344">222</jats:related-article> , published online 30 August) provide a detailed analysis of a high-quality Denisovan genome. The genomic sequence provides evidence for very low rates of heterozygosity in the Denisova, probably not because of recent inbreeding, but instead because of a small population size. The genome sequence also illuminates the relationships between humans and archaics, including Neandertals, and establishes a catalog of genetic changes within the human lineage. </jats:p>

<jats:title>Distinguishing Right from Left</jats:title> <jats:p> In most vertebrates during embryonic development, rotational movement of the cilia within a structure in the embryo, known as the node, generates unidirectional flow required for future left-right asymmetry of the internal organs. The flow may transport a determinant molecule or provide mechanical force. However, it is not clear how the flow is sensed. <jats:bold> Yoshiba <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" page="226" related-article-type="in-this-issue" vol="338" xlink:href="10.1126/science.1222538">226</jats:related-article> , published online 13 September; see the Perspective by <jats:bold> <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6104" page="206" related-article-type="in-this-issue" vol="338" xlink:href="10.1126/science.1230401"> <jats:bold>Norris and Grimes</jats:bold> </jats:related-article> </jats:bold> ) show that nodal flow in mouse embryos is sensed by the cilia of perinodal cells located at the edge of the node, in a manner dependent on Pkd2, a Ca <jats:sup>2+</jats:sup> -permeable cation channel that has been implicated in polycystic kidney disease in humans. </jats:p>

<jats:title>Bend to Straighten</jats:title> <jats:p> At low temperatures, the behavior of disordered solids, such as glasses, deviates from that of ordered crystals. The deviations may stem from the ability of some atomic entities to tunnel between two sites of almost identical energy, forming two low-energy states; such two-level systems (TLSs) are also thought to be a major contributor to the decoherence of superconducting qubits. <jats:bold> Grabovskij <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" page="232" related-article-type="in-this-issue" vol="338" xlink:href="10.1126/science.1226487">232</jats:related-article> ) used mechanical strain to control the splitting between the energy levels of TLSs formed in the disordered barrier of the Josephson junction in a superconducting qubit. For some of the detected TLSs, the splitting exhibited the predicted minimum as a function of strain, verifying the TLS model of disordered solids. </jats:p>

<jats:title>Relatively Cold</jats:title> <jats:p> Temperature is essentially a measure of relative atomic or molecular motion. Low temperature does not necessarily imply a sample at absolute rest—what is important is for every member of the sample to be moving (or not moving) at the same velocity. Techniques for studying reactions under extreme cooling have nonetheless tended to focus on slowing down molecules. <jats:bold> Henson <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" page="234" related-article-type="in-this-issue" vol="338" xlink:href="10.1126/science.1229141">234</jats:related-article> ) now demonstrate an alternative approach in which two beams of distinct gas-phase reagents are merged so as to continue forward with very little spread in their velocity. The interactions thus occur at millikelvin temperatures, revealing signatures of nonclassical dynamics such as oscillatory ionization probabilities with small shifts in energy. </jats:p>

<jats:title>Vesta to the Core</jats:title> <jats:p> Vesta is one of the largest bodies in the main asteroid belt. Unlike most other asteroids, which are fragments of once larger bodies, Vesta is thought to have survived as a protoplanet since its formation at the beginning of the solar system (see the Perspective by <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6104" page="203" related-article-type="in-this-issue" vol="338" xlink:href="10.1126/science.1228328">Binzel</jats:related-article> , published online 20 September). Based on data obtained with the Gamma Ray and Neutron Detector aboard the Dawn spacecraft, <jats:bold> Prettyman <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" page="242" related-article-type="in-this-issue" vol="338" xlink:href="10.1126/science.1225354">242</jats:related-article> , published online 20 September) show that Vesta's reputed volatile-poor regolith contains substantial amounts of hydrogen delivered by carbonaceous chondrite impactors. Observations of pitted terrain on Vesta obtained by Dawn's Framing Camera and analyzed by <jats:bold> Denevi <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" page="246" related-article-type="in-this-issue" vol="338" xlink:href="10.1126/science.1225374">246</jats:related-article> , published online 20 September), provide evidence for degassing of volatiles and hence the presence of hydrated materials. Finally, paleomagnetic studies by <jats:bold> Fu <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" page="238" related-article-type="in-this-issue" vol="338" xlink:href="10.1126/science.1225648">238</jats:related-article> ) on a meteorite originating from Vesta suggest that magnetic fields existed on the surface of the asteroid 3.7 billion years ago, supporting the past existence of a magnetic core dynamo. </jats:p>

<jats:title>Vesta to the Core</jats:title> <jats:p> Vesta is one of the largest bodies in the main asteroid belt. Unlike most other asteroids, which are fragments of once larger bodies, Vesta is thought to have survived as a protoplanet since its formation at the beginning of the solar system (see the Perspective by <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6104" page="203" related-article-type="in-this-issue" vol="338" xlink:href="10.1126/science.1228328">Binzel</jats:related-article> , published online 20 September). Based on data obtained with the Gamma Ray and Neutron Detector aboard the Dawn spacecraft, <jats:bold> Prettyman <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" page="242" related-article-type="in-this-issue" vol="338" xlink:href="10.1126/science.1225354">242</jats:related-article> , published online 20 September) show that Vesta's reputed volatile-poor regolith contains substantial amounts of hydrogen delivered by carbonaceous chondrite impactors. Observations of pitted terrain on Vesta obtained by Dawn's Framing Camera and analyzed by <jats:bold> Denevi <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" page="246" related-article-type="in-this-issue" vol="338" xlink:href="10.1126/science.1225374">246</jats:related-article> , published online 20 September), provide evidence for degassing of volatiles and hence the presence of hydrated materials. Finally, paleomagnetic studies by <jats:bold> Fu <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" page="238" related-article-type="in-this-issue" vol="338" xlink:href="10.1126/science.1225648">238</jats:related-article> ) on a meteorite originating from Vesta suggest that magnetic fields existed on the surface of the asteroid 3.7 billion years ago, supporting the past existence of a magnetic core dynamo. </jats:p>