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<jats:title>Imaging reactive surface water</jats:title> <jats:p> Recent developments in transmission electron microscopy (TEM) have enabled imaging of single atoms, but adsorbed gas molecules have proven more challenging because of a lack of sufficient image contrast. Yuan <jats:italic>et al.</jats:italic> adsorbed water and carbon monoxide (CO) on a reconstructed nanocrystalline anatase titanium dioxide (TiO <jats:sub>2</jats:sub> ) surface that has protruding TiO <jats:sub>3</jats:sub> ridges every four unit cells, which provide regions of distinct contrast. Water adsorption on this surface during environmental TEM experiments led to the formation of twinned protrusions. These structures developed dynamic contrast as the water reacted with coexposed CO to form hydrogen and carbon dioxide. </jats:p> <jats:p> <jats:italic>Science</jats:italic> , this issue p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6476" page="428" related-article-type="in-this-issue" vol="367" xlink:href="10.1126/science.aay2474">428</jats:related-article> </jats:p>

<jats:title>Filling in the gaps</jats:title> <jats:p> In a plant seed, the embryo lies dormant surrounded by nutritive endosperm while awaiting suitable conditions to germinate. A hydrophobic cuticle around the embryo protects it from catastrophic water loss during the early days of growth. Doll <jats:italic>et al.</jats:italic> identified a back-and-forth signaling pathway that ensures an intact cuticle. The precursor of a signaling peptide is made in the embryo and transferred to the endosperm, where it is processed into an active form. The activated peptide diffuses back into the embryo to activate receptor-like kinases that drive cuticle development. Serve and return continues until all leaks in the cuticle are filled in and the peptide can no longer cross the barrier. </jats:p> <jats:p> <jats:italic>Science</jats:italic> , this issue p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6476" page="431" related-article-type="in-this-issue" vol="367" xlink:href="10.1126/science.aaz4131">431</jats:related-article> </jats:p>

<jats:title>Taking the stress out of life</jats:title> <jats:p> In the model organism <jats:italic>Caenorhabditis elegans</jats:italic> , a roundworm, it has been shown that neurons can communicate proteostasis to the periphery to affect aging. Frakes <jats:italic>et al.</jats:italic> have now identified astrocytelike glial cells that also act as central regulators of systemic protein homeostasis and aging (see the Perspective by Miklas and Brunet). They found that the life span of <jats:italic>C. elegans</jats:italic> can be extended by expression of a constitutively active version of the transcription factor XBP-1s, which mediates the unfolded protein response of the endoplasmic reticulum (UPR <jats:sup>ER</jats:sup> ), in a specific subset of glial cells. Glial XBP-1s initiates induction of the UPR <jats:sup>ER</jats:sup> in distal intestinal cells, which makes the worms more resistant to chronic ER stress. Neuropeptide signaling was required for glial-mediated longevity and induction of the peripheral UPR <jats:sup>ER</jats:sup> , suggesting a distinct mechanism from that initiated by neuronal XBP-1s. Thus, in this animal model of aging, a mere four cells can control organismal physiology and aging </jats:p> <jats:p> <jats:italic>Science</jats:italic> , this issue p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6476" page="436" related-article-type="in-this-issue" vol="367" xlink:href="10.1126/science.aaz6896">436</jats:related-article> ; see also p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6476" page="365" related-article-type="in-this-issue" vol="367" xlink:href="10.1126/science.aba4474">365</jats:related-article> </jats:p>

<jats:title>Interneurons control brain arousal states</jats:title> <jats:p> The underlying circuit mechanisms coordinating brain arousal and motor activity are poorly understood. Liu <jats:italic>et al.</jats:italic> found that glutamic acid decarboxylase 2 (GAD2)–expressing, but not parvalbumin-expressing, interneurons in a part of the brain known as the substantia nigra promote sleep (see the Perspective by Wisden and Franks). Parvalbuminergic neurons fire at higher rates in states of high motor activity, and their activation increases movement termination consistent with the function of the substantia nigra in suppressing unwanted movements during action selection. By contrast, GAD2 neurons are preferentially active in states of low motor activity. In addition to motor suppression, their activation powerfully enhances the transition from quiet wakefulness to sleep, which differ mainly in the arousal level rather than motor behavior. GAD2 interneurons thus provide general suppression of both motor activity and brain arousal to promote states of quiescence. </jats:p> <jats:p> <jats:italic>Science</jats:italic> , this issue p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6476" page="440" related-article-type="in-this-issue" vol="367" xlink:href="10.1126/science.aaz0956">440</jats:related-article> ; see also p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6476" page="366" related-article-type="in-this-issue" vol="367" xlink:href="10.1126/science.aba4485">366</jats:related-article> </jats:p>

<jats:title>A one-two, CAR-T cell punch</jats:title> <jats:p> Chimeric antigen receptor (CAR)–T cells have been clinically effective in killing certain hematological malignancies, but achieving long-term patient responses for solid tumors remains a challenge. Reinhard <jats:italic>et al.</jats:italic> describe a two-part “CARVac” strategy to overcome poor CAR-T cell stimulation and responses in vivo. They introduce the tight junction protein claudin 6 (CLDN6) as a new CAR-T cell target and designed a nanoparticulate RNA vaccine encoding a chimeric receptor directed toward CLDN6. This lipoplex RNA vaccine promotes CLDN6 expression on the surface of dendritic cells, which in turn stimulates and enhances the efficacy of CLDN6-CAR-T cells for improved tumor therapy. </jats:p> <jats:p> <jats:italic>Science</jats:italic> , this issue p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6476" page="446" related-article-type="in-this-issue" vol="367" xlink:href="10.1126/science.aay5967">446</jats:related-article> </jats:p>

<jats:title>Shaping the early amniote embryo</jats:title> <jats:p> Gastrulation is an essential step in development in which the internal tissues of the body are set apart. In birds and mammals, a similar cascade of molecular events is known to specify embryonic territories, but how they are physically remodeled has remained elusive. Working with avian embryos, Saadaoui <jats:italic>et al.</jats:italic> identified a cable that encircles the embryo as the engine of gastrulation and described the collective cell movements as similar to the motion of a fluid. One side of this contractile ring pulls more strongly than the other, entraining the large-scale tissue movements that shape the early body plan. The embryo margin, previously known to function in molecular regulation, thus emerges as a dual mechanical and molecular organizer of development. </jats:p> <jats:p> <jats:italic>Science</jats:italic> , this issue p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6476" page="453" related-article-type="in-this-issue" vol="367" xlink:href="10.1126/science.aaw1965">453</jats:related-article> </jats:p>

<jats:title>A twisted small-molecule synthesis</jats:title> <jats:p> Some molecules are easy to draw on paper, whereas others contain rings and contortions that require one to think in three dimensions. Reisberg <jats:italic>et al.</jats:italic> set out to synthesize the bicyclic small molecule tryptorubin A but found that their initial attempt produced a molecule with the right bonds but the wrong molecular shape, a form of noncanonical atropisomerism. The authors then devised a synthesis where they locked in the correct isomer before forming the second ring, which produced a product indistinguishable from the authentic natural product. Such structural isomers may be lurking when working with complex small molecules with constrained rotation. </jats:p> <jats:p> <jats:italic>Science</jats:italic> , this issue p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6476" page="458" related-article-type="in-this-issue" vol="367" xlink:href="10.1126/science.aay9981">458</jats:related-article> </jats:p>

<jats:title>Keeping the noise down</jats:title> <jats:p> Protein concentrations in a cell fluctuate considerably because of stochasticity in gene expression and variations in the cell's microenvironment. How cells cope with concentration fluctuations when precision is important is unclear. Klosin <jats:italic>et al.</jats:italic> used a combination of theoretical and experimental work to demonstrate that phase-separated compartments can effectively reduce protein concentration noise in cells (see the Perspective by Riback and Brangwynne). The results suggest that phase separation provides a mechanism to enhance the robustness of biological systems. </jats:p> <jats:p> <jats:italic>Science</jats:italic> , this issue p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6476" page="464" related-article-type="in-this-issue" vol="367" xlink:href="10.1126/science.aav6691">464</jats:related-article> ; see also p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6476" page="364" related-article-type="in-this-issue" vol="367" xlink:href="10.1126/science.aba0446">364</jats:related-article> </jats:p>