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<jats:title>Examining Y</jats:title> <jats:p> The evolution of human populations has long been studied with unique sequences from the nonrecombining, male-specific Y chromosome (see the Perspective by <jats:bold> <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6145" page="465" related-article-type="in-this-issue" vol="341" xlink:href="10.1126/science.1242899">Cann</jats:related-article> </jats:bold> ). <jats:bold> Poznik <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6145" page="562" related-article-type="in-this-issue" vol="341" xlink:href="10.1126/science.1237619">562</jats:related-article> ) examined 9.9 Mb of the Y chromosome from 69 men from nine globally divergent populations—identifying population and individual specific sequence variants that elucidate the evolution of the Y chromosome. Sequencing of maternally inherited mitochondrial DNA allowed comparison between the relative rates of evolution, which suggested that the coalescence, or origin, of the human Y chromosome and mitochondria both occurred approximately 120 thousand years ago. <jats:bold> Francalacci <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6145" page="565" related-article-type="in-this-issue" vol="341" xlink:href="10.1126/science.1237947">565</jats:related-article> ) investigated the sequence divergence of 1204 Y chromosomes that were sampled within the isolated and genetically informative Sardinian population. The sequence analyses, along with archaeological records, were used to calibrate and increase the resolution of the human phylogenetic tree. </jats:p>

<jats:title>Protecting the Guts</jats:title> <jats:p> Regulatory T cells (T <jats:sub>regs</jats:sub> ) in the gut are important sentinels in maintaining the peace between our gut and its trillions of resident bacteria and have been shown to be regulated by specific strains of bacteria in mouse models. <jats:bold> Smith <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6145" page="569" related-article-type="in-this-issue" vol="341" xlink:href="10.1126/science.1241165">569</jats:related-article> , published online 4 July; see the Perspective by <jats:bold> <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6145" page="463" related-article-type="in-this-issue" vol="341" xlink:href="10.1126/science.1242674">Bollrath and Powrie</jats:related-article> </jats:bold> ) asked whether metabolite(s) generated by resident bacterial species may regulate T <jats:sub>regs</jats:sub> in the gut. Indeed, short-chain fatty acids (SCFAs), bacterial fermentation products of dietary fibers produced by a range of bacteria, restored colonic T <jats:sub>reg</jats:sub> numbers in mice devoid of a gut microbiota and increased T <jats:sub>reg</jats:sub> numbers in colonized mice. The effects of SCFAs on T <jats:sub>regs</jats:sub> were mediated through GPCR43, a receptor for SCFAs, which is expressed on colonic T <jats:sub>regs</jats:sub> . Mice fed SCFAs were protected against experimentally induced colitis in a manner that was dependent on GPR43-expressing T <jats:sub>regs</jats:sub> . </jats:p>

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<jats:title>Epigenetic Brainscape</jats:title> <jats:p> Epigenetic modifications and their potential changes during development are of high interest, but few studies have characterized such differences. <jats:bold> Lister <jats:italic>et al.</jats:italic> </jats:bold> ( <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://www.sciencemag.org/content/341/6146/1237905.full">1237905</jats:ext-link> , published online 4 July; see the Perspective by <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6146" page="626" related-article-type="in-this-issue" vol="341" xlink:href="10.1126/science.1242671"> <jats:bold>Gabel and Greenberg</jats:bold> </jats:related-article> ) report whole-genome base-resolution analysis of DNA cytosine modifications and transcriptome analysis in the frontal cortex of human and mouse brains at multiple developmental stages. The high-resolution mapping of DNA cytosine methylation (5mC) and one of its oxidation derivatives (5hmC) at key developmental stages provides a comprehensive resource covering the temporal dynamics of these epigenetic modifications in neurons compared to glia. The data suggest that methylation marks are dynamic during brain development in both humans and mice. </jats:p>

<jats:sec> <jats:title>Background</jats:title> <jats:p>During the last few decades, progress has been made in manipulating the architecture of synthetic polymer materials. However, the primary structure—that is, the sequential arrangement of monomer units in a polymer chain—is generally poorly controlled in synthetic macromolecules. Common synthetic polymers are usually homopolymers, made of the same monomer unit, or copolymers with simple chain microstructures, such as random or block copolymers. These polymers are used in many areas but do not have the structural and functional complexity of sequence-defined biopolymers, such as nucleic acids or proteins. Indeed, monomer sequence regulation plays a key role in biology and is a prerequisite for crucial features of life, such as heredity, self-replication, complex self-assembly, and molecular recognition. In this context, developing synthetic polymers containing controlled monomer sequences is an important area for research.</jats:p> </jats:sec> <jats:sec> <jats:title>Advances</jats:title> <jats:p>Various synthetic methods for controlling monomer sequences in polymers have been identified, and two major trends in the field of sequence-controlled polymers have emerged. Some approaches use biological concepts that have been optimized by nature for sequence regulation. For instance, DNA templates, enzymes, or even living organisms can be used to prepare sequence-defined polymers. These natural mechanisms can be adapted to tolerate nonnatural monomers. The other trend is the preparation of sequence-controlled polymers by synthetic chemistry. In the most popular approach, monomer units are attached one by one to a support, which is an efficient method but demanding in practice. Recently, some strategies have been proposed for controlling sequences in chain-growth and step-growth polymerizations. These mechanisms usually allow fast and large-scale synthesis of polymers. Specific kinetics and particular catalytic or template conditions allow sequence regulation in these processes.</jats:p> </jats:sec> <jats:sec> <jats:title>Outlook</jats:title> <jats:p>The possibility of controlling monomer sequences in synthetic macromolecules has many scientific and technological implications. Information can be controlled at the molecular level in synthetic polymer chains. This opens up interesting perspectives for the field of data storage. In addition, having power over monomer sequences could mean structural control of the resulting polymer, as it strongly influences macromolecular folding and self-assembly. For instance, functional synthetic assemblies that mimic the properties of globular proteins, such as enzymes and transporters, can be foreseen. Moreover, monomer sequence control influences some macroscopic properties. For example, bulk properties such as conductivity, rigidity, elasticity, or biodegradability can be finely tuned in sequence-controlled polymers. The behavior of polymers in solution, particularly in water, is also strongly dependent on monomer sequences. Thus, sequence regulation may enable a more effective control of structure-property relations in tomorrow’s polymer materials.</jats:p> </jats:sec>