Editors' Choice

Science  05 Jan 2018:
Vol. 359, Issue 6371, pp. 44
  1. Parasite Genomics

    Single-cell sequencing of malarial genomes

    1. Laura M. Zahn

    Single-cell sequencing of Plasmodium, here released from lysed red blood cells, allows for tracking of variation in the host.

    PHOTO: DENNIS KUNKEL MICROSCOPY/SCIENCE SOURCE

    Infection with the parasite Plasmodium falciparum causes malaria. Individuals may be infected with multiple strains of P. falciparum, some of which may be drug-resistant. Understanding the complexity of these infections may provide information about the diversity of the parasite population and aid in drug-targeting strategies. Overcoming the difficulties caused by AT bias in the Plasmodium genome, Trevino et al. optimized single-cell sequencing for late-stage P. falciparum parasites within infected individuals. From this analysis, they documented at least seven distinct parasitic haplotypes, traced meiotic events and hence relatedness among parasitic lineages, and found distinct single-nucleotide variants that could be used for bulk analysis.

    Genome Biol. Evol. 10.1093/gbe/evx256 (2017).

  2. Signal Transduction

    Unconventional thyroid hormone signals

    1. L. Bryan Ray

    Thyroid hormone canonically signals through thyroid hormone receptors to enhance transcription of target genes. There is also evidence that thyroid hormone can activate nontranscriptional signaling mechanisms. To sort out the relative importance of canonical and noncanonical signaling, Hones et al. generated mice in which thyroid hormone receptors were altered to prevent DNA binding and transcriptional effects (but noncanonical signaling remained) and compared thyroid hormone action in these animals with that in wild-type mice or mice lacking thyroid hormone receptors entirely. They found that in vivo, several physiological actions of thyroid hormone—including regulation of body temperature, glucose and triglyceride concentrations in the blood, and heart rate—all appear to be mediated by noncanonical or nontranscriptional mechanisms.

    Proc. Natl. Acad. Sci. U.S.A. 10.1073/pnas.1706801115 (2017).

  3. Biocatalysis

    Guiding an enzyme all around a ring

    1. Jake Yeston

    Most compounds of interest for pharmaceuticals, agrochemicals, and cosmetics have many C–H bonds, interspersed with a few carbon bonds to heavier elements that give them their distinct properties. Chemists therefore prize methods that let them selectively modify a variety of C–H bonds. Gilbert et al. report a versatile strategy that relies on a tethered amine to steer an engineered cytochrome P450 enzyme around 11- or 12-membered rings, transforming specific C–H bonds into C–O bonds. Subtle structural variation of the tether through click chemistry tunes the site selectivity.

    ACS Cent. Sci. 10.1021/acscentsci.7b00450 (2017).

  4. Minor Planets

    An object from beyond the solar system

    1. Keith T. Smith

    Gravitational interactions occasionally eject small bodies from the solar system, and this process is thought to have been particularly common while the system was first forming. The same thing should have occurred around other stars, casting comets and asteroids into interstellar space, but no such interstellar objects have been identified. Meech et al. discovered a small object, now formally designated 1I/2017 U1 ('Oumuamua), whose trajectory indicates that it arrived from interstellar space. Changes in its brightness demonstrate that 'Oumuamua is rotating and is several times longer than it is wide. 'Oumuamua is quickly passing through the solar system and soon will resume its interstellar journey.

    Nature 10.1038/nature25020 (2017).

  5. Microbiota

    Eats leaves and grooms

    1. Caroline Ash

    Social interaction among Verreaux's sifaka is responsible for transmission of gut microbes that are essential for digestion of their leaf-based diet.

    PHOTO: HAJAKELY/SHUTTERSTOCK.COM

    The gut microbiota influences many aspects of mammalian development and physiology. Yet we have a poor understanding of how the gut microbiota is acquired and assembled. We know that social networks are important for the transmission of pathogens, but are they also implicated in transmission of symbionts? Perofsky et al. investigated the microbiota of a social primate, a lemur species called Verreaux's sifaka, living in the wild in Madagascar. These lemurs eat leaves and have a distinctive microbiota capable of digesting and detoxifying plant matter. The authors found that sex, dominance, and age influenced gut microbial composition, but social group membership explained 58% of the variation. Grooming and scent-marking are essential for lemur social cohesion, and commensal microbes are transferred between individuals through this type of intimate contact, rather than being regulated by genetics or diet.

    Proc. R. Soc. B 284, 20172274 (2017).

  6. Biology

    Cytoplasmic transfer to tumor cells

    1. Gemma Alderton

    Macrophages are innate immune cells that, when recruited to tumors, can promote tumor progression. Macrophage activity and phenotype can be influenced by molecules secreted by tumor cells. To monitor macrophage behavior, Roh-Johnson et al. used time-lapse imaging of a zebrafish model of melanoma. Unexpectedly, macrophages not only bound to but also transferred their cytoplasm into melanoma cells, which promoted metastasis. Macrophage cytoplasmic transfer to melanoma cells also correlated with metastasis in mice. This unusual mechanism of cell-cell signaling raises questions about how such intercellular communication is regulated and what molecules are transferred to melanoma cells to promote their metastasis.

    Dev. Cell 43, 549 (2017).

  7. Translation

    Ribosomes ignore the stop sign

    1. Michael A. Funk

    Aminoglycoside antibiotics bind to bacterial ribosomes and inhibit protein synthesis. Eukaryotic ribosomes, in contrast, are not strongly inhibited by these molecules but show errors such as inaccurate translation and read-through of stop codons. Prokhorova et al. determined structures of the eukaryotic ribosome in complex with aminoglycoside antibiotics and investigated how these molecules alter the conformation of the ribosome. They found distinct binding sites for different classes of aminoglycosides and multiple possible binding sites on each ribosome. The conformational changes induced by these molecules suggest multiple mechanisms by which the antibiotics interfere with eukaryotic translation.

    Proc. Natl. Acad. Sci. U.S.A. 10.1073/pnas.1715501114 (2017).