This Week in Science

Science  06 Dec 2019:
Vol. 366, Issue 6470, pp. 1209
  1. Stem Cells

    Stem cells reshape a lymphatic niche

    1. Beverly A. Purnell

    Immunofluorescence imaging of lymphatics associated with hair follicles in mouse skin

    CREDIT: E. FUCHS AND S. GUR-CHOEN/THE ROCKEFELLER UNIVERSITY

    Adult stem cells can both self-renew and regenerate new tissue upon demand. They reside in microenvironments (niches) that balance these decisions to avoid tissue overgrowth, cancer, and aging. Using murine skin as a model, Gur-Cohen et al. uncovered a lymphatic network of capillaries associated with the stem cell niche of hair follicles (see the Perspective by Harvey). Stem cells reshaped their lymphatic environment by switching their secretome to coordinate lymphatic-niche association. During tissue regeneration, a dynamic change in epithelial-lymphatic communication remodeled this association, synchronizing stem cell and niche behavior.

    Science, this issue p. 1218; see also p. 1193

  2. Conservation Ecology

    Vulnerability to habitat fragmentation

    1. Andrew M. Sugden

    Habitat fragmentation caused by human activities has consequences for the distribution and movement of organisms. Betts et al. present a global analysis of how exposure to habitat fragmentation affects the composition of ecological communities (see the Perspective by Hargreaves). In a dataset consisting of 4489 animal species, regions that historically experienced little disturbance tended to harbor a higher proportion of species vulnerable to fragmentation. Species in more frequently disturbed regions were more resilient. High-latitude areas historically experienced more disturbance and harbor more resilient species, which suggests that extinction has removed fragmentation-sensitive species. Thus, conservation efforts to limit fragmentation are particularly important in the tropics.

    Science, this issue p. 1236; see also p. 1196

  3. Biocatalysis

    Maximal efficiency from enzyme cascades

    1. Michael A. Funk

    Enzymes are highly selective catalysts that can be useful for specific transformations in organic synthesis. Huffman et al. combined designer enzymes in a multistep cascade reaction (see the Perspective by O'Reilly and Ryan). The approach eliminates purification steps, recycles expensive cofactors, and couples favorable and unfavorable reactions. With the target molecule islatravir, an experimental HIV drug, they optimized five enzymes by directed evolution to be compatible with unnatural substrates and stable in the reaction conditions. Stereochemical purity was amplified at every enzymatic step, and the final synthesis was both atom economical and efficient.

    Science, this issue p. 1255; see also p. 1199

  4. Mesoscopic Physics

    Transmitting quantum states

    1. Jelena Stajic

    The coherence of electrons in mesoscopic structures is thought to be unlikely to survive in a disordered environment. Duprez et al. show that this is not necessarily the case. They studied a metallic island as an example of a disordered environment. They made an electron interferometer and incorporated the island in one of the two paths through the interferometer. At sufficiently low temperatures and in the quantum Hall regime, they observed a clear interference pattern, indicating successful transmission of the electrons' quantum state across the island.

    Science, this issue p. 1243

  5. Ultrafast Optics

    Tracking excitations

    1. Ian S. Osborne

    Illumination can be used to excite a sample from its ground state to a number of excited states. Typically, however, the details of the excitation dynamics are hidden from view because they decay so fast. Piatkowski et al. combined pump-probe transient absorption and two-pulse photoluminescence correlation spectroscopy, allowing them to assess stimulated emission and ground-state bleaching contributions to the transient absorption signal. This approach provides a window on the excitation dynamics within single nanocrystals and should also be useful for ultrafast nanocharacterization of complex samples.

    Science, this issue p. 1240

  6. Human Retina

    Sensing light without forming images

    1. Pamela J. Hines

    In the rodent retina, intrinsically photosensitive retinal ganglion cells (ipRGCs) entrain circadian rhythms, modulate mood, and signal pupillary accommodation. Such responses are light-driven but not image-based. Working with donated human organ tissues, Mure et al. used electrophysiological approaches to identify ipRGCs in the human retina. The human retina has more cones than the retinas of nocturnal mice and rats. Differences in sensitivity, latency, and duration of responses identified three subtypes of human ipRGCs.

    Science, this issue p. 1251

  7. Cancer

    A childhood tumor—from the beginning

    1. Paula A. Kiberstis

    Many adult cancers arise from clonal expansions of mutant cells in normal tissue. These premalignant expansions are defined by somatic mutations shared by the cancers. Whether pediatric cancers originate in a similar way is unknown. Coorens et al. studied Wilms tumor, a childhood kidney cancer. Phylogenetic analyses revealed large clones of mutant cells in histologically and functionally normal kidney tissue long before tumor development. Thus, like adult tumors, Wilms tumor appears to arise from a premalignant tissue bed.

    Science, this issue p. 1247

  8. Cancer

    Finding tumor cells and killing them, too

    1. Yevgeniya Nusinovich

    Treatments targeting the androgen receptor are a mainstay of prostate cancer therapy. However, these treatments do not usually cure the disease and eventually lose their effectiveness. A major cause of this therapeutic resistance is the presence of neuroendocrine tumor cells, which are not sensitive to androgen inhibition. Li et al. found that neuroendocrine prostate cancer cells express a chemokine receptor called CXCR2. The receptor could be used to help identify these cells in tumors and represents a viable therapeutic target.

    Sci. Transl. Med. 11, eaax0428 (2019).

  9. Atmospheric Science

    Here comes the flood

    1. Kip Hodges

    Atmospheric rivers (ARs) are extratropical storms that produce extreme precipitation on the west coasts of the world's major landmasses. Flood damage causes huge financial losses in U.S. West Coast communities. Now, researchers have found a possible link between ARs and flood damage. Corringham et al. found that increases in AR intensity and duration correspond with an estimated 10-fold increase in flood damages. The authors categorized ARs on a scale of one to five, with stages four and five representing the most intense ARs. This approach could potentially increase the efficiency of emergency preparedness for extreme flooding.

    Sci. Adv. 10.1126/sciadv.aax4631 (2019).

  10. HIV Vaccines

    Engineering better bnAbs

    1. Priscilla N. Kelly

    A highly effective HIV vaccine has been the goal of vaccinologists for nearly 35 years. A successful vaccine would need to induce broadly neutralizing antibodies (bnAbs) that are capable of neutralizing multiple HIV strains (see the Perspective by Agazio and Torres). Steichen et al. report a strategy in which the first vaccine shot can lead to immune responses that generate desired bnAbs. By combining knowledge of human antibody repertoires and structure to guide design, they validated candidate immunogens through functional preclinical testing. Saunders et al. designed immunogens with differences in binding strength for bnAb precursors, which enabled selection of rare mutations after immunization. The immunogens promoted bnAb precursor maturation in humanized mice and macaques.

    Science, this issue p. eaax4380, p. eaay7199; see also p. 1197

  11. Asteroids

    Bennu ejects material from its surface

    1. Keith T. Smith

    Most asteroids appear inert, but remote observations show that a small number experience mass loss from their surfaces. Lauretta and Hergenrother et al. describe close-range observations of mass loss on the near-Earth asteroid Bennu (see the Perspective by Agarwal). Shortly after arriving at Bennu, navigation cameras on the OSIRIS-REx (Origins, Spectral Interpretation, Resource Identification, and Security—Regolith Explorer) spacecraft detected objects 1 to 10 centimeters in diameter moving above the surface. Analysis of the objects' trajectories showed that they originated in discrete ejection events from otherwise unremarkable locations on Bennu. Some objects remained in orbit for several days, whereas others escaped into interplanetary space. The authors suggest multiple plausible mechanisms that could underlie this activity.

    Science, this issue p. eaay3544; see also p. 1192

  12. Volcanology

    Caldera collapse and flank eruption

    1. Brent Grocholski

    Real-time monitoring of volcanic eruptions involving caldera-forming events are rare (see the Perspective by Sigmundsson). Anderson et al. used several types of geophysical observations to track the caldera-forming collapse at the top of Kīlauea Volcano, Hawai'i, during the 2018 eruption. Gansecki et al. used near–real-time lava composition analysis to determine when magma shifted from highly viscous, slow-moving lava to low-viscosity, fast-moving lava. Patrick et al. used a range of geophysical tools to connect processes at the summit to lava rates coming out of far-away fissures. Together, the three studies improve caldera-collapse models and may help improve real-time hazard responses.

    Science, this issue p. 1225, p. eaaz0147, p. eaay9070; p. eaaz1822; see also p. 1200

  13. Solid-State Physics

    A timely look into electron-phonon coupling

    1. Jelena Stajic

    The coupling between electrons and phonons—lattice vibrations in solids—is responsible for macroscopic quantum phenomena such as superconductivity. Yet, experimentally measuring this coupling as a function of momentum and for a particular phonon mode is tricky. Na et al. used time- and angle-resolved photoemission spectroscopy to excite electrons in graphite and monitor their decay, which was accompanied by the release of phonons. The time constants of these decay processes provided direct information on electron-phonon couplings in this system.

    Science, this issue p. 1231

  14. Quantum Information

    Divacancies in a diode

    1. Jelena Stajic

    Solid-state defects hold great promise as the building blocks for quantum computers. Most research has focused on defects in diamond, which are difficult to integrate with existing semiconductor technologies. An alternative two-vacancy neutral defect in silicon carbide (SiC) has a long coherence time but suffers from broad optical linewidths and charge instability. Anderson et al. fabricated these defects in a diode made out of commercially available SiC. Reverse voltage created large electric fields within the diode, tuning the frequencies of the defect's transitions by hundreds of gigahertz. The electric fields also caused charge depletion, leading to a dramatic narrowing of the transitions. The technique should be readily generalizable to other quantum defects.

    Science, this issue p. 1225

  15. Structural Biology

    Regulating synaptic signals

    1. Valda Vinson

    In the brain, AMPA-type glutamate receptors (AMPARs) are ion channels that play key roles in synaptic plasticity, cognition, learning, and memory. Two classes of subunits, the claudin family and the cornichon family, regulate AMPAR gating and trafficking. Previous structures have been presented of AMPAR bound to claudin homologs. Now, Nakagawa reports a high-resolution structure of AMPAR bound to the cornichon homolog CNIH3, determined by cryo–electron microscopy (see the Perspective by Schwenk and Fakler). In contrast to a predicted topology of three transmembrane helices and an intracellular amino terminus, CNIH3 has four transmembrane helices, and both the amino and carboxyl termini are extracellular. The structure reveals the architecture of the interaction interface between AMPAR and CNIH3 and suggests a role for lipids in regulating the assembly and function of the AMPAR-CNIH3 complex.

    Science, this issue p. 1259; see also p. 1194

  16. Physiology

    Translating into a bigger pancreas

    1. Wei Wong

    The messenger RNA translation factor eIF5A promotes cell proliferation during development and in tumors. This ability depends on eIF5A hypusination, a posttranslational modification specific to eIF5A. Levasseur et al. found that eIF5A hypusination was critical for postnatal expansion of pancreatic β cell mass. Mice that could not perform hypusination in β cells did not produce sufficient cyclin D2 to sustain cell cycling and developed diabetes in response to diet-induced obesity. Thus, eIF5A hypusination enables β cells to proliferate, which is required to increase insulin production and maintain glucose homeostasis.

    Sci. Signal. 12, eaax0715 (2019).

  17. Immunodeficiencies

    Putting JNK1 on the immunodeficiency map

    1. Ifor Williams

    Impaired T helper 17 cell immunity is the shared element among a group of inherited immunodeficiencies that are associated with chronic mucocutaneous candidiasis (CMC). Li et al. studied three patients from a single family who had a combination of CMC and an atypical form of connective tissue disorder that had some features of Ehlers-Danlos syndrome. Whole-exome sequencing identified a loss-of-function splice-site mutation in the MAPK8 gene encoding c-Jun N-terminal kinase 1 (JNK1) that causes JNK1 haploinsufficiency with autosomal dominant inheritance. The complex clinic al phenotype in these patients results from defects in signaling downstream of both interleukin-17 and transforming growth factor–β (TGF-β) cytokines. Thus, JNK1-mediated signaling plays a critical role in maintaining normal immunity to Candida, and TGF-β promotes homeostasis of connective tissues.

    Sci. Immunol. 4, eaax7965 (2019).

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