This Week in Science

Science  26 Mar 2021:
Vol. 371, Issue 6536, pp. 1328
  1. Climatology

    Arctic response to a warming world

    1. Kip Hodges

    Cave deposits collected in northern Greenland provide a record of climate in the Arctic ∼560,000 years ago.

    PHOTO: ROBBIE SHONE

    Regional studies of paleoclimate provide important insights into how different parts of the Earth system respond to global climate change. Geochemical data gathered for cave deposits from northeast Greenland have now provided the first paleoclimate record for the High Arctic during an interglacial warming event extending from 588 to 549 thousand years ago. Moseley et al. show that the High Arctic at that time was at least 3.5°C warmer than today during that interval, with extensive permafrost thaw and markedly increased precipitation. Comparisons with datasets for that interval from elsewhere in the world suggest that the Arctic regions were affected more substantially during this warming event, and the same can be anticipated as anthropogenic global warming continues into the future.

    Sci. Adv. 10.1126/sciadv.abe1260 (2021).

  2. Paleoceanography

    Carbon cycle history

    1. H. Jesse Smith

    Marine carbon includes organic and inorganic components, both of which must be accounted for to understand the global carbon cycle. Paytan et al. assembled a record of stable strontium isotopes (88Sr and 86Sr) derived from pelagic marine barite and used it to reconstruct changes in the deposition and burial of biogenic calcium carbonate in marine sediments. These data, when combined with measurements of 87Sr/86Sr, can help to reveal past changes in the sources and sinks of strontium, as well as variations in carbonate deposition that affect the carbon cycle.

    Science, this issue p. 1346

  3. Plant Science

    Cell cycle regulation

    1. Pamela J. Hines

    The hormone cytokinin regulates various aspects of plant development and physiology, largely by managing cell proliferation. Yang et al. show that cytokinin promotes nuclear localization of the transcription factor MYB3R4, which activates the expression of two importins and genes that tip the cell into the next phase of the cell cycle. The importins facilitate further MYB3R4 accumulation within the nucleus, accelerating the progression into mitosis. MYB3R4 and the importins dissipate when the nuclear membrane dissolves at prometaphase, so there is only one round of mitotic activation per cell cycle.

    Science, this issue p. 1350

  4. Spectroscopy

    Mapping nanostructure surface excitations

    1. Ian S. Osborne

    Three-dimensional reconstruction of electromagnetic local density of states in a magnesium oxide cube

    CREDIT: LI ET AL.

    Atomic vibrations (phonons) govern many physical properties of materials, especially those related to heat and thermal transport. They also provide fingerprints of the chemistry of a wide variety of materials, from solids to molecules. The behavior of phonons in nanostructures can be appreciably modified because of confinement effects. Li et al. combined several electron microscopy techniques to map out the phonon-polariton excitations across the surface of magnesium oxide nanostructures with high spatial, spectral, and angular resolution. The reconstruction of the surface excitation maps in three dimensions will be useful for understanding and optimizing the properties of the nanostructured materials for advanced functionality.

    Science, this issue p. 1364

  5. Coronavirus

    Targeting the SARS-CoV-2 main protease

    1. Valda Vinson

    Vaccines are an important tool in the fight against COVID-19, but developing antiviral drugs is also a high priority, especially with the rise of variants that may partially evade vaccines. The viral protein main protease is required for cleaving precursor polyproteins into functional viral proteins. This essential function makes it a key drug target. Qiao et al. designed 32 inhibitors based on either boceprevir or telaprevir, both of which are protease inhibitors approved to treat hepatitis C virus. Six compounds protected cells from viral infection with high potency, and two of these were selected for in vivo studies based on pharmokinetic experiments. Both showed strong antiviral activity in a mouse model.

    Science, this issue p. 1374

  6. Quantum Control

    Dynamic stabilization of an array

    1. Ian S. Osborne

    Large-scale systems comprising one-dimensional chains and two-dimensional arrays of excited atoms held in a programmable optical lattice are a powerful platform with which to simulate emergent phenomena. Bluvstein et al. built an array of up to 200 Rydberg atoms and subjected the system to periodic excitation. Under such driven excitation, they found that the array of atoms stabilized, freezing periodically into what looked like time crystals. Understanding and controlling the dynamic interactions in quantum many-body systems lies at the heart of contemporary condensed matter physics and the exotic phenomena that can occur.

    Science, this issue p. 1355

  7. Solar Cells

    Perovskite synthesis out in the open

    1. Phil Szuromi

    Although methods have been developed that create the photoactive black perovskite phase of formamidinium lead iodide (α-FAPbI3), these routes are temperature and humidity sensitive and less compatible with large-scale solar cell production. Hui et al. report an alternative route in which vertically aligned lead iodide thin films are grown from the ionic liquid methylamine formate. Nanoscale channels in the films lower the barrier to permeation of formamidinium iodide and enable transformation to α-FAPbI3, even at high humidity and room temperature. Solar cells made with these films have power conversion efficiencies as high as 24.1% that display high stability.

    Science, this issue p. 1359

  8. Cancer

    The STAR of the show

    1. Courtney S. Malo

    Chimeric antigen receptor T (CAR-T) cells have revolutionized treatment for hematological cancers, but this success has not translated to solid tumors. To address this challenge, Liu et al. engineered a synthetic T cell receptor and antigen receptor (STAR) that combines the specificity of a CAR and the internal signaling machinery of an endogenous T cell receptor. STAR-T cells outperformed their CAR-T cell counterparts in controlling multiple murine tumors and did not display evidence of the exhaustion frequently observed in CAR-T cells. These results suggest that STAR-T cells may be an attractive option for treating patients with solid tumors.

    Sci. Transl. Med. 13, eabb5191 (2021).

  9. Coronavirus

    Mutations in emerging variants

    1. Gemma Alderton

    The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein mediates host cell entry and contains key epitopes for antibody binding. Emerging SARS-CoV-2 variants, which seem to have originated in immunocompromised patients with prolonged infections, have mutations in the spike protein. Some of these mutations recur in independent lineages and some may compensate for deleterious effects of others and thereby arise together. In a Perspective, McCormick et al. discuss emerging variants and mutations that may reduce antibody-mediated neutralization of the virus and, potentially, vaccine efficacy.

    Science, this issue p. 1306

  10. Cancer Microbiome

    Separating microbes and cancers

    1. Priscilla N. Kelly,
    2. Caroline Ash

    The role of microorganisms in causing and sustaining cancers has been in dispute for centuries. Through the lens of gut- and tumor-associated microbes, Sepich-Poore et al. review our current understanding of the microbiota in cancer, building a “microbially conscious” framework. The authors argue that humans should be considered as a meta-organism, but how our microbiota influences cancer is still not well understood mechanistically. Nevertheless, advances in microbiome research are improving our understanding of immuno-oncology and driving new diagnostic and therapeutic approaches.

    Science, this issue p. eabc4552

  11. Immunology

    An IFN-γ feedback loop

    1. Seth Thomas Scanlon

    Innate lymphoid cells (ILCs) play important roles in tissue homeostasis and host defense. Type 1 ILCs (ILC1s) produce interferon-γ (IFN-γ) and require the transcriptional master regulator T-bet. The pathways underlying how these cells develop and differentiate have remained poorly understood. Bai et al. found that the adult mouse liver contains a population of Lin–Sca-1+Mac-1+ hematopoietic stem cells (LSM HSCs) that preferentially differentiate into tissue-resident liver ILC1s. They further show that IFN-γ produced by mature ILC1s promotes the expansion and differentiation of LSM HSCs into ILC1s but not natural killer cells. This work expands our understanding of extramedullary hematopoiesis and underscores the unique immune status of the liver.

    Science, this issue p. eaba4177

  12. Immunology

    WAVE-ing T cell activation off

    1. Seth Thomas Scanlon

    The WAVE regulatory complex (WRC) is a pentameric complex that regulates actin cytoskeleton dynamics. The precise role for the WRC in immunity has not been established, although recent work has implicated WRC components such as HEM1 in certain human immunodeficiencies. Liu et al. characterized mice with a conditional knockout of the WRC constituent WAVE2 (see the Perspective by Hambleton). These mice exhibited progressive severe autoimmune and inflammatory disease associated with the activation and accelerated differentiation of T cells. WAVE2's suppression of T cell activation was not mediated by the T cell receptor but rather by its inhibition of mammalian target of rapamycin (mTOR) binding to RAPTOR and RICTOR. Accordingly, the autoimmune phenotype of these mice could be ameliorated by pharmacological inhibitors of mTOR signaling.

    Science, this issue p. eaaz4544; see also p. 1309

  13. Signal Transduction

    Laser-controlled receptor clustering

    1. L. Bryan Ray

    A strategy that allows light-controlled local confinement of a heterotrimeric guanine nucleotide–binding protein (G protein)–coupled receptor may help to elucidate signal transduction mechanisms. Sánchez et al. developed just such an approach using a poly-L-lysine-graft-polyethylene glycol copolymer with a photoactivatable head. Laser light could locally activate a chelator that rapidly (within seconds) captured polyhistidine-tagged neuropeptide Y receptors. Such receptor confinement enhanced calcium signaling and increased spreading and cell motility in cultured human cells. The ability to control the location, size, and density of receptor clusters may help to elucidate receptor signaling mechanisms.

    Science, this issue p. eabb7657

  14. Wildlife Disease

    A lethal combination

    1. Sacha Vignieri

    Although many human activities have clear negative effects on the natural world, there are also unforeseen consequences. Bald eagle mass death events in the southeastern United States may be one such downstream effect of human activity. After considerable effort, Breinlinger et al. identified the cause of these events as an insidious combination of factors. Colonization of waterways by an invasive, introduced plant provided a substrate for the growth of a previously unidentified cyanobacterium. Exposure of this cyanobacterium to bromide, typically anthropogenic in origin, resulted in the production of a neurotoxin that both causes neuropathy in animals that prey on the plants and also bioaccumulates to kill predators such as bald eagles.

    Science, this issue p. eaax9050

  15. Coronavirus

    Age-specific contact

    1. Caroline Ash

    How can the resurgent epidemics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during 2020 be explained? Are they a result of students going back to school? To address this question, Monod et al. created a contact matrix for infection based on data collected in Europe and China and extended it to the United States. Early in the pandemic, before interventions were widely implemented, contacts concentrated among individuals of similar age were the highest among school-aged children, between children and their parents, and between middle-aged adults and the elderly. However, with the advent of nonpharmaceutical interventions, these contact patterns changed substantially. By mid-August 2020, although schools reopening facilitated transmission, the resurgence in the United States was largely driven by adults 20 to 49 years of age. Thus, working adults who need to support themselves and their families have fueled the resurging epidemics in the United States.

    Science, this issue p. eabe8372

  16. Speciation

    Choosy females drive isolation

    1. Sacha Vignieri

    Rapid radiations of recently diverged species represent an excellent opportunity for exploring drivers of speciation. The capuchino seedeaters, a group of South American birds, include a number of species that, in the field, are often discernable only through male plumage and song. Turbek et al. used genomes and behavioral experiments to identify potential isolating factors in two members of this group and found that, though entirely sympatric, females mated only with conspecific males and that only a few genes differed between the species (see the Perspective by Jarvis). Thus, a small reshuffling of genes and reinforcement through mate choice has driven divergence in these overlapping and very similar species.

    Science, this issue p. eabc0256; see also p. 1312

  17. Organic Chemistry

    Heteroaromatics lured into cycloadditions

    1. Jake Yeston

    The Diels-Alder reaction is widely used to produce six-membered carbon rings from alkenes and dienes. Heteroaromatics such as quinolines resemble dienes in principle, but in practice their pairs of double bonds are inert toward cycloadditions because of aromatic stabilization. Ma et al. report that by using an iridium photosensitizer, they could excite quinolines and related azaarenes to triplet states, thereby disrupting the aromaticity and enabling intermolecular, Diels-Alder–like reactivity toward alkenes (see the Perspective by Schmidt). The reactions proceeded exclusively at the flanking carbons outside the nitrogen-containing ring.

    Science, this issue p. 1338; see also p. 1313

  18. Plasmonics

    Nanorod alignment for optical asymmetry

    1. Phil Szuromi

    The high polarizability of chiral nanoassemblies of plasmonic nanoparticles can lead to strong chiral dichroism, but strong light scattering causes the fraction of polarized photons generated, as measured by g-factors, to be much lower than that for chiral liquid crystals. Lu et al. used supramolecular interactions of gold nanorods with human islet amyloid peptides to assemble metallic superstructures with unusually high cholesteric order (see the Perspective by Nam and Kim). The long, straight helices increased the g-factor by 4600-fold, and this effect was used to screen small-molecule binding to amyloids.

    Science, this issue p. 1368; see also p. 1311

  19. Coronavirus

    Halting transmission

    1. Caroline Ash

    The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) glycoprotein binds to host cells and initiates membrane fusion and cell infection. This stage in the virus life history is currently a target for drug inhibition. De Vries et al. designed highly stable lipoprotein fusion inhibitors complementary to a conserved repeat in the C terminus of S that integrate into host cell membranes and inhibit conformational changes in S necessary for membrane fusion. The authors tested the performance of the lipoproteins as a preexposure prophylactic in a ferret-to-ferret transmission study. Intranasal administration of the peptide 2 days before cohousing with an infected ferret for 24 hours completely protected animals in contact from infection and showed efficacy against mutant viruses. Because ferrets do not get sick from SARS-CoV-2, disease prevention could not be tested in this model.

    Science, this issue p. 1379

  20. Immunology

    In non-eutherians, a third type of T cell

    1. Seth Thomas Scanlon

    The two established T cell lineages found in jawed vertebrates use either an αβ or a γδ T cell receptor (TCR) to detect antigens. Recently, another type of TCR chain (TCRµ) was found in marsupials and monotremes. Morrissey et al. analyzed T cells from the gray short-tailed opossum and uncovered a third lineage resident in the spleen that uses a γµ TCR (see the Perspective by Criscitiello). The authors then characterized the crystal structures of two different γµ TCRs, which exhibited an architecture distinct from αβ or γδ TCRs in which a highly diverse, unpaired immunoglobulin-like variable domain was predicted to be the major antigen recognition determinant. Like camelid VHH and shark IgNAR antibodies, γµ TCRs could potentially inform future nanobody development.

    Science, this issue p. 1383; see also p. 1308

  21. Immunology

    Flipping the switch in T cells

    1. John F. Foley

    The cytoplasmic domains of some CD3 subunits in the T cell receptor complex localize along the inner leaflet of the plasma membrane through electrostatic interactions, which inhibits their activation. Connolly et al. found that the scramblase TMEM16F, which redistributes phosphatidylserine from the inner to the outer leaflet of the plasma membrane, enabled the cytoplasmic domains of CD3 subunits in bystander T cell receptors to disengage from the plasma membrane, leading to enhanced T cell activation. These bystander TCRs were close to antigen-stimulated TCRs and amplified T cell signaling.

    Sci. Signal. 14, eabb5146 (2021).

  22. Transplantation

    Memories of rejection

    1. Dan A. Erkes

    Long-term graft survival after organ transplantation can be hindered by immune-mediated allograft rejection; therefore, understanding these immune responses is crucial to developing new transplant-supporting therapies. Tissue-resident memory T cells (TRMs), a subset of memory T cells that reside in barrier tissues and do not recirculate, are detectable in transplanted organs, but it is unclear whether they contribute to allograft rejection. Abou-Daya et al. created a mouse model of T cell–mediated kidney transplant rejection, showing that adoptively transferred, kidney antigen–specific effector T cells differentiated into functional, nonrecirculating antigen-specific TRMs in the transplanted kidneys. These kidney antigen–specific TRMs induced allograft rejection. Targeting alloreactive TRMs might improve long-term graft survival in transplant recipients.

    Sci. Immunol. 6, eabc8122 (2021).

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