This Week in Science

Science  26 Feb 2021:
Vol. 371, Issue 6532, pp. 901
  1. Molecular Motors

    Ciliary motors locked closed by Shulin

    1. Stella M. Hurtley

    Scanning electron microscopy image of a freshwater ciliate, Tetrahymena thermophila, covered in motile cilia, which are beating cellular projections powered by the molecular motor dynein

    IMAGE: DENNIS KUNKEL MICROSCOPY/SCIENCE SOURCE

    Motile cilia and flagella are vital cellular organelles with functions that include setting up the left-right body axis, clearing airways of mucus, and driving single-cell movements. Cilia beating is powered by arrays of dynein motors, the key force generators being the outer dynein arm (ODA) complexes. Using the protozoan Tetrahymena, Mali et al. identified a factor, which they name Shulin, that binds newly synthesized ODAs. Cryo–electron microscopy revealed how Shulin locks the dynein motors together by shutting off motor activity and facilitating delivery of ODAs from the cytoplasm to their final position in the cilia.

    Science, this issue p. 910

  2. Coronavirus

    Vaccine prioritization

    1. Caroline Ash

    There is likely to be high demand for the limited supplies of vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), so how should vaccine distribution be prioritized? Bubar et al. modeled across countries how uncertainty about a vaccine's characteristics affects prioritization strategies for reducing deaths and transmission (see the Perspective by Fitzpatrick and Galvani). In the model, vaccine efficacy and its ability to reduce disease and/or block transmission was accounted for in relation to age-related variations in susceptibility, fatality rates, and immune decline. In almost all circumstances, reducing fatalities required distributing the vaccine to those who are most at risk of death, usually persons over 60 years of age and those with comorbidities. If a vaccine is leaky or poorly efficacious in older adults, then priority could be given to younger age groups. To increase the available doses, further priority should be given to seronegative individuals.

    Science, this issue p. 916; see also p. 890

  3. Atmospheric Chemistry

    On the surface

    1. H. Jesse Smith

    The uptake and hydrolysis of N2O5 from the atmosphere by aqueous aerosols was long thought to occur by solvation and subsequent hydrolysis in the bulk of the aerosol. However, this mechanistic hypothesis was unverifiable because of the fast reaction kinetics. Galib et al. used molecular simulations to show instead that the mechanism is the inverse: Interfacial hydrolysis is followed by solvation into the interior. Their reactive uptake model is consistent with some existing experimental observations.

    Science, this issue p. 921

  4. Paleontology

    Not enough room

    1. Sacha Vignieri

    Modern carnivore communities include species that span a range of body sizes. For example, on the African savannah, there are small species (mongooses), medium species (wild dogs), and large species (lions). This variation reflects available prey sources that best suit each group. Carnivorous dinosaur communities, however, were missing species that fall into the middle, or mesocarnivore, group as adults. Schroeder et al. looked across communities, space, and time and found that this absence appears to have been driven by the distinctive biology of dinosaurs, in which giant adults start out as tiny hatchlings. Growing juvenile dinosaurs thus filled the other niches and limited trophic species diversity.

    Science, this issue p. 941

  5. Geophysics

    Waiting for earthquakes to call

    1. Brent Grocholski

    Instrumenting the vast ocean floor is difficult and expensive but important for monitoring earthquakes and tsunamis. Zhan et al. used the polarization of regular telecommunication traffic to detect earthquakes and water swells in a 10,000-kilometer-long fiber-optic submarine cable (see the Perspective by Wilcock). The deep-water Curie cable is not as noisy as terrestrial counterparts, allowing the authors to detect strain from the cable. Results from the 9-month observation period showed how current submarine fiber-optic cables can also be used as a geophysical tool.

    Science, this issue p. 931; see also p. 882

  6. Transplantation

    A ratio to predict rejection

    1. Courtney S. Malo

    Current strategies to identify rejection of transplanted kidneys rely on invasive surveillance biopsies or have limited predictive value. Therefore, an early and noninvasive biomarker to predict rejection is needed. Cherukuri et al. characterized the ratio of interleukin-10 to tumor necrosis factor–α expressed by transitional B cells as a biomarker of early T cell–mediated allograft rejection. The authors found that this ratio predicted rejection at 3 months after transplantation in three patient cohorts, and it may be an effective biomarker that can be used clinically to tailor therapy based on risk of rejection.

    Sci. Transl. Med. 13, eabe4929 (2021).

  7. Nano-Optical Writing

    Toward next-generation optical disks

    1. Laura Na Liu

    Subdiffraction information bits can be written using superresolution methods to achieve extremely high-density information storage. Using lanthanide-doped upconversion nanoparticles to locally reduce graphene oxide flakes through upconversion resonance energy transfer upon engineered illumination, Lamon et al. achieved an estimated storage capacity of 700 terabytes on a 12-centimeter optical disk by nanoscale optical writing, comparable to a storage capacity of 28,000 single-layer Blu-ray disks. This technology offers an inexpensive solution for the next generation of high-capacity optical data storage and enables energy-efficient nanofabrication of flexible, graphene-based electronics.

    Sci. Adv. 10.1126/sciadv.abe2209 (2021).

  8. Chemical Dynamics

    Intriguing dynamics pattern in F + HD

    1. Yury Suleymanov

    The scattering pattern for the F + HD reaction reveals the fine structure of partial waves.

    CREDIT: CHEN ET AL.

    Despite decades of studies, the role of relativistic spin-orbit interactions in the dynamics of chemical reactions remains an intriguing topic. Using a high-resolution velocity map imaging crossed beams technique, Chen et al. observed an interesting pattern in the differential cross sections in the F + HD → HF + D reaction near the partial wave resonances (see the Perspective by Rakitzis). Further theoretical analysis showed that this pattern originates from quantum interference between spin-orbit split partial wave resonances with different total parities. The effect of the fine structure of the partial waves observed for this long known yet not completely explored three-atom system represents one more remarkable demonstration of the truly quantum nature of chemical reaction dynamics.

    Science, this issue p. 936; see also p. 886

  9. 3D Genomics

    Visualizing the 3D genome in situ

    1. Laura M. Zahn

    The conformation of the genome within the cell changes depending on cell state, such that being able to visualize genome structure can identify cis and trans interactions among regulatory genetic elements. Payne et al. have developed an unbiased genome-sequencing technique in single cells in situ that can infer the chromatin structure by imaging. They were able to identify sequences at subnuclei locations to analyze the proximity relationships among genetic elements within and across chromosomes in single cells. Using this technique, they could detect chromosome territories and distinctions between different types of repetitive sequences and chromosomal features. This method can map and image genomic coordinates with submicrometer resolution in intact single cells.

    Science, this issue p. eaay3446

  10. Neurodegeneration

    The many faces of tau

    1. Gemma Alderton

    The protein tau is implicated in several brain disorders, including Alzheimer's disease, suggesting that it could be a target of therapeutics. However, because it is unclear how the pleiotropic roles of tau lead to neural pathology in different brain diseases, drug development remains challenging. Chang et al. review the possible mechanisms of tau in brain diseases and possible paths forward to improving research and drug development.

    Science, this issue p. eabb8255

  11. Cancer Genomics

    Following cancer through the body

    1. Laura M. Zahn

    The heterogeneity of mammalian tumors has been well documented, but it remains unknown how differences between individual cells lead to metastasis and spread throughout the body. Quinn et al. created a Cas9-based lineage tracer and used single-cell sequencing to generate phylogenies and follow the movement of metastatic human cancer cells implanted in the lung of a mouse xenograph model. Using this model, they found that within the same cell line, cancer cells exhibited diverse metastatic phenotypes. These subclones exhibited differential gene expression profiles, some of which were previously associated with metastasis.

    Science, this issue p. eabc1944

  12. Lineage Tracing

    Zoning in on liver growth

    1. Beverly A. Purnell

    For organ homeostasis or regrowth after injury or disease, one or more stem cell populations is needed to rebuild lost tissue. There is considerable debate about the source of new cells in the liver. Two groups now identify the source of new hepatocytes (see the Perspective by Andersson). Although the liver may seem to lack major variation across its structure, its lobule is organized into concentric zones where hepatocytes express different metabolic enzymes. Wei et al. sought to systematically define the source of new liver cells by comparing 14 fate-mapping mice that label different liver cell types. They found that different regions of the liver lobule exhibit differences in hepatocyte turnover, with zone 2 representing a primary source of new hepatocytes during homeostasis and regeneration. Similarly, He et al. designed a genetic approach to record cell proliferation in vivo with high spatial and temporal resolution to enable continuous recording of proliferative events of any specific cell type at the whole-cell population level. Using this method, they identified zone 2 as having the highest proliferative activity and contributing the most to liver regrowth. These findings have implications for the cellular basis of chronic disease pathogenesis, cancer development, and regenerative medicine strategies.

    Science, this issue p. eabb1625, p. eabc4346; see also p. 887

  13. Coronavirus

    A single sugar makes all the difference

    1. Seth Thomas Scanlon

    Antibodies are divided into several classes based on their nonvariable tail (Fc) domains. These regions interact with disparate immune cell receptors and complement proteins to help instruct distinct immune responses. The Fc domain of immunoglobulin G (IgG) antibodies contains a conserved N-linked glycan at position 297. However, the particular glycan used at this position is highly variable. IgG lacking core fucosylation at this position initiates enhanced antibody-dependent cellular cytotoxicity by increased affinity to the Fc receptor FcRIIIa. Larsen et al. report that COVID-19 patients with severe symptoms have increased levels of anti–severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG afucosylation compared with patients with mild disease. These findings suggest that treatment of COVID-19 patients with fucosylated anti–SARS-CoV-2 antibodies may circumvent pathologies associated with severe COVID-19.

    Science, this issue p. eabc8378

  14. Coronavirus

    Hurting the virus by targeting the host

    1. Valda Vinson

    Many host proteins play a role in the life cycle of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and some are required for viral replication and translation. There are efforts toward finding drugs that target viral proteins, but a complementary approach is to target these required host proteins. White et al. explored the antiviral activity of the cyclic depsipeptide drug plitidepsin, which targets the hosts cell's translational machinery (see the Perspective by Wong and Damania). The authors show that in cells, the drug is substantially more potent than remdesivir against SARS-CoV-2, with limited cellular toxicity. Prophylactic treatment protected mice against SARS-CoV-2 infection, so further investigation of plitidepsin as a therapeutic is warranted.

    Science, this issue p. 926; see also p. 884

  15. Optoelectronics

    Laser-based generation of random numbers

    1. Ian S. Osborne

    The security of our digital networks is underpinned by the ability to generate streams of random numbers or bits. As networks expand in an ever-connected way, the challenge is to increase the generation rate of the random numbers to keep pace with demand. Kim et al. designed a chip-scale laser diode that generates random bits at an ultrahigh rate (see the Perspective by Fischer and Gauthier). By tailoring the geometry of the cavity, they were able to exploit the spatiotemporal interference of many lasing modes to generate picosecond-scale emission intensity fluctuations in space and time, producing ultrafast random bit streams in parallel. Such a device will find a wide range of applications requiring an ultrafast, compact, robust, and energy-efficient random bit generator.

    Science, this issue p. 948; see also p. 889

  16. Molecular Biology

    Resolving R-loops for ribosomes

    1. Wei Wong

    RNA-DNA hybrid structures called R-loops formed during gene transcription can alter gene expression. Jiang et al. found that the Microprocessor complex resolved R-loops for ribosomal protein–encoding genes. Mice deficient in the Microprocessor complex component Drosha had decreased ribosomal protein abundance and protein synthesis in erythrocyte progenitor cells, as well as defects in erythropoiesis that resembled anemias caused by ribosome insufficiency or dysfunction. Nutrient deprivation induced the degradation of Drosha, which suppressed protein synthesis.

    Sci. Signal. 14, eabd2639 (2021).

  17. Natural Killer Cells

    NK cells ride the uterine cycle

    1. Ifor Williams

    Tissue-resident natural killer (NK) cells in the uterus promote successful pregnancies by regulating the depth of placental trophoblast invasion. Endometrial tissue is naturally subject to constant remodeling in response to hormonal fluctuations during the menstrual cycle, but how the changing uterine microenvironment influences the heterogeneity of uterine NK (uNK) cells is poorly understood. Strunz et al. used proteomic and transcriptomic techniques to profile human uNK cells recovered from different stages of the menstrual cycle and during pregnancy. This analysis identified sequentially expressed uNK cell surface markers that define a recurring cycle of differentiation in response to progesterone-regulated release of stromal interleukin-15. These findings pave the way for further studies on how uNK cell functions are modulated by the dynamic endometrial microenvironment.

    Sci. Immunol. 6, eabb7800 (2021).

  18. Nuclear Astrophysics

    The origin of r-process elements

    1. Keith T. Smith

    Theoretical models predict that the synthesis of heavy elements by the rapid neutron capture process (r-process) occurs in extreme astrophysical environments such as neutron star mergers or some types of supernovae. Testing those predictions by comparing them with the isotopic record has been difficult. Côté et al. examined two r-process isotopes, iodine-129 and curium-247, both of which have half-lives of 15.6 million years. Therefore, their ratio remains constant even long after the nucleosynthesis event. The ratio of those isotopes at the time of Solar System formation is recorded in meteorites. Comparing this value with nuclear astrophysics calculations shows that the most likely source was moderately neutron-rich material ejected from a binary neutron star merger.

    Science, this issue p. 945

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