This Week in Science

Science  02 Apr 2021:
Vol. 372, Issue 6537, pp. 43
  1. Marine Conservation

    An ever-growing human footprint

    1. Sacha Vignieri

    Human activities—especially fishing—are disrupting marine life, like these Steller's sea lions, at an ever-increasing scale.

    PHOTO: MIKE SCHARER/ALAMY STOCK PHOTO

    Human activities are increasingly affecting the marine environment but understanding how much and in what ways is an extreme challenge given the vastness of this system. O'Hara et al. looked at a suite of human-induced stressors on >1000 marine species over the course of 13 years. They found that species are experiencing increasing levels of stress over more than half of their ranges, with some species having an even higher proportion of their ranges affected. Fishing has the largest impact, but other stressors, such as climate change, are also important and growing.

    Science, this issue p. 84

  2. Neurogenomics

    DNA repair within neurons

    1. Laura M. Zahn

    Humans have only a limited capacity to generate new neurons. These cells thus need to repair errors in the genome. To better understand this process, Reid et al. developed Repair-seq, a method to locate DNA repair within the genome of stem cell–derived neurons. DNA repair hotspots (DRHs) were more likely to occur within specific genomic features such as gene bodies as well as in genomic formations, open chromatin, and active regulatory regions. This method showed that repair was enriched at sites involved in neuronal function and identity. Furthermore, proteomic data indicated that genes in DRHs are enriched in Alzheimer's disease and that DRHs are more active in aging. These observations link neuronal DNA repair to aging and neurodegeneration.

    Science, this issue p. 91

  3. Transcription

    Mediating transcription

    1. Di Jiang

    The Mediator complex is recruited by transcription factors to all protein-coding genes in eukaryotes and helps to assemble the machinery necessary to transcribe the gene. Abdella et al. present the cryo–electron microscopy structure of the human Mediator-bound preinitiation complex (Med-PIC). The structure shows how Mediator positions the long, flexible C-terminal domain of RNA polymerase II to be phosphorylated by the kinase CDK7, a crucial step for further processing of the RNA into a mature RNA. Most sites where transcription factors bind to Mediator are flexibly tethered to the complex, allowing the large Med-PIC to assemble at any gene.

    Science, this issue p. 52

  4. Paleoecology

    The birth of modern rainforests

    1. Andrew M. Sugden

    The origin of modern rainforests can be traced to the aftermath of the bolide impact at the end of the Cretaceous. Carvalho et al. used fossilized pollen and leaves to characterize the changes that took place in northern South American forests at this time (see the Perspective by Jacobs and Currano). They not only found changes in species composition but were also able to infer changes in forest structure. Extinctions were widespread, especially among gymnosperms. Angiosperm taxa came to dominate the forests over the 6 million years of recovery, when the flora began to resemble that of modern lowland neotropical forest. The leaf data also imply that the forest canopy evolved from relatively open to closed and layered, leading to increased vertical stratification and a greater diversity of plant growth forms.

    Science, this issue p. 63; see also p. 28

  5. Quantum Optics

    A dissipative quantum gas of light

    1. Ian S. Osborne

    Our textbook understanding of quantum systems tends to come from modeling these systems isolated from the environment. However, an emerging focus is understanding how many-body quantum systems behave when interacting with their surroundings and how they subsequently become dissipative, or non-Hermitian, systems. Öztürk et al. formed a quantum condensate of light by trapping photons in an optical cavity, a system that is naturally dissipative. By altering the trapping conditions, they demonstrated that the system provides a powerful platform with which to explore the complex dynamics and phase transitions occurring in dissipative quantum systems.

    Science, this issue p. 88

  6. Biosensors

    A simple sweat test for cystic fibrosis

    1. Caitlin Czajka

    Cystic fibrosis is often diagnosed in infants using dried blood spot testing, but this method can have poor sensitivity and a high false-positive rate. Toward the goal of developing a noninvasive, simple test for cystic fibrosis, Ray et al. devised an adhesive microfluidic device, or “sweat sticker,” to capture and analyze sweat in real time with colorimetric readout. Elevated chloride concentrations in sweat are indicative of cystic fibrosis. Benchtop testing and validation in patients with cystic fibrosis showed that smartphone imaging of sweat stickers adhered to the skin could monitor sweat chloride concentrations. Results support further testing of the sweat stickers in larger studies.

    Sci. Transl. Med. 13, eabd8109 (2021).

  7. Heart Physiology

    Blocking the nuclear option for GRK5

    1. Wei Wong

    Myocardial infarction results in pressure overload on the heart, which stimulates β-adrenergic signaling and the translocation of G protein–coupled receptor kinase 5 (GRK5) to the nucleus, where it promotes changes in gene expression that lead to hypertrophy. Coleman et al. investigated whether blocking the nuclear translocation of GRK5 could prevent the pathological signaling of this kinase. The N-terminus of GRK5 contains a sequence that is required for nuclear translocation, and mice expressing a peptide encompassing the GRK5 N-terminus developed less cardiac hypertrophy, fibrosis, and dysfunction after pressure overload.

    Sci. Signal. 14, eabb5968 (2021).

  8. Catalysis

    Isolating and stabilizing boron

    1. Phil Szuromi

    Oxidative dehydrogenation of propane can produce propene from shale gas and help to replace petroleum as a propene feedstock. Boron-based catalysts can have high selectivity to propene, but the water by-product can deactivate the catalyst by hydrolyzing boron. Zhou et al. synthesized boron-doped silicate zeolites containing isolated boron sites that were stable against hydrolysis. The catalyst could achieve one-pass propane conversions up to ∼44% with selectivities for propene and >80% for ethene. They observed no deactivation after a 210-hour continuous test.

    Science, this issue p. 76

  9. Protein Design

    Integrating form and function for design

    1. Valda Vinson

    Antibodies are broadly used in therapies and as research tools because they can be generated against a wide range of targets. Efficacy can often be increased by clustering antibodies in multivalent assemblies. Divine et al. designed antibody nanocages from two components: One is an antibody-binding homo-oligomic protein and the other is the antibody itself. Computationally designed proteins drive the assembly of antibody nanocages in a range of architectures, allowing control of the symmetry and the antibody valency. The multivalent display enhances antibody-dependent signaling, and nanocages displaying antibodies against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein effectively neutralize pseudovirus.

    Science, this issue p. eabd9994

  10. Medicine

    Bias in medical devices

    1. Gemma Alderton

    One of the many causes of inequities in health care are medical devices that underserve specific demographic groups. In a Perspective, Kadambi discusses the types of bias found in medical devices, such as physical bias from devices that are more effective on white skin and computational bias, in which diagnostic performance is trained on more men than women and thus performs better on men. There is also interpretation bias caused by “correction factors” that are applied to device readings that determine patient prioritization. Lessons learned from efforts to overcome bias in computational science could also be applied to medical devices to ensure fairness and help to prevent health inequity.

    Science, this issue p. 30

  11. Human Genomics

    Resolving genomic structural variation

    1. Laura M. Zahn

    Many human genomes have been reported using short-read technology, but it is difficult to resolve structural variants (SVs) using these data. These genomes thus lack comprehensive comparisons among individuals and populations. Ebert et al. used long-read structural variation calling across 64 human genomes representing diverse populations and developed new methods for variant discovery. This approach allowed the authors to increase the number of confirmed SVs and to describe the patterns of variation across populations. From this dataset, they identified quantitative trait loci affected by these SVs and determined how they may affect gene expression and potentially explain genome-wide association study hits. This information provides insights into patterns of normal human genetic variation and generates reference genomes that better represent the diversity of our species.

    Science, this issue p. eabf7117

  12. Animal Culture

    We are not alone

    1. Sacha Vignieri

    Before the mid-20th century, it was generally assumed that culture, behavior learned from others, was specific to humans. However, starting with identification in a few species, evidence that animals can learn and transmit behaviors has accumulated at an ever-increasing pace. Today, there is no doubt that culture is widespread among animal species, both vertebrates and invertebrates, marine and terrestrial. Whiten reviews evidence for animal culture and elaborates on the wide array of forms that such culture takes. Recognizing that other species have complex and varied culture has implications for conservation and welfare and for understanding the evolution of this essential component of animal societies, including our own.

    Science, this issue p. eabe6514

  13. Cancer

    CAR-T cells rest to get back in the race

    1. Yevgeniya Nusinovich

    Chimeric antigen receptor (CAR)–T cells, which are engineered to target specific tumor antigens, are increasingly used as an immunotherapy. CAR-T cells have shown promising results in patients, particularly in hematologic cancers, but their anticancer activity can be limited by the onset of exhaustion and the loss of effectiveness. Weber et al. characterized the phenotypic and epigenomic changes associated with CAR-T cell exhaustion caused by continuous activity and the beneficial effects of transient rest periods (see the Perspective by Mamonkin and Brenner). The authors tested different approaches for providing these rest periods, such as using the drug dasatinib to temporarily suppress T cell activity, which helped to prevent exhaustion and improved antitumor activity in mouse models.

    Science, this issue p. eaba1786; see also p. 34

  14. Neuroscience

    Brain region coordination in learning

    1. Peter Stern

    Gamma-frequency oscillations have been hypothesized as a physiological mechanism of interregional communication in the brain. However, until now, all supporting data have been correlational and thus indirect. Fernández-Ruiz et al. examined gamma-frequency activity and spike coupling between the entorhinal cortex and hippocampal dentate gyrus during learning and after selective perturbation of gamma-frequency spike timing. They observed an integrated neuron, gamma-band, and task-specific organization of the entorhinal cortex–hippocampal circuits. These data demonstrate that specific, projected gamma-frequency oscillation patterns dynamically engage functionally related cell assemblies across brain regions in a task-specific manner.

    Science, this issue p. eabf3119

  15. Neuroscience

    How to model hallucinations in mice

    1. Peter Stern

    There has not been enough progress in our understanding of the basic mechanisms underlying psychosis. Studying psychotic disorders in animal models is difficult because the diagnosis relies on self-reported symptoms that can only be assessed in humans. Schmack et al. developed a paradigm to probe and rigorously measure experimentally controlled hallucinations in rodents (see the Perspective by Matamales). Using dopamine-sensor measurements and circuit and pharmacological manipulations, they demonstrated a brain circuit link between excessive dopamine and hallucination-like experience. This could potentially be useful as a translational model of common psychotic symptoms described in various psychiatric disorders. It may also help in the development of new therapeutic approaches based on anatomically selective modulation of dopamine function.

    Science, this issue p. eabf4740; see also p. 33

  16. Mars

    Burying Mars' ancient water in the crust

    1. Keith T. Smith

    Mars once had oceans of liquid water on its surface but little of that water remains today in the planet's ice caps and atmosphere. This discrepancy is usually interpreted as loss of water to space, supported by the atmospheric deuterium/hydrogen (D/H) ratio, but this has been difficult to reconcile with other constraints. Scheller et al. propose that water could instead have been incorporated into minerals in the planet's crust, which were later buried (see the Perspective by Kurokawa). They simulated the evolution of the D/H ratio and atmospheric loss rates for a range of plausible conditions, finding that 30 to 99% of Mars' initial water was buried in the crust.

    Science, this issue p. 56; see also p. 27

  17. Interface Physics

    Engineering interface polarization

    1. Phil Szuromi

    Many properties can emerge at the interface of van der Waals materials created by rotating the layers of a single material or by creating heterointerfaces between different materials. Akamatsu et al. formed an interface that intentionally broke in-plane inversion symmetry by combining crystals of tungsten diselenide with threefold rotational symmetry and black phosphorus with twofold rotational symmetry. This interface creates in-plane electronic polarization that results in a spontaneous photovoltaic effect only along the polarization direction. This effect was explained in terms of a shift current mechanism.

    Science, this issue p. 68

  18. Topological Optics

    Nonlinear control of topology

    1. Ian S. Osborne

    Controlling the topological properties of physical systems provides a platform for developing devices and technology that are robust to defects. Xia et al. present a photonic platform in which the underlying dynamics are driven and tuned by the interplay among topology, non-Hermiticity, and nonlinearity (see the Perspective by Roztocki and Morandotti). Using photonic lattices consisting of laser-written waveguides that are continuous (“gain”) and sectioned (“loss”) and coupled to an interface defect, they demonstrate the nonlinear control of parity-time symmetry and nonlinearity-induced restoration and/or destruction of non-Hermitian topological states. Such concepts are applicable to a broad spectrum of non-Hermitian systems that have intensity-dependent gain or loss and may enable new approaches for light manipulation.

    Science, this issue p. 72; see also p. 32

  19. Materials Science

    Smart contact lens and eyelid patch

    1. Dae-Hyeong Kim

    Although chronic ocular surface inflammatory diseases are prevalent, appropriate devices to monitor the disease condition quantitatively in daily life have not yet been developed. Point-of-care devices for controlled therapy in response to biosensing are also not available. Jang et al. report wearable devices for the monitoring and treatment of ocular surface inflammation. A smart contact lens using graphene biosensors integrated with wireless communication units monitors a biomarker of ocular inflammation and sends data wirelessly to a mobile device. A transparent skin patch mounted on the eyelid provides feedback thermotherapy, which is controlled by the mobile device through wireless communication. In vivo applications to animal and human subjects confirmed the potential of this wearable health care platform.

    Sci. Adv. 10.1126/sciadv.abf7194 (2021).

  20. Immunotherapy

    CAR-T cells collaborate to fight tumors

    1. Claire Olingy

    Chimeric antigen receptor (CAR)–T cells have achieved clinical success in treating B cell malignancies. Boulch et al. used intravital microscopy to visualize in situ interactions between tumors and anti-CD19 CD4+ or CD8+ CAR T cells and single-cell transcriptomics to examine subsequent changes to the tumor microenvironment in an immunocompetent mouse model of B cell lymphoma. Although CD4+ CAR-T cells were more effective at stimulating host immune responses, CD8+ CAR-T cells excelled at direct tumor cell killing, both of which required CAR-T cell–intrinsic interferon (IFN)-γ expression. Host sensing of IFN-γ and interleukin-12 production were also required for CAR-T cell function, supporting the idea that crosstalk between CAR-T cells and the tumor microenvironment is necessary for optimal CAR-T cell efficacy against tumors.

    Sci. Immunol. 6, eabd4344 (2021).

  21. Pesticides

    A shifting burden

    1. Sacha Vignieri

    In 1962, Rachel Carson's Silent Spring was published, and the world was forced to take notice of the unintended impacts of pesticides on wildlife. Since then, there has been a perceived reduction in the amount of pesticides used and a shift in the kinds of pesticides available. Schulz et al. looked at the type, amount, and toxicity of pesticides applied over the last 25 years. They found that despite decreasing total amounts applied and decreased impacts on vertebrates, toxicity—in particular to insects and aquatic invertebrates—has increased substantially.

    Science, this issue p. 81

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