This Week in Science

Science  01 Nov 2019:
Vol. 366, Issue 6465, pp. 583
  1. Immune Regulation

    Pharmacological retraining for T cells

    1. Ifor Williams

    A T regulatory cell (red) and an antigen-presenting cell (blue), as seen by scanning electron microscopy


    Regulatory T cells (Tregs) expressing the Foxp3 transcription factor play a critical role in dampening overactive immune responses, including autoimmune diseases. Akamatsu et al. screened a library of small molecules and identified a compound that promotes Treg differentiation by inhibiting the cyclin-dependent kinases CDK8 and CDK19. The Treg-promoting activity of the CDK8/19 inhibitor reduced disease activity in mouse models of autoimmune diabetes and encephalomyelitis. CDK8/19 inhibitors are thus a new class of immunomodulatory drugs capable of generating Tregs with potential clinical applications in promoting tolerance and reducing autoimmunity.

    Sci. Immunol. 4, eaaw2707 (2019).

  2. Viral Immunology

    The toll of measles on the immune system

    1. Paula A. Kiberstis

    Many of the deaths attributable to measles virus are caused by secondary infections because the virus infects and functionally impairs immune cells. Whether measles infection causes long-term damage to immune memory has been unclear. This question has become increasingly important given the resurgence in measles epidemics worldwide. Using a blood test called VirScan, Mina et al. comprehensively analyzed the antibody repertoire in children before and after natural infection with measles virus as well as in children before and after measles vaccination. They found that measles infection can greatly diminish previously acquired immune memory, potentially leaving individuals at risk for infection by other pathogens. These adverse effects on the immune system were not seen in vaccinated children.

    Science, this issue p. 599

  3. Cell Biology

    Order in the cytoplasm

    1. L. Bryan Ray

    Extracts of the very large eggs of the African clawed frog, Xenopus laevis, have proven a valuable model system for the study of cell division. Cheng and Ferrell found that after homogenization, such cytoplasm can reorganize back into cell-like structures and undergo multiple rounds of division (see the Perspective by Mitchison and Field). This reorganization apparently occurs without the usual factors that are known to lead to such structural changes during cell division, such as F-actin, myosin II, various individual kinesins, aurora kinase A, or DNA. What is required is energy from adenosine triphosphate, microtubule polymerization, cytoplasmic dynein activity, and a specific kinase-involved cell cycle progression. Nongenetic information in the cytoplasm is apparently sufficient for basic spatial organization of the cell.

    Science, this issue p. 631; see also p. 569

  4. Structural Virology

    Unveiling African swine fever virus

    1. Valda Vinson

    African swine fever virus (ASFV) is highly contagious and often lethal. With no vaccine or effective treatment, infections often require large-scale culling of pigs. Wang et al. apply cutting-edge cryo–electron microscopy techniques to determine the structure of this very large DNA virus. An 8.8-angstrom-resolution reconstruction shows the five layers of the virus, and the fourth capsid layer could be reconstructed at 4.8-angstrom resolution. The structure reveals epitopes in the major capsid protein that distinguish ASFV from other nucleocytoplasmic large DNA viruses and shows how the minor capsid proteins stabilize the capsid.

    Science, this issue p. 640

  5. Isotopic Separation

    Quantum sieves for hydrogen isotopes

    1. Phil Szuromi

    One method for improving the efficiency of separation of hydrogen from deuterium (D) is to exploit kinetic quantum sieving with nanoporous solids. This method requires ultrafine pore apertures (around 3 angstroms), which usually leads to low pore volumes and low D2 adsorption capacities. Liu et al. used organic synthesis to tune the pore size of the internal cavities of organic cage molecules. A hybrid cocrystal contained both a small-pore cage that imparted high selectivity and a larger-pore cage that enabled high D2 uptake.

    Science, this issue p. 613

  6. Anthropology

    Symbolic behavior in Neanderthals

    1. Aaron Clauset

    Bones from an eagle talon with parallel cut marks


    A new discovery provides rare evidence of symbolic behavior in Neanderthal communities and extends the record further geographically and temporally across Europe. Rodríguez-Hidalgo et al. analyzed recently unearthed Spanish imperial eagle phalanges, which were found along the Iberian Peninsula, and inferred that Neanderthal communities used these talons for symbolic purposes. Neanderthals most likely cut the eagle phalanges to extract the talon, presumably for use as pendants. These findings address questions around the recurrent appearance of large raptor talons throughout the Middle Paleolithic time frame.

    Sci. Adv. 10.1126/sciadv.aax1984 (2019).

  7. Black Holes

    A black hole hiding in a binary star

    1. Keith T. Smith

    As material falls toward a black hole, it heats up and emits x-rays. Almost all black holes are discovered by this x-ray emission. Thompson et al. observed light from a giant star that is Doppler shifted, indicating an orbit around a binary companion. The companion object must weigh more than 2.6 solar masses, but it emits no light, including x-rays. This indicates the presence of a black hole that is not currently consuming any material. There may be a population of similarly hidden black holes that have been missed by x-ray observations.

    Science, this issue p. 637

  8. Batteries

    Controlling electrode growth

    1. Marc S. Lavine

    Batteries with metal anodes can grow dendrites during cycling, which can cause short circuits in a battery or subsequently reduce the charge capacity. Zheng et al. developed a process to electrodeposit zinc on a graphene-coated stainless-steel electrode, such that the zinc forms plates with preferential orientation parallel to the electrode. This is achieved by depositing a graphene layer on stainless steel designed to epitaxially match the basal (002) plane of metallic zinc, minimizing lattice strain. During cycling, the zinc will redeposit in plate form rather than as a dendrite such that the batteries show excellent reversibility over thousands of cycles.

    Science, this issue p. 645

  9. Medicine

    Cryptic signs of aging in our blood

    1. Paula A. Kiberstis

    Time is not a friend to our DNA. Aging is associated with an accumulation of somatic mutations in normal dividing cells, including the hematopoietic stem cells (HSCs) that give rise to all blood cells. Certain mutations in HSCs confer a fitness advantage that results in clonal expansions of mutant blood cells that sometimes—but not always—forecast the development of cancer and other age-related diseases. Jaiswal and Ebert review this process of “clonal hematopoiesis,” including the mechanisms by which it arises and the current state of knowledge regarding its effects on human health.

    Science, this issue p. eaan4673

  10. Microbiology

    Animal sociability through microbes

    1. Gemma Alderton

    Accumulating evidence suggests that the microbiota living in and on animals has important functions in the social architecture of those animals. Sherwin et al. review how the microbiota might facilitate neurodevelopment, help program social behaviors, and facilitate communication in various animal species, including humans. Understanding the complex relationship between microbiota and animal sociability may also identify avenues for treating social disorders in humans.

    Science, this issue p. eaar2016

  11. Combustion Physics

    Achieving unconfined supersonic explosions

    1. Keith T. Smith

    In some forms of supernovae and chemical explosions, a flame moving at subsonic speeds (deflagration) spontaneously evolves into one driven by a supersonic shock (detonation), vastly increasing the power output. The mechanism of this deflagration-to-detonation transition (DDT) is poorly understood. Poludnenko et al. developed an analytical model to describe DDTs, then tested it with lab experiments and numerical simulations. Their model successfully reproduced the DDT seen in the experiments and predicted a DDT in type Ia supernovae, which is consistent with observational constraints. The same mechanism may apply to DDTs in any unconfined explosion.

    Science, this issue p. eaau7365

  12. Butterfly Genomics

    Following gene flow in butterfly genomes

    1. Laura M. Zahn

    The role of hybridization in evolution and species radiations has long been debated. In Heliconius butterflies, introgression was a major factor in their radiation, and the genetic variation it imparted into species is variable across the genome. Edelman et al. developed a new sequencing strategy and produced 20 Heliconius genomes (see the Perspective by Rieseberg). They also developed a means by which to identify genetic variation that originates from incomplete lineage sorting versus hybridization. Applying this model to their newly developed genomes, they investigated the evolutionary history of the genus and, in particular, the impact of introgression.

    Science, this issue p. 594; see also p. 570

  13. Radical Enzymes

    Itaconate brings metalloenzyme to a halt

    1. Michael A. Funk

    Controlled radicals enable unusual enzymatic transformations, but radical generation and management require dedicated systems. Ruetz et al. investigated how the immunometabolite itaconate might undermine these intricate systems to inhibit propionate metabolism, a crucial metabolic pathway in pathogenic Mycobacterium tuberculosis (Mtb) (see the Perspective by Boal). They found that the coenzyme A (CoA) derivative of itaconate can irreversibly inhibit the enzyme methylmalonyl-CoA mutase (MCM), which uses the radical-generating cofactor adenosylcobalamin, or coenzyme B12. Itaconyl-CoA derails the normal radical reaction catalyzed by MCM, forming a long-lived, biradical species, which is incapable of completing the catalytic cycle and cannot be recycled by the endogenous coenzyme B12 regeneration machinery. Itaconate blocks Mtb growth on propionate, and this inhibition mechanism may be relevant to how macrophages resist Mtb infection.

    Science, this issue p. 589; see also p. 574

  14. Plant Microbiota

    Protecting plants from the inside out

    1. Caroline Ash

    Some soils show a remarkable ability to suppress disease caused by plant pathogens, an ability that is attributed to plant-associated microbiota. Carrión et al. investigated the role of endophytes, the intimate microbial community found within roots, in fungal disease suppression (see the Perspective by Tringe). The wilt fungus Rhizoctonia solani infects sugar beets, whereupon transcriptional analysis shows that several bacterial endophyte species activate biosynthetic gene clusters to cause disease suppression. These organisms produce antifungal effectors, including enzymes that can digest fungal cell walls, and secondary metabolites, including phenazines, polyketides, and siderophores, which may contribute to the antifungal phenotype.

    Science, this issue p. 606; see also p. 568

  15. Neuroscience

    Fluid dynamics during sleep

    1. Peter Stern

    During non–rapid eye movement sleep, low-frequency oscillations in neural activity support memory consolidation and neuronal computation. Sleep is also associated with increased interstitial fluid volume and clearance of metabolic waste products. It is unknown why these processes co-occur and how they are related. Fultz et al. simultaneously measured electrophysiological, hemodynamic, and flow signals in the human brain (see the Perspective by Grubb and Lauritzen). Large oscillations of fluid inflow to the brain appeared during sleep and were tightly coupled to functional magnetic resonance imaging signals and entrained to electroencephalogram slow waves. Slow oscillatory neuronal activity thus leads to oscillations in blood volume, drawing cerebrospinal fluid into and out of the brain.

    Science, this issue p. 628; see also p. 572

  16. Neonicotinoids

    Cascading effects of pesticide use

    1. Sacha Vignieri

    It is now well known that neonicotinoids negatively affect pollinators. As research has expanded, it has become clear that these globally used insecticides directly affect other ecosystem components, including vertebrates. Yamamuro et al. now show that these compounds are indirectly affecting species through trophic cascades (see the Perspective by Jensen). Since the application of neonicotinoids to agricultural fields began in the 1990s, zooplankton biomass has plummeted in a Japanese lake surrounded by these fields. This decline has led to shifts in food web structure and a collapse of two commercially harvested freshwater fish species. The authors argue that such dynamics are likely occurring widely.

    Science, this issue p. 620; see also p. 566

  17. Surface Magnetism

    Single molecules sense spin

    1. Phil Szuromi

    Imaging surface magnetism, and, in particular, spin excitations of adsorbed molecules or films, is challenging. Verlhac et al. demonstrate spin-sensing capability by using the magnetic exchange interaction between a surface sample and the spin-excited states of a nickelocene molecule attached to a scanning tunneling microscope tip. The spatial dependence of the exchange field at the atomic scale enabled imaging of magnetic corrugation with atomic-scale lateral resolution for iron atoms and small islands of cobalt atoms absorbed on nonmagnetic copper surfaces.

    Science, this issue p. 623

  18. Regenerative Medicine

    Secreting healing factors

    1. Mattia Maroso

    One of the main complications associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs) is the development of gastric ulcers. Proton-pump inhibitors are used to alleviate this condition; however, they are also associated with serious adverse events. Xia et al. developed a porcine model of NSAID-induced gastric ulcers and showed that intragastric administration of adipose tissue–derived mesenchymal stem cells rapidly promoted healing and reduced gastric inflammation. The therapeutic effect was mediated by activation of signaling pathways in ulcer tissue induced by stem cell–secreted factors. Mesenchymal stem cells or their secretome could be useful in treating NSAID-induced gastric ulcers.

    Sci. Transl. Med. 11, eaat7455 (2019).

  19. Fibrosis

    Protecting against liver fibrosis

    1. Annalisa M. VanHook

    Chronic liver disease stimulates hepatic stellate cells and ultimately leads to fibrosis. Sundaram et al. found that mice lacking the pseudoprotease iRhom2, which activates the metalloprotease ADAM17, showed increased stellate cell activation and susceptibility to liver fibrosis induced by bile duct ligation (see the Focus by Badenes and Adrain). iRhom2-activated ADAM17 promoted the shedding of tumor necrosis factor (TNF) receptors from stellate cells. Treating iRhom2-deficient mice with the TNF-α inhibitor etanercept reduced liver fibrosis induced by bile duct ligation.

    Sci. Signal. 12, eaax1194, eaaz0444 (2019).

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