This Week in Science

Science  28 Jun 2019:
Vol. 364, Issue 6447, pp. 1247
  1. Evolutionary Biology

    Loss of genetic diversity in Atlantic cod

    1. Jeremy Jackson

    Atlantic cod in the Greenland Sea

    PHOTO: POELZER WOLFGANG/ALAMY STOCK PHOTO

    The collapse of the Northern cod population was one of the largest crashes of any marine vertebrate in the 20th century. Despite fishing bans, the species has yet to recover to historical levels. Kess et al. reconstructed these trends over the last century to illustrate how chromosomal structural diversity can mediate genetic, phenotypic, and demographic variation and how overfishing may have led to a loss of genetic diversity in Northern cod. They warn that removal of genomic diversity through overfishing may also reduce the buffering effect provided by phenotypic diversity in these populations, which increases the possibility of future collapse and alters the overall ecological function and composition of the Northwest Atlantic.

    Sci. Adv. 10.1126/sciadv.aav2461 (2019).

  2. Gene Regulation

    Variants affect gene expression over time

    1. Laura M. Zahn

    Genetic variation drives the spectrum of human phenotypes but in some cases has been linked to pathological conditions. Strober et al. set out to explore how genetic diversity regulates gene expression in cell differentiation over time. They examined expression quantitative trait loci (eQTLS)—genetic variants correlated with gene expression—in induced pluripotent stem cell lines from 19 Yoruban individuals at 16 time points during differentiation into cardiomyocytes. They identified hundreds of developmental stage–specific eQTLs. Thus, the impact of genetic variations depends on the developmental context or tissue under observation.

    Science, this issue p. 1287

  3. Topological Matter

    Majorana on a hinge

    1. Jelena Stajic

    One of the early proposals for the physical implementation of Majorana zero modes (MZMs) centered on inducing superconductivity in a topological insulator (TI) by placing it in contact with a superconductor. Jäck et al. used scanning tunneling spectroscopy to observe MZMs in a similar heterostructure. In their devices, the TI is a hexagonal bismuth island placed on top of a layer of superconducting niobium. The bismuth island had topological boundary hinge states on every other edge of the hexagon. Placing a cluster of iron atoms on the hinge generated a zero-bias peak characteristic of MZMs at the interface between the cluster and the hinge state.

    Science, this issue p. 1255

  4. Antitumor Immunity

    Dying cells resurrect tumor rejection

    1. Anand Balasubramani

    Dying cells can activate the immune system. Snyder et al. engineered cells that can be induced to undergo necroptotic cell death. They injected these cells directly into tumors and examined the ability of these dying cells to promote antitumor responses in situ and at more-distant tumors. In addition to promoting immune response in situ, the cells drove a systemic immune response that promoted regression of tumor at the distant site as well. Most impressively, the dying cells did not need to express tumor-specific antigens to promote antitumor immunity.

    Sci. Immunol. 4, eaaw2004 (2019).

  5. Neuroscience

    Brain changes after overeating

    1. Peter Stern

    A brain region called the lateral hypothalamic area is an integral node in the neurocircuitry controlling feeding behavior. In a mouse model of obesity, Rossi et al. found that a distinct class of neurons within this region acts as a brake on feeding, suppressing food intake (see the Perspective by Borgland). These neurons were potently and uniquely modified by diet-induced obesity. Thus, discrete populations of lateral hypothalamic area neurons are fundamental regulators of feeding behavior that might be targeted to treat eating disorders.

    Science, this issue p. 1271; see also p. 1233

  6. Microbiology

    Lipid droplets help anti-TB drug efficacy

    1. Stella M. Hurtley

    Correlated electron and ion microscopy shows macrophage lipid droplets and bacteria accumulating anti-tuberculosis drug (colored).

    CREDIT: DANIEL J. GREENWOOD AND HAIBO JIANG

    Improving chemotherapies against intracellular pathogens requires understanding how antibiotic distribution within infected cells affects efficacy. Greenwood et al. developed an approach to visualize antibiotics in human macrophages infected with the tubercle bacillus (see the Perspective by Smith and Aldridge). They showed that the antitubercular (anti-TB) drug bedaquiline accumulated in host lipid droplets. Lipid droplets seemed to act as an antibiotic reservoir that could be transferred to bacteria during host lipid consumption. Indeed, alterations in host lipid droplet content affected the anti-TB activity of bedaquiline against intracellular bacilli.

    Science, this issue p. 1279; see also p. 1234

  7. Materials Science

    Nacre-inspired toughened glass

    1. Marc S. Lavine

    Nacre is a biological composite that is present in seashells. This composite contains a small amount of organic material that toughens brittle ceramics, such that a highly regular three-dimensional brick-and-mortar assembly of microscopic mineral tablets is bonded together with biopolymers. Synthetic nacres have not been able to capture the large-scale sliding of the bricks that is key to enhancing toughness. Yin et al. applied this model to toughening glass, where square or hexagonal borosilicate glass sheets were bonded together using ethylene-vinyl acetate interlayers (see the Perspective by Datsiou). This generated a structure that allows glass plates to slide past each other. The resulting five-layered glass composite was deformable and impact resistant, while maintaining high stiffness, flexural strength, surface hardness, and transparency.

    Science, this issue p. 1260; see also p. 1232

  8. Quantum Fluids

    Clustering vortices

    1. Jelena Stajic

    Many-body systems generally become more disordered as more energy is pumped into them. A curious exception to this rule was predicted in the context of turbulent flow by the physical chemist Lars Onsager. He suggested that the entropy of certain two-dimensional (2D) systems can decrease with increasing energy, corresponding to an effective negative temperature. Using 2D Bose-Einstein condensates of atoms, Gauthier et al. and Johnstone et al. put Onsager's theory to the test. They provided energy to the system by perturbing the condensate, creating vortices and antivortices. With increasing energy, the system became more ordered as clusters containing either only vortices or only antivortices emerged.

    Science, this issue p. 1264, p. 1267

  9. Composites

    Hierarchical functional nanocomposites

    1. Brent Grocholski

    Composite materials are constructed from materials that vary in size. Nanoscale materials have unique properties that may be very useful for developing new types of devices. Begley et al. review synthesis and assembly methods for functional nanocomposites with a focus on potential applications. Some challenges include scaling and ensuring mechanical stability. Combining new developments from a range of disciplines will be key for enabling advanced device concepts.

    Science, this issue p. eaav4299

  10. Cancer Genomics

    APOBEC3A hairpin passenger hotspots

    1. Laura M. Zahn

    Genomic features are often examined at extremes to determine the impact of mutations. These genomic regions span from the trinucleotide context to megabases that underlie chromatin and chromosomal features. Examining mutational dynamics at the mesoscale, the intermediate span of the genome, Buisson et al. characterized the mutational dynamics of cancer (see the Perspective by Carter). They found that mutations caused by the APOBEC enzyme in DNA stem-loops, a mesoscale feature of the genome, could drive recurrent mutations. Many of these types of mutations have been identified as likely drivers of cancer. However, APOBEC-generated mutations outside of stem-loops were more likely to be cancer driver mutations, providing a genomic context for separating cancer driver from passenger mutations.

    Science, this issue p. eaaw2872; see also p. 1228

  11. Oocyte Division

    A new phase in egg biology

    1. Stella M. Hurtley

    Chromosome segregation typically requires centrosomes, which generate the microtubule spindle. However, mammalian eggs build a spindle and segregate chromosomes without centrosomes. How acentrosomal spindles are organized has remained elusive. So et al. show that centrosomal and microtubule-associated proteins are repurposed into a large “liquid-like meiotic spindle domain” (LISD) in eggs. The domains localized to spindle poles and also extended to the spindle fibers that connect to kinetochores. LISDs formed by phase separation and were required for spindle assembly, serving as reservoirs that locally sequester and mobilize spindle assembly factors within the large egg cytoplasm.

    Science, this issue p. eaat9557

  12. Ultrafast Optics

    Pulses with a twist and torque

    1. Ian S. Osborne

    Structured light beams can serve as vortex beams carrying optical angular momentum and have been used to enhance optical communications and imaging. Rego et al. generated dynamic vortex pulses by interfering two incident time-delayed vortex beams with different orbital angular momenta through the process of high harmonic generation. A controlled time delay between the pulses allowed the high harmonic extreme-ultraviolet vortex beam to exhibit a time-dependent angular momentum, called self-torque. Such dynamic vortex pulses could potentially be used to manipulate nanostructures and atoms on ultrafast time scales.

    Science, this issue p. eaaw9486

  13. Neuroscience

    Replay of activity in the human brain

    1. Peter Stern

    Electrophysiological recordings in rats and mice have shown that specific hippocampal neuronal activity patterns are sequentially reactivated during rest periods or sleep. Does the human hippocampus also replay activity sequences, even in a nonspatial task, such as, for example, decision-making? Schuck and Niv studied functional magnetic resonance imaging signals in subjects after they had learned a decision-making task. While people rested, the replay of activity patterns in the hippocampus reflected the order of previous task-state sequences. Thus, sequential hippocampal reactivation might participate in decision-making in humans.

    Science, this issue p. eaaw5181

  14. Neuroscience

    Rethinking primary visual cortex function

    1. Peter Stern

    Understanding how color is coded in the brain is central to vision research. The presently dominant model suggests that color and orientation are separately extracted in the primate primary visual cortex. These characteristics are thought to be represented by neurons located in different cortical columns that project separately to higher visual areas for further processing. Working with macaques, Garg et al. recorded from thousands of neurons using two-photon calcium imaging with single-neuron resolution. Nearly half of sampled hue-selective neurons responded more strongly to equiluminant colored stimuli than to full-contrast achromatic stimuli. A majority of strongly color-preferring neurons were also orientation selective. Processing of orientation and color is thus combined at the earliest stages of visual processing, which challenges existing models.

    Science, this issue p. 1275

  15. Structural Biology

    Positive reinforcement in a GPCR

    1. Valda Vinson

    Many drug discovery efforts focus on G protein–coupled receptors (GPCRs), a class of receptors that regulate many physiological processes. An exemplar is the β2-adrenergic receptor (β2AR), which is targeted by both blockers and agonists to treat cardiovascular and respiratory diseases. Most GPCR drugs target the primary (orthosteric) ligand binding site, but binding at allosteric sites can modulate activation. Because such allosteric sites are less conserved, they could possibly be targeted more specifically. Liu et al. report the crystal structure of β2AR bound to both an orthosteric agonist and a positive allosteric modulator that increases receptor activity. The structure suggests why the modulator compound is selective for β2AR over the closely related β1AR. Furthermore, the structure reveals that the modulator acts by enhancing orthosteric agonist binding and stabilizing the active conformation of the receptor.

    Science, this issue p. 1283

  16. Conservation

    Protecting insects around the world

    1. Julia Fahrenkamp-Uppenbrink

    Reports of plummeting insect biomass and threats to insect pollinators have prompted urgent calls for enhanced insect conservation efforts. In a Perspective, Basset and Lamarre outline some of the key steps that need to be taken to protect insect populations. Scientific knowledge needs to be enhanced by performing continuous monitoring studies to inform conservation efforts, especially in the tropics, where knowledge is very limited. Mitigating climate change, reducing pesticide use, and halting habitat loss and fragmentation will also be crucial. Last but not least, engaging the public will help to increase interest in protecting insects beyond iconic species such as bees and butterflies.

    Science, this issue p. 1230

  17. Conservation

    Toward a better world for people and nature

    1. Julia Fahrenkamp-Uppenbrink

    Over the past century, rapid growth in human populations and their resource consumption levels have put increasing pressure on the natural world. In a Perspective, Ellis explains that efforts to make the world a fairer place for both human populations and the rest of nature are already under way. To build on these efforts, human societies will need to leverage economies of scale by making cities denser and agriculture more productive. At the same time, increased conservation efforts must be implemented in such a way as to benefit people as well as the wider natural world.

    Science, this issue p. 1226

  18. Neuroscience

    Halting amyloid-induced dementia

    1. Leslie K. Ferrarelli

    In Alzheimer's disease, amyloid-β accumulation is implicated in the changes in neuronal morphology that underlie cognitive decline. Henderson et al. used a transgenic mouse model for familial Alzheimer's disease. Treating these mice with inhibitors of either the Rho-associated kinase ROCK2 or its downstream serine and threonine kinase target LIMK1 prevented the neuronal morphology alterations subsequently caused by amyloid-β accumulation. Thus, these inhibitors, which are in preclinical or clinical trials for cancer patients, may be prophylactic in individuals at high risk for developing Alzheimer's disease.

    Sci. Signal. 12, eaaw9318 (2019).

  19. Cancer

    Challenging assumptions in immunogenicity

    1. Lindsey Pujanandez

    Cancers with lower mutation rates, such as pediatric acute lymphoblastic leukemia (ALL), have not shown high immunotherapy response rates, possibly because there are fewer neoepitopes for T cells to recognize. To better understand antitumor responses, Zamora et al. examined samples from pediatric patients with ALL. They predicted peptide neoepitopes that could bind patients' human leukocyte antigen for presentation to T cells and generated tetramers. Somewhat surprisingly, almost all the predicted peptides were recognizable by patient T cells and induced functional responses in vitro. Thus, low mutation burden tumors should not be assumed to be immunogenically silent, as they could respond to checkpoint blockade or other T cell–targeted therapies.

    Sci. Transl. Med. 11, eaat8549 (2019).