This Week in Science

Science  22 Jan 2021:
Vol. 371, Issue 6527, pp. 358
  1. Sexual Dimorphism

    Enhancer-gene interactions drive split

    1. Laura M. Zahn

    The wing spot on the male side of a bilateral gynandromorph Drosophila biarmipes fly is the result of a complex, sex-linked expression pattern.

    IMAGE: D. DHARMADHIKARI/N. GOMPEL ©2019

    In many species across the animal kingdom, male and female phenotypes differ. One such example is the wing spot seen in male Drosophila biarmipes flies but not the female flies. Galouzis and Prud'homme investigate the X-linked yellow gene and its enhancer. Investigating the genetics of the trait, they found evidence that the male-specific phenotype is caused by a trans interaction between the enhancer and gene that silences the gene when it is present in only one copy in the male (which only has a single X chromosome) versus the two copies found in the female. This gene thus appears to be regulated by differing genomic interactions in male and female flies and is an example of the phenomenon known as transvection.

    Science, this issue p. 396

  2. Immunometabolism

    A metabolic circuit in T cell immunity

    1. Seth Thomas Scanlon

    Naïve T cells are metabolically reprogrammed when they differentiate into T effector (Teff) cells, transitioning from a reliance on mitochondrial oxidative phosphorylation to aerobic glycolysis. Xu et al. found that lactate dehydrogenase A (LDHA), a glycolytic enzyme that converts pyruvate to lactate, is a key player in this process. Teff cells that differentiate in mice infected with the bacterium Listeria monocytogenes turned on LDHA through phosphoinositide 3-kinase (PI3K) signaling. By promoting adenosine triphosphate (ATP) production, LDHA in turn facilitated PI3K-dependent inactivation of the transcription factor Foxo1 needed for effective Teff cell responses. Thus, glycolytic ATP acts like a rheostat that both gauges and regulates PI3K-dependent signaling. This type of positive feedback circuit may also provide a mechanistic explanation for the Warburg effect observed in cancer cells.

    Science, this issue p. 405

  3. Metabolic Evolution

    Yeast switches for glucose and galactose

    1. Laura M. Zahn

    False-color transmission electron microscope image of Brewer's yeast

    IMAGE: EYE OF SCIENCE/SCIENCE SOURCE

    Some organisms can switch metabolic pathways depending on their environment. One such example is yeast, which can transition between the sugars glucose and galactose as carbon sources. Boocock et al. show that this ability has undergone selection, resulting in the maintenance of two incompatible metabolic pathways in a select set of yeast strains within a single species. A phylogenetic analysis supports that these different pathways are mediated by three genes that differ between strains within and among yeast species and likely have been maintained over 10 million to 20 million years.

    Science, this issue p. 415

  4. Cosmochemistry

    Two-part formation of the Solar System

    1. Keith T. Smith

    Measurements of meteorites have shown that the inner and outer Solar System formed from two distinct reservoirs of material. Existing models have proposed that these were split by Jupiter forming first, which would open a gap in the protoplanetary disc. Lichtenberg et al. instead argue that the snow line, the boundary between regions containing water vapor and solid ice, migrated first outward and then inward, forming two separate populations of planetesimals. Those planetesimals then grew through collisions to form the planets. Their simulation of this model explains the meteorite data and is consistent with astronomical observations of protoplanetary disks around other stars.

    Science, this issue p. 365

  5. Solar Cells

    Opening charge transport pathways

    1. Phil Szuromi

    In perovskite solar cells, the insulating nature of passivation layers needed to boost open-circuit voltage also increases the series resistance of the cell and limits the fill factor. Most improvements in power conversion efficiency have come from higher open-circuit voltage, with most fill factor improvements reported for very small-area cells. Peng et al. used a nanostructured titanium oxide electron transport layer to boost the fill factor of larger-area cells (1 square centimeter) to 0.84 by creating local regions with high conductivity.

    Science, this issue p. 390

  6. Convergent Evolution

    From offense to defense

    1. Sacha Vignieri

    Venom in snakes is largely used to subdue and/or kill prey, and most venoms have clear actions that facilitate death or paralysis. In one group of snakes, however, venom has evolved and shifted from predation to protection. Specifically, in three different lineages of “spitting” snakes, venom is used to deter predators. Kazandjian et al. show that similar adaptions have occurred within these lineages that transform cytotoxic components into a mixture that acts on mammalian sensory neurons and causes pain. The authors argue that increased predation on these lineages led to similar shifts in venom function.

    Science, this issue p. 386

  7. Cancer

    An innate response to ovarian cancer

    1. Courtney S. Malo

    Favorable outcomes for patients with epithelial ovarian cancer have been associated with infiltration of immune cells into tumors. Foord et al. investigated the contribution of a subset of immune cells, γδ T cells, to clinical outcomes in these patients. The authors demonstrate that tumor-infiltrating γδ T cells isolated from patients with ovarian cancer have distinct T cell receptors and exhibit more innate immune cell–like functions compared with blood- or ascites-derived γδ T cells. Furthermore, γδ T cell infiltration into tumors was associated with increased survival in patients with ovarian cancer. These findings suggest that promoting γδ T cell responses may be a therapeutic option for ovarian cancer.

    Sci. Transl. Med. 13, eabb0192 (2021).

  8. Animal Robots

    Resonance on the pulse

    1. Michael M. Lee

    Jellyfish and squid efficiently propel themselves through water by pulse-jetting, a cyclic process of expanding and contracting a hollow cavity in their bodies that in turn drives the intake and expulsion of fluid. Inspired by these creatures, Bujard et al. developed a squid-like robot that mimics their propulsive behavior. The flexible, self-propelled robot can achieve a swimming efficiency that is comparable to its biological counterparts by leveraging resonance to enhance its jetting propulsion.

    Sci. Robot. 6, abd2971 (2021).

  9. Coronavirus

    Antiviral responses differ with sex

    1. Gemma Alderton

    COVID-19 poses a higher risk of death to men than women, raising questions about whether there are biological factors that may explain this difference. In a Perspective, Takahashi and Iwasaki discuss how antiviral immune responses differ in men and women, particularly with age. They also discuss sex differences in immune response profiling in patients with COVID-19 and whether this might affect mortality, reinfection, and vaccine responses. These considerations may have implications for antiviral responses in people with hormone changes (such as hormone therapies and women undergoing menopause), disorders of sex development, and in transgender individuals.

    Science, this issue p. 347

  10. Neurodevelopment

    From development to disease

    1. Pamela J. Hines

    When brain development goes awry, whether in genes or cells or circuits, neurodevelopmental disorders ensue. Klingler et al. review how disrupted development leads to clinical symptoms, with a particular focus on the linkage between cortical malformations and neuropsychiatric disorders. The complexity of the developmental process may underlie the variability in symptoms.

    Science, this issue p. eaba4517

  11. Chromatin

    Cryo-EM uncovers polycomb interactions

    1. Beverly A. Purnell

    Polycomb family enzymes include the chromatin modifiers PRC1 and PRC2, which are involved in gene repression. Although the catalytic functions of these complexes are well known, their functional relationship is not. Kasinath et al. used cryo–electron microscopy (cryo-EM) to visualize the interactions between nucleosomes containing ubiquitinated histone H2A, the product of PRC1, and the PRC2-activating cofactors JARID2 and AEBP2, providing the molecular basis for PRC1-dependent recruitment of PRC2. They also show that JARID2 and AEBP2 partially overcome the inhibitory effect of PRC2 by two trimethyl lysine transcription marks on histones. This work suggests that PRC2 regulation involves an intricate interplay between PRC2 cofactors and histone posttranslational modifications.

    Science, this issue p. eabc3393

  12. Chromatin

    Cross-talk between histone modifications

    1. Beverly A. Purnell

    Histone modifications play pivotal roles within the intricate protein networks that underlie transcription and gene silencing in eukaryotic genomes. The enzymes that deposit them undergo spatiotemporal fine-tuning of their catalytic activity; one example is trans-histone cross-talk, in which one histone modification activates an enzyme responsible for another histone modification. Valencia-Sánchez et al. show that histone H4 lysine 16 acetylation (H4K16ac), a hallmark of decondensed, transcriptionally permissive chromatin, directly stimulates the Dot1 histone H3 lysine 79 methyltransferase. Structural, biochemical, and cellular data explain Dot1's regulation by H4K16ac and show how it coordinates with a second positive regulator of Dot1, histone H2B ubiquitination.

    Science, this issue p. eabc6663

  13. Single-Cell Genomics

    Cellular beauty is skin deep

    1. Laura M. Zahn

    Human skin works as barrier, preventing the entry of pathogens, among other functions. Reynolds et al. used single-cell sequencing to generate an atlas of the human skin from both developing and adult sources, identifying differences and similarities across heterogeneous populations of skin cells. In this atlas, gene expression in the two disease states studied—atopic dermatitis and psoriasis—varied from that in a healthy adult, suggesting that a fetal skin signature is expressed in adult inflamed skin. Furthermore, differences in immune cell composition between healthy fetal and adult skin and that of individuals suffering from disease were observed.

    Science, this issue p. eaba6500

  14. Ultrafast Microscopy

    Watching a phase transition unfold

    1. Jelena Stajic

    The layered material 1 T-polytype of tantalum disulfide has several intricate charge-ordered phases. How exactly one phase transitions into another is tricky to observe directly with current technologies. Danz et al. used pump-probe ultrafast dark-field electron microscopy to follow such a transition with fine spatial and temporal resolution (see the Perspective by Kogar). To achieve that goal, they shaped the electron beam used as the probe to bring out the features peculiar to the transition.

    Science, this issue p. 371; see also p. 341

  15. Surface Chemistry

    Modeling single-atom reactivity

    1. Phil Szuromi

    Noble metals often perform best for demanding reactions such as oxygen reduction, an effect often explained by the position of their d-band. One way to minimize the cost of noble metals is to disperse them as single atoms. To model the reactivity of supported single atoms, Hulva et al. evaporated different transition metals such as nickel, silver, and iridium on an Fe3O4(001) support. Single atoms adsorbed in the same twofold site between underlying rows of surface iron atoms. In studies of CO adsorption as a proxy for reactivity, the d-band was strongly affected by the charge transfer to the support and CO-induced structural changes. These effects can weaken the adsorption energy compared with the expected values based on electronic structure alone.

    Science, this issue p. 375

  16. Organic Chemistry

    Keeping Z-olefins intact with iridium

    1. Jake Yeston

    Transition metal catalysis offers a versatile means of modifying carbon centers adjacent to carbon-carbon double bonds. However, in the course of these reactions, the double bond tends to get weakened, allowing its substituents to swivel back and forth. Thus, if two large groups start out on the same side of the bond axis (a geometry known as a Z-olefin), they end up on opposite sides in the product. Jiang et al. report a chiral iridium catalyst that prevents this swiveling just long enough to substitute the adjacent carbon enantioselectively (see the Perspective by Malcolmson).

    Science, this issue p. 380; see also p. 345

  17. Host Defense

    Salmonella profits from immunometabolism

    1. Seth Thomas Scanlon

    Extensive metabolic rewiring occurs in various immune cells during the course of infection. Whether these changes can be exploited by intracellular pathogens remains an open question. Rosenberg et al. report that infection with Salmonella enterica serovar Typhimurium (S. Tm) induces the accumulation of the metabolite succinate in macrophages (see the Perspective by Lynch and Lesser). This key intermediate in the citric acid cycle activates virulence genes in S. Tm, leading to microbial resistance. Moreover, the active transport of succinate through the C4-dicarboxylate transporter DcuB is required for S. Tm virulence and survival within macrophages. Sensing of citric acid cycle intermediates may more generally serve as a cue to initiate the resistance programs of intracellular pathogens.

    Science, this issue p. 400; see also p. 344

  18. Mosquito Biology

    Cuticular pheromone circadian regulation

    1. Caroline Ash

    Several species of anopheline mosquitoes are important malaria vectors in Africa. Male mosquitoes show species-specific swarming behaviors at certain times of the day to attract females for mating. Wang et al. found that transcriptional patterns of metabolic and immune function genes apparently showed a diurnal rhythm that correlated with the physiological demands of mating flight swarming (see the Perspective by Manoukis). By altering temperature and light regimes and by knocking out the master genes period and timeless for circadian clock regulation, the authors disrupted mating flight behavior in a combination of cage experiments and enclosed field conditions. Knocking out the rhythmically expressed desaturase enzyme reduced cuticular hydrocarbon pheromone production and limited mating success. These key interacting components of the diurnal regulation of mosquito mating behavior are potential targets for alternative malaria control strategies.

    Science, this issue p. 411; see also p. 340

  19. Developmental Biology

    Deubiquitylation errors cause disease

    1. Neal Sondheimer

    Many proteins require reversible modification of ubiquitylation for normal function, and failure of deubiquitylation can cause disease. Beck et al. identified a defect in the X-linked OTUD5 gene and assembled a cohort of male patients with similar phenotype, all with missense variants in OTUD5. Through an analysis of patient tissues and animal models, they identified a common defect in deubiquitylation and demonstrated that this error impaired neuroectodermal differentiation, a disorder they named LINKED syndrome (linkage-specific-deubiquitinylation-deficiency-induced embryonic defects). This work demonstrates the critical importance of linkage-specific ubiquitin cleavage to the chromatin remodeling process and development.

    Sci. Adv. 10.1126/sciadv.abe2116 (2021).

  20. Immunotherapy

    PD-1 blockade carries perils

    1. Ifor Williams

    The potentiation of T cell–mediated antitumor responses achieved in multiple types of cancer through inhibition of the programmed death-1 (PD-1) checkpoint pathway has led to suggestions that anti–PD-1 therapy might also boost T cell immunity in chronic infections, including tuberculosis. Kauffman et al. examined the effect of anti–PD-1 antibody treatment on the clinical course of Mycobacterium tuberculosis (Mtb) infection in rhesus macaques. CD8 T cell responses were boosted in monkeys receiving anti–PD-1 infusions, but the stronger CD8 T cell responses were coupled with increases in proinflammatory cytokines, impaired CD4 T cell function, and higher bacterial loads in lung granulomas. These findings in a nonhuman primate model signal that anti–PD-1–based therapy needs to be used cautiously in cancer patients with a history of Mtb exposure.

    Sci. Immunol. 6, eabf3861 (2021).

  21. Physiology

    A shared Toll for innate immunity

    1. Leslie K. Ferrarelli

    Toll-like receptor 2 (TLR2) is found in various tissues, but it is best known for activating immune cells in response to infection or injury. Using a mouse model, McCoy et al. found that TLR2 also mediated innate immune signaling by the endothelium (see the Focus by Mahfoud and Petrova). TLR2 in endothelial cells activated proinflammatory signaling that promoted angiogenesis and immune cell recruitment in response to various “danger” signals, such as those produced during infection or tissue damage. Endothelial TLR2 also supported tumor growth in a mouse model of prostate cancer.

    Sci. Signal. 14, eabc5371, eabf4701 (2021).

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