This Week in Science

Science  20 Mar 2020:
Vol. 367, Issue 6484, pp. 1336
  1. Biotechnology

    From genetics to material to behavior

    1. Steve Mao

    Artist's conception of neurons, some of which are genetically engineered to produce a membrane-associated conducting polymer

    IMAGE: ELLA MARU STUDIO AND YOON SEOK KIM/JIA LIU, DEISSEROTH/BAO LABORATORIES, STANFORD UNIVERSITY

    Introducing new genes into an organism can endow new biochemical functions or change the patterns of existing functions, but extending these manipulations to structure at the tissue level is challenging. Combining genetic engineering and polymer chemistry, Liu et al. directly leveraged complex cellular architectures of living organisms to synthesize, fabricate, and assemble bioelectronic materials (see the Perspective by Otto and Schmidt). An engineered enzyme expressed in genetically targeted neurons synthesized conductive polymers in tissues of freely moving animals. These polymers enabled modulation of membrane properties in specific neuron populations and manipulation of behavior in living animals.

    Science, this issue p. 1372; see also p. 1303

  2. Applied Physics

    Electricity from thermal sources

    1. Ian S. Osborne

    It is desirable to harvest as much energy as possible from processes that produce useful amounts of heat and convert it from waste into electrical power. Thermoelectrics and thermophotovoltaics can harness and convert heat waste but tend to operate at high temperatures. Davids et al. designed and fabricated a complementary metal-oxide semiconductor infrared photonic device that can harvest and recover energy from low-temperature thermal sources (see the Perspective by Raman). Using a new conversion mechanism, they experimentally demonstrate large thermal-to-electrical power generation in a bipolar grating-coupled tunneling device, rivaling the best thermoelectric devices. The device design could be used for energy harvesting of waste heat and the development of compact thermal batteries.

    Science, this issue p. 1341; see also p. 1301

  3. Cell Biology

    PI(4)P regulates mitochondrial fission

    1. Stella M. Hurtley

    Mitochondria are dynamic intracellular organelles, the shape and number of which are regulated by various cell-signaling pathways. Mitochondrial division is driven by the recruitment of a constricting guanosine triphosphatase protein at sites of contact with the endoplasmic reticulum, but other factors, including lysosomes, are also involved. Nagashima et al. now document an essential role for Golgi-derived vesicles bearing a specific lipid—phosphatidylinositol 4-phosphate, or PI(4)P—in the final steps of mitochondrial division. Disruption of PI(4)P production results in mitochondrial morphological defects indicative of an inability to complete fission.

    Science, this issue p. 1366

  4. Computer Vision

    Dodgeball for drones

    1. MML

    A drone dodges objects using event-based cameras and onboard processing.

    IMAGE: DAVIDE SCARAMUZZAUNIVERSITY OF ZURICH

    Uncrewed aerial vehicles, or drones, use frame-based cameras for object perception. However, these cameras have exposure times on the order of milliseconds, which limits their responsiveness. Falanga et al. instead used event cameras with reaction times of microseconds. For sense-and-avoid maneuvers, these bioinspired neuromorphic cameras are more responsive than conventional cameras because they measure changes of brightness in an image (events), thus effectively sensing motion. With the addition of event-based detection algorithms, the authors have designed a drone that can dodge multiple objects.

    Sci. Robot. 5, eaaz9712 (2020).

  5. Chemical Engineering

    Every twig and splinter used

    1. Michael A. Funk

    Plant-based production of commodity chemicals faces steep competition from fossil resources, which are often cheaper and easier to partition. Sustainable use of renewable resources requires strategies for converting complex and recalcitrant biomolecules into streams of chemicals with extraordinary efficiency. Liao et al. developed a biorefinery concept in which wood is eventually fully converted into useful chemicals: phenol, propylene, pulp amenable to ethanol production, and phenolic oligomers that can be incorporated into ink production (see the Perspective by Zhang). A life-cycle assessment and techno-economic analysis highlight the efficiency of the process and reveal the potential for such biorefinery strategies to contribute to sustainable chemicals markets.

    Science, this issue p. 1385; see also p. 1305

  6. Antibodies

    Antibody assembly in lampreys

    1. Ifor Williams

    For B lymphocytes in jawless vertebrates to produce antibodies, a combination of gene cassettes must be stitched together to create a functional antibody gene. Circumstantial evidence based on gene expression data previously implicated the cytidine deaminase CDA2 in this process. Morimoto et al. used CRISPR-Cas9–mediated mutagenesis to show that loss-of-function mutations in the CDA2 gene result in the loss of antibody gene assembly without disrupting the formation of functional genes encoding lamprey T cell receptors. These methods establish lampreys as a genetically tractable model system.

    Sci. Immunol. 5, eaba0925 (2020).

  7. Structural Biology

    Choosing a partner that fits

    1. Valda Vinson

    G protein–coupled receptors (GPCRs) are responsible for transducing diverse signals from outside to inside cells. This process requires specificity both in ligand binding to GPCRs and in coupling between GPCRs and their intracellular partners, G proteins. Qiao et al. determined the structure of the human glucagon receptor (GCGR), a type B GPCR, bound to glucagon and one of two heterotrimeric G proteins, Gs or Gi1. GCGR signals mainly through Gs, and the structures provide a basis for this specificity. Conformational changes in GCGR, relative to the inactive state, create a binding cavity for the G proteins. The pocket is opened sufficiently to accommodate a bulky binding motif in Gs. Gi1 can still bind but the pocket does not close around it, so there is a smaller interaction interface.

    Science, this issue p. 1346

  8. Geomorphology

    Erosion-vegetation interactions

    1. Brent Grocholski

    The impact of vegetation on erosion rates is hard to gauge. Although vegetation can hold soils in place mechanically, root systems can also loosen soils or even help to fracture rock. These processes can increase erosion, especially because areas of heavy vegetation tend to be in areas with high precipitation rates. Starke et al. tackled this issue using a large set of observations that span 3500 km of the Andes mountain range. They found a complex set of interactions where increasing vegetation decreases erosion in more arid regions but can accelerate erosion in vegetation dense regions.

    Science, this issue p. 1358

  9. Human Genetics

    Genomes from around the globe

    1. Laura M. Zahn

    Genomic sequencing of diverse human populations to understand overall genetic diversity has lagged behind in-depth examination of specific populations. To add to our understanding of human genetic diversity, Bergström et al. generated whole-genome sequences surveying individuals in the Human Genome Diversity Project, which is a panel of global populations that has been instrumental in understanding the history of human populations. The authors' study adds data about African, Oceanian, and Amerindian populations and indicates that diversity tends to result from differences at the single-nucleotide level rather than copy number variation. An analysis of archaic sequences in modern populations identifies ancestral genetic variation in African populations that likely predates modern humans and has been lost in most non-African populations.

    Science, this issue p. eaay5012

  10. Nutrition

    Clarifying diet studies

    1. Gemma Alderton

    The effect of foods, nutrients, and eating patterns on human health has become a source of confusion for many. In a Perspective, Hall argues that this is exacerbated by nutrition studies that do not provide food to study participants and instead rely on adherence to dietary programs. The author argues that domiciled feeding studies, in which subjects are housed and fed in specialized facilities, are an important addition to achieving dietary adherence and monitoring. Such controlled studies could allow better characterization of the mechanisms by which diet influences health.

    Science, this issue p. 1298

  11. Cortical Genetics

    Genetic determination of cortex structure

    1. Laura M. Zahn

    The human cerebral cortex is important for cognition, and it is of interest to see how genetic variants affect its structure. Grasby et al. combined genetic data with brain magnetic resonance imaging from more than 50,000 people to generate a genome-wide analysis of how human genetic variation influences human cortical surface area and thickness. From this analysis, they identified variants associated with cortical structure, some of which affect signaling and gene expression. They observed overlap between genetic loci affecting cortical structure, brain development, and neuropsychiatric disease, and the correlation between these phenotypes is of interest for further study.

    Science, this issue p. eaay6690

  12. Solar Cells

    Mapping perovskite trap states

    1. Phil Szuromi

    The high efficiency of hybrid inorganic-organic perovskite solar cells is mainly limited by defects that trap the charge carriers and lead to unproductive recombination. Ni et al. used drive-level capacitance profiling to map the spatial and energetic distribution of trap states in both polycrystalline and single-crystal perovskite solar cells. The interface trap densities were up to five orders of magnitude higher than the bulk trap densities. Deep traps were mainly located at the interface of perovskites and hole-transport layers, where processing created a high density of nanocrystals. These results should aid efforts aimed at avoiding trap-state formation or passivating such defects.

    Science, this issue p. 1352

  13. Neuroscience

    Responsible use of psychostimulants

    1. Peter Stern

    Psychostimulants have a place in the therapy of attentional disorders. However, they are also widely used off-label to enhance cognitive performance, and their mechanisms of action remain elusive. Westbrook et al. studied the effects of these drugs and concurrently measured striatal dopamine synthesis capacity in young, healthy participants (see the Perspective by Janes). They administered a placebo, methylphenidate (a dopamine and noradrenaline reuptake blocker), and sulpiride (a selective D2 receptor antagonist) while participants made explicit cost-benefit decisions about whether to engage in cognitive effort. Higher dopamine synthesis capacity in the caudate nucleus was associated with greater willingness to allocate cognitive effort. In addition, methylphenidate and sulpiride increased subjective values and motivation to work specifically for people with low dopamine synthesis capacity. Cognition-enhancing drugs may thus act at the motivational level rather than directly boosting cognition per se.

    Science, this issue p. 1362; see also p. 1300

  14. Hybridization

    Choosing mates wisely

    1. Sacha Vignieri

    Hybridization between species has long been seen as an accidental contributor to evolution in some cases and as a dead end in others. New evidence is emerging, however, that hybridization may have played important, and nonrandom, roles in adaptation. Chen and Pfennig describe just such a case where female Plains spadefoot toads preferentially choose males from another toad species, the Mexican spadefoot, as mates, but only under certain environmental conditions (see the Perspective by Zuk). The offspring of this preferred hybrid mating event have higher fitness than nonhybrids in the same environment. Thus, not only do hybrids have an advantage, but females of one species are exerting a selective influence on the other species.

    Science, this issue p. 1377; see also p. 1304

  15. Pyroptosis

    Macrophages cFLIP out

    1. Seth Thomas Scanlon

    Pathogens have evolved to survive within hosts in part by interfering with host signaling cascades. Yersinia bacteria use the effector protein YopJ to thwart MAP kinase signaling downstream of Toll-like receptor activation. In response to YopJ, host cells can release interleukin-1β and initiate pyroptosis by inhibition of the kinase TAK1 and subsequent caspase-8–directed cleavage of gasdermin D, a protein that forms cell membrane pores. Muendlein et al. report that cFLIP, a major antiapoptotic regulator, plays a central role in this process. Knockdowns of the long but not short cFLIP isoform in macrophages removes the requirement for TAK1 inhibition. Rather, deficiency of the long isoform fuels caspase-8 activation, mitochondrial complex II formation, pyroptosis, and interleukin-1β secretion in response to lipopolysaccharide alone, underscoring its importance for cell death and inflammation.

    Science, this issue p. 1379

  16. Imaging

    Ciliopathy insights

    1. Caitlin Czajka

    Primary ciliary dyskinesia (PCD) results from genetic mutations and structural defects that impair the motility of cilia, the cellular protrusions that sweep mucus along the surface of the airway. Liu et al. developed a quantitative imaging workflow to improve the diagnosis of PCD. Using superresolution microscopy on nasal airway cells isolated from patients with PCD, they detected mislocalized PCD-related proteins, cellular structural defects, and impairments in ciliary beating. These imaging and analysis methods could complement standard methods of diagnosis, such as genetic testing, and provide insight into pathology caused by variants of uncertain importance.

    Sci. Transl. Med. 12, eaay0071 (2020).

  17. Cell Biology

    Stressed into generating amyloid-β

    1. Leslie K. Ferrarelli

    The enzyme γ-secretase cleaves amyloid precursor protein (APP) to generate amyloid-β, the aggregation of which is associated with Alzheimer's disease. However, clinical use of γ-secretase inhibitors is limited by disruption of the cleavage of other substrates. Jung et al. identified the protein SERP1 as an activator of γ-secretase under metabolic stress conditions that biased its cleavage activity toward APP. SERP1 knockdown in cells or mouse hippocampus decreased amyloid-β production. Blocking SERP1 may be more selective than γ-secretase inhibitors in reducing amyloid-β plaque accumulation.

    Sci. Signal. 13, eaax8949 (2020).

  18. Neuroscience

    Sex differentiation in the human social brain

    1. Kevin S. LaBar

    Understanding divergence in social brain morphology between men and women living in different social environments is challenging because such differences are subtle and multifaceted. Kiesow et al. applied probabilistic generative modeling to ∼10,000 UK Biobank participants and found sex-specific brain volume effects linked to, among other things, frequency and intensity of social contact. Using this approach to find more generalized differences in brain anatomy, the authors conclude that sex differentiation in the social brain of this population can be measured by degree but not by kind.

    Sci. Adv. 10.1126/sciadv.aaz1170 (2020).

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