Editors' Choice

Science  21 Feb 2020:
Vol. 367, Issue 6480, pp. 865
  1. Plant Science

    Fixing the Fc of plantibodies

    1. Pamela J. Hines

    Nicotiana benthamiana plants, which are related to tobacco, are a model organism used in the production of proteins, including antibodies.

    PHOTO: SEAN GALLUP/GETTY IMAGES

    Plants offer a cost-effective means to produce therapeutically useful monoclonal antibodies. However, antibodies produced in plants differ from those produced in mammalian cells. Notably, the glycan composition of plant antibodies can affect their binding activity. Stelter et al. generated variants of a broadly neutralizing HIV monoclonal antibody in the plant Nicotiana benthamiana that differed by glycosylation. Plant-generated antibodies with typical plant glycosylation patterns were less able to engage with the cell-surface receptors required for immune activation. However, cell-binding affinity was successfully improved by targeted glycoengineering. The plant-produced antibodies were also more susceptible to oxidation of methionine residues in the Fc region. Oxidation reduced the affinity of the antibodies for the protective neonatal Fc receptor, which in turn reduced their half-life and therapeutic window. This phenomenon requires a solution before plant-produced antibodies can fulfill their therapeutic promise.

    Plant Biotechnol. J. 18, 402 (2020).

  2. Heart Disease

    Targeting the core of atherosclerosis

    1. Paula A. Kiberstis

    A fatty plaque inside a coronary artery, visualized by false-color scanning electron microscopy

    CREDIT: PROF. P.M. MOTTA, G. MACCHIARELLI, S.A. NOTTOLA/SCIENCE SOURCE

    A major villain in heart attacks and stroke is the inflamed necrotic core of atherosclerotic plaque. When the plaque ruptures, debris from this necrotic core, which largely consists of dead and dying cells, is released into the bloodstream, where it can cause blood clots and arterial blockage. Flores et al. designed and tested a nanoparticle-based therapy aimed at inducing certain immune cells to clear away the dead cells. They loaded single-walled carbon nanotubes with a drug that stimulated macrophages localized within atherosclerotic plaque to engulf and destroy dead and dying cells by a process called efferocytosis. Administration of the nanoparticles to mice predisposed to develop atherosclerosis reduced plaque burden without detectable damage to healthy tissue.

    Nat. Nanotechnol. 15, 154 (2020).

  3. Immunometabolism

    Lipid restriction enhances suppression

    1. Priscilla N. Kelly

    Regulatory T cells (Tregs) suppress immune responses to maintain tolerance and limit autoimmunity. Because lipid metabolism is crucial for the activity of Tregs, Field et al. explored the role of the lipid chaperone fatty-acid binding protein 5 (FABP5) in mouse and human Treg function. Targeting FABP5 through either genetic or pharmacological means caused mitochondrial dysfunction, which depressed oxidative phosphorylation and promoted a switch to glycolysis. FABP5 inhibition enhanced the suppressive activity of Tregs through a mechanism involving mitochondrial DNA release and subsequent cGAS-STING–dependent type I interferon signaling. The researchers found that the lipid-restrictive nature of the tumor microenvironment influenced Fabp5 gene expression and facilitated Treg suppressor function.

    Cell Metab. 31, 422 (2019).

  4. Organic Synthesis

    Advancing C–H functionalization

    1. Yury Suleymanov

    The ability to selectively functionalize C–H bonds of complex molecules is one of the longstanding challenges for the organic synthesis community. Huang et al. demonstrate a practically useful method for highly regioselective C–H functionalization of ethers by using trisaminocyclopropenium as the electrophotocatalyst in the presence of a mild electrochemical potential and visible-light irradiation. The method was successfully applied to couple ethers with alkenes, alkynes, isoquinolines, and other azoles with no need of an external oxidizing agent. The electrophotocatalytic cycle involves hydrogen atom transfer from the substrate to the photoexcited catalyst radical dication. High regioselectivities for the less-hindered a position are achieved thanks to the steric effects of the catalyst structure.

    J. Am. Chem. Soc. 142, 1698 (2020).

  5. Human Genetics

    Alternative polygenic associations

    1. Laura M. Zahn

    To predict traits and/or disease from genomic information, we must understand the genetics of the associations between genotype and phenotype. Polygenic risk scores are increasingly used to make predictions of phenotype on the basis of all the loci that correlate with a specific trait identified in genome-wide association studies (GWASs). However, population-level genetics and variable environmental effects can affect GWAS results. To determine the extent of any skewed GWAS results, Mostafavi et al. examined the accuracy of GWASs in a relatively homogeneous population: individuals of European-British descent within the UK Biobank. They found that sex, age, and socioeconomic status can affect GWAS signals. The authors suggest that using data from families within GWASs should help pull out direct and indirect effects, such as shared environmental factors and assortative mating to increase the accuracy of polygenic risk score prediction.

    eLife 9, e48376 (2020).

  6. Visa Policy

    Quotas, delays…no thanks, bye

    1. Brad Wible

    Allocating permanent residency visas on the basis of per-country quotas rather than demand for skilled workers caused delays that led many Chinese and Indian STEM Ph.Ds to give up and take their talents home instead of staying in the United States. Kahn and MacGarvie show that delays in processing EB-2 visas disproportionately affected retention in fields that have driven economic growth and in which U.S.-born talent cannot satisfy industry demand, such as electrical and computer engineering. They also show that improvements in the quality of scientific enterprise in the individuals' home countries influenced decisions to leave the United States.

    Res. Policy 10.1016/j.respol.2019.103879 (2019).

  7. 2D Materials

    Straining free-standing graphene

    1. Brent Grocholski

    Graphene is known, at least theoretically, to have a very high stiffness, which has been difficult to measure experimentally. Part of the challenge is being able to stretch and monitor a free-standing single-crystal monolayer of graphene instead of one that is supported. Cao et al. developed a new protocol for transferring, shaping, and straining graphene inside the scanning electron microscope. The authors found that free-standing graphene, even with edge defects, has mechanical properties close to the theoretical estimates and mechanical robustness attractive for many applications.

    Nat. Commun. 11, 284 (2020).

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