Editors' Choice

Science  16 Jul 2021:
Vol. 373, Issue 6552, pp. 292
  1. Physiology

    Too hot to freeze

    1. Sacha Vignieri

    A small-spotted catshark (Scyliorhinus canicular) embryo within its translucent egg case

    PHOTO: INGO ARNDT/MINDEN PICTURES

    Embryonic sharks grow within external cases that are often translucent. In response to signs of predators, the embryos of several shark species become motionless (or “freeze”). The amount of time that they can remain still is limited by their need for oxygen exchange stimulated by their movement. Ripley et al. exposed small-spotted catshark embryos to water at 15° and 20°C, and found that the time they could remain motionless was reduced by sevenfold at the higher temperature. Although the precise mechanism was not clear, the authors conclude that this was in part a result of higher metabolic requirements at higher temperatures. Thus, the ability to “freeze” at higher temperatures may be compromised, leading to higher rates of predation in warmer oceans.

    Conserv. Physiol. 9, coab045 (2021).

  2. Lipid Membranes

    Permeability depends on chirality

    1. Michael A. Funk

    In biological systems, nucleic acids, proteins, and lipids, which are the building blocks of cells, have set chirality, whereas natural secondary metabolites and synthetic drugs can have more varied stereochemistry, even when using familiar elements such as amino acids or sugars. Hu et al. investigated how varying the chirality of alkyne-labeled amino acids changed their permeability through a phospholipid bilayer in a specially designed microfluidics setup. There were considerable differences for some amino acids and dipeptides, which could be eliminated by using achiral lipids or reversed by using abiological lipids of opposite chirality.

    Nat. Chem. 10.1038/s41557-021-00708-z (2021).

  3. Cell Biology

    Keeping warm one cell at a time

    1. Stella M. Hurtley

    Adipose thermogenesis is a conserved response to environmental cold or dietary excess and is classically triggered by ligand-dependent receptor activation. Johansen et al. report that cold regulation of Gs-coupled receptor expression represents a parallel point of control. Gpr3 turns out to be the most cold-induced Gs-coupled receptor in both brown and beige thermogenic adipose tissues. GPR3 has high basal Gs-coupled activity in the absence of an exogenous ligand. Mimicking the cold induction of Gpr3 triggered cAMP production, activated the thermogenic response, and counteracted metabolic disease in mice. A disease-associated genetic variant in GPR3 in patient-derived adipocytes revealed that GPR3 also acts as a regulator of human thermogenic adipose tissue. Targeting GPR3 could thus enable therapeutic stimulation of thermogenic adipose tissue in metabolic disease.

    Cell 184, 3502 (2021).

  4. Cancer Immunology

    I'll see melanoma too

    1. Seth Thomas Scanlon

    Type 2 innate lymphoid cells (ILC2s) are known to help initiate and coordinate allergic and anthelmintic immunity. Recent studies have also pointed to the role that ILC2s play in the promotion and inhibition of various cancers. Jacquelot et al. show that in melanoma, ILC2s infiltrate tumors and control antitumor immunity. Tumor-infiltrating ILC2s produce the proinflammatory cytokine GM-CSF, which in turn enhances the recruitment, activation, and survival of anti-melanoma eosinophils. Notably, these ILC2s also express programmed cell death protein-1 (PD-1), which dampens their antitumor activity. When the authors combined anti–PD-1 immunotherapy with administration of the ILC2-activating cytokine interleukin-33 in a mouse model of melanoma, they saw better antitumor responses. ILC2 and eosinophil accumulation in tumors correlated with improved melanoma patient survival, suggesting that these cell populations have potential as cancer immunotherapy targets.

    Nat. Immunol. 22, 851 (2021).

  5. Structural Biology

    Transmembrane targets

    1. Valda Vinson

    Model for the structure of the putative SARS-CoV-2 transmembrane ion channel dimer ORF3A at 2.1 Å

    PHOTO: NAT. STRUCT. MOL. BIOL. 10.1038/S41594-021-00619-0 (2021).

    In the battle against COVID-19, attention has focused on the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein, which initiates viral entry into host cells, and on viral proteins directly involved in replication. However, other viral proteins also play a role in pathogenicity and are potential drug targets. Kern et al. focused on ORF3A, a transmembrane protein that is implicated in apoptosis and inhibition of autophagy and may form an ion channel. The authors used electron microscopy to determine the structure of a dimer at 2.1-angstrom resolution. Although a polar cavity extends from the cytoplasm into the membrane, conformational changes would be required to open a conduction pathway across the membrane. In liposomes, SARS-CoV-2 3a has a non selective cation channel activity that is blocked by polycation channel inhibitors.

    Nat. Struct. Mol. Biol. 10.1038/s41594-021-00619-0 (2021).

  6. Organic Chemistry

    Catalyst versatility

    1. Jake Yeston

    Asymmetric catalysis relies on subtle interactions that bias a reaction toward one product at the expense of its mirror image. Strassfeld et al. studied the particular influences at play in a squaramide-catalyzed ring opening of oxetanes (C–C–C–O cycles). They found that two different mechanisms were operating simultaneously, respectively co-catalyzed by Lewis and Brønsted acids. The optimal catalyst induced high selectivity in both of them, attributable through modeling to favorable cation-pi and hydrogen-bonding interactions. Results such as these can shed light more generally on the nature of privileged catalyst motifs that prove selective in multiple distinct reaction scenarios.

    J. Am. Chem. Soc. 143, 9585 (2021).

  7. Astroparticle Physics

    Supernova neutrinos reveal no secrets

    1. Keith T. Smith

    In the Standard Model of particle physics, neutrinos only interact through the weak nuclear force. Several proposed extensions to the Standard Model introduce additional ways that neutrinos could interact with each other (but not with different types of particles), and these are known as secret interactions. Shalgar et al. calculated how any secret interactions would affect core-collapse supernovae, in which an explosion is driven by a vast flux of neutrinos flowing outward from a dying star's core. If there were secret interactions, then neutrinos would become trapped in the core and no supernova would occur. The authors used this to set upper limits on neutrino physics beyond the Standard Model.

    Phys. Rev. D 103, 123008 (2021).

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