This Week in Science

Science  03 Jul 2020:
Vol. 369, Issue 6499, pp. 45
  1. Malaria

    Defending the liver

    1. Anand Balasubramani

    A colored scanning microscope image of Plasmodium berghei, which is a useful model for malaria vaccine studies, infecting a mouse red blood cell

    IMAGE: SPL/SCIENCE SOURCE

    The liver is an important site of replication for Plasmodium parasites, and therefore a key goal in vaccination against malaria is to induce robust antiparasitic immunity in the liver. Using Plasmodium berghei as a model to study malaria in mice, Holz et al. developed a glycolipid-peptide conjugate vaccine that induced robust T cell responses in the liver and was able to protect mice challenged with P. berghei. Inclusion of the glycolipid adjuvant α-galactosylceramide, which activates natural killer T cells, was vital to promoting antiparasitic immunity in the liver. The authors propose that agonists that activate natural killer T cells could be useful in priming immune responses in the liver in the context of malaria and other hepatotropic diseases.

    Sci. Immunol. 5, eaaz8035 (2020).

  2. Climate Responses

    Some cope better than others

    1. Sacha Vignieri

    Increasingly, research is revealing how organisms may, or may not, adapt to a changing climate. Understanding the limitations placed by a species's physiology can help to determine whether it has an immediate potential to deal with rapid change. Many studies have looked at physiological tolerance to climate change in fishes, with results indicating a range of responses. Dahlke et al. conducted a meta-analysis to explore how life stage may influence a species's ability to tolerate temperature change (see the Perspective by Sunday). They found that embryos and breeding adult fishes are much more susceptible to temperature change than those in other life stages and that this factor must therefore be considered in evaluations of susceptibility.

    Science, this issue p. 65; see also p. 35

  3. Coronavirus

    Vaccine candidate tested in monkeys

    1. Priscilla N. Kelly

    Global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to an urgent race to develop a vaccine. Gao et al. report preclinical results of an early vaccine candidate called PiCoVacc, which protected rhesus macaque monkeys against SARS-CoV-2 infection when analyzed in short-term studies. The researchers obtained multiple SARS-CoV-2 strains from 11 hospitalized patients across the world and then chemically inactivated the harmful properties of the virus. Animals were immunized with one of two vaccine doses and then inoculated with SARS-CoV-2. Those that received the lowest dose showed signs of controlling the infection, and those receiving the highest dose appeared more protected and did not have detectable viral loads in the pharynx or lungs at 7 days after infection. The next steps will be testing for safety and efficacy in humans.

    Science, this issue p. 77

  4. Dielectrics

    Defect-enhanced energy storage

    1. Brent Grocholski

    Dielectric capacitors are vital components of electronics and power systems. The thin-film materials of which capacitors are composed are usually optimized by changing the material composition. However, Kim et al. found that postprocessing an already effective thin-film dielectric by high-energy ion bombardment further improved the material because of the introduction of specific types of defects that ultimately improved the energy storage performance. The results suggest that postprocessing may be important for developing the next generation of capacitors.

    Science, this issue p. 81

  5. Solar Cells

    Stable perovskites with ionic salts

    1. Phil Szuromi

    Ionic liquids have been shown to stabilize organic-inorganic perovskite solar cells with metal oxide carrier-transport layers, but they are incompatible with more readily processible organic analogs. Lin et al. found that an ionic solid, a piperidinium salt, enhanced the efficiency of positive-intrinsic-negative layered perovskite solar cells with organic electron and hole extraction layers. Aggressive aging testing showed that this additive retarded segregation into impurity phases and pinhole formation in the perovskite layer.

    Science, this issue p. 96

  6. HIV

    Sourcing HIV-1 infection

    1. Caroline Ash

    HIV-1 has a multitude of strain variants, but sexual transmission of HIV-1 is assumed to result from productive infection by only one virus particle. Knowing the genetics of the virus strains that are transmitted could be crucial for developing successful vaccine strategies. Using epidemiological and genetic data from 112 pairs of sexual partners, Villabona-Arenas et al. found that individuals with acute infections are more likely to transmit multiple founder virus strains. In a phylodynamic approach that integrated phylogenetic analysis of sequence data with simulation of a transmission chain, the authors showed that multiple variant transmission is doubled during the first 3 months of infection irrespective of whether transmission was heterosexual or by men who have sex with men.

    Science, this issue p. 103

  7. Organic Chemistry

    Using hydrocarbons as reagents

    1. Jake Yeston

    Adding small alkyl groups to complex molecules usually relies on alkyl halide reagents. Laudadio et al. now report a convenient method to add ethane and propane directly across conjugated olefins with no prefunctionalization or byproducts (see the Perspective by Oksdath-Mansilla). The C–H bond scission in this hydroalkylation is accomplished by a decatungstate photocatalyst that also acts as a hydrogen atom transfer agent to complete the process. The reaction, optimized under flow conditions, works with methane as well, albeit with lower efficiency.

    Science, this issue p. 92; see also p. 34

  8. Pain

    Inflammatory pain revisits development

    1. Leslie K. Ferrarelli

    An increase in N-methyl-d-aspartate (NMDA) glutamate receptors (NMDARs) containing the GluN2B subunit in sensory neuronal synapses is associated with enhanced nociception and pain. In rodents, Zhang et al. found that GluN2B content in sensory neurons was progressively restricted during early development and maintained at low abundance by the E3 ubiquitin ligase Cbl-b during adulthood. Peripheral inflammation impaired the interaction of Cbl-b with GluN2B, and the increase in GluN2B abundance enhanced NMDAR activity and neuronal sensitivity to touch.

    Sci. Signal. 13, eaaw1519 (2020).

  9. Immunology

    Research goes wild

    1. Gemma Alderton

    Like many fields of biology, immunology research often relies on the use of a limited set of animal models for discovery and biomedical research. However, accumulating examples point to the importance of diversifying immunology research to consider numerous animals and environments. In a Perspective, Flies et al. discuss the use of diverse animals to study immunology, as well as “wild” or “dirty” environments to more closely model immune development and responses. Expanding the reach of immunology studies is expected to improve conservation efforts, understanding of emerging infectious diseases, and translational biomedical research.

    Science, this issue p. 37

  10. Microbiology

    Nutritional interdependencies

    1. Caroline Ash

    Bacteria and archaea show a wide range of nutritional specialism. Not every organism can synthesize essential components and may need to trade for them. Taking as an example a diverse and interesting family of enzyme cofactors—the cobalt-containing cobamides, which include vitamin B12—Sokolovskaya et al. reviewed the interdependencies among microorganisms for this suite of nutrients. Cobamides are required for many processes, from catabolism of carbon sources to nucleotide biosynthesis, and are needed by a majority of microbes, from those in the gut to those in the oceans. Availability of cobamides is patchy and habitat specific, and nonspecific scavenging may not be adequate to obtain a specific cobamide structure required by an organism. Therefore, a variety of mutualisms have evolved to deliver and import specific structural variants of cobamides between organisms or among consortia of eukaryotes and prokaryotes by an equal variety of subtle and distinct mechanisms.

    Science, this issue p. eaba0165

  11. Cancer

    A real-time trial of a cancer blood test

    1. Paula A. Kiberstis

    Cancers diagnosed early are often more responsive to treatment. Blood tests that detect molecular markers of cancer have successfully identified individuals already known to have the disease. Lennon et al. conducted an exploratory study that more closely reflects the way in which such blood tests would be used in the future. They evaluated the feasibility and safety of incorporating a multicancer blood test into the routine clinical care of 10,000 women with no history of cancer. Over a 12-month period, the blood test detected 26 cancers of different types. A combination of the blood test and positron emission tomography–computed tomography (PET-CT) imaging led to surgical removal of nine of these cancers. Use of the blood test did not result in a large number of futile follow-up procedures.

    Science, this issue p. eabb9601

  12. Histone Function

    Enzymatic activity of histones

    1. Beverly A. Purnell

    Eukaryotic histones serve as structural elements to package DNA. However, they contain a copper-binding site for which the biological relevance is unknown. Copper homeostasis is critical for several fundamental eukaryotic processes, including mitochondrial respiration. Attar et al. hypothesized that histones may play a critical role in cellular copper utilization (see the Perspective by Rudolph and Luger). Using a multifaceted approach ranging from in vitro biochemistry to in vivo genetic and molecular analyses, they found that the histone H3-H4 tetramer is an oxidoreductase enzyme that catalyzes reduction of cupric ions, thereby providing biologically usable cuprous ions for various cellular processes. This work opens a new front for chromatin biology, with implications for eukaryotic evolution and human biology and disease.

    Science, this issue p. 59; see also p. 33

  13. Coronavirus

    Intestinal organoids as an infection model

    1. Beverly A. Purnell

    Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes an influenza-like disease with a respiratory transmission route; however, patients often present with gastrointestinal symptoms such as diarrhea, vomiting, and abdominal pain. Moreover, the virus has been detected in anal swabs, and cells in the inner-gut lining express the receptor that SARS-CoV-2 uses to gain entry to cells. Lamers et al. used human intestinal organoids, a “mini-gut” cultured in a dish, to demonstrate that SARS-CoV-2 readily replicates in an abundant cell type in the gut lining—the enterocyte—resulting in the production of large amounts of infective virus particles in the intestine. This work demonstrates that intestinal organoids can serve as a model to understand SARS-CoV-2 biology and infectivity in the gut.

    Science, this issue p. 50

  14. CRISPR Biology

    An infallible inhibitor of Cas13

    1. Stella M. Hurtley

    CRISPR-Cas13 protects bacterial populations from viral infections by indiscriminately destroying the RNA of the cell and its invader, simultaneously arresting the growth of infected hosts and the spread of the virus. This response is mediated by the Cas13 nuclease, which unleashes massive RNA degradation after recognition of viral transcripts that are complementary to its guide RNA. Meeske et al. discovered AcrVIA1, a viral-encoded inhibitor that binds to Cas13 to occlude the RNA guide and prevent the activation of the nuclease (see the Perspective by Barrangou and Sontheimer). As opposed to inhibitors of DNA-cleaving CRISPR-Cas systems, which require multiple infections to neutralize all Cas nucleases of the host, production of AcrVIA1 by a single virus is sufficient to overcome the CRISPR-Cas13 response.

    Science, this issue p. 54; see also p. 31

  15. Biofilms

    Biofilm formation from cell fountains

    1. Stella M. Hurtley

    Bacteria form three-dimensional communities called biofilms that are ubiquitous in nature and underlie human infections. Medically, biofilms are problematic because they protect resident cells from antibiotics. Although biofilms have been intensively studied, we do not understand how they develop cell by cell. Micron-sized bacteria are densely packed within biofilms, making it exceptionally challenging to track their movements. Qin et al. studied biofilm formation in the pathogen and model biofilm former Vibrio cholerae (see the Perspective by Dal Co and Brenner). The authors combined light-sheet microscopy with cell labeling to map the trajectories of a biofilm founder cell and its descendants in space and time as they built a biofilm. The findings revealed that as the bacteria reproduce, a bacterial “fountain” drives biofilm expansion and dictates the final positions of the offspring.

    Science, this issue p. 71; see also p. 30

  16. Quantum Gases

    A gas junction

    1. Jelena Stajic

    In superconductors, electrons form a macroscopic wave function that has a definite phase. If two superconductors with different wave function phases are placed in contact with each other through an insulating link, a current will flow through this so-called Josephson's junction without any external voltage. Luick et al. and Kwon et al. observed an analogous phenomenon in a setup that involved two reservoirs of superfluid Fermi gases. Both groups measured the so-called current-phase relation: the dependence of the magnitude of the current on the relative phase. By tuning an external magnetic field, they were able to study how the interactions between fermions affected the nature of the superfluid state.

    Science, this issue p. 89, p. 84

  17. Coronavirus

    Spike selection

    1. Lindsey Pujanandez

    A vaccine for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is urgently needed. Ravichandran et al. immunized rabbits with different SARS-CoV-2 spike proteins to profile the quality of induced antibody responses. Although all antigens produced neutralizing antibodies, immunization with the receptor binding domain led to the highest affinity antibodies. The authors went on to map epitopes on the spike protein recognized by the rabbit antibodies. This qualitative study could inform antigen selection for SARS-CoV-2 vaccines.

    Sci. Transl. Med. 12, eabc3539 (2020).

  18. Coronavirus

    Recombination and origin of SARS-CoV-2

    1. Trudy Morrison

    A burning question in research on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been the virus's origin and relationship to other known coronaviruses, including those that have caused past disease outbreaks. Analysis of their evolution must consider the high frequency of recombination between different coronaviruses. Li et al. performed an analysis of recombination break points across the SARS-CoV-2 genome coupled with phylogenetic and structural analysis of the sequences between the break points. They provide evidence that the receptor binding domain of the spike protein, which initiates infection, was acquired by a bat coronavirus through recombination with a pangolin coronavirus. Spike protein sequences acquired through recombination underwent subsequent purifying selection and are believed to enable enhanced viral entry into human cells, likely contributing to infection efficiency.

    Sci. Adv. 10.1126/sciadv.abb9153 (2020).

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