This Week in Science

Science  04 May 2018:
Vol. 360, Issue 6388, pp. 503
  1. Malaria

    Saturating malaria mutagenesis

    1. Caroline Ash

    Red blood cells infected by malaria parasites

    CREDIT: LONDON SCHOOL OF HYGIENE & TROPICAL MEDICINE/SCIENCE SOURCE

    Malaria is caused by eukaryotic Plasmodium spp. parasites that classically infect red blood cells. These are difficult organisms to investigate genetically because of their AT-rich genomes. Zhang et al. have exploited this peculiarity by using piggyBac transposon insertion sites to achieve saturation-level mutagenesis for identifying and ranking essential genes and drug targets (see the Perspective by White and Rathod). Genes that are current candidates for drug targets were identified as essential, in contrast to many vaccine target genes. Notably, the proteasome degradation pathway was confirmed as a target for developing therapeutic interventions because of the several essential genes involved and the link to the mechanism of action of the current frontline drug, artemisinin.

    Science, this issue p. eaap7847; see also p. 490

  2. Nanomaterials

    Retrosynthesizing complex nanostructures

    1. Phil Szuromi

    The solution synthesis of complex and asymmetric nanostructures is still challenging. For many applications, it will be important to gain simultaneous control over particle size and morphology, constituent materials, and internal interfaces. Fenton et al. have developed a strategy that mimics chemical retrosynthesis, starting with simple nanoparticle synthons—in this case, Cu1.8S nanoparticles, nanorods, and nanosheets. Various types of interfaces and junctions can be introduced, for example, by cation substitution. This intervention breaks the symmetry of the synthons and assembles them into higher-order structures. The nanostructures can thus be formed with asymmetric, patchy, porous, or sculpted regions.

    Science, this issue p. 513

  3. Membranes

    Turing structures at the nanoscale

    1. Marc S. Lavine

    Turing structures arise when imbalances in diffusion rates make a stable steady-state system sensitive to small heterogeneous perturbations. For example, Turing patterns occur in chemical reactions when a fast-moving inhibitor controls the motion of a slower-moving activator. Tan et al. grew polyamide membranes by using interfacial polymerization, where the reactions occur at the interface between oil and water layers. The addition of polyvinyl alcohol to the aqueous phase reduced the diffusion of the monomer. This process generates membranes with more bumps, voids, and islands, which prove to be better for water desalination.

    Science, this issue p. 518

  4. SIV

    Emptying the reservoir

    1. Orla M. Smith

    Antiretroviral therapy can halt HIV-1 replication but cannot clear the hidden reservoirs of latent virus. Lim et al. treated simian immunodeficiency virus (SIV)–infected rhesus macaques on antiretroviral therapy with up to 19 doses of the Toll-like receptor 7 agonists GS-986 or GS-9620. By the third dose, all macaques experienced transient SIV plasma viremia within 48 hours. Dosing was also associated with activation of lymphocytes and reductions in SIV DNA in cells from the peripheral blood, lymph nodes, and gastrointestinal tract. When antiretroviral therapy ceased, two of nine treated macaques did not suffer rebound of virus and remained apparently virus-free and disease-free for more than 2 years.

    Sci. Transl. Med. 10, eaao4521 (2018).

  5. Paleogenomics

    Relationships among North Africans

    1. Laura M. Zahn

    The general view is that Eurasians mostly descend from a single group of humans that dispersed outside of sub-Saharan Africa around 50,000 to 100,000 years ago. Present-day North Africans share a majority of their ancestry with present-day Near Easterners, but not with sub-Saharan Africans. To investigate this conundrum, Van de Loosdrecht et al. sequenced high-quality DNA obtained from bone samples of seven individuals from Taforalt in eastern Morocco dating from the Later Stone Age, about 15,000 years ago. The Taforalt individuals were found to be most closely related to populations from the Near East (Natufians), with a third of their ancestry from sub-Saharan Africa. No evidence was found for introgression with western Europeans, despite attribution to the Iberomaurusian culture. None of the present-day or ancient Holocene African groups are a good proxy for the sub-Saharan genetic component.

    Science, this issue p. 548

  6. Immunology

    PTEN prevents the cytokine storm

    1. John F. Foley

    An uncontrolled infection leads to sepsis, in which excessive production of proinflammatory cytokines, or a “cytokine storm,” can cause potentially fatal tissue damage and organ failure. Sisti et al. found that septic mice had increased expression of the mRNA encoding the lipid and protein phosphatase PTEN. Mice lacking PTEN in myeloid cells showed greater inflammation, tissue injury, and mortality from sepsis. PTEN activity in the nucleus of macrophages induced the production of microRNAs that targeted Myd88 mRNA, which encodes an adaptor protein required for cytokine production.

    Sci. Signal. 11, eaai9085 (2018).

  7. Systems Biology

    How to build a better morphogen gradient

    1. L. Bryan Ray

    To translate insights in developmental biology into medical applications, techniques are needed to ensure correct cell localization. Morphogen gradients allow precise and highly reproducible pattern formation during development. Through in vitro experiments and modeling, Li et al. tested the effects of unusual properties of Hedgehog (HH) signaling. The HH morphogen's receptor, Patched (PTCH), sends an inhibitory signal when no ligand is bound, which is relieved by ligand binding. PTCH also regulates spatial distribution of the signal by sequestering the HH ligand. Furthermore, signaling through the receptor promotes synthesis of more inhibitory receptor. These characteristics help speed gradient formation and explain the robustness of the system to changes in the rate of morphogen production.

    Science, this issue p. 543

  8. Plant Science

    Multiple, diverse, and complex

    1. Pamela J. Hines

    Calcium currents characterize the developing pollen tube in the small mustard plant Arabidopsis and correlate with growth at the tip of the pollen tube. This system constitutes a practical model for screening for Ca2+-signaling mechanisms in plants. Wudick et al. analyzed multiple variants of glutamate receptor–like (GLR) channels and discovered that some work alone and others work in pairs or trios. Subcellular localization of GLRs is a complex response to CORNICHON sorting proteins, which leave some GLRs at the plasma membrane and ferry others to internal calcium reservoirs. The calcium current at the tip of the growing pollen tube apparently integrates multiple intracellular currents.

    Science, this issue p. 533

  9. Structural Biology

    How calcium gates a potassium channel

    1. Valda Vinson

    Small-conductance Ca2+-activated K+ (SK) channels are expressed throughout the nervous system and affect both the intrinsic excitability of neurons and synaptic transmission. An increase in the concentration of intracellular calcium opens the channels to conduct potassium across the cell membrane. Lee and MacKinnon report cryo–electron microscopy structures of human SK4-calmodulin channel complexes. Activation occurs when calcium binds to calmodulin, a protein with two lobes, known as C and N, separated by a flexible region. Each monomer in the channel tetramer binds constitutively to the C-lobe of calmodulin. The N-lobe of calmodulin is reasonably unconstrained until it binds calcium. With calcium bound, it then binds to the channel and induces conformational changes that open the pore.

    Science, this issue p. 508

  10. Metallurgy

    Smaller but more thermally stable

    1. Brent Grocholski

    Synthesizing metals with extremely small (nanoscale) grain sizes makes for much stronger materials. However, very small–grained materials start to coarsen at relatively low temperatures, wiping out their most desirable properties. Zhou et al. discovered a way to avoid this problem by mechanically grinding copper and nickel at liquid nitrogen temperatures. The processing method creates low-angle grain boundaries between the nanograins, which promotes thermal stability.

    Science, this issue p. 526

  11. Neuroscience

    Loss of touch receptors leads to itch

    1. Peter Stern

    Itch in response to light touch of the skin is an aging-associated problem. This phenomenon is called alloknesis and can become a major medical condition associated with dry skin. Feng et al. discovered that loss or dysfunction of Merkel cells causes scratching in mice (see the Perspective by Lewis and Grandl). Reduction of Merkel cell numbers results in reduced firing patterns and frequencies and changes the activation thresholds of slowly adapting afferent nerve fibers. Like hair cells, Merkel cells are lost with age. A painful scratch will temporarily alleviate itch because it induces enough activity through the remaining Merkel cells.

    Science, this issue p. 530; see also p. 492

  12. Neuroscience

    Setting conscious perception alight

    1. Peter Stern

    What are the neuronal mechanisms that enable conscious perception? Why do some images remain subliminal? Van Vugt et al. trained monkeys to detect low-contrast images and compared neuronal activity in brain areas V1, V4, and the dorsolateral prefrontal cortex. Some stimuli made it into consciousness, and others were subliminal depending on their propagation, which can be variable for weak stimuli (see the Perspective by Mashour). Strongly propagated stimuli initiated a state in the higher brain areas called “ignition” that caused information about a brief stimulus to become sustained and broadcasted back through recurrent interactions between many brain areas.

    Science, this issue p. 537; see also p. 493

  13. Immunology

    Complement is a CD8+ T cell metabolic rheostat

    1. Seth Thomas Scanlon

    Systemic lupus erythematosus (SLE) is associated with deficiencies in the complement protein C1q. Although C1q plays a role in the clearance of apoptotic cells, there are several redundant clearance pathways. Disruption of one pathway does not lead to an autoimmune defect. In a chronic graft-versus-host disease model of SLE, Ling et al. show that C1q dampens CD8+ T cell responses to self-antigens. C1q modulates metabolism through the mitochondrial cell-surface protein p32/gC1qR. The lack of C1q during a viral infection also enhances CD8+ T cell responses. Thus, C1q plays a role as a “metabolic rheostat” for effector CD8+ T cells.

    Science, this issue p. 558

  14. Biodiversity

    Financing biodiversity conservation

    1. Julia Fahrenkamp-Uppenbrink

    Global funds for protecting biodiversity are too low to prevent wildlife populations from falling and species extinctions from increasing. In a Perspective, Barbier et al. call for a global agreement for biodiversity modeled on the Paris Climate Agreement, with national targets, policies, and timelines. The overall goal is ambitious: to conserve at least 50% of terrestrial, inland water, coastal, and marine habitats by 2050. Formal involvement of the private sector, particularly in areas such as seafood, forestry, agriculture, and insurance, will be crucial to raise the necessary funds.

    Science, this issue p. 486

  15. Immunogenomics

    Establishing NK cell identity

    1. Ifor Williams

    The transcription factor ID2 is required for normal differentiation of all innate lymphoid cells. ID2 supports full maturation of natural killer (NK) cells into cytotoxic effectors. To investigate the transcriptional programming steps that underpin NK cell differentiation, Zook et al. characterized ID2-deficient NK cells. ID2 limited chromatin accessibility at multiple lymphocyte-associated genes to enable an effector-gene program to take hold.

    Sci. Immunol. 3, eaao2139 (2018).

  16. Surface Chemistry

    Direct plasmon chemistry

    1. Phil Szuromi

    Light can excite plasmons at a metal surface, which can then decay and create hot electrons that induce chemical reactions of adsorbed molecules. Kazuma et al. used a scanning tunneling microscope (STM) to induce and map out the surface dissociation of a dimethyl disulfide molecule on silver and copper surfaces. A silver STM tip created localized plasmons at different distances from the molecule. The plasmons drove the reaction directly by exciting the valence electrons of the molecule into unoccupied states and cleaving the sulfur-sulfur bond.

    Science, this issue p. 521

  17. Biomaterials

    Curving bones

    1. Marc S. Lavine

    On larger length scales, bone is known to have a hierarchical structure in which small crystals of calcium phosphates arrange themselves around helices of collagen. These make up larger structures, such as the osteons found in compact bone. However, at smaller lengths, does the hierarchical structure persist? By combining three-dimensional electron tomography with two-dimensional electron microscopy, Reznikov et al. observed structural ordering from the nanoscale upward. At the smallest scale, needle-shaped mineral units form platelets that organize into stacks bridging multiple collagen units.

    Science, this issue p. eaao2189

  18. Structural Biology

    Staying attached through division

    1. Valda Vinson

    When a cell prepares to divide, it copies its DNA into pairs of each chromosome, called chromatids. Microtubules attach to the chromosome pairs through protein complexes called kinetochores. During cell division, microtubule depolymerization pulls the chromatids apart. Jenni and Harrison describe the structure of an essential component of the yeast kinetochore, the DASH/Dam1c complex, that forms a ring around a microtubule. The structure shows how the DASH/Dam1c ring interacts with the microtubule and kinetochore components so that the kinetochore can track to the end of the microtubule through cycles of growth and shrinkage.

    Science, this issue p. 552