This Week in Science

Science  01 Jan 2021:
Vol. 371, Issue 6524, pp. 39
  1. Cloud Physics

    Aerosols give clouds a lift

    1. H. Jesse Smith

    Atmospheric aerosols invigorate thunderstorms by increasing humidity and thus stimulating convection.

    PHOTO: ANDREAS THALLER/ALAMY STOCK PHOTO

    It has been observed that atmospheric aerosols can strengthen updrafts in deep convective clouds such as those that form in thunderstorms. Past work has linked such invigoration with the latent heat released by water condensation or freezing in chains of processes that depend on aerosol concentrations. Abbott and Cronin suggest a third possibility in which updrafts intensify because high aerosol concentrations increase environmental humidity by mixing more condensed water into the surrounding air, which in turn favors stronger updrafts.

    Science, this issue p. 83

  2. Cell Cycle

    Checking fidelity in cell division

    1. L. Bryan Ray

    Everything has to go right during cell division, so a checkpoint mechanism known as the spindle-assembly checkpoint prevents mitosis from proceeding unless the kinetochores that attach chromosomes to the spindle microtubules are properly engaged. Two papers now reveal the detailed molecular choreography that allows a single, unattached kinetochore to arrest cell division: Lara-Gonzalez et al. used a visual probe that tracks a specific form of one of the checkpoint complex proteins, and Piano et al. used a biochemical reconstitution of the checkpoint. Together, these studies reveal how protein interaction, spatial constraints, phosphorylation, and catalytic conversion of the protein Mad2 to its active form allow this all-important sensor to function.

    Science, this issue p. 64, p. 67

  3. Protein Folding

    One sequence encoding two structures

    1. Valda Vinson

    Most proteins have stable, folded structures, but there are rare examples of metamorphic proteins that can switch between two different folds that may each have a different function. Dishman et al. investigated the evolution of XCL1, which is a member of the chemokine family that interconverts between the chemokine fold and a second, noncanonical fold that forms dimers. The authors used nuclear magnetic resonance spectroscopy to investigate the structures of inferred evolutionary ancestral sequences. Their results suggest that XCL1 evolved from an ancestor with the chemokine fold and then transitioned to prefer the noncanonical fold before reaching the modern-day metamorphic protein.

    Science, this issue p. 86

  4. Materials Science

    Stretching diamond to the limit

    1. Brent Grocholski

    Diamond is thought of as being unbendable, but thin samples can actually deform elastically. Applying relatively large amounts of strain to diamond may shift its electronic properties, which is of interest for a number of applications. Dang et al. elastically stretched micrometer-sized plates of diamond along different crystallographic directions. These relatively large samples show that deep-strain engineering can be accomplished in more uniform diamond specimens and may have a large impact on the electronic properties.

    Science, this issue p. 76

  5. Protein Synthesis

    Co-co assembly for oligomers

    1. Stella M. Hurtley

    Most of the human proteome forms oligomeric protein complexes, but how they assemble is poorly understood. Bertolini et al. used a ribosome-profiling approach to explore the existence of a cotranslational assembly mode based on the interaction of two nascent polypeptides, which they call the “co-co” assembly. Proteome-wide data were used to show whether, when, and how efficiently nascent complex subunits interact. The findings also show that human cells use co-co assembly to produce hundreds of different homo-oligomers. Co-co assembly involving ribosomes translating one messenger RNA may resolve the longstanding question of how cells prevent unwanted interactions between different protein isoforms to efficiently produce functional homo-oligomers.

    Science, this issue p. 57

  6. Active Matter

    Shake, rattle, and help each other along

    1. Marc S. Lavine

    A trio of robots capable of emulating collective behaviors

    CREDIT: CHVYKOV ET AL.

    In classical statistical mechanics, the deterministic dynamics of a many-body system are replaced by a probabilistic description. Chvykov et al. work toward a similar description for the nonequilibrium self-organization of collectives of active particles. In these systems, continuously input energy drives localized fluctuations, but larger-scale ordering can emerge, such as in the flight of a flock of birds. A key concept in their theory is the importance of rattling, whereby ordered patterns emerge through local collisions between neighbors at specific frequencies. The authors demonstrate this behavior using a set of flapping robots and produce related simulations of the robot behavior.

    Science, this issue p. 90

  7. Tumor Immunology

    Autophagy protects tumors from T cells

    1. Dan A. Erkes

    Tumors evade antitumor T cells by various mechanisms. Young et al. used a CRISPR screen to show that tumor necrosis factor–α (TNFα) and autophagy play a role in the T cell–mediated killing of tumor cells. Pharmacologic or genetic inhibition of autophagy in tumor cells increased TNFα-mediated T cell killing of tumor cells. Deletion of the gene Rb1cc1 in tumor cells improved the efficacy of immune checkpoint blockade in a mouse tumor model. However, deleting the TNFα receptor in tumor cells partially abrogated the improved efficacy of immune checkpoint blockade in the absence of Rb1cc1. Thus, autophagy inhibition may improve T cell–mediated immunotherapies in patients who have cancer.

    Sci. Immunol. 5, eabb9561 (2020).

  8. Neurodegeneration

    Saving neurons in Parkinson's disease

    1. Leslie K. Ferrarelli

    Parkinson's disease is characterized by the progressive loss of dopaminergic neurons that leads to loss of motor control and cognitive decline. Kim et al. found that activating the kinase Akt1, such as with chlorogenic acid (a polyphenol found in coffee), prevented both neuronal death and motor and cognitive impairments in two mouse models of Parkinson's disease. Akt1 inhibited neuronal death by transcriptionally activating a gene involved in regulating programmed cell death. The clinical relevance of this mechanism was supported by correlative data collected from postmortem patient brain tissue.

    Sci. Signal. 13, eaax7119 (2020).

  9. Coronavirus

    Effects on cancer in Africa

    1. Gemma Alderton

    The COVID-19 pandemic struck many countries in Africa as they were already facing multiple public health challenges, in particular high incidence and mortality rates from cancer. In a Perspective, Addai and Ngwa discuss the effects of the COVID-19 response on cancer care, treatment, and outreach aimed at diagnosing patients early. The allocation of limited resources to COVID-19 patients, rather than to cancer patients, could increase the number of late-stage cancer diagnoses and resulting mortality. There have also been effects on fundraising and patient mental health, as well as on cancer research and training. However, opportunities have also been created, such as the development of localized diagnostic capability, more efficient radiotherapy administration, increased focus on understanding phytomedicine use, and use of telemedicine and online learning.

    Science, this issue p. 25

  10. Medicine

    RNA targets in neuromuscular diseases

    1. Gemma Alderton

    Neuromuscular diseases, such as Duchenne muscular dystrophy, are caused by dysfunction of skeletal muscle or the nervous system that controls muscle, with debilitating effects. However, several recent approvals of RNA therapies for some neuromuscular diseases highlight encouraging progress for treatment. In a Perspective, Ferlini et al. discuss antisense oligonucleotides that have been developed, and in some cases approved, for the treatment of neuromuscular diseases. They also discuss challenges in widening the applications of next-generation antisense oligonucleotides and possibly preventing the development of some neuromuscular diseases.

    Science, this issue p. 29

  11. Circadian Rhythms

    Doubts in cancer-rhythms connections

    1. L. Bryan Ray

    Circadian clocks help to coordinate physiological processes with the daily cycles of light and dark and periods of feeding, activity, and rest. Being out of sync with such 24-hour cycles can have unhealthy effects. Sancar and Van Gelder review the available evidence regarding circadian disruption and predisposition to cancer and circadian variations in response to cancer chemotherapy. The literature can be difficult to interpret. For example, complete knockouts of clock genes are not the same as shift work. Overall, they find that the jury is still out on whether circadian disruption can promote cancer in general and if the timing of cancer treatment can be optimized. However, enough indications are present that further research is recommended.

    Science, this issue p. eabb0738

  12. Structural Biology

    Anticoagulants take over

    1. Michael A. Funk

    In its fully reduced form, vitamin K helps to catalyze an oxidation reaction essential for blood coagulations, but it must be regenerated in each reaction through reduction. Liu et al. determined the structures of the enzyme responsible, vitamin K epoxide reductase, bound to an oxidized vitamin K substrate or with anticoagulants, including the widely prescribed drug warfarin. Understanding how these molecules bind and inhibit explains some variations in the therapeutic response as well as resistance for anticoagulants used in pest control.

    Science, this issue p. eabc5667

  13. Transcription

    How to stop RNA polymerase

    1. Di Jiang

    Timely and tunable cessation of RNA synthesis is vital for cellular homeostasis. RNA helicases such as the archetypal termination factor r actively dismantle transcription complexes, but the transitory nature of termination makes the process hard to study structurally. Said et al. assembled ρ-bound transcription complexes and studied them using cryo–electron microscopy with an approach that captured a series of functional states en route to termination. They found an extensive and dynamic network of r interactions with RNA polymerase, nucleic acids, and accessory Nus factors. ρ mediates stepwise rearrangements of these contacts, transforming an actively transcribing complex into a moribund pretermination intermediate.

    Science, this issue p. eabd1673

  14. Stress Responses

    Transcriptional control of proteostasis

    1. Stella M. Hurtley

    Tissue homeostasis requires the coordinated activity of multiple cell types to initiate and then resolve inflammation. Intrinsic cellular stress-response pathways facilitate adaptation to stress and tissue restitution. Among these stress pathways, the unfolded protein response can elicit two divergent outcomes: adaptation to endoplasmic reticulum (ER) stress or termination by programmed cell death. You et al. identified QRICH1 as a transcriptional regulator controlling adaptation to ER stress at the level of protein translation and secretion. The authors further demonstrate the role of the QRICH1 program in inflammatory diseases of the colon and liver.

    Science, this issue p. eabb6896

  15. Stem Cells

    Protecting the lung from hypoxic stress

    1. Beverly A. Purnell

    The lung experiences constantly changing oxygen concentrations and must recognize and respond to a low-oxygen environment. Shivaraju et al. reveal that airway stem cells directly sense hypoxia and respond by differentiating into protective neuroendocrine (NE) cells that secrete a peptide that mitigates tissue damage (see the Perspective by Zacharias). This work suggests that the observed NE cell hyperplasia that accompanies lung diseases such as asthma, cystic fibrosis, and chronic obstructive pulmonary disease represents a compensatory physiologic response. More broadly, it raises the possibility that stem cells throughout the body sense hypoxia and differentiate into organ-specific NE cells.

    Science, this issue p. 52; see also p. 32

  16. Batteries

    When two is better than four

    1. Marc S. Lavine

    Batteries based on the reaction of zinc and oxygen have been used for more than a century, but these have been primary (that is, nonrechargeable) cells. These batteries use an alkaline electrolyte and require a four-electron reduction of oxygen to water, which is a slow process. Sun et al. show that with the right choice of nonalkaline electrolyte, the battery can operate using a two-electron zinc-oxygen/zinc peroxide chemistry that is far more reversible. By making the electrolyte hydrophobic, water is excluded from the near surface of the cathode, thus preventing the four-electron reduction. These batteries also show higher energy density and better cycling stability.

    Science, this issue p. 46

  17. Membranes

    Finding the path to better desalination

    1. Marc S. Lavine

    Polyamide membranes have been used in large-scale desalination for decades. However, because of the thinness of the membranes and their internal variability, it has been hard to determine which aspects of the membranes most affect their performance. Culp et al. combined electron tomography, nanoscale three-dimensional (3D) polyamide density mapping, and modeling of bulk water permeability with zero adjustable parameters to quantify the effect of 3D nanoscale variations in polymer mass on water transport within the polyamide membrane (see the Perspective by Geise). They found that variability in local density most affects the performance of the membranes. Better synthesis methods could thus improve performance without affecting selectivity.

    Science, this issue p. 72; see also p. 31

  18. Coronavirus

    Pandemic progress in Kenya

    1. Caroline Ash

    By the end of July 2020, Kenya h ad reported only 341 deaths and ∼20,000 cases of COVID-19. This is in marked contrast to the tens of thousands of deaths reported in many higher-income countries. The true extent of COVID-19 in the community was unknown and likely to be higher than reports indicated. Uyoga et al. found an overall seroprevalence among blood donors of 4.3%, peaking in 35- to 44-year-old individuals (see the Perspective by Maeda and Nkengasong). The low mortality can be partly explained by the steep demographics in Kenya, where less than 4% of the population is 65 or older. These circumstances combine to result in Kenyan hospitals not currently being overwhelmed by patients with respiratory distress. However, the imposition of a strict lockdown in this country has shifted the disease burden to maternal and child deaths as a result of disruption to essential medical services.

    Science, this issue p. 79; see also p. 27

  19. Coronavirus

    Avoiding spread of SARS-CoV-2 in cars

    1. Karen K. Gleason

    The evidence has become clear that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is transmitted by aerosols, so enclosed spaces such as automobiles are thus high risk. Mathai et al. numerically calculated the flow patterns of aerosol droplets inside the cabin of a four-windowed car. Having the windows closed and the air-conditioner on results in considerable transfer of air and aerosols between occupants. However, having all the windows fully open separates the airflows on the right and left sides of the cabin and thus best reduces disease transmission if the passenger is seated in the back, on the opposite side from the driver.

    Sci. Adv. 10.1126/sciadv.abe0166 (2020).

  20. Aging

    Slowing cellular senescence

    1. Melissa Norton

    Whereas cellular senescence is known to promote aging, many of the mechanisms controlling this process remain poorly understood. Using human mesenchymal precursor cells (hMPCs) carrying pathogenic mutations of the premature aging diseases Werner syndrome and Hutchinson-Gilford progeria syndrome, Wang et al. conducted a genome-wide CRISPR-Cas9–based screen to identify genes that could affect cellular senescence. They identified KAT7, a histone acetyltransferase gene, as a driver of senescence in hMPCs. Inactivation of Kat7 in mice aging normally and in prematurely aging progeroid mice extended their life span. Although KAT7 requires further study in other cell types, these experiments highlight the value of genome-wide CRISPR-Cas9 screens and further illuminate the mechanisms controlling senescence.

    Sci. Transl. Med. 13, eabd2655 (2020).

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