This Week in Science

Science  27 Jul 2018:
Vol. 361, Issue 6400, pp. 375
  1. Eusociality

    The benefits of being well fed

    1. Sacha Vignieri

    A transcriptomics approach reveals the underpinnings of queen versus worker ants.

    CREDIT: DANIEL KRONAUER

    In eusocial insects, the vast majority of individuals sacrifice their reproductive potential to support the reproductive queen. Although this system has evolved repeatedly, there is still much debate surrounding its origin. Working with seven different species of ants, Chandra et al. used a transcriptomic approach to show that a single gene is consistently up-regulated in queens. This gene seems to confer reproductive status through integration with increased nutrition. In a clonal ant, larval signals disrupt this gene up-regulation, destabilizing the division of reproductive labor. Increasing levels of the associated peptide override these larval signals and establish eusociality.

    Science, this issue p. 398

  2. Device Technology

    Cooler electrons for transistors

    1. Phil Szuromi

    The operating power of field-effect transistors is constrained in part by the minimum change in voltage needed to change the current output. This subthreshold swing (SS) limit is caused by hotter electrons from a thermal electron source leaking over the potential of the gate electrode. Qiu et al. show that graphene can act as a Dirac source that creates a narrower distribution of electron energies. When coupled to a carbon nanotube channel, the decrease in SS would allow the supply voltage to be decreased from 0.7 to 0.5 volts.

    Science, this issue p. 387

  3. Microbiota

    Sticky bacteria tolerated as future food

    1. Caroline Ash

    Dictyostelium discoideum amoebae consume bacteria until the supply is exhausted. Then the amoeba cells clump together into a “slug” and initiate a complex multicellular reproductive phase. Specialized cells within aggregates rid the slug of any extracellular bacteria. However, some strains of amoeba tolerate live, intracellular bacteria. Dinh et al. discovered that these carrier strains bear surface lectins that bind Klebsiella bacteria, promote cell entry, and prevent the bacteria from being immediately digested. These bacteria then provide a future food source. Moreover, the internalized bacteria transfer DNA into the amoeba nucleus, resulting in transient genetic transformation.

    Science, this issue p. 402

  4. Neuroscience

    Support for the memory index theory

    1. Peter Stern

    The link between contextual memory representations and locations or routes represented by hippocampal place cells during exploration remains unknown. Tanaka et al. examined spatial firing properties of neurons in hippocampal area CA1 on the basis of whether they had recently expressed the immediate-early activity-induced gene c-Fos in response to a novel context. The c-Fos–positive neurons displayed a more on-off firing pattern than the c-Fos–negative cells during context discrimination. In a contextual recognition paradigm, these results support the index theory of hippocampal function over a cognitive mapping theory.

    Science, this issue p. 392

  5. Gut Inflammation

    Inflammation promotes gut polyposis

    1. Seth Thomas Scanlon

    Peutz–Jeghers Syndrome (PJS) causes benign polyps in the gut and a higher risk of several cancers caused by mutations in the tumor suppressor gene STK11, which encodes liver kinase B1 (LKB1). LKB1's role in this disease is thought to be related to its tumor suppressor function. Now, Poffenberger et al. show that the T cell–specific heterozygous deletion of Stk11 is sufficient to reproduce PJS symptoms in mice (see the Perspective by Hollstein and Shaw). Polyps in mice and humans are characterized by immune cell infiltration, enhanced STAT3 signaling, and increased levels of inflammatory cytokines such as interleukin-6 (IL-6). Targeting STAT3 signaling, IL-6, or T cells ameliorated the polyps, suggesting potential therapies for this disease.

    Science, this issue p. 406; see also p. 332

  6. Climatology

    Colder Siberian winters in a warming world

    1. Kip Hodges

    Siberian winters are becoming colder, despite global warming.

    PHOTO: DMITRY FEOKTISTOV/CONTRIBUTOR/GETTY IMAGES

    Winters have been more severe in Siberia over the past decade, even while loss of sea ice indicates dramatic warming of the Arctic. One hypothesis proposed to explain this apparent paradox is that Arctic sea ice loss forces a change in atmospheric circulation patterns that leads to colder Siberian winters. Using comprehensive atmospheric circulation models, Zhang et al. demonstrate that late autumn sea ice loss in the Barents-Kara Seas should result in a colder climate in Siberia the following winter. Their experiments also suggest that changes in the stratosphere, particularly shifts in and weakening of the stratospheric polar vortex owing to a reduction in sea ice, contribute substantially to the severity of winters in Siberia.

    Sci. Adv. 10.1126/sciadv.aat6025 (2018).

  7. Cancer

    Blocking activin actively treats cancer

    1. Yevgeniya Nusinovich

    Platinum-based chemotherapy is a mainstay of treatment for lung cancer. However, resistance to this therapy is common, as are dose-limiting side effects, particularly kidney toxicity. To search for mechanisms contributing to treatment resistance, Marini et al. performed a whole-genome RNA interference screen, which implicated the activin pathway. Inhibition of this pathway offered a dual benefit by potentiating the effects of platinum drugs in mouse models of cancer and protecting the animals from kidney damage. Thus, activin inhibitors could be a valuable addition to platinum chemotherapy, enhancing the efficacy of treatment while also allowing higher doses or longer periods of drug use.

    Sci. Transl. Med. 10, eaat3504 (2018).

  8. Molecular Biology

    Phase separation and gene control

    1. Steve Mao

    Many components of eukaryotic transcription machinery—such as transcription factors and cofactors including BRD4, subunits of the Mediator complex, and RNA polymerase II—contain intrinsically disordered low-complexity domains. Now a conceptual framework connecting the nature and behavior of their interactions to their functions in transcription regulation is emerging (see the Perspective by Plys and Kingston). Chong et al. found that low-complexity domains of transcription factors form concentrated hubs via functionally relevant dynamic, multivalent, and sequence-specific protein-protein interaction. These hubs have the potential to phase-separate at higher concentrations. Indeed, Sabari et al. showed that at super-enhancers, BRD4 and Mediator form liquid-like condensates that compartmentalize and concentrate the transcription apparatus to maintain expression of key cell-identity genes. Cho et al. further revealed the differential sensitivity of Mediator and RNA polymerase II condensates to selective transcription inhibitors and how their dynamic interactions might initiate transcription elongation.

    Science, this issue p. eaar2555, p. eaar3958, p. 412; see also p. 329

  9. Biotechnology

    Transcriptome mapping in the 3D brain

    1. Steve Mao

    RNA sequencing samples the entire transcriptome but lacks anatomical information. In situ hybridization, on the other hand, can only profile a small number of transcripts. In situ sequencing technologies address these shortcomings but face a challenge in dense, complex tissue environments. Wang et al. combined an efficient sequencing approach with hydrogel-tissue chemistry to develop a multidisciplinary technology for three-dimensional (3D) intact-tissue RNA sequencing (see the Perspective by Knöpfel). More than 1000 genes were simultaneously mapped in sections of mouse brain at single-cell resolution to define cell types and circuit states and to reveal cell organization principles.

    Science, this issue p. eaat5691; see also p. 328

  10. Climate

    Improving climate model projections

    1. Julia Fahrenkamp-Uppenbrink

    How much will Earth's atmosphere warm if the carbon dioxide concentration doubles? Climate models give different answers to this question, making it difficult to determine how much carbon can be emitted while avoiding dangerous levels of climate change. In a Perspective, Soden et al. argue that the radiative forcing (i.e., the warming) from carbon dioxide is much less uncertain than model results suggest. The uncertainty is reduced substantially when a more sophisticated method is used to calculate the forcing, but models cannot adopt this method because it is too computationally expensive. Ensuring that model parameterizations are vetted against the more accurate calculations would help to reduce uncertainty in this crucial component of climate modeling.

    Science, this issue p. 326

  11. Cancer Therapy

    Modeling chemotherapy-drug combinations

    1. Leslie K. Ferrarelli

    Pharmacological inhibitors of DNA repair pathways can enhance the efficacy of chemotherapy. Alkan et al. modeled cancer cell responses to various chemotherapies and tested the efficacy of combining chemotherapy with DNA repair inhibition. In addition to the expected synergy between chemotherapy and an inhibitor of ATR (a DNA repair pathway kinase) in cultured cells and in vivo, there were some unexpected differences in outcome when applying low-versus high-dose chemotherapy regimens. Thus, modeling in cells can help inform therapeutic development.

    Sci. Signal. 11, eaat0229 (2018).

  12. T Cell Differentiation

    Signal strength seals fate

    1. Christiana N. Fogg

    T cell differentiation into effector and memory T cell subsets is influenced by T cell receptor (TCR) signals. Snook et al. examined how TCR signals influence CD4+ T cell differentiation by using a panel of cloned TCRs that recognize the same MHC (major histocompatibility complex) class II–restricted epitope of lymphocytic choriomeningitis virus. Strong TCR signals were associated with T helper (TH1) differentiation, whereas lower TCR signal strength corresponded with follicular helper T (Tfh) and memory T cell differentiation. Low CD25 expression by early effector T cells also predicted memory differentiation, although CD25 expression levels were not predictive of recall responses. Enhanced TCR signaling via knockdown of SHP-1 favored TH1 over Tfh and memory T cell differentiation. Thus, stronger TCR signaling promotes terminal effector TH1 differentiation.

    Sci. Immunol. 3, eaas9103 (2018).

  13. Organic Chemistry

    Silicon smooths the way to vinyl cations

    1. Jake Yeston

    Saturated carbon centers often undergo substitution reactions by initial cleavage of a carbon-halogen or carbon-oxygen bond, which leaves the carbon positively charged. Analogous cations have proven much harder to access from vinylic carbons that are engaged in double bonds. Popov et al. now show that silicon cations paired with noncoordinating anions can pull triflate groups off such vinylic carbons under ambient conditions (see the Perspective by Kennedy and Klumpp). The resultant vinyl cations react with simple alkanes through C–H insertion. Theoretical and mechanistic studies suggest that these reactions proceed through nonclassical pathways that bifurcate after the transition state.

    Science, this issue p. 381; see also p. 331