Editors' Choice

Science  14 Feb 2020:
Vol. 367, Issue 6479, pp. 753
  1. Organoids

    Modeling neuromuscular biology and disease

    1. Beverly A. Purnell

    Magnified view of neuromuscular junctions, which are complex assemblages of neurons and muscle cells that can now be replicated in organoids.

    IMAGE: ERIC GRAVE/SCIENCE SOURCE

    Producing organs on demand is an ambitious goal for cell and developmental biologists. The complexity of structure and function for many organs is a difficult challenge. As of now, organoids are the closest approximation. Faustino Martins et al. used human pluripotent stem cells as starting material to assemble neuromuscular organoids containing spinal cord neurons, associated neuromuscular junctions, and skeletal muscle cells. Neural and mesodermal cells were tracked through development by single-cell RNA sequencing. The neuromuscular organoids contracted and displayed neuronal circuits and were also induced to recapitulate the pathology of myasthenia gravis.

    Cell Stem Cell 10.1016/j.stem.2019.12.007 (2020).

  2. Education

    Not all mentors are equal

    1. Melissa McCartney

    Effective mentoring is a critical component of scientific training, especially at the undergraduate level. Even though prior research suggests that negative mentoring experiences are common, little is known about mentoring experiences in general. Limeri et al. report on a qualitative study designed to define and characterize negative mentoring experiences of undergraduate life science researchers. Thirty-three life science undergraduate researchers were interviewed about their experience with mentors, including mentor behaviors and characteristics and mentoring situations and events. The results identified seven major categories of negative mentoring: absenteeism, abuse of power, interpersonal mismatch, lack of career and technical support, lack of psychosocial support, misaligned expectations, and unequal treatment. These data could be useful to future and current mentors reflecting on their mentoring practice.

    CBE Life Sci. Educ. 18, ar61 (2019).

  3. Infection

    Trouble brewing in the gut

    1. Seth Thomas Scanlon

    Candida albicans, shown here, is a fungus often found in the gut, but it can become pathogenic and invasive after surgery.

    IMAGE: 3D4MEDICAL/SCIENCE SOURCE

    Invasive infections with fungi like Candida albicans can be a serious complication of organ transplantation and chemotherapy. One possible explanation is that these procedures alter the intestinal microbiota, which may provide an opening for opportunistic fungi. For better insight into this relationship, Zhai et al. investigated patients receiving allogeneic hematopoietic stem cell transplants. They used high-resolution mycobiota and microbiota sequencing of recipients' blood and feces to track the dynamics of infection. A pronounced loss of bacterial microbiota and diversity (especially of anaerobes) was accompanied by expansion of pathogenic Candida species in the intestine. This overgrowth in the gut preceded bloodstream Candida infections. In the future, similar monitoring approaches may be used to better target patients at risk for invasive fungal infections.

    Nat. Med. 26, 59 (2020).

  4. Signal Transduction

    miRNAs mediate mTORC1 effects

    1. L. Bryan Ray

    Too much signaling by the mammalian target of rapamycin complex 1 (mTORC1) protein kinase complex is a bad thing in part because it enhances production of particular microRNAs (miRNAs). Mouse cells engineered to lack the mTORC1 inhibitor component Tsc1 and thus exhibit excessive mTORC1 signaling also showed altered glucose metabolism. Liko et al. traced this effect to enhanced production of miRNAs from an imprinted locus (that is, expressed from the alleles from one parent of origin only) on chromosome 12. Expression of these miRNAs increased production of enzymes that catalyze gluconeogenesis and resulted in glucose intolerance. Precisely how the miRNAs work is unclear, but they may provide a previously unrecognized target for managing metabolic diseases.

    Proc. Natl. Acad. Sci. U.S.A.117, 1524 (2020).

  5. Nutrition

    High-protein diet affects circulation

    1. Gemma Alderton

    Diets that are high in protein can be used to promote weight loss. The downside is that recent evidence suggests that high dietary protein is associated with increased incidence of cardiovascular disease, particularly atherosclerosis. Zhang et al. fed pro-atherogenic mice a high-protein diet and found that more atherosclerotic plaques formed. They observed that the resulting high concentrations of amino acids in the blood activated mammalian target of rapamycin (mTOR) signaling in macrophages in atherosclerotic plaques. mTOR integrates numerous amino acid–sensing pathways, and its activation in macrophages leads to the accumulation of dysfunctional mitochondria and apoptosis. This work provides important mechanistic insight into how dietary nutrients can influence systemic homeostasis.

    Nat. Metab. 2, 110 (2020).

  6. Organic Synthesis

    Closing rings with porous templates

    1. Phil Szuromi

    The closure of large rings from linear substrates (macrocyclization) must avoid the competing coupling between molecules and the entropic penalty for folding long chains. Hydrophobic nanoscale cavities can assist in both folding of chains and avoiding intermolecular reactions. Liu et al. used a self-assembling molecule bearing bent chains of aromatic groups to create two-dimensional sheets with ∼2-nanometer pores. A palladium(0) catalyst performed Suzuki couplings on linear substrates bound in the pores to create >30-mer macrocycles. On formation, the macrocycles released spontaneously to enable subsequent rounds of reaction.

    J. Am. Chem. Soc. 142, 1904 (2020).

  7. Psychology

    Altruism reduces physical pain

    1. Tage S. Rai

    The physical sensation of pain may depend on how people psychologically construe it. Wang et al. conducted a series of studies to demonstrate that engaging in painful activities to help others is associated with reduced perceptions of pain. In follow-up studies, they found that experimentally manipulating people to donate to charitable causes reduces pain sensations. Brain areas related to pain sensation demonstrated reduced activation when participants donated. In a final study, cancer patients randomly assigned to engage in helping behaviors over the course of a week reported less chronic pain. These results suggest that engaging in prosocial behaviors may have alleviative properties for the individual performer.

    Proc. Acad. Natl. Sci. U.S.A.117, 950 (2020).

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