COVER The skeleton of Hope, a young female blue whale that beached in Ireland in 1891, is suspended from the ceiling of London’s Natural History Museum, pictured here empty of visitors while the museum was closed during the COVID-19 pandemic. Hope’s skull features in new research on mammals that shows how the ecology and life history of species shape the tempo of their evolution. See pages 355 and 377.

Photo: Jonathan Jackson; © The Trustees of the Natural History Museum, London

ONLINE COVER Optomechanical resonators are micro- or nanodevices powered and detected by optical forces. Highly sensitive, these devices detect molecular substances—such as polymers, proteins, and viruses—in vacuum, air, and liquid media. Asano et al. manufactured optomechanical probes consisting of two microbottles. They found that the device is not only capable of high molecular sensitivity in water, but also allows previously unreported free access to the target location. Further development could extend the twin-microbottle resonator’s use in viscous gel-like media and pioneer research towards ultrasensitive biochips and rheometers.

ONLINE COVER Mangled Myelin. This month’s cover depicts a normal myelin sheath wrapped around the axon of a neuron next to a damaged myelin sheath impairing nerve function. Autoreactive T cells specific for epitopes in myelin proteins trigger demyelination in human multiple sclerosis and mice with experimental autoimmune encephalomyelitis (EAE). Yi and Miller et al. report that chimeric antigen receptor (CAR) T cells displaying a complex of MHC class II and a peptide from myelin oligodendrocyte protein (MOG) selectively target pathogenic T cells for elimination in mouse EAE initiated by MOG immunization, thereby preventing and treating autoimmune symptoms. Using CAR T cells with different functional efficacy, the authors found that higher affinity autoreactive T cells are required for initiation of disease onset but lower affinity cells are sufficient to maintain ongoing disease.

ONLINE COVER Physical Connections. Morphological computing leverages the dynamics of mechanical bodies for computation with the aim to decentralize the computing load. Inspired by artificial neural networks, Lee et al. have realized a mechanical neural network that uses interconnected beams with tunable stiffness to learn mechanical behaviors. Genetic and partial pattern search algorithms were applied to the mechanical neural network. This month's cover is a photograph of the mechanical neural network in operation.

ONLINE COVER This week, Murakami et al. discovered that inflamed macrophages secrete Semaphorin 4D, which acts as a proinflammatory cytokine that drives cartilage degeneration and accelerates inflammatory arthritis in mice. The image shows a cross section through the ankle of a healthy mouse.

ONLINE COVER Pathological Pathways in Heart Failure. Shown is an immunofluorescence microscopy image of human dilated left ventricle heart tissue stained for TRIM35 (magenta), troponin-I (green), wheat germ agglutinin (red), and nuclei (blue). Lorenzana-Carrillo et al. observed that the ubiquitin ligase TRIM35 is induced in the failing human heart. TRIM35 ubiquitinated and degraded nuclear pyruvate kinase M2 (PKM2), decreasing expression of the prosurvival transcription factors GATA4 and GATA6 while inducing the proapoptotic transcription factor P53. Overexpressing TRIM35 in cardiomyocytes promoted heart failure in transgenic mice. These results help uncover how TRIM35 and PKM2 regulate cardiomyocyte apoptosis and dilated heart failure.