The thymus provides a nurturing environment for the differentiation and selection of T cells, a process orchestrated by their interaction with multiple thymic cell types. We used single-cell RNA sequencing to create a cell census of the human thymus across the life span and to reconstruct T cell differentiation trajectories and T cell receptor (TCR) recombination kinetics. Using this approach, we...
A myriad of cellular events are regulated by allostery; therefore, evolution of this process is of fundamental interest. Here, we use ancestral sequence reconstruction to resurrect ancestors of two colocalizing proteins, Aurora A kinase and its allosteric activator TPX2 (targeting protein for Xklp2), to experimentally characterize the evolutionary path of allosteric activation. Autophosphorylation...
Biased agonists of G protein–coupled receptors (GPCRs) preferentially activate a subset of downstream signaling pathways. In this work, we present crystal structures of angiotensin II type 1 receptor (AT1R) (2.7 to 2.9 angstroms) bound to three ligands with divergent bias profiles: the balanced endogenous agonist angiotensin II (AngII) and two strongly β-arrestin–biased analogs....
Macrocycles can restrict the rotation of substituents through steric repulsions, locking in conformations that provide or enhance the activities of pharmaceuticals, agrochemicals, aroma chemicals, and materials. In many cases, the arrangement of substituents in the macrocycle imparts an element of planar chirality. The difficulty in predicting when planar chirality will arise, as well as the...
Many animals can associate object shapes with incentives. However, such behavior is possible without storing images of shapes in memory that are accessible to more than one sensory modality. One way to explore whether there are modality-independent internal representations of object shapes is to investigate cross-modal recognition—experiencing an object in one sensory modality and later...
Quantum control of complex objects in the regime of large size and mass provides opportunities for sensing applications and tests of fundamental physics. The realization of such extreme quantum states of matter remains a major challenge. We demonstrate a quantum interface that combines optical trapping of solids with cavity-mediated light-matter interaction. Precise control over the frequency and...
Two-dimensional materials from layered van der Waals (vdW) crystals hold great promise for electronic, optoelectronic, and quantum devices, but technological implementation will be hampered by the lack of high-throughput techniques for exfoliating single-crystal monolayers with sufficient size and high quality. Here, we report a facile method to disassemble vdW single crystals layer by layer into...
Mycorrhizal fungi provide plants with a range of benefits, including mineral nutrients and protection from stress and pathogens. Here we synthesize current information about how the presence and type of mycorrhizal association affect plant communities. We argue that mycorrhizal fungi regulate seedling establishment and species coexistence through stabilizing and equalizing mechanisms such as soil...