The radical response of peripheral nerves to injury (Wallerian degeneration) is the cornerstone of nerve repair. We show that activation of the transcription factor c-Jun in Schwann cells is a global ...regulator of Wallerian degeneration. c-Jun governs major aspects of the injury response, determines the expression of trophic factors, adhesion molecules, the formation of regeneration tracks and myelin clearance and controls the distinctive regenerative potential of peripheral nerves. A key function of c-Jun is the activation of a repair program in Schwann cells and the creation of a cell specialized to support regeneration. We show that absence of c-Jun results in the formation of a dysfunctional repair cell, striking failure of functional recovery, and neuronal death. We conclude that a single glial transcription factor is essential for restoration of damaged nerves, acting to control the transdifferentiation of myelin and Remak Schwann cells to dedicated repair cells in damaged tissue.
► Schwann cell c-Jun is a master regulator of the PNS injury response ► c-Jun activates a defined repair program in Schwann cells of damaged nerves ► c-Jun controls transdifferentiation of differentiated Schwann cells to repair cells ► Schwann cell c-Jun is essential for neuronal survival and functional recovery
Unlike the central nervous system, injured peripheral nerves regenerate to restore function after injury. Arthur-Farraj et al. show that this repair potential depends on glial (Schwann) cell expression of the transcription factor c-Jun.
With the emergence of applications based on short-wavelength infrared light, indium arsenide quantum dots are promising candidates to address existing shortcomings of other infrared-emissive ...nanomaterials. However, III-V quantum dots have historically struggled to match the high-quality optical properties of II-VI quantum dots. Here we present an extensive investigation of the kinetics that govern indium arsenide nanocrystal growth. Based on these insights, we design a synthesis of large indium arsenide quantum dots with narrow emission linewidths. We further synthesize indium arsenide-based core-shell-shell nanocrystals with quantum yields up to 82% and improved photo- and long-term storage stability. We then demonstrate non-invasive through-skull fluorescence imaging of the brain vasculature of murine models, and show that our probes exhibit 2-3 orders of magnitude higher quantum yields than commonly employed infrared emitters across the entire infrared camera sensitivity range. We anticipate that these probes will not only enable new biomedical imaging applications, but also improved infrared nanocrystal-LEDs and photon-upconversion technology.
Boron neutron capture therapy (BNCT) is an emerging treatment modality aimed at improving the therapeutic ratio for traditionally difficult to treat tumors. BNCT utilizes boronated agents to ...preferentially deliver boron-10 to tumors, which, after undergoing irradiation with neutrons, yields litihium-7 and an alpha particle. The alpha particle has a short range, therefore preferentially affecting tumor tissues while sparing more distal normal tissues. To date, BNCT has been studied clinically in a variety of disease sites, including glioblastoma multiforme, meningioma, head and neck cancers, lung cancers, breast cancers, hepatocellular carcinoma, sarcomas, cutaneous malignancies, extramammary Paget's disease, recurrent cancers, pediatric cancers, and metastatic disease. We aim to provide an up-to-date and comprehensive review of the studies of each of these disease sites, as well as a review on the challenges facing adoption of BNCT.
Synthesizing many-body quantum systems with various ranges of interactions facilitates the study of quantum chaotic dynamics. Such extended interaction range can be enabled by using nonlocal degrees ...of freedom such as photonic modes in an otherwise locally connected structure. Here, we present a superconducting quantum simulator in which qubits are connected through an extensible photonic-bandgap metamaterial, thus realizing a one-dimensional Bose-Hubbard model with tunable hopping range and on-site interaction. Using individual site control and readout, we characterize the statistics of measurement outcomes from many-body quench dynamics, which enables in situ Hamiltonian learning. Further, the outcome statistics reveal the effect of increased hopping range, showing the predicted crossover from integrability to ergodicity. Our work enables the study of emergent randomness from chaotic many-body evolution and, more broadly, expands the accessible Hamiltonians for quantum simulation using superconducting circuits.
Cellular compartments that cannot be biochemically isolated are challenging to characterize. Here we demonstrate the proteomic characterization of the synaptic clefts that exist at both excitatory ...and inhibitory synapses. Normal brain function relies on the careful balance of these opposing neural connections, and understanding how this balance is achieved relies on knowledge of their protein compositions. Using a spatially restricted enzymatic tagging strategy, we mapped the proteomes of two of the most common excitatory and inhibitory synaptic clefts in living neurons. These proteomes reveal dozens of synaptic candidates and assign numerous known synaptic proteins to a specific cleft type. The molecular differentiation of each cleft allowed us to identify Mdga2 as a potential specificity factor influencing Neuroligin-2′s recruitment of presynaptic neurotransmitters at inhibitory synapses.
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•APEX proteomics extended to open cellular domains, cell surface, and primary cells•199 glutamatergic and 42 GABAergic synaptic cleft proteins enriched•Ten candidates validated as synaptic proteins by imaging and/or synaptosome blotting•Mdga2 regulates specificity of presynaptic recruitment to inhibitory post-synapses
An approach enabling proteomic analysis of subcellular compartments that are not membrane enclosed reveals unique features of excitatory and inhibitory synapses.
Producing quantum states at random has become increasingly important in modern quantum science, with applications being both theoretical and practical. In particular, ensembles of such randomly ...distributed, but pure, quantum states underlie our understanding of complexity in quantum circuits
and black holes
, and have been used for benchmarking quantum devices
in tests of quantum advantage
. However, creating random ensembles has necessitated a high degree of spatio-temporal control
placing such studies out of reach for a wide class of quantum systems. Here we solve this problem by predicting and experimentally observing the emergence of random state ensembles naturally under time-independent Hamiltonian dynamics, which we use to implement an efficient, widely applicable benchmarking protocol. The observed random ensembles emerge from projective measurements and are intimately linked to universal correlations built up between subsystems of a larger quantum system, offering new insights into quantum thermalization
. Predicated on this discovery, we develop a fidelity estimation scheme, which we demonstrate for a Rydberg quantum simulator with up to 25 atoms using fewer than 10
experimental samples. This method has broad applicability, as we demonstrate for Hamiltonian parameter estimation, target-state generation benchmarking, and comparison of analogue and digital quantum devices. Our work has implications for understanding randomness in quantum dynamics
and enables applications of this concept in a much wider context
.
Quantum many-body scar states are many-body states with finite energy density in non-integrable models that do not obey the eigenstate thermalization hypothesis. Recent works have revealed "towers" ...of scar states that are exactly known and are equally spaced in energy, specifically in the AKLT and spin-1 XY models, and a spin-1/2 model that conserves the number of domain walls. We provide a common framework to understand and prove known exact towers of scars in these systems, by evaluating the commutator of the Hamiltonian and a ladder operator. In particular, we provide a simple proof of the scar towers in the integer-spin 1D AKLT models by studying two-site spin projectors. Through this picture we deduce a family of Hamiltonians that share the scar tower with the AKLT model, and also find common parent Hamiltonians for the AKLT and XY model scars. We also introduce new towers of exact states, organized in a "pyramid" structure, in the spin-1/2 model through the successive application of a nonlocal ladder operator.
Metabolism alterations are hallmarks of cancer, but the involvement of lipid metabolism in disease progression is unclear. We investigated the role of lipid metabolism in prostate cancer using tissue ...from patients with prostate cancer and patient-derived xenograft mouse models. We showed that fatty acid uptake was increased in human prostate cancer and that these fatty acids were directed toward biomass production. These changes were mediated, at least partly, by the fatty acid transporter CD36, which was associated with aggressive disease. Deleting
in the prostate of cancer-susceptible
mice reduced fatty acid uptake and the abundance of oncogenic signaling lipids and slowed cancer progression. Moreover, CD36 antibody therapy reduced cancer severity in patient-derived xenografts. We further demonstrated cross-talk between fatty acid uptake and de novo lipogenesis and found that dual targeting of these pathways more potently inhibited proliferation of human cancer-derived organoids compared to the single treatments. These findings identify a critical role for CD36-mediated fatty acid uptake in prostate cancer and suggest that targeting fatty acid uptake might be an effective strategy for treating prostate cancer.
The η-pairing states are a set of exactly known eigenstates of the Hubbard model on hypercubic lattices, first discovered by Yang C. N. Yang, Phys. Rev. Lett. 63, 2144 (1989). These states are not ...many-body scar states in the Hubbard model because they occupy unique symmetry sectors defined by the so-called η-pairing SU(2) symmetry. We study an extended Hubbard model with bond-charge interactions, popularized by Hirsch J. E. Hirsch, Physica C 158, 326 (1989), where the η-pairing states survive without the η-pairing symmetry and become true scar states. We also discuss similarities between the η-pairing states and exact scar towers in the spin-1 XY model found by Schecter and Iadecola M. Schecter and T. Iadecola, Phys. Rev. Lett. 123, 147201 (2019), and systematically arrive at all nearest-neighbor terms that preserve such scar towers in one dimension. We also generalize these terms to arbitrary bipartite lattices. Our study of the spin-1 XY model also leads us to several scarred models, including a spin-1/2 J1−J2 model with Dzyaloshinskii-Moriya interaction, in realistic quantum magnet settings in one and two dimensions.
Immunotherapies that block inhibitory checkpoint receptors on T cells have transformed the clinical care of patients with cancer
. However, whether the T cell response to checkpoint blockade relies ...on reinvigoration of pre-existing tumor-infiltrating lymphocytes or on recruitment of novel T cells remains unclear
. Here we performed paired single-cell RNA and T cell receptor sequencing on 79,046 cells from site-matched tumors from patients with basal or squamous cell carcinoma before and after anti-PD-1 therapy. Tracking T cell receptor clones and transcriptional phenotypes revealed coupling of tumor recognition, clonal expansion and T cell dysfunction marked by clonal expansion of CD8
CD39
T cells, which co-expressed markers of chronic T cell activation and exhaustion. However, the expansion of T cell clones did not derive from pre-existing tumor-infiltrating T lymphocytes; instead, the expanded clones consisted of novel clonotypes that had not previously been observed in the same tumor. Clonal replacement of T cells was preferentially observed in exhausted CD8
T cells and evident in patients with basal or squamous cell carcinoma. These results demonstrate that pre-existing tumor-specific T cells may have limited reinvigoration capacity, and that the T cell response to checkpoint blockade derives from a distinct repertoire of T cell clones that may have just recently entered the tumor.
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