Native qudit entanglement in a trapped ion quantum processor.

Quantum information carriers, just like most physical systems, naturally occupy high-dimensional Hilbert spaces. Instead of restricting them to a two-level subspace, these high-dimensional (qudit) quantum systems are emerging as a powerful resource for the next generation of quantum processors. Yet harnessing the potential of these systems requires efficient ways of generating the desired interaction between them. Here, we experimentally demonstrate an implementation of a native two-qudit entangling gate up to dimension 5 in a trapped-ion system. This is achieved by generalizing a recently proposed light-shift gate mechanism to generate genuine qudit entanglement in a single application of the gate. The gate seamlessly adapts to the local dimension of the system with a calibration overhead that is independent of the dimension.

Content-aware image restoration: pushing the limits of fluorescence microscopy.

Fluorescence microscopy is a key driver of discoveries in the life sciences, with observable phenomena being limited by the optics of the microscope, the chemistry of the fluorophores, and the maximum photon exposure tolerated by the sample. These limits necessitate trade-offs between imaging speed, spatial resolution, light exposure, and imaging depth. In this work we show how content-aware image restoration based on deep learning extends the range of biological phenomena observable by microscopy. We demonstrate on eight concrete examples how microscopy images can be restored even if 60-fold fewer photons are used during acquisition, how near isotropic resolution can be achieved with up to tenfold under-sampling along the axial direction, and how tubular and granular structures smaller than the diffraction limit can be resolved at 20-times-higher frame rates compared to state-of-the-art methods. All developed image restoration methods are freely available as open source software in Python, FIJI, and KNIME.

Polypterus and the evolution of fish pectoral musculature.

Polypterus, a member of the most primitive living group of ray-finned fishes, has demonstrated the ability to perform fin-assisted terrestrial locomotion, a behavior that indicates a complex pectoral musculoskeletal system. Review of the literature reveals that many aspects of the pectoral muscular anatomy of Polypterus are still unclear, with a number of conflicting descriptions. We provide a new interpretation of the pectoral musculature using soft tissue-enhanced microCT scanning and gross anatomical dissection. The results demonstrate a complex musculature, with six independent muscles crossing the glenoid-fin joint. Comparisons with other bony-fish (Osteichthyes), including both ray-finned (Actinopterygii) and lobed-fin (Sarcopterygii) fish, indicate the presence of novel muscles within Polypterus: coracometapterygialis I+II and the zonopropterygialis medialis. Examination of these muscular additions in the context of osteichthyan phylogeny indicates that this represents a previously unrecognized event in the evolution of pectoral musculature in Osteichthyes. Despite its phylogenetic position as a basal actinopterygian, the musculature of Polypterus has more similarities both anatomically and functionally with that of sarcopterygians. This anatomy, along with other features of Polypterus anatomy such as lobed fins, ventral paired lungs, and a large spiracle, may make it a good model for inferences of stem tetrapod locomotion.

Composition of isolated synaptic boutons reveals the amounts of vesicle trafficking proteins.

Synaptic vesicle recycling has long served as a model for the general mechanisms of cellular trafficking. We used an integrative approach, combining quantitative immunoblotting and mass spectrometry to determine protein numbers; electron microscopy to measure organelle numbers, sizes, and positions; and super-resolution fluorescence microscopy to localize the proteins. Using these data, we generated a three-dimensional model of an "average" synapse, displaying 300,000 proteins in atomic detail. The copy numbers of proteins involved in the same step of synaptic vesicle recycling correlated closely. In contrast, copy numbers varied over more than three orders of magnitude between steps, from about 150 copies for the endosomal fusion proteins to more than 20,000 for the exocytotic ones.

A small pool of vesicles maintains synaptic activity in vivo.

Chemical synapses contain substantial numbers of neurotransmitter-filled synaptic vesicles, ranging from approximately 100 to many thousands. The vesicles fuse with the plasma membrane to release neurotransmitter and are subsequently reformed and recycled. Stimulation of synapses in vitro generally causes the majority of the synaptic vesicles to release neurotransmitter, leading to the assumption that synapses contain numerous vesicles to sustain transmission during high activity. We tested this assumption by an approach we termed cellular ethology, monitoring vesicle function in behaving animals (10 animal models, nematodes to mammals). Using FM dye photooxidation, pHluorin imaging, and HRP uptake we found that only approximately 1-5% of the vesicles recycled over several hours, in both CNS synapses and neuromuscular junctions. These vesicles recycle repeatedly, intermixing slowly (over hours) with the reserve vesicles. The latter can eventually release when recycling is inhibited in vivo but do not seem to participate under normal activity. Vesicle recycling increased only to ≈ 5% in animals subjected to an extreme stress situation (frog predation on locusts). Synapsin, a molecule binding both vesicles and the cytoskeleton, may be a marker for the reserve vesicles: the proportion of vesicles recycling in vivo increased to 30% in synapsin-null Drosophila. We conclude that synapses do not require numerous reserve vesicles to sustain neurotransmitter release and thus may use them for other purposes, examined in the accompanying paper.

Amyloid precursor protein is trafficked and secreted via synaptic vesicles.

A large body of evidence has implicated amyloid precursor protein (APP) and its proteolytic derivatives as key players in the physiological context of neuronal synaptogenesis and synapse maintenance, as well as in the pathology of Alzheimer's Disease (AD). Although APP processing and release are known to occur in response to neuronal stimulation, the exact mechanism by which APP reaches the neuronal surface is unclear. We now demonstrate that a small but relevant number of synaptic vesicles contain APP, which can be released during neuronal activity, and most likely represent the major exocytic pathway of APP. This novel finding leads us to propose a revised model of presynaptic APP trafficking that reconciles existing knowledge on APP with our present understanding of vesicular release and recycling.

The same synaptic vesicles drive active and spontaneous release.

Synaptic vesicles release neurotransmitter both actively (on stimulation) and spontaneously (at rest). It has been assumed that identical vesicles use both modes of release; however, recent evidence has challenged this view. Using several assays (FM dye imaging, pHluorin imaging and antibody-labeling of synaptotagmin) in neuromuscular preparations from Drosophila, frog and mouse, as well as rat cultured neurons, we found that the same vesicles participate in active and spontaneous release.