Multiple sclerosis (MS) is a disease of the central nervous system that is associated with leukocyte recruitment and subsequent inflammation, demyelination and axonal loss. Endothelial vascular cell adhesion molecule-1 (VCAM-1) and its ligand, α 4 β 1 integrin, are key mediators of leukocyte recruitment and new selective inhibitors that bind to the α 4 subunit of α 4 β 1 substantially reduce clinical relapse in MS. Urgently needed is a molecular imaging technique to accelerate diagnosis, quantify disease activity and guide specific therapy.We report in vivo detection of VCAM-1 in acute brain inflammation, using MRI in a mouse model, at a time when pathology is otherwise undetectable. Antibody-conjugated microparticles carrying a high payload of iron oxide provided potent, quantifiable contrast effects that delineated the architecture of activated cerebral blood vessels. Rapid clearance from blood resulted in minimal background contrast. This technology is adaptable to monitor expression of endovascular molecules in vivo in a range of pathologies.Multiple sclerosis (MS) is a disease of the central nervous system characterized by multifocal white matter lesions 1 . Current diagnostic criteria for MS, incorporating both clinical and magnetic resonance imaging (MRI) characteristics, require the demonstration of lesion dissemination in both time and space 2 , 3 T2-weighted and gadolinium-enhanced T1-weighted MRI detect some, but not all, lesions while advanced MRI techniques such as diffusion imaging 4 , magnetization transfer 5 and MR spectroscopy 6 may provide additional insights. However, these approaches are limited in two key respects: (1) they image downstream injury, reflecting relatively advanced pathology and (2) while providing an indication of severity, current imaging techniques can not accurately assess disease activity 7 .

How features of the visual scene are encoded in the population activity of retinal ganglion cells (RGCs) targeting specific regions of the brain is not well understood. To address this, we have used a genetically encoded reporter of presynaptic function (SyGCaMP3) to record visually evoked activity in the population of RGC axons innervating the zebrafish tectum. Using unbiased voxel-wise analysis of SyGCaMP3 signals, we identify three subtypes of direction-selective and two subtypes of orientation-selective retinal input. Composite parametric functional maps generated across many larvae show laminar segregation of direction- and orientation-selective responses and unexpected retinotopic biases in the distribution of functional subtypes. These findings provide a systematic description of the form, organization, and dimensionality of visual inputs to the brain and will serve as a platform for understanding emergent properties in tectal circuits associated with visually driven behavior.

Bouveret's syndrome, first described in 1896, is gastric obstruction by a gallstone following a cholecystoduodenal fistula. Endoscopy is the mainstay of diagnosis, but radiographic examination such as upper gastrointestinal contrast series and abdominal radiography can also contribute to the diagnosis. Diagnosis by computed tomography and ultrasonography has also been described. The syndrome can be diagnosed and treated endoscopically, with stone extraction or mechanical lithotripsy. Extracorporeal shockwave lithotripsy has also been used successfully. Surgery is required in over 90% of cases, with mortality rates ranging from 19% to 24%. One-stage and two-stage procedures have been described, including enterolithotomy, cholecystectomy, and fistula repair, no convincing data are available to show which of these two approaches provides a better outcome. Although the condition is rare, Bouveret's syndrome should be considered in elderly patients with a history of chronic cholecystitis who present with pain, vomiting or haematemesis.

Motor neurons project axons from the hindbrain and spinal cord to muscle, where they induce myofibre contractions through neurotransmitter release at neuromuscular junctions. Studies of neuromuscular junction formation and homeostasis have been largely confined to in vivo models. In this study, three powerful tools have been merged—pluripotent stem cells, optogenetics, and microfabrication—and an open microdevice is designed in which motor axons grow from a neural compartment containing embryonic stem cell‐derived motor neurons and astrocytes through microchannels to form functional neuromuscular junctions with contractile myofibres in a separate compartment. Optogenetic entrainment of motor neurons in this reductionist neuromuscular circuit enhances neuromuscular junction formation more than twofold, mirroring the activity‐dependence of synapse development in vivo. An established motor neuron disease model is incorporated into the system and it is found that coculture of motor neurons with SOD1G93A astrocytes results in denervation of the central compartment and diminishes myofibre contractions, a phenotype which is rescued by the receptor interacting serine/threonine kinase 1 inhibitor necrostatin. This coculture system replicates key aspects of nerve–muscle connectivity in vivo and represents a rapid and scalable alternative to animal models of neuromuscular function and disease.