A correlative super-resolution protocol to visualise structural underpinnings of fast second-messenger signalling in primary cell types.

Nanometre-scale cellular information obtained through super-resolution microscopies are often unaccompanied by functional information, particularly transient and diffusible signals through which life is orchestrated in the nano-micrometre spatial scale. We describe a correlative imaging protocol which allows the ubiquitous intracellular second messenger, calcium (Ca), to be directly visualised against nanoscale patterns of the ryanodine receptor (RyR) Ca channels which give rise to these Ca signals in wildtype primary cells. This was achieved by combining total internal reflection fluorescence (TIRF) imaging of the elementary Ca signals, with the subsequent DNA-PAINT imaging of the RyRs.

Insoluble Aβ overexpression in an knock-in mouse model alters microstructure and gamma oscillations in the prefrontal cortex, affecting anxiety-related behaviours.

We studied a new amyloid-beta precursor protein () knock-in mouse model of Alzheimer's disease ( ), containing the Swedish KM670/671NL mutation, the Iberian I716F mutation and the Artic E693G mutation, which generates elevated levels of amyloid beta (Aβ) and Aβ without the confounds associated with APP overexpression. This enabled us to assess changes in anxiety-related and social behaviours, and neural alterations potentially underlying such changes, driven specifically by Aβ accumulation. knock-in mice exhibited subtle deficits in tasks assessing social olfaction, but not in social motivation tasks.

The within-subject application of diffusion tensor MRI and CLARITY reveals brain structural changes in deletion mice.

Background: Of the many genetic mutations known to increase the risk of autism spectrum disorder, a large proportion cluster upon synaptic proteins. One such family of presynaptic proteins are the neurexins (NRXN), and recent genetic and mouse evidence has suggested a causative role for in generating altered social behaviours. Autism has been conceptualised as a disorder of atypical connectivity, yet how single-gene mutations affect such connectivity remains under-explored.

Three-Dimensional and Chemical Mapping of Intracellular Signaling Nanodomains in Health and Disease with Enhanced Expansion Microscopy.

Nanodomains are intracellular foci which transduce signals between major cellular compartments. One of the most ubiquitous signal transducers, the ryanodine receptor (RyR) calcium channel, is tightly clustered within these nanodomains. Super-resolution microscopy has previously been used to visualize RyR clusters near the cell surface.

The developmental transcriptome of the human heart.

The human heart develops through complex mechanisms producing morphological and functional changes during gestation. We have recently demonstrated using diffusion tensor MRI that over the relatively short space of 40 days, between 100-140 days gestational age, the ventricular myocardium transforms from a disorganised tissue to the ordered structure characteristic of mature cardiac tissue. However, the genetic basis underpinning this maturation is unclear.