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Neuronal networks’ hyperexcitability often results from an unbalance between excitatory and inhibitory neurotransmission; however, underlying synaptic alterations leading to this condition remains poorly understood. Here, we assess synaptic changes in the visual cortex of epileptic tetanus neurotoxin-injected mice. Using an ultrastructural measure of synaptic activity, we quantified functional differences at excitatory and inhibitory synapses. We found homeostatic changes in hyperexcitable networks, expressed as an early onset lengthening of active zones at inhibitory synapses followed by spatial reorganization of recycled vesicles at excitatory synapses. A proteomic analysis of synaptic content revealed an upregulation of Carboxypeptidase E (CPE) following Tetanus NeuroToxin (TeNT) injection. Remarkably, inhibition of CPE rapidly decreased network discharges in vivo . These analyses reveal a complex landscape of homeostatic changes affecting the epileptic synaptic release machinery, differentially at inhibitory and excitatory terminals. Our study unveil homeostatic presynaptic mechanisms which may impact release timing rather than synaptic strength.

In a polychrome artefact, coloured paint layers are applied on architectural elements or sculptures. Paint layers are made up of the colour, which is most typically an inorganic pigment and, with the exception of frescos, an organic binder, which enables the pigment to be dispersed and applied with a brush. From an analytical point of view the characterisation of organic paint binders is very challenging: the organic matter represents a very small amount of the total weight of the sample which is very small and aged. In this paper we describe the analytical approach applied for the characterisation of samples collected from a selection Gandhara polychromies. The analytical strategies and techniques employed are described and examples of the results obtained are presented., Restauro Archeologico, Vol. 27 No. 1 (2019)

MALDI mass spectrometry imaging is able to simultaneously determine the spatial distribution of hundreds of molecules directly from tissue sections, without labeling and without prior knowledge. Ultra-high mass resolution measurements based on Fourier-transform mass spectrometry have been utilized to resolve isobaric lipids, metabolites and tryptic peptides. Here we demonstrate the potential of 15T MALDI-FTICR MSI for molecular pathology in a mouse model of high-grade glioma. The high mass accuracy and resolving power of high field FTICR MSI enabled tumor specific proteoforms, and tumor-specific proteins with overlapping and isobaric isotopic distributions to be clearly resolved. The protein ions detected by MALDI MSI were assigned to proteins identified by region-specific microproteomics (0.8 mm2 regions isolated using laser capture microdissection) on the basis of exact mass and isotopic distribution. These label free quantitative experiments also confirmed the protein expression changes observed by MALDI MSI and revealed changes in key metabolic proteins, which were supported by in-situ metabolite MALDI MSI.