A mesoscale finite element modeling approach for understanding brain morphology and material heterogeneity effects in chronic traumatic encephalopathy.

Chronic Traumatic Encephalopathy (CTE) affects a significant portion of athletes in contact sports but is difficult to quantify using clinical examinations and modeling approaches. We use an in silico approach to quantify CTE biomechanics using mesoscale Finite Element (FE) analysis that bridges with macroscale whole head FE analysis. The sulci geometry produces complex stress waves that interact with one another to create increased shear stresses at the sulci depth that are significantly larger than in analyses without sulci (from 0.5 to 18.0 kPa). Sulci peak stress concentration regions coincide with experimentally observed CTE sites documented in the literature. HighlightsSulci introduce stress localizations at their depth in the gray matterSulci stress fields interact to produce stress concentration sites in white matterDifferentiating brain tissue properties did not significantly affect peak stresses.

Mutations of RegIalpha are associated with enterochromaffin-like cell tumor development in patients with hypergastrinemia.

BACKGROUND & AIMS: The RegIalpha gene (Reg) encodes a secretory protein proposed to regulate islet beta-cell and gastric mucous cell growth. Reg is expressed in rat gastric enterochromaffin-like (ECL) cells. The aim of this study was to examine Reg expression in human corpus and to determine the identity of Reg in ECL cell carcinoid tumors in hypergastrinemic patients. METHODS: Reg messenger RNA (mRNA) abundance was quantified by Northern blot in extracts of gastric corpus from patients with and without ECL cell tumors and in AR4-2J cells stimulated by gastrin; cellular origins were determined by immunocytochemistry. Mutations of Reg were determined by reverse-transcription polymerase chain reaction, cloning, and sequencing, and the mutated protein was expressed in HIT-T15 cells. RESULTS: Reg mRNA abundance was increased approximately threefold in the corpus of hypergastrinemic patients compared with controls, and was enriched in 3 of 7 ECL cell carcinoid tumors but not in non-endocrine cell gastric polyps. In AR4-2J cells, gastrin stimulated Reg mRNA abundance; this was eliminated by the gastrin/cholecystokinin B antagonist L-740,093 (10(-9) mol/L). Immunocytochemistry indicated that Reg was located in both chief cells and ECL cells in human corpus. Mutations of Reg were identified in 3 of 5 patients with ECL cell carcinoid tumors; in 2 cases, mutation of the initiator methionine residue led to exclusion of the protein from the secretory pathway. CONCLUSIONS: Gastrin regulates Reg mRNA abundance in human corpus. Mutations of Reg that prevent secretion are associated with ECL cell carcinoids, suggesting a function as an autocrine or paracrine tumor suppressor.

Small cardioactive peptide gene: structure, expression and mass spectrometric analysis reveals a complex pattern of co-transmitters in a snail feeding neuron.

The small cardioactive peptides (SCPs) are an important group of neural cotransmitters in molluscs where they are known to play both central and peripheral modulatory roles in the control of feeding behaviour. Here we show that in the snail Lymnaea the SCP gene exists in one interrupted copy that produces a single species of transcript which encodes a prepropeptide containing two structurally related SCPs SGYLAFPRMamide (SCP(A)) and pQNYLAFPRMamide (SCP(B)). In situ hybridization was used to localize expression specifically to the soma of several types of motoneurons in the feeding system of Lymnaea, including the giant B2 foregut motoneurons. The peptide content of individual B2 cell bodies was analysed by matrix-assisted laser desorption/ionization mass spectrometry and the structures of the SCPs predicted from the cloned gene were confirmed in these cells by post-source decay fragmentation analysis. Identical stimulatory activity for the two SCP peptides was demonstrated by their application to the isolated foregut, suggesting that their co-release from the B2 cells may play an important part in the co-modulation of gut motility, together with acetylcholine and the myomodulin family of peptides.

Distance modulation of neural activity in the visual cortex.

Humans use distance information to scale the size of objects. Earlier studies demonstrated changes in neural response as a function of gaze direction and gaze distance in the dorsal visual cortical pathway to parietal cortex. These findings have been interpreted as evidence of the parietal pathway's role in spatial representation. Here, distance-dependent changes in neural response were also found to be common in neurons in the ventral pathway leading to inferotemporal cortex of monkeys. This result implies that the information necessary for object and spatial scaling is common to all visual cortical areas.