Eosinophil-mediated cholinergic nerve remodeling

Eosinophils are observed to localize to cholinergic nerves in a variety of inflammatory conditions such as asthma, rhinitis, eosinophilic gastroenteritis, and inflammatory bowel disease, where they are also responsible for the induction of cell signaling.Wehypothesized that a consequence of eosinophil localization to cholinergic nerves would involve a neural remodeling process. Eosinophil co-culture with cholinergic IMR32 cells led to increased expression of the M2 muscarinic receptor, with this induction being mediated via an adhesion-dependent release of eosinophil proteins, including major basic protein and nerve growth factor. Studies on the promoter sequence of the M2 receptor indicated that this induction was initiated at a transcription start site 145 kb upstream of the gene-coding region. This promoter site contains binding sites for a variety of transcription factors including SP1, AP1, and AP2. Eosinophils also induced the expression of several cholinergic genes involved in the synthesis, storage, and metabolism of acetylcholine, including the enzymes choline acetyltransferase, vesicular acetylcholine transferase, and acetylcholinesterase. The observed eosinophil-induced changes in enzyme content were associated with a reduction in intracellular neural acetylcholine but an increase in choline content, suggesting increased acetylcholine turnover and a reduction in acetylcholinesterase activity, in turn suggesting reduced catabolism of acetylcholine. Together these data suggest that eosinophil localization to cholinergic nerves induces neural remodeling, promoting a cholinergic phenotype.peer-reviewe

Failure by fracture in bulk metal forming

This paper revisits formability in bulk metal forming in the light of fundamental concepts of plasticity,ductile damage and crack opening modes. It proposes a new test to appraise the accuracy, reliability and validity of fracture loci associated with crack opening by tension and out-of-plane shear under loading conditions different from those found in conventional tests for bulk formability based on cylindrical,tapered and flanged specimens.The new formability test consists of expanding rings of various wall thicknesses with a stepped conical punch and allows investigating the onset of failure by cracking under three-dimensional states of stress subjected to various magnitudes of stress triaxiality.The presentation is supported by finite element analysis and experimentation in aluminium AA2030-T4 and results show that failure by fracture under three-dimensional loading conditions can be easily and effectively characterized in the space of equivalent strain to fracture and stress triaxiality.© 2014 Elsevier B.V. All rights reserved