Identification, physiological actions, and distribution of TPSGFLGMRamide: A novel tachykinin-related peptide from the midgut and stomatogastric nervous system of Cancer crabs

In most invertebrates, multiple species-specific isoforms of tachykinin-related peptide (TRP) are common. In contrast, only a single conserved TRP isoform, APSGFLGMRamide, has been documented in decapod crustaceans, leading to the hypothesis that it is the sole TRP present in this arthropod order. Previous studies of crustacean TRPs have focused on neuronal tissue, but the recent demonstration of TRPs in midgut epithelial cells in Cancer species led us to question whether other TRPs are present in the gut, as is the case in insects. Using direct tissue matrix assisted laser desorption/ionization Fourier transform mass spectrometry, in combination with sustained off-resonance irradiation collision-induced dissociation, we found that at least one additional TRP is present in Cancer irroratus, Cancer borealis, Cancer magister, and Cancer productus. The novel TRP isoform, TPSGFLGMRamide, was present not only in the midgut, but also in the stomatogastric nervous system (STNS). In addition, we identified an unprocessed TRP precursor APSGFLGMRG, which was detected in midgut tissues only. TRP immunohistochemistry, in combination with preadsorption studies, suggests that APSGFLGMRamide and TPSGFLGMRamide are co-localized in the stomatogastric ganglion (STG), which is contained within the STNS. Exogenous application of TPSGFLGMRamide to the STG elicited a pyloric motor pattern that was identical to that elicited by APSGFLGMRamide, whereas APSGFLGMRG did not alter the pyloric motor pattern. © 2007 The Authors

The Genetic Identification and Physiological Characterization of a Novel Locus for Non-Progressive Hearing Loss on Mouse Chromosome 17

Thesis (Ph.D.)--University of Washington, 2014Presbycusis, the progressive loss of hearing that occurs with aging, is a widespread condition with serious economical and social ramifications. Mice with age-related hearing loss (AHL) are commonly used as models of presbycusis because of their physiological and genetic homology to the human auditory system. The inbred mouse, 129S6/SvEvTac (129S6), often used to study its resistance to noise-induced hearing loss (NIHL) also has early-onset progressive hearing loss. However, little is known about the AHL trait of 129S6 or the identity of the underlying genes. This dissertation will describe studies conducted in 129S6 to understand the physiological mechanisms associated with AHL, its genetic manifestation and inheritance, and the physical location of the causal genes. Hearing sensitivity was examined in subjects using non-invasive auditory-evoked potentials and otoacoustic emissions. My research will show that hearing loss in 129S6 is early-onset, slow progressive, and a combination between sensory and conductive hearing loss. The research will show that hearing loss in the 129S6 strain is autosomal recessive with possible contribution by multiple genes. Selective breeding and the creation of recombinant-inbred mice were used to define a novel 3.7 megabase (Mb) locus for non-progressive hearing loss (nphl) on mouse proximal Chromosome (Chr) 17 that contributes exclusively to high-frequency (>24 kHz). The nphl locus is linked genetically to the same region on Chr 17 exhibiting resistance to NIHL and a progressive hearing loss (PHL) locus. Collectively, the work in this dissertation more accurately defines the physiological and genetic characteristics of hearing loss in the 129S6 mouse. The understanding of this phenotype and the effects in mice will provide insight to future therapeutic advantages and preventative measures for homologous human conditions