The purpose of this study was to generate, by real-time PCR, a quantitative expression level profile of the 19 human UDP-glucuronosyltransferases (UGTs) of subfamilies 1A, 2A and 2B, in 26 adult and 3 fetal tissues, for better understanding of their roles in xenobiotic and endobiotic metabolism. Adult liver contained the highest level of combined UGTs mRNA, and UGT2B4 was the most abundant isoform in this tissue (40% of total). Other well expressed hepatic UGTs, in decreasing order of mRNA level, were 1A9, 2B7, 1A4, 2B10, 1A1, 1A6, 2B11, 2B15, 1A3, 2A3, 2B17 and 2B28. UGT2B4 was by far the most abundant isoform in the fetal liver (90% of total). The combined UGT mRNA expression in both adult and fetal olfactory epithelium was high, about 20% the adult hepatic level. Interestingly, a large developmental change was found in this tissue from high UGT2A1 and UGT2A2 expression in the fetus to UGT1A6 in the adult. The most abundantly expressed UGTs in the small intestine were 2A3, 1A10, 1A1, 1A6 and 2B7, while 1A10 and 2A3 predominated in the colon. The results provide the most comprehensive data to date on the tissue distribution of the human UGTs.

Although the heteromeric combination of type 1 taste receptors 2 and 3 (T1r2 + T1r3) is well established as the major receptor for sugars and noncaloric sweeteners, there is also evidence of T1r-independent sweet taste in mice, particularly so for sugars. Before the molecular cloning of the T1rs, it had been proposed that sweet taste detection depended on ( a ) activation of sugar-gated cation channels and/or ( b ) sugar binding to G protein-coupled receptors to initiate second-messenger cascades. By either mechanism, sugars would elicit depolarization of sweet-responsive taste cells, which would transmit their signal to gustatory afferents. We examined the nature of T1r-independent sweet taste; our starting point was to determine if taste cells express glucose transporters (GLUTs) and metabolic sensors that serve as sugar sensors in other tissues. Using RT-PCR, quantitative PCR, in situ hybridization, and immunohistochemistry, we determined that several GLUTs (GLUT2, GLUT4, GLUT8, and GLUT9), a sodium–glucose cotransporter (SGLT1), and two components of the ATP-gated K + (K ATP ) metabolic sensor [sulfonylurea receptor (SUR) 1 and potassium inwardly rectifying channel (Kir) 6.1] were expressed selectively in taste cells. Consistent with a role in sweet taste, GLUT4, SGLT1, and SUR1 were expressed preferentially in T1r3-positive taste cells. Electrophysiological recording determined that nearly 20% of the total outward current of mouse fungiform taste cells was composed of K ATP channels. Because the overwhelming majority of T1r3-expressing taste cells also express SUR1, and vice versa, it is likely that K ATP channels constitute a major portion of K + channels in the T1r3 subset of taste cells. Taste cell-expressed glucose sensors and K ATP may serve as mediators of the T1r-independent sweet taste of sugars.

Until recently, reliable markers for adult stem cells have been lacking for many regenerative mammalian tissues. Lgr5 (leucine-rich repeat-containing G-protein coupled receptor 5) has been identified as a marker for adult stem cells in intestine, stomach, and hair follicle; Lgr5-expressing cells give rise to all types of cells in these tissues. Taste epithelium also regenerates constantly, yet the identity of adult taste stem cells remains elusive. In this study, we found that Lgr5 is strongly expressed in cells at the bottom of trench areas at the base of circumvallate and foliate taste papillae and weakly expressed in the basal area of taste buds and that Lgr5-expressing cells in posterior tongue are a subset of K14-positive epithelial cells. Lineage-tracing experiments using an inducible Cre knock-in allele in combination with Rosa26-LacZ and Rosa26-tdTomato reporter strains showed that Lgr5-expressing cells gave rise to taste cells, perigemmal cells, along with self-renewing cells at the bottom of trench areas at the base of circumvallate and foliate papillae. Moreover, using subtype-specific taste markers, we found that Lgr5-expressing cell progeny include all three major types of adult taste cells. Our results indicate that Lgr5 may mark adult taste stem or progenitor cells in the posterior portion of the tongue.

Background/Objective Chronic rhinosinusitis (CRS) is a complex heterogeneous inflammatory disease that affects the nasal cavity, yet the pathological examination of the olfactory mucosa (OM) in this disease has been limited. Methods Nasal biopsies were obtained from 20 control subjects and 50 CRS patients in conjunction with clinical assessments. Histopathology of these nasal biopsies was performed and immunohistochemistry was used to characterize non-neuronal, neuronal and inflammatory cells in the OM. These OM characteristics were then evaluated to determine the degree to which pathological features may be related to smell loss in CRS. Results Histopathological examination of control and CRS OM revealed changes in the normal pseudostratified olfactory epithelium (OE): intermixing of goblet cells, metaplasia to squamous-like cells, and erosion of the OE. Lower percentages of normal epithelium and olfactory sensory neurons were found in CRS OE compared with controls. Relative to other CRS patients, those with anosmia had the greatest amount of OE erosion, the highest density of eosinophils infiltrating the OE and exhibited the most extensive abnormalities on CT and endoscopic examination, including being significantly more likely to exhibit nasal polyposis. Conclusion Our results suggest that OM pathology observed in nasal biopsies can assist in understanding the degree of epithelial change and sensorineural damage in CRS and the potential for olfactory loss.

To enhance bite force at the canines, feliform carnivorans have short rostra relative to caniform carnivorans. Rostral reduction in feliforms results in less rostrocaudal space for the maxilloturbinals, the complex set of bones involved in conditioning inspired air and conserving water. It is unknown whether the maxilloturbinals might show adaptations to adjust for this loss, such as greater complexity than what is observed in longer snouted caniforms. To understand the impact of rostral shortening on turbinals in feliforms, we used high resolution CT scans to quantify turbinal surface areas (SA) in 16 feliforms and compared them with published data on 20 caniforms. Results indicate that feliforms have reduced maxilloturbinal SA for their body mass relative to caniforms, but comparable fronto-ethmoturbinal SA. However, anterior portions of the ethmoturbinals in feliforms extend forward into the snout and are positioned within the respiratory pathway. When the SA of these anterior ethmoturbinals is added to maxilloturbinal SA to produce an estimated respiratory SA, feliforms and caniforms are similar in respiratory SA. This transfer of ethmoturbinal SA to respiratory function results in feliforms having less estimated olfactory SA relative to caniforms. Previous work on canids found a positive association between olfactory surface area and diet, but this was not found for felids. Results are consistent with feliforms having somewhat reduced olfactory ability relative to caniforms. If confirmed by behavioral data, the relative reduction in olfactory SA in many feliforms may reflect a greater reliance on vision in foraging relative to caniforms.