MUC4 involvement in ErbB2/ErbB3 phosphorylation and signaling in response to airway cell mechanical injury

The receptor tyrosine kinases ErbB2 and ErbB3 are phosphorylated in response to injury of the airway epithelium. Since we have shown that the membrane mucin MUC4 can act as a ligand/modulator for ErbB2, affecting its localization in polarized epithelial cells and its phosphorylation, we questioned whether Muc4 was involved, along with ErbB2 and ErbB3, in the damage response of airway epithelia. To test this hypothesis, we first examined the localization of MUC4 in human airway samples. Both immunocytochemistry and immunofluorescence showed a co‐localization of MUC4 and ErbB2 at the airway luminal surface. Sequential immunoprecipitation and immunoblotting from airway cells demonstrated that the MUC4 and ErbB2 are present as a complex in airway epithelial cells. To assess the participation of MUC4 in the damage response, cultures of NCI‐H292 or airway cells were scratch‐wounded, then analyzed for association of phospho‐ErbB2 and ‐ErbB3 with MUC4 by sequential immunoprecipitation and immunoblotting. Wounded cultures exhibited increased phosphorylation of both receptors in complex with MUC4. Scratch wounding also increased activation of the downstream pathway through Akt, as predicted from our previous studies on Muc4 effects on ErbB2 and ErbB3. The participation of MUC4 in the phosphorylation response was also indicated by siRNA repression of MUC4 expression, which resulted in diminution of the phosphorylation of ErbB2 and ErbB3. These studies provide a new model for the airway epithelial damage response, in which the MUC4–ErbB2 complex is a key element in the sensor mechanism and phosphorylation of the receptors. J. Cell. Biochem. 107: 112–122, 2009. © 2009 Wiley‐Liss, Inc.     

Interrelationships of Staphyliniform groups inferred from 18S and 28S rDNA sequences, with special emphasis on Hydrophiloidea (Coleoptera, Staphyliniformia)

The series Staphyliniformia is one of the mega‐diverse groups of Coleoptera, but the relationships among the main families are still poorly understood. In this paper we address the interrelationships of staphyliniform groups, with special emphasis on Hydrophiloidea and Hydraenidae, based on partial sequences of the ribosomal genes 18S rDNA and 28S rDNA. Sequence data were analysed with parsimony and Bayesian posterior probabilities, in an attempt to overcome the likely effect of some branches longer than the 95% cumulative probability of the estimated normal distribution of the path lengths of the species. The inter‐family relationships in the trees obtained with both methods were in general poorly supported, although most of the results based on the sequence data are in good agreement with morphological studies. In none of our analyses a close relationship between Hydraenidae and Hydrophiloidea was supported, contrary to the traditional view but in agreement with recent morphological investigations. Hydraenidae form a clade with Ptiliidae and Scydmaenidae in the tree obtained with Bayesian probabilities, but are placed as basal group of Staphyliniformia (with Silphidae as subordinate group) in the parsimony tree. Based on the analysed data with a limited set of outgroups Scarabaeoidea are nested within Staphyliniformia. However, this needs further support. Hydrophiloidea s.str., Sphaeridiinae, Histeroidea (Histeridae + Sphaeritidae), and all staphylinoid families included are confirmed as monophyletic, with the exception of Hydraenidae in the parsimony tree. Spercheidae are not a basal group within Hydrophiloidea, as has been previously suggested, but included in a polytomy with other Hydrophilidae in the Bayesian analyses, or its sistergroup (with the inclusion of Epimetopidae) in the parsimony tree. Helophorus is placed at the base of Hydrophiloidea in the parsimony tree. The monophyly of Hydrophiloidea s.l. (including the histeroid families) and Staphylinoidea could not be confirmed by the analysed data. Some results, such as a placement of Silphidae as subordinate group of Hydraenidae (parsimony tree), or a sistergroup relationship between Ptiliidae and Scydmaenidae, appear unlikely from a morphological point of view.     

Identification of respiratory vagal feedback in awake normal subjects using pseudorandom unloading.

Evidence of the Hering-Breuer reflex has been found in humans during anesthesia and sleep but not during wakefulness. Cortical influences, present during wakefulness, may mask the effects of this reflex in awake humans. We hypothesized that, if lung volume were increased in awake subjects unaware of the stimulus, vagal feedback would modulate breathing on a breath-to-breath basis. To test this hypothesis, we employed proportional assist ventilation in a pseudorandom sequence to unload the respiratory system above and below the perceptual threshold in 17 normal subjects. Tidal volume, integrated respiratory muscle pressure per breath, and inspiratory time were recorded. Both sub- and suprathreshold stimulation evoked a significant increase in tidal volume and inspiratory flow rate, but a significant decrease in inspiratory time was present only during the application of a subthreshold stimulus. We conclude that vagal feedback modulates respiratory timing on a breath-by-breath basis in awake humans, as long as there is no awareness of the stimulus.     

Diet changes in the carbon and nitrogen content of the copepod Metridia lucens

Diel changes in the near-surface (0–50 m) abundance, prosomelength, and carbon and nitrogen content of the copepod Metridialucens were measured in Deep Cove, Doubtful Sound, New Zealand(45°27'S, 167°9'E) between 3 and 6 September 1996. Metridialucens showed maximal abundance a night, suggesting a patternof normal diel vertical migration (DVM). The change in abundancesuggested that the descent of the population occurred –1h prior to dawn and the ascent –1 h after dusk. However,a proportion of the population remained near the surface duringthe day. Although there was no diel pattern in the prosome lengthof M.lucens collected near the surface, there was a marked dielcycle in the measured carbon and nitrogen contents, with maximalvalues being measured towards the end of the night prior tothe downward migration. We suggest that this diet cycle in themeasured elemental content was caused by DVM occurring morestrongly in those animals which had a better body condition,i.e. a higher elemental content per unit length.     

Clinical aspects of ECL-cell abnormalities.

ECL cell hyperplasia results from hypergastrinemia, and in man this occurs due to achlorhydria in atrophic gastritis (pernicious anemia [PA]) and gastrinoma (Zollinger-Ellison syndrome [ZES]). Progression to neoplasia, i.e., ECL cell carcinoids (usually small, multicentric and non-functional), occurs in some five to 10 percent of patients with PA where they remain gastrin-dependent and reversible by normalization of serum gastrin by antrectomy. Even if untreated, the carcinoids are almost invariably benign and do not cause death. In ZES, ECL cell hyperplasia is progressive due to hypergastrinemia. However, carcinoids develop only in the MEN-I subtype but pose no additional threat of malignancy. A conservative approach is recommended for small multicentric carcinoids, and the tumors do not need removal. By contrast, single, large, non-gastrin-dependent carcinoids represent a different biological and clinical problem and are frequently malignant.     

Behaviour, natural history, and annual cycle of the Henderson Island rail Porzana atra (Aves: Rallidae)

The little known endemic Henderson Island rail (or Henderson rail) Porzflna atra , inhabits forest on the coastal plain and upraised plateau of Henderson Island. Rails were studied for 15 months from January 1991 to March 1992. The population was estimated at c. 6200 individuals living in pairs or cooperative groups of 3–4 adults on territories averaging about 1 ha. Two or three eggs were laid in covered or open nests near the ground from mid-July to mid-February. Up to five consecutive nesting attempts were made in cases where eggs or young chicks were lost. Adults laid a second clutch when chicks were fully feathered at about one month of age. Both sexes incubated and helped rear the young. Older chicks sometimes helped feed younger siblings. Dispersal of juveniles from the natal territory took place in April. Adult birds underwent a rapid, simultaneous post-nuptial moult of the remiges in February-April; the post-juvenile moult involved body feathers only. Data on morphometries, breeding ecology, courtship behaviour and voice are compared with available information for the spotless crake P. tabuensis , the Henderson rail's closest relative and probable ancestor. These comparisons provide some information on how these two taxa have differentiated since rails arrived on Henderson Island some time in the last 380000 years.