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Olfactory responses are intensely enhanced with the addition of endogenous and engineered primarily-elemental small zinc nanoparticles (NPs). With aging, oxidation of these Zn nanoparticles eliminated the observed enhancement. The design of a polyethylene glycol coating to meet storage requirements of engineered zinc nanoparticles is evaluated to achieve maximal olfactory benefit. The zinc nanoparticles were covered with 1000 g/mol or 400 g/mol molecular weight polyethylene glycol (PEG). Non-PEGylated and PEGylated zinc nanoparticles were tested by electroolfactogram with isolated rat olfactory epithelium and odorant responses evoked by the mixture of eugenol, ethyl butyrate and (±) carvone after storage at 278 K (5 oC), 303 K (30 oC) and 323 K (50 oC). The particles were analyzed by atomic force microscopy, transmission electron microscopy, X-ray photoelectron spectroscopy, and laser Doppler velocimetry. Our data indicate that stored ZnPEG400 nanoparticles maintain physiologically-consistent olfactory enhancement for over 300 days. These engineered Nanoparticles support future applications in olfactory research, sensitive detection, and medicine. [ABSTRACT FROM AUTHOR]

Mammalian olfactory epithelium can withstand the external environment, undergo life-long regeneration, and respond to thousands of odorant stimuli, making it an attractive system for a variety of studies. Previously, we described a long-lived olfactory coculture of olfactory epithelium and bulb tissues and we present here the kinetic properties of that culture system. Neonatal mouse epithelial-bulbar explants were grown for periods as long as 121 days in vitro (DIV), nearly doubling the survival time of our previously longest lived cultures. Cultures at all ages responded to air-borne odorants. The youngest cultures (1-15 DIV) showed shorter half-rise and half-decay times than older cultures (21-121 DIV), and were more variable in their half-decay times. Zinc nanoparticles enhanced electro-olfactogram responses of both younger and older cultures and both groups were immunopositive for olfactory marker protein. The results show that our olfactory culture model can support mature, odorant-responsive olfactory receptor neurons that possess many of the response features of in situ olfactory receptor neurons. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Zinc metal nanoparticles in picomolar concentrations strongly enhance odorant responses of olfactory sensory neurons. One- to 2-nm metallic particles contain 40–300 zinc metal atoms, which are not in an ionic state. We exposed rat olfactory epithelium to metal nanoparticles and measured odorant responses by electroolfactogram and whole-cell patch clamp. A small amount of zinc nanoparticles added to an odorant or an extracellular/intracellular particle perfusion strongly increases the odorant response in a dose-dependent manner. Zinc nanoparticles alone produce no odor effects. Copper, gold, or silver nanoparticles do not produce effects similar to those of zinc. If zinc nanoparticles are replaced by Zn+2 ions in the same concentration range, we observed a reduction of the olfactory receptor neuron odorant response. Based on these observations, we hypothesize that zinc nanoparticles are closely located to the interface between the guanine nucleotide-binding protein and the receptor proteins and are involved in transferring signals in the initial events of olfaction. Our results suggest that zinc metal nanoparticles can be used to enhance and sustain the initial olfactory events. [ABSTRACT FROM PUBLISHER]

Exposure to the estrogen receptor alpha (ERα) ligand diethylstilbesterol (DES) between neonatal days 2 to 12 induces penile adipogenesis and adult infertility in rats. The objective of this study was to investigate the in vivo interaction between DES-activated ERα and the proadipogenic transcription factor peroxisome proliferator-activated receptor gamma (PPARγ). Transcripts for PPARs α, β, and γ and γ1a splice variant were detected in Sprague-Dawley normal rat penis with PPARγ predominating. In addition, PPARγ1b and PPARγ2 were newly induced by DES. The PPARγ transcripts were significantly upregulated with DES and reduced by antiestrogen ICI 182, 780. At the cellular level, PPARγ protein was detected in urethral transitional epithelium and stromal, endothelial, neuronal, and smooth muscular cells. Treatment with DES activated ERα and induced adipocyte differentiation in corpus cavernosum penis. Those adipocytes exhibited strong nuclear PPARγ expression. These results suggest a biological overlap between PPARγ and ERα and highlight a mechanism for endocrine disruption. [ABSTRACT FROM AUTHOR]

Explanations for the chemosensory abilities of newborn mammals focus primarily on food (milk) acquisition and communication (e.g., maternal–infant bonding). However, the relative importance of the main and accessory (vomeronasal) olfactory systems is hypothesized to differ at birth between altricial and precocial mammals. Strepsirrhines (lemurs and lorises) possess main and accessory olfactory systems, and vary in life-history traits related to infant dependency and maturation. Accordingly, this study examines the size and maturational characteristics of vomeronasal (VNNE) and olfactory (OE) neuroepithelia in strepsirrhines. Serially sectioned heads of 18 infant cadavers were examined microscopically for neuroepithelial distribution. Measurements were taken on the length of the nasal fossa on one side that was occupied by VNNE and OE. The data were corrected for body size using the cranial length or body mass, and were then examined for correlation with several life-history variables, as well as activity pattern. In addition, immunohistochemistry was used to identify cells in the VNNE and OE that express olfactory marker protein (OMP), a marker of mature olfactory neurons. Relative OE extent was not significantly correlated with any of the life-history variables. Relative VNNE length was negatively correlated with relative gestation length and relative neonatal mass (P<0.05). However, when we corrected for phylogenetic relationships, we found no significant correlations between either of the neuroepithelial measurements and life-history variables. Immunohistochemical findings suggest that OE has more OMP-reactive cells than VNNE in all species. OMP-reactive cells appear to be less numerous in diurnal species compared to most nocturnal species. These results indicate that the VNNE may be relatively longer at birth in altricial species. However, it remains uncertain how phylogeny and/or ontogeny may explain these findings. Am. J. Primatol. 69:74–85, 2007. © 2006 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Reports that RGS2 protein reduces cAMP production by odorant-stimulated olfactory epithelium membranes in which the [alpha[SUB s] family member [alpha[SUB olf] links odorant receptors to adenlyl cyclase activation. Mechanism for controlling the activities of adenylyl cyclases.

We have previously shown that human alpha-defensins can block the release of IL-1beta from LPS-activated human monocytes. The objective of this study is to use defensins as tools to determine the molecular mechanism by which IL-1beta is processed and secreted from human monocytes. LPS-activated (20 ng/ml, 2 h), 35S-methionine-labeled (1 h) human monocytes were treated with human alpha-defensin HD-5 in the presence or absence of ATP, staphylococcal alpha-toxin (SAT), or nigericin (Nig) for 3 h. Media and cell-associated fractions were harvested separately. IL-1beta was recovered from each by immunoprecipitation and caspase-1 was examined by western blot analysis. It was found that HD-5 blocked the release of mature IL-1beta from cells treated with ATP or Nig, while HD-5 did not inhibit ATP- or Nig-induced caspase-1 activation and externalization. However, SAT-induced caspase-1 activation was blocked by HD-5 and cytosolic mature IL-1beta was not detected in cells treated with SAT and HD-5. To our knowledge, HD-5 is the first known endogenous inhibitor of IL-1beta release. This study suggest that although both IL-1beta and caspase-1 are detected in the extracellular milieu after ATP stimulation, mature IL-1beta and its converting enzyme caspase-1 are secreted via different pathways. [ABSTRACT FROM AUTHOR]

Adiponectin (Acrp30) is an adipokine secreted exclusively by white adipose tissue with profound insulin-sensitizing, anflammatory and anti-atherogenie properties. Several lines of evidence suggest that adiponectin localized in the Golgi is an important source of intracellular adiponectin available for secretion. However, the mechanism by which adiponectin trafficking and secretion occurs is not well understood. We investigated the role of myosin II, an actin-based motor, in the trafficking and secretion of adiponectin in 3T3-L1 adipocytes. Myosin II (IIA and IIB) isoforms colocalized with adiponectin as determined by immunoflourescence. Transmission electron microscopy of purified adiponectin-containing vesicles also demonstrated that myosin IIA and IIB are present in adiponectin-containing vesicles. Immunofluorescent microscopy and immunogold microscopy revealed that myosin IIA and IIB are scattered in the cytoplasm of the cell while exhibiting perinuclear localization. Myosin IIA and IIB were localized in the TGN/Golgi region as evidenced by partial colocalization with the cis-Golgi marker, p115 and the TGN marker, γ-Adaptin. Inhibition of myosin IIA and lib activity by blebbistatin (a specific myosin II inhibitor), and latrunculin B (an actin depolymerizing agent), dispersed myosin IIA and IIB towards the periphery while significantly inhibiting adiponectin secretion. Therefore, adiponectin trafficking appear's to be actin-dependent in the adipocyte. Furthermore, the actin-based motors, myosin IIA and IIB, are involved in the intracellular trafficking and constitutive secretion of adiponectin in 3T3-L1 adipocytes. [ABSTRACT FROM AUTHOR]

An obituary for Pasquale P. C. Graziadei, a pioneer in olfactory-system research and was a professor of Biological Science and Neuroscience at Florida State University is presented.