Search

It is well understood that odorants interact with specialized G-protein coupled receptors embedded in the ciliary membrane of olfactory sensory neurons (OSN) which initiates a voltage-generating intracellular cascade of signal transduction events that can be recorded at the epithelial level as an electroolfactogram (EOG). While the depolarizing excitatory pathway in vertebrates involving cyclic adenosine monophosphate (cAMP)-induced Na + /Ca 2+ influx and calcium-induced Cl - efflux is well established, there is evidence of potassium-associated inhibitory currents that correspond with cellular activation. While several Ca 2+ -dependent feedback mechanisms contribute to cellular deactivation which have been commonly attributed to these inhibitory currents, the frequently observed positive ionic conductance prior to excitatory depolarization have led many to suggest an additional earlier inhibitory mechanism at the receptor level that may be independent of downstream calcium influx. Due to conflicting conclusions, the role and mechanism behind Ca 2+ -independent inhibitory currents in olfactory cells is not fully understood. We investigated the functional and temporal involvement of potassium channels in odor transduction by comparing electroolfactogram (EOG) recordings in rat olfactory epithelia following ion channel inhibition and targeted activation of downstream components with or without potassium-blocking. Several K + -channel blocking agents (4-Aminopyridine, charybdotoxin, & iberiotoxin) demonstrated a diminished pre-action potential positive current that corresponded with reduced excitatory response to odor stimulation that was recovered when blockers were removed. We further assessed EOG responses in the absence of odor or with odor response enhancing zinc nanoparticles. Chemically eliciting membrane excitation in the absence of odor stimulation with a phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine (IBMX), in combination with K + -channel inhibition, further indicated potassium channel activation precedes excitatory events and is independent of cAMP-induced calcium influx. These results support previous findings of odor-activated inhibitory potassium currents that may play a functional role in subsequent G-protein activity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Hagerty, Pustovyy, Globa, Vodyanoy and Singletary.)

Organic nitrogen (N) is abundant in soils, but early conceptual frameworks considered it nonessential for plant growth. It is now well recognised that plants have the potential to take up organic N. However, it is still unclear whether plants supplement their N requirements by taking up organic N in situ: at what rate is organic N diffusing towards roots and are plants taking it up? We combined microdialysis with live-root uptake experiments to measure amino acid speciation and diffusion rates towards roots of Eriophorum vaginatum. Amino acid diffusion rates (321 ng N cm -2  h -1 ) were c. 3× higher than those for inorganic N. Positively charged amino acids made up 68% of the N diffusing through soils compared with neutral and negatively charged amino acids. Live-root uptake experiments confirmed that amino acids are taken up by plants (up to 1 µg N g -1  min -1 potential net uptake). Amino acids must be considered when forecasting plant-available N, especially when they dominate the N supply, and when acidity favours proteolysis over net N mineralisation. Determining amino acid production pathways and supply rates will become increasingly important in projecting the extent and consequences of shrub expansion, especially considering the higher C : N ratio of plants relative to soil., (© 2021 The Authors New Phytologist © 2021 New Phytologist Foundation.)

The role of zinc in neurobiology is rapidly expanding. Zinc is especially essential in olfactory neurobiology. Naturally occurring zinc nanoparticles were detected in olfactory and nasal respiratory epithelia and cilia in animals. The addition of these nanoparticles to a mixture of odorants, including ethyl butyrate, eugenol, and carvone, considerably increased the electrical responses of the olfactory sensory receptors. Studies of these nanoparticles by ransmission electron microscopy (TEM) and selected area electron diffraction revealed metal elemental crystalline zinc nanoparticles 2-4 nm in diameter. These particles did not contain oxidized zinc. The enhancement of the odorant responses induced by the endogenous zinc nanoparticles appears to be similar to the amplification produced by engineered zinc nanoparticles. Zinc nanoparticles produce no odor response but increase odor response if mixed with an odorant. These effects are dose-dependent and reversible. Some other metal nanoparticles, such as copper, silver, gold, and platinum, do not have the effects observed in the case of zinc nanoparticles. The olfactory enhancement was observed in young and mature mouse olfactory epithelium cultures, in the dissected olfactory epithelium of rodents, and in live conscious dogs. The physiological significance of the detected endogenous metal nanoparticles in an animal tissue has been demonstrated for the first time. Overall, our results may advance the understanding of the initial events in olfaction.

Background: The development of novel cannabis research methods that are compatible with current federal regulations is imperative to conduct studies of the effects of legal market cannabis. There is very little research on higher strength, higher Δ9-tetrahydrocannabinol (THC), which has become increasingly available since legalization. Research on strains containing cannabidiol (CBD), a second primary, but nonpsychotomimetic, cannabinoid, is very limited. Materials and Methods: Using a novel observational methodology, regular cannabis users were asked to use one of two legal market cannabis strains that they purchased from a local dispensary (one strain containing 8% THC and 16% CBD (THC+CBD) and one containing a 17% THC concentration, but no CBD (THC). After using their suggested cannabis strain as they typically would for a 3-day period, participants returned to the laboratory immediately after their final use. Measures included a blood draw to measure cannabinoid blood levels and circulating cytokines, self-reported subjective drug effects, and verbal recall memory. Results: Analysis of CBD/THC concentration levels in the blood following the 3-day strain manipulation suggests that all, but one participant ( n =23/24) followed instructions and used their assigned strain. Individuals in the THC group ( n =11) smoked no more than their usual amount, and participants who used the THC+CBD ( n =12) strain smoked more than their reported usual amount, but did not have significantly different THC+metabolite blood levels from the THC group. The THC+CBD strain was also associated with less desire to smoke, lower levels of subjective drug effects, and lower levels of circulating cytokines (TNF-α, IL-6, and IL-1β) immediately after use. Conclusions: Initial results support the feasibility of this novel observational methodology involving brief manipulation of strain use. Preliminary findings indicate that participants may self-titrate cannabis use based on cannabinoid concentration and the THC+CBD strain was associated with lower levels of cannabis craving, subjective intoxication, and circulating cytokines., Competing Interests: No competing financial interests exist.

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.

Electrical responses of olfactory sensory neurons to odorants were examined in the presence of zinc nanoparticles of various sizes and degrees of oxidation. The zinc nanoparticles were prepared by the underwater electrical discharge method and analyzed by atomic force microscopy and X-ray photoelectron spectroscopy. Small (1.2 ± 0.3 nm) zinc nanoparticles significantly enhanced electrical responses of olfactory neurons to odorants. After oxidation, however, these small zinc nanoparticles were no longer capable of enhancing olfactory responses. Larger zinc oxide nanoparticles (15 nm and 70 nm) also did not modulate responses to odorants. Neither zinc nor zinc oxide nanoparticles produced olfactory responses when added without odorants. The enhancement of odorant responses by small zinc nanoparticles was explained by the creation of olfactory receptor dimers initiated by small zinc nanoparticles. The results of this work will clarify the mechanisms for the initial events in olfaction, as well as to provide new ways to alleviate anosmia related to the loss of olfactory receptors.

Human population growth and development have heavily degraded coastal ecosystems with cascading impacts across multiple trophic levels. Understanding both the direct and indirect trophic effects of human activities is important for coastal conservation. In New England, recreational overfishing has triggered a regional trophic cascade. Predator depletion releases the herbivorous purple marsh crab from consumer control and leads to overgrazing of marsh cordgrass and salt marsh die-off. The direct and indirect trophic effects of predator depletion on basal trophic levels, however, are not understood. Using observational and experimental data, we examined the hypotheses that (1) direct trophic effects of predator depletion decrease meiofaunal abundance by releasing deposit feeding fiddler crabs from consumer control, and/or (2) indirect trophic effects of predator depletion increase meiofaunal abundance by releasing blue carbon via the erosion of centuries of accreted marsh peat. Experimental deposit feeder removal led to 23% higher meiofaunal density at die-off than at healthy sites, while reciprocally transplanting sediment from die-off and healthy sites revealed that carbon-rich die-off sediment increased meiofauna density by over 164%: six times stronger than direct trophic effects. Recovering sites had both carbon-rich sediment and reduced deposit feeding leading to higher meiofauna densities than both die-off and healthy sites. This suggests that consequences of the trophic downgrading of coastal habitats can be driven by both direct and indirect trophic mechanisms that may vary in direction and magnitude, making their elucidation dependent on experimental manipulations.

Osteoarthritis (OA) is the most common cause of disability in the United States. With an aging population, its incidence is only likely to rise. Articular cartilage has a poor capacity to heal. The advent of regenerative medicine has heralded a new approach to early treatment of degenerative conditions such as osteoarthritis by focusing on regenerating damaged tissue rather than focusing on replacement. Platelet-rich plasma (PRP) is one such treatment that has received much recent attention and has been used particularly for tendon healing. Recent studies have focused on assessing its use on degenerative conditions such as OA. In this article, we review the evidence for the pathologic basis for the use of PRP in OA and also the clinical outcomes pertaining to its use. Finally, we also consider reasons for the inconsistent clinical success pertaining to its use.

S1P has been demonstrated to protect against the formation of lipopolysaccharide (LPS)-induced lung edema when administered concomitantly with LPS. In the current study, we sought to determine the effectiveness of S1P to attenuate lung injury in a translationally relevant canine model of ALI when administered as rescue therapy. Secondarily, we examined whether the attenuation of LPS-induced physiologic lung injury after administration of S1P was, at least in part, caused by an alteration in local and/or systemic inflammatory cytokine expression. We examined 18, 1-year-old male beagles prospectively in which we instilled bacterial LPS (2-4 mg/kg) intratracheally followed in 1 h with intravenous S1P (85 microg/kg) or vehicle and 8 h of high-tidal-volume mechanical ventilation. S1P attenuated the formation of Q(s)/Q(t) (32%), and both the presence of protein (72%) and neutrophils (95%) in BAL fluid compared with vehicle controls. Although lung tissue inflammatory cytokine production was found to vary regionally throughout the LPS-injured lung, S1P did not alter the expression pattern. Similarly, BAL cytokine production was not altered significantly by intravenous S1P in this model. Interestingly, S1P potentiated the LPS-induced systemic production of 3 inflammatory cytokines, TNF-alpha (6-fold), KC (1.2-fold), and IL-6 (3-fold), without resulting in end-organ dysfunction. In conclusion, intravenous S1P reduces inflammatory lung injury when administered as rescue therapy in our canine model of LPS-induced ALI. This improvement is observed in the absence of changes in local pulmonary inflammatory cytokine production and an augmentation of systemic inflammation.

Chromatin remodeling is tightly controlled under physiological conditions. Alterations in chromatin structure are involved in the pathogenesis of neuronal systems. We found that the monoallelic deletion of CREB binding protein (CBP) results in the induction of ERG-associated protein with SET domain (ESET) and increases trimethylation of histone H3 (K9) and condensation of pericentromeric heterochromatin structure in neurons. Nested deletion and mutational analysis of the ESET promoter further demonstrated that the Ets-2 transcription factor regulates transcriptional activity of the ESET gene. In CBP+/- mice, Ets-2 occupancy in the ESET promoter DNA was markedly elevated. Our results suggest that CBP is a transcriptional repressor of ESET gene expression by limiting Ets-2 transcriptional activity, while CBP siRNA enhances basal and Ets-2-dependent ESET transcriptional activity. Altered expression of the ESET gene and hypertrimethylation of H3 (K9) correlate with striatal neuron atrophy and dysfunction in CBP+/- mice. These results establish an alternative pathway that loss of CBP leads to the pericentric heterochromatin condensation through ESET expression and trimethylation of H3 (K9).