EVIDENCE OF AN ADSORPTION-DESORPTION MODEL FOR HUMAN IRRITANT PERCEPTION

The temporal irritant response was evaluated for six concentrations of capsaicin, cinnamaldehyde, andpiperine, using time-intensity (TI) methodology. TI curves were evaluated using six TI parameters: maximum intensity (I_max), time-to-maximum (T_max), plateau time (T_plat), total time (T_tot), maximum rate of onset (M_onset) and maximum rate of decay (M_decay) of perception. Maximum intensity was used to evaluate the appropriateness of the Beidler taste equation, calculate the degree of affinity of the stimuli for the receptor (K_b), Gibbs free energy values, and the other TI parameter were used to quantify the adsorption desorptionprocesses. For cinnamaldehyde and capsaicin, correlation coefficients for the proposed Beidler taste model were 0.999, and 0.996, respectively. The large association constants (K_b) for cinnamaldehyde (25 M₋₁) and capsaicin (5.2 × 10⁴ M₋₁), compared to taste compounds, were consistent with their steep psychophysical functions and their persistent aftertastes. Concentration dependencies of T_max T_plat, T_tot, M_onset and M_decay, fit linear and semi-hyperbolic functions and were congruous with the proposed adsorption- desorption model for irritant perception.     

DESCRIPTIVE ANALYSIS OF ORAL PUNGENCY1

Pungent spices are well-recognized for their aromatic and pungent nature; however, relatively little is known about their pungent or ‘burning’ responses. Therefore, this research was undertaken to characterize oral pungency of the principal irritants or red pepper (capsaicin), black pepper (piperine), cinnamon (cinnamaldehyde), cumin (cuminaldehyde), cloves (eugenol), ginger (ginger oleoresin), and alcohol (ethanol). These compounds were evaluated for four pungent qualities (burning, tingling, numbing, overall), two temporal qualities (lag time, overall duration), and three spatial qualities (longitudinal location, lateral location, localized/diffuse). The pungency of cinnamaldehyde was primarily burning and tingling. It had a quick onset and rapid decay. The pungency of eugenol had a long-lasting, predominantly numbing effect. The pungency piperine, capsaicin and ginger were primarily burning, but had different temporal and spatial responses. The pungency of ethanol was most diffuse in nature, with some burning and tingling sensations. It had the shortest perceived onset and overall duration. The pungency of cuminaldehyde was equally burning, tingling and numbing.     

TIME INTENSITY PROFILES OF FLAVOR POTENTIATORS (MSG, IMP, GMP)

This research characterized the time-intensity (TI) profiles of monosodium glutamate (MSG), disodium 5'-inosinate (IMP), and disodium 5'-guanylate (GMP). Twenty subjects rated total taste intensity of single solutions of 2.5, 5 and 10 mM MSG, 0.63 and 2.5 mM IMP and GMP, and some of their mixtures, using the TI method. The profiles generated were atypical of other taste modalities. Time to maximum intensity waslong (16–20s), followed by a plateau at maximum intensity, and a persistent aftertaste (50–96s duration). Maximum intensities of the samples varied (p < 0.001), with mixtures of 10 and 5 mM MSG with 2.5 mM IMP or GMP yielding the highest intensities. Similar differences were found for total duration and area under the curve. These results indicate that flavor potentiators may increase total flavor during consumption. Synergism between flavor potentiators was demonstrated.     

Differential decay of human faecal Bacteroides in marine and freshwater

Genetic markers from Bacteroides and other faecal bacteria are being tested for inclusion in regulations to quantify aquatic faecal contamination and estimate public health risk. For the method to be used quantitatively across environments, persistence and decay of markers must be understood. We measured concentrations of contaminant molecular markers targeting Enterococcus and Bacteroides spp. in marine and freshwater microcosms spiked with human sewage and exposed to either sunlight or dark treatments. We used Bayesian statistics with a delayed Chick-Watson model to estimate kinetic parameters for target decay. DNA- and RNA-based targets decayed at approximately the same rate. Molecular markers persisted (could be detected) longer in marine water. Sunlight increased the decay rates of cultured indicators more than those of molecular markers; sunlight also limited persistence of molecular markers. Within each treatment, Bacteroides markers had similar decay profiles, but some Bacteroides markers significantly differed in decay rates. The role of extracellular DNA in persistence appeared unimportant in the microcosms. Because conditions were controlled, microcosms allowed the effects of specific environmental variables on marker persistence and decay to be measured. While marker decay profiles in more complex environments would be expected to vary from those observed here, the differences we measured suggest that water matrix is an important factor affecting quantitative source tracking and microbial risk assessment applications.     

Distribution of Myxomycetes on coarse woody debris of <Emphasis Type="Italic">Pinus densiflora</Emphasis> at different decay stages in secondary forests of western Japan

The relationship between myxomycete species and the decay stage of wood of Pinus densiflora coarse woody debris was investigated in warm temperate secondary forests of western Japan. The number of species and species diversity of the myxomycete community reached the maximum on moderately decayed wood. The 25 dominant species recorded from 8 or more samples of the total 1530 samples were arranged in order of the succession index corresponding to the stage of decay. Species on slightly decayed hard pine wood were characterized by Stemonitis splendens, Enerthenema papillatum, and Physarum viride, whereas species of Cribrariaceae were found on brittle decayed soft wood increasing abundance according to the decay stages. Most of the species occurred where there was sufficient moisture preserved in the environment of the decaying wood, although S. splendens specifically emerged in low-moisture environments. Because the myxomycete species had preference to different decay stages of wood, it appears that they change sequentially during myxomycete community succession on dead pine wood according to the progression of decay.     

Influence of curcumin, capsaicin, and piperine on the rat liver drug-metabolizing enzyme system in vivo and in vitro

The effect of dietary supplementation of spice-active principles, curcumin (0.2%), capsaicin (0.015%), and piperine (0.02%) on the activities of the liver drug-metabolizing enzyme system was examined. All the 3 dietary spice principles significantly stimulated the activity of aryl hydroxylase. A synergistic action of dietary curcumin and capsaicin with respect to stimulating the activity of aryl hydroxylase was also evidenced when fed in combination. The activity of N-demethylase essentially remained unaffected by dietary curcumin, capsaicin, or their combination, but was significantly lowered as a result of piperine feeding. Uridine dinucleotide phosphate (UDP)-glucuronyl transferase activity was decreased by dietary piperine and the combination of curcumin and capsaicin. NADPH-cytochrome c reductase activity was significantly decreased by dietary piperine. The levels of hepatic microsomal cytochrome P450 and cytochrome b5 were not influenced by any of the dietary spice-active principles. These spice-active principles were also examined for their possible in vitro influence on the components of the hepatic drug-metabolizing enzyme system in rat liver microsomal preparation. Piperine significantly decreased the activity of liver microsomal aryl hydroxylase activity when included in the assay medium at 1 x 10(-6) mol/L, 1 x 10(-5) mol/L, and 1x 10(-4) mol/L level. Lowered activity of N-demethylase was observed in presence of capsaicin or piperine at 1 x 10(-6) mol/L in the assay medium. Hepatic microsomal glucuronyl transferase activity was significantly decreased in vitro by addition of capsaicin or piperine. Capsaicin and piperine brought about significant decrease in liver microsomal cytochrome P450 when included at 1 x 10(-6) mol/L and 1 x 10(-5) mol/L, the effect being much higher in the case of piperine. The results suggested that whereas the 3 spice principles have considerable similarity in structure, piperine is exceptional in its influence on the liver drug-metabolizing enzyme system. The study also indicated that a combination of curcumin and capsaicin does not produce any significant additive effect on the liver drug-metabolizing enzyme system.     

Temporal interactions between oral irritants: piperine, zingerone, and capsaicin

Sequential presentation of 2 irritants may produce cross-sensitization or cross-adaptation effects upon introduction of the second irritant. In Experiment 1, subjects were given either 34 min of stimulation with zingerone, capsaicin, or piperine or one of those irritants for 23 min followed by blanks for 23 min. In Experiment 2, subjects received one irritant for 23-min irritants, followed immediately by another for 23 min (piperine --> zingerone, piperine --> capsaicin, zingerone --> piperine, or zingerone --> capsaicin). Cross-sensitization was observed for the piperine --> zingerone, zingerone --> piperine, and piperine --> capsaicin groups; cross-adaptation was observed for the zingerone --> capsaicin group. Cross-adaptation and cross-sensitization were predicted by adding the independent time courses of the respective irritants, starting the second at the offset of the first. These responses were also predicted by a mathematical model of central processing of primary afferent responses.     

Inhibition and Stimulation Effects in Communities of Wood Decay Fungi: Exudates from Colonized Wood Influence Growth by Other Species

The effects of exudates from uncolonized and from partly decayed beech wood on the extension rates of 16 later stage decay fungi were investigated. The partly decayed wood had been colonized by the pyrenomycete Eutypa spinosa, or the basidiomycetes Fomes fomentarius, Stereum hirsutum, and Trametes versicolor, all known as common early decay agents in European beech forests. Sterilized wood pieces were placed onto 0.5% malt agar, opposite to small agar plugs containing the test fungi. The latter showed very variable and species-specific growth responses to the various wood types. The presence of uncolonized wood stimulated extension rates in many species, whereas the four previously decayed wood types had variable stimulatory or inhibitory effects. Wood decayed by S. hirsutum resulted in reduced extension rate, delayed growth, or total inhibition in the majority of species, thus it is suggested that this species uses secondary metabolites in a defensive strategy. A single species was, however, stimulated in the presence of S. hirsutum-decayed wood. In contrast, the presence of wood decayed by F. fomentarius was stimulatory to 45% of the species. The other previously decayed wood types generally resulted in more variable responses, depending upon species. The results are discussed in an ecological context and it is suggested that the exudates from the partly decayed wood that are responsible for the reported effects may function as infochemicals, structuring microbial communities in wood.     

Longitudinal kinetics of RBD+ antibodies in COVID-19 recovered patients over 14 months

We describe the longitudinal kinetics of the serological response in COVID-19 recovered patients over a period of 14 months. The antibody kinetics in a cohort of 192 recovered patients, including 66 patients for whom follow-up serum samples were obtained at two to four clinic visits, revealed that RBD-specific antibodies decayed over the 14 months following the onset of symptoms. The decay rate was associated with the robustness of the response in that antibody levels that were initially highly elevated after the onset of symptoms subsequently decayed more rapidly. An exploration of the differences in the longitudinal kinetics between recovered patients and naïve vaccinees who had received two doses of the BNT162b2 vaccine showed a significantly faster decay in the naïve vaccinees, indicating that serological memory following natural infection is more robust than that following to vaccination. Our data highlighting the differences between serological memory induced by natural infection vs. vaccination contributed to the decision-making process in Israel regarding the necessity for a third vaccination dose.     

Modulation of oral heat and cold pain by irritant chemicals

Common food irritants elicit oral heat or cool sensations via actions at thermosensitive transient receptor potential (TRP) channels. We used a half-tongue, 2-alternative forced-choice procedure coupled with bilateral pain intensity ratings to investigate irritant effects on heat and cold pain. The method was validated in a bilateral thermal difference detection task. Capsaicin, mustard oil, and cinnamaldehyde enhanced lingual heat pain elicited by a 49 degrees C stimulus. Mustard oil and cinnamaldehyde weakly enhanced lingual cold pain (9.5 degrees C), whereas capsaicin had no effect. Menthol significantly enhanced cold pain and weakly reduced heat pain. To address if capsaicin's effect was due to summation of perceptually similar thermal and chemical sensations, one-half of the tongue was desensitized by application of capsaicin. Upon reapplication, capsaicin elicited little or no irritant sensation yet still significantly enhanced heat pain on the capsaicin-treated side, ruling out summation. In a third experiment, capsaicin significantly enhanced pain ratings to graded heat stimuli (47 degrees C to 50 degrees C) resulting in an upward shift of the stimulus-response function. Menthol may induce cold hyperalgesia via enhanced thermal gating of TRPM8 in peripheral fibers. Capsaicin, mustard oil, and cinnamaldehyde may induce heat hyperalgesia via enhanced thermal gating of TRPV1 that is coexpressed with TRPA1 in peripheral nociceptors.     

Differences in the chemesthetic subqualities of capsaicin, ibuprofen, and olive oil

Chemesthetic sensations elicited by ibuprofen, extra-virgin olive oil, and capsaicin were compared to quantify perceptual differences between known agonists of TRPA1 and TRPV1. Extra virgin olive oil contains a phenolic compound, oleocanthal, which is thought to share unique chemesthetic qualities with the nonsteroidal anti-inflammatory drug, ibuprofen. Pilot work suggested participants had difficulty distinguishing between multiple chemesthetic subqualities (e.g., burn, sting, itch, tickle, etc.) in a multiattribute rating task. Here, we assessed overall irritation via direct scaling, and a check all that apply task was used to collect information about chemesthetic subqualities over time. Replicated ratings were collected at discrete intervals using the generalized labeled magnitude scale to generate time-intensity curves; maximum intensity (Imax) and area under the curve were extracted for each participant. Intensity responses varied substantially across participants, and within a participant, the relationship was strongest between ibuprofen and olive oil. However, there were also positive, albeit weaker, correlations between capsaicin and ibuprofen and capsaicin and olive oil. The correlation found between olive oil and capsaicin may suggest the presence of unknown TRPV1 agonists in olive oil. This view was also supported by the qualitative data: capsaicin was described most often as burning and warm/hot, whereas ibuprofen was numbing and tickling. Olive oil shared characteristics with both capsaicin (warm/hot) and ibuprofen (tickle).     

Oral irritant properties of piperine and nicotine: psychophysical evidence for asymmetrical desensitization effects.

Using a bipolar rating scale, human subjects rated the intensity of irritation sensation evoked by repeated application of piperine (75 p.p.m.) or nicotine (0.12%) to one side of the dorsal surface of the tongue. The intensity of irritation elicited by repeated application of piperine significantly increased, while irritation elicited by repeated nicotine significantly decreased. We additionally tested if nicotine or piperine desensitized the tongue. After either piperine or nicotine was repeatedly applied to one side of the tongue, a 5 or 10 min rest period ensued, followed by re-application of piperine or nicotine to both sides of the tongue. Subjects were asked to choose which side of the tongue gave rise to a stronger irritation in a two-alternative forced choice (2-AFC) paradigm. In addition, they gave separate ratings of the intensity of irritation on the two sides of the tongue. When piperine was applied bilaterally after unilateral pretreatment with piperine and a 10 min rest period, subjects consistently chose the non-pretreated side to yield stronger irritation and assigned significantly higher ratings to that side, indicative of piperine self-desensitization. A similar self-desensitization effect was found when bilateral application of nicotine followed unilateral treatment with nicotine and a 5 min rest period. Unilateral treatment with piperine also reduced nicotine-evoked irritation on the pretreated side (cross-desensitization), but treatment with nicotine did not affect piperine-evoked irritation. This asymmetrical cross-desensitization pattern is similar to that observed between capsaicin and nicotine and constitutes an additional similarity between piperine and capsaicin.     

Sensory perception is related to the rate of change of volatile concentration in-nose during eating of model gels.

The relationship between perceived aroma and the volatile concentration measured in-nose was investigated during eating of a model food. Sensory ranking and time-intensity analysis (TI) were used to measure perceived aroma, while in-nose volatile concentration was monitored by atmospheric pressure ionization mass spectrometry, which produced time release data. A gelatine-sucrose gel with a range of gelatine concentrations (2-8% w/w) and flavoured with furfuryl acetate was used as the model food. Sensory scaling showed decreased flavour intensities and TI showed a decrease in the flavour perceived over time, as the gelatine concentration increased. Studies in model systems and in people demonstrated that the different rates of release observed for different gelatine concentrations were not due to binding of volatile to protein in the gel, nor to mucous membranes, but were due to different rates of gel breakdown in-mouth. There were no significant differences in the maximum in-nose volatile concentrations for the different gelatine concentrations, so the amount of volatile present did not correlate well with the sensory analysis. However, the rates of volatile release were different for the different gels and showed a good correlation with sensory data.     

Control of respiratory pattern in conscious dog: effects of heat and CO2

We measured tidal volume (VT) and inspiratory (TI) and expiratory (TE) durations in five conscious tracheostomized dogs breathing air or 5% CO2 in air either at normal (20 degrees C) or elevated (30 degrees C) ambient temperatures. Respiratory frequency ranged between 16 and 333/min due to changes in both TI and TE. During panting TI exceeded TE. During air inhalation instantaneous ventilation (V) spontaneously ranged from 100 to 1,600 ml . kg-1 . min-1. Hypercapnia, heat stress, or both, increased this range of V by increasing maximum V, primarily due to increases in mean inspiratory flow. Under these conditions, changes in TI accounted for more of the spontaneous changes in breath duration. During inhalation of air and 5% CO2, a positive correlation between VT and TI was obtained for TI between 0.13 and 1.05 s; above 1.05 s VT decreased. Heat stress increased VT at a given TI. We suggest that either the decay rate or position of the inspiratory off-switch threshold curve (Clark and von Euler, J. Physiol. London 222: 267, 1972) varies in conscious dogs. Shifts in either the reset (onset) value or decay rate of the curve yield a positive correlation between VT and TI. This modification to the Clark-von Euler model implies that the primary effect of anesthesia on respiratory control is fixation of the inspiratory off-switch threshold curve.     

Factors affecting the survival of sclerotia of Sclerotium cepivorum in the Fraser Valley of British Columbia

Sclerotia of Sclerotium cepivorum buried in muck soil in the Fraser Valley decayed with time. The rate of decay of sclerotia was influenced by local environmental conditions. A mixture of soil with sclerotia increased their survival but there was no difference in the rates of decay in three different soils. The decay was greatest during winter when Fraser Valley fields are often flooded. Sclerotial decay was also affected by pretreatment of the sclerotia. Dried sclerotia decayed significantly (P < 0.05) faster than sclerotia which had not been dried, a phenomenon which is apparently due to changes in micro-organisms on the sclerotia. Dried sclerotia which had been incubated in moist soil had fewer bacteria and more fungi than sclerotia which had been incubated in soil without being dried. The increase in fungi on the dried sclerotia was due to a dramatic increase in Trichoderma spp.     

Variation in life cycle affects the distance decay of similarity among bluegill sunfish parasite communities

Rates of community similarity decay were examined among parasite communities of the bluegill sunfish from isolated populations located throughout the midwestern and southeastern United States. Rates of decay were compared for assemblages composed of all species, autogenic species only, and allogenic species only. Rates of similarity decay were calculated by regressing a matrix of intercommunity distance against a matrix of intercommunity Sorenson similarity for each group of species. Significance was determined with the use of a Mantel test using 1,000 permutations. Significant rates of decay were found for all groups; however, allogenic similarity decayed according to an exponential function, whereas autogenic similarity decayed according to a linear function. Overall, the results suggest that autogenic-allogenic status is an important factor determining the rate at which similarity decays, but illustrate the need for more insight regarding the factors that affect parasite dispersal ability.     

Wood decomposing abilities of diverse lignicolous fungi on nondecayed and decayed beech wood

We tested the decay abilities of 28 isolates from 28 lignicolous fungal species (Basidiomycota, Ascomycota and Zygomycota) with the pure culture test. We used beech wood powder in varying moisture conditions and decay stages (nondecayed, intermediately decayed and well decayed) as substrates. The weight loss in wood powder was -0.2-17.8%. Five isolates of Basidiomycota (Bjerkandera adusta, Mycena haematopus, Omphalotus guepiniformis, Trametes hirsuta, Trametes versicolor) caused high weight losses in nondecayed wood. We detected significant effects of decay stage on weight loss in wood in most isolates tested, whereas moisture content rarely had an effect on weight loss. Among Basidiomycota and Xylariaceae in Ascomycota weight loss was greater for nondecayed wood than for intermediately and well decayed wood. In contrast four isolates in Ascomycota (Scytalidium lignicola, Trichoderma hamatum, T. harzianum, T. koningii) caused substantial weight loss in intermediately and well decayed wood, although they rarely caused weight loss in nondecayed wood. Zygomycota caused low weight loss in wood. Wood decay stages also affected decomposition of wood chemical components. Acid-unhydrolyzable residue (AUR) decomposition was reduced, whereas holocellulose decomposition was stimulated by some strains of Basidiomycota and Ascomycota in well decayed wood. T. harzianum in particular caused significant weight loss of holocellulose in well decayed wood, although this fungus caused negligible weight loss of both AUR and holocellulose in nondecayed wood. We discuss these changes in the decay patterns of AUR and holocellulose with varying wood decay stages in relation to the role of fungal decomposition of woody debris in forests.     

Dictyostelium discoideum mRNAs developmentally regulated during spore germination have short half-lives.

mRNA decay was studied during spore germination in Dictyoselium discoideum by the use of three previously isolated cDNA clones, pLK109, pLK229, and pRK270, which are specific for mRNAs developmentally regulated during spore germination. The half-life of a constitutive mRNA, pLK125, which is present throughout germination, growth, and development, as also determined. Nogalamycin, a DNA-intercalating compound, was used to inhibit RNA synthesis. Total RNA was isolated at intervals after addition of the drug, and the decay of mRNAs specific for the cDNA clones was determined by both Northern blot and RNA dot hybridization. If nogalamycin was added immediately after activation of dormant spores, neither pLK229 nor pLK109 mRNA decayed, but pLK125 mRNA did decay. Although pLK109 mRNA did not decay under these conditions, the RNA was smaller 1 h after activation than in dormant spores, indicating that it was processed normally. At 1 h after activation, pLK229-, pLK125-specific mRNAs decayed exponentially, with half-lives of 24, 39, and 165 min, respectively. Under the same conditions, decay of pLK109-specific mRNA was biphasic. Thirty-eight percent of the mRNA decayed with a half-life of 5.5 min, and the remainder decayed with a half-life of 115 min. It seems likely that nogalamycin inhibits the synthesis of an unstable component of the mRNA degradative pathway which is needed continuously for the decay of pLK109 mRNA. By extrapolating the curve representing the rapidly decaying component, a half-life of 18 min was calculated for pLK109-specific mRNA. The mRNAs developmentally regulated during spore germination have half-lives shorter than that of the constitutive messenger and shorter than the average half-life of 3 to 4 h previously determined for total Dicyostelium polyadenylated mRNA.     

Dynamics of latent HIV under clonal expansion

The HIV latent reservoir exhibits slow decay on antiretroviral therapy (ART), impacted by homeostatic proliferation and activation. How these processes contribute to the total dynamic while also producing the observed profile of sampled latent clone sizes is unclear. An agent-based model was developed that tracks individual latent clones, incorporating homeostatic proliferation of cells and activation of clones. The model was calibrated to produce observed latent reservoir dynamics as well as observed clonal size profiles. Simulations were compared to previously published latent HIV integration data from 5 adults and 3 children. The model simulations reproduced reservoir dynamics as well as generating residual plasma viremia levels (pVL) consistent with observations on ART. Over 382 Latin Hypercube Sample simulations, the median latent reservoir grew by only 0.3 log₁₀ over the 10 years prior to ART initiation, after which time it decreased with a half-life of 15 years, despite number of clones decreasing at a faster rate. Activation produced a maximum size of genetically intact clones of around one million cells. The individual simulation that best reproduced the sampled clone profile, produced a reservoir that decayed with a 13.9 year half-life and where pVL, produced mainly from proliferation, decayed with a half-life of 10.8 years. These slow decay rates were achieved with mean cell life-spans of only 14.2 months, due to expansion of the reservoir through proliferation and activation. Although the reservoir decayed on ART, a number of clones increased in size more than 4,000-fold. While small sampled clones may have expanded through proliferation, the large sizes exclusively arose from activation. Simulations where homeostatic proliferation contributed more to pVL than activation, produced pVL that was less variable over time and exhibited fewer viral blips. While homeostatic proliferation adds to the latent reservoir, activation can both add and remove latent cells. Latent activation can produce large clones, where these may have been seeded much earlier than when first sampled. Elimination of the reservoir is complicated by expanding clones whose dynamic differ considerably to that of the entire reservoir.