The gustin (CA6) gene polymorphism, rs2274333 (A/G), as a mechanistic link between PROP tasting and fungiform taste papilla density and maintenance

Taste sensitivity to PROP varies greatly among individuals and is associated with polymorphisms in the bitter receptor gene TAS2R38, and with differences in fungiform papilla density on the anterior tongue surface. Recently we showed that the PROP non-taster phenotype is strongly associated with the G variant of polymorphism rs2274333 (A/G) of the gene that controls the salivary trophic factor, gustin. The aims of this study were 1) to investigate the role of gustin gene polymorphism rs2274333 (A/G), in PROP sensitivity and fungiform papilla density and morphology, and 2) to investigate the effect of this gustin gene polymorphism on cell proliferation and metabolic activity. Sixty-four subjects were genotyped for both genes by PCR techniques, their PROP sensitivity was assessed by scaling and threshold methods, and their fungiform papilla density, diameter and morphology were determined. In vitro experiments examined cell proliferation and metabolic activity, following treatment with saliva of individuals with and without the gustin gene mutation, and with isolated protein, in the two iso-forms. Gustin and TAS2R38 genotypes were associated with PROP threshold (p=0.0001 and p=0.0042), but bitterness intensity was mostly determined by TAS2R38 genotypes (p<0.000001). Fungiform papillae densities were associated with both genotypes (p<0.014) (with a stronger effect for gustin; p=0.0006), but papilla morphology was a function of gustin alone (p<0.0012). Treatment of isolated cells with saliva from individuals with the AA form of gustin or direct application of the active iso-form of gustin protein increased cell proliferation and metabolic activity (p<0.0135). These novel findings suggest that the rs2274333 polymorphism of the gustin gene affects PROP sensitivity by acting on fungiform papilla development and maintenance, and could provide the first mechanistic explanation for why PROP super-tasters are more responsive to a broad range of oral stimul

Biomarker dynamics affecting neoadjuvant therapy response and outcome of HER2-positive breast cancer subtype

HER2+ breast cancer (BC) is an aggressive subtype genetically and biologically heterogeneous. We evaluate the predictive and prognostic role of HER2 protein/gene expression levels combined with clinico-pathologic features in 154 HER2+ BCs patients who received trastuzumab-based neoadjuvant chemotherapy (NACT). The tumoral pathological complete response (pCR) rate was 40.9%. High tumoral pCR show a scarce mortality rate vs subjects with a lower response. 93.7% of ypT0 were HER2 IHC3+ BC, 6.3% were HER2 IHC 2+/SISH+ and 86.7% of ypN0 were HER2 IHC3+, the remaining were HER2 IHC2+/SISH+. Better pCR rate correlate with a high percentage of infiltrating immune cells and right-sided tumors, that reduce distant metastasis and improve survival, but no incidence difference. HER2 IHC score and laterality emerge as strong predictors of tumoral pCR after NACT from machine learning analysis. HER2 IHC3+ and G3 are poor prognostic factors for HER2+ BC patients, and could be considered in the application of neoadjuvant therapy. Increasing TILs concentrations, lower lymph node ratio and lower residual tumor cellularity are associated with a better outcome. The immune microenvironment and scarce lymph node involvement have crucial role in clinical outcomes. The combination of all predictors might offer new options for NACT effectiveness prediction and stratification of HER2+ BC during clinical decision-making

New findings on the blowfly labellar taste response of Protophormia terraenovae

An electrophysiological investigation was performed to analyse activity recorded in response to stimulation with concentrated and diluted solutions of NaCl, sucrose, formamidine acetate, and sodium acetate from labellar chemosensilla of the dipteran Protophormia terraenovae. A computerized analysis of this activity led to the finding of four kinds of spikes (A, B, C, and D) which differed in their wave forms. The forms of spikes A, B, and C are described in the literature as being evoked by activation of the specific salt, water, and sugar neurones respectively. The fourth type of spike (D) recorded in response to formamidine acetate and sodium acetate is probably generated by a fourth chemosensorial cell that has not yet been defined functionally. These two acetates evoke activities that are equivalent both in spike frequency and time distribution even at low concentrations. The results suggest that the acetate ion in the blowfly effectively stimulates the fourth chemosensory neuron present in the sensillum. The activation appears to be involved in signalling acidity to the insect

New insight into the antennal chemosensory function of Opius concolor (Hymenoptera, Braconidae)

The presence of taste and olfactory chemosensilla is demonstrated by using both morphological and electrophysiological techniques on antennae of Opius concolor, a parasitoid of tephritid larvae. Observation under the Scanning Electron Microscope revealed the presence of large sensilla trichodea with an apical pore, and of flat plates (sensilla placodea) extending almost the entire length of each antennomere. By means of currently used electrophysiological techniques, it was possible to record both the gustatory activity generated by sensilla trichodea following contact with KCl 100 mM and sucrose 100 mM solutions, and olfactory activity probably generated by sensilla placodea in response to volatile stimuli. The analysis of gustatory activity showed that each sensillum trichodeum consisted of at least three chemosensory units. This supports the assumption that in O. concolor single sensilla may, by providing different spike discharge patterns, which depend on the quality and intensity of the stimulus, provide the CNS with adequate information for peripheral discrimination among stimulating chemicals. Study of the sensory input of O. concolor with electrophysiological techniques may be of great scientific importance for possible applications in biocontrol of the olive fly

Variations in salt sensitivity related to type and position of labellar chemosensilla in Protophormia terraenovae

Electrophysiological responses to NaCl in the concentration range 1-1000 mM were obtained from each of the 11 intermediate and 13 large labellar chemosensilla in the blowfly Protophormia terraenovae. Up to three of the four chemoreceptor cells associated with each chemosensillum responded to NaCl in both sensillum types; the spike discharges of two of these cells were analysed and cross-compared. Differences in chemoreceptor sensitivity and response pattern resulted between intermediate and large sensilla. Sensitivity differences were found, by means of the cluster analysis, within each sensillum type in relation to sensillar topology and are discussed in the light of a possible spatial contribution to the sensory coding process