Cloning of the Vanilloid-like Receptor VR-L and investigation of its interaction with members of the transient receptor potential family of receptors

Early pharmacological studies (Szolcsanyi and Jancso-Gabor, 1975, Wood, 1988) showed that capsaicin, the pungent ingredient of chilli peppers and other vanilloids, can specifically stimulate the C unmyelinated fibres which transmit nociceptive information i.e. information about noxious thermal, chemical and mechanical stimuli. The specific action of capsaicin on this subset of sensory neurons led researchers to postulate the existence of a capsaicin receptor. Caterina et al (1997) cloned Vanilloid Receptor 1 (VR1) from dorsal root ganglia, where the somata of C fibres reside. VR1 responds to capsaicin, heat, protons and to the cannabinoid ligand, anandamide (Zygmunt et al., 1999). Discrepancies between the pharmacological profile of VR1 and native vanilloid responses fuelled research for the identification of other vanilloid receptors. In this thesis, the cloning of a new member of the vanilloid receptor family is described using bioinformatics tools. The novel receptor was named Vanilloid Receptor-like (VR-L) and was found to share 49% identity with VR1 and 20% with members of the Transient Receptor Potential (TRP) family. VR-L transcripts were identified in a wide range of tissues including the capsaicin insensitive dorsal root ganglia neurons. The expression of the channel in these neurons can be upregulated by Nerve Growth Factor, as it was established with semi-quantitative RT- PCR. Co-immunoprecipitation studies were carried out to investigate the possibility that VR-L interacts with VR1 and other members of the TRP family to regulate indirectly vanilloid and other responses. VR1 and VR-L were found to form homomultimers and also to interact with each other and with members of the TRP family. A VR-L stable cell line was generated to study the functional significance of the interactions identified

Changes in nasal resonance following septoplasty in adults: Acoustic and perceptual characteristics

<p><i>Objectives</i>. Patients undergoing surgery for a deviated nasal septum (septoplasty) often report that their voice sounds different or less hyponasal. However, such a relationship between septoplasty and vocal resonance remains without scientific evidence. The purpose of this work is to investigate whether nasal septal surgery has any effect on nasal resonance, both in terms of objective measurements and patient perception. <i>Methods</i>. The research carried out was a prospective case–control study. We recruited patients who underwent septoplasty (study group) and healthy volunteers (control group). We obtained voice recordings of the nasal consonant /m/ pre- and four weeks postoperatively and twice at similar time intervals in the control group. We investigated objective changes by means of acoustic analysis of the voice recordings and calculated the total amount of acoustic energy in different bandwidths on a wide-band spectrogram. We also utilized a questionnaire to explore patient perception. <i>Results</i>. A total of 34 participants entered the study. ANOVA testing revealed significant changes in average total acoustic energy, phlegm, and throat dryness postoperatively. Regarding patient perception, a considerable number of our patients felt that their voice had changed for the better upon direct questioning. However, statistical analysis of the questionnaire items related to nasality of voice did not show a significant change. <i>Conclusions</i>. In this study it has been demonstrated that surgical correction of septal deviation causes significant spectrographic changes. In particular it causes changes in the average total acoustic energy during the production of a nasal consonant. A considerable number of our patients reported change in their vocal resonance for the better. We recommend that patients be advised that their voice may sound different after surgery, or less hyponasal.</p

Effects of experimentally-induced maternal hypothyroidism on crucial offspring rat brain enzyme activities

Hypothyroidism is known to exert significant structural and functional changes to the developing central nervous system, and can lead to the establishment of serious mental retardation and neurological problems. The aim of the present study was to shed more light on the effects of gestational and/or lactational maternal exposure to propylthiouracil-induced experimental hypothyroidism on crucial brain enzyme activities of Wistar rat offspring, at two time-points of their lives: at birth (day-1) and at 21 days of age (end of lactation). Under all studied experimental conditions, offspring brain acetylcholinesterase (AChE) activity was found to be significantly decreased due to maternal hypothyroidism, in contrast to the two studied adenosinetriphosphatase (Na(+),K(+)-ATPase and Mg(2+)-ATPase) activities that were only found to be significantly altered right after birth (increased and decreased, respectively, following an exposure to gestational maternal hypothyroidism) and were restored to control levels by the end of lactation. As our findings regarding the pattern of effects that maternal hypothyroidism has on the above-mentioned crucial offspring brain enzyme activities are compared to those reported in the literature, several differences are revealed that could be attributed to both the mode of the experimental simulation approach followed as well as to the time-frames examined. These findings could provide the basis for a debate on the need of a more consistent experimental approach to hypothyroidism during neurodevelopment as well as for a further evaluation of the herein presented and discussed neurochemical (and, ultimately, neurodevelopmental) effects of experimentally-induced maternal hypothyroidism, in a brain region-specific manner

Study of the Fiber Bragg’s Grating Sensor Sensibility

International audienceThis study investigates the performance of Fiber Bragg Grating sensors bonded with an cyanoacrylate adhesive to different substrate materials (titanium, aluminum, and carbon-fiber-reinforced polymers) for Structural Health Monitoring applications in the aeronautical industry. The results show that thermal aging alters the adhesive layer, ultimately modifying the FBG sensor's sensing ability. A finite element model is used to study the most influential factors on the bonding agent and FBG sensor durability

Experimentally-induced maternal hypothyroidism alters crucial enzyme activities in the frontal cortex and hippocampus of the offspring rat.

Thyroid hormone insufficiency during neurodevelopment can result into significant structural and functional changes within the developing central nervous system (CNS), and is associated with the establishment of serious cognitive impairment and neuropsychiatric symptomatology. The aim of the present study was to shed more light on the effects of gestational and/or lactational maternal exposure to propylthiouracil (PTU)-induced hypothyroidism as a multilevel experimental approach to the study of hypothyroidism-induced changes on crucial brain enzyme activities of 21-day-old Wistar rat offspring in a brain region-specific manner. This experimental approach has been recently developed and characterized by the authors based on neurochemical analyses performed on newborn and 21-day-old rat offspring whole brain homogenates; as a continuum to this effort, the current study focused on two CNS regions of major significance for cognitive development: the frontal cortex and the hippocampus. Maternal exposure to PTU in the drinking water during gestation and/or lactation resulted into changes in the activities of acetylcholinesterase and two important adenosinetriphosphatases (Na(+),K(+)- and Mg(2+)-ATPase), that seemed to take place in a CNS-region-specific manner and that were dependent upon the PTU-exposure timeframe followed. As these findings are analyzed and compared to the available literature, they: (i) highlight the variability involved in the changes of the aforementioned enzymatic parameters in the studied CNS regions (attributed to both the different neuroanatomical composition and the thyroid-hormone-dependent neurodevelopmental growth/differentiation patterns of the latter), (ii) reveal important information with regards to the neurochemical mechanisms that could be involved in the way clinical hypothyroidism could affect optimal neurodevelopment and, ultimately, cognitive function, as well as (iii) underline the need for the adoption of more consistent approaches towards the experimental simulation of congenital and early-age-occurring hypothyroidism

Supplementary Material for: Stromal-Derived Factor 1 Signalling Regulates Radial and Tangential Migration in the Developing Cerebral Cortex

Stromal-derived factor 1 (SDF-1), a known chemoattractant, and its receptor CXCR4 are widely expressed in the developing and adult cerebral cortex. Recent studies have highlighted potential roles for SDF-1 during early cortical development. In view of the current findings, our histological analysis has revealed a distinct pattern of SDF-1 expression in the developing cerebral cortex at a time when cell proliferation and migration are at peak. To determine the role of chemokine signalling during early cortical development, embryonic rat brain slices were exposed to a medium containing secreted SDF-1 to perturb the endogenous levels of chemokine. Alternatively, brain slices were treated with 40 µM of T140 or AMD3100, known antagonists of CXCR4. Using these experimental approaches, we demonstrate that chemokine signalling is imperative for the maintenance of the early cortical plate. In addition, we provide evidence that both neurogenesis and radial migration are concomitantly regulated by this signalling system. Conversely, interneurons, although not dependent on SDF-1 signalling to transgress the telencephalic boundary, require the chemokine to maintain their tangential migration. Collectively, our results demonstrate that SDF-1 with its distinct pattern of expression is essential and uniquely positioned to regulate key developmental events that underlie the formation of the cerebral cortex

Exposure to ethanol during neurodevelopment modifies crucial offspring rat brain enzyme activities in a region-specific manner.

The experimental simulation of conditions falling within "the fetal alcohol spectrum disorder" (FASD) requires the maternal exposure to ethanol (EtOH) during crucial neurodevelopmental periods; EtOH has been linked to a number of neurotoxic effects on the fetus, which are dependent upon the extent and the magnitude of the maternal exposure to EtOH and for which very little is known with regard to the exact mechanism(s) involved. The current study has examined the effects of moderate maternal exposure to EtOH (10 % v/v in the drinking water) throughout gestation, or gestation and lactation, on crucial 21-day-old offspring Wistar rat brain parameters, such as the activities of acetylcholinesterase (AChE) and two adenosine triphosphatases (Na(+),K(+)-ATPase and Mg(2+)-ATPase), in major offspring CNS regions (frontal cortex, hippocampus, hypothalamus, cerebellum and pons). The implemented experimental setting has provided a comparative view of the neurotoxic effects of maternal exposure to EtOH between gestation alone and a wider exposure timeframe that better covers the human third trimester-matching CNS neurodevelopment period (gestation and lactation), and has revealed a CNS region-specific susceptibility of the examined crucial neurochemical parameters to the EtOH exposure schemes attempted. Amongst these parameters, of particular importance is the recorded extensive stimulation of Na(+),K(+)-ATPase in the frontal cortex of the EtOH-exposed offspring that seems to be a result of the deleterious effect of EtOH during gestation. Although this stimulation could be inversely related to the observed inhibition of AChE in the same CNS region, its dependency upon the EtOH-induced modulation of other systems of neurotransmission cannot be excluded and must be further clarified in future experimental attempts aiming to simulate and to shed more light on the milder forms of the FASD-related pathophysiology