No description available.

Proprioception, the often forgotten sixth sense, is frequently impaired following stroke, with rehabilitationists addressing this loss within the therapeutic techniques presented to resolve motor problems. The aims of the current studies were to (i) establish the current clinical reality of somatosensory assessment undertaken by physiotherapists nationwide, (ii) how proprioceptive loss in particular was addressed, (iii) explore upper limb weightbearing within everyday activity, (iv) evaluate the proprioceptive response in normal subjects having differences in age and activity. Proprioceptive loss following brain insult has been shown to have an adverse effect on outcome (iv) undertake a series of single case-studies to explore the effect of therapeutic intervention of weightbearing. The findings showed that (i) there was a high degree of agreement in the clinical practice of somatosensory assessment undertaken, (ii) therapeutic intervention of weightbearing was found to be recommended for both motor and proprioceptive loss (iii) upper limb weightbearing was found to be a non-trivial component of everyday life, (iv) positive effects of upper limb weightbearing were found on the proprioceptive responses of stroke victims. The implications of this research are that upper limb weightbearing activities should be incorporated in therapeutic activities to re-establish and maintain proprioceptive control of both upper and lower limbs.

A habilidade de se preparar para futuros eventos é essencial para o comportamento. No presente trabalho, investigamos como diferentes formas de expectativa temporal podem modular o processamento de estímulos sensoriais. Por meio de 4 experimentos psicofísicos, sendo 2 com registro eletroencefalográfico (EEG) concomitante, nós estudamos o efeito da ação motora voluntária e da expectativa temporal em diferentes estágios do processamento sensorial. Nossos resultados sugerem que mecanismos ligados à preparação motora influenciam a percepção temporal das consequências desta ação. Além disso, nossos resultados mostraram que a atenção temporal pode modular estágios motores e sensoriais do processamento. Em conjunto, nossos resultados sugerem que expectativas temporais podem influenciar diferentes estágios do processamento principalmente por meio do controle de excitabilidade cortical de regiões do sistema nervoso central ligadas àquela tarefa. / The ability to anticipate future events is essential for behavior. On the present work, we investigated how different forms of temporal expectations can modulate stimuli processing. In four psychophysical experiments (two of them with EEG) we studied how voluntary action and temporal attention can influence processing at different stages. Our results suggest that mechanisms related to motor preparation can bias the temporal perception of the consequences of this action. Moreover, we found that temporal attention can modulate perceptual and motor stages of stimulus processing. Altogether, our results suggest that temporal expectations can influence different levels of target processing, mainly by controlling cortical excitability of task-relevant regions of the central nervous system.

A habilidade de se preparar para futuros eventos é essencial para o comportamento. No presente trabalho, investigamos como diferentes formas de expectativa temporal podem modular o processamento de estímulos sensoriais. Por meio de 4 experimentos psicofísicos, sendo 2 com registro eletroencefalográfico (EEG) concomitante, nós estudamos o efeito da ação motora voluntária e da expectativa temporal em diferentes estágios do processamento sensorial. Nossos resultados sugerem que mecanismos ligados à preparação motora influenciam a percepção temporal das consequências desta ação. Além disso, nossos resultados mostraram que a atenção temporal pode modular estágios motores e sensoriais do processamento. Em conjunto, nossos resultados sugerem que expectativas temporais podem influenciar diferentes estágios do processamento principalmente por meio do controle de excitabilidade cortical de regiões do sistema nervoso central ligadas àquela tarefa. / The ability to anticipate future events is essential for behavior. On the present work, we investigated how different forms of temporal expectations can modulate stimuli processing. In four psychophysical experiments (two of them with EEG) we studied how voluntary action and temporal attention can influence processing at different stages. Our results suggest that mechanisms related to motor preparation can bias the temporal perception of the consequences of this action. Moreover, we found that temporal attention can modulate perceptual and motor stages of stimulus processing. Altogether, our results suggest that temporal expectations can influence different levels of target processing, mainly by controlling cortical excitability of task-relevant regions of the central nervous system.

No description available.

abstract: All organisms need to be able to sense and respond to their environment. Much of this process takes place via proteins embedded in the cell membrane, the border between a living thing and the external world. Transient receptor potential (TRP) ion channels are a superfamily of membrane proteins that play diverse roles in physiology. Among the 27 TRP channels found in humans and other animals, TRP melastatin 8 (TRPM8) and TRP vanilloid 1 (TRPV1) are the primary sensors of cold and hot temperatures, respectively. They underlie the molecular basis of somatic temperature sensation, but beyond this are also known to be involved in body temperature and weight regulation, inflammation, migraine, nociception, and some types of cancer. Because of their broad physiological roles, these channels are an attractive target for potential therapeutic interventions. This dissertation presents experimental studies to elucidate the mechanisms underlying TRPM8 and TRPV1 function and regulation. Electrophysiology experiments show that modulation of TRPM8 activity by phosphoinositide interacting regulator of TRP (PIRT), a small membrane protein, is species dependent; human PIRT attenuates TRPM8 activity, whereas mouse PIRT potentiates the channel. Direct binding experiments and chimeric mouse-human TRPM8 channels reveal that this regulation takes place via the transmembrane domain of the channel. Ligand activation of TRPM8 is also investigated. A mutation in the linker between the S4 and S5 helices is found to generally decrease TRPM8 currents, and to specifically abrogate functional response to the potent agonist icilin without affecting icilin binding. The heat activation thermodynamics of TRPV1 are also probed using temperature-controlled electrophysiology. The magnitude of the gating enthalpy of human TRPV1 is found to be similar to other species reported in the literature. Human TRPV1 also features an apparent heat inactivation process that results in reduced heat sensitivity after exposure to elevated temperatures. The work presented in this dissertation sheds light on the varied mechanisms of thermosensitive TRP channel function and regulation. / Dissertation/Thesis / Doctoral Dissertation Biochemistry 2019

No description available.

O sistema olfatório de mamífero pode discriminar milhares de odores presentes no meio ambiente. Aproximadamente 1000 diferentes receptores olfatórios (ORs) são expressos no epitélio olfatório (OE) do nariz, Os ORs detectam os odores e transmitem os sinais resultantes para o bulbo olfatório (OB) no cérebro. Os ORs pertencem a super família dos receptores acoplados a proteína G (GPCR) e apresentam sete domínios transmembrânicos putativos. Por razões desconhecidas, os ORs são retidos no retículo endoplasmático quando expressos em linhagens de células de mamíferos heterólogas. Provavelmente, proteínas acessórias sejam requeridas para o endereçamento dos Ors para a superficie celular. No presente estudo, utilizamos o OR M93 para estudar os mecanismos de expressão de um ORo A dissertação teve como objetivos específicos: (l) construção de um vetor para expressão do OR M93 em fusão com GFP em levedura e análise de sua localização celular; (2) identificar proteínas expressas no epitélio olfatório de camundongo que interajam com os ORs. A análise por microscopia de fluorescência revelou que a expressão do OR M93 fusionado a GFP demonstrou um padrão de fluorescência que sugere a retenção do OR M93 no retículo endoplasmático. Nós utilizamos o sistema de duplo híbrido em levedura para varrer uma biblioteca de cDNA de epitélio olfatório de camundongo com uma isca correspondente à região N-terminal do OR M93. Quatro proteínas candidatas foram identificadas: HLA-B associado ao transcrito 3 (BAT-3/ Scythe), superfamília transmembrana 4 (membro CD82), superfamília transmembrana 4 (membro OAP-I) e sindecan (membro SDC2) (\"GenBank accession numbers\": BC026647, D14883, BC0430n e BC047144). A análise da hibridação in situ destas proteínas, revelou que a proteína OAP-1 é a melhor candidata a interação com OR M93. Dessa maneira, nós indicamos a proteína OAP-1 como possível proteína candidata a auxiliar o OR a ser expresso de maneira funcional em sistemas heterólogos. / The mammalian olfactory system can discrim inate thousands of odorants present in the environrnent. Approximately 1000 different olfactory receptors (ORs) are expressed in the olfactory epithelium (OE) of the nose. The ORs detect odorants and transmit the resulting signals to the olfactory bulb (OB) of the brain. ORs belong to the G-protein-coupled receptor (GPCR) super family and have seven putative transmembrane domains. For unknown reasons, the ORs are retained in the endoplasmatic reticulum when expressed in heterologous mammalian cell lines. Probably accessory proteins are required for the sorting of the ORs to the cell surface. In the present work, we used the OR M93 to study the mechanisms of OR expression. Our goals were to (1) construct an expression vector for OR M93 in fusion with GFP in yeast and (2) to identify proteins expressed in the mouse OE that interact with ORs. The analysis by fluorescence microscopy suggested that OR M93 in fusion with GFP was retained in the endoplasmic reticulum (ER) of yeast. We used the yeast two-hybrid system to screen a mouse OE cDNA library with a bait corresponding to the N-terminal region ofthe üR M93. Four potential candidates were identified: HLA-B associated transcript 3 (BAT-3/Scythe), transmembrane 4 superfamily (CD82 member), transmembrane 4 superfamily (TSPN-3 member) and syndecan (SDC2). In situ hybridization analysis suggests that OAP-l protein represents the best candidate for interaction with OR M93. We suggest the OAP-l protein could be an accessory protein required for the sorting of the ORs to the cell surface in heterologous cell lines.

O sistema olfatório de mamífero pode discriminar milhares de odores presentes no meio ambiente. Aproximadamente 1000 diferentes receptores olfatórios (ORs) são expressos no epitélio olfatório (OE) do nariz, Os ORs detectam os odores e transmitem os sinais resultantes para o bulbo olfatório (OB) no cérebro. Os ORs pertencem a super família dos receptores acoplados a proteína G (GPCR) e apresentam sete domínios transmembrânicos putativos. Por razões desconhecidas, os ORs são retidos no retículo endoplasmático quando expressos em linhagens de células de mamíferos heterólogas. Provavelmente, proteínas acessórias sejam requeridas para o endereçamento dos Ors para a superficie celular. No presente estudo, utilizamos o OR M93 para estudar os mecanismos de expressão de um ORo A dissertação teve como objetivos específicos: (l) construção de um vetor para expressão do OR M93 em fusão com GFP em levedura e análise de sua localização celular; (2) identificar proteínas expressas no epitélio olfatório de camundongo que interajam com os ORs. A análise por microscopia de fluorescência revelou que a expressão do OR M93 fusionado a GFP demonstrou um padrão de fluorescência que sugere a retenção do OR M93 no retículo endoplasmático. Nós utilizamos o sistema de duplo híbrido em levedura para varrer uma biblioteca de cDNA de epitélio olfatório de camundongo com uma isca correspondente à região N-terminal do OR M93. Quatro proteínas candidatas foram identificadas: HLA-B associado ao transcrito 3 (BAT-3/ Scythe), superfamília transmembrana 4 (membro CD82), superfamília transmembrana 4 (membro OAP-I) e sindecan (membro SDC2) (\"GenBank accession numbers\": BC026647, D14883, BC0430n e BC047144). A análise da hibridação in situ destas proteínas, revelou que a proteína OAP-1 é a melhor candidata a interação com OR M93. Dessa maneira, nós indicamos a proteína OAP-1 como possível proteína candidata a auxiliar o OR a ser expresso de maneira funcional em sistemas heterólogos. / The mammalian olfactory system can discrim inate thousands of odorants present in the environrnent. Approximately 1000 different olfactory receptors (ORs) are expressed in the olfactory epithelium (OE) of the nose. The ORs detect odorants and transmit the resulting signals to the olfactory bulb (OB) of the brain. ORs belong to the G-protein-coupled receptor (GPCR) super family and have seven putative transmembrane domains. For unknown reasons, the ORs are retained in the endoplasmatic reticulum when expressed in heterologous mammalian cell lines. Probably accessory proteins are required for the sorting of the ORs to the cell surface. In the present work, we used the OR M93 to study the mechanisms of OR expression. Our goals were to (1) construct an expression vector for OR M93 in fusion with GFP in yeast and (2) to identify proteins expressed in the mouse OE that interact with ORs. The analysis by fluorescence microscopy suggested that OR M93 in fusion with GFP was retained in the endoplasmic reticulum (ER) of yeast. We used the yeast two-hybrid system to screen a mouse OE cDNA library with a bait corresponding to the N-terminal region ofthe üR M93. Four potential candidates were identified: HLA-B associated transcript 3 (BAT-3/Scythe), transmembrane 4 superfamily (CD82 member), transmembrane 4 superfamily (TSPN-3 member) and syndecan (SDC2). In situ hybridization analysis suggests that OAP-l protein represents the best candidate for interaction with OR M93. We suggest the OAP-l protein could be an accessory protein required for the sorting of the ORs to the cell surface in heterologous cell lines.

Neuroethology and ecomorphology seek to understand ecology and behaviour from the perspective of specialised adaptations of sensory systems, such as vision. Sharks display a large variety of visual specialisations reflecting the diversity of different ecological niches they occupy. Many shark species are long-lived and wide ranging and often select different habitats for reproduction, growth, and feeding. Habitat complexity, ambient lighting conditions and feeding strategies can therefore change throughout a shark’s lifetime or between populations. Few comprehensive investigations of visual function exist for sharks as studies typically focus on a narrow aspect of visual function or a particular life history stage. Consequently, there is limited data on within-species plasticity of visual function in response to acclimation to different visual environments or ontogenetic development. The aim of this thesis is to undertake a functional analysis of the shark visual system. An integrated approach is employed to investigate optical, anatomical and physiological specialisations, linking such specialisations to known habitat and/or behavioural traits, with particular emphasis on ontogenetic, inter-population and inter-specific variability. Fundamental capabilities of the visual system are examined, including optical quality, eye morphology, spectral range, irradiance sensitivity, spatial and temporal resolution, contrast discrimination, and temporal and spatial summation. The main study species is the sandbar shark (<i>Carcharhinis plumbeus</i>; Carcharhinidae), a cosmopolitan species of ecological and economic importance. <i>C. plumbeus</i> occupies a wide range of natural habitats from highly turbid coastal estuaries, to relatively clear waters off the outer continental shelves and near pristine clear waters over the slopes of oceanic islands. This provides an opportunity to explore the relationship between habitat variability and the adaptation of visual specialisations and subsequent behaviour. For inter-specific comparison, the visual systems of two other species of shark with contrasting ecological niches are also assessed: the shortspine spurdog (<i>Squalus mitsukurii</i>; Squalidae) and the tiger shark (<i>Galeocerdo cuvier</i>; Carcharhinidae). The study finds marked differences in visual specialisations of the three species studied. The eyes of <i>S. mitsukurii</i> are adapted to enhance retinal illumination within a dim light environment with a large eye, immobile pupil, reflective tapetum and a relatively high optical sensitivity (2.72 μm² steradians). Visual features include a short wavelength lenticular filter, a high spatial resolving power (7.2 cycles/degree) and a large binocular overlap in the dorsal visual field, suggesting adaptations may facilitate the visualisation of bioluminescent prey. In contrast, the eyes of <i>C. plumbeus</i> are optimised for vision under variable light conditions with a mobile pupil and an occlusible tapetum. The sandbar shark shows an optical sensitivity of 1.11 μm² steradians. Visual resolution is highest in the lateral visual field, reaching a peak spatial resolution of 8.9 cycles/degree. An ERG derived spectral response curve for this species indicates maximal response to blue light between 460-490 nm. Interestingly, the tiger shark is maximally sensitive to a brighter range of light intensities compared to sandbar sharks, implying that tiger sharks occupy a more photopic light environment. However, sandbar sharks have a visual system with higher temporal resolution, as evaluated by the ERG response, (54 Hz) than tiger sharks (38 Hz). These results may reflect a difference in the importance of motion perception between <i>C. plumbeus</i> and <i>G. cuvier</i>. Phenotypic variability in visual function is shown between different populations of <i>C. plumbeus</i> occupying habitats with different ambient light conditions. This study provides new evidence of plasticity of visual function in response to acclimation to different visual environments within the same species. Sandbar sharks show an adaptive plasticity in visual sensitivity and temporal resolution, which appears to enable both temporal and population-specific adaptations to local light environments. In addition, the eyes of <i>C. plumbeus</i> and <i>S. mitsukurii</i> continue to grow even in adulthood. Visual performance, with respect to spatial resolving power and optical sensitivity, improve with eye growth. For example, peak spatial resolution increases with eye growth from 4.3 to 8.9 cycles/degree in <i>C. plumbeus</i> and from 5.7 to 7.2 cycles/degree in <i>S. mitsukurii</i>. These studies suggest that the light environment strongly influences visual function in this ancient class of vertebrates. Anthropogenically induced changes in water clarity may, therefore, impact on visually-mediated behaviours such as prey detection, agonistic signals or vertical migration. Anatomical and physiological parameters obtained from these studies provide a platform from which to model visual behaviours such as 1). Prey detection capabilities, 2). The impacts of water clarity on the limits of visually-mediated behaviour, and 3). The visual strategies that would allow sharks to maximise visual function, such as spatial and temporal summation under low light conditions. In conclusion, neuroethological studies can be a useful means to enrich information obtained from life-history and tagging studies and, together, can inform us of the functional role of sharks in marine ecosystems.