Cardiovascular and metabolic effects of dietary selenomethionine exposure in fishes

Selenium (Se) is an essential micronutrient involved in important metabolic functions for all vertebrate species. As Se is reported to have a narrow margin between essentiality and toxicity, there is growing concern surrounding the adverse effects of elevated Se exposure caused by anthropogenic activities. Recent studies have reported that elevated dietary exposure of fish to selenomethionine (Se-Met) can alter aerobic metabolic capacity, energetics and swimming performance. My thesis aimed to further investigate mechanisms of sublethal Se-Met toxicity, particularly potential underlying cardiovascular implications of chronic exposure to environmentally relevant concentrations of dietary Se-Met in adult zebrafish (Danio rerio) and juvenile (yearling) rainbow trout (Oncorhynchus mykiss). In my first experiment, adult zebrafish were fed either control food (1.1 μg Se/g dry mass [d.m.]) or Se-Met spiked food (10.3 or 28.8 μg Se/g d.m.) for 90 d at 5% body weight per day. In the second experiment, juvenile rainbow trout were fed either control food (1.3 μg Se/g d.m.) or Se-Met spiked food (6.4, 15.8 or 47.8 μg Se/g d.m.) for 60 d at 5% body weight per day. Following exposure, ultrahigh resolution B-mode and Doppler ultrasound was used to characterize cardiac function. Chronic dietary exposure to elevated Se-Met had opposing results in zebrafish when compared to the rainbow trout. Zebrafish exposed to the highest dietary concentrations of Se-Met (28.8 μg Se/g d.m.) had significantly reduced ventricular contractile rate, stroke volume, and cardiac output, while Se-Met exposed rainbow trout had significantly greater stroke volume, ejection fraction, and cardiac output. Following ultasonography, energy stores were measured via whole body (zebrafish) and liver, heart and muscle (rainbow trout) glycogen and triglyceride concentrations. Zebrafish in the highest exposure group were observed to have greater whole body glycogen concentrations when compared to the control group, while rainbow trout exposed to Se-Met concentrations greater than 15.8 μg Se/g showed significant increases in both glycogen and triglycerides in liver relative to the control group. In addition, rainbow trout in the highest exposure group had significantly reduced capability of managing blood glucose levels as was evident after 48hrs in a glucose tolerance test. Exposure to Se-Met significantly decreased mRNA expression of a key cardiac remodelling enzyme, matrix metalloproteinase 2 (MMP2), in adult zebrafish heart, however significantly increased it (MMP9) in rainbow trout heart. Selenomethionine significantly increased echodensity at the junction between atrium and ventricle in zebrafish, and these results combined with increased MMP2 expression are consistent with cardiac remodelling and fibrosis. However, rainbow trout did not show any fibrosis and also had a significant decrease in SERPINH mRNA abundance, a molecular chaperone essential for the post-translational folding of fibril-forming collagens. This, taken together with the increase in MMP9, suggests an anti-fibrotic response in the rainbow trout heart, compared to the fibrosis seen in the zebrafish, which could help explain why there were opposing cardiovascular results. Due to the anti-fibrotic response in rainbow trout, the heart was apparently able to pump blood more effectively leading to the increase in stroke volume, ejection fraction, and cardiac output observed. The results of this study suggest that chronic exposure to dietary Se-Met can impact cardiac function, energy homeostasis and cause cellular perturbations, and such physiological consequences could reduce the aerobic capacity and survivability of fish. The varying results seen could be attributed to species sensitivity differences or perhaps due to the cold vs warm water fish selenium sensitivity

An Essential Role for the Tetraspanin LHFPL4 in the Cell-Type-Specific Targeting and Clustering of Synaptic GABAReceptors

Inhibitory synaptic transmission requires the targeting and stabilization of GABAA receptors (GABAARs) at synapses. The mechanisms responsible remain poorly understood, and roles for transmembrane accessory proteins have not been established. Using molecular, imaging, and electrophysiological approaches, we identify the tetraspanin LHFPL4 as a critical regulator of postsynaptic GABAAR clustering in hippocampal pyramidal neurons. LHFPL4 interacts tightly with GABAAR subunits and is selectively enriched at inhibitory synapses. In LHFPL4 knockout mice, there is a dramatic cell-type-specific reduction in GABAAR and gephyrin clusters and an accumulation of large intracellular gephyrin aggregates in vivo. While GABAARs are still trafficked to the neuronal surface in pyramidal neurons, they are no longer localized at synapses, resulting in a profound loss of fast inhibitory postsynaptic currents. Hippocampal interneuron currents remain unaffected. Our results establish LHFPL4 as a synapse-specific tetraspanin essential for inhibitory synapse function and provide fresh insights into the molecular make-up of inhibitory synapses

Boulder: evolution of a city

Includes index.Revised editionEarly Boulder photographers -- Downtown business district: the Pearl Street Mall -- South-central Boulder: floods, minorities, and the railroads -- North-central Boulder: culture and religion -- West-central Boulder: at the foot of the mountains -- East central Boulder: working man's neighborhood -- North Boulder: vanishing farmlands -- University of Colorado: alone on the hill -- University Hill and Chautauqua: becoming established -- South Boulder: postwar growth -- End of an era: the city mature

A. -The selection of male-sterile lines in alfalfa. B. -The witches' broom virus disease of alfalfa in British Columbia

In the hope of finding male-sterile alfalfa strains for use in the production of hybrid alfalfa, a microscopic study of the pollen produced by approximately 1000 lines of alfalfa grown at the University of British-Columbia was conducted. This study revealed 4 lines that consistently showed an absence of viable pollen under different environments. 2 of the male-sterile lines produced no seed on selfing and 2 produced very small quantities of seed. In plants grown from open-pollinated seed of the 4 male-sterile lines, the F₁ segregation for male-sterile to male-fertile were as follows: 1:7.9, 1:7.3, 1:6.8, and 1:8.3, for an incomplete count. These ratios suggest that the male-sterility is controlled by cytoplasmic factors in addition to recessive genes. However, the mode of inheritance will only be factorially interpreted by F₂ and backcross data. It appears that the sterility is caused by a breakdown in meiosis, as the pollen sacs are full of an amorphous material suggestive of arrested development of the pollen grains. The male-sterility should eventually prove of great economic value in the production of hybrid alfalfa seed. Male-sterility has not previously been isolated in alfalfa, although it is common in the plant kingdom. Over the past 10 years the Witches' Broom virus disease of alfalfa has developed into serious proportions in the Interior of B.C. - this was first pointed out by quadrat results obtained in 1942-44. The disease is known to be distributed throughout the low rainfall areas of the province where it is widespread although sporadic. The disease is shown to be the same disease that occurs in Washington and in Australia. Witches' Broom of Alfalfa causes severe dwarfing of the affected plants and a decimation of alfalfa stands. Drastic shortening of internodes and reduction in size of leaves is accompanied by proliferation of crowns and nodes. Up to 3000 thin spindly shoots are commonly produced by a single diseased crown. Typically, leaves are marginally chlorotic; inflorescences are reduced to 3-4 florets per raceme; and, very little, if any, seed is produced. Crowns and roots are symptomless until late stages of the disease are reached, when they show severe rotting. Affected plants gradually die in a period of 3 months to 2 years. However, 2 plants were shown to apparently recover from the disease when brought into the U.B.C. greenhouse from the Nicola Valley. A histological comparison of the healthy and diseased plants showed gummosis of the xylem vessels, a breakdown and degeneration of the chloropasts of the affected leaves, and a mechanical breakdown of the palisade layer in the outer edge of diseased leaves. Storage of starch in the crowns of plants was found to be depleted according to the stage of the disease, with no storage starch present in severely diseased crowns. However, sucrose was found to be present in storage in diseased crowns but not in healthy crowns. The disease was found to be easily transmitted by crown grafts. Out of 142 attempted grafts, union of scion and stock was achieved in 31 cases with positive transmission in 27 cases. Seed transmission and inoculations by expressed crown juice have given negative results to date. Quadrats were plotted in 1950 in the interior of B.C. to further study the disease. Twinning experiments were set up to study natural resistance of the members of the genus Medicago. Results from both of these studies will not be ready for publication for at least 2 more years. A nursery plot was established at U.B.C. and a replicate plot at Kamloops, B.C. One year after planting the Kamloops plot, several of the alfalfa plants were found producing symptoms of the disease, and to be badly diseased in 15 months time. None of the plants at U.B.C. showed any signs of the disease. From a potted plant yield trial conducted at U.B.C. the diseased plants were shown to have a statistically significant reduction in yields as compared to healthy plants.Land and Food Systems, Faculty ofGraduat

The relationship between depressive dispositions and responses to stressful life events in college students

Bibliography: p. 129-153

New synaptic organizing proteins and their roles in excitatory and inhibitory synapse development

The brain consists of billions of neurons. During development, these neurons must migrate to their proper position and form connections with neighboring neurons to form networks. The specificity and maturation of these connections, or synapses, are critical for proper brain function, including learning, memory and cognition. Many cell adhesion molecules (CAMs) are involved in the formation and maturation of synapses, including the well-characterized neuroligin-neurexin pair. In this study, two new synapse modifying proteins, calsyntenin and MDGA, are characterized using in vitro assays and primary hippocampal neuron cultures. Calsyntenin-3 was identified in an un-biased screen to search for new synaptogenic proteins. It is a post-synaptic transmembrane protein that induces the formation of excitatory and inhibitory presynaptic specializations in contacting axons via extracellular cadherin and LNS domains. Overexpression of calsyntenin-3 in neurons increases presynaptic protein clustering. Interestingly, calsyntenin-3 binds to α-neurexins with high affinity, suggesting presynaptic induction is mediated through trans-synaptic signaling with neurexins. MDGAs are a family of synaptic GPI-linked proteins that bind neuroligin-2 with high affinity. MDGA1 blocks the presynaptic induction activity of neuroligin-2, through blocking binding to neurexins, via extracellular immunoglobulin domains. Overexpression of MDGA1 in neurons specifically decreases inhibitory synapses, while knockdown increases inhibitory synapses. Interestingly, like other synaptic proteins including neurexin and neuroligin, MDGAs have recently been linked to autism spectrum disorders and schizophrenia. Thus, the characterization of the synapse-promoting calsyntenin-3 and the synapse-reducing MDGA1 shed new light on the mechanisms by which synaptogenesis is regulated. Investigating the complex interplay between molecular players during synaptogenesis is critical not only for understanding normal brain development, but also for providing insight into neurodevelopmental disorders.Medicine, Faculty ofGraduat

Vuelo ADG41500

El presente Trabajo Fin de Máster se presenta como culmen del Máster de Arquitectura y Patrimonio Histórico de la Universidad de Sevilla, aunando los conocimientos obtenidos en protección, investigación, conservación, materialización, musealización y difusión del patrimonio con nuevas aperturas a otros modos de aproximación a nuestro entorno cultural cotidiano para aumentar las posibilidades del enfoque metodológico en la intervención patrimonial. Es por ello necesario recalcar desde un principio que el trabajo no cuenta con el esquema de desarrollo académico convencional. Gracias a nuestro aprendizaje a lo largo del año, hemos entendido que, para interpretar el patrimonio, vivo y en continuo proceso de cambio, es necesario romper los esquemas establecidos para buscar nuevas miradas que nos permitan reconocer el ámbito de estudio desde diferentes perspectivas subjetivadas, en relación con la identificación personal y colectiva a un enclave que nos aporten visiones patrimoniales no perceptibles a simple vista. El estudio realizado es el resultado de una acumulación de conocimiento desde diferentes especialidades, materias, campos y capas de análisis; ha viajado por un vaivén de divagaciones, ha sido cuestionado desde diferentes ángulos; ha sido deconstruido, repartido, reacondicionado y vuelto a construir. Tras la colmatación de la asignatura de Metodología de Intervención, la cual consistió en un taller compuesto por un equipo de alumnos de carácter multidisciplinar, y donde se realizó un estudio crítico de miradas patrimonialistas hacia Alcalá de Guadaíra y su territorio, se abrieron varias líneas de trabajo interesantes de abordar en pos de revitalizar y reactivar el patrimonio, visible y no tan visible, de esta localidad de Los Alcores. En este caso, las autoras hemos considerado como línea principal de documentación y análisis la concepción patrimonialista de la localidad de Alcalá de Guadaíra desde una aproximación e interpretación de su paisaje, entendiendo éste como pieza clave y fundamental para la comprensión de los valores patrimoniales históricos y culturales que ofrece Alcalá en relación con la capital hispalense y la comarca de Los Alcores.Universidad de Sevilla. Grado en Fundamentos de Arquitectur