Study of insulin-like growth factor signaling in mitochondrial function

Insulin-like Growth Factor-1 (IGF-1) signalling promotes cell growth and is associated with cancer progression, including metastasis, epithelial-mesenchymal transition (EMT), and resistance to therapy. Mitochondria play an essential role in cancer cell metabolism and accumulating evidence demonstrates that dysfunctional mitochondria associated with release of mitochondrial reactive oxygen species (ROS) can influence cancer cell phenotype and invasive potential. We previously isolated a mitochondrial UTP carrier (PNC1/SLC25A33) whose expression is regulated by IGF-1, and which is essential for mitochondrial maintenance. PNC1 suppression in cancer cells results in mitochondrial dysfunction and acquisition of a profound ROS-dependent invasive (EMT) phenotype. Moreover, over-expression of PNC1 in cancer cells that exhibit an EMT phenotype is sufficient to suppress mitochondrial ROS production and reverse the invasive phenotype. This led us to investigate the IGF-1-mitochondrial signalling axis in cancer cells. We found that IGF-1 signalling supports increased mitochondrial mass and Oxphos potential through a PI3K dependant pathway. Acute inhibition of IGF-1R activity with a tyrosine kinase inhibitor results in dysfunctional mitochondria and cell death. We also observed an adaptive response to IGF-1R inhibition upon prolonged exposure to the kinase inhibitor, where increased expression of the EGF receptor can compensate for loss of mitochondrial mass through activation of PI3K/mTOR signalling. However, these cells exhibit impaired mitochondrial biogenesis and mitophagy. We conclude that the IGF-1 is required for mitochondrial maintenance and biogenesis in cancer cells, and that pharmacological inhibition of this pathway may induce mitochondrial dysfunction and may render the cells more sensitive to glycolysis-targeted drugs.

Parallel nonconvex generalized Benders decomposition for natural gas production network planning under uncertainty

A scenario-based two-stage stochastic programming model for gas production network planning under uncertainty is usually a large-scale nonconvex mixed-integer nonlinear programme (MINLP), which can be efficiently solved to global optimality with nonconvex generalized Benders decomposition (NGBD). This paper is concerned with the parallelization of NGBD to exploit multiple available computing resources. Three parallelization strategies are proposed, namely, naive scenario parallelization, adaptive scenario parallelization, and adaptive scenario and bounding parallelization. Case study of two industrial natural gas production network planning problems shows that, while the NGBD without parallelization is already faster than a state-of-the-art global optimization solver by an order of magnitude, the parallelization can improve the efficiency by several times on computers with multicore processors. The adaptive scenario and bounding parallelization achieves the best overall performance among the three proposed parallelization strategies.

The technical and artistic branches and ways of organizing production in Argentine soap operas

Production processes and work organization in the cultural industries have been little discussed. For this reason, the study focuses on the production phases and the division of labor in technical and artistic branches in Argentine soap operas. There are six branches: production, direction, photography, art, sound and edition. We explain the branches, the workers involved and their function and activities. This research is based on a communicational perspective, the Political Economy of Communication and recovers contributions of the Sociology of Labour. From this combination, we attempt to provide elements of analysis to understand the functioning and organisation of daily television series. In the same way, we examine the creative work, the types of work redundant or random, the division of labour and the economies of time. The methodological approach is qualitative. In this way, the examination is based on the production of interviews with key actors of the sector and the documentary and bibliographical survey so as to systematize the data for the research.

Who is in charge? An L2 Discourse Intonation Study on Four Prosodic Parameters to Exert the Pragmatic Function of Dominance and Control in the Context of L2 Non-specialist Public Speaking

This paper reports the findings from a study of the learning of English intonation by Spanish speakers within the discourse mode of L2 oral presentation. The purpose of this experiment is, firstly, to compare four prosodic parameters before and after an L2 discourse intonation training programme and, secondly, to confirm whether subjects, after the aforementioned L2 discourse intonation training, are able to match the form of these four prosodic parameters to the discourse-pragmatic function of dominance and control. The study designed the instructions and tasks to create the oral and written corpora and Brazil’s Pronunciation for Advanced Learners of English was adapted for the pedagogical aims of the present study. The learners’ pre- and post-tasks were acoustically analysed and a pre / post- questionnaire design was applied to interpret the acoustic analysis. Results indicate most of the subjects acquired a wider choice of the four prosodic parameters partly due to the prosodically-annotated transcripts that were developed throughout the L2 discourse intonation course. Conversely, qualitative and quantitative data reveal most subjects failed to match the forms to their appropriate pragmatic functions to express dominance and control in an L2 oral presentation.

Obestatin as a key regulator of metabolism and cardiovascular function with emerging therapeutic potential for diabetes

Obestatin is a 23-amino acid C-terminally amidated gastrointestinal peptide derived from preproghrelin and which forms an alpha helix. Although obestatin has a short biological half-life and is rapidly degraded, it is proposed to exert wide-ranging pathophysiological actions. Whilst the precise nature of many of its effects is unclear, accumulating evidence supports positive actions on both metabolism and cardiovascular function. For example, obestatin has been reported to inhibit food and water intake, body weight gain, and gastrointestinal motility, and to also mediate promotion of cell survival and prevention of apoptosis. Obestatin-induced increases in β-cell mass, enhanced adipogenesis and improved lipid metabolism have been noted along with upregulation of genes associated with β-cell regeneration, insulin production and adipogenesis. Furthermore, human circulating obestatin levels generally demonstrate an inverse association with obesity and diabetes, whilst the peptide has been shown to confer protective metabolic effects in experimental diabetes, suggesting that it may hold therapeutic potential in this setting. Obestatin also appears to be involved in blood pressure regulation and to exert beneficial effects on endothelial function, with experimental studies indicating that it may also promote cardioprotective actions against, for example, ischaemia-reperfusion injury. This review will present a critical appraisal of the expanding obestatin research area and discuss the emerging therapeutic potential of this peptide for both metabolic and cardiovascular complications of diabetes. 

Risque de prix et décisions de production et d'exportation : le cas de l'agriculture au Québec

Cette thèse porte sur l’effet du risque de prix sur la décision des agriculteurs et les transformateurs québécois. Elle se divise en trois chapitres. Le premier chapitre revient sur la littérature. Le deuxième chapitre examine l’effet du risque de prix sur la production de trois produits, à savoir le maïs grain, la viande de porc et la viande d’agneau dans la province Québec. Le dernier chapitre est centré sur l’analyse de changement des préférences du transformateur québécois de porc pour ce qui est du choix de marché. Le premier chapitre vise à montrer l’importance de l’effet du risque du prix sur la quantité produite par les agriculteurs, tel que mis en évidence par la littérature. En effet, la littérature révèle l’importance du risque de prix à l’exportation sur le commerce international. Le deuxième chapitre est consacré à l’étude des facteurs du risque (les anticipations des prix et la volatilité des prix) dans la fonction de l’offre. Un modèle d’hétéroscédasticité conditionnelle autorégressive généralisée (GARCH) est utilisé afin de modéliser ces facteurs du risque. Les paramètres du modèle sont estimés par la méthode de l’Information Complète Maximum Vraisemblance (FIML). Les résultats empiriques montrent l’effet négatif de la volatilité du prix sur la production alors que la prévisibilité des prix a un effet positif sur la quantité produite. Comme attendu, nous constatons que l’application du programme d’assurance-stabilisation des revenus agricoles (ASRA) au Québec induit une plus importante sensibilité de l’offre par rapport au prix effectif (le prix incluant la compensation de l’ASRA) que par rapport au prix du marché. Par ailleurs, l’offre est moins sensible au prix des intrants qu’au prix de l’output. La diminution de l’aversion au risque de producteur est une autre conséquence de l’application de ce programme. En outre, l’estimation de la prime marginale relative au risque révèle que le producteur du maïs est le producteur le moins averse au risque (comparativement à celui de porc ou d’agneau). Le troisième chapitre consiste en l’analyse du changement de préférence du transformateur québécois du porc pour ce qui est du choix de marché. Nous supposons que le transformateur a la possibilité de fournir les produits sur deux marchés : étranger et local. Le modèle théorique explique l’offre relative comme étant une fonction à la fois d’anticipation relative et de volatilité relative des prix. Ainsi, ce modèle révèle que la sensibilité de l’offre relative par rapport à la volatilité relative de prix dépend de deux facteurs : d’une part, la part de l’exportation dans la production totale et d’autre part, l’élasticité de substitution entre les deux marchés. Un modèle à correction d’erreurs est utilisé lors d’estimation des paramètres du modèle. Les résultats montrent l’effet positif et significatif de l’anticipation relative du prix sur l’offre relative à court terme. Ces résultats montrent donc qu’une hausse de la volatilité du prix sur le marché étranger par rapport à celle sur le marché local entraine une baisse de l’offre relative sur le marché étranger à long terme. De plus, selon les résultats, les marchés étranger et local sont plus substituables à long terme qu’à court terme.

Occupational exposure to Aspergillus spp. in poultry and swine feed production

Workers from feed production often develop allergic respiratory symptoms and fungi are likely to be a significant contributing factor to these symptoms. This study intended to characterize fungal contamination in two feed production units, one for poultry and other for swine consumption. We aimed at identifying which unit presented the highest risk of occupational exposure to Aspergillus spp.

Asymptotic and structural properties of special cases of the Wright function arising in probability theory

This analysis paper presents previously unknown properties of some special cases of the Wright function whose consideration is necessitated by our work on probability theory and the theory of stochastic processes. Specifically, we establish new asymptotic properties of the particular Wright function 1Ψ1(ρ, k; ρ, 0; x) = X∞ n=0 Γ(k + ρn) Γ(ρn) x n n! (|x| < ∞) when the parameter ρ ∈ (−1, 0)∪(0, ∞) and the argument x is real. In the probability theory applications, which are focused on studies of the Poisson-Tweedie mixtures, the parameter k is a non-negative integer. Several representations involving well-known special functions are given for certain particular values of ρ. The asymptotics of 1Ψ1(ρ, k; ρ, 0; x) are obtained under numerous assumptions on the behavior of the arguments k and x when the parameter ρ is both positive and negative. We also provide some integral representations and structural properties involving the ‘reduced’ Wright function 0Ψ1(−−; ρ, 0; x) with ρ ∈ (−1, 0) ∪ (0, ∞), which might be useful for the derivation of new properties of members of the power-variance family of distributions. Some of these imply a reflection principle that connects the functions 0Ψ1(−−;±ρ, 0; ·) and certain Bessel functions. Several asymptotic relationships for both particular cases of this function are also given. A few of these follow under additional constraints from probability theory results which, although previously available, were unknown to analysts.

Supplementation of cattle fed tropical grasses with microalgae increases microbial protein production and average daily gain

A series of 3 experiments were conducted to evaluate the use of microalgae as supplements for ruminants consuming low-CP tropical grasses. In Exp. 1, the chemical composition and in vitro protein degradability of 9 algae species and 4 protein supplements were determined. In Exp. 2, rumen function and microbial protein (MCP) production were determined in Bos indicus steers fed speargrass hay alone or supplemented with Spirulina platensis, Chlorella pyrenoidosa, Dunaliella salina, or cottonseed meal (CSM). In Exp. 3, DMI and ADG were determined in B. indicus steers fed speargrass hay alone or supplemented with increasing amounts of NPN (urea combined with ammonia sulfate), CSM, or S. platensis. In Exp. 1, the CP content of S. platensis and C. pyrenoidosa (675 and 580 g/kg DM) was highest among the algae species and higher than the other protein supplements evaluated, and Schizochytrium sp. had the highest crude lipid (CL) content (198 g/kg DM). In Exp. 2, S. platensis supplementation increased speargrass hay intake, the efficiency of MCP production, the fractional outflow rate of digesta from the rumen, the concentration of NH3N, and the molar proportion of branched-chain fatty acids in the rumen fluid of steers above all other treatments. Dunaliella salina acceptance by steers was low and this resulted in no significant difference to unsupplemented steers for all parameters measured for this algae supplement. In Exp. 3, ADG linearly increased with increasing supplementary N intake from both S. platensis and NPN, with no difference between the 2 supplements. In contrast, ADG quadratically increased with increasing supplementary N intake from CSM. It was concluded that S. platensis and C. pyrenoidosa may potentially be used as protein sources for cattle grazing low-CP pastures.

'Don't stop': re-thinking the function of endings in narrative television

This thesis argues that the study of narrative television has been limited by an adherence to accepted and commonplace conceptions of endings as derived from literary theory, particularly a preoccupation with the terminus of the text as the ultimate site of cohesion, structure, and meaning. Such common conceptions of endings, this thesis argues, are largely incompatible with the realities of television’s production and reception, and as a result the study of endings in television needs to be re-thought to pay attention to the specificities of the medium. In this regard, this thesis proposes a model of intra-narrative endings, islands of cohesion, structure, and meaning located within television texts, as a possible solution to the problem of endings in television. These intra-narrative endings maintain the functionality of traditional endings, whilst also allowing for the specificities of television as a narrative medium. The first two chapters set out the theoretical groundwork, first by exploring the essential characteristics of narrative television (serialisation, fragmentation, duration, repetition, and accumulation), then by exploring the unique relationship between narrative television and the forces of contingency. These chapters also introduce the concept of intra-narrative endings as a possible solution to the problems of television’s narrative structure, and the medium’s relationship to contingency. Following on from this my three case studies examine forms of television which have either been traditionally defined as particularly resistant to closure (soap opera and the US sitcom) or which have received little analysis in terms of their narrative structure (sports coverage). Each of these case studies provides contextual material on these televisual forms, situating them in terms of their narrative structure, before moving on to analyse them in terms of my concept of intra-narrative endings. In the case of soap opera, the chapter focusses on the death of the long running character Pat Butcher in the British soap EastEnders (BBC, 1985-), while my chapter on the US sitcom focusses on the varying levels of closure that can be located within the US sitcom, using Friends (NBC, 1993-2004) as a particular example. Finally, my chapter on sports coverage analyses the BBC’s coverage of the 2012 London Olympics, and focusses on the narratives surrounding cyclists Chris Hoy and Victoria Pendleton. Each of these case studies identifies their chosen events as intra-narrative endings within larger, ongoing texts, and analyses the various ways in which they operate within those wider texts. This thesis is intended to make a contribution to the emerging field of endings studies within television by shifting the understanding of endings away from a dominant literary model which overwhelmingly focusses on the terminus of the text, to a more televisually specific model which pays attention to the particular contexts of the medium’s production and reception.

Assessment of iodine intake and related cognitive function impairments in elementary schoolchildren from Terceira Island, Azores (Portugal)

Dissertação de Mestrado, Ciências Biomédicas, 28 de Junho de 2016, Universidade dos Açores.

THE DISTRIBUTION AND FUNCTION OF DENITRIFICATION GENES: EXPLORING AGRICULTURAL MANAGEMENT AND SOIL CHEMICAL IMPLICATIONS

Denitrification is a microbially-mediated process that converts nitrate (NO3-) to dinitrogen (N2) gas and has implications for soil fertility, climate change, and water quality. Using PCR, qPCR, and T-RFLP, the effects of environmental drivers and land management on the abundance and composition of functional genes were investigated. Environmental variables affecting gene abundance were soil type, soil depth, nitrogen concentrations, soil moisture, and pH, although each gene was unique in its spatial distribution and controlling factors. The inclusion of microbial variables, specifically genotype and gene abundance, improved denitrification models and highlights the benefit of including microbial data in modeling denitrification. Along with some evidence of niche selection, I show that nirS is a good predictor of denitrification enzyme activity (DEA) and N2O:N2 ratio, especially in alkaline and wetland soils. nirK was correlated to N2O production and became a stronger predictor of DEA in acidic soils, indicating that nirK and nirS are not ecologically redundant.

Sorghum Crop Modeling and Its Utility in Agronomy and Breeding

Crop models are simplified mathematical representations of the interacting biological and environmental components of the dynamic soil–plant–environment system. Sorghum crop modeling has evolved in parallel with crop modeling capability in general, since its origins in the 1960s and 1970s. Here we briefly review the trajectory in sorghum crop modeling leading to the development of advanced models. We then (i) overview the structure and function of the sorghum model in the Agricultural Production System sIMulator (APSIM) to exemplify advanced modeling concepts that suit both agronomic and breeding applications, (ii) review an example of use of sorghum modeling in supporting agronomic management decisions, (iii) review an example of the use of sorghum modeling in plant breeding, and (iv) consider implications for future roles of sorghum crop modeling. Modeling and simulation provide an avenue to explore consequences of crop management decision options in situations confronted with risks associated with seasonal climate uncertainties. Here we consider the possibility of manipulating planting configuration and density in sorghum as a means to manipulate the productivity–risk trade-off. A simulation analysis of decision options is presented and avenues for its use with decision-makers discussed. Modeling and simulation also provide opportunities to improve breeding efficiency by either dissecting complex traits to more amenable targets for genetics and breeding, or by trait evaluation via phenotypic prediction in target production regions to help prioritize effort and assess breeding strategies. Here we consider studies on the stay-green trait in sorghum, which confers yield advantage in water-limited situations, to exemplify both aspects. The possible future roles of sorghum modeling in agronomy and breeding are discussed as are opportunities related to their synergistic interaction. The potential to add significant value to the revolution in plant breeding associated with genomic technologies is identified as the new modeling frontier.

Immune function, gene expression, blood indices and performance in transition dairy cows affected by diet and inflammation

The transition period is associated with the peak incidence of production problems, metabolic disorders and infectious diseases in dairy cows (Drackley, 1999). During this time the cow’s immune system seems to be weakened; it is apparent that metabolic challenges associated with the onset of lactation are factors capable of affecting immune function. However, the reasons for this state are not entirely clear (Goff, 2006). The negative energy balance associated with parturition leads to extensive mobilization of fatty acids stored in adipose tissue, thus, causing marked elevations in blood non-esterified fatty acids (NEFA) and B-hydroxybutyrate (BHBA) concentrations (Drackley et al., 2001). Prepartal level of dietary energy can potentially affect adipose tissue deposition and, thus, the amount of NEFA released into blood and available for metabolism in liver (Drackley et al., 2005). The current feeding practices for pregnant non-lactating cows has been called into question because increasing amounts of moderate-to-high energy diets (i.e. those more similar to lactation diets in the content of energy) during the last 3 wk postpartum have largely failed to overcome peripartal health problems, excessive body condition loss after calving, or declining fertility (Beever, 2006). Current prepartal feeding practices can lead to elevated intakes of energy, which can increase fat deposition in the viscera and upon parturition lead to compromised liver metabolism (Beever, 2006, Drackley et al., 2005). Our general hypothesis was that overfeeding dietary energy during the dry period, accompanied by the metabolic challenges associated with the onset of lactation would render the cow’s immune function less responsive early postpartum. The chapters in this dissertation evaluated neutrophil function, metabolic and inflammation indices and gene expression affected by the plane of dietary energy prepartum and an early post-partum inflammatory challenge in dairy cows. The diet effect in this experiment was transcendental during the transition period and potentially during the entire lactation. Changes in energy balance were observed and provided a good model to study the challenges associated with the onset of lactation. Overall the LPS model provided a consistent response representing an inflammation incident; however the changes in metabolic indices were sudden and hard to detect in most of the cases during the days following the challenge. In general overfeeding dietary energy during the dry period resulted in a less responsive immune function during the early postpartum. In other words, controlling the dietary energy prepartum has more benefits for the dairy cow during transition.

Transfer function-noise modeling and spatial interpolation to evaluate the risk of extreme (shallow) water-table levels in the Brazilian Cerrados

Water regimes in the Brazilian Cerrados are sensitive to climatological disturbances and human intervention. The risk that critical water-table levels are exceeded over long periods of time can be estimated by applying stochastic methods in modeling the dynamic relationship between water levels and driving forces such as precipitation and evapotranspiration. In this study, a transfer function-noise model, the so called PIRFICT-model, is applied to estimate the dynamic relationship between water-table depth and precipitation surplus/deficit in a watershed with a groundwater monitoring scheme in the Brazilian Cerrados. Critical limits were defined for a period in the Cerrados agricultural calendar, the end of the rainy season, when extremely shallow levels (< 0.5-m depth) can pose a risk to plant health and machinery before harvesting. By simulating time-series models, the risk of exceeding critical thresholds during a continuous period of time (e.g. 10 days) is described by probability levels. These simulated probabilities were interpolated spatially using universal kriging, incorporating information related to the drainage basin from a digital elevation model. The resulting map reduced model uncertainty. Three areas were defined as presenting potential risk at the end of the rainy season. These areas deserve attention with respect to water-management and land-use planning.