Pyruvate dehydrogenase activity in response to skeletal muscle contraction at two stimulation frequencies in pyruvate dehydrogenase kinase 2 knockout mice

Pyruvate dehydrogenase (PDH) plays an important role in regulating carbohydrate oxidation in skeletal muscle. PD H is deactivated by a set of PD H kinases (PD K 1-4) with PDK2 and 4 being the predominant isoforms in skeletal muscle. PDK2 is highly sensitive to pyruvate inhibition, and is the most abundant isoform, while PDKI and 4 protein content are normally lower. This study examined the PDK isoform content and PDHa activation in muscle at rest and 10 and 40 Hz stimulation from PDK2 knockout (PDK2KO) mice to delineate the role of PDK2 in activating the PDH complex during low and moderate intensity muscle contraction. PDHa activity was lower in PDK2KO mice during contraction while total PDK actitvity was -4 fold lower. PDK4 protein was not different, however PDKI partially compensated for the lack of PDK2 and was -56% higher than WT. PDKI is a very potent inhibitor of the PDH complex due to its phosphorylation site specificity and allosteric regulation. These results suggest that the site specificity and allosteric regulatory properties of the individual PDK isoforms are more important than total PDK activity in determining transformation of the complex and PDHa activity during acute muscle contraction.

A phenomenological approach to understanding the psychological response to chronic low back pain

Chronic low back pain (CLBP) is a complex health problem of psychological manifestations not fully understood. Using interpretive phenomenological analysis, 11 semi-structured interviews were conducted to help understand the meaning of the lived experience of CLBP; focusing on the psychological response to pain and the role of depression, catastrophizing, fear-avoidance behavior, anxiety and somatization. Participants characterized CLBP as persistent tolerable low back pain (TLBP) interrupted by periods of intolerable low back pain (ILBP). ILBP contributed to recurring bouts of helplessness, depression, frustration with the medical system and increased fear based on the perceived consequences of anticipated recurrences, all of which were mediated by the uncertainty of such pain. During times of TLBP all participants pursued a permanent pain consciousness as they felt susceptible to experience a recurrence. As CLBP progressed, participants felt they were living with a weakness, became isolated from those without CLBP and integrated pain into their self-concept.

The carbon disclosure project, an evolution in international environmental corporate governance : motivations and determinants of market response to voluntary disclosures

This paper examines the factors associated with Canadian firms voluntarily disclosing climate change information through the Carbon Disclosure Project. Five hypotheses are presented to explain the factors influencing management's decision to disclose this information. These hypotheses include a response to shareholder activism, domestic institutional investor shareholder activism, signalling, litigation risk, and low cost publicity. Both binary logistic regressions as well as a cross-sectional analysis of the equity market's response to the environmental disclosures being made were used to test these hypotheses. Support was found for shareholder activism, low cost publicity, and litigation risk. However, the equity market's response was not found to be statistically significant.

Mapping one university's response to internationalization : a case study

This study explored one university's response to the internationalization of higher education. Case study methodology was employed through a review of current and archival documents and interviews with key actors in the international spheres of the university. The historical, current, and future contexts were considered to situate the case study on a time line. Data analysis revealed that there were several points of division among the university community related to the response to internationalization, but also a major point of coherence in the centrality of inter-cultural understanding in efforts to internationalize. Other key findings included strengths, areas for improvement, and future directions of the university's response to internationalization. All of these findings were contextualized in findings related to the history of the university. In addition to these major findings, three themes in relation to the vision for internationalization at the institution were revealed: ( a) intercultural understanding, (b) the comprehensive status of the university, and (c) the financial benefits of internationalization. Recommendations are made for practice at the university in order to clarify this vision to develop a clear foundation from which to further build a response to internationalization that is solidly based on inter-cultural understanding, and recommendations for future research into the process of internationalization at the institutional level in Canada are suggested.

Innovation and adaptation in the Ontario grape and wine industry: An integrated, transdisciplinary response to climate change

With scientific consensus supporting a 4oC increase in global mean temperature over the next century and increased frequency of severe weather events, adaptation to climate change is critical. Given the dynamic and complex nature of climate change, a transdisciplinary approach toward adaptation can create an environment that supports knowledge sharing and innovation, improving existing strategies and creating new ones. The Ontario wine industry provides a case study to illustrate the benefits of this approach. We describe the formation and work of the Ontario Grape and Wine Research Network within this context, and present some preliminary results to highlight the opportunities for innovation that will drive the successful adaption of the Ontario grape and wine industry.

Phosphorylation of Skeletal Muscle Pyruvate Dehydrogenase Phosphatase in Response to Insulin Stimulation

Pyruvate dehydrogenase phosphatase (PDP) regulates carbohydrate oxidation through the pyruvate dehydrogenase (PDH) complex. PDP activates PDH, enabling increased carbohydrate flux towards oxidative energy production. In culture myoblasts, both PDP1 and PDP2 undergo covalent activation in response to insulin–stimulation by protein kinase C delta (PKCδ). Our objective was to examine the effect of insulin on PDP phosphorylation and PDH activation in skeletal muscle. Intact rat extensor digitorum longus muscles were incubated (oxygenated at 25°C, 1g of tension) for 30min in basal or insulin–stimulated (10 mU/mL) media. PDH activity increased 58% following stimulation, (p=0.057, n=11). Serine phosphorylation of PDP1 (p=0.047) and PDP2 (p=0.006) increased by 29% and 48%, respectively (n=8), and mitochondrial PKCδ protein content was enriched by 45% in response to stimulation (p=0.0009, n=8). These data suggest that the insulin–stimulated increase in PDH activity in whole tissue is mediated through mitochondrial migration of PKCδ and subsequent PDP phosphorylation.

Bone markers and cytokines in response to low-impact, high-intensity exercise

A low-impact, high-intensity interval exercise (HIE) bout was used to determine whether an association exists between cytokines and bone turnover markers following an acute bout of exercise. Twenty-three recreationally active males (21.8±2.4yr) performed a single HIE bout on a cycle ergometer at 90% relative intensity. Venous blood samples were collected prior to exercise, 5-minutes, 1-hour, and 24-hours post-exercise, and were analyzed for serum levels of pro-inflammatory (IL-6, IL-1α, IL-1β, and TNF-α) and anti- inflammatory cytokines (IL-10) and markers of bone formation (BAP, OPG) and resorption (NTX, RANKL). Significant effects were observed with all bone markers, especially 5-minutes post-exercise with BAP, OPG, and RANKL increasing from baseline (p<0.05). Significant effects were also observed for IL-1α, IL-1β, IL-6, and TNF-α (p<0.00, p=0.04, p=0.03, p<0.00). In addition, post-exercise changes in NTX, BAP, and OPG were significantly correlated pro- and anti-inflammatory cytokines, suggesting that an interaction exists between the immune and skeletal response to exercise.

Effects of social context on endocrine function and Zif268 expression in response to an acute stressor in adolescent and adult rats

There is a paucity of studies comparing social buffering in adolescents and adults, despite their marked differences in social behaviour. I investigated whether greater effects of social buffering on plasma corticosterone concentrations and expression of Zif268 in neural regions after an acute stressor would be found in adolescent compared with adult rats. Samples were obtained before and after one hour of isolation stress and after either one or three hours of recovery back in the colony with either a familiar or unfamiliar cage partner. Adolescent and adult rats did not differ in plasma concentrations of corticosterone at any time point. Corticosterone concentrations were higher after one hour isolation than at baseline (p < 0.001), and rats with a familiar partner during the recovery phase had lower corticosterone concentrations than did rats with an unfamiliar partner (p = 0.02). Zif268 immunoreactive cell counts were higher in the arcuate nucleus in both age groups after isolation (p = 0.007) and higher in the paraventricular nucleus of adolescents compared with adults during the recovery phase irrespective of partner familiarity. There was a significant decrease in immunoreactive cell counts after one hour isolation compared to baseline in the basolateral amygdala, central nucleus of the amygdala, and in the pyramidal layer of the hippocampus (all p < 0.05). An effect of partner familiarity on Zif268 immunoreactive cell counts was found in the granule layer of the dentate gyrus irrespective of age (higher in those with a familiar partner, p = 0.03) and in the medial prefrontal cortex in adolescents (higher with an unfamiliar partner, p = 0.02). Overall, the acute stress and partner familiarity produced a similar pattern of results in adolescents and adults, with both age groups sensitive to the social context.

Algal and protozoan response to Holocene climate change and anthropogenic impact: a case study from Sluice Pond, MA

Sluice Pond is a small (18 ha) and deep (Zmax 20.0 m) partially meromictic, pond in Lynn, Massachusetts that contains a diverse dinocyst record since the early Holocene. High dinocyst concentrations, including morphotypes not previously described, as well as the preservation of several specimens of cellulosic thecae are attributed to low dissolved oxygen (DO) in the basin. The fossil protozoan record supports the interpretation- thecamoebians were unable to colonize the basin until the middle Holocene and only became abundant when the drought-induced lowstand oxygenated the bottom waters. Protozoans tolerant of low DO became abundant through the late Holocene as water levels rose and cultural eutrophication produced a sharp increase in biochemical oxygen demand (BOD) beginning in the 17th century. Recent sediments contain a dominance of Peridinium willei, indicating cultural eutrophication and the planktonic ciliate Codonella cratera and the thecamoebian Cucurbitella tricuspis in the deep basin. Above the chemocline however, a diverse difflugiid thecamoebian assemblage is present.

Brief Report: Response to National Institutes of Health Report

The article discusses the National Institutes of Health Report and its lack of research on sensory problems in autism.

Prediction of the clinical response to psychostimulant by the basal and reactive salivary cortisol in children with ADHD.

Le trouble du déficit de l’attention/hyperactivité (TDA/H) est un des troubles comportementaux le plus commun chez les enfants. TDAH a une étiologie complexe et des traitements efficaces. Le médicament le plus prescrit est le méthylphénidate, un psychostimulant qui bloque le transporteur de la dopamine et augmente la disponibilité de la dopamine dans la fente synaptique. Des études précliniques et cliniques suggèrent que le cortisol peut potentialiser les effets de la dopamine. Un dysfonctionnement du système hypothalamo-hypophyso-surrénalien (HHS) est associé avec plusieurs maladies psychiatriques comme la dépression, le trouble bipolaire, et l’anxiété. Nous avons fait l’hypothèse que le cortisol influence l’efficacité du traitement des symptômes du TDAH par le méthylphénidate. L’objectif de cette étude est de mesurer les niveaux de cortisol le matin au réveil et en réponse à une prise de sang dans un échantillon d’enfants diagnostiqué avec TDAH âgé de 8 ans. Le groupe était randomisé dans un protocole en chassé croisé et en double aveugle avec trois doses de méthylphénidate et un placebo pour une période de quatre semaines. Les enseignants et les parents ont répondu aux questionnaires SWAN et à une échelle d’évaluation des effets secondaires. Les résultats ont démontrés qu’un niveau de cortisol élevé au réveil prédit les sujets qui ne répondent pas au traitement du TDAH, si on se fie aux rapports des parents. En plus, la réactivité au stress élevé suggère un bénéfice additionnel d’une dose élevée de méthylphénidate selon les enseignants. Aussi, les parents rapportent une association entre la présence de troubles anxieux co-morbide avec le TDAH et une meilleure réponse à une dose élevée. Cette étude suggère qu’une forte réactivité de l’axe HHS améliore la réponse clinique à des doses élevées, mais qu’une élévation chronique du niveau de cortisol pourrait être un marqueur pour les non répondeurs. Les résultats de cette étude doivent être considérés comme préliminaires et nécessitent des tests plus approfondis des interactions possibles entre les médicaments utilisés pour traiter le TDAH et l’axe HHS.

Brain tumor and brain endothelial cells' response to ionizing radiation and phytochemical treatments

Le glioblastome multiforme (GBM) représente la tumeur cérébrale primaire la plus agressive et la plus vascularisée chez l’adulte. La survie médiane après le diagnostic est de moins d’un an en l’absence de traitement. Malheureusement, 90% des patients traités avec de la radiothérapie après la résection chirurgicale d’un GBM développent une récidive tumorale. Récemment, le traitement des GBM avec radiothérapie et témozolomide, un agent reconnu pour ses propriétés antiangiogéniques, a permis de prolonger la survie médiane à 14,6 mois. Des efforts sont déployés pour identifier des substances naturelles capables d’inhiber, de retarder ou de renverser le processus de carcinogenèse. Epigallocatechin-3-gallate (EGCG), un polyphénol retrouvé dans le thé vert, est reconnu pour ses propriétés anticancéreuses et antiangiogéniques. L’EGCG pourrait sensibiliser les cellules tumorales cérébrales et les cellules endothéliales dérivées des tumeurs aux traitements conventionnels. Le chapitre II décrit la première partie de ce projet de doctorat. Nous avons tenté de déterminer si l’EGCG pourrait sensibiliser la réponse des GBM à l’irradiation (IR) et si des marqueurs moléculaires spécifiques sont impliqués. Nous avons documenté que les cellules U-87 étaient relativement radiorésistantes et que Survivin, une protéine inhibitrice de l’apoptose, pourrait être impliquée dans la radiorésistance des GBM. Aussi, nous avons démontré que le pré-traitement des cellules U-87 avec de l’EGCG pourrait annuler l’effet cytoprotecteur d’une surexpression de Survivin et potentialiser l’effet cytoréducteur de l’IR. Au chapitre III, nous avons caractérisé l’impact de l’IR sur la survie de cellules endothéliales microvasculaires cérébrales humaines (HBMEC) et nous avons déterminé si l’EGCG pouvait optimiser cet effet. Bien que les traitements individuels avec l’EGCG et l’IR diminuaient la survie des HBMEC, le traitement combiné diminuait de façon synergique la survie cellulaire. Nous avons documenté que le traitement combiné augmentait la mort cellulaire, plus spécifiquement la nécrose. Au chapitre IV, nous avons investigué l’impact de l’IR sur les fonctions angiogéniques des HBMEC résistantes à l’IR, notamment la prolifération cellulaire, la migration cellulaire en présence de facteurs de croissance dérivés des tumeurs cérébrales, et la capacité de tubulogenèse. La voie de signalisation des Rho a aussi été étudiée en relation avec les propriétés angiogéniques des HBMEC radiorésistantes. Nos données suggèrent que l’IR altère significativement les propriétés angiogéniques des HBMEC. La réponse aux facteurs importants pour la croissance tumorale et l’angiogenèse ainsi que la tubulogenèse sont atténuées dans ces cellules. En conclusion, ce projet de doctorat confirme les propriétés cytoréductrices de l’IR sur les gliomes malins et propose un nouveau mécanisme pour expliquer la radiorésistance des GBM. Ce projet documente pour la première fois l’effet cytotoxique de l’IR sur les HBMEC. Aussi, ce projet reconnaît l’existence de HBMEC radiorésistantes et caractérise leurs fonctions angiogéniques altérées. La combinaison de molécules naturelles anticancéreuses et antiangiogéniques telles que l’EGCG avec de la radiothérapie pourrait améliorer l’effet de l’IR sur les cellules tumorales et sur les cellules endothéliales associées, possiblement en augmentant la mort cellulaire. Cette thèse supporte l’intégration de nutriments avec propriétés anticancéreuses et antiangiogéniques dans le traitement des gliomes malins pour sensibiliser les cellules tumorales et endothéliales aux traitements conventionnels.