The effects of R(+)-lipoic acid supplementation on regulation of human skeletal muscle pyruvate dehydrogenase

This thesis investigated whole body glucose disposal and the adaptive changes in skeletal muscle carbohydrate metabolism following 28 d of supplementation with 1000 mg R(+)-lipoic acid in young sedentary males (age, 22.1 ± 0.67 yr, body mass, 78.7 ± 10.3 kg, n=9). In certain individuals, lipoic acid decreased the 180-min area under the glucose concentration and insulin concentration curve during an oral glucose tolerance test (OGTT) (n=4). In the same individuals, lipoic acid supplementation decreased pyruvate dehydrogenase kinase activity (PDK) (0.09 ± 0.024 min"^ vs. 0.137 ± 0.023 min'\ n=4). The fasting levels of the activated form of pyruvate dehydrogenase (PDHa) were decreased following lipoic acid (0.42 ± 0.13 mmol-min'kg'^ vs. 0.82 ± 0.32 mmolrnin'^kg"\ n=4), yet increased to a greater extent during the OGTT (1.21 ± 0.34 mmol-min'kg"' vs. 0.81 ±0.13 mmolmin"'kg'\ n=4) following hpoic acid supplementation. No changes were demonstrated in the remaining subjects (n=5). It was concluded that improved glucose clearance during an OGTT following lipoic acid supplementation is assisted by increased muscle glucose oxidation through increased PDHa activation and decreased PDK activity in certain individuals.

Response rainbow trout (Salmon gairdneri) blood gas transport system to temperature, oxygen availability and photoperiod

Hematological status in rainbow trout, Salmo gairdneri, was examined in relation to eight combinations of three environmental fa ctors; temperature (5°, 20°C), oxygen availability «35%, >70% saturation) and photoperiod (16L:8D, 8L:16D) and evaluated by 3-factor analysis of variance. Hemog l obin and hematocrit , indicators of oxygenc arrying capacity increased significantly at the higher temperature, following exposure to hypoxia and in relation to reduced light period. Significant variations in mean corpuscular hemoglobin concentration were not detected. The effects of temperature and oxygen availability were more pronounced than that of photoperiod which was generally masked. Although oxygen availability and photoperiod did not interact with temperature, the interaction of the former fac tors was significant. Elec trophoresis revealed twelve hemoglobin isomorphs. Relative concentration changes were found in re lation to the factors c onsidered with temperature>hypoxia>photoperiod. Howeve r , in terms of absolute concentration, effects were hypoxia>temperature>photoperiod. Photoperiod effects were again masked by temperature and (or) hypoxia. Red cell +2 l eve ls of [CI ] and [Mg ], critical elements in the hemoglobin-oxygen affinity regulating system, were also significantly altered. Red cell CI +2 was influenced only by temperature ; Mg by temper ature and oxygen. No photoperiod influence on either ions was observed. Under nominal 'summer' conditions, these changes point to the likelihood of increases in oxygen-c arrying c apac ity coupled with low Hb-02 affinity adjustments which would be expected to increase oxygen delivery rates to their more rapidly metabolising tissues.

The effects of temperature on nickel tocicity in goldfish (carassius auratus L.)

Although it is widely assumed that temperature affects pollutant toxicity, few studies have actually investigated this relationship. Moreover, such research as has been done has involved constant temperatures; circumstances which are rarely, if ever, actually experienced by north temperate, littoral zone cyprinid species. To investigate the effects of temperature regime on nickel toxicity in goldfish (Carassius auratus L.), 96- and 240-h LCSO values for the heavy metal pollutant, nickel (NiCI2.6H20), were initially determined at 2DoC (22.8 mg/L and 14.7 mg/L in artificially softened water). Constant temperature bioassays at 10°C, 20°C and 30°C were conducted at each of 0, 240-h and 96-h LCSO nickel concentrations for 240 hours. In order to determine the effects of temperature variation during nickel exposure it was imperative that the effects of a single temperature change be investigated before addressing more complex regimes. Single temperature changes of + 10°C or -10°C were imposed at rates of 2°C/h following exposures of between 24 hand 216 h. The effects of a single temperature change on mortality, and duration of toxicant exposure at high and low temperatures were evaluated. The effects of fluctuating temperatures during exposure were investigated through two regimes. The first set of bioassays imposed a sinewave diurnal cycle temperature (20.±.1DOC) throughout the 10 day exposure to 240-h LeSO Ni. The second set of investigations approximated cyprinid movement through the littoral zone by imposing directionally random temperature changes (±2°C at 2-h intervals), between extremes of 10° and 30°C, at 240-h LC50 Ni. Body size (i.e., total length, fork length, and weight) and exposure time were recorded for all fish mortalities. Cumulative mortality curves under constant temperature regimes indicated significantly higher mortality as temperature and nickel concentration were increased. At 1DOC no significant differences in mortality curves were evident in relation to low and high nickel test concentrations (Le., 16 mg/L and 20 mg/L). However at 20°C and 30°C significantly higher mortality was experienced in animals exposed to 20 mg/L Ni. Mortality at constant 10°C was significantly lower than at 30°C with 16 mg/L and was significantly loWer than each of 2DoC and 39°C tanks at 20 mg/L Ni exposure. A single temperature shift from 20°C to 1DoC resulted in a significant decrease in mortality rate and conversely, a single temperature shift from 20°C to 30°C resulted in a significant increase in mortality rate. Rates of mortality recorded during these single temperature shift assays were significantly different from mortality rates obtained under constant temperature assay conditions. Increased Ni exposure duration at higher temperatures resulted in highest mortality. Diurnally cycling temperature bioassays produced cumulative mortality curves approximating constant 20°C curves, with increased mortality evident after peaks in the temperature cycle. Randomly fluctuating temperature regime mortality curves also resembled constant 20°C tanks with mortalities after high temperature exposures (25°C - 30°C). Some test animals survived in all assays with the exception of the 30°C assays, with highest survival associated with low temperature and low Ni concentration. Post-exposure mortality occurred most frequently in individuals which had experienced high Ni concentrations and high temperatures during assays. Additional temperature stress imposed 2 - 12 weeks post exposure resulted in a single death out of 116 individuals suggesting that survivors are capable of surviving subsequent temperature stresses. These investigations suggest that temperature significantly and markedly affects acute nickel toxicity under both constant and fluctuating temperature regimes and plays a role in post exposure mortality and subsequent stress response.

Autonomic regulation and blood pressure in children

Vagal baroreflex sensitivity (BRS) is a measure of short term blood pressure (BP) regulation through alterations in heart rate. Low BRS reflects impaired autonomic system regulation and has been found to be a surrogate marker for cardiovascular health. In particular, it has found to be associated with the pathogenesis of adult hypertension. However, only limited information exists as to the negative consequences of childhood BP on baroreflex function. The objective of this study was to investigate BRS in children with 2 different BP profiles while controlling for the effects of age, maturation, sex, and body composition. A preliminary subsample of 11-14 year-old children from the HBEAT (Heart Behavioural Environmental Assessment Team) Study was selected. The children were divided into 2 BP groups; high BP (HBP; 2:95tl1 percentile, n=21) and normal BP (NBP; <90th percentile, n=85). Following an initial 15 minutes of supine rest, 5 minutes of continuous beat-to-beat BP (Finapres) and RR interval (RRI) were recorded (standard ECG). Spectral indices were computed using Fast Fourier Transform and transfer function analysis was used to compute BRS. High frequency (HF) and low frequency (LF) power spectral areas were set to 0.15-0.4 Hz and 0.04-0.15 Hz, respectively. Body composition was measured using body mass index. After adjusting for body composition, maturation, age and sex ANCOV A results were as follows; LF and HF BRS, LF and HF RRI, and RRI total power were lower in the HBP versus NBP participants (p<0.05). As well, LF IHF SBP ratio was significantly higher in the HBP compared to the NBP group (p<0.05). The regression coefficients (unstandardized B) indicated that in changing groups (NBP to HBP) LF and HF BRS decreases by 4.04 and 6.18 ms/mmHg, respectively. Thus, as BP increases, BRS decreases. These data suggest that changes in autonomic activity occur in children who have HBP, regardless of age, sex, maturation, and body composition. Thus, despite their young age and relatively short amount of time having high BP compared with adults, these children are already demonstrating poor BP regulation and reduced cardiovagal activity. Given that childhood BP is associated with hypertension in adulthood, there is a growing concern in regards to the current cardiovascular health of our children and future adults.

Liquidity, institutional ownership and regulation fair disclosure

There is a body of academic literature addressing two issues of importance for leveling the playing field for all classes of investors: 1) the impact of institutional investors on liquidity; and 2) the impact of Regulation Fair Disclosure on institutional investors and liquidity. Our study addresses both issues with the purpose of attaining a better understanding and explanation of this relationship. We classify institutional ownership according to Bushee's (1998, 2001) methodology; transient institutions, dedicated institutions and quasi-indexers. Our results indicate that while transient institutions and quasi-indexers have a positive impact on liquidity, dedicated institutional ownership is negatively associated with liquidity. This result is consistent with prior theoretical studies. We also find that the effectiveness ofthe Regulation Fair Disclosure in improving liquidity is limited to firms with higher transient institutional ownership, whereas quasi-indexed institutions have not been significantly affected by the regulations. In fact, the liquidity of firms is lower for firms with higher dedicated institutional holdings, which is evidence of the "chilling effect".

The Fast Regulation of Photosynthesis in Diatoms: an inquiry into the physiological and physical origins of non-photochemical chlorophyll fluorescence quenching.

Diatoms are renowned for their robust ability to perform NPQ (Non-Photochemical Quenching of chlorophyll fluorescence) as a dissipative response to heightened light stress on photosystem II, plausibly explaining their dominance over other algal groups in turbulent light environs. Their NPQ mechanism has been principally attributed to a xanthophyll cycle involving the lumenal pH regulated reversible de-epoxidation of diadinoxanthin. The principal goal of this dissertation is to reveal the physiological and physical origins and consequences of the NPQ response in diatoms during short-term transitions to excessive irradiation. The investigation involves diatom species from different originating light environs to highlight the diversity of diatom NPQ and to facilitate the detection of core mechanisms common among the diatoms as a group. A chiefly spectroscopic approach was used to investigate NPQ in diatom cells. Prime methodologies include: the real time monitoring of PSII excitation and de-excitation pathways via PAM fluorometry and pigment interconversion via transient absorbance measurements, the collection of cryogenic absorbance spectra to measure pigment energy levels, and the collection of cryogenic fluorescence spectra and room temperature picosecond time resolved fluorescence decay spectra to study excitation energy transfer and dissipation. Chemical inhibitors that target the trans-thylakoid pH gradient, the enzyme responsible for diadinoxanthin de-epoxidation, and photosynthetic electron flow were additionally used to experimentally manipulate the NPQ response. Multifaceted analyses of the NPQ responses from two previously un-photosynthetically characterised species, Nitzschia curvilineata and Navicula sp., were used to identify an excitation pressure relief ‘strategy’ for each species. Three key areas of NPQ were examined: (i) the NPQ activation/deactivation processes, (ii) how NPQ affects the collection, dissipation, and usage of absorbed light energy, and (iii) the interdependence of NPQ and photosynthetic electron flow. It was found that Nitzschia cells regulate excitation pressure via performing a high amplitude, reversible antenna based quenching which is dependent on the de-epoxidation of diadinoxanthin. In Navicula cells excitation pressure could be effectively regulated solely within the PSII reaction centre, whilst antenna based, diadinoxanthin de-epoxidation dependent quenching was implicated to be used as a supplemental, long-lasting source of excitation energy dissipation. These strategies for excitation balance were discussed in the context of resource partitioning under these species’ originating light climates. A more detailed investigation of the NPQ response in Nitzschia was used to develop a comprehensive model describing the mechanism for antenna centred non-photochemical quenching in this species. The experimental evidence was strongly supportive of a mechanism whereby: an acidic lumen triggers the diadinoxanthin de-epoxidation and protonation mediated aggregation of light harvesting complexes leading to the formation of quencher chlorophyll a-chlorophyll a dimers with short-lived excited states; quenching relaxes when a rise in lumen pH triggers the dispersal of light harvesting complex aggregates via deprotonation events and the input of diadinoxanthin. This model may also be applicable for describing antenna based NPQ in other diatom species.