When an organism is dehydrated, neurons in the Organum vasculosum lamina terminalis (OVL T) sense this variation in plasma osmolality (OSM) and excite magnocellular neurosecretory cells (MNCs) in the supraoptic nucleus (SON) via glutamatergic synapses. The resulting action potential firing of MNCs will result in the secretion of vasopressin (VP) into the blood, which will promote water reabsorption from the kidney. The relationship between plasma VP and OSM (know as the VP-OSM ratio) is known to change in sensitivity during the course of a day. / Lorsqu'un organisme est déshydraté, les neurones dans l'Organum vasculosum lamina terminalis (OVL T) détectent le changement dans l'osmolalité du plasma (OSM) et excitent les cellules magnocellulaires neurosécrétoires (MNCs) dans le noyau supraoptique (SON) avec des synapses glutamatergique. La décharge des potentiels d'action qui survient dans les MNCs génère la sécrétion de vasopressine (VP) dans le sang, qui permettra la réabsorption d'eau au niveau du rein. Le rapport entre la VP et OSM (connu comme étant le rapport VP/OSM) subit des changements de sensibilité durant une journée.

Despite the overwhelming evidence for atrophy of the NGF-dependant Basal Forebrain Cholinergic neurons during aging, there is no persuasive evidence towards a decrease in NGF and/or NGF mRNA content in the brain of aged animals. Previous experiments from our laboratory have shown that NGF is released as a precursor protein and cleaved into the mature form in the extracellular space under the influence of a complex protease cascade. These recent findings have lead us to propose that any alterations in levels and/or activity of this maturation/degradation cascade might affect NGF's biological activity and perhaps lead to cognitive impairments in a subset of aged rats. To investigate this possibility, we measured protein and mRNA levels of the protease cascade players (NGF, pro-NGF, tPA, plasminogen, plasmin, MMP-9, neuroserpin). We found significantly decreased levels of both pro-NGF protein and NGF mRNA, but no difference in the remaining elements of the protease cascade, when comparing aged impaired (Al) to the aged unimpaired (AU) animals. Our second objective was to investigate whether animals trained in the Morris Water Maze would preserve their cognitive status in two additional behavioral paradigms, the Novel Object Location (NOL, spatial memory) and Novel Object Recognition (NOR, nonspatial memory) tasks. We found that both AU and AI animals in the MWM were impaired in the NOL when compared to the young controls, with the AI animals performing significantly worse than the AU in this particular task. In the NOR tasks, AI animals performed significantly worse compared to both young and AU animals. In conclusion, further experiments are required to better understand the implication of the complex protease cascade involved in NGF's maturation and degradation as well as its effect on memory of aged animals. In addition, because the segregation of animals (aged impaired/unimpaired) is a crucial step in aging research, we now have additional behavioral paradigms (NOL/NOR) that confirm the cognitive status of these animals.

Muscle tissue development (myogenesis) involves the formation of specific fibers (myotubes) from muscle cells (myoblasts). For this to occur, the sequential expression of Myogenic Regulatory Factors (MRFs), such as MyoD and myogenin, is required. The expression of these MRFs is regulated posttranscriptionally by the RNA-binding protein HuR, whereby HuR associates with the 3'-untranslated regions of MyoD and myogenin mRNA, leading to a significant increase in their half-lives. Here we show that the cleavage of HuR by caspases at the aspartate (D) 226 residue is one of the main regulators of its pro-myogenic function. This proteolytic activity generates two cleavage products (CPs), HuR-CP1 and HuR-CP2, that differentially affect the myogenic process. Myoblasts overexpressing HuR-CP1 or the non-cleavable mutant of HuR, HuRD226A, are not able to engage myogenesis, while overexpressing HuR-CP2 enhances myotube formation. HuR-CP2 but not -CP1 promotes myogenesis by stabilizing the MyoD and myogenin mRNAs to the same levels as wt-HuR. Conversely, the inhibitory effects of HuR-CP1 and HuRD226A depend on their abilities to associate during myogenesis with the HuR import receptor, Trn2, leading to HuR accumulation in the cytoplasm. Therefore, we propose a model whereby the caspase-mediated cleavage of HuR generates two CPs that collaborate to regulate myogenesis; HuR-CP1 by interfering with the Trn2-mediated import of HuR and HuR-CP2 by participating in the stabilization of mRNAs encoding key MRFs.

Several aspects of the physiology of the fat mouse Steatomys pratensis natalensis were studied in the laboratory using standard techniques and custom-made data-logging equipment. The fat was studied both from a morphological and functional point of view. The measurement of metabolic rates showed that euthermic S.pratensis have very low basal metabolic rates of 36% of expected, with torpor saving up to 69% of expended energy. Body temperatures, oxygen consumption, and activity patterns monitored over 24 hour periods with a data-logging system showed that Sipratensis have very low body temperatures of 31.3 to 35.0°C which fluctuate on a circadian rhythm with activity and oxygen consumption, all being lower during the day and higher at night. Torpor started very early in the morning and lasted for 5.5 to 11.7 hours. Huddling with a mate could reduce energy expenditure by 18%. Torpid body temperatures lay just above ambient from 15 to 35°C, below which all animals tried to arouse. Forced arousal at 10 to 30°C was slow and depended on ambient temperature while no mouse could arouse at O°C. Thermal conductance was 97.4 % of expected but cooling rates of dead S.pratensis were slow due to the heavy fat layer. Non-shivering thermogensis (measured after noradrenaline injection) was normal at 369% of BMR but maximum metabolism was twice as much, indicating other means of thermogenesis used additively with NST. Dissection showed extremely heavy fat deposits in the normal mammalian positions and also three additional deposits. Histological studies revealed most deposits as white fat but there was brown fat in the interscapular region. Soxhlet analysis showed an extremely wide range of body fat content from normal mammalian levels to contents higher than in hibernating rodents. Deprivation of food and water, or food alone, was found to induce torpor and cause the mice to become non-reproductive. Deprivation of water but not food, and deprivation of a cage mate, triggered torpor in only 40 - 44% of the cases studied. The mice took 5 to 12 days to lose 30% of their mass, but theoretically could survive longer. Weekly measurements showed no annual mass fluctuations in the laboratory but the mice became reproductively active mid-summer to early winter while torpor was at a maximum around late winter. All animals showed torpor, young more than adults and females more than males. It is suggested that the low body temperature and metabolism of S.pratensis may have evolved to prevent overheating caused by their inability to lose heat through the heavy fat layer. The species could then disperse into areas where their low energetic demands would permit them to compete successfully with high metabolic rate rodents. / Thesis (M.Sc.)-University of Natal, Durban, 1990.

No description available.

Glycosaminoglycan-peptide complexes (GAG-P) and some proteoglycans from long bones, breast muscle, comb, crop, gizzard, heart, infundibulum, intestines, isthmus, kidney, leg muscle, liver, lung, magnum, oesophagus, ovary, pancreas, proventriculus, skin, shell gland, spleen, trachea, vagina, wattle, cecum, egg yolk and adipose tissue of the white leghorn hen were isolated and analysed for constituent units. Techniques of identification included infrared spectroscopy, cellulose acetate electrophoresis, colorimetric reactions, ion-exchange chromatography and scanning electron microscopy. The in vivo incorporation of {('14)C}-glucosamine (GlcN) and {('14)C}-galactosamine (GalN) for 1-, 2-, 120-, and 240-hour periods, and {('14)C}-glucose (Glc) and {('14)C}-galactose (Gal) for a 48-hour period into whole tissues, acetone-extracted tissues and GAG-P were investigated. Radioactivity in excreta was measured. ('14)CO(,2) from the {('14)C}-hexose treated birds was determined. In vitro incorporation of ('14)C from {('14)C}-Glc, {('14)C}-Gal, {('14)C}-GlcN, {('14)C}-GalN, {('14)C}-fructose and {('14)C}N-acetylneuraminic acid were studied.

Phytosterols occur naturally in the non-saponifiable material of plant oils. Sitostanol, the saturated derivative of beta-sitosterol, is found in negligible concentrations in plant sources and, hence, is almost absent from typical Western diets. Tall oil extracts, on the other hand, contain about 20% (w/w) sitostanol. Phytosterols have been shown to lower plasma total cholesterol levels in animals and humans while sitostanol exhibited stronger reducing effects. Several studies have suggested that phytosterols lower plasma total cholesterol levels by either inhibiting cholesterol absorption or altering the activities of enzymes critical in cholesterol metabolism and excretion. However, results obtained demonstrate inconsistency regarding the effects of phytosterols on cholesterol absorption rates and cholesterogenesis. In addition, few studies have determined quantitatively the changes in the rate of cholesterol absorption and biosynthesis. Hence, the objective of this thesis was to investigate further the impact of different sources of phytosterols on plasma lipid profiles and to develop a new methodology for simultaneous measurement of percent cholesterol absorption and cholesterol synthesis rates in animals and humans. The stable isotopes, 13C-, 18 O-cholesterol, and deuterium oxide were utilized for the dual isotope plasma ratio and deuterium uptake methodologies. Results from the series of animal experiments conducted demonstrate (i) a gender effect of phytosterols in modulating plasma lipid profile in hamsters, (ii) that sitostanol was more potent in lowering plasma and hepatic lipid concentrations than beta-sitosterol in hamsters and rabbits and (iii) that this lowering effect was due to a reduction in fractional cholesterol absorption and an increase in cholesterol excretion rates. Concomitantly, an up-regulation in cholesterogenesis was observed in hamsters. Furthermore, in humans tall oil phytosterols lowered total cholesterol levels in hypercholesterole

To gain an understanding of the transcriptional regulation of sucrose transport and metabolism in wheat and to examine their relationships with dry matter accumulation in seeds, this study has characterized the expression patterns of two sucrose transporters (TaSUT1 and TaSUT2) and two sucrose synthase (TaSuSy1 and TaSuSy2) genes in five spring wheat cultivars at different seed developmental stages. Cultivar ‘AC Andrew’ with higher TaSUT1 and TaSuSy2 transcript abundance particularly during the early grain filling stage, exhibited higher dry grain weight than other cultivars. The result, overall, suggests the significance of coordinated expression between TaSUT1 and TaSuSy2 for grain growth. This study also demonstrated the seed specificity of high molecular weight glutenin promoter subunit Dy10, which can be used as an important tool to drive the expression of any sucrose and starch related genes specifically in wheat grains to further our understanding of carbon partitioning and/or increase wheat starch yield.

Glioblastoma (GBM), similar to many other cancers, exhibits enhanced aerobic glycolysis with concomitant lactate production, a phenomenon known as the Warburg effect. We have demonstrated that preferential expression of Hexokinase 2 (HK2) is a critical mediator of metabolic reprograming in GBMs and its inhibition is a potential therapeutic strategy for sensitization of GBM tumors to radiation (RAD) and/or temozolomide (TMZ). Our results indicate that conditional HK2 inhibition disrupts energy homeostasis and sensitizes GBMs to radiochemotherapy under hypoxia. In GBM xenografts, conditional HK2 loss sensitizes GBM tumors to concomitant RAD/TMZ and results in a significant survival benefit in the mice. Moreover, loss of HK2 resulted in GBM remodeling with HK2 knockdowns showing increased necrosis, hypoxia, inflammatory infiltration and reduced vascularization. We anticipate that targeting a key metabolic enzyme involved in the Warburg effect might improve the efficacy of current therapeutic regimen and provide a unique paradigm for the management of GBMs.

No description available.