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    High versus low carbohydrate in Skimo race performance: a randomized controlled trial
    (Montana State University - Bozeman, College of Education, Health & Human Development, 2024) Topf, Rachel Marie; Chairperson, Graduate Committee: Mary P. Miles; This is a manuscript style paper that includes co-authored chapters.
    Ski mountaineering (skimo) is a high-intensity sport with several race disciplines of varying lengths in which competitors face many challenges that can make consuming food and fluids difficult. There is currently a scarcity of literature on skimo, particularly on nutrition in individual-format races. Exercise >1.5 h, as in an individual skimo race, may benefit from high carbohydrate consumption of > or = 90 g/h compared to lower recommendations of 60 g/h. However, gastrointestinal upset is worsened with increasing amounts of carbohydrate consumption, especially during high-intensity exercise. Highly-branched cyclic dextrin is a glucose polymer with a low osmolality allowing it to have a fast gastric emptying rate which can decrease gastrointestinal upset during exercise. The first purpose of this study was to survey skimo athletes about their nutrition knowledge and practices. With this new information combined with recommendations on carbohydrate and fluid intake, the second purpose of this study was to test an 18% solution of highly-branched cyclic dextrin + fructose (3:1) in a skimo race. It was hypothesized that an 18% solution (90G) would improve performance in an individual race compared to a 6% solution (30G) without contributing to gastrointestinal upset. Fifteen participants completed the randomized controlled crossover trials. Average carbohydrate consumed was 27 and 85 g/h and race time 105 and 107 min in 30G and 90G, respectively. Overall race times were not significantly different. Gastrointestinal upset trended higher in 90G (p=0.07). When the four participants with high gastrointestinal upset (rating >4/10) were removed from analysis, there was a main effect for drink on percent lap time change (p<0.001), with 30G having a greater percent increase in lap time throughout the trial. In conclusion, a high-carbohydrate drink was created to address the needs of skimo athletes. It was found that an 18% carbohydrate solution had significantly higher gastrointestinal upset ratings and did not confer additional performance benefit compared to a 6% solution. Additionally, high gastrointestinal upset with the 18% solution appears to have contributed to slower time; however, those without high gastrointestinal upset with the 18% solution had a lesser percentage change in lap time throughout the trial compared to 6%.
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    The synthesis and characterization of fluorescently labeled, lactose-functionalized poly(amidoamine) (PAMAM) dendrimers
    (Montana State University - Bozeman, College of Letters & Science, 2024) Frometa, Magalee Rose; Chairperson, Graduate Committee: Mary J. Cloninger
    Cellular uptake of lactose-functionalized poly(amidoamine) dendrimers (PAMAM) has yet to be fully understood and deeply studied. Before sufficient cellular uptake studies can be made, optimization of the synthesis of the lactoside, and the coupling and purification of dye-tagged lactose-functionalized PAMAM had to be completed, as reported here. The synthesis of the requisite lactoside derivative for dendrimer functionalization was optimized. The coupling of the dye, Alexa Fluor 647, to the lactoside-functionalized PAMAM was performed in the presence of a sodium acetate buffer and utilized size separation methods to ensure purity. The structures of the lactoside derivatives and of lactose functionalized PAMAMs were confirmed via nuclear magnetic resonance (NMR) spectroscopy. The purity and degree of labeling (DOL) of the dye labeled, lactose-functionalized PAMAMs were determined with UV-vis. Results show high success of yield and purity resulting from the optimized procedure described in this study.
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    When a lectin binds a sugar, and other sweet tales
    (Montana State University - Bozeman, College of Letters & Science, 2019) Bernhard, Samuel Pruitt; Chairperson, Graduate Committee: Mary J. Cloninger; Mackenzie S. Fricke was an author and Katharina Achazi, Paul Hillman, Willy Totten, Rainer Haag and Mary J. Cloningerwere co-authors of the article, 'The toxicity, uptake, and impact on galectin-3 mediated apoptosis of lactose functionalized dendrimers' submitted to the journal 'Biomolecules Special Issue: Moving Forward with Dendrimers' which is contained within this dissertation.
    The current state of chemotherapy and cancer treatment leaves much to be desired. Treatment is generally non-specific and relies on high dosage to achieve therapeutically relevant concentrations at target sites. Glycopolymer-drug conjugates, featuring targeting molecules and therapeutic prodrug on a water-soluble polymeric scaffold, offer a solution to these contemporary problems. Here, the complexity of glycopolymer design is explored through the lens of a biologically significant carbohydrate-binding receptor. In particular, galectin-3 is a complex Beta-galactoside binding lectin that experiences altered expression in many cancer pathologies and is implicated in metastasis, angiogenesis and poor overall prognosis. Galectin-3 mediates undesired cancer promoting processes through carbohydrate binding and oligomerization. A more complete understanding of the role galectin-3 plays in cancer progression will guide development of methods in the therapeutic intervention of these processes. In the interest of understanding galectin-3 and using it as a targeted receptor, its binding characteristics have been assessed through fluorescence lifetime and dynamic light scattering measurements. Employment of carbohydrates and glycopolymers including mannose, lactose, and lactose functionalized poly(amidoamine) (PAMAM) dendrimers, dendritic polyglycerols (dPG), and linear polymers (LP) provided insight into the carbohydrate binding avidity of galectin-3 and its propensity to oligomerize or form micron scale aggregates. A relationship between scaffold size and receptor recruitment was observed, which sheds light into multivalent binding motifs initiated by these glycopolymers and establishes a threshold for minimum requisite lactose functionality on lactose functionalized dendritic polyglycerols. In vitro cell based glycopolymer studies with AlexaFluor 647 and lactose functionalized PAMAM dendrimers revealed size-dependent uptake and demonstrated that accumulation occurs within the lysosome. Cellular aggregation experiments revealed that lactose functionalized LPs and dPGs influence galectin-3 mediated homotypic cellular aggregation and, in fact, augment this aggregation through receptor recruitment and cross-linking. The results reported here have provided a more fundamental understanding of galectin-3 binding interactions and have laid the groundwork for optimized glycopolymer-drug conjugate design.
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    Multivalently presented carbohydrates can be used as drug delivery vehicles and to study protein carbohydrate interactions
    (Montana State University - Bozeman, College of Letters & Science, 2018) VanKoten, Harrison Wesley; Chairperson, Graduate Committee: Mary J. Cloninger; Wendy M. Dlakic, Robert Engel and Mary J. Cloninger were co-authors of the article, 'Synthesis and biological activity of highly cationic dendrimer antibiotics' in the journal 'Molecular pharmaceutics' which is contained within this thesis.; Rebecca Moore, Coleen Murphy and Mary J. Cloninger were co-authors of the article, 'Probing the LEC-1 and LEC-10 oxidative stress pathway in Caenorhabditis elegans using GALBeta1-4FUC dendrimers' which is contained within this thesis.
    Dendrimers in general excel as drug delivery vehicles since there are many different ways they can be assembled and different ways to tailor them to the system being studied. Glycodendrimers are generally nontoxic and can be further developed to meet the needs of what is being studied. For instance, in the studies below, a quaternity ammonium compound (QAC) has been attached to a glycodendrimer to determine the antimicrobial activity of a multivalently presented QAC in studies of minimum inhibitory concentration (MIC), biofilm prevention, and bacterial resistance. Results include comparable MICs to those of established antibiotics, prevention of biofilm formation but not disruption of an established biofilm, and establishment of multivalency as a strategy to counteract bacterial resistance. Another heterogeneously functionalized dendrimer was synthesized to study drug release characteristics of a prodrug attached to a cleavable substrate. In these studies, the upregulation of several proteins during cancer progression was taken advantage of including; MMP-2, -7, -9, and galectin-3. Glycodendrimers are tools used to study protein carbohydrate interactions. Study of galectins and their corresponding Beta-galactosides have illuminated their role in several essential biological processes. Multivalency plays a crucial role in many protein-carbohydrate interactions. Galectins are known to interact multivalently with various ligands. Although the role of galectins in this process is not yet fully understood, galectins have been proposed to serve as protective proteins during periods of high oxidative stress. We describe the synthesis of GalBeta1-4Fuc functionalized poly(amidoamine) (PAMAM) dendrimers in order to test C. elegans' response to high oxidative stress. In order to test the function of GalBeta1-4Fuc in vivo, C. elegans were treated with RNAi to knockdown lec-1 or lec-10, and then treated with glycodendrimer and exposed to oxidative stress. C. elegans that were pre-treated with the glycodendrimers were less susceptible to oxidative stress than untreated controls. The glycodendrimers mainly appeared within the digestive tract of the worms, and uptake into the vulva and proximal gonads could also be observed in some instances. This study indicates that multivalently presented GalBeta1-4Fuc can protect C. elegans from oxidative stress by binding to galectins.
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    Effects of clipping on carbohydrate reserves and dry matter yields of basin wildrye
    (Montana State University - Bozeman, College of Agriculture, 1972) Perry, Lawrence Joseph
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    Carbohydrate reserves of green needlegrass (Stipa viridula Trin.) as affected by clipping and fertilization
    (Montana State University - Bozeman, College of Agriculture, 1972) White, Larry Melvin
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    The carbohydrate associated with myrosinase
    (Montana State University - Bozeman, College of Letters & Science, 1962) Huotari, Frances
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    The effect of a low carbohydrate diet versus an optimal percentage of carbohydrate on handball playing performance
    (Montana State University - Bozeman, College of Education, Health & Human Development, 1983) Boe, Alison Anne
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    Carbohydrate chemistry : synthetic and structural investigation of the phytotoxins found in Helminthosporium sacchari, and Rhynochosporium secalis
    (Montana State University - Bozeman, College of Letters & Science, 1980) Beier, Ross Carlton
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