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Background: There are a number of biological pathways that affect our ingestive behaviours, including energy homeostasis, food reward, and taste. Given that carbohydrates such as sugars, provide energy and a sweet taste, examining candidate genes in each pathway may help explain differences in carbohydrate consumption behaviours. Objective: To determine whether variations in genes encoding a glucose transporter (GLUT2), a dopamine receptor (DRD2), and sweet taste receptor (TAS1R2) are associated with differences in sugar consumption in two distinct populations. Methods: Population 1 included diabetes-free young adults where dietary intake was assessed using a one month 196-item food frequency questionnaire (FFQ). Population 2 consisted of individuals with type 2 diabetes. Dietary intake was assessed using 3-day food records administered 2 weeks apart; food record 1 (FR1) and 2 (FR2). Subjects were genotyped for the Thr110Ile variation in GLUT2 (n1=587; n2=100), the C957T variation in DRD2 (n1=313; n2=100), and the Ser9Cys and Ile191Val variations in TAS1R2 (n1=1037; n2=100) using real-time PCR. Results: In comparison to individuals homozygous for the GLUT2 Thr allele, consumption of sugars was higher among Ile carriers in population 1 (133 ± 5 vs 118 ± 3 g/d, p=0.006) and population 2 on two separate food records (FR1: 112 ± 9 vs 87 ± 5 g/d, p=0.02; FR2: 105 ± 8 vs 78 ± 4 g/d, p=0.002). For the C957T variation in population 1, we detected a significant DRD2xSex interaction with the consumption of sucrose decreasing with each T allele among men (p=0.03) and a heterosis mode of inheritance among women where heterozygotes consumed the most (p=0.01). For TAS1R2, we detected a significant TAS1R2xBMI interaction and among overweight individuals, carriers of the Val allele consumed less sugars than those with the Ile/Ile genotype (103 ± 6 vs122 ± 6 g/d, p=0.01). In population 2, carriers of the Val allele consumed less sugars than individuals with the Ile/Ile genotype (83 ± 6 vs 99 ± 6 g/d, p=0.04) on FR2. Conclusions: Our findings demonstrate that genetic variation in GLUT2, DRD2 and TAS1R2 affect habitual sugar consumption and suggest that selection of dietary sugars can be influenced by different biological pathways.

Bakgrund: Under senare tid har mediedebatten fokuserats kring olika dieters påverkan på viktminskning och välbefinnande. De moderna dieterna har debatterats av läkare, forskare och myndigheter, då extrema lågkolhydratsdieter innehåller alltför mycket fett vilket vissa menar kan leda till framtida folksjukdomar. Syfte: Syftet var att undersöka ett begränsat antal dieters påverkan på viktminskning och välmående samt att belysa betydelsen av en helhetssyn på våra kostvanor. Metod: Denna litteraturstudie är baserad på fyra vetenskapliga artiklar som var relevanta och intressanta för syftet. Resultat: Samtliga av de artiklar som undersökte sambandet mellan olika dieter och vikt visade på en tydlig viktminskning hos alla deltagare. LCHF-dieten gav den snabbaste viktminskningen. När det gäller välmående visade samtliga i alla studiegrupper en förbättring i sitt psykologiska välbefinnande och välmående. Den undersökning som behandlade kostvanor kom fram till att det behövs en helhetssyn på skolmåltiden för att få en optimal måltidsupplevelse med tanke på elevernas hälsa och välbefinnande. Slutsats: Undersökningen visar på en tydlig viktminskning oavsett diet och att det fysiska och psykologiska välbefinnandet förbättrades, det fordras däremot ytterligare forskning för att studera de olika dieternas långsiktiga påverkan samt att det krävs en helhetssyn på våra kostvanor redan i unga år för att leva ett friskare och mer välmående liv. / B-uppsatser

Background Carbohydrate counting is a method used to calculate insulin doses to meals, in the treatment of diabetes type 1. Few studies are available with a clear consensus on its efficacy and effect on anthropometrics in children and adolescents. Aim To evaluate if carbohydrate counting as treatment method in diabetes type 1 improved glycemic control and anthropometrics compared to conventional treatment, one and two years after onset in children and adolescents at Astrid Lindgren children’s hospital. A secondary aim was to explore patients and caregivers perception of insulin dosage to meals with focus on efficacy, time consumption and adherence. Method A clinical prospective study was performed on data collected from the Swedish pediatric quality registry (Swediabkids). Children with diabetes onset between 2010 and 2014 registered at Astrid Lindgren Children’s hospital (n=371) were included and divided into two groups, carbohydrate counters and non-carbohydrate counters. Normal distribution was assumed and parametric tests were performed. The registry data was complemented with a web-based questionnaire providing information on perception of carbohydrate counting, answered by 78 subjects. Results Carbohydrate counting reduced insulin requirements (p<0.001) and eliminated differences between pump- and pen users (p<0.001) as well as differences between boys and girls. Glycemic control was not improved by carbohydrate counting one and two years after diabetes onset (p=0.233, p=0.295). An adverse effect was increased body mass index standard deviation score (BMI-sds) (p=0.044), especially amongst girls (p=0.038). Conclusion Carbohydrate counting lowers insulin requirements with maintained glycemic control. Contradictory, greater weight gain was found in the carbohydrate counting group, especially among girls. A plausible explanation is that carbohydrates have taken focus off protein- and fat intake in combination with a more liberal approach to energy dense foods, causing excess energy intake. The strength of carbohydrate counting does not lie in its ability to lower HbA1c-values but as a helpful tool, which patients are happy to use. / Bakgrund Kolhydraträkning är en metod som används för att beräkna insulindoser till måltider, i behandlingen av diabetes typ 1. Få studier finns för att ge en samlad konsensus gällande dess effekt på glykemisk kontroll och tillväxt hos barn och ungdomar. Syfte Att utvärdera om införandet av kolhydraträkning som behandlingsmetod vid diabetes typ 1 påverkat metabol kontroll och tillväxt i jämförelse med konventionell metod, ett och två år efter diabetesdebut. Ett andra syfte var att utforska patienters och vårdnadshavares uppfattning om insulindosering till måltider med fokus på effektivitet, tidskonsumtion och följsamhet. Metod En klinisk prospektiv studie utfördes med data inhämtad från Nationellt kvalitetsregister för barn och ungdomar med diabetes (Swediabkids). Barn och ungdomar som debuterade med diabetes typ 1 på Astrid Lindgrens barnsjukhus mellan 2010 och 2014 (n=371) inkluderades i studien och delades in i två grupper baserat på debutdatum; kolhydraträknare och icke-kolhydraträknare. Materialet bedömdes som normalfördelat och parametriska test utfördes. En tvärsnittsenkät administrerades till studiedeltagarna för att införskaffa fördjupad information om patienters och vårdnadshavares uppfattning om insulindosering till måltider. Den webbaserade enkäten besvarades av 78 deltagare. Resultat Kolhydraträkning reducerade insulinbehovet (p<0.001) och jämställde insulinbehovet mellan pump- och pennanvändare (p<0.001) liksom skillnader mellan pojkar och flickor inom gruppen. Glykemisk kontroll förändrades inte av kolhydraträkning ett och två år efter debut (p=0.233, p=0.295). En oönskad effekt av kolhydraträkningen var en ökning i BMI-sds (p=0.044), speciellt hos flickor (p=0.038). Slutsats Kolhydraträkning från diabetesdebut sänker insulinbehov med bibehållen glykemisk kontroll. Motsägelsefullt, så fanns en viktökning i gruppen som använde kolhydraträkning, speciellt hos flickor. En möjlig förklaring är att kolhydrater har tagit fokus från protein- och fettintag tillsammans med en mer frikostig syn på energität mat, vilket har orsakat ökat energiintag. Styrkan i kolhydraträkning ligger inte i dess förmåga att förbättra glykemisk kontroll men som ett användarvänligt verktyg som patienterna är nöjda med.

Recently, a one-chain monoclinic unit cell for Cellulose IIII having a single glucose in the asymmetric unit was proposed based on high-resolution diffraction patterns. The new work challenged a two-chain structure published 25 years earlier, although it did not provide new three-dimensional coordinates. Our goals were to solve the structure by modeling, find whether modeling would reject the previously determined two-chain unit cell, and compare the model with the anticipated experimental structure. Combinations of the O2, O3, and O6 hydroxyls produced 54 starting structures. Clusters of 13 cellotetraose chains terminated by methyl groups for each of the 54 starting structures were optimized with MM3(96). Hydroxyl groups on 16 of these 54 structures reoriented to give very similar hydrogenbonding schemes in the interiors, along with the lowest energies. The one-chain cell models had much lower energy. The eight best “up” one-chain models agree well with the structure newly determined by experiment.

To prevent damaging ATP depletion during periods of intense activity‚ intrinsic mechanisms within skeletal muscle are activated and lead to myoprotection; a process known as muscle fatigue. It has been proposed that the primary mechanism of fatigue is a submaximal sarcoplasmic reticulum Ca2+ release and decreased force generation‚ however‚ what triggers this mechanism remains controversial. It is possible that glycogen may act as a trigger as studies have repeatedly shown a direct correlation between glycogen content at the beginning of activity and time to fatigue. In previous studies‚ a fatigue bout and/or period of fasting to deplete glycogen was used. However, this leaves investigators to differentiate between the effects of glycogen depletion methodology causing a metabolic stress and effects of glycogen itself. One objective of this M.Sc. project was to produce a low glycogen model without a prior metabolic stress that could forgo these limitations. It was extended to differentiate between the role of glycogen and extracellular glucose during fatigue as well as fatigue pre-conditioning (FPC)‚ a phenomenon in which fatigue resistance increases for about 2 hours after a first fatigue bout. During a single‚ first fatigue bout (one contraction every sec for 3 min) a mean decrease in glycogen from 95 to 20 μmol/g dry wt. had no effect on the decrease in tetanic [Ca2+]i‚ i.e. the [Ca2+]i during tetanic contractions‚ whereas removing glucose from the physiological solution led to a 46% greater decrease in tetanic [Ca2+]i than when glucose was present. During a subsequent fatigue bout (i.e. FPC) a greater amount of glycogen was used as glycogen content was 27% greater than prior to the first fatigue bout. When glycogen and/or glucose was limited‚ FPC was abolished. It is concluded that extracellular glucose is critical to prevent fatigue. Additionally, whereas glycogen is important for FPC‚ it appears to be much less important during a first fatigue bout initiated in absence of any prior metabolic stress.

Thesis advisor: Kian L. Tan / Chapter 1. We reported the first synthesis of all-carbon quaternary centers via hydroformylations using a catalytic directing group. With the ability of reversibly and covalently binding to a substrate, and coordinating to a metal center, scaffolding catalyst 1.1 is able to direct the branch-selective hydroformylation of 1,1-disubstituted olefins under mild temperature. Chapter 2. We have designed and synthesized a chiral organocatalyst 2.11. This catalyst is able to covalently bind to one hydroxyl, and utilize the induced intramolecularity to stereoselectively functionalize the other hydroxyl within a cis-1,2-diol via electrophile transfer. Catalyst 2.11 was used in the desymmetrization of meso-1,2-diols under mild conditions (4 C to room temperature), leading to high yields and selectivities for a broad substrate scope. Chapter 3. Catalyst 3.1 and 3.6 were demonstrated to selectively bind to primary hydroxyls over secondary hydroxyls. By combining the binding selectivity with asymmetric catalysis, these scaffolding catalysts were shown to promote the selective silylation of secondary hydroxyls within terminal (S)-1,2-diols. The reversal of substrate bias was further applied to a regiodivergent kinetic resolution of racemic terminal 1,2-diols, producing secondary protected products in synthetically practical levels of enantioselectivity (>95:5 er) and yields (≥40%). Time course studies of this reaction further revealed the optimal condition to form the primary silylated product in high s-factor. Chapter 4. Based on the previous understanding of catalyst 4.5 and 4.6, the exclusive catalyst recognition of cis-1,2-diols within polyhydroxylated molecules was further discovered. This unique functional group display recognition was further allied with the catalyst's ability to stereoselectively differentiate hydroxyls within cis-1,2-diols, enabling the site-selective protection, functionalization, and activation of the inherently less reactive axial hydroxyl groups within carbohydrates. This methodology also enables the selective functionalization of multiple complex molecules, including digoxin, mupirocin, and ribonucleosides, demonstrating the potential power of scaffolding catalysis in the rapid access to valuable synthetic derivatives of polyhydroxylated compounds. / Thesis (PhD) — Boston College, 2013. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

The purposes of this dissertation were to examine the effect of a protein and carbohydrate recovery beverage versus a placebo on weightlifting performance, its effect on muscle morphological changes and specific muscle protein accretion. The following are major finding from the dissertation: 1) Protein and carbohydrate recovery supplementation does not appear to have influence on performance measure in trained weightlifters. This finding may be associated with the short-term nature of this study and the trained population used. 2) Compared with placebo, a protein and carbohydrate beverage provided greater benefits on cross sectional area of type I and type II muscle fibers. Additionally, the block periodization protocol incorporating phase potentiation improved cross sectional area of both groups compared to baseline. 3) Finally, protein and carbohydrate supplementation provided greater benefits on total mTOR and myosin heavy chains 6 & 7. These findings indicate that a protein and carbohydrate beverage provide greater benefits compared with a placebo on cellular signaling, myosin heavy gene expression and muscle fiber increases in trained weightlifters. Improved cross sectional area and increased myosin heavy chains indicate positive adaptations to resistance training combined with supplementation and may indicate improved skeletal muscle qualities necessary for increased power output. The mTOR pathway is the master regulator of cellular growth and increases in total mTOR indicate a greater proclivity for cellular growth and greater activity resulting from resistance training may increase synthesis and accretion of muscle contractile proteins. This dissertation highlighted several benefits of recovery supplementation, however further longitudinal studies utilizing block periodization and well-trained athletes are necessary to fully elucidate benefits for strength and power athletes.

Synthesis of novel amphiphilic copolymers based on sugar moieties: development of new architectures and biomedical applications As early as in the 50’s, amphiphilic copolymers started to attract much interest in the frame of polymer science thanks to their self-assemblies as organized nano-structures in a selective solvent. The resulting micelles or vesicles have emerged as potentially useful materials in the biomedical field such as drug delivery systems when matching the specific conditions of size, coating nature and functionalization,… Moreover, active cell-targeting increases the therapeutic effect by selectively delivering the drug to the required cells. Accordingly, carbohydrates have drawn much attention due to the cell recognition processes they can mediate. Carbohydrates are thus incorporated in polymer backbones to mimic the naturally occurring substrate for the adapted cell receptors. The originality of this thesis is based on the use of sugar moieties as potential multi-hydroxylated initiators for the polymerization of various lactones. This leads to well-defined amphiphilic polymer architectures along with the development of a more facile route for the incorporation of carbohydrates in polymer chains to promote active cell-targeting of the as-obtained nano-structures. The first part of the thesis aims at describing the synthesis of novel amphiphilic brush-like polymers via two pathways. A first approach relies upon the synthesis of polyester arms initiated from the alcohol groups of pending sugars distributed along a preformed hydrophilic polymethacrylate backbone obtained by controlled radical polymerization (via ATRP). Various metal-based and organic catalysts/activators have been studied to lead to the desired architectures using this “grafting from” technique. In another synthetic strategy, the lactone polymerization using a carbohydrate initiator has been carried out, followed by end-chain derivatization reactions yielding brush-like copolymers via a “grafting through” technique. Slight modifications of the end-chain functionalities have also afforded the possibility to synthesize amphiphilic mikto-arm copolymers which self-assemble in aqueous medium in micelles characterized by interesting size features affording promising applications as new drug delivery systems. On the other hand this thesis also focuses on the use of carbohydrate moieties in amphiphilic diblock copolymers such as poly(ε-caprolactone)-b-poly(methacrylate-graft-poly(ethylene oxide)-co-6-O-methacryloyl-D-galactopyranose) or poly(ε-caprolactone)-b-poly(methacrylate-graft-poly(ethylene oxide)-co-1-O-methacryloyl-D-mannofuranose), using the combination of lactone ring-opening polymerization with ATRP of the respective functionalized comonomers, followed by selective post-polymerization sugar deprotection. Next to these copolymers based on polylactones and polymethacrylates, fully degradable amphiphilic block copolymers composed of a polycarbonate backbone have been originally designed. To that end, a multi-step procedure involving the synthesis of sugar-substituted cyclic carbonates, block copolymerization reactions and ultimate selective sugar deprotection, has been investigated. The self-organization of the resulting copolymers, e.g., poly(trimethylene carbonate)-b-poly(3-O-(5’-methyl,5’-carboxy-1’,3’-dioxan-2’-one)-D-glucopyranose), has been studied in aqueous medium. Interestingly, the so-formed polymeric micelles proved to display remarkable living cell-targeting properties. Fabian Suriano

Protected DHA units, known as dioxanones, are interesting compound which can be used as the building blocks for synthesis of polyoxygenated natural products. The direct aldol reaction is employed for converting of those inexpensive starting materials into enantioenriched products of complexed structures. The stereocontrol in the first aldol reaction is achieved by using organocatalysis. Second aldol reaction is conducted by lithium enolate chemistry leading to anticisanti aldols as a major isomer. On the other hand boron chemistry provides antitransanti products. This strategy is used for synthesis of higher sugars.