Formation and immunological evaluation of Moraxella catarrhalis glycoconjugates based on synthetic oligosaccharides.

Published work has shown that glycoconjugate vaccines, based on truncated detoxified lipopolysaccharides from Moraxella catarrhalis attached through their reducing end to a carrier protein, gave good protection for all three serotypes A, B, and C in mice immunisation experiments. The (from the non-reducing end) truncated LPS structures were obtained from bacterial glycosyl transferase knock-out mutants and contained the de-esterified Lipid A, two Kdo residues and five glucose moieties. This work describes the chemical synthesis of the same outer Moraxella LPS structures, spacer-equipped and further truncated from the reducing end, i.e., without the Lipid A part and containing four or five glucose moieties or four glucose moieties and one Kdo residue, and their subsequent conjugation to a carrier protein via a five­carbon bifunctional spacer to form glycoconjugates. Immunisation experiments both in mice and rabbits of these gave a good antibody response, being 2-7 times that of pre-immune sera. However, the sera produced only recognized the immunizing glycan immunogens and failed to bind to native LPS or whole bacterial cells. Comparative molecular modelling of three alternative antigens shows that an additional (2 â†’ 4)-linked Kdo residue, not present in the synthetic structures, has a significant impact on the shape and volume of the molecule, with implications for antigen binding and cross-reactivity.

Synthesis of the 3'-O-sulfated TF antigen with a TEG-N3 linker for glycodendrimersomes preparation to study lectin binding.

The synthesis of gram quantities of the TF antigen (ß-ᴅ-Gal-(1→3)-α-ᴅ-GalNAc) and its 3'-sulfated analogue with a TEG-N3 spacer attached is described. The synthesis of the TF antigen comprises seven steps, from a known N-Troc-protected galactosamine donor, with an overall yield of 31%. Both the spacer (85%) and the galactose moiety (79%) were introduced using thioglycoside donors in NIS/AgOTf-promoted glycosylation reactions. The 3'-sulfate was finally introduced through tin activation in benzene/DMF followed by treatment with a sulfur trioxide-trimethylamine complex in a 66% yield.

The effects of interpersonal development programmes with sport coaches and parents on youth athlete outcomes: A systematic review and meta-analysis.

Interpersonal coach-and parent development programmes (CDP and PDP, respectively), have the goal to foster positive youth sport experiences through high-quality relations between coaches, parents, and youth athletes. In this paper we systematically reviewed the extant literature and estimate the overall magnitude of such programmes and how they can inform future interventions. Specifically, we aimed to: (a) conduct a systematic review on the literature of interpersonal CDPs and PDPs within the youth sport context; (b) examine the effects of such interventions on youth athlete outcomes via a meta-analysis. English written peer-reviewed publications and grey literature was identified through electronic search in databases and manual searches of reference lists. By utilising a priori criteria for inclusion and exclusion, 33 studies describing interpersonal CDPs, and PDPs were identified in the systematic review. Studies that presented required data for estimation of Hedge's g effect sizes were included in the meta-analysis (k = 27). By and large, the included studies used a quasi-experimental design (58%), sampled from team sports (79%), and reported several delivery methods (e.g., workshops, audio feedback, observations, peer group discussions) and outcome measures (e.g., anxiety, autonomous motivation, self-confidence). Some interventions were based on the same delivery protocols (e.g., Coach Effectiveness Training, Mastery Approach to Coaching) or theoretical frameworks (e.g., Achievement Goal Theory, Self-Determination Theory). The meta-analysis showed statistically significant small, and medium, effect sizes on a subsample of youth athlete outcomes (e.g., task-related climate, fun and enjoyment, anxiety), indicating that coach interpersonal skills can contribute to positive youth sport experiences. Theory-based interpersonal CDPs and PDPs are recommended to expand the knowledge in this field of research.

Synthesis of fluoro- and seleno-containing D-lactose and D-galactose analogues.

Synthetic deoxy-fluoro-carbohydrate derivatives and seleno-sugars are useful tools in protein-carbohydrate interaction studies using nuclear magnetic resonance spectroscopy because of the presence of the 19F and 77Se reporter nuclei. Seven saccharides containing both these atoms have been synthesized, three monosaccharides, methyl 6-deoxy-6-fluoro-1-seleno-ß-D-galactopyranoside (1) and methyl 2-deoxy-2-fluoro-1-seleno-α/ß-D-galactopyranoside (2α and 2ß), and four disaccharides, methyl 4-O-(ß-D-galactopyranosyl)-2-deoxy-2-fluoro-1-seleno-ß-D-glucopyranoside (3), methyl 4-Se-(ß-D-galactopyranosyl)-2-deoxy-2-fluoro-4-seleno-ß-D-glucopyranoside (4), and methyl 4-Se-(2-deoxy-2-fluoro-α/ß-D-galactopyranosyl)-4-seleno-ß-D-glucopyranoside (5α and 5ß), the three latter compounds with an interglycosidic selenium atom. Selenoglycosides 1 and 3 were obtained from the corresponding bromo sugar by treatment with dimethyl selenide and a reducing agent, while compounds 2α/2ß, 4, and 5α/5ß were synthesized by the coupling of a D-galactosyl selenolate, obtained in situ from the corresponding isoselenouronium salt, with either methyl iodide or a 4-O-trifluoromethanesulfonyl D-galactosyl moiety. While benzyl ether protecting groups were found to be incompatible with the selenide linkage during deprotection, a change to acetyl esters afforded 4 in a 17% overall yield and over 9 steps from peracetylated D-galactosyl bromide. The synthesis of 5 was performed similarly, but the 2-fluoro substituent led to reduced stereoselectivity in the formation of the isoselenouronium salt (α/ß âˆ¼ 1 : 2.3). However, the ß-anomer of the uronium salt could be obtained almost pure (∼98%) by precipitation from the reaction mixture. The following displacement reaction occurred without anomerisation, affording, after deacetylation, pure 5ß.

Synthesis of a library of 2-fluoro-2-deoxy-derivatives of the trimannoside methyl α-D-Man-(1 → 3)-[α-D-Man-(1 → 6)]-α-D-Man and the dimannosides methyl α-D-Man-(1 → 3)-α-D-Man and methyl α-D-Man-(1 → 6)-α-D-Man.

A library of sixteen compounds, 1-16, comprising all (mono-, di-, and tri-) 2-fluoro-2-deoxy-derivatives of the N-glycan core trimannoside α-D-Man-(1 â†’ 3)-[α-D-Man-(1 â†’ 6)]-D-Man, including the corresponding 2-fluoro-2-deoxy disaccharide part structures and the non-fluorinated parent compounds, have been synthesized as their α-methyl glycosides for use as tools in 19F NMR-based lectin-carbohydrate interaction studies. Two methyl 2-fluoro-2-deoxy-mannoside acceptors, 21 (3-OH) and 22 (6-OH), were constructed and used in combination with the corresponding non-fluorinated mannose acceptors, 24 (6-OH) and 25 (3-OH), the 2-fluoro-2-deoxy mannosyl bromide donor 18 and the non-fluorinated bromide donor 23 to efficiently afford the target di-and trisaccharides (disaccharides, 2-3 steps, 47-66% overall yield; trisaccharides, 4 steps, 25-40% overall yield).

Increased risk of child maltreatment and mental health problems among adolescents with restrictions regarding choice of future partner: Results from a Swedish school-based survey.

Background: Honour-related violence and oppression is a violation of human rights and a public health problem. Oppression can be manifested by not being allowed to choose future partners and can increase the risk of abuse and mental health problems. Aims: The aim of this study was to investigate associations between restrictions regarding choice of future partner (RCP), child maltreatment and mental health problems among adolescents in Sweden. Methods: The study was based on cross-sectional data, including a nationally representative sample of 4741 pupils from grade nine in primary school and second year in high school. Pearson's chi-square tests and binary logistical regression analyses adjusting for socio-demographic factors were conducted. Results: RCP was significantly associated to child maltreatment, including poly-victimisation, and mental health problems. In the adjusted analysis, an increased risk for all types of maltreatment, poly-victimisation (adjusted odds ratio (aOR) 10.2, confidence interval (CI) 5.6-18.4), self-harm (aOR 1.9, CI 1.1-3.2) and suicide attempt (aOR 2.4, CI 1.3-4.7) were shown in adolescents exposed to RCP compared to non-exposed. Conclusions: There is an increased risk of child maltreatment including poly-victimisation and mental health problems among adolescents exposed to RCP compared to non-exposed. The study emphasizes the matter as a public health problem requiring immediate preventive measures to ensure the rights of children and adolescents.

Synthesis of Double-Modified Xyloside Analogues for Probing the ß4GalT7 Active Site.

Monosubstituted naphthoxylosides have been shown to function as substrates for, and inhibitors of, the enzyme ß4GalT7, a key enzyme in the biosynthetic pathway leading to glycosaminoglycans and proteoglycans. In this article, we explore the synthesis of 16 xyloside analogues, modified at two different positions, as well as their function as inhibitors of and/or substrates for the enzyme. Seemingly simple compounds turned out to require complex synthetic pathways. A meta-analysis of the synthetic work shows that, regardless of the abundance of methods available for carbohydrate synthesis, even simple modifications can turn out to be problematic, and double modifications present additional challenges due to conformational, steric, and stereoelectronic effects.