Generalizing Glycosylation: Synthesis of the Blood Group Antigens Le^a, Le^b, and Le^x Using a Standard Set of Reaction Conditions

Because there are no general reaction conditions for any glycosylation method, biologically interesting oligosaccharides can only be made in a small number of laboratories in the world. To make carbohydrate synthesis accessible to nonspecialists, it is critical to have glycosylation methods that will work in a wide range of cases under a single set of conditions. The Lewis blood group antigens have attracted the attention of numerous synthetic carbohydrate groups because of their structural complexity. Although they have been synthesized many times, they have never been made using a single glycosylation method under one set of reaction conditions. In this paper, we show that the sulfoxide glycosylation method can be used to form all of the glycosidic linkages in the Lewis blood group antigens Lea (1), Leb (2), and Lex (3) stereoselectively under a uniform set of reaction conditions. This work highlights the flexibility of the sulfoxide method and demonstrates its utility for constructing families of related oligosaccharides

Generalizing Glycosylation: Synthesis of the Blood Group Antigens Le^a, Le^b, and Le^x Using a Standard Set of Reaction Conditions

Because there are no general reaction conditions for any glycosylation method, biologically interesting oligosaccharides can only be made in a small number of laboratories in the world. To make carbohydrate synthesis accessible to nonspecialists, it is critical to have glycosylation methods that will work in a wide range of cases under a single set of conditions. The Lewis blood group antigens have attracted the attention of numerous synthetic carbohydrate groups because of their structural complexity. Although they have been synthesized many times, they have never been made using a single glycosylation method under one set of reaction conditions. In this paper, we show that the sulfoxide glycosylation method can be used to form all of the glycosidic linkages in the Lewis blood group antigens Lea (1), Leb (2), and Lex (3) stereoselectively under a uniform set of reaction conditions. This work highlights the flexibility of the sulfoxide method and demonstrates its utility for constructing families of related oligosaccharides

The number (<i>a</i>), cross-sectional area (<i>b</i>) and volume (<i>c</i>) of pulmonary metastases in PAI-1^−/− and wild-type mice fed the AIN93G or the high-fat diet.

<p>Two-way ANOVA and Tukey contrasts were performed to test for differences among the groups. Values (means ± SEM) with different superscripts are significantly different at <i>p</i>≤0.05 (n = 22 per group for PAI-1^−/− mice, n = 28 per group for wild-type mice). AIN WT: AIN93G-fed wild-type mice, AIN PAI-1^−/−: AIN93G-fed PAI-1^−/− mice, HF WT: high-fat fed wild-type mice, HF PAI-1^−/−: high-fat fed PAI-1^−/− mice.</p

Body weight.

<p>Two-way ANOVA and Tukey contrasts were performed to test for differences among the groups. The high-fat diet, compared to the AIN93G diet, increased body weights; the difference was significant starting 4 weeks after the initiation of experimental feeding (<i>p</i><0.01), and the significant increase continued throughout the experiment. Compared to wild-type mice, PAI-1 deficiency lowered body weights, and the difference was significant starting at week 6 of the experiment (<i>p</i>≤0.05). Values are means ± SEM (n = 11 per group for PAI-1^−/− mice, n = 14 per group for wild-type mice; second cohort). AIN WT: AIN93G-fed wild-type mice, AIN PAI-1^−/−: AIN93G-fed PAI-1^−/− mice, HF WT: high-fat fed wild-type mice, HF PAI-1^−/−: high-fat fed PAI-1^−/− mice.</p

Adipose concentration of PAI-1 and plasma concentrations of adipokines (PAI-1, MCP-1, TNF-α, leptin) and uPA¹.

1<p>Two-way ANOVA and Tukey contrasts were performed to compare differences among the groups of LLC-bearing mice; <i>a priori</i> contrasts were performed to compare differences in AIN93G-fed wild-type mice with or without LLC (control vs. AIN WT). Values (means ± SEM) in a row with different superscripts are significantly different at <i>p</i>≤0.05 for LLC-bearing groups (n = 10 per group).</p><p>*<i>p</i><0.01 compared to AIN WT. Control: AIN93G-fed non-tumor-bearing wild-type mice, AIN WT: AIN93G-fed wild-type mice, AIN PAI-1^−/−: AIN93G-fed PAI-1^−/− mice, HF WT: high-fat fed wild-type mice, HF PAI-1^−/−: high-fat fed PAI-1^−/− mice, D × G: diet × gene interaction, N.D.: not detectable.</p>2<p>Adipose PAI-1.</p><p>Adipose concentration of PAI-1 and plasma concentrations of adipokines (PAI-1, MCP-1, TNF-α, leptin) and uPA^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0110869#nt104" target="_blank">1</a>}.</p

Plasma concentrations of angiogenic factors (VEGF, TIMP-1), insulin and glucose¹.

1<p>Two-way ANOVA and Tukey contrasts were performed to compare differences among the groups of LLC-bearing mice; <i>a priori</i> contrasts were performed to compare differences in AIN93G-fed wild-type mice with or without LLC (control vs. AIN WT). Values (means ± SEM) in a row with different superscripts are significantly different at <i>p</i>≤0.05 for LLC-bearing groups (n = 10 per group). *<i>p</i><0.01 compared to AIN WT. Control: AIN93G-fed non-tumor-bearing wild-type mice, AIN WT: AIN93G-fed wild-type mice, AIN PAI-1^−/−: AIN93G-fed PAI-1^−/− mice, HF WT: high-fat fed wild-type mice, HF PAI-1^−/−: high-fat fed PAI-1^−/− mice, D × G: diet × gene interaction.</p><p>Plasma concentrations of angiogenic factors (VEGF, TIMP-1), insulin and glucose^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0110869#nt107" target="_blank">1</a>}.</p

Body fat mass ratio, lean mass ratio, absolute lean mass weight and caloric intake of mice¹.

1<p>Two-way ANOVA was performed to test for differences among the groups. Values are means ± SEM (n = 22 per group for PAI-1^−/− mice, n = 28 per group for wild-type mice or n = 6 per group for caloric intake). AIN WT: AIN93G-fed wild-type mice, AIN PAI-1^−/−: AIN93G-fed PAI-1^−/− mice, HF WT: high-fat fed wild-type mice, HF PAI-1^−/−: high-fat fed PAI-1^−/− mice.</p><p>Body fat mass ratio, lean mass ratio, absolute lean mass weight and caloric intake of mice^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0110869#nt103" target="_blank">1</a>}.</p

Composition of experimental diets.

a<p>Reference 21.</p>b<p>n = 3 for each diet.</p><p>Composition of experimental diets.</p

Writing to the unknown: bloggers and the presence of backpackers

Purpose – In this paper, the aim is to study virtual presence in travel blogs. The paper seeks to argue that though some conceptualization of virtual presence has been made in the literature, this only took account of one's presence among a community of “known” others. Increasingly, however, in blogging and other online communities, users do not necessarily know the “others” but they nevertheless interact with them and develop friendships and lasting relationships. This stresses the multidimensional character of the study; one which sees presence as the core topic by considering different perspectives to it. Design/methodology/approach – An exploratory case study is conducted with a backpackers' blogging site, its members and audience; a setting that was considered suitable for finding answers to the research questions. The data are analysed qualitatively following a thematic analysis approach. Findings – It was found that the invisible and unknown audience has an important role to play in backpackers' presence online. In particular, the study highlights the role played by the audience in shaping the blogging experience and the sense of presence that this experience develops. Research limitations/implications – The exploratory case study carries a number of limitations. The findings are based on: reflections and views shared with the researchers by the bloggers, through interviews; a discussion forum; and on an enacted audience through their reflections. Practical implications – For practitioners, the study has implications in the areas of attracting and keeping audiences' interest and also in how to develop and support shared identity among independent travellers. Originality/value – The paper contributes to a better understanding of online communities and virtual social networks in general by showing how virtual worlds reshape social space and social interactions

Table_3_Time-restricted feeding restores metabolic flexibility in adult mice with excess adiposity.xlsx

IntroductionObesity is prevalent with the adult population in the United States. Energy-dense diets and erratic eating behavior contribute to obesity. Time-restricted eating is a dietary strategy in humans that has been advanced to reduce the propensity for obesity. We hypothesized that time-restricted feeding (TRF) would improve metabolic flexibility and normalize metabolic function in adult mice with established excess adiposity.MethodsMale C57BL/6NHsd mice were initially fed a high-fat diet (HFD) for 12 weeks to establish excess body adiposity, while control mice were fed a normal diet. Then, the HFD-fed mice were assigned to two groups, either ad libitum HFD or TRF of the HFD in the dark phase (12 h) for another 12 weeks.Results and discussionEnergy intake and body fat mass were similar in TRF and HFD-fed mice. TRF restored rhythmic oscillations of respiratory exchange ratio (RER), which had been flattened by the HFD, with greater RER amplitude in the dark phase. Insulin sensitivity was improved and plasma cholesterol and hepatic triacylglycerol were decreased by TRF. When compared to HFD, TRF decreased transcription of circadian genes Per1 and Per2 and genes encoding lipid metabolism (Acaca, Fads1, Fads2, Fasn, Scd1, and Srebf1) in liver. Metabolomic analysis showed that TRF created a profile that was distinct from those of mice fed the control diet or HFD, particularly in altered amino acid profiles. These included aminoacyl-tRNA-biosynthesis, glutathione metabolism, and phenylalanine, tyrosine, and tryptophan biosynthesis pathways. In conclusion, TRF improved metabolic function in adult mice with excess adiposity. This improvement was not through a reduction in body fat mass but through the restoration of metabolic flexibility.</p