Synthesis of oligosaccharides resembling the Streptococcus suis serotype 18 capsular polysaccharide as a basis for glycoconjugate vaccine development

Here we report the first total synthesis of several oligosaccharides resembling the capsular polysaccharide of swine pathogen S. suis serotype 18 repeating unit [→3)-d-GalNAc(α1-3)[d-Glc(β1-2)]-d-GalA4OAc(β1-3)-d-GalNAc(α1-3)-d-BacNAc4NAc(α1→]n. Access to the pentasaccharide repeating unit antigen proved to be very challenging due to the poor reactivity in the context of the trisaccharide. The challenge was overcome by the creation of a galacturonic acid in a late stage of the synthesis

Elderly people in many respects benefit from interaction with dogs

Over the course of evolution, humans and animals have entered into a close relationship. By domesticating animals, humans were able to use them to their own advantage. However, animals should not only be seen as mere providers of material value; in fact, they actually enrich humans' lives on an emotional level. The classic examples for this evolution are dogs: they are considered loyal companions, particularly for children and elderly people. This relationship between humans and animals is the subject of this research study and is examined from a gerontological perspective by employing qualitative social research methods. Conclusion: The results of the study reveal the manifold meanings that pets - in particular dogs - can and do have to the elderly. At this point, it should also be noted that there is still a strong need for further research into this topic from a gerontological perspective

Detection of an optical filament in the Monogem Ring

The Monogem Ring is a huge bright soft X-ray enhancement with a diameter of ~ 25\degr. This 0.3 kpc distant structure is a peculiar Galactic supernova remnant in that it is obviously visible only in X-rays, due to its expansion into a region of extremely low ambient density: hence, practically no optical emission or a neutral HI shell was expected to be detectable. - Here we report on the discovery of a very faint arc-like nebula on a POSS II R film copy, at the south-eastern borders of the MR. Spectroscopy revealed this filament to have a very large [SII]$\lambda$ 6716+6731/Halpha ratio of up to ~ 1.8, indicating shock excitation, and a low density of N_e <100 cm^{-3}. There is no hint of [OIII] emission in the spectra. On deep wide-field direct images in Halpha and in [SII] the nebula appears as a ~ 20 arcmin long, thin (~ 1 arcmin), structured filament, stretching N-S. We believe that this filament belongs to the MR and became visible due to the interaction of the expanding remnant with a mild density increase in the interstellar medium. Only one other possible optical filament of the MR has been reported in the literature, but no spectrum was provided.Comment: 6 pages, 4 figures, of which 2 in jpeg format and degraded because of size constraints. Accepted for publication in A&

Volatile anaesthetics and positive pressure ventilation reduce left atrial performance: a transthoracic echocardiographic study in young healthy adults

Background Animal and in vitro studies suggest that volatile anaesthetics affect left atrial (LA) performance. We hypothesized that human LA pump function and dimensions are altered by volatile anaesthetics in vivo. Methods We performed transthoracic echocardiographic (TTE) measurements in 59 healthy subjects (aged 18-48 yr) undergoing minor surgery under general anaesthesia. The unpremedicated patients were randomly assigned to anaesthesia with sevoflurane, desflurane, or isoflurane. TTE examinations were performed at baseline and after induction of anaesthesia and upon placement of a laryngeal mask during spontaneous breathing. After changing to intermittent positive pressure ventilation (IPPV), an additional TTE was performed. The study focused on the velocity-time integral of late peak transmitral inflow velocity (AVTI) and maximum LA volume. Results We found no evidence for relevant differences in the effects of the three volatile anaesthetics. AVTI decreased significantly from 4.1 (1.2) cm at baseline to 3.2 (1.1) cm during spontaneous breathing of 1 minimum alveolar concentration of volatile anaesthetics. AVTI decreased further to 2.8 (1.0) cm after changing to IPPV. The maximum LA volume was 45.4 (18.6) cm3 at baseline and remained unchanged during spontaneous breathing but decreased to 34.5 (16.7) cm3 during IPPV. Other parameters of LA pump function and dimensions decreased similarly. Conclusions Volatile anaesthetics reduced active LA pump function in humans in vivo. Addition of IPPV decreased LA dimensions and further reduced LA pump function. Effects in vivo were less pronounced than previously found in in vitro and animal studies. Further studies are warranted to evaluate the clinical implications of these findings. Clinical trial registration NCT002445

Oligosaccharide and Glycoprotein Microarrays as Tools in HIV Glycobiology Glycan-Dependent gp120/Protein Interactions

AbstractDefining HIV envelope glycoprotein interactions with host factors or binding partners advances our understanding of the infectious process and provides a basis for the design of vaccines and agents that interfere with HIV entry. Here we employ carbohydrate and glycoprotein microarrays to analyze glycan-dependent gp120-protein interactions. In concert with new linking chemistries and synthetic methods, the carbohydrate arrays combine the advantages of microarray technology with the flexibility and precision afforded by organic synthesis. With these microarrays, we individually and competitively determined the binding profiles of five gp120 binding proteins, established the carbohydrate structural requirements for these interactions, and identified a potential strategy for HIV vaccine development

Different effects of sevoflurane, desflurane, and isoflurane on early and late left ventricular diastolic function in young healthy adults†

Background Knowledge on the effects of volatile anaesthetics on left ventricular (LV) diastolic function in humans in vivo is limited. We tested the hypothesis that sevoflurane, desflurane, and isoflurane do not impair LV diastolic function in young healthy humans. Methods Sixty otherwise healthy subjects (aged 18-48 yr) undergoing minor procedures under general anaesthesia were studied. After randomization for the anaesthetic, transthoracic echocardiographic examinations were performed at baseline and under anaesthesia with 1 minimum alveolar concentration (MAC) of the volatile anaesthetics during spontaneous breathing and intermittent positive pressure ventilation (IPPV). Peak early (E′) and late (A′) diastolic velocities of the mitral annulus were studied as the main echocardiographic indicators of diastolic function. Results During anaesthesia with 1 MAC under spontaneous breathing, E′ increased with desflurane (P<0.001), was not significantly different with isoflurane (P=0.030), and decreased with sevoflurane (P=0.006). During IPPV, E′ was similar to baseline with desflurane (P=0.550), insignificantly decreased with isoflurane (P=0.029), and decreased with the sevoflurane group (P<0.001). In contrast, A′ was similarly reduced in all groups during spontaneous breathing without further changes during IPPV. Haemodynamic changes were comparable in all study groups. Conclusions The findings of this in vivo study indicate that desflurane and isoflurane, and most likely sevoflurane, have no relevant direct negative effect on early diastolic relaxation in young healthy humans. In contrast, all three volatile anaesthetics appear to impair late diastolic LV filling during atrial contraction. Trial Registration #: NCT002445

Neighboring Group Participation of Benzoyl Protecting Groups in C3- and C6-Fluorinated Glucose

Fluorination is a potent method to modulate chemical properties of glycans. Here, we study how C3- and C6-fluorination of glucosyl building blocks influence the structure of the intermediate of the glycosylation reaction, the glycosyl cation. Using a combination of gas-phase infrared spectroscopy and first-principles theory, glycosyl cations generated from fluorinated and non-fluorinated monosaccharides are structurally characterized. The results indicate that neighboring group participation of the C2-benzoyl protecting group is the dominant structural motif for all building blocks, correlating with the β-selectivity observed in glycosylation reactions. The infrared signatures indicate that participation of the benzoyl group in enhanced by resonance effects. Participation of remote acyl groups such as Fmoc or benzyl on the other hand is unfavored. The introduction of the less bulky fluorine leads to a change in the conformation of the ring pucker, whereas the structure of the active dioxolenium site remains unchanged

Synthesis and biological activity of α-glucosyl C24:0 and C20:2 ceramides

a-Glucosyl ceramides 4 and 5 have been synthesised and evaluated for their ability to stimulate the activation and expansion of human iNKT cells. The key challenge in the synthesis of both target molecules was the stereoselective synthesis of the a-glycosidic linkage. Of the methods examined, glycosylation using per-TMS-protected glucosyl iodide 16 was completely a-selective and provided gram quantities of amine 11, from which a-glucosyl ceramides 4 and 5 were obtained by N-acylation. a-GlcCer 4, containing a C24 saturated acyl chain, stimulated a marked proliferation and expansion of human circulating iNKT cells in short-term cultures. a-GlcCer 5, which contains a C20 11,14-cis-diene acyl chain (C20:2),induced extremely similar levels of iNKT cell activation and expansion

Continuous flow processes for photoconjugation of high-molecular chemical entities

The invention relates to a continuous flow process for the photoconjugation of chemical entities selected from the group comprising carbohydrates, including mono-, oligo- and polysaccharides, amino acids, peptides and proteins, unbranched and branched oligomers and polymers, including dendrimers, which process comprises at least the following steps: a) providing a mixture of the reactants dissolved in an aqueous or organic solvent; b) passing said mixture through a continuous flow reactor and concomitantly irradiating the mixture with light in order to initiate and perform the photoreaction. In preferred embodiments, the photoconjugation is a thiol-ene conjugation or a [2+2] cycloaddition. A further aspect of the invention relates to the conjugates obtainable by this continuous flow process, in particular dendronized polymers such as carbohydrate-dendronized polymers