4“-O-Alkylated α-Galactosylceramide Analogues as iNKT-Cell Antigens: Synthetic,Biological, and Structural Studies

Invariant natural killer T-cells (iNKT) are a glycolipid-responsive subset of T-lymphocytes that fulfill a pivotal role in the immune system. The archetypical synthetic glycolipid, α-galactosylceramide (α-GalCer), whose molecular framework is inspired by a group of amphiphilic natural products, remains the most studied antigen for iNKT-cells. Nonetheless, the potential of α-GalCer as an immunostimulating agent is compromised by the fact that this glycolipid elicits simultaneous secretion of Th1- and Th2-cytokines. This has incited medicinal chemistry efforts to identify analogues that are able to perturb the Th1/Th2 balance. In this work, we present the synthesis of an extensive set of 4“-O-alkylated α-GalCer analogues, which were evaluated in vivo for their cytokine induction. We have found that conversion of the 4”-OH group to ether moieties decreases the immunogenic potential in mice relative to α-GalCer. Yet, the benzyl-modified glycolipids are able to produce a distinct pro-inflammatory immune response. The crystal structures suggest an extra hydrophobic interaction between the benzyl moiety and the α2-helix of CD1d.     

Economic feasibility studies for Carbon Capture and Utilization technologies: a tutorial review

Clean Technologies and Environmental Policy - Carbon Capture and Utilization (CCU) involves the capture and use of CO2 as a resource to create valuable products. The competitiveness of various CCU...     

Cheese and Cardiovascular Disease Risk: A Review of the Evidence and Discussion of Possible Mechanisms

Currently, the effect of dairy products on cardiovascular risk is a topic much debated and with conflicting results. The purpose of this review is to give an overview of the existing literature regarding the effect of cheese intake and risk of cardiovascular disease (CVD). Studies included reporting the intake of cheese and risk of CVD or risk markers of CVD represent four human intervention studies, nine prospective studies, one prospective case-cohort study, one prospective nested case-control study, five case-control studies, five cross-sectional studies and three correlation studies. The possible mechanisms that may be of importance include calcium, protein, fermentation and the fatty acid composition of cheese. Results from four prospective studies reported no association between cheese intake and CVD risk, whereas one reported an increased risk, two reported a decreased risk and one reported no association in men but a decreased risk in women. In addition, results from four intervention studies indicated no harmful effect on cholesterol concentrations when comparing fat intake from cheese with fat from butter. The underlying mechanisms for these findings still need to be elucidated.     

Origin of the low carrier lifetime edge zone in multicrystalline PV silicon

An investigation of impurities, crystal defects and microstructure has been performed on the edge zone, i.e. close to the crucible wall, which experiences reduced carrier lifetime in a directionally solidified multicrystalline p‐doped silicon ingot. The characterization methods applied have been QSSPC, FTIR, μW‐PCD, EBSD, CDI, PVScan, optical microscopy, FeB‐pair splitting and GDMS. The results of the minority carrier lifetime measurements have revealed strongly reduced values in the vicinity of the edge (< 1 μs). Increased values were obtained starting at 15–17 mm from the edge. Light elements analyses showed that the O, N and C concentrations, interstitially or in particles, did not increase in the edge zone, neither did the dislocation density. GDMS analyses detected traces of aluminium, iron, copper, titanium and chromium. The total iron concentration showed an increase towards the edge, though high concentrations were occasionally detected in the bulk. FeB pair analysis revealed large concentrations of Fe (∼1 × 10¹³ cm⁻³) in the vicinity of the edge with a distinctively decreasing trend moving away from the edge. The detected FeB‐concentrations are sufficient to account for the majority of the lifetime degradation close to the edge (0‐‐15 mm). In addition, Fe, in the form of FeB pairs, was extensively observed as object to internal gettering to high angle boundaries and dislocations. Fe, in the form of FeB pairs, is furthermore believed to originate from solid state diffusion from the crucible and coating. Copyright © 2008 John Wiley & Sons, Ltd.     

Pediocin PA-1 and a pediocin producing Lactobacillus plantarum strain do not change the HMA rat microbiota

The bacteriocin pediocin PA-1 has potential use as a food biopreservative, and understanding its effect on the commensal gut microbiota is important for assessment of consumer risks associated with the use of biopreservative cultures. Effects of ingested (i) pediocin PA-1 producing Lactobacillus plantarum DDEN 11007, (ii) the plasmid cured pediocin negative L. plantarum DDEN 12305, or (iii) supernatants of either of these two strains on the composition of the intestinal microbiota of Human Microbiota Associated (HMA) rats were examined by selective cultivation and molecular methods. The culturable microbiota was in all treatments dominated by lactic acid bacteria and coliforms and no changes in the rat commensal microbiota were detected after ingestion of either of the two L. plantarum strains as determined by both culturable methods and molecular methods (DGGE). Both strains were detected in the faeces after ingestion. Pediocin PA-1 did not mediate changes of the rat microbiota, and a biological assay indicated that the bacteriocin was degraded or inactivated during passage through the intestine.     

Low level cyclic adenosine 3',5'-monophosphate accumulation analysis of [des-His1, des- Phe6, Glu9] glucagon-NH2 identifies glucagon antagonists from weak partial agonists/antagonists

[des-His1, des-Phe6,Glu9]Glucagon-NH2 is a newly designed glucagon antagonist. This analog has a binding IC50 of 48 nM (compared to glucagon IC50 of 1.5 nM) and demonstrates pure antagonism in an adenylate cyclase assay. Although the number of glucagon antagonists has grown rapidly recently, closer examination suggested that many of these antagonists retained very low, almost imperceptible levels of cAMP accumulation that were sufficient to elicit an in vivo biological response. To investigate more carefully this secondary biological signal, we measured cAMP accumulation in a revised assay using isolated hepatocytes in the presence of the phosphodiesterase (PDE) inhibitor Rolipram. The PDE inhibitors Rolipram and isobutyl-1-methylxanthine (IBMX) increased the sensitivity of the cAMP accumulation assay from approximately 10-fold for the native hormone to 35-fold above basal levels. On the other hand, amrinone, another PDE inhibitor, did not affect the cAMP accumulation caused by glucagon. The use of PDE inhibitors indicated that three glucagon analogs that had previously been reported to have strong antagonist properties in classical adenylate cyclase assays were actually weak partial agonists in this new assay system. [N alpha-Trinitrophenyl-His1, homo-Arg12]glucagon, [des-amino-His1,D-Phe4,Tyr5, Arg12, Lys17,18,Glu21]glucagon, and [des-His1,Glu9]glucagon-NH2 demonstrated 233%, 21%, and 5.5% cAMP accumulation relative to the native hormone in the presence of 25 microM Rolipram. On the other hand, [des-His1,des-Phe6,Glu9]glucagon-NH2, a newly designed glucagon antagonist, did not activate adenylate cyclase in the presence of Rolipram up to a maximal physiological concentration of 1 microM, indicating that it was a pure antagonist of glucagon-induced adenylate cyclase activity and also the first one in this class. This compound and others were tested in a glycogen phosphorylase assay. As [des-His1,des- Phe6,Glu9]glucagon-NH2 did not activate phosphorylase activity, it was chosen as our candidate for in vivo testing in streptozotocin-induced diabetic rats. An initial dose of 0.75 mg/kg was found to cause the greatest lowering of blood glucose levels (to 63% of the initial levels in 15 min) when the bolus was followed by continuous infusion of 25 micrograms/kgxmin for 1 h.     

Effects of brown midrib corn silage on the energy balance of dairy cattle

Effects of genotype and level of intake on net energy for lactation values of corn silage were evaluated by indirect calorimetry in two experiments using lactating and dry, nonpregnant dairy cows. In experiment 1, six multiparous Holstein cows in early lactation were fed experimental diets containing either brown midrib (bm3) or isogenic normal corn silage. Dietary treatments were isogenic and bm3 diets fed ad libitum, and the bm3 diets restricted-fed. Dry matter (DM) intake was 2.4 kg/d greater for cows fed the bm3 diet ad libitum compared with cows fed the isogenic diet. Apparent digestibilities of DM, organic matter, neutral detergent fiber, and acid detergent fiber were greater for cows restricted-fed bm3 than the isogenic diet. In experiment 2, six dry, nonpregnant Holstein cows were fed maintenance diets containing either bm3 or isogenic corn silage. Apparent digestibilities of DM, organic matter, neutral detergent fiber, and acid detergent fiber were greater for cows fed bm3 compared with isogenic corn silage. Digestible energy and metabolizable energy were greater for maintenance diets containing bm3 compared with isogenic corn silage, respectively. These data indicate increased milk production seen in other studies is a result of increased DMI rather than an increase in energy efficiency. Increased organic matter digestibility of bm3 corn silage resulted in greater digestible energy and metabolizable energy values in cows fed at maintenance energy intake. However, calculated net energy for lactation values of bm3 and isogenic corn silages were similar at both productive and maintenance levels of feeding.     

Reducing the item number to obtain same-length self-assessment scales: a systematic approach using result of graphical loglinear Rasch modeling

The Revised Danish Learning Styles Inventory (R-D-LSI) (Nielsen 2005), which is an adaptation of Sternberg-Wagner Thinking Styles Inventory (Sternberg, 1997), comprises 14 subscales, each measuring a separate learning style. Of these 14 subscales, 9 are eight items long and 5 are seven items long. For self-assessment, self-scoring and self-interpretational purposes it is deemed prudent that subscales measuring comparable constructs are of the same item length. Consequently, in order to obtain a self-assessment version of the R-D-LSI with an equal number of items in each subscale, a systematic approach to item reduction based on results of graphical loglinear Rasch modeling (GLLRM) was designed. This approach was then used to reduce the number of items in the subscales of the R-D-LSI which had an item-length of more than seven items, thereby obtaining the Danish Self-Assessment Learning Styles Inventory (D-SA-LSI) comprising 14 subscales each with an item length of seven. The systematic approach to item reduction based on results of GLLRM will be presented and exemplified by its application to the R-D-LSI.