Interaction of five -mannose-specific lectins with a series of synthetic branched trisaccharides

The interaction of a series of synthetic, branched trisaccharides with five -mannose-specific lectins was studied by precipitation-inhibition assay. The branched methyl [alpha]--mannotrioside, [alpha]--Manp-(1-->3)-[[alpha]--Manp-(1-->6)-[alpha]--ManpOMe, the best inhibitor of the Con A--Dextran interaction, was 42 times more potent than [alpha]--ManpOMe, and 3-6 times more potent than the two trisaccharides substituted with -glucosyl groups, and 8-15 times those with -galactosyl groups. Surprisingly, methyl O-[alpha]--mannopyranosyl-(1-->3)-[alpha]--mannopyranoside was bound to Con A 8-fold more avidly than methyl [alpha]--mannopyranoside. However, the related pea lectin (PSA) was singularly different from Con A in its carbohydrate-binding activity, showing no significantly enhanced binding to any of the sugars examined. The trisaccharides containing terminal, nonreducing, (1-->3)-linked [alpha]--mannopyranosyl groups, i.e., [alpha]--Manp-(1-->3)-[[alpha]--Glcp-(1-->6)-[alpha]--ManpOMe, [alpha]--Manp-(1-->3)-][alpha]--Galp-(1-->6)]-[alpha]--ManpOMe, and [alpha]--Manp-(1-->3)-[[alpha]--Manp-(1-->6)]-[alpha]-- ManpOMe, were the best inhibitors of the snowdrop lectin (GNA)--mannan precipitation system. On the other hand, all branched trisaccharides exhibited very similar inhibitory potencies toward the daffodil lectin (NPA)--mannan interaction, whereas [alpha]--Manp-(1-->3)-[[alpha]--Galp-(1-->6)]-[alpha]--ManpOMe and [alpha]--Manp-(1-->3)-[[alpha]--Manp-(1-->6)]-[alpha]--ManpOMe were somewhat better inhibitors than the other branched trisaccharides of the amaryllis lectin (HHA)--mannan precipitation reaction. Of the oligosaccharides studied, the linear trisaccharide [alpha]--Manp-(1-->6)-[alpha]--Manp-(1-->6)--Man appears to be the most complementary to the combining site(s) of NPA and HHA.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29275/1/0000334.pd

DETAILED ACCIDENT ANALYSIS FOR THE HIGH LEVEL WSTE PREPARATION PHASE OF THE COMMERCIAL NUCLEAR WASTE VITRIFICATION PROJECT

The environmental consequences and the probability of conceivable accidents occurring during the high level waste preparation (HLWP) phase of the Commercial Nuclear Waste Vitrification Project (CNWVP) were analyzed. The maximum environmental consequences of postulated accidents were calculated to result in low radiation doses: a 50-year dose commitment of 0.3 rem to the whole body for a maximum individual, and of 20 man-rem to the whole body for the surrounding population. This may be compared to Department of Energy (DOE) values, in Manual Chapter Appendix 0524, of 0.5-rem whole-body annual dose commitment to individuals at points of maximum probable exposure in uncontrolled areas. The calculated whole-body relative dose risk to individuals from accidents is low (1.6 x 10{sup -6} rem/yr) as compared to that received from natural background radiation (approximately 1.5 x 10{sup -1 } rem/yr) and as compared to levels specified in Nuclear Regulatory Commission (NRC) requirements for routine releases from nuclear power reactors (5.0 x 10{sup -3} rem/yr). Therefore, the design and operational plans for the HLWP phase are judged not to represent an undue environmental risk from accident conditions

Evidence for Concurrent Effects of Exposure to Environmental Cadmium and Lead on Hepatic CYP2A6 Phenotype and Renal Function Biomarkers in Nonsmokers

We examined the interrelationships between phenotype of hepatic cytochrome P450 2A6 (CYP2A6), nephropathy, and exposure to cadmium and lead in a group of 118 healthy Thai men and women who had never smoked. Their urinary Cd excretion ranged from 0.05 to 2.36 μg/g creatinine, whereas their urinary Pb excretion ranged from 0.1 to 12 μg/g creatinine. Average age and Cd burden of women and men did not differ. Women, however, on average showed a 46% higher urinary Pb excretion (p < 0.001) and lower zinc status, suggested by lower average serum Zn and urinary Zn excretion compared with those in men. Cd-linked nephropathy was detected in both men and women. However, Pb-linked nephropathy was seen only in women, possibly because of higher Pb burden coupled with lower protective factors, notably of Zn (p < 0.001), in women compared with men. In men, Pb burden showed a negative association with CYP2A6 activity (adjusted β= −0.29, p = 0.003), whereas Cd burden showed a positive association with CYP2A6 activity (adjusted β= 0.38, p = 0.001), suggesting opposing effects of Cd and Pb on hepatic CYP2A6 phenotype. The weaker correlation between Cd burden CYP2A6 activity in women despite similarity in Cd burden between men and women is consistent with opposing effects of Pb and Cd on hepatic CYP2A6 phenotypic expression. A positive correlation between Cd-linked nephropathy (urinary N-acetyl-β-d-glucosaminidase excretion) and CYP2A6 activity in men (r = 0.39, p = 0.002) and women (r = 0.37, p = 0.001) suggests that Cd induction of hepatic CYP2A6 expression and Cd-linked nephropathy occurred simultaneously

The interaction of fluorinated glycomimetics with DC-SIGN: multiple binding modes disentangled by the combination of NMR methods and MD simulations

Fluorinated glycomimetics are frequently employed to study and eventually modulate protein–glycan interactions. However, complex glycans and their glycomimetics may display multiple binding epitopes that enormously complicate the access to a complete picture of the protein–ligand complexes. We herein present a new methodology based on the synergic combination of experimental 19F-based saturation transfer difference (STD) NMR data with computational protocols, applied to analyze the interaction between DC-SIGN, a key lectin involved in inflammation and infection events with the trifluorinated glycomimetic of the trimannoside core, ubiquitous in human glycoproteins. A novel 2D-STD-TOCSYreF NMR experiment was employed to obtain the experimental STD NMR intensities, while the Complete Relaxation Matrix Analysis (CORCEMA-ST) was used to predict that expected for an ensemble of geometries extracted from extensive MD simulations. Then, an in-house built computer program was devised to find the ensemble of structures that provide the best fit between the theoretical and the observed STD data. Remarkably, the experimental STD profiles obtained for the ligand/DC-SIGN complex could not be satisfactorily explained by a single binding mode, but rather with a combination of different modes coexisting in solution. Therefore, the method provides a precise view of those ligand–receptor complexes present in solution.We thank Agencia Estatal de Investigación (Spain) for grants RTI2018-094751-B-C21 and B-C22, CTQ2015-68756-R, and for FPI and FPU fellowships to J.D.M. and P.V., respectively, and for the Severo Ochoa Excellence Accreditation (SEV-2016-0644). J.J.-B. also thanks to the European Research Council (RECGLYCANMR, Advanced Grant no. 788143). S.O. thanks the SFI Award 13/IA/1959Peer reviewe

Dissociation constants and thermodynamic properties of amino acids used in CO2 absorption from (293 to 353) K

The second dissociation constants of the amino acids βalanine, taurine, sarcosine, 6-aminohexanoic acid, DL-methionine, glycine, L-phenylalanine, and L-proline and the third dissociation constants of L-glutamic acid and L-aspartic acid have been determined from electromotive force measurements at temperatures from (293 to 353) K. Experimental results are reported and compared to literature values. Values of the standard state thermodynamic properties are derived from the experimental results and compared to the values of commercially available amines used as absorbents for CO 2 capture.

Exploring functional pairing between surface glycoconjugates and human galectins using programmable glycodendrimersomes

Precise translation of glycan-encoded information into cellular activity depends critically on highly specific functional pairing between glycans and their human lectin counter receptors. Sulfoglycolipids, such as sulfatides, are important glycolipid components of the biological membranes found in the nervous and immune systems. The optimal molecular and spatial design aspects of sulfated and nonsulfated glycans with high specificity for lectin-mediated bridging are unknown. To elucidate how different molecular and spatial aspects combine to ensure the high specificity of lectin-mediated bridging, a bottom-up toolbox is devised. To this end, negatively surface-charged glycodendrimersomes (GDSs), of different nanoscale dimensions, containing sulfo-lactose groups are self-assembled in buffer from a synthetic sulfatide mimic: Janus glycodendrimer (JGD) containing a 3′-O-sulfo-lactose headgroup. Also prepared for comparative analysis are GDSs with nonsulfated lactose, a common epitope of human membranes. These self-assembled GDSs are employed in aggregation assays with 15 galectins, comprising disease-related human galectins, and other natural and engineered variants from four families, having homodimeric, heterodimeric, and chimera architectures. There are pronounced differences in aggregation capacity between human homodimeric and heterodimeric galectins, and also with respect to their responsiveness to the charge of carbohydrate-derived ligand. Assays reveal strong differential impact of ligand surface charge and density, as well as lectin concentration and structure, on the extent of surface cross-linking. These findings demonstrate how synthetic JGD-headgroup tailoring teamed with protein engineering and network assays can help explain how molecular matchmaking operates in the cellular context of glycan and lectin complexity

Rapid reduction of arsenate in the medium mediated by plant roots

Microbes detoxify arsenate by reduction and efflux of arsenite. Plants have a high capacity to reduce arsenate, but arsenic efflux has not been reported. Tomato (Lycopersicon esculentum) and rice (Oryza sativa) were grown hydroponically and supplied with 10 mu M marsenate or arsenite, with or without phosphate, for 1-3 d. The chemical species of As in nutrient solutions, roots and xylem sap were monitored, roles of microbes and root exudates in As transformation were investigated and efflux of As species from tomato roots was determined. Arsenite remained stable in the nutrient solution, whereas arsenate was rapidly reduced to arsenite. Microbes and root exudates contributed little to the reduction of external arsenate. Arsenite was the predominant species in roots and xylem sap. Phosphate inhibited arsenate uptake and the appearance of arsenite in the nutrient solution, but the reduction was near complete in 24 h in both -P- and +P-treated tomato. Phosphate had a greater effect in rice than tomato. Efflux of both arsenite and arsenate was observed; the former was inhibited and the latter enhanced by the metabolic inhibitor carbonylcyanide m-chlorophenylhydrazone. Tomato and rice roots rapidly reduce arsenate to arsenite, some of which is actively effluxed to the medium. The study reveals a new aspect of As metabolism in plants

Willingness to pay for municipality hospital services in rural Japan: a contingent valuation study

<p>Abstract</p> <p>Background</p> <p>The Japanese healthcare system has undergone reforms to address the struggles that municipality hospitals face. Reform guidelines clearly define criteria for administrative improvement. However, criteria to evaluate the demand for healthcare provisions in rural Japan, including the needs of rural residents for municipality hospitals in particular have not been specified. The purpose of this paper is to measure residents' willingness to pay (WTP) for municipality hospital services using the contingent valuation method, and to evaluate municipality hospital valuation on the basis of WTP. K town, located in the Hokkaido prefecture of Japan, was selected as the location for this study. Participants were recruited by a town hall healthcare administrator, hospital and clinic staff, and a local dentist. Participants were asked what amount they would be willing to pay as taxes to continue accessing the services of the municipality hospital for one year by using open-ended questions in face-to-face interviews.</p> <p>Findings</p> <p>Forty-eight residents were initially recruited, and 40 participants were selected for the study (response rate 83%). As compared to K town's population, this data slanted toward the elderly, although there was no significant difference in frequency among the characteristics. The median WTP was estimated at 39,484 yen ($438.71), with a 95$308.95-615.96). Logistic regression revealed no significant factors affecting WTP.</p> <p>Conclusions</p> <p>If the total amount of residents' WTP for the municipality hospital were to be estimated by this result, it would calculate with 129,586,000 yen ($1,439,844). This is approximately equal to the amount of money to be transferred from the general account of the government of K town, more than one-half of the town tax of K town, and about two-fold in comparison to Japan as a whole. This showed that K town's residents placed a high valuation on the municipality hospital, which nearly equalled the amount that the K town government provided to the municipality hospital to cover its annual deficit. K town residents had come to expect not only general clinical practice, but also emergency medical services and night practice provided by their own town's municipality hospital. WTP can be used as a measure of hospital evaluation because it reflects the importance of the hospital to the residents in its region.</p