Mechanistic Studies for the Rational Design of Multivalent Glycodendrimers

We have synthesized B-antigen-displaying dendrimers (16-mers) with different sizes and evaluated their affinity to their IgM antibody in order to investigate which design features lead to effective multivalency. Unexpectedly, the smallest dendrimer, which cannot chelate the multiple binding sites of IgM, clearly exhibited multivalency, together with an affinity similar to or higher than those of the larger dendrimers. These results indicate that the statistical rebinding model, which involves the rapid exchange of clustered glycans, significantly contributes to the multivalency of glycodendrimers. Namely, in the design of glycodendrimers, high-density glycan presentation to enhance statistical rebinding should be considered in addition to the ability to chelate multiple binding sites. This notion stands in contrast to the currently prevailing scientific consensus, which prioritizes the chelation model. This study thus provides new and important guidelines for molecular design of glycodendrimers.     

Strain-Induced Ring Expansion Reactions of Calix[3]pyrrole-Related Macrocycles

The recent discovery of calix[3]pyrrole, a porphyrinogen-like tripyrrolic macrocycle, has provided an unprecedented strain-induced ring expansion reaction into calix[6]pyrrole. Here, we synthesized calix[n]furan[3-n]pyrrole (n=1∼3) macrocycles to investigate the reaction scope and mechanism of the ring expansion. Single crystal X-ray analysis and theoretical calculations revealed that macrocyclic ring strain increases as the number of inner NH sites increases. While calix[1]furan[2]pyrrole exhibited almost quantitative conversion into calix[2]furan[4]pyrrole within 5 minutes, less-strained calix[2]furan[1]pyrrole and calix[3]furan were inert. However, N-methylation of calix[2]furan[1]pyrrole induced a ring-expansion reaction that enabled the isolation of a linear reaction intermediate. The mechanism analysis revealed that the ring expansion consists of regioselective ring cleavage and subsequent cyclodimerization. This reaction was further utilized for synthesis of calix[6]-type macrocycles.     

Folding thermodynamics of PET-hydrolyzing enzyme Cut190 depending on Ca2+ concentration

The enzyme, cutinase from Saccharomonospora viridis AHK190 (Cut190), can hydrolyze the inner block of polyethylene terephthalate (PET). Cut190 has a unique feature that both its activity and thermal stability are increased upon Ca²⁺ binding. In consideration of the glass transition temperature of PET, which is between 60 and 65 °C, the increased activity and thermal stability are of great interest to apply for PET bio-recycling. Our previous mutational analysis showed that the S226P/R228S mutant (Cut190*) has a higher activity and thermal stability than those of the wild type. In this study, we analyzed the folding thermodynamics of the inactive mutant of Cut190*, Cut190*S176A, using circular dichroism and differential scanning calorimetry. The results show that the denaturation temperature increases from 54 to 71 °C due to the addition of 250 mM Ca²⁺, in a Ca²⁺ concentration-dependent manner. The increased thermal stability is mainly due to the increased enthalpy change, partially compensated by the increased entropy change. Based on the crystal structure of Cut190*S176A bound to Ca²⁺, molecular dynamics simulations were carried out to analyze the effects of Ca²⁺ on the structural dynamics, showing that the Ca²⁺-bound structure fluctuated less than the Ca²⁺-free structure. Structural analysis indicates that Ca²⁺ binding increases the intramolecular interactions of the enzyme, while decreasing its fluctuation, which are in good correlation with the experimental results of the folding thermodynamics.

     

Period-doubling cascades of canards from the extended Bonhoeffer-van der Pol oscillator

This Letter investigates the period-doubling cascades of canards, generated in the extended Bonhoeffer-van der Pol oscillator. Canards appear by Andronov-Hopf bifurcations (AHBs) and it is confirmed that these AHBs are always supercritical in our system. The cascades of period-doubling bifurcation are followed by mixed-mode oscillations. The detailed two-parameter bifurcation diagrams are derived, and it is clarified that the period-doubling bifurcations arise from a narrow parameter value range at which the original canard in the non-extended equation is observed.     

The Relationship between Age and Change in Physical Functions after Exercise Intervention. Trainability of Japanese Community-Dwelling Older Elderly

The purposes of this study were to evaluate the relationship between age and changes in physical measurements after exercise intervention and to investigate the trainability of the older elderly. Two hundred seventy-six community-dwelling people aged 60 years and older practiced exercise intervention for 3 months. The measurements of physical functions were one-legged standing with eyes open and closed (OLS-O, OLS-C), functional reach test (FR), timed up and go test (TUG), maximum walking velocity, flexibility, and muscle strength. We evaluated the associations between age and the changes in these physical measurements. All measurements except for OLS-C significantly improved after intervention. The magnitude of the changes in hand-grip strength and FR after the intervention showed weak negative correlations with the subject''s age, but other measurements showed no correlations. In addition, there were no differences between younger elderly persons and older elderly persons with regard to changes in any measurements. These results suggested that the exercise intervention we applied could improve physical fitness in community-dwelling older people, regardless of their age. The older elderly were comparable to the younger elderly in trainability to improve physical fitness.     

CEMS study on diluted magneto titanium oxide films prepared by pulsed laser deposition

6% ⁵⁷Fe doped titanium oxide films, prepared by pulsed laser deposition (PLD) on sapphire substrate at 650°C under various vacuum conditions, were characterized mainly by conversion electron Mössbauer spectrometry (CEMS). Two magnetic sextets with hyperfine fields 33 and 29 T, and one doublet were observed in the CEMS spectra of TiO₂ films prepared under PO₂ = 10^?6 and 10^?8 torr, which showed ferromagnetism at room temperature, whereas only the doublet of paramagnetic Fe³⁺ species was observed for the film prepared under PO₂ = 10^?1 torr.     

Development of rapid plutonium analysis for environmental samples by isotope dilution/inductively coupled plasma mass spectrometry with on-line column.

This paper describes our development of a rapid on-line column/ID-ICP-MS technique for the analysis of plutonium (Pu) in environmental samples using an UTEVA extraction chromatograph resin (UTEVA resin) column. It took only 40 min to separate and measure Pu in the sample solution, including the time for conditioning the resin column for the next analysis. In our method, Pu in a 3 M nitric acid solution was fed to the UTEVA resin, and then eluted from the resin by reducing Pu to Pu(III) with 3 M nitric acid mixed with 0.01 M ascorbic acid after washing the resin. The outflow from the resin column was directly introduced to an ICP-MS system. The low concentration of ascorbic acid and the small volume of the eluting solution (0.6 mL) made successive stable analysis possible without any skimmer cone clogging. The chemical recovery of Pu during column operation was 70%, and typical lower detection limits for 239Pu, 240Pu and 242Pu were 9.2, 4.3 and 7.5 fg (21, 36 and 1.1 microBq), respectively. We analyzed five international standard materials for Pu, and obtained good results.     

Normally contracting Lie group actions

We show that there are no normally contracting actions of unimodular Lie groups on closed manifolds.