Ageritin—The Ribotoxin-like Protein from Poplar Mushroom (Cyclocybe aegerita) Sensitizes Primary Glioblastoma Cells to Conventional Temozolomide Chemotherapy

Here, we propose Ageritin, the prototype of the ribotoxin-like protein family, as an adjuvant treatment to control the growth of NULU and ZAR, two primary human glioblastoma cell lines, which exhibit a pharmacoresistance phenotype. Ageritin is able to inhibit NULU and ZAR growth with an IC50 of 0.53 ± 0.29 µM and 0.42 ± 0.49 µM, respectively. In this study, Ageritin treatment highlighted a macroscopic genotoxic response through the formation of micronuclei, which represents the morphological manifestation of genomic chaos induced by this toxin. DNA damage was not associated with either the deregulation of DNA repair enzymes (i.e., ATM and DNA-PK), as demonstrated by quantitative PCR, or reactive oxygen species. Indeed, the pretreatment of the most responsive cell line ZAR with the ROS scavenger N-acetylcysteine (NAC) did not follow the reverse cytotoxic effect of Ageritin, suggesting that this protein is not involved in cellular oxidative stress. Vice versa, Ageritin pretreatment strongly enhanced the sensitivity to temozolomide (TMZ) and inhibited MGMT protein expression, restoring the sensitivity to temozolomide. Overall, Ageritin could be considered as a possible innovative glioblastoma treatment, directly damaging DNA and downregulating the MGMT DNA repair protein. Finally, we verified the proteolysis susceptibility of Ageritin using an in vitro digestion system, and considered the future perspective use of this toxin as a bioconjugate in biomedicine.     

Enzymatic transformation of cephalosporin C to 7-ACA by simultaneous action of immobilized d-amino acid oxidase and glutaryl-7-ACA acylase

The enzymatic transformation of cephalosporin C (CEPH C) to 7-amino-cephalosporanic acid (7-ACA) using D-amino acid oxidase (DAO) and glutaryl-7-ACA acylase (G1-7-ACA) is reported. The enzymes have been immobilized separately on different carriers, in order to maximize the catalytic activity and the stability. The reaction has been carried out in single-step-like conditions, using the two enzymes simultaneously. The effect of catalase contamination, present in the DAO preparations, was balanced by addition of extra hydrogen peroxide. In optimum conditions, the conversion of CEPH C to 7-ACA was higher than 90%, with byproduct formation lower than 4%. The mixture of immobilized enzymes was reused in repeated reaction cycles, showing an appreciable operational stability.     

Mechanism of the oxidation of sulfides by dioxiranes. 1. Intermediacy of a 10-S-4 hypervalent sulfur adduct

Earlier studies established that dimethyldioxirane (1a) reacts with sulfides 2 in two consecutive concerted electrophilic oxygen-transfer steps to give first sulfoxides 3 and then sulfones 4. The same sequential electrophilic oxidation model was assumed for the reaction of sulfides 2 with the strongly electrophilic methyl(trifluoromethyl)dioxirane (1b). In this paper we report on a systematic and general study on the mechanism of the reaction of simple sulfides 2 with DMDO (1a) and TFDO (1b) which provides clear evidence for the involvement of hypervalent sulfur species in the oxidation process. In the oxidation of sulfides 2a-c, diphenyl sulfide (2d), para-substituted aryl methyl sulfides 2e-i, and phenothiazine 2k with 1b, the major product was the corresponding sulfone 4, even when a 10-fold excess of sulfide relative to 1b was used. The sulfone:sulfoxide 4:3 ratio depends among other factors on the dioxirane 1a or 1b used, the sulfide substitution pattern, the polar, protic, or aprotic character of the solvent, and the temperature. The influence of these factors and also deuterium and (18)O tracer experiments performed allow a general mechanism to be depicted for these oxidations in which the key step is the reversible cyclization of a zwitterionic intermediate, 6, to form a hypervalent sulfur species, 7. The classical sequential mechanism which establishes that sulfides are oxidized first to sulfides and then to sulfones can be enclosed in our general picture of the process and represents just those particular cases in which the zwitterionic intermediate 6 decomposes prior to undergoing ring closure to afford the hypervalent sulfurane intermediate 7.     

Synthesis and Solid-State Conformation of a Calix[8]arene 1,5-Diquinone Derivative

The first example of a calix[8]quinone derivative, hexamethoxy-p-tert-butylcalix[8]-1,5-diquinone 5, has been synthesized from p-tert-butylcalix[8]arene 1by exploiting a protection-deprotection procedure. The structure of the 5·toluene inclusion compound has been determined by a single crystal X-ray diffraction study. The calix[8]arene molecule possesses a crystallographic inversion centre and assumes a ‘pseudo-chair-like’ conformation, with two opposite 3/4-cone moieties, which resembles the previously reported chair-like conformation of p-tert-butylcalix[8]arene. The 4 toluene molecules per unit cell occupy interstitial voids and are released in the temperature range of 30–160 °C.This revised version was published online in July 2005 with a corrected issue number.     

Muonic atom X-ray spectroscopy for non-destructive analysis of archeological samples

Journal of Radioanalytical and Nuclear Chemistry - The implementation in the RIKEN-RAL negative muons facility of a new muon beamline monitoring and novel digital data acquisition system for gamma...     

Tunable Interfacial Properties in Silk Ionomer Microcapsules with Tailored Multilayer Interactions

Microencapsulation techniques represent a critical step in realizing highly controlled transport of functional materials in multiphase systems. The first demonstration of microcapsules prepared from minimally grafted silk ionomers (silk fibroin modified with cationic/anionic charge groups) are presented here. These tailored biomacromolecules have shown significantly increased biocompatibility over traditional polyelectrolytes and heavily grafted silk ionomers, but the low grafting density had previously limited attempts to fabricate stable microcapsules. In addition, the first microcapsules from polyethylene‐glycol‐grafted silk ionomers are fabricated and the corresponding impact on microcapsule behavior is demonstrated. The materials are shown to exhibit pH‐responsive properties, with the microcapsules demonstrating an approx. tenfold decrease in stiffness and an approx. threefold change in diffusion coefficient when moving from acidic to basic buffer. Finally, the effect of assembly conditions of the microcapsules are shown to play a large role in determining final properties, with microcapsules prepared in acidic buffers showing lower roughness, stiffness, and an inversion in transport behavior (i.e., permeability decreases at higher pH).     

The Cauchy problem for a class of Kovalevskian pseudo-differential operators

We prove the well-posedness of the forward Cauchy problem for a pseudo-differential operator of order with the Log-Lipschitz continuous symbol in the time variable. The characteristic roots of are distinct and satisfy the necessary Lax-Mizohata condition Im . The Log-Lipschitz regularity has been tested as the optimal one for well-posedness in the case of second-order hyperbolic operators. Our main aim is to present a simple proof which needs only a little of the basic calculus of standard pseudo-differential operators.