A Novel LRRK2 Variant p.G2294R in the WD40 Domain Identified in Familial Parkinson’s Disease Affects LRRK2 Protein Levels

Leucine-rich repeat kinase 2 (LRRK2) is a major causative gene of late-onset familial Parkinson’s disease (PD). The suppression of kinase activity is believed to confer neuroprotection, as most pathogenic variants of LRRK2 associated with PD exhibit increased kinase activity. We herein report a novel LRRK2 variant—p.G2294R—located in the WD40 domain, detected through targeted gene-panel screening in a patient with familial PD. The proband showed late-onset Parkinsonism with dysautonomia and a good response to levodopa, without cognitive decline or psychosis. Cultured cell experiments revealed that p.G2294R is highly destabilized at the protein level. The LRRK2 p.G2294R protein expression was upregulated in the patient’s peripheral blood lymphocytes. However, macrophages differentiated from the same peripheral blood showed decreased LRRK2 protein levels. Moreover, our experiment indicated reduced phagocytic activity in the pathogenic yeasts and α-synuclein fibrils. This PD case presents an example wherein the decrease in LRRK2 activity did not act in a neuroprotective manner. Further investigations are needed in order to elucidate the relationship between LRRK2 expression in the central nervous system and the pathogenesis caused by altered LRRK2 activity.     

On the one-wayness against chosen-plaintext attacks of the Loidreau's modified McEliece PKC

McEliece public-key cryptosystem (PKC) is one of a few alternatives for the current PKCs that are mostly based on either the integer factoring problem (IFP) or the discrete logarithm problem (DLP) that would be solved in polynomial time after the emergence of quantum computers. The security of the McEliece PKC is based on the decoding problem and it is known that it satisfies, with an appropriate conversion, the strongest security notion, i.e., INDistinguishability of encryption against adaptively Chosen-Ciphertext Attacks (IND-CCA2), in the random oracle model under the assumption that the underlying primitive McEliece PKC satisfies a weak security notion of One-Wayness against Chosen-Plaintext Attacks (OW-CPA). OW-CPA is said to be satisfied if it is infeasible for chosen plaintext attacks to recover the whole plaintext of an arbitrarily given ciphertext. Currently, the primitive McEliece PKC satisfies OW-CPA if a parameter n/spl ges/2048 with optimum t and k is chosen since the binary work factor for (n,k,t)=(2048,1278,70) to break it with the best CPA is around 2/sup 106/, which is infeasible even if world-wide computational power is used. While the binary work factor for the next smaller parameter n=1024 is in a gray level of 2/sup 62/, it will be improved by applying Loidreau's modification that employs Frobenius automorphism in Goppa codes. In this paper, we carefully investigate the one-wayness of the Loidreau's modified McEliece PKC against ever known CPAs and new CPAs we propose, and then show that it certainly improves the one-wayness against ever known CPAs but it is vulnerable against our new CPAs. Thus, it is rather harmful to apply the new modification to the McEliece PKC.     

Apoptosis occurs in granulosa cells but not cumulus cells in the atretic antral follicles in pig ovaries

The porcine antral follicles, 3-6 mm in diameter, were dissected from the ovaries of mature pigs, and then granulosa and cumulus cells were isolated from each follicle. In atretic follicles, high activity of neutral Ca2+/Mg2+-dependent endonuclease and DNA ladder formation, estimated by electrophoresis, were noted in granulosa cells but not in cumulus cells. Extremely low activity of the endonuclease and no DNA ladder formation were observed in both types of cells obtained from healthy follicles. Moreover, apoptotic cells were observed histochemically among granulosa cells only. A good correlation (r = 0.987) between the endonuclease activity of granulosa cells and the progesterone/estradiol ratio of follicular fluid in each follicle was found. These results suggest that apoptosis occurs in granulosa cells but not cumulus cells in the atretic antral follicles in pigs.     

Radiation therapy for stage I-II non-small cell lung cancer in patients aged 75 years and older

Vaccination with peptides that induce a specific immune response is a potential prophylactic or therapeutic strategy against viral infections and tumors. Because of the extensive polymorphism of the HLA loci, synthetic peptide vaccines must consist of a cocktail of peptides that bind specifically to different HLA molecules. Such cocktails should be optimized for the target population as each population has its specific HLA gene frequencies. To achieve maximum population coverage with a minimum number of peptides, information is needed on the ranking of the most frequent HLA phenotypes. We introduce the minimal phenotype panel, which is the smallest combination of HLA antigens selected so that the proportion of individuals in a population that express at least one of the antigens in the panel exceeds a desired minimum value. We developed a method for assembling minimal phenotype panels based on known HLA class I gene frequencies. We give an example based on a set of 2446 well-defined HLA-typed, random, healthy, unrelated, Dutch Caucasoid individuals. In addition, we discuss the possibility of assembling minimal phenotype panels based on two-locus haplotypes, which enables the assembly of phenotype panels from the antigens of both loci.     

Stereoselectivity in cutaneous hydrolysis and transdermal transport of propranolol prodrug

This review is written to evaluate the stereoselectivity in cutaneous hydrolysis and transdermal transport of propranolol prodrug. This discussion will be useful in the development of knowledge about stereoselective cutaneous hydrolysis and its influence on stereoselective transdermal transport of many other chiral prodrugs and drugs. Propranolol prodrugs undergo stereoselective hydrolysis in hairless mouse skin homogenate and in excised skin samples during permeation; the stereoselectivity is markedly biased towards hydrolysis of the (R) isomer. Unlike the liver, the esterase activity of the skin is high in its cytosolic fraction. Most of the lipophilic propranolol prodrugs cause stereoselective permeation across hairless mouse skin. A mechanism of stereoselective permeation of propranolol prodrug across the skin has been proposed, which indicates that the stereoselectivity in permeation is resulted from the stereoselective hydrolysis of lipophilic prodrug during permeation.     

Comparison of activities in selective catalytic reduction of NOx by C3H8 over Co/MFI, Fe/MFI, and H/MFI zeolite catalysts

The Co/MFI(SiO₂/Al₂O₃ = 30) were prepared by a precipitation method with NaOCl in alkali solutions exhibited high activities to N₂ at 250 °C for the selective catalytic reduction (SCR) of NO_x. These catalysts showed two UV–vis bands at 700 and 400 nm, indicating the presence of octahedral Co(III) as well as tetrahedral Co(II). The high SCR activity over such Co(III, II)/MFI(30) seems to come from Co(III)---O moieties. The Co(II)MFI(30) catalysts prepared from Co(II)Cl₂ exhibited low SCR activities due to the presence of tetrahedral Co(II) ions in MFI. Less CO formation occurred over Co/MFI catalysts. The Fe/MFI(30) catalyst exhibited high activity due to the presence of some Fe---O species in MFI but more amount of CO were produced during SCR. H/MFI(30) catalyst exhibited a good SCR activity. However, more amount of carbonaceous deposits were produced on it. The correlation between acid concentration and SCR activity was discussed over H/MFIs.     

Preparation of polyimide-epoxy composites

The formation of a three dimensional network of crosslinked epoxy leads all unmodified epoxies to have inherent brittleness and relatively low degradation temperatures. Polyimides, on the other hand, are widely used for applications that require high degrees of flexibility and thermal resistance. Here, we have focused on the preparation of epoxy systems cured with polyamic acids instead of traditional amino-group-containing hardening agents. The cure behavior and potential reaction mechanisms of EPON 828 resin and polyamic acid mixtures were evaluated by DSC and TGA. Thermal analysis showed a complex reaction sequence taking place in the mixture and also determined the extent of reaction of the polyamic acid with itself and the competitive reaction of the polyamic acid with the epoxy. The compositions of the mixtures were varied to see the dependence of the cure behavior on component concentrations. Solutions of the two components did not phase separate and also phase separation was not apparent either optically or microscopically in the cured samples. This phase behavior was attributed to a unique in situ reaction. A novel solvent system for the polyamic acid precursor was also used.     

Preferential Oxidation of CO in H2-Rich Gas at Low Temperatures over Au Nanoparticles Supported on Metal Oxides

We investigated Au catalysts supported on TiO₂, Fe₂O₃, and ZnO for their preferential oxidation of CO in a H₂-rich atmosphere. Both full conversion and selectivity were achieved over Au/Fe₂O₃ and Au/ZnO around room temperature, but at higher temperatures the CO conversion was suppressed due to competition between CO and H₂.