Relationships between drinking habits, psychological resilience, and salivary cortisol responses on the Trier Social Stress Test-Online among Japanese people.

BACKGROUND: This study aimed to determine whether individual differences in resilience interacted with those in alcohol consumption habits in situations involving exposure to psychosocial stressors (Trier Social Stress Test-Online; TSST-OL). Additionally, we investigated whether individuals exhibiting resilience in their psychological scale scores showed biological responses that could be interpreted as resilience in stressful situations, such as the TSST-OL. We hypothesized that there would be no association between drinking habits and stress responses in the high-resilience group. Furthermore, high drinking habits would be associated with high stress responses in the low-resilience group. METHODS: We recruited 22 and 20 individuals from the high and low-resilience groups, respectively, from among those who completed the online survey comprising the Alcohol Use Disorders Identification Test (AUDIT) and resilience scales; we excluded individuals with AUDIT scores of 15 or higher, and divided them by the median total resilience scale score. During the TSST-OL, self-rated stress measurement and saliva sample collection were performed seven times. Frozen samples were collected at the Tokyo site, and salivary hormonal (cortisol and dehydroepiandrosterone) levels were measured after transport in frozen state. Finally, 36 participants were included in the analysis of self-rated stress and cortisol levels. RESULTS: We observed the typical subjective stress responses to the TSST-OL. People with higher psychological scale scores for resilience traits showed significantly higher salivary cortisol levels than those with lower scores. Due to deficiencies in the survey and experimental design, the classification criteria were changed and an exploratory analysis was performed to investigate the interaction of individual differences in resilience and drinking habits. In contrast to our expectation, those with low resilience scores showed stress responses, regardless of their drinking habits. Furthermore, those with high resilience and drinking habits showed a specific insensitivity to salivary cortisol levels. Their self-rated stress scores were similar to those of other groups. CONCLUSIONS: Our study showed the applicability of the TSST-OL in the Japanese population, the individual relationship between psychological resilience measures and biological stress responses, and a specific insensitivity in the salivary cortisol response as a result of individual differences in high resilience and drinking habits.

One-Pot Tandem Coupling Method for the Short-Step Formal Synthesis of Riccardin C.

One-pot reactions reduce reagent amounts and circumvent process treatments, such as work-up and purifications in multi-step reactions. In this study, we achieved the formal total synthesis of riccardin C through a one-pot reaction by simultaneously linking four units through two Sonogashira coupling reactions and one Suzuki coupling reaction, followed by reduction and deprotection. Thus, this one-pot method comprised five steps and did not require the purification of intermediate reaction mixtures, which saves resources, such as reagents and solvents, and expedites the work process.

Chlamydial Infection-Dependent Synthesis of Sphingomyelin as a Novel Anti-Chlamydial Target of Ceramide Mimetic Compounds.

The obligate intracellular bacterium Chlamydia trachomatis is the major causative agent of bacterial sexually transmitted diseases worldwide. In infected cells, the ceramide transport protein (CERT) is recruited to inclusions, where C. trachomatis replicates using host-synthesized ceramide. The ceramide is converted to sphingomyelin (SM) by a chlamydial infection-dependent SM synthesis (cidSM-synthesis) pathway, which occurs even in the absence of the SM synthases (SMS)-1 and -2 of host cells. The ceramide mimetic compound (1R,3S)-HPA-12 and the nonmimetic compound E16A, both of which are potent inhibitors of CERT, repressed the proliferation of C. trachomatis in HeLa cells. Unexpectedly, (1R,3R)-HPA-12, a ceramide mimetic compound that lacks CERT inhibitory activity, also exhibited potent anti-chlamydial activity. Using endogenous SMS-knockout mutant HeLa cells, we revealed that (1R,3R)-HPA-12 mildly inhibited cidSM-synthesis. In addition, LC-MS analysis revealed that (1R,3R)-HPA-12 is converted to a phosphocholine-conjugated metabolite in an infection-dependent manner. Imaging analysis with a fluorescent analog of ceramide suggested that cidSM-synthesis occurs in the bacterial bodies and/or inclusions. Collectively, these results suggested that (1R,3R)-HPA-12 exerts its anti-chlamydia activity not only as an inhibitor of cidSM-synthesis, but also via putative toxic effects of its phosphocholine adduct, which is most likely produced by the cidSM-synthesis route.

Practical method for hydroxyl-group protection using strontium metal and readily available silyl chlorides.

We have found that the etherification of silyl-protected secondary alcohols proceeds smoothly in the presence of strontium metal using silyl chloride instead of the expensive, yet more reactive, and commonly used silyl triflate. The reaction occurred almost completely with various alcohols.

Selective Hydrogenation of Nitriles to Primary Amines Catalyzed by a Polysilane/SiO2-Supported Palladium Catalyst under Continuous-Flow Conditions.

Hydrogenation of nitriles to primary amines with heterogeneous catalysts under liquid-phase continuous-flow conditions is described. Newly developed polysilane/SiO2-supported Pd was found to be an effective catalyst and various nitriles were converted into primary amine salts in almost quantitative yields under mild reaction conditions. Interestingly, a complex mixture was obtained under batch conditions. Lifetime experiments showed that this catalyst remained active for more than 300 h (TON≥10 000) without loss of selectivity and no metal leaching from the catalyst occurred. By using this continuous-flow hydrogenation, synthesis of venlafaxine, an antidepressant drug, has been accomplished.

The relationship between fear extinction and resilience to drug-dependence in rats.

Some individuals recover quickly from stressful events, while others do not; this suggests that there are individual differences in stress resilience. Previous studies in rats have shown that an animal's ability to extinguish conditioned fear can predict their stress resilience. In the present study, we investigated whether rats who are resilient or vulnerable to fear conditioning would consistently show resilient or vulnerable behaviors in other behavioral tests. Male Wistar-Imamichi rats were subjected to a series of behavioral tests, including open field, conditioned place-preference (CPP), forced swim and auditory fear conditioning. The subjects were assigned to one of two different groups: resilient or vulnerable, based on their level of freezing during fear extinction, and their other behavioral phenotypes were then compared. Rats in the resilient group showed faster extinction in the methamphetamine-induced CPP test than rats in the vulnerable group. The results suggest that resilience to stressful events is associated with drug-dependence and that individuals' abilities to recover from stressful situations and drug-dependence may share a common mechanism.

Retrieval-induced forgetting in rats.

"Retrieval-induced forgetting" in rats was evaluated using a modified spontaneous object recognition test. The test consisted of a sample phase, retrieval or interference phase, and a test phase with 60-min delay period inserted between the phases. Rats were randomly assigned to one of three groups (control, retrieval and interference) and allowed to explore the field in which two different objects (A, B) were placed in the sample phase. In the retrieval phase, two identical objects (B, B), which were the same as one of the objects presented in the sample phase, were placed again. In the interference phase, two identical objects (C, C), which were novel for animals, were placed. In the test phase, two different objects (A, D), one of which was identical to that presented in sample phase (familiar object) and the other was novel, were placed and the time spent exploring each object was analyzed. While the exploration of the novel object was significantly longer than that of the familiar object in rats subjected to the interference phase, rats subjected to the retrieval phase could not discriminate between the familiar and the novel objects at the test phase. These results demonstrate the "retrieval-induced forgetting" phenomenon in a spontaneous object recognition test in rats.

Allylation reactions of aldehydes with allylboronates in aqueous media: unique reactivity and selectivity that are only observed in the presence of water.

Zn(OH)2-catalyzed allylation reactions of aldehydes with allylboronates in aqueous media have been developed. In contrast to conventional allylboration reactions of aldehydes in organic solvents, the α-addition products were obtained exclusively. A catalytic cycle in which the allylzinc species was generated through a B-to-Zn exchange process is proposed and kinetic studies were performed. The key intermediate, an allylzinc species, was detected by HRMS (ESI) analysis and by online continuous MS (ESI) analysis. This analysis revealed that, in aqueous media, the allylzinc species competitively reacted with the aldehydes and water. An investigation of the reactivity and selectivity of the allylzinc species by using several typical allylboronates (6a-6d) clarified several important roles of water in this allylation reaction. The allylation reactions of aldehydes with allylboronic acid 2,2-dimethyl-1,3-propanediol esters proceeded smoothly in the presence of catalytic amounts of Zn(OH)2 and achiral ligand 4d in aqueous media to afford the corresponding syn-adducts in high yields with high diastereoselectivities. In all cases, the α-addition products were obtained and a wide substrate scope was tolerated. Furthermore, this reaction was applied to asymmetric catalysis by using chiral ligand 9. Based on the X-ray structure of the Zn-9 complex, several nonsymmetrical chiral ligands were also found to be effective. This reaction was further applied to catalytic asymmetric alkylallylation, chloroallylation, and alkoxyallylation processes and the synthetic utility of these reactions has been demonstrated.

Revised stereochemistry of ceramide-trafficking inhibitor HPA-12 by X-ray crystallography analysis.

In response to Berkes's report revising the stereochemistry of HPA-12, an important ceramide-trafficking inhibitor that was discovered and synthesized and its stereochemistry determined in 2001, the synthesis and the stereochemistry were reinvestigated. A large-scale synthetic method for HPA-12 based on a Zn-catalyzed asymmetric Mannich-type reaction in water was developed. Single crystals of HPA-12 for X-ray crystallographic analysis were obtained from ethyl propionate/n-hexane, and the stereochemistry was definitely determined to be 1R,3S, consistent with Berkes's revised structure.

Chiral-Sc catalyzed asymmetric Michael addition/protonation of thiols with enones in water.

Asymmetric Michael reactions and enantioselective protonations between enones and thiols were catalyzed by a Sc(OTf)(3)-chiral 2,2'-bipyridine complex in water. The remarkable governing of the enantioselectivity for simple introduction of protons despite their abnormally high mobility in water may provide us with new synthetic opportunities as well as significant chemical advances.

Bismuth catalysts in aqueous media.

Several bismuth-catalyzed synthetic reactions, which proceed well in aqueous media, are discussed. Due to increasing demand of water as a solvent in organic synthesis, catalysts that can be used in aqueous media are becoming more and more important. Although bismuth Lewis acids are not very stable in water, it has been revealed that they can be stabilized by basic ligands. Chiral amine and related basic ligands combined with bismuth Lewis acids are particularly useful in asymmetric catalysis in aqueous media. On the other hand, bismuth hydroxide is stable and works as an efficient catalyst for carbon-carbon bond-forming reactions in water.

[World constructed by self-organization of some amphiphils--with a focus on vesicle formation--].

The world constructed by self-organization of some amphiphils was discussed on the basis of micelle formation, vesicle formation, and oriented-nano-wire formation. First, the micelle formation of a both water- and oil- soluble surfactant, Aerosol OT, was discussed. Solution states of micelles and monomer were discussed on the basis of thermodinamic and NMR spectroscopic analyses of micelle formation. Next, micelle-vesicle transition was discussed. It was proposed that the phospholipid LUV formation by removing detergents and destruction by adding detergents occurred via 4 stages. The 4 stage model instead of the 3 stage model could not only elucidate the complicated phenomena observed during micelle-vesicle transition, but predicted the size and properties of the vesicles formed by detergent removal from mixed micelles. Next, the vesicle formation of a fatty acid with a single hydrophobic chain different from phospholipid, which has two hydorophobic chains, was discussed. The vesicle formation was strongly affected by the presence of preformed vesicles and the size was biased on the preformed vesicles. It was shown there exist two pass ways in the process of micelle-vesicle transition by pH jump. One is fission of the preformed vesicles after transfer of monomers from newly added oleate micelles and the other is transition from the mixed micelles after partial solubilization by the oreate micelles. Then, the vesicle formation of HCO-10, which has 3 hydrophobic chains, the mixed vesicle formation of phosphatidylethanolamine and lysophosphtidylcholine, which can not form vesicles, and the phospholipid vesicle formation and destruction by removing and adding PEG-lipid, were discussed. Lastly, oriented nano wire formation of mulamyldipeptid-conjugated lipids with ca 5 nm of diameter was discussed.

Chiral Sc-catalyzed asymmetric Michael reactions of thiols with enones in water.

Asymmetric Michael reactions of thiols with enones were catalyzed by a Sc(OTf)(3)-chiral bipyridine complex at room temperature in water without using any organic solvents, to afford the desired sulfides in high yields with high enantioselectivities.

Aldehyde allylation with allylboronates providing alpha-addition products.

Zn(OH)(2)-catalyzed allylation reactions of allylboronates with aldehydes proceeded smoothly in aqueous media; when alpha-substituted allylboronates were employed, the alpha-addition products were obtained exclusively, and syn-adducts were formed selectively in most cases; the use of Zn(OH)(2) with dmp (ligand) in aqueous media is the key to these reactions.

A gold-immobilized microchannel flow reactor for oxidation of alcohols with molecular oxygen.

Golden capillaries: A gold-immobilized capillary column reactor allows oxidation of alcohols to carbonyl compounds using molecular oxygen. These capillary columns (see picture) can be used for at least four days without loss of activity.

Catalytic use of indium(0) for carbon-carbon bond transformations in water: general catalytic allylations of ketones with allylboronates.

We have discovered the unprecedented catalytic use of In(0) for catalytic C-C bond transformations. Remarkably, these general catalytic allylations of ketones proceeded smoothly in water as a sole solvent under mild conditions, and water proved to be essential for these reactions. Both the displayed substrate scope and the functional group tolerance were excellent. Importantly, the In metal catalyst could be easily recovered and reused without loss of catalytic activity. Moreover, when an alpha-substituted allylboronate was used, an unusual constitutional selectivity was observed providing exclusively the formal alpha-adduct. Additionally, the resulting tertiary homoallylic alcohols were obtained with exceptionally high diastereoselectivities. The applicability of this concept to asymmetric catalysis in water by using In(0) combined with a chiral bis(oxazoline) ligand was demonstrated as well.

Conformational change of apolipoprotein A-I and HDL formation from model membranes under intracellular acidic conditions.

The molecular mechanism by which nascent HDL forms via the interaction of apolipoprotein A-I (apoA-I) and transmembrane ABCA1 is poorly understood. Here, because ABCA1 has been reported to localize to acidic intracellular compartments, including the Golgi and endosome, we studied the interaction of apoA-I with model membranes under acidic conditions. Pure phosphatidylcholine liposomes were persistent against apoA-I at pH levels above 5.0, but were progressively transformed into reconstituted HDLs (rHDLs) by apoA-I at lower pH. Circular dichroism spectral measurements and 8-anilino-1-naphthalenesulfonic acid fluorescence measurements of lipid-free apoA-I ascribed this accelerated rHDL formation to the conformational change of the protein into a rather hydrophobic alpha-helical structure under acidic conditions. The addition of phosphatidylserine (PS) increased acidity at the bilayer surface and enabled the formation of discoidal rHDLs even at the pH of the endosome and slightly lower pH of the Golgi. These results suggest the following new scenario of nascent HDL formation: ABCA1, which colocalizes with apoA-I in acidic intracellular compartments, including the Golgi and endosome, increases acidity at the membrane surface on the luminal side by PS translocase activity and causes apoA-I to form nascent HDL.