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Ivabradine is a heart rate (HR)-lowering agent that blocks hyperpolarization-activated cyclic nucleotide-gated channel in the sinus node without a negative inotropic effect on cardiac function. Here we report a case of catecholamine-dependent heart failure, who was intolerant to β blockers, and successfully withdrew catecholamine by administering ivabradine. A 39-year-old male acute decompensated heart failure (ADHF) patient with severe systolic cardiac failure, refractory to diuretic and dobutamine treatment was transferred to our hospital. In addition to titration of dobutamine support, intra-aortic balloon pump, mechanical ventilation, and continuous hemodiafiltration therapy were initiated. These mechanical supports could stabilize ADHF and were removed. Upon stabilization of ADHF, we attempted to initiate a low dose of bisoprolol and taper dobutamine, but the patient could not tolerate even a low dose of bisoprolol nor tapering of dobutamine. Since his HR was consistently above 100 beats per minute and ivabradine was reported to improve stroke volume (SV), we initiated ivabradine, and his SV remarkably increased after initiation. Consequently, the dose of dobutamine was successfully tapered. Also, additional clinical advantage of ivabradine, assessed through hemodynamic parameters, appeared to be a reduction in afterload. < Learning objective: Ivabradine is a heart rate (HR)-lowering agent that blocks the hyperpolarization-activated cyclic nucleotide-gated channel in the sinus node without a negative inotropic effect. In this present catecholamine-dependent advanced heart failure case, the patient could not tolerate even a low dose of bisoprolol nor tapering of dobutamine. Being intolerant to beta-blockers, we initiated the administration of ivabradine. And the initiation of ivabradine resulted in not only the reduction of HR, but also the improvement in stroke volume resulting in the reduction of afterload.> [ABSTRACT FROM AUTHOR]

Interaction between the gut microbiome and host plays a key role in human health. Here, we perform a metagenome shotgun-sequencing-based analysis of Japanese participants to reveal associations between the gut microbiome, host genetics, and plasma metabolome. A genome-wide association study (GWAS) for microbial species (n = 524) identifies associations between the PDE1C gene locus and Bacteroides intestinalis and between TGIF2 and TGIF2-RAB5IF gene loci and Bacteroides acidifiaciens. In a microbial gene ortholog GWAS, agaE and agaS , which are related to the metabolism of carbohydrates forming the blood group A antigen, are associated with blood group A in a manner depending on the secretor status determined by the East Asian-specific FUT2 variant. A microbiome-metabolome association analysis (n = 261) identifies associations between bile acids and microbial features such as bile acid metabolism gene orthologs including bai and 7β-hydroxysteroid dehydrogenase. Our publicly available data will be a useful resource for understanding gut microbiome-host interactions in an underrepresented population. [Display omitted] • Construction of Japanese multi-omics datasets (gut microbiome, plasma metabolome, host genome) • Genome-wide association analysis of the gut microbiome with 524 Japanese individuals • ABO blood type was associated with the microbial genes related to N-galactosamine metabolism • Microbiome-metabolome association analysis highlights the association involving bile acids Tomofuji et al. constructed Japanese multi-omics datasets (gut microbiome, plasma metabolome, and host genome). Their shotgun-sequencing-based gut microbiome analysis identified associations with the host genome and plasma metabolome including those involving microbial genes. Multi-omics analysis in the underrepresented population would contribute to expanding the diversity of the studied populations. [ABSTRACT FROM AUTHOR]

Highlights • We investigated activation of mirror neuron system during gait observation. • Participants were sub-acute stroke patients and healthy persons. • Activation of the mirror neuron system was observed in those participants. • Gait observation treatment may improve gait ability in sub-acute stroke patients. Abstract The observation of walking improves gait ability in chronic stroke survivors. It has also been suggested that activation of the mirror neuron system contributes to this effect. However, activation of the mirror neuron system during gait observation has not yet been assessed in sub-acute stroke patients. The objective of this study was to clarify the activation of mirror neuron system during gait observation in sub-acute stroke patients and healthy persons. In this study, we sequentially enrolled five sub-acute stroke patients who had undergone gait training and nine healthy persons. We used fMRI to detect neuronal activation during gait observation. During the observation period in the stroke group, neural activity in the left inferior parietal lobule, right and left inferior frontal gyrus was significantly higher than during the rest period. In the healthy group, neural activity in the left inferior parietal lobule, left inferior frontal gyrus, left middle frontal gyrus, left superior temporal lobule and right and left middle temporal gyrus was significantly higher than during the rest period. The results indicate that the mirror neuron system was activated during gait observation in sub-acute stroke patients who had undergone gait training and also in healthy persons. Our findings suggest that gait observation treatment may provide a promising therapeutic strategy in sub-acute stroke patients who have experienced gait training. [ABSTRACT FROM AUTHOR]

The effect of a mental health promotion program based on cognitive behavioral therapy and social-emotional learning called “You Can Do It! Education” on the resilience of elementary school students was evaluated. Participants were fourth grade students at elementary schools in the Tokyo Metropolitan Area, who were assigned to the intervention ( n = 78) or control ( n = 47) group. The intervention group was taught eight program lessons by a visiting counselor, which covered topics related to resilience and the relationships of thinking, feeling, and behaving. The intervention group showed significant improvements in resilience and social support, whereas the control group did not. We discuss the program’s feasibility for enhancing resilience and its limitations in Japanese school settings. [ABSTRACT FROM AUTHOR]

Background: Increasing attention is being paid to the left atrial appendage (LAA) in the context of risk stratification in cardioembolic stroke (CES) and the requirement for meticulous planning of percutaneous closure device implantation. However, detailed systematic assessment of the LAA remains limited.Methods: This study evaluated the anatomy and function of LAA using 3-dimensional transesophageal echocardiography (3D-TEE) on 194 consecutive patients older than 50 years old hospitalized exclusively for CES. Patients were stratified into 3 groups on the basis of cardiac rhythm: (1) chronic atrial fibrillation (AF), n = 53; (2) paroxysmal AF, n = 26; and (3) no detected AF, n = 115.Results: Significant differences between the groups were observed for anatomical (orifice area [OA], depth, diastolic volume) and functional parameters (ejection fraction [EF], flow velocity [FV]), as measured by 3D-TEE. The anatomical parameters were consistently the greatest, and functional parameters were the poorest, in the group with chronic AF. There were significant inverse correlations between them (r = -.33, P = .0003 for depth and EF; r = -.27, P = .0020 for depth and FV; r = -.22, P = .016 for OA and EF; and r = -.38, P < .0001 for OA and FV).Conclusions: LAA morphology and function were strongly affected by cardiac rhythm disturbances. Patients with chronic AF had the greatest LAA dimensions, areas, and volumes as well as the lowest LAA functions. An inverse correlation was observed between LAA size and function. [ABSTRACT FROM AUTHOR]

Abstract: CBP501 is a chemically modified peptide composed of twelve unnatural d-amino acids, which inhibits Chk kinase and abrogates G2 arrest induced by DNA-damaging agents. Here we identified an alphaC helix in 14-3-3 protein as a CBP501-binding site using T7 phage display technology. An affinity selection of T7 phage-displayed peptide using biotinylated CBP501 identified a 14-mer peptide NSDCIISRKIEQKE. This peptide sequence showed similarity to a portion of the alphaC helix of human 14-3-3ε, suggesting that CBP501 may bind to this region. Surface plasmon resonance (SPR) and ELISA demonstrated that CBP501 interacts with 14-3-3ε specifically at the screen-guided region. An avidin-agarose bead pull-down assay showed that CBP501 also binds to other 14-3-3 isoforms in Jurkat cells. Among the other known Chk kinase inhibitors tested, CBP501 showed the strongest affinity for 14-3-3ε. Thus, we conclude that in addition to the direct inhibition of Chk kinase activity, CBP501 directly binds to cellular 14-3-3 proteins through alphaC helix. [Copyright &y& Elsevier]

Abstract: The purpose of the present study is to investigate the influence of CO2 hydrate on the flow of liquid CO2 injected in the porous media. In order to clarify the influence of CO2 hydrate, differential pressure and temperature are measured under both condition of CO2 hydrate generated and not generated. As the results, in the case of the hydrate generation, it is confirmed that temperature of the test section rise. And it is identified that the differential pressure become large compared with the case of not generated. It is suggested that flow resistance arises due to choking of CO2 hydrate in the porous media. Friction factor is also compared with the Ergun’s equation which is proposed for single-phase flow in a porous media. The measured friction factor is larger than that estimated from Ergun’s equation. [Copyright &y& Elsevier]

Abstract: The object of the present study is to investigate the effect of pressure history of the water on CO2 hydrate nucleation. We measured the induction time which is the time from putting liquid CO2 droplet into the pressure chamber to forming the hydrate film to clarify the effect. Various conditions of ion-exchanged water was filled in a pressure chamber under 40 MPa and 277.6 K. In using water that had previously frozen as ice and melted at hydrate formation conditions or previously kept at hydrate formation for a long time, the hydrate formation was observed. [Copyright &y& Elsevier]

Abstract: Bicyclic dioxetanes bearing a 3-hydroxyphenyl moiety substituted with an amidomethyl group (3a–c ) or a hydroxymethyl group ( 4 ) were synthesized. On treatment with tetrabutylammonium fluoride in CH3CN, they decomposed rapidly with accompanying emission of blue light. Their decomposition rates and chemiluminescence efficiencies were found to be affected by the intramolecular hydrogen bonding between the phenoxy anion and the adjacent proton-donating group. [Copyright &y& Elsevier]

The relationship between oxidative stress and longevity is a matter of concern in various organisms. We isolated mutants resistant to peracute from nematode Caenorhabditis elegans. One mutant named mev-4 was long- lived and showed cross-resistance to heat and Dyf phenotype (defective in dye filling). Genetic and sequence analysis revealed that mev-4 had a nonsense mutation on the che-11 gene, homologues of which are involved in formation of cilia and flagella in other organisms. The peracute resistance was commonly observed in various Dyf mutants and did not depend on the daf-16 gene, whereas the extension of life span did depend on it. Expression of antioxidant enzyme genes seemed normal. These results suggest that chemosensory neurons are a target of oxidative stress and influence longevity dependent on the daf-16 signaling in C. elegants. [ABSTRACT FROM AUTHOR]

• NICE addresses limitations of cognitive-behavioral oriented school-based programs. • NICE promotes interpersonal relationships between teachers and young students. • NICE supports the bottom-up regulation of cognitive abilities. • NICE was offered as a brief program or an information intervention. • NICE enhanced students' perceived social support and prosocial behaviors. Social innovation in mental health education is imperative in Japan. Mental health problems such as depression and anxiety disorders among Japanese children that may compromise their education and future occupational performances have become prevalent. Accordingly, the early prevention of mental health problems with cognitive-behavioral oriented Social and Emotional Learning (SEL) programs, which have mostly been developed in western countries, have been implemented. However, studies have revealed that cognitive-behavioral oriented programs tend to have limited efficacies within the Japanese context due to culturally unique challenges such as low confidence and time and resource constraints. Research in neuroscience has found that cognitive oriented top-down approaches that focus on cognitive change predominantly may not be developmentally appropriate for Japanese children. Consequently, the efficacy and feasibility of a neuroscience-informed child education (NICE) program was developed and examined in this study to address the demands of the Japanese school context by integrating neuroscientific perspectives into a cognitive-behavioral oriented school-based SEL program. Teachers and first-grade students (6–7 years old) were divided into two groups. In the program group, teachers conducted an eight-session NICE program during 20-minute after-class periods. In the information group, teachers applied the approach and skills in daily class management. While the students completed questionnaires regarding their class adjustment and social support awareness at three-time points, the teachers assessed students' behaviors, including difficulties and prosocial behavior. The results supported the efficacy of the NICE program for promoting psychological well-being and increasing social support awareness and prosocial behaviors among Japanese students. [ABSTRACT FROM AUTHOR]

• Provenance study reveals that the Higher Himalayan Crystallines (HHC) supplied detritus to the Lower Siwalik sub-group. • Detrital staurolite and Mg-rich garnets appeared in the Lower Siwalik sub-group at 13–10 Ma in western and central Nepal. • Regional-scale denudation of the HHC rocks accompanied by an out-of-sequence thrust activity occurred at 13–10 Ma. • Denudation and exposure of the HHC rock progressed from the west toward east in the Central Himalaya. The Middle Miocene to Early Pleistocene Siwalik Group is composed of sediments deposited in the Himalayan foreland basin. In this study, the heavy mineral assemblage and chemical composition of detrital garnets from the sandstones in the Lower Siwalik sub-group, which are exposed along the Karnali River in western Nepal and the Tinau Khola in central Nepal, are studied and the provenance shift during the Middle Miocene is discussed. The heavy mineral assemblage in the lower section of the Lower Siwalik sub-group is characterized as predominantly zircon-tourmaline-rutile. Chemical analysis of the detrital garnets showed a monomodal almandine-rich composition with low pyrope (Prp <10) and moderate grossular (Grs 10-20) content. The composition pattern subsequently changed to a bimodal distribution with an increase in pyrope (Prp 10-25) and low grossular (Grs <10) content with the appearance of detrital staurolite. These results indicate that the Middle Miocene erosion of the Higher Himalayan Crystallines (HHC) are the source of the deposits in the Siwalik Group. Changes in the heavy mineral assemblage and garnet composition are recognized in the Karnali River section at 14–12 Ma and in the Tinau Khola section at 11–10 Ma, which suggests that the denudation of the HHC progressed from west to east in the western and central Nepal Himalayas. [ABSTRACT FROM AUTHOR]

• The transcription-reverse transcription concerted (TRC) method for Mycobacterium avium-intracellulare complex can consistently identify M. chimaera as M. intracellulare. • A clinical isolate identified as M. intracellulare by polymerase chain reaction did not react to TRC. • The 16S ribosomal RNA sequencing failed to precisely identify the isolate. • Whole-genome shotgun sequencing and average nucleotide identity analysis led to the identification as M. chimaera. • Mutations in 16S ribosomal RNA gene could have caused the false-negative reaction to TRC. To report an isolate of Mycobacterium intracellulare subsp. chimaera with multiple mutations in 16S ribosomal RNA (rRNA) gene, resulting in the false-negative reaction to the transcription-reverse transcription concerted (TRC) method for Mycobacterium avium-intracellulare complex. We used TRC, polymerase chain reaction (PCR), and Matrix-assisted laser desorption/ionization Time-of-Flight/Mass Spectrometry (MALDI-TOF/MS) methods to identify a clinical isolate in 2021. Due to the discordant results between TRC and PCR or MALDI-TOF MS methods, 16S rRNA sequencing, whole-genome shotgun (WGS) sequencing, and average nucleotide identity (ANI) analysis were employed to identify the isolate. A mycobacterial isolate from a sputum sample gave negative results for the detection of Mycobacterium tuberculosis complex or M. avium-intracellulare complex by the TRC method. However, the isolate was identified as M. intracellulare by both PCR method and MALDI-TOF MS method. WGS sequencing of 16S rRNA genome revealed eight substitution mutations and one insertion mutation within the region, which could hamper the correct reaction to TRC method. Subsequent ANI analysis between the isolate and various species of nontuberculosis mycobacteria revealed that the isolate could be identified as M. intracellulare subsp. chimaera. Rare mutations within the 16S rRNA genome resulted in the false-negative identification of Mycobacterium chimaera by the TRC method. WGS sequencing and ANI analysis was necessary to identify the isolate. [ABSTRACT FROM AUTHOR]

Abstract: In cattle, bovine leukocyte antigens (BoLAs) have been extensively used as markers for bovine diseases and immunological traits. In this study, we sequenced alleles of the BoLA class II loci, BoLA-DRB3 and BoLA-DQA1, from 650 Japanese cattle from six herds [three herds (507 animals) of Japanese Black cattle and three herds (143 animals) of Holstein cattle] using polymerase chain reaction-sequence-based typing (PCR-SBT) methods. We identified 26 previously reported distinct DRB3 alleles in the two populations: 22 in Japanese Black and 17 in Holstein. The number of DRB3 alleles detected in each herd ranged from 9 to 20. Next, we identified 15 previously reported distinct DQA1 alleles: 13 in Japanese Black and 10 in Holstein. The number of alleles in each herd ranged from 6 to 10. Thus, allelic divergence is significantly greater for DRB3 than for DQA1. A population tree on the basis of the frequencies of the DRB3 and DQA1 alleles showed that, although the genetic distance differed significantly between the two cattle breeds, it was closely related within the three herds of each breed. In addition, Wu–Kabat variability analysis indicated that the DRB3 gene was more polymorphic than the DQA1 gene in both breeds and in all herds, and that the majority of the hypervariable positions within both loci corresponded to pocket-forming residues. The DRB3 and DQA1 heterozygosity for both breeds within each herd were calculated based on the Hardy–Weinberg equilibrium. Only one Japanese Black herd showed a significant difference between the expected and observed heterozygosity at both loci. This is the first report presenting a detailed study of the allelic distribution of BoLA-DRB3 and -DQA1 genes in Japanese Black and Holstein cattle from different farms in Japan. These results may help to develop improved livestock breeding strategies in the future. [ABSTRACT FROM AUTHOR]

Abstract: Four bicyclic dioxetanes bearing a 4-(benzothiazol-2-yl)-3-hydroxyphenyl or 4-(benzoxazol-2-yl)-3-hydroxyphenyl group were synthesized. These dioxetanes underwent base-induced decomposition with accompanying emission of light with high efficiency in NaOH/H2O as well as in tetrabutyl ammonium fluoride (TBAF)/acetonitrile. Among them, benzothiazol-analogs decomposed faster in the aqueous solution than in acetonitrile. [Copyright &y& Elsevier]

Recently, we documented two Japanese cases of myelin-oligodendrocyte glycoprotein (MOG) antibody-associated relapsing encephalitis among patients who had been diagnosed with probable neuro-Behçet's disease (NBD). They presented partial systemic BD symptoms, brainstem lesions, and the human leukocyte antigen (HLA) B51 allele and responded well to steroid therapy. Our cases suggest that we need to differentiate anti-MOG antibody-associated encephalitis from probable NBD because both disorders can present with brainstem or cerebral lesions, CSF pleocytosis, and elevated levels of CSF IL-6 and respond to steroid treatment. Furthermore, oral ulceration, skin lesions, and HLA-B51 might be observed nonspecifically in patients with anti-MOG antibody-associated encephalitis. Unlabelled Image • Anti-MOG antibody-associated encephalitis can mimic neuro-Behçet's disease. • Neuroimaging and CSF findings can be similar between these disorders. • The HLA B51 allele can be positive in anti-MOG antibody-associated encephalitis. • Detection of anti-MOG antibodies is necessary to differentiate these two disorders. [ABSTRACT FROM AUTHOR]

Purpose: We developed a novel method which is applicable to visualize contrast according to myelin components in the human brain using relaxation time derived from quantitative parameter mapping magnetic resonance imaging (QPM-MRI).Materials and Methods: Using healthy volunteer data (n = 10), we verified that our method demonstrated that the myelin-weighted contrast increased proportionally by products R1 and R2*, i.e., QPM-myelin-weighted image, in which modified T1-weighted/T2-weighted (T1w/T2w) ratio mapping method was applied. We compared measurement values in white matter (WM) and gray matter (GM) regions of the T1w/T2w ratio and R1·R2* product maps of healthy volunteers. Linear regression analysis between each value. Mann Whitney U test between WM and GM signals in each myelin map. In addition, Additionally, QPM-myelin-weighted image was applied to a 32-year-old female MS patient.Results: Linear regression analysis showed a highly significant correlation between conventional T1w/T2w ratios and R1·R2* products derived from QPM (R = 0.73, P < 0.0001). Moreover, there is a significant difference between WM and GM structures in each myelin images (both, P < 0.0001). Additionally, in a clinical case, MS lesions enabled observation of not only MS plaques but also heterogeneous myelin signal loss associated with demyelination more clearly than T2w image and conventional T1w/T2w ratio image.Conclusion: Our myelin-weighted imaging technique using QPM may be useful for myelin visualization and is expected to become independent of measurement conditions due to having quantitative characteristics of QPM itself. [ABSTRACT FROM AUTHOR]

Our research found that the 2-hydroxyacetophenone derivative is an outstanding linker between the 1,1-bistrifluoromethylcarbinol moiety and the imidazolidine-2,4-dione moiety to enhance the potency and β-selectivity of liver X receptor (LXR) agonist in our head-to-tail molecular design. The incorporation of this linker is 20-fold more potent than our previous compound ( 2 ) for LXR β agonistic activity (EC 50 ) in a GAL-4 luciferase assay. Furthermore, we also identified 5-[5-(1-methylethoxy)pyridyl-2-yl]-5-methylimidazoline-2,4-dione ( 54 ), which lowers the lipophilicity of 2-hydroxyacetophenone derivative. We revealed that a combination of our newly developed linker and hydantoin ( 54 ) plays a pivotal role in improving the potency and selectivity of LXRβ. The optically separated (−)- 56 increases high-density lipoprotein cholesterol levels without elevating plasma triglyceride levels and results in a decrease of the lipid accumulation area in the aortic arch in a high-fat- and cholesterol-fed low-density lipoprotein receptor knock-out mice. In this manuscript, we report that (−)- 56 is a highly potent and β-selective LXR agonist for use in the treatment of atherosclerosis. [ABSTRACT FROM AUTHOR]

Decomposition of aqueous monofluorophenols (MFPs) was investigated by contact glow discharge electrolysis (CGDE). During CGDE, both MFPs and the corresponding total organic carbon (TOC) in water were consumed smoothly, suggesting that carbon atoms of benzene nucleus could be eventually mineralized to inorganic carbon (IC). And all the fluorine atoms in the MFPs were equally converted to fluoride ions. Based on the primary intermediates from each starting materials, it showed that aromatic hydroxylation preferentially occurred at the para- or ortho- position to the phenolic OH group of each MFPs. The disappearance of both MFPs and TOC followed the first-order rate law. The apparent rate constants for the decay of MFPs were independent from the p K a values of MFPs. [ABSTRACT FROM AUTHOR]

Abstract: In cattle, bovine leukocyte antigens (BoLAs) have been extensively used as markers for diseases and immunological traits. However, none of the highly adapted Latin American Creole breeds have been characterized for BoLA gene polymorphism by high resolution typing methods. In this work, we sequenced exon 2 of the BoLA class II DRB3 gene from 179 cattle (113 Bolivian Yacumeño cattle and 66 Colombian Hartón del Valle cattle breeds) using a polymerase chain reaction sequence-based typing (PCR-SBT) method. We identified 36 previously reported alleles and three novel alleles. Thirty-five (32 reported and three new) and 24 alleles (22 reported and two new) were detected in Yacumeño and Hartón del Valle breeds, respectively. Interestingly, Latin American Creole cattle showed a high degree of gene diversity despite their small population sizes, and 10 alleles including three new alleles were found only in these two Creole breeds. We next compared the degree of genetic variability at the population and sequence levels and the genetic distance in the two breeds with those previously reported in five other breeds: Holstein, Japanese Shorthorn, Japanese Black, Jersey, and Hanwoo. Both Creole breeds presented gene diversity higher than 0.90, a nucleotide diversity higher than 0.07, and mean number of pairwise differences higher than 19, indicating that Creole cattle had similar genetic diversity at BoLA-DRB3 to the other breeds. A neutrality test showed that the high degree of genetic variability may be maintained by balancing selection. The FST index and the exact G test showed significant differences across all cattle populations (FST =0.0478; p<0.001). Results from the principal components analysis and the phylogenetic tree showed that Yacumeño and Hartón del Valle breeds were closely related to each other. Collectively, our results suggest that the high level of genetic diversity could be explained by the multiple origins of the Creole germplasm (European, African and Indicus), and this diversity might be maintained by balancing selection. [Copyright &y& Elsevier]

Abstract: Perfluorooctane sulfonate (PFOS) is a pollutant widely found throughout nature and is toxic to animals. We created a PFOS analogue on a polyethylene glycol polyacrylamide copolymer and isolated peptides that preferentially bound the PFOS analogue using a T7 phage display system. Bioinformatic analysis using the FASTAskan program on the RELIC bioinformatics server showed several human proteins that likely bound PFOS. Among them, we confirmed binding between PFOS and a recombinant soluble form of monocyte differentiation antigen CD14 (sCD14) by a surface plasmon biosensor. Furthermore, PFOS inhibited TNF-α production induced by the sCD14 in mouse macrophage RAW264.7 cells. [Copyright &y& Elsevier]

Abstract: Camptothecin (CPT) is an anti-tumor natural product that forms a ternary complex with topoisomerase I (top I) and DNA (CPT-top I-DNA). In this study, we identified the direct interaction between CPT and human heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) using the T7 phage display technology. On an avidin-agarose bead pull down assay, hnRNP A1 protein was selectively pulled down in the presence of C20-biotinylated CPT derivative (CPT-20-B) both in vitro and in vivo. The interaction was also confirmed by an analysis on a quartz-crystal microbalance (QCM) device, yielding a K D value of 82.7nM. A surface plasmon resonance (SPR) analysis revealed that CPT inhibits the binding of hnRNP A1 to top I (K D: 260nM) in a non-competitive manner. Moreover, an in vivo drug evaluation assay using Drosophila melanogaster showed that the knockout of the hnRNP A1 homolog Hrb87F gene showed high susceptibility against 5–50μM of CPT as compared to a wild-type strain. Such susceptibility was specific for CPT and not observed after treatment with other cytotoxic drugs. Collectively, our data suggests that CPT directly binds to hnRNP A1 and non-competitively inhibits the hnRNP A1/top I interaction in vivo. The knockout strain loses the hnRNP A1 homolog as a both CPT-binding partner and naïve brakes of top I, which enhances the formation of the CPT-top I-DNA ternary complexes and subsequently sensitizes the growth inhibitory effect of CPT in D. melanogaster. [Copyright &y& Elsevier]

Abstract: Urinary 8-OH-dG is commonly analyzed as a marker of oxidative stress. For its analysis, ELISA and HPLC methods are generally used, although discrepancies in the data obtained by these methods have often been discussed. To clarify this problem, we fractionated human urine by reverse-phase HPLC and assayed each fraction by the ELISA method. In addition to the 8-OH-dG fraction, a positive reaction was observed in the first eluted fraction. The components in this fraction were examined by the ELISA. Urea was found to be the responsible component in this fraction. Urea is present in high concentrations in the urine of mice, rats, and humans, and its level is influenced by many factors. Therefore, certain improvements, such as a correction based on urea content or urease treatment, are required for the accurate analysis of urinary 8-OH-dG by the ELISA method. In addition, performance of the ELISA at 4°C reduced the recognition of urea considerably and improved the 8-OH-dG analysis. [Copyright &y& Elsevier]

Abstract: Here, we report on the identification of trimannoside-recognizing peptide sequences from a T7 phage display screen using a quartz-crystal microbalance (QCM) device. A trimannoside derivative that can form a self-assembled monolayer (SAM) was synthesized and used for immobilization on the gold electrode surface of a QCM sensor chip. After six sets of one-cycle affinity selection, T7 phage particles displaying PSVGLFTH (8-mer) and SVGLGLGFSTVNCF (14-mer) were found to be enriched at a rate of 17/44, 9/44, respectively, suggesting that these peptides specifically recognize trimannoside. Binding checks using the respective single T7 phage and synthetic peptide also confirmed the specific binding of these sequences to the trimannoside-SAM. Subsequent analysis revealed that these sequences correspond to part of the primary amino acid sequence found in many mannose- or hexose-related proteins. Taken together, these results demonstrate the effectiveness of our T7 phage display environment for affinity selection of binding peptides. We anticipate this screening result will also be extremely useful in the development of inhibitors or drug delivery systems targeting polysaccharides as well as further investigations into the function of carbohydrates in vivo. [Copyright &y& Elsevier]

Abstract: A series of diazepinylbenzoic acid derivatives were synthesized and tested in the inhibition assay of the transactivation of RXR. Oral treatment of cyano derivatives (16f) was found to show anti-diabetic and anti-obesity effects in KK-Ay mice. [Copyright &y& Elsevier]

[Display omitted] • A nucleophilic addition/ring contraction of α-bromo N -iminolactam was developed. • A variety of Grignard and organolithium reagents were utilized. • A series of the 2-acyl pyrrolidines were synthesized in one-pot procedure. • The 2-acyl pyrrolidine products can be transformed into other useful compounds. A sequential nucleophilic addition/ring contraction of α-bromo N -iminolactam with organometallic reagents for the synthesis of 2-acyl pyrrolidines has been developed. The reaction allows facial construction of 2-acyl pyrrolidines incorporating not only aryl and heteroaryl groups, but alkenyl, alkynyl, and alkyl groups. Moreover, 2-acyl pyrrolidine products can be further transformed into the pyrrolidinyl alcohol, epoxide, β-lactam, and pyrazole. [ABSTRACT FROM AUTHOR]