(2-Aryl-5-methylimidazol-4-ylcarbonyl)guanidines and (2-aryl-5-methyloxazol-4-ylcarbonyl)guanidines as NHE-1 inhibitors

A series of (2-aryl-5-methylimidazol-4-ylcarbonyl)guanidines and (2-aryl-5-methyloxazol-4-ylcarbonyl)guanidines were synthesized and evaluated as NHE-1 inhibitors. The structure–activity relationships well matched those of furan derivatives, which were previously investigated. The (2,5-disubstituted)phenyl compounds showed better activities than the other analogues in both imidazole and oxazole compounds. Especially, 2-(2,5-dichlorophenyl)imidazole 52, and 2-(2-methoxy-5-chlorophenyl)imidazole 54 compounds exhibited potent cardioprotective efficacy both in vitro and in vivo as well as high NHE-1 inhibitory activities.     

A hybrid model for erythrocyte membrane: a single unit of protein network coupled with lipid bilayer

To investigate the nanomechanics of the erythrocyte membrane we developed a hybrid model that couples the actin-spectrin network to the lipid bilayer. This model features a Fourier space Brownian dynamics model of the bilayer, a Brownian dynamics model of the actin protofilament, and a modified wormlike-chain model of the spectrin (including a cable-dynamics model to predict the oscillation in tension). This model enables us to predict the nanomechanics of single or multiple units of the protein network, the lipid bilayer, and the effect of their interactions. The present work is focused on the attitude of the actin protofilament at the equilibrium states coupled with the elevations of the lipid bilayer through their primary linkage at the suspension complex in deformations. Two different actin-spectrin junctions are considered at the junctional complex. With a point-attachment junction, large pitch angles and bifurcation of yaw angles are predicted. Thermal fluctuations at bifurcation may lead to mode-switching, which may affect the network and the physiological performance of the membrane. In contrast, with a wrap-around junction, pitch angles remain small, and the occurrence of bifurcation is greatly reduced. These simulations suggest the importance of three-dimensional molecular junctions and the lipid bilayer/protein network coupling on cell membrane mechanics.     

Enhancement of YD spin relaxation by the CaMn4 cluster in photosystem II detected at room temperature: A new probe for the S-cycle

The long-lived, light-induced radical Y_D^• of the Tyr161 residue in the D2 protein of Photosystem II (PSII) is known to magnetically interact with the CaMn₄ cluster, situated ∼ 30 Å away. In this study we report a transient step-change increase in Y_D^• EPR intensity upon the application of a single laser flash to S₁ state-synchronised PSII-enriched membranes from spinach. This transient effect was observed at room temperature and high applied microwave power (100 mW) in samples containing PpBQ, as well as those containing DCMU. The subsequent decay lifetimes were found to differ depending on the additive used. We propose that this flash-induced signal increase was caused by enhanced spin relaxation of Y_D^• by the OEC in the S₂ state, as a consequence of the single laser flash turnover. The post-flash decay reflected S₂ → S₁ back-turnover, as confirmed by their correlations with independent measurements of S₂ multiline EPR signal and flash-induced variable fluorescence decay kinetics under corresponding experimental conditions. This flash-induced effect opens up the possibility to study the kinetic behaviour of S-state transitions at room temperature using Y_D^• as a probe.     

Lack of association between AQP4 polymorphisms and risk of inflammatory demyelinating disease in a Korean population

Multiple sclerosis (MS) and neuromyelitis optica (NMO) are demyelinating autoimmune inflammatory diseases that affect the central nervous system (CNS). Previous genome-wide or candidate gene studies have suggested that genetic variants might be associated with the risk of MS or NMO. Aquaporin 4 (AQP4) is a commonly distributed water channel in astrocytes of the CNS, and its expression is decreased in NMO lesions due to astrocyte cytotoxicity. Previous studies have suggested the associations of AQP4 single nucleotide polymorphisms (SNPs) with MS and/or NMO. However, there have been few replication studies in various ethnic populations. This study, as the first of its kind performed in an Asian population, investigated associations of AQP4 SNPs with the risk of inflammatory demyelinating disease (IDD), including MS and NMO, in a Korean population. A total of seven common AQP4 SNPs were selected based on status of linkage disequilibrium (LD), and then genotyped in 178 IDD cases (79 MS and 99 NMO patients) and 237 normal controls. Statistical analyses showed no significant associations between AQP4 SNPs/haplotypes and development of IDD, including MS and NMO (P > 0.05). Further replications in larger cohorts and other ethnic groups are needed.     

Inactivation of Listeria monocytogenes in brine and saline by alternating high-voltage pulsed current

The inactivating efficiency of alternating high-voltage pulsed (AHVP) current was investigated in brine (20 w/v% NaCl) and saline (0.9 w/v% NaCl) inoculated with 1x 107 cells/ml of Listeria monocytogenes. AHVP current at 12 V with 1 pulse completely inactivated L. monocytogenes in brine within 3 ms, while the bacteria in saline were fully inactivated by 10-pulsed electric treatment at 12 V within the same time. Electron microscopic observation demonstrated substantial structural damage of electrically treated L. monocytogenes in brine. These results suggest that AHVP treatment would be effective for the rapid and complete inactivation of L. monocytogenes in brine or saline solution.     

Complete Genome Sequence of Human Respiratory Syncytial Virus Genotype A with a 72-Nucleotide Duplication in the Attachment Protein G Gene

The complete genome sequence of human respiratory syncytial virus genotype A (HRSV-A) with a 72-nucleotide duplication in the C-terminal part of the attachment protein G gene was determined and analyzed. The genome was 15,277 bp in length, and 0.46 to 6.03% variations were identified at the nucleotide level compared with the previously reported complete genome of HRSV-A. Characterization of the genome will improve understanding of the diversity of the HRSV-A major antigens and enable an in-depth analysis of its genetics.     

Associations between the FAS ?670?A/G and ?1,377?G/A polymorphisms and susceptibility to autoimmune rheumatic diseases: a meta-analysis

The aim of this study was to explore whether FAS ?670?A/G and ?1,377?G/A polymorphisms confer susceptibility to autoimmune rheumatic diseases. A meta-analysis was conducted on the associations between the FAS ?670?A/G and ?1,377?G/A polymorphisms and autoimmune rheumatic diseases using allele contrast, a recessive model, a dominant model, and an additive model. Thirteen articles with 21 comparison studies (16 on FAS ?670?A/G and 5 on ?1,377?G/A polymorphisms) including systemic lupus erythematosus (SLE), four systemic sclerosis, four Sjogren’s syndrome, three rheumatoid arthritis (RA), one juvenile idiopathic arthritis, and one spondyloarthropathy were available for the meta-analysis. Meta-analysis revealed an association between rheumatic diseases and the FAS ?670?A/G polymorphism in the dominant model (odds ratio [OR]?=?0.761, 95?% confidence interval [CI]?=?0.621–0.932, p?=?0.008]. Stratification by ethnicity indicated an association between the FAS ?670?G allele carrier and rheumatic diseases in Asian (OR?=?0.569, 95?% CI?=?0.409–0.791, p?=?0.001). Furthermore, stratification by disease indicated an association between the FAS ?670?G allele carrier and SLE and RA (OR?=?0.578, 95?% CI?=?0.358–0.934, p?=?0.025; OR?=?0.609, 95?% CI?=?0.398–0.934, p?=?0.023, respectively). The FAS ?670?G allele was negatively associated with SLE susceptibility. Meta-analysis of the FAS ?1,377?G/A polymorphism stratified by disease showed an association between the FAS ?1,377 A allele and SLE (OR?=?0.783, 95?% CI?=?0.613–0.997, p?=?0.047). Meta-analyses using the dominant model also showed a significant association in SLE (OR?=?0.712, 95?% CI?=?0.528–0.961, p?=?0.027). This meta-analysis demonstrates that the FAS ?670?A/G polymorphism confers susceptibility to rheumatic diseases in Asians and SLE and RA, and the FAS ?1,377?G/A polymorphism is associated with SLE susceptibility.