Kinetics of Anti-SARS-CoV-2 Antibody Response Following Two Doses of the BNT162b2 mRNA Vaccine: A Japanese Single-Center Primary Care Clinic Report Involving Volunteers and Patients with Autoimmune Disease.

Despite the promising effectiveness of the coronavirus disease 2019 vaccination using an mRNA vaccine, the short efficacy duration and some poor responses to the vaccination remain major concerns. We aimed to clarify the monthly kinetics of the anti-SARS-CoV-2 spike receptor-binding domain antibody response after two doses of the BNT162b2 vaccine in a Japanese population. A chemiluminescent enzyme immunoassay (CLIA) and an enzyme-linked immunosorbent assay were used to measure the antibody levels in 81 Japanese adults (age, <65 years). The antibody levels increased 10-fold at 2−3 weeks following the second dose of BNT162b2 and declined thereafter to approximately 50%, 20%, and 10% of the peak levels at 2, 3, and 6 months, respectively. To compare the antibody titers among different groups, older adults (age, >65 years; n = 38) and patients with systemic lupus erythematosus (SLE, n = 14) were also investigated. A decline in the mean relative antibody titers was observed in older men compared with younger men and in patients with SLE compared with individuals aged <65 years. Although the antibody levels increased drastically following two BNT162b2 doses, they then declined rapidly. Furthermore, poor responders to the vaccination were observed. Repeated vaccinations are required to maintain high antibody levels.

Synthesis and surface activity of photoresponsive hybrid surfactants containing both fluorocarbon and hydrocarbon chains.

HYPOTHESIS: Hybrid surfactants containing both alkyl and fluoroalkyl chains within the same molecule where modification of the azobenzene group will enable us to switch the superhydrophobic nature with an external light source, and the optical behavior will vary depending on the structure of the hydrophobic chains. EXPERIMENTS: Surface activity and its optically-induced variation of the azobenzene-modified hybrid surfactants were characterized using the surface tensiometry, UV-vis and NMR spectroscopy and theoretical calculation. FINDINGS: The hybrid surfactants are superhydrophobic in nature reducing the surface tension of water to near 20 mN/m. Photo-isomerization of the azobenzene group induces a drastic surface tension variation (Δγ), and particularly the compositions containing the octyl-fluorocarbon chain exhibit remarkable Δγ as much as 30 mN/m which is even higher than that of the conventional surfactants (Δγ ≈ 14-20 mN/m). Theoretical calculation suggests significantly higher hydrophilicity of the cis isomer, causing the drastic switch in the surface activity. These results indicate the promise of the hybrid surfactants as efficient surface/interface manipulators.

First report of KPC-2 Carbapenemase-producing Klebsiella pneumoniae in Japan.

We investigated a novel Japanese isolate of sequence type 11 (ST11), the Klebsiella pneumoniae carbapenemase-2 (KPC-2)-producing K. pneumoniae strain Kp3018, which was previously obtained from a patient treated at a Brazilian hospital. This strain was resistant to various antibiotic classes, including carbapenems, and harbored the gene blaKPC-2, which was present on the transferable plasmid of ca. 190 kb, in addition to the blaCTX-M-15 gene. Furthermore, the ca. 2.3-kb sequences (ISKpn8-blaKPC-2-ISKpn6-like), encompassing blaKPC-2, were found to be similar to those of K. pneumoniae strains from China.

Inheritance patterns of lateral dimorphism examined through breeding experiments in Tanganyikan cichlid (Julidochromis transcriptus) and Japanese Medaka (Oryzias latipes).

The asymmetry of mouth morphology, in which the mouth opens either leftward or rightward, is a unique example of antisymmetry that is widely found in fishes, such as Tanganyikan scale-eating cichlids, herbivorous cichlids, and the Japanese freshwater goby. This dimorphism is thought to be heritable in a Mendelian manner similar to that of the dominance of the lefty allele over righty, with homozygotes of lefty alleles being absent. This study aims to reveal whether this trait is inherited in the same Mendelian manner in fishes other than those examined to date, and whether the absence of the dominant homozygote is due to a lethal effect. We conducted F(1) and F(2) breeding experiments using the Tanganyikan cichlid Julidochromis transcriptus and Japanese medaka Oryzias latipes. For both J. transcriptus and O. latipes, the F(1) generations produced by incrossing lefty parents showed a lefty:righty ratio of 2:1, whereas incrosses of righties produced only righty offspring. Test crosses between lefty and righty produced a 1:1 ratio of lefty and righty offspring. These results are consistent with the inheritance model in which righty is homozygous for a recessive righty allele and lefty is heterozygous for dominant lefty and recessive righty alleles, in agreement with previous observations. The F(2) test cross also confirmed this pattern. Furthermore, no lethal effects on hatchability of O. latipes were detected, refuting the suggestion that the dominant homozygote is embryonic lethal. We conclude that mouth laterality is inherited in the same Mendelian manner in these two species, similar to that other fish species studied previously. However, the reason for absence of the dominant homozygote remains unclear.

Compound and digenic heterozygosity in desmosome genes as a cause of arrhythmogenic right ventricular cardiomyopathy in Japanese patients.

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a hereditary disorder mostly caused by desmosome gene mutations. Recent comprehensive desmosome mutation analyses of Caucasian ARVC patients have revealed the presence of not only a single heterozygous mutation, but also compound and digenic heterozygosity. However, the genetic basis of Japanese ARVC remains poorly elucidated. METHODS AND RESULTS: The subjects were 7 definite and 1 possible ARVC probands (6 males, 16-76 years of age), and their family members. Genetic screening for major ARVC-causing genes (junction plakoglobin, desmoplakin, plakophilin-2 (PKP2), desmoglein-2 (DSG2), and desmocollin-2) was performed. We identified 3 cases of compound heterozygosities (Case 1: DSG2 S194L and DSG2 R292C; Case 2: PKP2 2489+1G>A and PKP2 D812N; Case 3: PKP2 M565R and PKP2 D812N) and 1 of digenic heterozygosity (Case 4: PKP2 1728_1729insGATG and DSG2 R292C) among the definite ARVC patients. All family members we investigated have remained asymptomatic. They carried, if any, only a single variant, indicating that the probands carry in trans compound heterozygosity. These results suggest that each of these variants alone may not be sufficient and second variants may be required to manifest overt ARVC in Japanese patients. CONCLUSIONS: Our comprehensive genetic analysis of desmosome genes identified 3 cases of compound heterozygosities in trans and 1 of digenic heterozygosity among 7 definite Japanese ARVC patients, providing novel insights into the genetic basis of Japanese ARVC.

Serum syndecan-4 is a novel biomarker for patients with chronic heart failure.

BACKGROUND: Syndecan-4 is a transmembrane heparan sulfate-carrying glycoprotein that mediates signal transduction pathways activated by growth factors and cell surface receptors, thereby modulating tissue regeneration, angiogenesis, and focal adhesion. The aim of the present study was to determine the clinical use of serum syndecan-4 concentration for diagnosis of heart failure. METHODS: Concentration of serum syndecan-4 and other biomarkers of heart failure was measured in 45 patients with heart failure and 21 healthy subjects. Clinical and echocardiographic parameters of cardiac function were recorded. RESULTS: Serum syndecan-4 concentration significantly increased in proportion to the decrease in ejection fraction (r=-0.599, p<0.001) and increase in the left ventricular (LV) mass index (r=0.315, p<0.05). Serum syndecan-4 concentration was significantly correlated with LV geometrical parameters (i.e. LV mass index, LV end-diastolic volume, and LV dimension), while B-type natriuretic peptide (BNP) was significantly correlated with pressure-related parameters [i.e. early transmitral flow velocity/early diastolic velocity of the mitral valve annulus (E/e'), right ventricular systolic pressure, and left atrial volume index]. Syndecan-4 concentration did not significantly correlate with plasma BNP, transforming growth factor-1, matrix metalloproteinase-2, and tenascin-C concentrations. Serum syndecan-4 concentration could predict cardiac death and re-hospitalization due to heart failure (area under curve, 0.706, p<0.05). CONCLUSION: Serum syndecan-4 concentration shows promise as a novel diagnostic and prognostic biomarker for heart failure. Since syndecan-4 correlated with LV geometrical rather than hemodynamic parameters, serum syndecan-4 may represent a biomarker of LV remodeling in the failing heart.

Multiple spontaneous coronary artery ruptures and cardiac tamponade in vascular Ehlers-Danlos syndrome.

We report a case of a 45-year-old woman with Ehlers-Danlos syndrome (EDS) type IV, the vascular type, who presented with multiple coronary artery ruptures causing cardiac tamponade. She had sudden onset of chest pain soon after transarterial embolization for right carotid-cavernous fistula. Transthoracic echocardiography confirmed cardiac tamponade and hypokinetic inferolateral wall. Enhanced CT and transesophageal echocardiography ruled out aortic dissection. Coronary angiography showed contrast extravasation from multiple sites of the right coronary artery and left circumflex coronary artery. We suspected EDS type IV, and a skin biopsy for DNA and RNA analysis was done after taking written informed consent. Polymerase chain reaction (PCR) and sequencing of the PCR product showed a heterozygous missense mutation of codon 85 in the COL3A1 gene, which converted glycine to aspartic acid, and thus a diagnosis of EDS type IV was established. To our best knowledge, this is the first case of EDS type IV causing multiple coronary artery ruptures.

The seabed-like appearance of atherosclerotic plaques: three-dimensional transesophageal echocardiographic images of the aortic arch causing cholesterol crystal emboli.

Cholesterol crystal embolism (CCE) is a rare but important complication of endovascular procedures or anticoagulation therapy. An 84-year-old man was referred to the Gunma University Graduate School of Medicine with the diagnosis of acute myocardial infarction. After successful emergency coronary angioplasty, his serum creatinine level increased continuously. A subsequent skin biopsy confirmed that the patient had CCE. Transesophageal echocardiography (TEE) clearly demonstrated the mobile mass protruding from the complex atheroma. Three-dimensional TEE provides more precise and attractive volumetric images of the atherosclerotic plaque than two-dimensional TEE. In addition, the findings of this case revealed contrast media-induced nephropathy and CCE as possible causes of renal dysfunction after endovascular procedures.

Identification of the zebrafish ventral habenula as a homolog of the mammalian lateral habenula.

The mammalian habenula consists of the medial and lateral habenulae. Recent behavioral and electrophysiological studies suggested that the lateral habenula plays a pivotal role in controlling motor and cognitive behaviors by influencing the activity of dopaminergic and serotonergic neurons. Despite the functional significance, manipulating neural activity in this pathway remains difficult because of the absence of a genetically accessible animal model such as zebrafish. To address the level of lateral habenula conservation in zebrafish, we applied the tract-tracing technique to GFP (green fluorescent protein)-expressing transgenic zebrafish to identify habenular neurons that project to the raphe nuclei, a major target of the mammalian lateral habenula. Axonal tracing in live and fixed fish showed projection of zebrafish ventral habenula axons to the ventral part of the median raphe, but not to the interpeduncular nucleus where the dorsal habenula projected. The ventral habenula expressed protocadherin 10a, a specific marker of the rat lateral habenula, whereas the dorsal habenula showed no such expression. Gene expression analyses revealed that the ventromedially positioned ventral habenula in the adult originated from the region of primordium lateral to the dorsal habenula during development. This suggested that zebrafish habenulae emerge during development with mediolateral orientation similar to that of the mammalian medial and lateral habenulae. These findings indicated that the lateral habenular pathways are evolutionarily conserved pathways and might control adaptive behaviors in vertebrates through the regulation of monoaminergic activities.

Evolution of feeding specialization in Tanganyikan scale-eating cichlids: a molecular phylogenetic approach.

BACKGROUND: Cichlid fishes in Lake Tanganyika exhibit remarkable diversity in their feeding habits. Among them, seven species in the genus Perissodus are known for their unique feeding habit of scale eating with specialized feeding morphology and behaviour. Although the origin of the scale-eating habit has long been questioned, its evolutionary process is still unknown. In the present study, we conducted interspecific phylogenetic analyses for all nine known species in the tribe Perissodini (seven Perissodus and two Haplotaxodon species) using amplified fragment length polymorphism (AFLP) analyses of the nuclear DNA. On the basis of the resultant phylogenetic frameworks, the evolution of their feeding habits was traced using data from analyses of stomach contents, habitat depths, and observations of oral jaw tooth morphology. RESULTS: AFLP analyses resolved the phylogenetic relationships of the Perissodini, strongly supporting monophyly for each species. The character reconstruction of feeding ecology based on the AFLP tree suggested that scale eating evolved from general carnivorous feeding to highly specialized scale eating. Furthermore, scale eating is suggested to have evolved in deepwater habitats in the lake. Oral jaw tooth shape was also estimated to have diverged in step with specialization for scale eating. CONCLUSION: The present evolutionary analyses of feeding ecology and morphology based on the obtained phylogenetic tree demonstrate for the first time the evolutionary process leading from generalised to highly specialized scale eating, with diversification in feeding morphology and behaviour among species.

Nucleotide sequences of pigeon feather keratin genes.

We analyzed two pigeon feather keratin clones from a cosmid pigeon genomic library. Each of the clones contained three feather keratin genes that had the same general structure: a 5' non-coding region separated by an intron, a protein-coding region encoding a protein of 100 amino acids, and a 3' non-coding region. Length and transcriptional organization of the genes were variable. The length variation, about 1.2-3.7 kb, was mainly due to the difference in the length of the 3' non-coding region, and the longer genes had opposite transcriptional organization in contrast to the shorter genes. The nucleotide sequences of the coding region were very similar among the six genes but not the same.