Prompt and Long-term Prophylactic Effect of Closed Loop Stimulation against Paroxysmal Atrial Fibrillation in a Patient with Sick Sinus Syndrome

A 72-year-old woman with sick sinus syndrome (SSS), who had frequent paroxysmal atrial fibrillations (PAfs) and normal cardiac function, was admitted to our hospital due to syncope. PAfs frequently occurred during the first week after DDD pacemaker implantation (PMI), with closed loop stimulation (CLS) rate-adaptive mode off, but were completely suppressed during the second week, with CLS on, and had been well-controlled over three years thereafter. However, PAfs occasionally occurred under intense sympathetic activity during 6 months after PMI as well, and were effectively terminated by disopyramide which had anticholinergic effect. Thus, the development and maintenance of PAf were thought to be associated with destabilized cardiac autonomic activities, that is, sympathetic and parasympathetic dominance, respectively. Additionally, heart rate variability analyses after implementation of CLS revealed the restoration of sympathetic and parasympathetic components. Accordingly, CLS mode was considered to play a critical role in preventing PAf by reflecting autonomic activity in heart rhythm in this SSS patient

High-Energy Electron Transfer Dissociation (HE-ETD) Using Alkali Metal Targets for Sequence Analysis of Post-Translational Peptides

Post-translational modifications (PTMs) of proteins are important in the activation, localization, and regulation of protein function in vivo. The usefulness of electron capture dissociation (ECD) and electron-transfer dissociation (ETD) in tandem mass spectrometry (MS/MS) using low-energy (LE) trap type mass spectrometer is associated with no loss of a labile PTM group regarding peptide and protein sequencing. The experimental results of high-energy (HE) collision induced dissociation (CID) using the Xe and Cs targets and LE-ETD were compared for doubly-phosphorylated peptides TGFLT(p)EY(p)VATR (1). Although HE-CID using the Xe target did not provide information on the amino acid sequence, HE-CID using the Cs target provided all the z-type ions without loss of the phosphate groups as a result of HE-ETD process, while LE-ETD using fluoranthene anion gave only z-type ions from z5 to z11. The difference in the results of HE-CID between the Xe and Cs targets demonstrated that HE-ETD process with the Cs target took place much more dominantly than collisional activation. The difference between HE-ETD using Cs targets and LE-ETD using the anion demonstrated that mass discrimination was much weaker in the high-energy process. HE-ETD was also applied to three other phosphopeptides YGGMHRQEX(p)VDC (2: X = S, 3: X = T, 4: X = Y). The HE-CID spectra of the doubly-protonated phosphopeptides (= [M + 2H]2+) of 2, 3, and 4 using the Cs target showed a very similar feature that the c-type ions from c7 to c11 and the z-type ions from z7 to z11 were formed via N–Cα bond cleavage without a loss of the phosphate group

A reversible oxygen redox reaction in bulk-type all-solid-state batteries

An all-solid-state lithium battery using inorganic solid electrolytes requires safety assurance and improved energy density, both of which are issues in large-scale applications of lithium-ion batteries. Utilization of high-capacity lithium-excess electrode materials is effective for the further increase in energy density. However, they have never been applied to all-solid-state batteries. Operational difficulty of all-solid-state batteries using them generally lies in the construction of the electrode-electrolyte interface. By the amorphization of Li₂RuO₃ as a lithium-excess model material with Li₂SO₄, here, we have first demonstrated a reversible oxygen redox reaction in all-solid-state batteries. Amorphous nature of the Li₂RuO₃-Li₂SO₄ matrix enables inclusion of active material with high conductivity and ductility for achieving favorable interfaces with charge transfer capabilities, leading to the stable operation of all-solid-state batteries

Plasma xanthine oxidoreductase activity in Japanese patients with type 2 diabetes across hospitalized treatment

Yusuke Kawachi; Yuya Fujishima; Hitoshi Nishizawa; Hirofumi Nagao; Takashi Nakamura; Seigo Akari; Takayo Murase; Naohiro Taya; Kazuo Omori; Akimitsu Miyake; Shiro Fukuda; Mitsuyoshi Takahara; Shunbun Kita; Naoto Katakami; Norikazu Maeda; Iichiro Shimomura. Plasma xanthine oxidoreductase activity in Japanese patients with type 2 diabetes across hospitalized treatment. J Diabetes Investig. 2020

Screening for resistance against Pseudomonas syringae in rice-FOX Arabidopsis lines identified a putative receptor-like cytoplasmic kinase gene that confers resistance to major bacterial and fungal pathogens in Arabidopsis and rice

Approximately 20 000 of the rice-FOX Arabidopsis transgenic lines, which overexpress 13 000 rice full-length cDNAs at random in Arabidopsis, were screened for bacterial disease resistance by dip inoculation with Pseudomonas syringae pv. tomato DC3000 (Pst DC3000). The identities of the overexpressed genes were determined in 72 lines that showed consistent resistance after three independent screens. Pst DC3000 resistance was verified for 19 genes by characterizing other independent Arabidopsis lines for the same genes in the original rice-FOX hunting population or obtained by reintroducing the genes into ecotype Columbia by floral dip transformation. Thirteen lines of these 72 selections were also resistant to the fungal pathogen Colletotrichum higginsianum. Eight genes that conferred resistance to Pst DC3000 in Arabidopsis have been introduced into rice for overexpression, and transformants were evaluated for resistance to the rice bacterial pathogen, Xanthomonas oryzae pv. oryzae. One of the transgenic rice lines was highly resistant to Xanthomonas oryzae pv. oryzae. Interestingly, this line also showed remarkably high resistance to Magnaporthe grisea, the fungal pathogen causing rice blast, which is the most devastating rice disease in many countries. The causal rice gene, encoding a putative receptor-like cytoplasmic kinase, was therefore designated as BROAD-SPECTRUM RESISTANCE 1. Our results demonstrate the utility of the rice-FOX Arabidopsis lines as a tool for the identification of genes involved in plant defence and suggest the presence of a defence mechanism common between monocots and dicots

Extreme deformability of insect cell membranes is governed by phospholipid scrambling

昆虫の細胞は柔らかい！ --細胞膜を柔らかくするタンパク質を発見--. 京都大学プレスリリース. 2021-06-09.Organization of dynamic cellular structure is crucial for a variety of cellular functions. In this study, we report that Drosophila and Aedes have highly elastic cell membranes with extremely low membrane tension and high resistance to mechanical stress. In contrast to other eukaryotic cells, phospholipids are symmetrically distributed between the bilayer leaflets of the insect plasma membrane, where phospholipid scramblase (XKR) that disrupts the lipid asymmetry is constitutively active. We also demonstrate that XKR-facilitated phospholipid scrambling promotes the deformability of cell membranes by regulating both actin cortex dynamics and mechanical properties of the phospholipid bilayer. Moreover, XKR-mediated construction of elastic cell membranes is essential for hemocyte circulation in the Drosophila cardiovascular system. Deformation of mammalian cells is also enhanced by the expression of Aedes XKR, and thus phospholipid scrambling may contribute to formation of highly deformable cell membranes in a variety of living eukaryotic cells

Reliability and validity of the patient disability-oriented diagnostic nomenclature system for prosthetic dentistry

Purpose: The Japan Prosthodontic Society (JPS) has proposed a new diagnostic nomenclature system (DNS), based on pathogenesis and etiology, to facilitate and improve prosthodontic treatment. This systemspecifies patient disability and the causative factor (i.e. ‘‘B (disability) caused by A (causative factor)’’). The purpose of this study was to examine the reliability and validity of this DNS. Study selection: The JPS Clinical Guideline Committee assessed mock patient charts and formulated disease names using the new DNS. Fifty validators, comprising prosthodontic specialists and dental residents, made diagnoses using the same patient charts. Reliability was evaluated as the consistency of the disease names among the validators, and validity was evaluated using the concordance rate of the disease names with the reference disease names. Results: Krippendorff’s α was 0.378 among all validators, 0.370 among prosthodontic specialists, and 0.401 among dental hospital residents. Krippendorff’s α for 10 validators (3 specialists and 7 residents) with higher concordance rates was 0.524. Two validators (1 specialist and 1 resident) with the highest concordance rates had a Krippendorff’s α of 0.648. Common disease names had higher concordance rates, while uncommon disease names showed lower concordance rates. These rates did not show correlation with clinical experience of the validator or time taken to devise the disease name. Conclusions: High reliability was not found among all validators; however, validators with higher concordance rates showed better reliability. Furthermore, common disease names had higher concordance rates. These findings indicate that the new DNS for prosthodontic dentistry exhibits clinically acceptable reliability and validity

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target