Decay rate of the eigenvalues of the Neumann-Poincar\'e operator

If the boundary of a domain in three dimensions is smooth enough, then the decay rate of the eigenvalues of the Neumann-Poincar\'e operator is known and it is optimal. In this paper, we deal with domains with less regular boundaries and derive quantitative estimates for the decay rates of the Neumann-Poincar\'e eigenvalues in terms of the H\"older exponent of the boundary. Estimates in particular show that the less the regularity of the boundary is, the slower is the decay of the eigenvalues. We also prove that the similar estimates in two dimensions. The estimates are not only for less regular boundaries for which the decay rate was unknown, but also for regular ones for which the result of this paper makes a significant improvement over known results.Comment: 21 page

Identification of a cis-regulatory element that directs prothoracicotropic hormone gene expression in the silkworm Bombyx mori

In the silkworm Bombyx mori and other insects, prothoracicotropic hormone (PITH) plays a central role in controlling molting and metamorphosis by stimulating the prothoracic glands to synthesize and release the molting hormone ecdysone. Using an AcNPV (Autographa californica nucleopolyhedrovirus)mediated transient gene transfer system, we identified a cis-regulatory element that participates in the decision to switch expression of PTTH on or off in PTTH-producing neurosecretory cells (PTPCs). The nucleotide sequence of this cis-regulatory element is similar to a cis-regulatory element that participates in direction of expression of diapause hormone-pheromone biosynthesis activating neuropeptide gene (DH-PBAN) (Shiomi et al., 2007). Furthermore, we found that B. mori Pitx (BmPitx), a bicoid-like homeobox transcription factor, binds the element and activates PITH expression. Therefore, we propose that the cell-specific expression of two neuropeptide hormone genes, PITH and DH-PBAN, is activated by the Pitx transcription factor, which may act as a pan-activator in the insect neuroendocrine system and in vertebrate pituitary cells. (C) 2011 Elsevier Ltd. All rights reserved.ArticleINSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY. 41(6):356-361 (2011)journal articl

Attenuation of conduction delay by ischemic preconditioning reduces ischemia-induced ventricular arrhythmias.

Ischemic preconditioning has been acknowledged as a powerful method of decreasing ischemic injury. However, the antiarrhythmic mechanism of ischemic preconditioning during ischemia is unclear. We studied the effects of ischemic preconditioning on arrhythmias and cardiac electrophysiology during ischemia in Langendorff rat hearts (n = 44). In the non-preconditioned group (PC(-); n = 24), the hearts underwent 5-min zero-flow global ischemia without any prior ischemic preconditioning. In the preconditioned group (PC(+); n = 20), the hearts were preconditioned by three cycles of 3-min zero-flow global ischemia and 5-min reperfusion before undergoing 5-min global ischemia. Ischemic preconditioning reduced the incidence of ischemia-induced arrhythmias (PC(-); 38.9%, PC(+): 8.3%, p < 0.05), shortened monophasic action potential duration (MAPD, P < 0.05), attenuated conduction delay (conduction time; PC(-): 234.2%, PC(+): 173.4%, P < 0.05) and increased the ventricular fibrillation threshold. Although the shortening of MAPD in PC(-) hearts was not influenced by the presence or absence of arrhythmias, conduction time prolongation at 3-min was more obvious in PC(-) hearts with arrhythmia than in PC(-) hearts without arrhythmia (PC(-) with arrhythmia: 220.2%, PC(-) without arrhythmia: 190.7%, P < 0.05). We concluded that ischemic preconditioning could protect the rat hearts from ischemia-induced arrhythmias and postulated that attenuation of conduction delay during ischemia might be an important factor in the antiarrhythmic action of ischemic preconditioning.</p

Relationship between advanced glycation end products and plaque progression in patients with acute coronary syndrome: the JAPAN-ACS Sub-study.

Background: The Japan Assessment of Pitavastatin and Atorvastatin in Acute Coronary Syndrome (JAPAN-ACS) trial demonstrated that early aggressive statin therapy in patients with ACS significantly reduces plaque volume (PV). Advanced glycation end products (AGEs) and the receptors of AGEs (RAGE) may lead to angiopathy in diabetes mellitus (DM) and may affect on the development of coronary PV. The present sub-study of JAPAN-ACS investigates the association between AGEs and RAGE, and PV.Methods: Intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) was undertaken, followed by the initiation of statin treatment (either 4 mg/day of pitavastatin or 20 mg/day of atorvastatin), in patients with ACS. In the 208 JAPAN-ACS subjects, PV using IVUS in non-culprit segment > 5 mm proximal or distal to the culprit lesion and, serum levels of AGEs and soluble RAGE (sRAGE) were measured at baseline and 8-12 months after PCI.Results: At baseline, no differences in the levels of either AGEs or sRAGE were found between patients with DM and those without DM. The levels of AGEs decreased significantly with statin therapy from 8.6 ± 2.2 to 8.0 ± 2.1 U/ml (p < 0.001), whereas the levels of sRAGE did not change. There were no significant correlations between changes in PV and the changes in levels of AGEs as well as sRAGE. However, high baseline AGEs levels were significantly associated with plaque progression (odds ratio, 1.21; 95% confidence interval, 1.01 - 1.48; p = 0.044) even after adjusting for DM in multivariate logistic regression models.Conclusions: High baseline AGEs levels were associated with plaque progression in the JAPAN-ACS trial. This relationship was independent of DM. These findings suggest AGEs may be related to long-term glucose control and other oxidative stresses in ACS.Trial registration: NCT00242944. © 2013 Fukushima et al.; licensee BioMed Central Ltd

Comparison of rapid immunochromatographic assays using sputum and urine for Streptococcus pneumoniae detection in adult patients with respiratory tract infection

Aim: Streptococcus pneumoniae is the most frequently detected bacterium in pneumonia. RAPIRUN Streptococcus pneumoniae (RAPIRUN) using sputum and BinaxNow Streptococcus pneumoniae (BinaxNow) using urine have been used as rapid diagnostic methods for S. pneumoniae detection in Japan; however, their correlation with quantitative culture tests has not been well evaluated.Methods: A prospective study was conducted on adult patients with respiratory tract infections whose sputum and urine samples were available in six hospitals. Sputum and urine samples were tested at each site, and quantitative sputum cultures were performed. The performance of RAPIRUN and BinaxNow was compared in cases in which quantitative culture showed S. pneumoniae.Results: A total of 192 patients were analyzed. Of these, 167 were diagnosed with pneumonia (87.0%) including 161 of community-acquired pneumonia. Of the 192 cases, 86 (44.8%) were culture-proven for S. pneumoniae. There were 83 and 57 RAPIRUN- and BinaxNow-positive cases, respectively. The sensitivity and specificity of RAPIRUN were 84.9% and 90.6%, respectively, and those of BinaxNOW were 55.8% and 91.5%, respectively, indicating that RAPIRUN was significantly superior in sensitivity (p < 0.0001) with almost equal specificity (p = 0.317). Positive and negative percent agreements of both tests were 59.3% (κ, 0.114 [95% CI, 0.053–0.281]) and 99.1% (κ, 0.942 [95% CI, 0.830–1]), respectively, indicating they were well matched in specificity but not in sensitivity. The positivity rate of RAPIRUN increased with an increase in the number of bacteria (p< 0.0001) but not BinaxNow (p = 0.275).Conclusion: In adult patients with respiratory tract infections in whom sputum collection is feasible, RAPIRUN will increase the diagnostic efficacy of S. pneumoniae infection

Epidemiology and Clinical Features of Pulmonary Nontuberculous Mycobacteriosis in Nagasaki, Japan

Background and Objectives: Recent reports indicate that the incidence of nontuberculous mycobacterial-lung disease (NTM-LD) is increasing. This study aimed to investigate the epidemiology and clinical features of NTM-LD patients in Nagasaki prefecture, Japan to identify the negative prognostic factors for NTM-LD in Japan. Methods: The medical records of patients newly diagnosed with NTM-LD in eleven hospitals in Nagasaki prefecture between January 2001 and February 2010 were reviewed. Data regarding the annual population of each region and the incidence of all forms of tuberculosis were collected to assess geographic variations in NTM-LD incidence, isolates, and radiological features. Results: A total 975 patients were diagnosed with NTM-LD. The incidence increased over the study period and reached 11.0 and 10.1 per 100,000 population in 2008 and 2009, respectively. M. intracellulare was the most common pathogen in the southern region, and M. avium most common in other regions. The most common radiographic pattern was the nodular-bronchiectatic pattern. Age >60 years, body mass index <18.5 kg/m2, underlying lung disease, and cavitary pattern were the negative prognostic factors at the 1-year follow-up. Conclusions: The incidence of NTM-LD has been increasing in Nagasaki prefecture. The isolates and radiographic features of patients vary markedly by region

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