Epidemiologic trends and distributions of imported infectious diseases among travelers to Japan before and during the COVID-19 pandemic, 2016 to 2021: a descriptive study

BACKGROUND: Little is known about the trends of imported infectious diseases among travelers to non-endemic countries during the COVID-19 pandemic. This article aimed to describe those among travelers to Japan. METHODS: This is a descriptive study based on national surveillance data. Imported infectious disease cases were defined as those with a reported overseas source of infection among 15 diseases pre-selected based on the probability and impact of importation. The number of notified cases from April 2016 to March 2021 were described by disease and time of diagnosis. The relative ratio and absolute difference in case counts-both by number and per arrival-were calculated by disease comparing those from the pandemic period (April 2020-March 2021) to the pre-pandemic period (April 2016-March 2020). RESULTS: A total of 3524 imported infectious disease cases were diagnosed during the study period, including 3439 cases before and 85 cases during the pandemic. The proportionate distribution of diseases changed but notification counts of all 15 diseases decreased during the pandemic. Accounting for arrivals, however, seven diseases showed a two-fold or greater increase, with a notable absolute increase per million arrivals for amebiasis (60.1; 95%CI, 41.5-78.7), malaria (21.7; 10.5-33.0), and typhoid fever (9.3; 1.9-16.8). CONCLUSION: The epidemiology of imported infectious diseases changed during the pandemic. While the number of imported infectious disease cases decreased, the number of cases per arrivals increased considerably both in relative and absolute terms for several diseases of public health and clinical importance

Community-wide assessment of GPCR structure modelling and ligand docking: GPCR Dock 2008

Recent breakthroughs in the determination of the crystal structures of G protein-coupled receptors (GPCRs) have provided new opportunities for structure-based drug design strategies targeting this protein family. With the aim of evaluating the current status of GPCR structure prediction and ligand docking, a community-wide, blind prediction assessment - GPCR Dock 2008 - was conducted in coordination with the publication of the crystal structure of the human adenosine A2Areceptor bound to the ligand ZM241385. Twenty-nine groups submitted 206 structural models before the release of the experimental structure, which were evaluated for the accuracy of the ligand binding mode and the overall receptor model compared with the crystal structure. This analysis highlights important aspects for success and future development, such as accurate modelling of structurally divergent regions and use of additional biochemical insight such as disulphide bridges in the extracellular loops

Reduced mortality during the COVID-19 outbreak in Japan, 2020: a two-stage interrupted time-series design.

BACKGROUND: Coronavirus disease 2019 (COVID-19) continues to be a major global health burden. This study aims to estimate the all-cause excess mortality occurring in the COVID-19 outbreak in Japan, 2020, by sex and age group. METHODS: Daily time series of mortality for the period January 2015-December 2020 in all 47 prefectures of Japan were obtained from the Ministry of Health, Labour and Welfare, Japan. A two-stage interrupted time-series design was used to calculate excess mortality. In the first stage, we estimated excess mortality by prefecture using quasi-Poisson regression models in combination with distributed lag non-linear models, adjusting for seasonal and long-term variations, weather conditions and influenza activity. In the second stage, we used a random-effects multivariate meta-analysis to synthesize prefecture-specific estimates at the nationwide level. RESULTS: In 2020, we estimated an all-cause excess mortality of -20 982 deaths [95% empirical confidence intervals (eCI): -38 367 to -5472] in Japan, which corresponded to a percentage excess of -1.7% (95% eCI: -3.1 to -0.5) relative to the expected value. Reduced deaths were observed for both sexes and in all age groups except those aged <60 and 70-79 years. CONCLUSIONS: All-cause mortality during the COVID-19 outbreak in Japan in 2020 was decreased compared with a historical baseline. Further evaluation of cause-specific excess mortality is warranted

FAMSD: A Powerful Protein Modeling Platform that Combines Alignment Methods, Homology Modeling, 3D Structure Quality Estimation and Molecular Dynamics

1335 The number of three-dimensional (3D) structures of proteins solved by experimental methods is rapidly increasing. As of June 2009, more than 58000 structures were available in the Protein Data Bank (PDB). 1) However, the number of amino acid sequences whose 3D structures have not been determined remains more than 100 times greater. Therefore, some approaches for accurate protein structure prediction are urgently required. One of the most effective approaches for protein structure prediction is a comparative modeling (CM) method. This technique uses 3D template structures that have high sequence identities with the target protein. In this paper, we describe our comparative modeling platform which consists of the following four steps: (1) generating and filtering sequence alignments between the target and template proteins; (2) constructing 3D structure models based on each alignment; (3) selecting the best structural model among the candidates; and 13) We participated in CASP8 as an automatic predictor using the server for which our FAMSD method was internally included. In this paper, the basic algorithm of the FAMSD and the results of the protein modeling for CASP8 targets are described. We show that the modeling method using FAMSD generates reliable 3D protein structures. The protein structures predicted with the FAMSD method should be extremely valuable for experimental researchers. -BLAST, SP3 2) and SPARKS2 3) were executed. SPARKS2 and SP3 programs were shown to be excellent in the CASP6 experiment. 19) Various alignments were obtained and were filtered with our original alignment score value. First, the alignment score value was calculated using the following Eq. 1 for six BLAST-related alignment methods. These methods were BLAST, PSI-BLAST, PSF-BLAST, RPS-BLAST, IMPALA and Pfam-BLAST. Here, Len represents the number of residues of the region aligned to the template protein, SEQid represents the sequence identity percent, SS is the degree of match between the predicted secondary structure elements (SSE) from the target sequence and the SSE of the template protein. The predicted SSE from the amino acid sequence was obtained with PSI-PRED. 20) The SSE of the template protein was assigned by STRIDE. 21) The k i value by which the significance weights are described in the six alignment methods is Science and Engineering, Chuo University; 1-13-27 Kasuga, Bunkyo-ku, Tokyo 112-8551, Japan. Received March 5, 2009; accepted September 8, 2009; published online September 30, 2009 The prediction of a protein three-dimensional (3D) structure is one of the most important challenges in computational structural biology. We have developed an automatic protein 3D structure prediction method called FAMSD. FAMSD is based on a comparative modeling method which consists of the following four steps: (1) generating and selecting sequence alignments between target and template proteins; (2) constructing 3D structure models based on each selected alignment; (3) selecting the best 3D structure model and (4) refining the selected model. In the FAMSD method, sequence alignment programs such as a series of BLAST programs, SP3 and SPARKS2 programs, the homology modeling program FAMS (Full Automatic Modeling System), the model quality estimation program CIRCLE and the molecular dynamics program APRICOT were used in combination to construct high quality protein models. To assess the FAMSD method we have participated in the 8th Critical Assessment of Techniques for Protein Structure Prediction (CASP8) experiment. The results of our original assessment indicate that the FAMSD method offers excellent capability in packing side-chains with the correct torsion angles while avoiding the formation of atom-atom collisions. Since side-chain packing plays a significant role in defining the biological function of proteins, this method is a valuable resource in biological, pharmaceutical and medicinal research efforts

Measles Virus Hemagglutinin Protein Epitopes: The Basis of Antigenic Stability

Globally eliminating measles using available vaccines is biologically feasible because the measles virus (MV) hemagglutinin (H) protein is antigenically stable. The H protein is responsible for receptor binding, and is the main target of neutralizing antibodies. The immunodominant epitope, known as the hemagglutinating and noose epitope, is located near the receptor-binding site (RBS). The RBS also contains an immunodominant epitope. Loss of receptor binding correlates with an escape from the neutralization by antibodies that target the epitope at RBS. Another neutralizing epitope is located near RBS and is shielded by an N-linked sugar in certain genotype strains. However, human sera from vaccinees and measles patients neutralized all MV strains with similar efficiencies, regardless of the N-linked sugar modification or mutations at these epitopes. Two other major epitopes exist at a distance from RBS. One has an unstructured flexible domain with a linear neutralizing epitope. When MV-H forms a tetramer (dimer of dimers), these epitopes may form the dimer-dimer interface, and one of the two epitopes may also interact with the F protein. The neutralization mechanisms of antibodies that recognize these epitopes may involve inhibiting the H-F interaction or blocking the fusion cascade after MV-H binds to its receptors

Erratum: Tahara, M., et al. Measles Virus Hemagglutinin Protein Epitopes: The Basis of Antigenic Stability. Viruses 2016, 8, 216

The authors wish to make the following change to their paper [1].[...

Relationship between Intratumoral Hemorrhage and Overexpression of Vascular Endothelial Growth Factor (VEGF) in Pituitary Adenoma

The authors investigated the relationship between hemorrhage and the expression of vascular endothelial growth factor (VEGF) in pituitary adenomas. The subjects were 39 patients with pituitary adenomas. Surgically obtained tumor tissue was immunohistochemically stained using antibodies against VEGF, CD-34, Ki-67, and anterior pituitary hormones. The expression of VEGF was graded as 0, 1+, and 2+. The relationship between intratumoral hemorrhage and factors such as tumor size, Ki-67 labeling indices, number of CD-34 positive vessels, and VEGF expression was examined by multivariate analysis. High-grade VEGF expression was the sole independent factor correlated with intratumoral hemorrhage. The number of CD-34 positive vessels had no effect on the incidence of hemorrhage in patients with pituitary adenomas. In conclusion, a positive relationship between VEGF expression and hemorrhage in pituitary adenoma was observed. The patho-mechanical significance of this correlation is under investigation

ASK1 restores the antiviral activity of APOBEC3G by disrupting HIV-1 Vif-mediated counteraction

APOBEC3G (A3G) is an innate antiviral restriction factor that strongly inhibits the replication of human immunodeficiency virus type 1 (HIV-1). An HIV-1 accessory protein, Vif, hijacks the host ubiquitin-proteasome system to execute A3G degradation. Identification of the host pathways that obstruct the action of Vif could provide a new strategy for blocking viral replication. We demonstrate here that the host protein ASK1 (apoptosis signal-regulating kinase 1) interferes with the counteraction by Vif and revitalizes A3G-mediated viral restriction. ASK1 binds the BC-box of Vif, thereby disrupting the assembly of the Vif-ubiquitin ligase complex. Consequently, ASK1 stabilizes A3G and promotes its incorporation into viral particles, ultimately reducing viral infectivity. Furthermore, treatment with the antiretroviral drug AZT (zidovudine) induces ASK1 expression and restores the antiviral activity of A3G in HIV-1-infected cells. This study thus demonstrates a distinct function of ASK1 in restoring the host antiviral system that can be enhanced by AZT treatment