Comparison of anterior chamber depth measurements by 3-dimensional optical coherence tomography, partial coherence interferometry biometry, Scheimpflug rotating camera imaging, and ultrasound biomicroscopy

PURPOSE: To evaluate the congruity of anterior chamber depth (ACD) measurements using 4 devices. SETTING: Saneikai Tsukazaki Hospital, Himeji City, Japan. DESIGN: Comparative case series. METHODS: In 1 eye of 42 healthy participants, the ACD was measured by 3-dimensional corneal and anterior segment optical coherence tomography (CAS-OCT), partial coherence interferometry (PCI), Scheimpflug imaging, and ultrasound biomicroscopy (UBM). The differences between the measurements were evaluated by 2-way analysis of variance and post hoc analysis. Agreement between the measurements was evaluated using Bland-Altman analysis. To evaluate the true ACD using PCI, the automatically calculated ACD minus the central corneal thickness measured by CAS-OCT was defined as PCI true. Two ACD measurements were also taken with CAS-OCT. RESULTS: The mean ACD was 3.72 mm G 0.23 (SD) (PCI), 3.18 G 0.23 mm (PCI true), 3.24 G 0.25 mm (Scheimpflug), 3.03G 0.25 mm (UBM), 3.14 G 0.24 mm (CAS-OCT auto), and 3.12 G 0.24 mm (CAS-OCT manual). A significant difference was observed between PCI biometry, Scheimpflug imaging, and UBM measurements and the other methods. Post hoc analysis showed no significant differences between PCI true and CAS-OCT auto or between the CAS-OCT auto and CAS-OCT manual. Strong correlations were observed between all measurements; however, Bland-Altman analysis showed good agreement only between PCI true and Scheimpflug imaging and between CAS-OCT auto and CAS OCT manual. CONCLUSION: The ACD measurements obtained from PCI biometry, Scheimpflug imaging, CAS-OCT, and UBM were significantly different and not interchangeable except for PCI true and CAS-OCT auto and CAS-OCT auto and CAS-OCT manual. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned

Role of the Carboxy-Terminal Region of the GluRε2 Subunit in Synaptic Localization of the NMDA Receptor Channel

AbstractThe synaptic localization of the N-methyl-D-aspartate (NMDA) type glutamate receptor (GluR) channel is a prerequisite for synaptic plasticity in the brain. We generated mutant mice carrying the carboxy-terminal truncated GluRε2 subunit of the NMDA receptor channel. The mutant mice died neonatally and failed to form barrelette structures in the brainstem. The mutation greatly decreased the NMDA receptor–mediated component of hippocampal excitatory postsynaptic potentials and punctate immunofluorescent labelings of GluRε2 protein in the neuropil regions, while GluRε2 protein expression was comparable. Immunostaining of cultured cerebral neurons showed the reduced punctate staining of the truncated GluRε2 protein at synapses. These results suggest that the carboxy-terminal region of the GluRε2 subunit is important for efficient clustering and synaptic localization of the NMDA receptor channel

A Host Small GTP-binding Protein ARL8 Plays Crucial Roles in Tobamovirus RNA Replication

Tomato mosaic virus (ToMV), like other eukaryotic positive-strand RNA viruses, replicates its genomic RNA in replication complexes formed on intracellular membranes. Previous studies showed that a host seven-pass transmembrane protein TOM1 is necessary for efficient ToMV multiplication. Here, we show that a small GTP-binding protein ARL8, along with TOM1, is co-purified with a FLAG epitope-tagged ToMV 180K replication protein from solubilized membranes of ToMV-infected tobacco (Nicotiana tabacum) cells. When solubilized membranes of ToMV-infected tobacco cells that expressed FLAG-tagged ARL8 were subjected to immunopurification with anti-FLAG antibody, ToMV 130K and 180K replication proteins and TOM1 were co-purified and the purified fraction showed RNA-dependent RNA polymerase activity that transcribed ToMV RNA. From uninfected cells, TOM1 co-purified with FLAG-tagged ARL8 less efficiently, suggesting that a complex containing ToMV replication proteins, TOM1, and ARL8 are formed on membranes in infected cells. In Arabidopsis thaliana, ARL8 consists of four family members. Simultaneous mutations in two specific ARL8 genes completely inhibited tobamovirus multiplication. In an in vitro ToMV RNA translation-replication system, the lack of either TOM1 or ARL8 proteins inhibited the production of replicative-form RNA, indicating that TOM1 and ARL8 are required for efficient negative-strand RNA synthesis. When ToMV 130K protein was co-expressed with TOM1 and ARL8 in yeast, RNA 5′-capping activity was detected in the membrane fraction. This activity was undetectable or very weak when the 130K protein was expressed alone or with either TOM1 or ARL8. Taken together, these results suggest that TOM1 and ARL8 are components of ToMV RNA replication complexes and play crucial roles in a process toward activation of the replication proteins' RNA synthesizing and capping functions

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

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

Exploring an Applied Ecological Model of the Effects of Household, School, and Community Environments on Adolescent Mental Health in Japan

Adolescent mental health is an urgent global public health issue and is affected by household, school, and community environments. However, few studies, and none in Japan, have used applied ecological models to identify environmental factors that affect adolescent mental health. This study aimed to examine an applied ecological model of sequential association between household, school, and community environmental factors and their effects on adolescent mental health in Japan (ECO-AM model). This was a secondary analysis of data from the 2013 Japanese Comprehensive Survey of Living Conditions. Participants were 893 adolescents aged 12-14 years and their household heads living in Japan. Data for 728 adolescents were analyzed after excluding participants with missing values (valid response rate: 81.5%). Screening using the six-item Kessler Psychological Distress Scale demonstrated that 33.8% of adolescents had mood and anxiety disorders. Covariance structure analysis yielded a model with strong goodness-of-fit that described associations between mood and anxiety disorder and vitality, and household, school and community environments. The explanatory variables accounted for 36% of mood and anxiety disorder scores. The study emphasizes the importance of the relationship between different environments and suggests that a better understanding of environmental factors would help support adolescent mental health